OA10980A - Substituted 6,6-hetero-bicyclic derivatives - Google Patents
Substituted 6,6-hetero-bicyclic derivatives Download PDFInfo
- Publication number
- OA10980A OA10980A OA9900039A OA9900039A OA10980A OA 10980 A OA10980 A OA 10980A OA 9900039 A OA9900039 A OA 9900039A OA 9900039 A OA9900039 A OA 9900039A OA 10980 A OA10980 A OA 10980A
- Authority
- OA
- OAPI
- Prior art keywords
- alkyl
- compound according
- methyl
- phenyl
- aikyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 223
- 102100021752 Corticoliberin Human genes 0.000 claims abstract description 20
- 229940088597 hormone Drugs 0.000 claims abstract description 7
- 239000005556 hormone Substances 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 155
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 65
- -1 hydroxy, fluoro, chloro, bromo, iodo Chemical group 0.000 claims description 55
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 33
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 30
- 125000002947 alkylene group Chemical group 0.000 claims description 29
- 229910052799 carbon Inorganic materials 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 26
- 125000001246 bromo group Chemical group Br* 0.000 claims description 24
- 125000001153 fluoro group Chemical group F* 0.000 claims description 24
- 125000002346 iodo group Chemical group I* 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 208000035475 disorder Diseases 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 239000001301 oxygen Substances 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 229910052684 Cerium Inorganic materials 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 239000011593 sulfur Chemical group 0.000 claims description 10
- 208000011580 syndromic disease Diseases 0.000 claims description 10
- 101710113174 Corticoliberin Proteins 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 9
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 9
- 230000003961 neuronal insult Effects 0.000 claims description 9
- 208000019022 Mood disease Diseases 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000006413 ring segment Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 108091008324 binding proteins Proteins 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 6
- 206010020751 Hypersensitivity Diseases 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 6
- 125000005605 benzo group Chemical group 0.000 claims description 6
- 235000020824 obesity Nutrition 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 5
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 206010012335 Dependence Diseases 0.000 claims description 5
- 208000030814 Eating disease Diseases 0.000 claims description 5
- 206010015549 Euthyroid sick syndrome Diseases 0.000 claims description 5
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 5
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 208000001132 Osteoporosis Diseases 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 206010037660 Pyrexia Diseases 0.000 claims description 5
- 208000005392 Spasm Diseases 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 206010046543 Urinary incontinence Diseases 0.000 claims description 5
- 230000007815 allergy Effects 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 235000014632 disordered eating Nutrition 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 231100000318 excitotoxic Toxicity 0.000 claims description 5
- 230000003492 excitotoxic effect Effects 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 208000014674 injury Diseases 0.000 claims description 5
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 230000036407 pain Effects 0.000 claims description 5
- 230000037324 pain perception Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 5
- 230000008733 trauma Effects 0.000 claims description 5
- 206010002027 Amyotrophy Diseases 0.000 claims description 4
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 4
- 208000020925 Bipolar disease Diseases 0.000 claims description 4
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 4
- 206010012289 Dementia Diseases 0.000 claims description 4
- 206010012735 Diarrhoea Diseases 0.000 claims description 4
- 241000283073 Equus caballus Species 0.000 claims description 4
- 241000287828 Gallus gallus Species 0.000 claims description 4
- 208000011688 Generalised anxiety disease Diseases 0.000 claims description 4
- 206010019196 Head injury Diseases 0.000 claims description 4
- 206010019233 Headaches Diseases 0.000 claims description 4
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 241001494479 Pecora Species 0.000 claims description 4
- 208000028017 Psychotic disease Diseases 0.000 claims description 4
- 208000025865 Ulcer Diseases 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 206010061592 cardiac fibrillation Diseases 0.000 claims description 4
- 235000013330 chicken meat Nutrition 0.000 claims description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 4
- 229960002069 diamorphine Drugs 0.000 claims description 4
- 230000002600 fibrillogenic effect Effects 0.000 claims description 4
- 208000029364 generalized anxiety disease Diseases 0.000 claims description 4
- 231100000869 headache Toxicity 0.000 claims description 4
- 208000026278 immune system disease Diseases 0.000 claims description 4
- 208000028867 ischemia Diseases 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 230000001314 paroxysmal effect Effects 0.000 claims description 4
- 208000019899 phobic disease Diseases 0.000 claims description 4
- 230000002980 postoperative effect Effects 0.000 claims description 4
- 210000000278 spinal cord Anatomy 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 231100000397 ulcer Toxicity 0.000 claims description 4
- 241000283690 Bos taurus Species 0.000 claims description 3
- 241000282472 Canis lupus familiaris Species 0.000 claims description 3
- 208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 3
- 201000004810 Vascular dementia Diseases 0.000 claims description 3
- 208000026725 cyclothymic disease Diseases 0.000 claims description 3
- 230000003993 interaction Effects 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 102000004169 proteins and genes Human genes 0.000 claims description 3
- 108090000623 proteins and genes Proteins 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 208000019116 sleep disease Diseases 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical class N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 2
- SQVZUGHPSMFDBH-UHFFFAOYSA-N 2-methyl-4-pentan-3-yloxy-8-(2,4,6-trimethylphenyl)quinoline Chemical compound C1=CC=C2C(OC(CC)CC)=CC(C)=NC2=C1C1=C(C)C=C(C)C=C1C SQVZUGHPSMFDBH-UHFFFAOYSA-N 0.000 claims description 2
- BHHMPZQRVWVAAR-UHFFFAOYSA-N 7-bromo-8-methylpyrido[2,3-b]pyrazine Chemical compound C1=CN=C2C(C)=C(Br)C=NC2=N1 BHHMPZQRVWVAAR-UHFFFAOYSA-N 0.000 claims description 2
- OCPRQWREMAXTOZ-UHFFFAOYSA-N 7-methyl-5-pentan-3-yloxy-1-(2,4,6-trimethylphenyl)-2h-pyrido[2,3-d][1,3]oxazin-4-one Chemical compound C1OC(=O)C=2C(OC(CC)CC)=CC(C)=NC=2N1C1=C(C)C=C(C)C=C1C OCPRQWREMAXTOZ-UHFFFAOYSA-N 0.000 claims description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 2
- 208000034189 Sclerosis Diseases 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 229960003920 cocaine Drugs 0.000 claims description 2
- 206010061428 decreased appetite Diseases 0.000 claims description 2
- 230000004064 dysfunction Effects 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 101150009274 nhr-1 gene Proteins 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000006085 pyrrolopyridyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 125000006850 spacer group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- 102000014914 Carrier Proteins Human genes 0.000 claims 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 206010015037 epilepsy Diseases 0.000 claims 2
- ZFRUGZMCGCYBRC-UHFFFAOYSA-N 1h-1,8-naphthyridin-2-one Chemical compound C1=CC=NC2=NC(O)=CC=C21 ZFRUGZMCGCYBRC-UHFFFAOYSA-N 0.000 claims 1
- URJKRCBBKTXOHS-UHFFFAOYSA-O 2-(2-hydroxy-phenyl)-3h-benzoimidazole-5-carboxamidine Chemical group N1C2=CC(C(=[NH2+])N)=CC=C2N=C1C1=CC=CC=C1O URJKRCBBKTXOHS-UHFFFAOYSA-O 0.000 claims 1
- OBYABPUZVBFQAU-UHFFFAOYSA-N 2-methyl-n-pentan-3-yl-8-(2,4,6-trimethylphenyl)quinolin-4-amine Chemical compound C1=CC=C2C(NC(CC)CC)=CC(C)=NC2=C1C1=C(C)C=C(C)C=C1C OBYABPUZVBFQAU-UHFFFAOYSA-N 0.000 claims 1
- LAQJGAKLLZAETL-UHFFFAOYSA-N 2h-pyrazin-3-one Chemical compound O=C1CN=CC=N1 LAQJGAKLLZAETL-UHFFFAOYSA-N 0.000 claims 1
- PUZLSXWSLTZXSJ-UHFFFAOYSA-N 4-[butyl(ethyl)amino]-2,6-dimethyl-8-(2,4,6-trimethylphenyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound O=C1C(C)CC=2C(N(CC)CCCC)=NC(C)=NC=2N1C1=C(C)C=C(C)C=C1C PUZLSXWSLTZXSJ-UHFFFAOYSA-N 0.000 claims 1
- UEJHCIZKAAFBCH-UHFFFAOYSA-N 4-chloro-7-methyl-5-pentan-3-yloxy-1-(2,4,6-trimethylphenyl)pyrido[2,3-d]pyrimidin-2-one Chemical compound O=C1N=C(Cl)C=2C(OC(CC)CC)=CC(C)=NC=2N1C1=C(C)C=C(C)C=C1C UEJHCIZKAAFBCH-UHFFFAOYSA-N 0.000 claims 1
- IPPBHNMFESFVGT-UHFFFAOYSA-N 6-methyl-8-pentan-3-yloxy-4-(2,4,6-trimethylphenyl)-2,3-dihydro-1h-pyrido[2,3-b]pyrazine Chemical compound C1CNC=2C(OC(CC)CC)=CC(C)=NC=2N1C1=C(C)C=C(C)C=C1C IPPBHNMFESFVGT-UHFFFAOYSA-N 0.000 claims 1
- 241000900241 Arua Species 0.000 claims 1
- 206010034912 Phobia Diseases 0.000 claims 1
- 208000008939 Pneumonic Pasteurellosis Diseases 0.000 claims 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims 1
- 208000001871 Tachycardia Diseases 0.000 claims 1
- 241000700605 Viruses Species 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 208000022531 anorexia Diseases 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 230000001537 neural effect Effects 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 230000006794 tachycardia Effects 0.000 claims 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims 1
- 239000005557 antagonist Substances 0.000 abstract description 5
- 150000003839 salts Chemical class 0.000 abstract description 4
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 abstract 2
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- 239000000203 mixture Substances 0.000 description 36
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- 239000003921 oil Substances 0.000 description 25
- 235000019198 oils Nutrition 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000002585 base Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
- 239000012442 inert solvent Substances 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 239000003480 eluent Substances 0.000 description 12
- 238000010438 heat treatment Methods 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 229910000085 borane Inorganic materials 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000013058 crude material Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 229910052744 lithium Inorganic materials 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 150000004703 alkoxides Chemical class 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 102000023732 binding proteins Human genes 0.000 description 4
- 208000000509 infertility Diseases 0.000 description 4
- 230000036512 infertility Effects 0.000 description 4
- 231100000535 infertility Toxicity 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 239000002841 Lewis acid Substances 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 3
- 150000007517 lewis acids Chemical class 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229940107700 pyruvic acid Drugs 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- UEZNSTAISYTERD-UHFFFAOYSA-N 6-methyl-8-pentan-3-yloxy-4-(2,4,6-trimethylphenyl)-1,3-dihydropyrido[2,3-b]pyrazin-2-one Chemical compound C1C(=O)NC=2C(OC(CC)CC)=CC(C)=NC=2N1C1=C(C)C=C(C)C=C1C UEZNSTAISYTERD-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 208000001640 Fibromyalgia Diseases 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- 206010039966 Senile dementia Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 239000003377 acid catalyst Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 150000002148 esters Chemical group 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
- 229910000105 potassium hydride Inorganic materials 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 229910052702 rhenium Inorganic materials 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- YHOBGCSGTGDMLF-UHFFFAOYSA-N sodium;di(propan-2-yl)azanide Chemical compound [Na+].CC(C)[N-]C(C)C YHOBGCSGTGDMLF-UHFFFAOYSA-N 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
- SYSFTTYJTWPOOR-UHFFFAOYSA-N (2-diphenylphosphanyl-1-naphthalen-1-yl-3h-naphthalen-2-yl)-diphenylphosphane Chemical group C1C=C2C=CC=CC2=C(C=2C3=CC=CC=C3C=CC=2)C1(P(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)C1=CC=CC=C1 SYSFTTYJTWPOOR-UHFFFAOYSA-N 0.000 description 1
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 1
- HOFCYSNYAFJTSI-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrido[2,3-b]pyrazine Chemical compound C1=CC=C2NCCNC2=N1 HOFCYSNYAFJTSI-UHFFFAOYSA-N 0.000 description 1
- XBYRMPXUBGMOJC-UHFFFAOYSA-N 1,2-dihydropyrazol-3-one Chemical class OC=1C=CNN=1 XBYRMPXUBGMOJC-UHFFFAOYSA-N 0.000 description 1
- GVSYRLGZIBEHOU-UHFFFAOYSA-N 1-(4-chloro-2,6-dimethylphenyl)-7-methyl-5-pentan-3-yloxy-2,4-dihydropyrido[2,3-d][1,3]oxazine Chemical compound C1OCC=2C(OC(CC)CC)=CC(C)=NC=2N1C1=C(C)C=C(Cl)C=C1C GVSYRLGZIBEHOU-UHFFFAOYSA-N 0.000 description 1
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 description 1
- DCBOUXKSNFDXER-UHFFFAOYSA-N 1h-pyrido[2,3-b]pyrazin-2-one Chemical compound C1=CC=C2NC(=O)C=NC2=N1 DCBOUXKSNFDXER-UHFFFAOYSA-N 0.000 description 1
- DUMUZNITRKJEPV-UHFFFAOYSA-N 2-(2,4,6-trimethylphenyl)aniline Chemical compound CC1=CC(C)=CC(C)=C1C1=CC=CC=C1N DUMUZNITRKJEPV-UHFFFAOYSA-N 0.000 description 1
- NYEMRULXSBFQLG-UHFFFAOYSA-N 2-chloro-n-[6-methyl-4-pentan-3-yloxy-2-(2,4,6-trimethylanilino)pyridin-3-yl]acetamide Chemical compound CCC(CC)OC1=CC(C)=NC(NC=2C(=CC(C)=CC=2C)C)=C1NC(=O)CCl NYEMRULXSBFQLG-UHFFFAOYSA-N 0.000 description 1
- HUHFKXALPJKHJO-UHFFFAOYSA-N 2-methyl-6-pentan-3-yloxy-4-n-(2,4,6-trimethylphenyl)pyrimidine-4,5-diamine Chemical compound CCC(CC)OC1=NC(C)=NC(NC=2C(=CC(C)=CC=2C)C)=C1N HUHFKXALPJKHJO-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- GYDDZMOYHZUBRS-UHFFFAOYSA-N 4-(4-bromo-2,6-dimethylphenyl)-6-methyl-8-pentan-3-yloxy-1,3-dihydropyrido[2,3-b]pyrazin-2-one Chemical compound C1C(=O)NC=2C(OC(CC)CC)=CC(C)=NC=2N1C1=C(C)C=C(Br)C=C1C GYDDZMOYHZUBRS-UHFFFAOYSA-N 0.000 description 1
- RQRIJQFEJHDYCB-UHFFFAOYSA-N 4-(4-chloro-2,6-dimethylphenyl)-1,6-dimethyl-8-pentan-3-yloxy-2,3-dihydropyrido[2,3-b]pyrazine Chemical compound C1CN(C)C=2C(OC(CC)CC)=CC(C)=NC=2N1C1=C(C)C=C(Cl)C=C1C RQRIJQFEJHDYCB-UHFFFAOYSA-N 0.000 description 1
- RFPDNKIRDJUFPF-UHFFFAOYSA-N 4-bromo-2-methyl-8-(2,4,6-trimethylphenyl)quinoline Chemical compound CC1=CC(C)=CC(C)=C1C1=CC=CC2=C(Br)C=C(C)N=C12 RFPDNKIRDJUFPF-UHFFFAOYSA-N 0.000 description 1
- JLEZZINLBBBGTK-UHFFFAOYSA-N 4-chloro-2,6-dimethyl-8-(2,4,6-trimethylphenyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound O=C1C(C)CC2=C(Cl)N=C(C)N=C2N1C1=C(C)C=C(C)C=C1C JLEZZINLBBBGTK-UHFFFAOYSA-N 0.000 description 1
- JZAVEKYAFUGNMQ-UHFFFAOYSA-N 4-chloro-2-methyl-8-(2,4,6-trimethylphenyl)quinoline Chemical compound CC1=CC(C)=CC(C)=C1C1=CC=CC2=C(Cl)C=C(C)N=C12 JZAVEKYAFUGNMQ-UHFFFAOYSA-N 0.000 description 1
- 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- CPFYUVGWIASMOO-UHFFFAOYSA-N 6-methyl-4-pentan-3-yloxy-2-(2,4,6-trimethylanilino)pyridine-3-carboxamide Chemical compound CCC(CC)OC1=CC(C)=NC(NC=2C(=CC(C)=CC=2C)C)=C1C(N)=O CPFYUVGWIASMOO-UHFFFAOYSA-N 0.000 description 1
- HQDCRCUUIUKXED-UHFFFAOYSA-N 6-methyl-4-pentan-3-yloxy-2-n-(2,4,6-trimethylphenyl)pyridine-2,3-diamine Chemical compound CCC(CC)OC1=CC(C)=NC(NC=2C(=CC(C)=CC=2C)C)=C1N HQDCRCUUIUKXED-UHFFFAOYSA-N 0.000 description 1
- YCLOADSMTOQKKC-UHFFFAOYSA-N 7-methyl-5-pentan-3-yloxy-1-(2,4,6-trimethylphenyl)-2,4-dihydropyrido[2,3-d][1,3]oxazine Chemical compound C1OCC=2C(OC(CC)CC)=CC(C)=NC=2N1C1=C(C)C=C(C)C=C1C YCLOADSMTOQKKC-UHFFFAOYSA-N 0.000 description 1
- YBOLEGUFTOHOGQ-UHFFFAOYSA-N 8-(4-bromo-2,6-dimethylphenyl)-2-methyl-4-pentan-3-yloxy-6,7-dihydro-5h-pyrido[2,3-d]pyrimidine Chemical compound C1CCC=2C(OC(CC)CC)=NC(C)=NC=2N1C1=C(C)C=C(Br)C=C1C YBOLEGUFTOHOGQ-UHFFFAOYSA-N 0.000 description 1
- LRAKEVLPPHAQCG-UHFFFAOYSA-N 8-(4-bromo-2,6-dimethylphenyl)-2-methyl-n-pentan-2-yl-6,7-dihydro-5h-pyrido[2,3-d]pyrimidin-4-amine Chemical compound C1CCC=2C(NC(C)CCC)=NC(C)=NC=2N1C1=C(C)C=C(Br)C=C1C LRAKEVLPPHAQCG-UHFFFAOYSA-N 0.000 description 1
- BSFYKMAJHSUHSC-UHFFFAOYSA-N 8-(4-bromo-2,6-dimethylphenyl)-2-methyl-n-pentan-3-yl-6,7-dihydro-5h-pyrido[2,3-d]pyrimidin-4-amine Chemical compound C1CCC=2C(NC(CC)CC)=NC(C)=NC=2N1C1=C(C)C=C(Br)C=C1C BSFYKMAJHSUHSC-UHFFFAOYSA-N 0.000 description 1
- QQGDDTBRBSMMAQ-UHFFFAOYSA-N 8-(4-bromo-2,6-dimethylphenyl)-n,n-diethyl-2-methyl-6,7-dihydro-5h-pyrido[2,3-d]pyrimidin-4-amine Chemical compound C1CCC=2C(N(CC)CC)=NC(C)=NC=2N1C1=C(C)C=C(Br)C=C1C QQGDDTBRBSMMAQ-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- VCJQTLOUICAEMC-UHFFFAOYSA-N 8-[ethyl(propyl)amino]-6-methyl-4-(2,4,6-trimethylphenyl)-1,3-dihydropyrido[2,3-b]pyrazin-2-one Chemical compound C1C(=O)NC=2C(N(CC)CCC)=CC(C)=NC=2N1C1=C(C)C=C(C)C=C1C VCJQTLOUICAEMC-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 125000006519 CCH3 Chemical group 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 101150047265 COR2 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 102400000739 Corticotropin Human genes 0.000 description 1
- 101800000414 Corticotropin Proteins 0.000 description 1
- 229940122010 Corticotropin releasing factor antagonist Drugs 0.000 description 1
- 102100032165 Corticotropin-releasing factor-binding protein Human genes 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- GUUVPOWQJOLRAS-UHFFFAOYSA-N Diphenyl disulfide Chemical compound C=1C=CC=CC=1SSC1=CC=CC=C1 GUUVPOWQJOLRAS-UHFFFAOYSA-N 0.000 description 1
- 206010013883 Dwarfism Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 101100258328 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) crc-2 gene Proteins 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 241000206607 Porphyra umbilicalis Species 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 229910006074 SO2NH2 Inorganic materials 0.000 description 1
- 101100467189 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) QCR2 gene Proteins 0.000 description 1
- 101100391171 Schizosaccharomyces pombe (strain 972 / ATCC 24843) for3 gene Proteins 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 229910007161 Si(CH3)3 Inorganic materials 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- YCHIEIAHVXSUGW-UHFFFAOYSA-N [6-methyl-4-pentan-3-yloxy-2-(2,4,6-trimethylanilino)pyridin-3-yl]methanol Chemical compound CCC(CC)OC1=CC(C)=NC(NC=2C(=CC(C)=CC=2C)C)=C1CO YCHIEIAHVXSUGW-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 208000029650 alcohol withdrawal Diseases 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 150000005347 biaryls Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- MAPRDOKILZKGDP-UHFFFAOYSA-N bromo-chloro-iodomethanesulfonic acid Chemical group OS(=O)(=O)C(Cl)(Br)I MAPRDOKILZKGDP-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
- 229960000258 corticotropin Drugs 0.000 description 1
- 239000002769 corticotropin releasing factor antagonist Substances 0.000 description 1
- 108010083720 corticotropin releasing factor-binding protein Proteins 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- HMOJUCUJIXEKOH-UHFFFAOYSA-N dicyanoalumanylformonitrile Chemical compound N#C[Al](C#N)C#N HMOJUCUJIXEKOH-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- LKHZKAFQINWNAH-UHFFFAOYSA-N ethyl 3-[4-chloro-2-methyl-6-(2,4,6-trimethylanilino)pyrimidin-5-yl]-2-methylpropanoate Chemical compound CCOC(=O)C(C)CC1=C(Cl)N=C(C)N=C1NC1=C(C)C=C(C)C=C1C LKHZKAFQINWNAH-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- QHCCDDQKNUYGNC-UHFFFAOYSA-N n-ethylbutan-1-amine Chemical compound CCCCNCC QHCCDDQKNUYGNC-UHFFFAOYSA-N 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- PQPFFKCJENSZKL-UHFFFAOYSA-N pentan-3-amine Chemical compound CCC(N)CC PQPFFKCJENSZKL-UHFFFAOYSA-N 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical compound N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 description 1
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
- A61P5/42—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of mineralocorticosteroids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Obesity (AREA)
- Nutrition Science (AREA)
- Rheumatology (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
- Urology & Nephrology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Virology (AREA)
- Child & Adolescent Psychology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2465996P | 1996-08-27 | 1996-08-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA10980A true OA10980A (en) | 2001-11-02 |
Family
ID=21821740
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA9900039A OA10980A (en) | 1996-08-27 | 1999-02-25 | Substituted 6,6-hetero-bicyclic derivatives |
Country Status (41)
| Country | Link |
|---|---|
| EP (1) | EP0925298B1 (fr) |
| JP (1) | JP2000502722A (fr) |
| KR (1) | KR100457759B1 (fr) |
| CN (2) | CN1191236C (fr) |
| AP (1) | AP1164A (fr) |
| AR (2) | AR009321A1 (fr) |
| AT (1) | ATE264327T1 (fr) |
| AU (1) | AU726771C (fr) |
| BG (1) | BG64316B1 (fr) |
| BR (1) | BR9711262A (fr) |
| CA (1) | CA2263913C (fr) |
| CO (1) | CO4930259A1 (fr) |
| CZ (1) | CZ67799A3 (fr) |
| DE (1) | DE69728676T2 (fr) |
| DK (1) | DK0925298T3 (fr) |
| DZ (1) | DZ2299A1 (fr) |
| EA (1) | EA002607B1 (fr) |
| ES (1) | ES2216157T3 (fr) |
| GT (1) | GT199700093A (fr) |
| HK (1) | HK1019597A1 (fr) |
| HR (1) | HRP970452A2 (fr) |
| ID (1) | ID18189A (fr) |
| IL (1) | IL128049A (fr) |
| IS (1) | IS4970A (fr) |
| MY (1) | MY132671A (fr) |
| NO (1) | NO316273B1 (fr) |
| NZ (1) | NZ333728A (fr) |
| OA (1) | OA10980A (fr) |
| PA (1) | PA8435001A1 (fr) |
| PE (1) | PE108698A1 (fr) |
| PL (1) | PL331988A1 (fr) |
| PT (1) | PT925298E (fr) |
| SI (1) | SI0925298T1 (fr) |
| SK (1) | SK22599A3 (fr) |
| TN (1) | TNSN97144A1 (fr) |
| TR (1) | TR199900408T2 (fr) |
| TW (1) | TW477787B (fr) |
| UA (1) | UA66345C2 (fr) |
| WO (1) | WO1998008846A1 (fr) |
| YU (1) | YU35697A (fr) |
| ZA (1) | ZA977652B (fr) |
Families Citing this family (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6124289A (en) * | 1996-07-24 | 2000-09-26 | Dupont Pharmaceuticals Co. | Azolo triazines and pyrimidines |
| US6191131B1 (en) | 1997-07-23 | 2001-02-20 | Dupont Pharmaceuticals Company | Azolo triazines and pyrimidines |
| US6060478A (en) * | 1996-07-24 | 2000-05-09 | Dupont Pharmaceuticals | Azolo triazines and pyrimidines |
| US6313124B1 (en) | 1997-07-23 | 2001-11-06 | Dupont Pharmaceuticals Company | Tetrazine bicyclic compounds |
| US7094782B1 (en) | 1996-07-24 | 2006-08-22 | Bristol-Myers Squibb Company | Azolo triazines and pyrimidines |
| CZ292806B6 (cs) | 1996-08-06 | 2003-12-17 | Pfizer Inc. | Pyrido- nebo pyrimido-6,6- nebo -6,7-bicyklické deriváty, farmaceutické kompozice na jejich bázi |
| JP2001511813A (ja) * | 1997-02-18 | 2001-08-14 | ニューロクライン バイオサイエンシーズ，インコーポレイテッド | Ｃｒｆレセプターアンタゴニストおよびそれらに関連する方法 |
| US6482836B1 (en) | 1997-04-22 | 2002-11-19 | Charles Huang | CRF antagonistic quino- and quinazolines |
| NL1010018C2 (nl) * | 1997-09-09 | 1999-03-10 | Duphar Int Res | Chinoline en chinazoline derivaten met corticotropine releasing factor (CRF) antagonistische werking. |
| US6187777B1 (en) | 1998-02-06 | 2001-02-13 | Amgen Inc. | Compounds and methods which modulate feeding behavior and related diseases |
| ES2180338T3 (es) | 1998-11-12 | 2003-02-01 | Neurocrine Biosciences Inc | Antagonistas del receptor de crf y metodos relacionados. |
| JP2002529469A (ja) | 1998-11-12 | 2002-09-10 | ニューロクライン バイオサイエンシーズ， インコーポレイテッド | Ｃｒｆレセプターアンタゴニストおよびそれに関する方法 |
| JP2002536445A (ja) * | 1999-02-12 | 2002-10-29 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | オレキシン受容体アンタゴニストとしてのフェニル尿素およびフェニルチオ尿素誘導体 |
| US6432989B1 (en) * | 1999-08-27 | 2002-08-13 | Pfizer Inc | Use of CRF antagonists to treat circadian rhythm disorders |
| CZ20021086A3 (cs) | 1999-09-30 | 2002-10-16 | Neurogen Corporation | Alkylendiaminem substituované heterocykly |
| JP2003510365A (ja) | 1999-10-01 | 2003-03-18 | ジョンソン・アンド・ジョンソン・コンシューマー・カンパニーズ・インコーポレイテッド | 個人用ケア組成物により人間を鎮静するための方法 |
| IL139197A0 (en) | 1999-10-29 | 2001-11-25 | Pfizer Prod Inc | Use of corticotropin releasing factor antagonists and related compositions |
| US6525067B1 (en) * | 1999-11-23 | 2003-02-25 | Pfizer Inc | Substituted heterocyclic derivatives |
| EP1120662B1 (fr) | 2000-01-26 | 2006-03-01 | EM Microelectronic-Marin SA | Procédé pour tester un circuit intégré comportant des parties matérielles et/ou logicielles ayant un caractère de confidentialité |
| AU2001232271A1 (en) * | 2000-02-14 | 2001-08-20 | Japan Tobacco Inc. | Preventives/remedies for postoperative stress |
| US7235551B2 (en) | 2000-03-02 | 2007-06-26 | Smithkline Beecham Corporation | 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
| US6500839B2 (en) | 2000-05-18 | 2002-12-31 | Neurocrine Biosciences, Inc. | CRF receptor antagonists and methods relating thereto |
| ES2372028T3 (es) | 2000-10-23 | 2012-01-13 | Glaxosmithkline Llc | Nuevo compuesto de 8h-pirido[2,3-d]pirimidin-7-ona trisustituida para el tratamiento de enfermedades mediadas por la csbp/p38 quinasa. |
| PL366934A1 (en) * | 2001-04-30 | 2005-02-07 | Glaxo Group Limited | Fused pyrimidines as antagonists of the corticotropin releasing factor (crf) |
| GB0117396D0 (en) * | 2001-07-17 | 2001-09-05 | Glaxo Group Ltd | Chemical compounds |
| GB2384563A (en) | 2002-01-29 | 2003-07-30 | Johnson & Johnson Consumer | Method of measuring the stress or relaxation level of a mammal |
| CN1646131A (zh) | 2002-04-19 | 2005-07-27 | 史密丝克莱恩比彻姆公司 | 新化合物 |
| US7067658B2 (en) | 2002-09-30 | 2006-06-27 | Bristol-Myers Squibb Company | Pyridino and pyrimidino pyrazinones |
| AU2004205642C1 (en) | 2003-01-14 | 2012-01-12 | Arena Pharmaceuticals, Inc. | 1,2,3-trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia |
| GB0308208D0 (en) * | 2003-04-09 | 2003-05-14 | Glaxo Group Ltd | Chemical compounds |
| AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| WO2005007658A2 (fr) * | 2003-07-14 | 2005-01-27 | Arena Pharmaceuticals, Inc. | Derives aryle et heteroaryle condenses utilises comme modulateurs du metabolisme et prophylaxie et traitement des troubles metaboliques |
| WO2005014557A1 (fr) | 2003-08-12 | 2005-02-17 | F.Hoffmann-La Roche Ag | Derives de la tetrahydroquinazoline en tant qu'antagonistes cfr |
| EP1656145A1 (fr) | 2003-08-12 | 2006-05-17 | F. Hoffmann-La Roche Ag | Tetrahydroquinazolines spiro-substituees utilisees en tant qu'antagonistes du facteur de liberation de la corticotrophine (crf) |
| TW200510425A (en) | 2003-08-13 | 2005-03-16 | Japan Tobacco Inc | Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor |
| JP2006232849A (ja) * | 2003-08-13 | 2006-09-07 | Japan Tobacco Inc | 含窒素縮合環化合物及びそのｈｉｖインテグラーゼ阻害剤としての利用 |
| BRPI0507609A (pt) * | 2004-02-13 | 2007-07-03 | Pfizer Prod Inc | combinações terapêuticas de anti-psicóticos atìpicos com antagonistas de fator de liberação de corticotropina |
| DE102004018198A1 (de) | 2004-04-15 | 2005-11-03 | Merck Patent Gmbh | Sulfonamide |
| EP1828186A1 (fr) | 2004-12-13 | 2007-09-05 | Sunesis Pharmaceuticals, Inc. | Pyridopyrimidinones, dihydropyrimidopyrimidinones et pteridinones utiles en tant qu'inhibiteurs des kinases raf |
| UY29439A1 (es) | 2005-03-25 | 2006-10-02 | Glaxo Group Ltd | Nuevos compuestos |
| MY145343A (en) | 2005-03-25 | 2012-01-31 | Glaxo Group Ltd | Novel compounds |
| MX2007012951A (es) | 2005-03-25 | 2008-01-11 | Glaxo Group Ltd | Procedimiento para preparar derivados de pirido[2,3-d] pirimidin-7-ona y 3,4-dihidropirimidino[4,5-d]pirimidin-2(1h)-ona. |
| JP2008535822A (ja) | 2005-03-25 | 2008-09-04 | グラクソ グループ リミテッド | 新規化合物 |
| AU2006228378A1 (en) | 2005-03-31 | 2006-10-05 | Pfizer Products Inc. | Cyclopentapyridine and tetrahydroquinoline derivatives |
| NZ569817A (en) | 2005-12-21 | 2011-10-28 | Abbott Lab | Anti-viral compounds |
| US7763731B2 (en) | 2005-12-21 | 2010-07-27 | Abbott Laboratories | Anti-viral compounds |
| WO2007081517A2 (fr) | 2005-12-21 | 2007-07-19 | Abbott Laboratories | Composes anti-viraux |
| EP2090577B1 (fr) * | 2006-10-19 | 2017-04-05 | Signal Pharmaceuticals, LLC | Composés héteroaryliques, compositions les contenant et leur utilisation en tant qu'inhibiteurs de protein kinases |
| CA2672737A1 (fr) | 2006-12-20 | 2008-11-06 | Abbott Laboratories | Composes antiviraux |
| BRPI0811745B1 (pt) * | 2007-05-17 | 2019-06-04 | Helperby Therapeutics Limited | Compostos de 4-(pirrolidin-1-il)quinolina, uso e processo para a preparação dos mesmos, formulação farmacêutica -- |
| US9139592B2 (en) | 2010-06-14 | 2015-09-22 | Trt Pharma Inc. | Modulators of Nrf2 and uses thereof |
| SG188548A1 (en) | 2010-09-22 | 2013-04-30 | Arena Pharm Inc | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| JP6258937B2 (ja) * | 2012-08-24 | 2018-01-10 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 新規二環式ピリジン誘導体 |
| DK3096756T3 (da) | 2014-01-21 | 2024-08-05 | Neurocrine Biosciences Inc | CRF1-receptorantagonister til behandling af medfødt adrenal hyperplasi |
| NZ734220A (en) | 2015-01-06 | 2022-01-28 | Arena Pharm Inc | Methods of treating conditions related to the s1p1 receptor |
| PE20180395A1 (es) | 2015-06-04 | 2018-02-28 | Pfizer | Formas de dosificacion solidas de palbociclib |
| KR102603199B1 (ko) | 2015-06-22 | 2023-11-16 | 아레나 파마슈티칼스, 인크. | Ｓ1ｐ1 수용체-관련 장애에서의 사용을 위한 (ｒ)-2-(7-(4-시클로펜틸-3-(트리플루오로메틸)벤질옥시)-1,2,3,4-테트라히드로시클로-펜타[ｂ]인돌-3-일)아세트산 (화합물 1)의 결정성 ｌ-아르기닌 염 |
| US10233188B2 (en) | 2016-08-15 | 2019-03-19 | Pfizer Inc. | CDK2/4/6 inhibitors |
| KR102009756B1 (ko) * | 2017-01-06 | 2019-08-12 | 고려대학교 세종산학협력단 | 신규한 퀴놀리논 유도체 및 이를 유효성분으로 포함하는 천식 또는 아토피 등의 알러지성 질환의 예방 또는 치료용 약학 조성물 |
| BR112020024762A2 (pt) | 2018-06-06 | 2021-03-23 | Arena Pharmaceuticals, Inc. | métodos de tratamento de condições relacionadas ao receptor s1p1 |
| BR112021010847A2 (pt) | 2018-12-07 | 2021-09-08 | Neurocrine Biosciences Inc. | Antagonista de receptor de crf1, formulações farmacêuticas e formas sólidas das mesmas para o tratamento de hiperplasia adrenal congênita |
| CN115160221B (zh) * | 2022-07-26 | 2024-10-18 | 恩祺生物科技(上海)有限公司 | 德立替尼晶型化合物和用途 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW370529B (en) * | 1992-12-17 | 1999-09-21 | Pfizer | Pyrazolopyrimidines |
| DK0674641T3 (da) * | 1992-12-17 | 1999-09-27 | Pfizer | Pyrrolopyrimidiner som CRF-antagonister |
| TW574214B (en) * | 1994-06-08 | 2004-02-01 | Pfizer | Corticotropin releasing factor antagonists |
| WO1995034563A1 (fr) * | 1994-06-16 | 1995-12-21 | Pfizer Inc. | Pyrazolo et pyrrolopyridines |
| EP0729758A3 (fr) * | 1995-03-02 | 1997-10-29 | Pfizer | Pyrazolopyrimidines et pyrrolopyrimidines pour traiter les troubles neuronaux et autres maladies |
| DE69603240T2 (de) * | 1995-05-12 | 2000-01-05 | Neurogen Corp., Branford | Neue deazapurinderivate; eine neue klasse von crf1-spezifischen liganden |
| US6403599B1 (en) * | 1995-11-08 | 2002-06-11 | Pfizer Inc | Corticotropin releasing factor antagonists |
| PT778277E (pt) * | 1995-12-08 | 2003-11-28 | Pfizer | Derivados heterociclicos substituidos como antagonistas do crf |
-
1997
- 1997-07-15 TW TW086109990A patent/TW477787B/zh not_active IP Right Cessation
- 1997-07-21 SK SK225-99A patent/SK22599A3/sk unknown
- 1997-07-21 NZ NZ333728A patent/NZ333728A/xx unknown
- 1997-07-21 CZ CZ99677A patent/CZ67799A3/cs unknown
- 1997-07-21 CA CA002263913A patent/CA2263913C/fr not_active Expired - Fee Related
- 1997-07-21 PL PL97331988A patent/PL331988A1/xx unknown
- 1997-07-21 DE DE69728676T patent/DE69728676T2/de not_active Expired - Fee Related
- 1997-07-21 SI SI9730642T patent/SI0925298T1/xx unknown
- 1997-07-21 CN CNB021020574A patent/CN1191236C/zh not_active Expired - Fee Related
- 1997-07-21 DK DK97929464T patent/DK0925298T3/da active
- 1997-07-21 EP EP97929464A patent/EP0925298B1/fr not_active Expired - Lifetime
- 1997-07-21 TR TR1999/00408T patent/TR199900408T2/xx unknown
- 1997-07-21 PT PT97929464T patent/PT925298E/pt unknown
- 1997-07-21 KR KR10-1999-7001619A patent/KR100457759B1/ko not_active IP Right Cessation
- 1997-07-21 ES ES97929464T patent/ES2216157T3/es not_active Expired - Lifetime
- 1997-07-21 WO PCT/IB1997/000904 patent/WO1998008846A1/fr not_active Application Discontinuation
- 1997-07-21 EA EA199900166A patent/EA002607B1/ru not_active IP Right Cessation
- 1997-07-21 JP JP10511427A patent/JP2000502722A/ja active Pending
- 1997-07-21 UA UA99020647A patent/UA66345C2/uk unknown
- 1997-07-21 AT AT97929464T patent/ATE264327T1/de not_active IP Right Cessation
- 1997-07-21 AU AU33557/97A patent/AU726771C/en not_active Ceased
- 1997-07-21 BR BR9711262A patent/BR9711262A/pt not_active Application Discontinuation
- 1997-07-21 IL IL12804997A patent/IL128049A/en not_active IP Right Cessation
- 1997-07-21 CN CNB971973555A patent/CN1138774C/zh not_active Expired - Fee Related
- 1997-07-30 PA PA19978435001A patent/PA8435001A1/es unknown
- 1997-08-13 GT GT199700093A patent/GT199700093A/es unknown
- 1997-08-21 AP APAP/P/1997/001076A patent/AP1164A/en active
- 1997-08-22 HR HR60/024,659A patent/HRP970452A2/hr not_active Application Discontinuation
- 1997-08-22 PE PE1997000751A patent/PE108698A1/es not_active Application Discontinuation
- 1997-08-25 ID IDP972952A patent/ID18189A/id unknown
- 1997-08-25 AR ARP970103851A patent/AR009321A1/es not_active Application Discontinuation
- 1997-08-26 CO CO97049282A patent/CO4930259A1/es unknown
- 1997-08-26 ZA ZA977652A patent/ZA977652B/xx unknown
- 1997-08-26 DZ DZ970149A patent/DZ2299A1/fr active
- 1997-08-26 MY MYPI97003918A patent/MY132671A/en unknown
- 1997-08-26 YU YU35697A patent/YU35697A/sr unknown
- 1997-08-26 TN TNTNSN97144A patent/TNSN97144A1/fr unknown
-
1999
- 1999-02-05 IS IS4970A patent/IS4970A/is unknown
- 1999-02-22 BG BG103192A patent/BG64316B1/bg active Active
- 1999-02-25 OA OA9900039A patent/OA10980A/en unknown
- 1999-02-25 NO NO19990892A patent/NO316273B1/no not_active IP Right Cessation
- 1999-10-25 HK HK99104747A patent/HK1019597A1/xx not_active IP Right Cessation
-
2001
- 2001-01-10 AR ARP010100097A patent/AR026826A1/es unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| OA10980A (en) | Substituted 6,6-hetero-bicyclic derivatives | |
| CA2262692C (fr) | Derives 6,6- ou 6,7-bicycliques contenant pyrido ou pyrimido substitues | |
| AU2023270195A1 (en) | 2,3-dihydroquinazolin compounds as NAV1.8 inhibitors | |
| EP0923582B1 (fr) | Derives 6,5-hetero-bicycliques substitues | |
| CN110382500B (zh) | 用于ido和tdo双重抑制剂的脲类化合物 | |
| JP5972964B2 (ja) | 抗腫瘍剤としての三環式および四環式ピラゾロ［３，４−ｂ］ピリジン化合物 | |
| JP2004203751A (ja) | 置換６，６−ヘテロ二環式誘導体 | |
| EP2789614A1 (fr) | Azaindazoles comme modulateurs de la kinase Btk et son utilisation | |
| CA2114727C (fr) | Derives quinoline utilises comme immunostimulants | |
| US6875769B2 (en) | Substituted6,6-hetero-bicyclicderivatives | |
| TW202434229A (zh) | 抑制ｐｋｍｙｔ１之化合物 | |
| TW202239409A (zh) | 化合物 | |
| JPH0959277A (ja) | ６−アミノメチル置換キノリン安息香酸類の製造方法 | |
| MXPA99001309A (en) | Substituted pyrido- or pyrimido-containing 6,6- or 6,7-bicyclic derivatives |