SK11402000A3 - Cyklické n-acylaminoderiváty - Google Patents

Cyklické n-acylaminoderiváty Download PDF

Info

Publication number: SK11402000A3
Authority: SK; Slovakia
Prior art keywords: group; lower alkyl; optionally substituted; phenyl; alkyl group
Prior art date: 1998-02-04

Application number

SK1140-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Yoshimi Tsuchiya

Takashi Nomoto

Hirokazu Ohsawa

Kumiko Kawakami

Kenji Ohwaki

Masaru Nishikibe

Original Assignee

Banyu Pharmaceutical Co., Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-02-04

Filing date

1999-02-03

Publication date

2001-03-12

1999-02-03 Application filed by Banyu Pharmaceutical Co., Ltd filed Critical Banyu Pharmaceutical Co., Ltd

2001-03-12 Publication of SK11402000A3 publication Critical patent/SK11402000A3/sk

Links

150000001875 compounds Chemical class 0.000 claims abstract description 311
125000000217 alkyl group Chemical group 0.000 claims abstract description 147
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 80
125000001931 aliphatic group Chemical group 0.000 claims abstract description 61
125000003118 aryl group Chemical group 0.000 claims abstract description 25
125000005843 halogen group Chemical group 0.000 claims abstract description 19
229910052731 fluorine Inorganic materials 0.000 claims abstract description 16
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 14
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 14
125000003545 alkoxy group Chemical group 0.000 claims abstract description 11
230000000241 respiratory effect Effects 0.000 claims abstract description 9
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 7
229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 6
125000004434 sulfur atom Chemical group 0.000 claims abstract description 5
208000014001 urinary system disease Diseases 0.000 claims abstract description 4
-1 3,3-difluorocyclopentyl group Chemical group 0.000 claims description 313
238000000034 method Methods 0.000 claims description 94
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 89
238000006243 chemical reaction Methods 0.000 claims description 81
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 55
125000001841 imino group Chemical group [H]N=* 0.000 claims description 54
125000006239 protecting group Chemical group 0.000 claims description 47
229910052739 hydrogen Inorganic materials 0.000 claims description 45
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 44
239000001257 hydrogen Substances 0.000 claims description 40
125000004432 carbon atom Chemical group C* 0.000 claims description 39
DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 38
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
125000004043 oxo group Chemical group O=* 0.000 claims description 29
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
238000006467 substitution reaction Methods 0.000 claims description 25
125000002837 carbocyclic group Chemical group 0.000 claims description 22
125000001424 substituent group Chemical group 0.000 claims description 22
125000003277 amino group Chemical group 0.000 claims description 21
238000002360 preparation method Methods 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 19
229910052757 nitrogen Inorganic materials 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims description 15
239000003814 drug Substances 0.000 claims description 14
229910052799 carbon Inorganic materials 0.000 claims description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 12
BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 claims description 12
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 9
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
230000008569 process Effects 0.000 claims description 7
238000006268 reductive amination reaction Methods 0.000 claims description 7
LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims description 6
150000001299 aldehydes Chemical class 0.000 claims description 6
238000010511 deprotection reaction Methods 0.000 claims description 6
230000002496 gastric effect Effects 0.000 claims description 6
125000000623 heterocyclic group Chemical group 0.000 claims description 6
150000002576 ketones Chemical class 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
102000007202 Muscarinic M3 Receptor Human genes 0.000 claims description 5
108010008405 Muscarinic M3 Receptor Proteins 0.000 claims description 5
ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical group C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 5
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
NGYPTZUYMBVDNN-UTKZUKDTSA-N (2r)-1-(2,8-diazaspiro[4.5]decan-8-yl)-2-[(1r)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylethanone Chemical compound C([C@H]1[C@](O)(C(=O)N2CCC3(CNCC3)CC2)C=2C=CC=CC=2)CC(F)(F)C1 NGYPTZUYMBVDNN-UTKZUKDTSA-N 0.000 claims description 3
WVAXSPFXHVXZHT-BEFAXECRSA-N (2r)-1-(4-amino-4-methylpiperidin-1-yl)-2-[(1r)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylethanone Chemical compound C1CC(C)(N)CCN1C(=O)[C@](O)(C=1C=CC=CC=1)[C@H]1CC(F)(F)CC1 WVAXSPFXHVXZHT-BEFAXECRSA-N 0.000 claims description 3
206010006458 Bronchitis chronic Diseases 0.000 claims description 3
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
206010010904 Convulsion Diseases 0.000 claims description 3
206010063057 Cystitis noninfective Diseases 0.000 claims description 3
208000008967 Enuresis Diseases 0.000 claims description 3
206010020651 Hyperkinesia Diseases 0.000 claims description 3
208000000269 Hyperkinesis Diseases 0.000 claims description 3
206010020853 Hypertonic bladder Diseases 0.000 claims description 3
206010027566 Micturition urgency Diseases 0.000 claims description 3
208000000693 Neurogenic Urinary Bladder Diseases 0.000 claims description 3
206010029279 Neurogenic bladder Diseases 0.000 claims description 3
102100035593 POU domain, class 2, transcription factor 1 Human genes 0.000 claims description 3
101710084414 POU domain, class 2, transcription factor 1 Proteins 0.000 claims description 3
208000007107 Stomach Ulcer Diseases 0.000 claims description 3
206010046543 Urinary incontinence Diseases 0.000 claims description 3
208000006673 asthma Diseases 0.000 claims description 3
206010006451 bronchitis Diseases 0.000 claims description 3
208000007451 chronic bronchitis Diseases 0.000 claims description 3
201000003139 chronic cystitis Diseases 0.000 claims description 3
230000001684 chronic effect Effects 0.000 claims description 3
206010009887 colitis Diseases 0.000 claims description 3
230000036461 convulsion Effects 0.000 claims description 3
230000002920 convulsive effect Effects 0.000 claims description 3
230000001079 digestive effect Effects 0.000 claims description 3
208000007784 diverticulitis Diseases 0.000 claims description 3
208000000718 duodenal ulcer Diseases 0.000 claims description 3
206010013990 dysuria Diseases 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
201000003152 motion sickness Diseases 0.000 claims description 3
230000001537 neural effect Effects 0.000 claims description 3
208000005346 nocturnal enuresis Diseases 0.000 claims description 3
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 3
230000002685 pulmonary effect Effects 0.000 claims description 3
208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
206010039083 rhinitis Diseases 0.000 claims description 3
230000016160 smooth muscle contraction Effects 0.000 claims description 3
208000011580 syndromic disease Diseases 0.000 claims description 3
TYQOUVZXRGAGRO-FJSNOKNSSA-N (2r)-2-[(1r)-3,3-difluorocyclopentyl]-1-(1-ethyl-2,8-diazaspiro[4.5]decan-8-yl)-2-hydroxy-2-phenylethanone Chemical compound CCC1NCCC11CCN(C(=O)[C@@](O)([C@H]2CC(F)(F)CC2)C=2C=CC=CC=2)CC1 TYQOUVZXRGAGRO-FJSNOKNSSA-N 0.000 claims description 2
MWDVJZGNPZBMOG-KLKIPRAKSA-N (2r)-2-[(1r)-3,3-difluorocyclopentyl]-2-hydroxy-1-(1-methyl-2,8-diazaspiro[4.5]decan-8-yl)-2-phenylethanone Chemical compound CC1NCCC11CCN(C(=O)[C@@](O)([C@H]2CC(F)(F)CC2)C=2C=CC=CC=2)CC1 MWDVJZGNPZBMOG-KLKIPRAKSA-N 0.000 claims description 2
GNSGYEFDWHNYFA-KLKIPRAKSA-N (2r)-2-[(1r)-3,3-difluorocyclopentyl]-2-hydroxy-1-(4-methyl-2,8-diazaspiro[4.5]decan-2-yl)-2-phenylethanone Chemical compound CC1CN(C(=O)[C@@](O)([C@H]2CC(F)(F)CC2)C=2C=CC=CC=2)CC11CCNCC1 GNSGYEFDWHNYFA-KLKIPRAKSA-N 0.000 claims description 2
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 claims 4
HDZDTLNHNKPXRL-FSFDPXQMSA-N (2r)-1-(2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrol-5-yl)-2-[(1r)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylethanone Chemical compound C([C@H]1[C@](O)(C(=O)N2CC3CNCC3C2)C=2C=CC=CC=2)CC(F)(F)C1 HDZDTLNHNKPXRL-FSFDPXQMSA-N 0.000 claims 1
JBVFPTKZYNRPII-KDOFPFPSSA-N (2r)-1-(4-aminopiperidin-1-yl)-2-[(1r)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylethanone Chemical compound C1CC(N)CCN1C(=O)[C@](O)(C=1C=CC=CC=1)[C@H]1CC(F)(F)CC1 JBVFPTKZYNRPII-KDOFPFPSSA-N 0.000 claims 1
206010022998 Irritability Diseases 0.000 claims 1
239000004480 active ingredient Substances 0.000 claims 1
230000000968 intestinal effect Effects 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 18
230000002411 adverse Effects 0.000 abstract description 5
208000010643 digestive system disease Diseases 0.000 abstract description 4
230000003551 muscarinic effect Effects 0.000 abstract description 4
230000009471 action Effects 0.000 abstract description 3
208000023504 respiratory system disease Diseases 0.000 abstract description 3
230000003042 antagnostic effect Effects 0.000 abstract description 2
230000003389 potentiating effect Effects 0.000 abstract description 2
230000002485 urinary effect Effects 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 138
239000000243 solution Substances 0.000 description 98
239000000203 mixture Substances 0.000 description 84
230000015572 biosynthetic process Effects 0.000 description 83
238000003786 synthesis reaction Methods 0.000 description 82
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 81
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 79
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
239000002904 solvent Substances 0.000 description 75
230000002829 reductive effect Effects 0.000 description 62
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 56
239000011541 reaction mixture Substances 0.000 description 54
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
229910001868 water Inorganic materials 0.000 description 39
239000012267 brine Substances 0.000 description 34
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
239000012230 colorless oil Substances 0.000 description 33
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
229920006395 saturated elastomer Polymers 0.000 description 25
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 24
239000003054 catalyst Substances 0.000 description 23
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
239000002585 base Substances 0.000 description 20
238000001816 cooling Methods 0.000 description 20
238000012360 testing method Methods 0.000 description 18
238000007792 addition Methods 0.000 description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
238000000746 purification Methods 0.000 description 17
239000000126 substance Substances 0.000 description 17
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 16
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 16
150000002431 hydrogen Chemical class 0.000 description 16
238000004519 manufacturing process Methods 0.000 description 16
238000006722 reduction reaction Methods 0.000 description 16
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 16
230000009467 reduction Effects 0.000 description 15
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 14
238000010898 silica gel chromatography Methods 0.000 description 14
239000007787 solid Substances 0.000 description 14
239000012156 elution solvent Substances 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 12
108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 12
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 description 11
239000012442 inert solvent Substances 0.000 description 11
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 11
102000005962 receptors Human genes 0.000 description 11
108020003175 receptors Proteins 0.000 description 11
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
230000008485 antagonism Effects 0.000 description 10
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
235000017557 sodium bicarbonate Nutrition 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
150000001721 carbon Chemical group 0.000 description 9
238000010531 catalytic reduction reaction Methods 0.000 description 9
238000012746 preparative thin layer chromatography Methods 0.000 description 9
238000003756 stirring Methods 0.000 description 9
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
235000019270 ammonium chloride Nutrition 0.000 description 8
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
125000004122 cyclic group Chemical group 0.000 description 8
239000012433 hydrogen halide Substances 0.000 description 8
229910000039 hydrogen halide Inorganic materials 0.000 description 8
WFLUEQCOAQCQLP-ZDUSSCGKSA-N (2r)-2-cyclopentyl-2-hydroxy-2-phenylacetic acid Chemical compound C1([C@](O)(C(=O)O)C=2C=CC=CC=2)CCCC1 WFLUEQCOAQCQLP-ZDUSSCGKSA-N 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
229910021529 ammonia Inorganic materials 0.000 description 7
JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 description 7
239000003826 tablet Substances 0.000 description 7
210000003437 trachea Anatomy 0.000 description 7
238000011282 treatment Methods 0.000 description 7
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Substances C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 7
GPUGYUSBIRXKND-MFKMUULPSA-N (2r)-2-[(1r)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetic acid Chemical compound C([C@H]1[C@](O)(C(=O)O)C=2C=CC=CC=2)CC(F)(F)C1 GPUGYUSBIRXKND-MFKMUULPSA-N 0.000 description 6
241000282472 Canis lupus familiaris Species 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 6
AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 6
229960004484 carbachol Drugs 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
229940079593 drug Drugs 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
229910052987 metal hydride Inorganic materials 0.000 description 6
150000004681 metal hydrides Chemical class 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
239000000843 powder Substances 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
230000035484 reaction time Effects 0.000 description 6
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
125000003710 aryl alkyl group Chemical group 0.000 description 5
238000003556 assay Methods 0.000 description 5
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
231100000673 dose–response relationship Toxicity 0.000 description 5
238000001914 filtration Methods 0.000 description 5
238000006317 isomerization reaction Methods 0.000 description 5
239000007788 liquid Substances 0.000 description 5
238000007248 oxidative elimination reaction Methods 0.000 description 5
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HGAFAPSNPSAJNE-UHFFFAOYSA-N tert-butyl 4-methyl-4-(phenylmethoxycarbonylaminomethyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(C)CNC(=O)OCC1=CC=CC=C1 HGAFAPSNPSAJNE-UHFFFAOYSA-N 0.000 description 1
PDTZMULNKGUIEJ-UHFFFAOYSA-N tert-butyl 4-methylidenepiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=C)CC1 PDTZMULNKGUIEJ-UHFFFAOYSA-N 0.000 description 1
CGMXZJTYQCMEKV-HXOBKFHXSA-N tert-butyl n-[1-[(2r)-2-[(1r)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetyl]piperidin-4-yl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1C(=O)[C@](O)(C=1C=CC=CC=1)[C@H]1CC(F)(F)CC1 CGMXZJTYQCMEKV-HXOBKFHXSA-N 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
150000003510 tertiary aliphatic amines Chemical class 0.000 description 1
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000007704 transition Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000003871 white petrolatum Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1
108020001612 μ-opioid receptors Proteins 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
- 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
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- 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
- C07D471/08—Bridged systems
- 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
- C07D471/10—Spiro-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pulmonology (AREA)
Urology & Nephrology (AREA)
Otolaryngology (AREA)
Rheumatology (AREA)
Hospice & Palliative Care (AREA)
Pain & Pain Management (AREA)
Nutrition Science (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Fats And Perfumes (AREA)
Other In-Based Heterocyclic Compounds (AREA)

SK1140-2000A 1998-02-04 1999-02-03 Cyklické n-acylaminoderiváty SK11402000A3 (sk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
JP3806398		1998-02-04
JP22872698		1998-07-29
PCT/JP1999/000462 WO1999040070A1 (fr)	1998-02-04	1999-02-03	Derives d'amine n-acyle cyclique

Publications (1)

Publication Number	Publication Date
SK11402000A3 true SK11402000A3 (sk)	2001-03-12

Family

ID=26377245

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1140-2000A SK11402000A3 (sk)	1998-02-04	1999-02-03	Cyklické n-acylaminoderiváty

Country Status (24)

Country	Link
US (1)	US6140333A (ja)
EP (1)	EP1061076B1 (ja)
JP (1)	JP3613179B2 (ja)
KR (1)	KR20010040693A (ja)
CN (1)	CN1290251A (ja)
AR (1)	AR015512A1 (ja)
AT (1)	ATE284389T1 (ja)
AU (1)	AU745995B2 (ja)
BG (1)	BG104663A (ja)
BR (1)	BR9908351A (ja)
CA (1)	CA2317444C (ja)
DE (1)	DE69922494T2 (ja)
EE (1)	EE200000458A (ja)
ES (1)	ES2235458T3 (ja)
HR (1)	HRP20000495B1 (ja)
HU (1)	HUP0102404A2 (ja)
IL (1)	IL137166A0 (ja)
IS (1)	IS5580A (ja)
PE (1)	PE20000263A1 (ja)
PL (1)	PL342735A1 (ja)
SK (1)	SK11402000A3 (ja)
TR (1)	TR200002241T2 (ja)
WO (1)	WO1999040070A1 (ja)
YU (1)	YU41100A (ja)

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SE0303090D0 (sv)	2003-11-20	2003-11-20	Astrazeneca Ab	Novel compounds
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AR095079A1 (es)	2013-03-12	2015-09-16	Hoffmann La Roche	Derivados de octahidro-pirrolo[3,4-c]-pirrol y piridina-fenilo
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SI3074400T1 (en)	2013-11-26	2018-03-30	F. Hoffmann-La Roche Ag	Octahydro-cyclobut (1,2-c, 3,4-cy) dipyrrole derivatives as autoantaxine inhibitors
CN106029667B (zh)	2014-03-26	2019-08-23	豪夫迈·罗氏有限公司	作为自分泌运动因子(atx)和溶血磷脂酸(lpa)生产抑制剂的稠合[1,4]二氮杂*化合物
MX370659B (es)	2014-03-26	2019-12-19	Hoffmann La Roche	Compuestos bicíclicos como inhibidores de producción de autotaxina (atx) y ácido lisofosfatídico (lpa).
US10857157B2 (en)	2015-01-26	2020-12-08	BioAxone BioSciences, Inc.	Treatment of cerebral cavernous malformations and cerebral aneurysms with rho kinase inhibitors
US9687483B2 (en)	2015-01-26	2017-06-27	BioAxone BioSciences, Inc.	Treatment of cerebral cavernous malformations and cerebral aneurysms with Rho kinase inhibitors
US10149856B2 (en)	2015-01-26	2018-12-11	BioAxone BioSciences, Inc.	Treatment of cerebral cavernous malformations and cerebral aneurysms with rho kinase inhibitors
US10106525B2 (en)	2015-01-26	2018-10-23	BioAxone BioSciences, Inc.	Rho kinase inhibitor BA-1049 (R) and active metabolites thereof
MA41898A (fr)	2015-04-10	2018-02-13	Hoffmann La Roche	Dérivés de quinazolinone bicyclique
KR20180043837A (ko)	2015-09-04	2018-04-30	에프. 호프만-라 로슈 아게	페녹시메틸 유도체
JP6846414B2 (ja)	2015-09-24	2021-03-24	エフ．ホフマン−ラロシュアーゲーＦ．Ｈｏｆｆｍａｎｎ−ＬａＲｏｃｈｅＡｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ	Ａｔｘ阻害剤としての二環式化合物
JP6876685B2 (ja)	2015-09-24	2021-05-26	エフ．ホフマン−ラロシュアーゲーＦ．Ｈｏｆｆｍａｎｎ−ＬａＲｏｃｈｅＡｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ	Ａｔｘ阻害剤としての二環式化合物
RU2724899C2 (ru)	2015-09-24	2020-06-26	Ф. Хоффманн-Ля Рош Аг	Новые бициклические соединения в качестве дуальных ингибиторов atx/ca
RU2725138C2 (ru)	2015-09-24	2020-06-30	Ф. Хоффманн-Ля Рош Аг	Новые бициклические соединения в качестве двойных ингибиторов аутотаксина (atx)/карбоангидразы (ca)
US11198680B2 (en)	2016-12-21	2021-12-14	BioAxone BioSciences, Inc.	Rho kinase inhibitor BA-1049 (R) and active metabolites thereof
CN110382484B (zh)	2017-03-16	2022-12-06	豪夫迈·罗氏有限公司	新的作为atx抑制剂的二环化合物
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1999
- 1999-02-03 EP EP99902825A patent/EP1061076B1/en not_active Expired - Lifetime
- 1999-02-03 AU AU22986/99A patent/AU745995B2/en not_active Ceased
- 1999-02-03 WO PCT/JP1999/000462 patent/WO1999040070A1/ja active IP Right Grant
- 1999-02-03 ES ES99902825T patent/ES2235458T3/es not_active Expired - Lifetime
- 1999-02-03 CA CA002317444A patent/CA2317444C/en not_active Expired - Fee Related
- 1999-02-03 AR ARP990100449A patent/AR015512A1/es unknown
- 1999-02-03 AT AT99902825T patent/ATE284389T1/de not_active IP Right Cessation
- 1999-02-03 SK SK1140-2000A patent/SK11402000A3/sk unknown
- 1999-02-03 YU YU41100A patent/YU41100A/sh unknown
- 1999-02-03 JP JP2000530500A patent/JP3613179B2/ja not_active Expired - Fee Related
- 1999-02-03 HU HU0102404A patent/HUP0102404A2/hu unknown
- 1999-02-03 TR TR2000/02241T patent/TR200002241T2/xx unknown
- 1999-02-03 PL PL99342735A patent/PL342735A1/xx unknown
- 1999-02-03 EE EEP200000458A patent/EE200000458A/xx unknown
- 1999-02-03 DE DE69922494T patent/DE69922494T2/de not_active Expired - Lifetime
- 1999-02-03 IL IL13716699A patent/IL137166A0/xx unknown
- 1999-02-03 BR BR9908351-5A patent/BR9908351A/pt not_active Application Discontinuation
- 1999-02-03 KR KR1020007008571A patent/KR20010040693A/ko not_active Application Discontinuation
- 1999-02-03 CN CN99802687A patent/CN1290251A/zh active Pending
- 1999-02-04 US US09/244,985 patent/US6140333A/en not_active Expired - Fee Related
- 1999-02-04 PE PE1999000093A patent/PE20000263A1/es not_active Application Discontinuation
2000
- 2000-07-21 HR HR20000495A patent/HRP20000495B1/xx not_active IP Right Cessation
- 2000-08-02 IS IS5580A patent/IS5580A/is unknown
- 2000-08-04 BG BG104663A patent/BG104663A/xx unknown

Also Published As

Publication number	Publication date
AU745995B2 (en)	2002-04-11
HUP0102404A2 (hu)	2001-11-28
YU41100A (sh)	2002-06-19
CA2317444C (en)	2008-12-02
IS5580A (is)	2000-08-02
EP1061076B1 (en)	2004-12-08
HRP20000495B1 (en)	2005-12-31
US6140333A (en)	2000-10-31
TR200002241T2 (tr)	2000-11-21
EP1061076A1 (en)	2000-12-20
JP3613179B2 (ja)	2005-01-26
CN1290251A (zh)	2001-04-04
EP1061076A4 (en)	2001-05-02
ATE284389T1 (de)	2004-12-15
WO1999040070A1 (fr)	1999-08-12
CA2317444A1 (en)	1999-08-12
PE20000263A1 (es)	2000-04-25
BG104663A (en)	2001-09-28
KR20010040693A (ko)	2001-05-15
HRP20000495A2 (en)	2003-06-30
BR9908351A (pt)	2001-11-20
DE69922494T2 (de)	2005-05-25
AU2298699A (en)	1999-08-23
DE69922494D1 (de)	2005-01-13
ES2235458T3 (es)	2005-07-01
AR015512A1 (es)	2001-05-02
IL137166A0 (en)	2001-07-24
EE200000458A (et)	2002-02-15
PL342735A1 (en)	2001-07-02

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