IL109316A - History 1, 5 - Benzodiazepines, their preparation and pharmaceutical preparations containing them - Google Patents

History 1, 5 - Benzodiazepines, their preparation and pharmaceutical preparations containing them

Info

Publication number: IL109316A
Authority: IL; Israel
Prior art keywords: phenyl; 4alkyl; group; formula; hydroxy
Prior art date: 1993-04-15

Application number

IL10931694A

Other languages

English (en)

Hebrew (he)

Other versions

IL109316A0 (en

Original Assignee

Glaxo Inc

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.)

1993-04-15

Filing date

1994-04-13

Publication date

1999-03-12

1994-04-13 Application filed by Glaxo Inc filed Critical Glaxo Inc

1994-07-31 Publication of IL109316A0 publication Critical patent/IL109316A0/xx

1999-03-12 Publication of IL109316A publication Critical patent/IL109316A/en

Links

238000002360 preparation method Methods 0.000 title claims description 10
239000008194 pharmaceutical composition Substances 0.000 title claims description 6
ZVAPWJGRRUHKGP-UHFFFAOYSA-N 1h-1,5-benzodiazepine Chemical class N1C=CC=NC2=CC=CC=C12 ZVAPWJGRRUHKGP-UHFFFAOYSA-N 0.000 title description 3
238000011282 treatment Methods 0.000 claims abstract description 13
239000003814 drug Substances 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 151
-1 cyano, carboxy Chemical group 0.000 claims description 78
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 64
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 53
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 40
239000001257 hydrogen Substances 0.000 claims description 33
229910052739 hydrogen Inorganic materials 0.000 claims description 33
150000001412 amines Chemical class 0.000 claims description 30
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 24
150000002431 hydrogen Chemical group 0.000 claims description 22
238000000034 method Methods 0.000 claims description 22
150000002367 halogens Chemical class 0.000 claims description 21
229910052736 halogen Inorganic materials 0.000 claims description 20
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
125000000217 alkyl group Chemical group 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 17
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 14
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 14
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
229910052757 nitrogen Inorganic materials 0.000 claims description 13
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 12
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
239000011737 fluorine Substances 0.000 claims description 11
229910052731 fluorine Inorganic materials 0.000 claims description 11
230000008569 process Effects 0.000 claims description 11
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
239000000460 chlorine Substances 0.000 claims description 9
229910052801 chlorine Inorganic materials 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 7
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 7
125000005605 benzo group Chemical group 0.000 claims description 7
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
239000012453 solvate Substances 0.000 claims description 7
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 claims description 6
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
125000001041 indolyl group Chemical group 0.000 claims description 5
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
125000003831 tetrazolyl group Chemical group 0.000 claims description 5
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 4
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
230000002496 gastric effect Effects 0.000 claims description 4
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000000623 heterocyclic group Chemical group 0.000 claims description 3
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
230000001225 therapeutic effect Effects 0.000 claims description 3
229930192474 thiophene Natural products 0.000 claims description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims description 2
SXEIOMJBLIDGON-UHFFFAOYSA-N [dimethylamino(hydroxy)methyl] hypofluorite Chemical compound CN(C)C(O)OF SXEIOMJBLIDGON-UHFFFAOYSA-N 0.000 claims description 2
MRSGWFMVFXCOIR-UHFFFAOYSA-N [fluoro(methyl)amino]-methoxymethanol Chemical compound COC(O)N(C)F MRSGWFMVFXCOIR-UHFFFAOYSA-N 0.000 claims description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
230000008901 benefit Effects 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
238000002560 therapeutic procedure Methods 0.000 claims description 2
229910006069 SO3H Inorganic materials 0.000 claims 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
239000000969 carrier Substances 0.000 claims 1
CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 claims 1
IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 abstract description 18
101800001982 Cholecystokinin Proteins 0.000 abstract description 15
102100025841 Cholecystokinin Human genes 0.000 abstract description 14
229940107137 cholecystokinin Drugs 0.000 abstract description 14
108010089335 Cholecystokinin A Receptor Proteins 0.000 abstract description 8
102100034927 Cholecystokinin receptor type A Human genes 0.000 abstract description 8
108010052343 Gastrins Proteins 0.000 abstract description 8
AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 abstract description 8
241000124008 Mammalia Species 0.000 abstract description 4
229940088597 hormone Drugs 0.000 abstract description 4
239000005556 hormone Substances 0.000 abstract description 4
208000008589 Obesity Diseases 0.000 abstract description 3
229940125709 anorectic agent Drugs 0.000 abstract description 3
239000002830 appetite depressant Substances 0.000 abstract description 3
235000020824 obesity Nutrition 0.000 abstract description 3
230000004580 weight loss Effects 0.000 abstract description 2
102100021022 Gastrin Human genes 0.000 abstract 1
230000001270 agonistic effect Effects 0.000 abstract 1
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 abstract 1
238000012423 maintenance Methods 0.000 abstract 1
230000003893 regulation of appetite Effects 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
239000000243 solution Substances 0.000 description 42
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 41
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 38
238000006243 chemical reaction Methods 0.000 description 36
235000019439 ethyl acetate Nutrition 0.000 description 36
239000000543 intermediate Substances 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 29
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
239000002904 solvent Substances 0.000 description 26
229910001868 water Inorganic materials 0.000 description 26
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
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238000004809 thin layer chromatography Methods 0.000 description 21
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 18
239000007787 solid Substances 0.000 description 16
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 15
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 15
230000002829 reductive effect Effects 0.000 description 15
238000005481 NMR spectroscopy Methods 0.000 description 14
238000003756 stirring Methods 0.000 description 14
239000004480 active ingredient Substances 0.000 description 11
230000000694 effects Effects 0.000 description 11
238000004007 reversed phase HPLC Methods 0.000 description 11
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
229960000583 acetic acid Drugs 0.000 description 10
230000008570 general process Effects 0.000 description 10
150000003141 primary amines Chemical class 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
229910052938 sodium sulfate Inorganic materials 0.000 description 10
235000011152 sodium sulphate Nutrition 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
239000000556 agonist Substances 0.000 description 9
239000000872 buffer Substances 0.000 description 9
235000019441 ethanol Nutrition 0.000 description 9
239000006260 foam Substances 0.000 description 9
235000019359 magnesium stearate Nutrition 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 8
238000001914 filtration Methods 0.000 description 8
239000000843 powder Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
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230000015572 biosynthetic process Effects 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 7
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239000003826 tablet Substances 0.000 description 7
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CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 6
229920000881 Modified starch Polymers 0.000 description 6
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-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
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 6
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
210000000232 gallbladder Anatomy 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
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239000012312 sodium hydride Substances 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 5
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
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ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 4
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 4
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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 4
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DVARZUUKZACNGW-UHFFFAOYSA-N 2-(phenylhydrazinylidene)propanedioyl dichloride Chemical compound ClC(=O)C(C(Cl)=O)=NNC1=CC=CC=C1 DVARZUUKZACNGW-UHFFFAOYSA-N 0.000 description 3
NFCPRRWCTNLGSN-UHFFFAOYSA-N 2-n-phenylbenzene-1,2-diamine Chemical compound NC1=CC=CC=C1NC1=CC=CC=C1 NFCPRRWCTNLGSN-UHFFFAOYSA-N 0.000 description 3
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DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
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BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0207—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)4-C(=0), e.g. 'isosters', replacing two amino acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Biophysics (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Crystallography & Structural Chemistry (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Obesity (AREA)
Hematology (AREA)
Gastroenterology & Hepatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Hydrogenated Pyridines (AREA)

IL10931694A 1993-04-15 1994-04-13 History 1, 5 - Benzodiazepines, their preparation and pharmaceutical preparations containing them IL109316A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB939307833A GB9307833D0 (en)	1993-04-15	1993-04-15	Modulators of cholecystokinin and gastrin

Publications (2)

Publication Number	Publication Date
IL109316A0 IL109316A0 (en)	1994-07-31
IL109316A true IL109316A (en)	1999-03-12

Family

ID=10733915

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
IL10931694A IL109316A (en)	1993-04-15	1994-04-13	History 1, 5 - Benzodiazepines, their preparation and pharmaceutical preparations containing them
IL10931594A IL109315A0 (en)	1993-04-15	1994-04-13	1, 5-benzodiazepine derivatives, their preparation and pharmaceutical compositions containing them

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
IL10931594A IL109315A0 (en)	1993-04-15	1994-04-13	1, 5-benzodiazepine derivatives, their preparation and pharmaceutical compositions containing them

Country Status (34)

Country	Link
US (2)	US5646140A (no)
EP (1)	EP0694039B1 (no)
JP (1)	JP3406317B2 (no)
KR (1)	KR100364948B1 (no)
CN (1)	CN1058487C (no)
AP (2)	AP462A (no)
AT (1)	ATE198894T1 (no)
AU (1)	AU681139B2 (no)
CA (1)	CA2158973C (no)
CZ (1)	CZ286695B6 (no)
DE (1)	DE69426624T2 (no)
DK (1)	DK0694039T3 (no)
EC (1)	ECSP941066A (no)
ES (1)	ES2154674T3 (no)
FI (1)	FI954853L (no)
GB (1)	GB9307833D0 (no)
GR (1)	GR3035641T3 (no)
HK (1)	HK1003943A1 (no)
HU (1)	HU223467B1 (no)
IL (2)	IL109316A (no)
IS (2)	IS4147A (no)
MY (2)	MY112237A (no)
NO (1)	NO311133B1 (no)
NZ (1)	NZ265272A (no)
OA (1)	OA10355A (no)
PE (2)	PE50994A1 (no)
PH (1)	PH30897A (no)
PL (1)	PL178790B1 (no)
PT (1)	PT694039E (no)
RU (1)	RU2135486C1 (no)
SK (1)	SK281211B6 (no)
TW (1)	TW487703B (no)
WO (1)	WO1994024149A1 (no)
ZA (2)	ZA942571B (no)

Families Citing this family (49)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0728748B1 (en) *	1993-12-28	2002-03-06	Shionogi & Co., Ltd.	Benzodiazepine derivatives
DE69510545T2 (de) *	1994-04-14	2000-01-13	Glaxo Wellcome Inc	Cck oder gastrin modulierende 5-heterocyclicyl-1,5-benzodiazepine
US5739129A (en) *	1994-04-14	1998-04-14	Glaxo Wellcome Inc.	CCK or gastrin modulating 5-heterocyclic-1, 5 benzodiazepines
PE27497A1 (es) *	1994-04-15	1997-08-07	Glaxo Inc	Derivados de 1,5 benzodiazepina
US5795887A (en) *	1994-04-15	1998-08-18	Glaxo Wellcome Inc.	Method of inducing cholecystokinin agonist activity using 1,4- Benzodiazepine compounds
US5910495A (en) *	1994-10-14	1999-06-08	Glaxo Wellcome Inc.	Use of 1,5-benzo b!1,4-diazepines to control gastric emptying
US5780464A (en) *	1994-10-14	1998-07-14	Glaxo Wellcome Inc.	Enteric coated compositions of 1,5-benzodiazepine derivatives having CCK antagonistic or agonistic activity
GB9420747D0 (en) *	1994-10-14	1994-11-30	Glaxo Inc	1,5 benzodiazepine derivatives
GB9420748D0 (en) *	1994-10-14	1994-11-30	Glaxo Inc	1,5 benzodiazepine derivatives
GB9420763D0 (en) *	1994-10-14	1994-11-30	Glaxo Inc	Acetamide derivatives
US5750353A (en) *	1995-12-11	1998-05-12	New England Medical Center Hospitals, Inc.	Assay for non-peptide agonists to peptide hormone receptors
KR100561963B1 (ko)	1995-12-11	2006-11-30	뉴 잉글랜드 메디컬 센터 호스피털스 인코퍼레이티드	펩타이드호르몬수용체리간드의검사방법및용도
CN1130351C (zh) *	1996-12-10	2003-12-10	泽里新药工业株式会社	1,5－苯并二氮杂䓬衍生物
GB2360520B (en)	1997-04-15	2001-11-07	Csir	Intermediates in the synthesis of appetite suppressant steroid glycosides
AR022044A1 (es) *	1999-05-06	2002-09-04	Glaxo Group Ltd	Derivados de 1,5-benzodiazepina
GB2355657B (en)	1999-10-27	2004-07-28	Phytopharm Plc	Inhibitors Of Gastric Acid Secretion
GB2363985B (en)	2000-06-30	2004-09-29	Phytopharm Plc	Extracts,compounds & pharmaceutical compositions having anti-diabetic activity and their use
US6768024B1 (en)	2000-08-04	2004-07-27	Lion Bioscience Ag	Triamine derivative melanocortin receptor ligands and methods of using same
US20020180095A1 (en) *	2001-05-29	2002-12-05	Berard Steven O.	Thermally conductive carbon fiber extrusion compounder and method of using same
ATE420644T1 (de) *	2002-02-20	2009-01-15	Abbott Lab	Kondensierte azabicyclischeverbindungen als inhibitoren des vanilloid-rezeptors 1 (vr1)
US7074805B2 (en) *	2002-02-20	2006-07-11	Abbott Laboratories	Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
US6933311B2 (en) *	2003-02-11	2005-08-23	Abbott Laboratories	Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
US7015233B2 (en) *	2003-06-12	2006-03-21	Abbott Laboratories	Fused compounds that inhibit vanilloid subtype 1 (VR1) receptor
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CN1333077C (zh) *	2005-04-15	2007-08-22	华南农业大学	缩胆囊素活性片段的串联表达及其应用
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1993
- 1993-04-15 GB GB939307833A patent/GB9307833D0/en active Pending
1994
- 1994-01-04 US US08/525,659 patent/US5646140A/en not_active Expired - Lifetime
- 1994-04-11 IS IS4147A patent/IS4147A/is unknown
- 1994-04-11 IS IS4148A patent/IS4148A/is unknown
- 1994-04-12 MY MYPI94000880A patent/MY112237A/en unknown
- 1994-04-12 MY MYPI94000884A patent/MY131569A/en unknown
- 1994-04-12 EC EC1994001066A patent/ECSP941066A/es unknown
- 1994-04-13 PE PE1994240027A patent/PE50994A1/es not_active Application Discontinuation
- 1994-04-13 US US08/522,363 patent/US5585376A/en not_active Expired - Fee Related
- 1994-04-13 AP APAP/P/1994/000634A patent/AP462A/en active
- 1994-04-13 IL IL10931694A patent/IL109316A/en not_active IP Right Cessation
- 1994-04-13 IL IL10931594A patent/IL109315A0/xx unknown
- 1994-04-13 AP APAP/P/1994/000635A patent/AP512A/en active
- 1994-04-13 PE PE1994240028A patent/PE50594A1/es not_active Application Discontinuation
- 1994-04-14 RU RU95117974A patent/RU2135486C1/ru not_active IP Right Cessation
- 1994-04-14 WO PCT/EP1994/001131 patent/WO1994024149A1/en active IP Right Grant
- 1994-04-14 PH PH48093A patent/PH30897A/en unknown
- 1994-04-14 AU AU65676/94A patent/AU681139B2/en not_active Ceased
- 1994-04-14 NZ NZ265272A patent/NZ265272A/en not_active IP Right Cessation
- 1994-04-14 CZ CZ19952675A patent/CZ286695B6/cs not_active IP Right Cessation
- 1994-04-14 AT AT94913580T patent/ATE198894T1/de not_active IP Right Cessation
- 1994-04-14 PT PT94913580T patent/PT694039E/pt unknown
- 1994-04-14 ZA ZA942571A patent/ZA942571B/xx unknown
- 1994-04-14 PL PL94311084A patent/PL178790B1/pl unknown
- 1994-04-14 SK SK1253-95A patent/SK281211B6/sk unknown
- 1994-04-14 HU HU9502978A patent/HU223467B1/hu not_active IP Right Cessation
- 1994-04-14 DK DK94913580T patent/DK0694039T3/da active
- 1994-04-14 CN CN94191773A patent/CN1058487C/zh not_active Expired - Fee Related
- 1994-04-14 EP EP94913580A patent/EP0694039B1/en not_active Expired - Lifetime
- 1994-04-14 ES ES94913580T patent/ES2154674T3/es not_active Expired - Lifetime
- 1994-04-14 DE DE69426624T patent/DE69426624T2/de not_active Expired - Lifetime
- 1994-04-14 KR KR1019950704491A patent/KR100364948B1/ko not_active Expired - Fee Related
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- 1994-04-14 JP JP52273494A patent/JP3406317B2/ja not_active Expired - Fee Related
- 1994-05-26 TW TW083104772A patent/TW487703B/zh not_active IP Right Cessation
1995
- 1995-10-12 FI FI954853A patent/FI954853L/fi unknown
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- 1995-10-13 NO NO19954090A patent/NO311133B1/no unknown
1998
- 1998-04-16 HK HK98103188A patent/HK1003943A1/xx not_active IP Right Cessation
2001
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Also Published As

Publication number	Publication date
PH30897A (en)	1997-12-23
CZ267595A3 (en)	1996-04-17
FI954853A0 (fi)	1995-10-12
ATE198894T1 (de)	2001-02-15
CZ286695B6 (en)	2000-06-14
JPH08508744A (ja)	1996-09-17
PT694039E (pt)	2001-06-29
HU9502978D0 (en)	1995-12-28
GR3035641T3 (en)	2001-06-29
DE69426624D1 (de)	2001-03-01
DK0694039T3 (da)	2001-05-21
IL109316A0 (en)	1994-07-31
ZA942571B (en)	1994-11-11
WO1994024149A1 (en)	1994-10-27
US5585376A (en)	1996-12-17
KR100364948B1 (ko)	2003-03-29
MY112237A (en)	2001-05-31
FI954853L (fi)	1995-10-12
AU6567694A (en)	1994-11-08
ZA942570B (en)	1994-11-11
IS4147A (is)	1994-10-16
EP0694039B1 (en)	2001-01-24
HUT74102A (en)	1996-11-28
CN1058487C (zh)	2000-11-15
AP9400634A0 (en)	1994-04-30
AU681139B2 (en)	1997-08-21
PL178790B1 (pl)	2000-06-30
AP512A (en)	1996-07-29
CA2158973A1 (en)	1994-10-27
IL109315A0 (en)	1994-07-31
RU2135486C1 (ru)	1999-08-27
JP3406317B2 (ja)	2003-05-12
AP9400635A0 (en)	1994-04-30
NO954090L (no)	1995-12-13
TW487703B (en)	2002-05-21
CN1120843A (zh)	1996-04-17
DE69426624T2 (de)	2001-06-21
NO954090D0 (no)	1995-10-13
ES2154674T3 (es)	2001-04-16
HK1003943A1 (en)	1998-11-13
SK125395A3 (en)	1996-06-05
HU223467B1 (hu)	2004-07-28
US5646140A (en)	1997-07-08
PE50994A1 (es)	1995-01-06
ECSP941066A (es)	1994-11-16
OA10355A (en)	2001-10-19
EP0694039A1 (en)	1996-01-31
CA2158973C (en)	2006-06-06
GB9307833D0 (en)	1993-06-02
MY131569A (en)	2007-08-30
NZ265272A (en)	1997-07-27
PL311084A1 (en)	1996-02-05
PE50594A1 (es)	1995-01-06
NO311133B1 (no)	2001-10-15
IS4148A (is)	1994-10-16
SK281211B6 (sk)	2001-01-18
AP462A (en)	1996-02-19

Publication	Publication Date	Title
AP512A (en)	1996-07-29	Derivatives of 1-aminocarbonylmethyl-3-amino-2,4-dioxo-1-5 benzodiazepines having CCKA agonist activity.
US5795887A (en)	1998-08-18	Method of inducing cholecystokinin agonist activity using 1,4- Benzodiazepine compounds
AU679085B2 (en)	1997-06-19	Benzodiazepine analogs
AU640113B2 (en)	1993-08-19	Benzodiazepine analogs
US5739129A (en)	1998-04-14	CCK or gastrin modulating 5-heterocyclic-1, 5 benzodiazepines
EP0756602B1 (en)	1999-06-30	Cck or gastrin modulating 5-heterocyclic-1,5-benzodiazepines
CA2158972A1 (en)	1994-10-27	1,5-benzodiazepine derivatives having cck and/or gastrin antogonistic activity
US5910495A (en)	1999-06-08	Use of 1,5-benzo b!1,4-diazepines to control gastric emptying

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Date	Code	Title
1999-09-22	FF	Patent granted
2000-07-26	KB	Patent renewed
2000-08-31	KB	Patent renewed
2004-06-01	KB	Patent renewed
2008-06-05	KB	Patent renewed
2012-11-29	MM9K	Patent not in force due to non-payment of renewal fees