JP2003510280A - バソプレッシンアゴニスト処方および製法 - Google Patents

バソプレッシンアゴニスト処方および製法

Info

Publication number: JP2003510280A
Authority: JP; Japan
Prior art keywords: pyrrolo; methanone; phenyl; pyrazol; methyl
Prior art date: 1999-09-27
Legal status (The legal status 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 status listed.): Pending

Application number

JP2001526180A

Other languages

English (en)

Japanese (ja)

Inventor

ジョゼフ・キュウン・ヨーン

リチャード・ウィリアム・ソーンダーズ

マーディ・バキル・ファウジ

Original Assignee

アメリカン・サイアナミド・カンパニー

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.)

1999-09-27

Filing date

2000-09-26

Publication date

2003-03-18

2000-09-26 Application filed by アメリカン・サイアナミド・カンパニー filed Critical アメリカン・サイアナミド・カンパニー

2003-03-18 Publication of JP2003510280A publication Critical patent/JP2003510280A/ja

Status Pending legal-status Critical Current

Links

229940083335 Vasopressin agonist Drugs 0.000 title abstract description 6
238000004519 manufacturing process Methods 0.000 title abstract description 4
239000000203 mixture Substances 0.000 claims abstract description 202
-1 sucrose fatty acid esters Chemical class 0.000 claims abstract description 114
229920001223 polyethylene glycol Polymers 0.000 claims abstract description 53
239000004094 surface-active agent Substances 0.000 claims abstract description 32
229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 31
235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 31
150000003839 salts Chemical class 0.000 claims abstract description 30
239000002202 Polyethylene glycol Substances 0.000 claims abstract description 29
229930006000 Sucrose Natural products 0.000 claims abstract description 24
239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 24
239000005720 sucrose Substances 0.000 claims abstract description 24
235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 19
239000000194 fatty acid Substances 0.000 claims abstract description 19
229930195729 fatty acid Natural products 0.000 claims abstract description 19
239000003963 antioxidant agent Substances 0.000 claims abstract description 15
239000003755 preservative agent Substances 0.000 claims abstract description 15
238000000034 method Methods 0.000 claims description 93
125000004432 carbon atom Chemical group C* 0.000 claims description 65
239000008194 pharmaceutical composition Substances 0.000 claims description 56
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 55
238000003756 stirring Methods 0.000 claims description 47
125000000217 alkyl group Chemical group 0.000 claims description 43
229910052757 nitrogen Inorganic materials 0.000 claims description 37
239000004480 active ingredient Substances 0.000 claims description 36
238000001816 cooling Methods 0.000 claims description 35
229910052739 hydrogen Inorganic materials 0.000 claims description 34
239000001257 hydrogen Substances 0.000 claims description 33
239000011734 sodium Substances 0.000 claims description 17
NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 16
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 claims description 16
FBLUCKXWFZKVCT-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(1h-pyrazol-5-yl)phenyl]methanone Chemical compound C1C2=CC=CN2CC2=CC=CC=C2N1C(=O)C(C=C1)=CC=C1C1=CC=NN1 FBLUCKXWFZKVCT-UHFFFAOYSA-N 0.000 claims description 15
229910052799 carbon Inorganic materials 0.000 claims description 14
239000003795 chemical substances by application Substances 0.000 claims description 14
229920000136 polysorbate Polymers 0.000 claims description 14
RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 13
CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 13
239000004615 ingredient Substances 0.000 claims description 13
229920001983 poloxamer Polymers 0.000 claims description 13
RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 claims description 12
238000002156 mixing Methods 0.000 claims description 12
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 12
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 12
229950008882 polysorbate Drugs 0.000 claims description 12
229920000053 polysorbate 80 Polymers 0.000 claims description 12
229940068968 polysorbate 80 Drugs 0.000 claims description 12
NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 11
125000002252 acyl group Chemical group 0.000 claims description 11
229910052708 sodium Inorganic materials 0.000 claims description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
239000007903 gelatin capsule Substances 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
NINOYJQVULROET-UHFFFAOYSA-N n,n-dimethylethenamine Chemical group CN(C)C=C NINOYJQVULROET-UHFFFAOYSA-N 0.000 claims description 9
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 9
RUGDMHJXYBWCOJ-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-fluoro-2-(trifluoromethyl)phenyl]methanone Chemical compound FC(F)(F)C1=CC(F)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 RUGDMHJXYBWCOJ-UHFFFAOYSA-N 0.000 claims description 8
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
230000000694 effects Effects 0.000 claims description 8
229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 7
229920001213 Polysorbate 20 Polymers 0.000 claims description 7
229920001219 Polysorbate 40 Polymers 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
229960000502 poloxamer Drugs 0.000 claims description 7
239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 claims description 7
235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 claims description 7
229940101027 polysorbate 40 Drugs 0.000 claims description 7
229940069328 povidone Drugs 0.000 claims description 7
230000002335 preservative effect Effects 0.000 claims description 7
229920001214 Polysorbate 60 Polymers 0.000 claims description 6
229920002651 Polysorbate 85 Polymers 0.000 claims description 6
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
125000003435 aroyl group Chemical group 0.000 claims description 6
150000001721 carbon Chemical group 0.000 claims description 6
RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 claims description 6
229960001091 chenodeoxycholic acid Drugs 0.000 claims description 6
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 6
JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 claims description 6
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 6
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 6
239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 6
235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 6
229940068977 polysorbate 20 Drugs 0.000 claims description 6
229940113124 polysorbate 60 Drugs 0.000 claims description 6
229940113171 polysorbate 85 Drugs 0.000 claims description 6
JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 claims description 6
229950004959 sorbitan oleate Drugs 0.000 claims description 6
AWDRATDZQPNJFN-VAYUFCLWSA-N taurodeoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 AWDRATDZQPNJFN-VAYUFCLWSA-N 0.000 claims description 6
RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 claims description 6
229960001661 ursodiol Drugs 0.000 claims description 6
JBSFTFLMZMRNLI-UHFFFAOYSA-N 2-chloro-4-(3-methylpyrazol-1-yl)benzoic acid Chemical compound N1=C(C)C=CN1C1=CC=C(C(O)=O)C(Cl)=C1 JBSFTFLMZMRNLI-UHFFFAOYSA-N 0.000 claims description 5
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
230000003078 antioxidant effect Effects 0.000 claims description 5
125000005842 heteroatom Chemical group 0.000 claims description 5
239000011630 iodine Substances 0.000 claims description 5
229910052740 iodine Inorganic materials 0.000 claims description 5
DSVIVXJNCSQFJO-UHFFFAOYSA-N (2,6-dichloropyridin-3-yl)-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound ClC1=NC(Cl)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 DSVIVXJNCSQFJO-UHFFFAOYSA-N 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
125000001246 bromo group Chemical group Br* 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
125000002346 iodo group Chemical group I* 0.000 claims description 4
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 4
MPIBVIPTXCXUNL-UHFFFAOYSA-N (4-bromo-2-chlorophenyl)-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound ClC1=CC(Br)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 MPIBVIPTXCXUNL-UHFFFAOYSA-N 0.000 claims description 3
GATZRWSXCKUPBW-UHFFFAOYSA-N 1-[3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]ethanone Chemical compound ClC1=CC(C(=O)C)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 GATZRWSXCKUPBW-UHFFFAOYSA-N 0.000 claims description 3
VTROYYKGGOPEPS-UHFFFAOYSA-N 2-chloro-4-cyanobenzoic acid Chemical compound OC(=O)C1=CC=C(C#N)C=C1Cl VTROYYKGGOPEPS-UHFFFAOYSA-N 0.000 claims description 3
BBZSYVXUJINLOO-UHFFFAOYSA-N 3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)-n-(dimethylaminomethylidene)benzamide Chemical compound ClC1=CC(C(=O)N=CN(C)C)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 BBZSYVXUJINLOO-UHFFFAOYSA-N 0.000 claims description 3
HGKPNPICICLENG-UHFFFAOYSA-N 4-(3-methylpyrazol-1-yl)-2-(trifluoromethyl)benzoic acid Chemical compound N1=C(C)C=CN1C1=CC=C(C(O)=O)C(C(F)(F)F)=C1 HGKPNPICICLENG-UHFFFAOYSA-N 0.000 claims description 3
UETYLZZBUKOJDA-UHFFFAOYSA-N 4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)-n-(dimethylaminomethylidene)benzamide Chemical compound C1=CC(C(=O)N=CN(C)C)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 UETYLZZBUKOJDA-UHFFFAOYSA-N 0.000 claims description 3
CGCNVGLIONLLAJ-UHFFFAOYSA-N 4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 CGCNVGLIONLLAJ-UHFFFAOYSA-N 0.000 claims description 3
IXJSDKIJPVSPKF-UHFFFAOYSA-N 4-bromo-1-methylpyrazole Chemical compound CN1C=C(Br)C=N1 IXJSDKIJPVSPKF-UHFFFAOYSA-N 0.000 claims description 3
WSWLBSBMRCHUEH-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(3-methylpyrazol-1-yl)-2-(trifluoromethyl)phenyl]methanone Chemical compound N1=C(C)C=CN1C(C=C1C(F)(F)F)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 WSWLBSBMRCHUEH-UHFFFAOYSA-N 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
239000011786 L-ascorbyl-6-palmitate Substances 0.000 claims description 3
QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 claims description 3
RTRBDFZJXIBNFC-UHFFFAOYSA-N [2-chloro-4-(3-methylpyrazol-1-yl)phenyl]-(9-methyl-6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound N1=C(C)C=CN1C(C=C1Cl)=CC=C1C(=O)N1C2=CC=CC=C2CN2C(C)=CC=C2C1 RTRBDFZJXIBNFC-UHFFFAOYSA-N 0.000 claims description 3
AULPIHFOCKNJAT-UHFFFAOYSA-N [2-chloro-4-(trifluoromethyl)pyrimidin-5-yl]-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound FC(F)(F)C1=NC(Cl)=NC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 AULPIHFOCKNJAT-UHFFFAOYSA-N 0.000 claims description 3
235000010385 ascorbyl palmitate Nutrition 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
ZPVFFORHLAKGQJ-UHFFFAOYSA-N methyl 2-chloro-4-(1h-pyrazol-5-yl)benzoate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1C1=NNC=C1 ZPVFFORHLAKGQJ-UHFFFAOYSA-N 0.000 claims description 3
PJEOOPYVEPEKFR-UHFFFAOYSA-N methyl 4-(3-methylpyrazol-1-yl)-2-(trifluoromethyl)benzoate Chemical compound C1=C(C(F)(F)F)C(C(=O)OC)=CC=C1N1N=C(C)C=C1 PJEOOPYVEPEKFR-UHFFFAOYSA-N 0.000 claims description 3
LNECVNPGDBLIEM-UHFFFAOYSA-N tributyl-(1-methylpyrazol-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=1C=NN(C)C=1 LNECVNPGDBLIEM-UHFFFAOYSA-N 0.000 claims description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
229910052727 yttrium Inorganic materials 0.000 claims description 3
RSNXWAKDYVODLM-UHFFFAOYSA-N (2-chloro-4-imidazol-1-ylphenyl)-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C(Cl)=CC=1N1C=CN=C1 RSNXWAKDYVODLM-UHFFFAOYSA-N 0.000 claims description 2
FBENLRZSVRQZHY-UHFFFAOYSA-N (2-chloro-4-pyrazol-1-ylphenyl)-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C(Cl)=CC=1N1C=CC=N1 FBENLRZSVRQZHY-UHFFFAOYSA-N 0.000 claims description 2
PFIHUWCMYUUTJM-UHFFFAOYSA-N (2-chloro-4-pyrrol-1-ylphenyl)-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C(Cl)=CC=1N1C=CC=C1 PFIHUWCMYUUTJM-UHFFFAOYSA-N 0.000 claims description 2
KVEZTRALEPCYLZ-UHFFFAOYSA-N (2-chloro-6-pyrazol-1-ylpyridin-3-yl)-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C(Cl)=NC=1N1C=CC=N1 KVEZTRALEPCYLZ-UHFFFAOYSA-N 0.000 claims description 2
DNNQFXFMXDRZKS-UHFFFAOYSA-N (9-bromo-6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)-[2-chloro-4-(3-methylpyrazol-1-yl)phenyl]methanone Chemical compound N1=C(C)C=CN1C(C=C1Cl)=CC=C1C(=O)N1C2=CC=CC=C2CN2C(Br)=CC=C2C1 DNNQFXFMXDRZKS-UHFFFAOYSA-N 0.000 claims description 2
UAKRIFYMKVWWSB-UHFFFAOYSA-N 1-[4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 UAKRIFYMKVWWSB-UHFFFAOYSA-N 0.000 claims description 2
BTKNUQFTTRAZPU-UHFFFAOYSA-N 1-methyl-4-(4-methylphenyl)pyrazole Chemical compound C1=CC(C)=CC=C1C1=CN(C)N=C1 BTKNUQFTTRAZPU-UHFFFAOYSA-N 0.000 claims description 2
MMSVCNAMGGBJOC-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-1-[3-[4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]pyrazol-1-yl]ethanone Chemical compound ClC1=CC(Cl)=CC=C1CC(=O)N1N=C(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C=C1 MMSVCNAMGGBJOC-UHFFFAOYSA-N 0.000 claims description 2
HVZFVUBTXOIJPM-UHFFFAOYSA-N 2-chloro-4-(1-methylpyrazol-4-yl)benzoic acid Chemical compound C1=NN(C)C=C1C1=CC=C(C(O)=O)C(Cl)=C1 HVZFVUBTXOIJPM-UHFFFAOYSA-N 0.000 claims description 2
DULZEHULKMVLMT-UHFFFAOYSA-N 2-chloro-4-(2-methyl-1,3-dihydropyrazol-3-yl)benzoic acid Chemical compound CN1NC=CC1C1=CC=C(C(O)=O)C(Cl)=C1 DULZEHULKMVLMT-UHFFFAOYSA-N 0.000 claims description 2
FLICMWMJGBRJBU-UHFFFAOYSA-N 3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)benzamide Chemical compound ClC1=CC(C(=O)N)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 FLICMWMJGBRJBU-UHFFFAOYSA-N 0.000 claims description 2
KUIQZKCWIAZFLF-UHFFFAOYSA-N 3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)benzoic acid Chemical compound ClC1=CC(C(=O)O)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 KUIQZKCWIAZFLF-UHFFFAOYSA-N 0.000 claims description 2
DSDRQBPGBZCVCN-UHFFFAOYSA-N 3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)benzonitrile Chemical compound ClC1=CC(C#N)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 DSDRQBPGBZCVCN-UHFFFAOYSA-N 0.000 claims description 2
JNLQMZREPWAVIE-UHFFFAOYSA-N 4-(1-methylpyrazol-4-yl)benzoic acid Chemical compound C1=NN(C)C=C1C1=CC=C(C(O)=O)C=C1 JNLQMZREPWAVIE-UHFFFAOYSA-N 0.000 claims description 2
GIZHJJZNSXEFFA-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[2-(3-methylpyrazol-1-yl)-4-(trifluoromethyl)pyrimidin-5-yl]methanone Chemical compound N1=C(C)C=CN1C(N=C1C(F)(F)F)=NC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 GIZHJJZNSXEFFA-UHFFFAOYSA-N 0.000 claims description 2
AGQQNLOIZRITKE-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[2-(4-methylpyrazol-1-yl)-4-(trifluoromethyl)pyrimidin-5-yl]methanone Chemical compound C1=C(C)C=NN1C(N=C1C(F)(F)F)=NC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 AGQQNLOIZRITKE-UHFFFAOYSA-N 0.000 claims description 2
HZKMKSBSEYMPCW-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[2-fluoro-4-(3-methylpyrazol-1-yl)phenyl]methanone Chemical compound N1=C(C)C=CN1C(C=C1F)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 HZKMKSBSEYMPCW-UHFFFAOYSA-N 0.000 claims description 2
IAUVQLCYHAXTKP-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[2-methoxy-4-(3-methylpyrazol-1-yl)phenyl]methanone Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C(OC)=CC=1N1C=CC(C)=N1 IAUVQLCYHAXTKP-UHFFFAOYSA-N 0.000 claims description 2
OWWMUVSLJDJKSG-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(1,2,4-triazol-1-yl)-2-(trifluoromethyl)phenyl]methanone Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C(C(F)(F)F)=CC=1N1C=NC=N1 OWWMUVSLJDJKSG-UHFFFAOYSA-N 0.000 claims description 2
ULGQCNKQHORZJF-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(1-ethylpyrazol-3-yl)phenyl]methanone Chemical compound CCN1C=CC(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)=N1 ULGQCNKQHORZJF-UHFFFAOYSA-N 0.000 claims description 2
IKKUPWQFBNZBRW-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(1-methylpyrazol-3-yl)phenyl]methanone Chemical compound CN1C=CC(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)=N1 IKKUPWQFBNZBRW-UHFFFAOYSA-N 0.000 claims description 2
MHPFBCSULPHXGZ-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(1-methylpyrazol-4-yl)phenyl]methanone Chemical compound C1=NN(C)C=C1C1=CC=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C=C1 MHPFBCSULPHXGZ-UHFFFAOYSA-N 0.000 claims description 2
APJKVNDKNAGLPV-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(1-propylpyrazol-3-yl)phenyl]methanone Chemical compound CCCN1C=CC(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)=N1 APJKVNDKNAGLPV-UHFFFAOYSA-N 0.000 claims description 2
DNUGMZYCBDREEU-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(1h-1,2,4-triazol-5-yl)phenyl]methanone Chemical compound C1C2=CC=CN2CC2=CC=CC=C2N1C(=O)C(C=C1)=CC=C1C1=NC=NN1 DNUGMZYCBDREEU-UHFFFAOYSA-N 0.000 claims description 2
VPXHSSXWSPVCQD-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(2,5-dimethyl-1,2,4-triazol-3-yl)phenyl]methanone Chemical compound CN1N=C(C)N=C1C1=CC=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C=C1 VPXHSSXWSPVCQD-UHFFFAOYSA-N 0.000 claims description 2
QWWZOSZEOQMREC-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(2-methyl-1,2,4-triazol-3-yl)phenyl]methanone Chemical compound CN1N=CN=C1C1=CC=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C=C1 QWWZOSZEOQMREC-UHFFFAOYSA-N 0.000 claims description 2
UMFTZSAXLWEBFQ-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(3-methyl-1,2,4-triazol-1-yl)-2-(trifluoromethyl)phenyl]methanone Chemical compound N1=C(C)N=CN1C(C=C1C(F)(F)F)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 UMFTZSAXLWEBFQ-UHFFFAOYSA-N 0.000 claims description 2
FIXNNTWIEYTAJW-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(4-methylimidazol-1-yl)-2-(trifluoromethyl)phenyl]methanone Chemical compound C1=NC(C)=CN1C(C=C1C(F)(F)F)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 FIXNNTWIEYTAJW-UHFFFAOYSA-N 0.000 claims description 2
ZMPHLGOCVGFJDM-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(4-methylpyrazol-1-yl)-2-(trifluoromethyl)phenyl]methanone Chemical compound C1=C(C)C=NN1C(C=C1C(F)(F)F)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 ZMPHLGOCVGFJDM-UHFFFAOYSA-N 0.000 claims description 2
KGQJGHDBXHNEBK-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(5-methyl-1h-1,2,4-triazol-3-yl)phenyl]methanone Chemical compound N1C(C)=NC(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)=N1 KGQJGHDBXHNEBK-UHFFFAOYSA-N 0.000 claims description 2
QOVQKXLSPAUMBR-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(5-methyl-1h-pyrazol-3-yl)phenyl]methanone Chemical compound N1C(C)=CC(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)=N1 QOVQKXLSPAUMBR-UHFFFAOYSA-N 0.000 claims description 2
FLXNQADSXVDDED-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-[1-(2-methylbenzoyl)pyrazol-3-yl]phenyl]methanone Chemical compound CC1=CC=CC=C1C(=O)N1N=C(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C=C1 FLXNQADSXVDDED-UHFFFAOYSA-N 0.000 claims description 2
PVZDWPABYHLARE-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-[1-(2-phenylbenzoyl)pyrazol-3-yl]phenyl]methanone Chemical compound C1C2=CC=CN2CC2=CC=CC=C2N1C(=O)C(C=C1)=CC=C1C(=N1)C=CN1C(=O)C1=CC=CC=C1C1=CC=CC=C1 PVZDWPABYHLARE-UHFFFAOYSA-N 0.000 claims description 2
IRJHPKKQWIRRDH-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-[1-(5-fluoro-2-methylbenzoyl)pyrazol-3-yl]phenyl]methanone Chemical compound CC1=CC=C(F)C=C1C(=O)N1N=C(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C=C1 IRJHPKKQWIRRDH-UHFFFAOYSA-N 0.000 claims description 2
QBUWLGWIBRDKEN-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-[1-(methoxymethyl)pyrazol-3-yl]phenyl]methanone Chemical compound COCN1C=CC(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)=N1 QBUWLGWIBRDKEN-UHFFFAOYSA-N 0.000 claims description 2
DVGMOKKLPURONZ-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-[1-[2-[4-(trifluoromethyl)phenyl]benzoyl]pyrazol-3-yl]phenyl]methanone Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)N1N=C(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C=C1 DVGMOKKLPURONZ-UHFFFAOYSA-N 0.000 claims description 2
AWLHGHTYQYATNQ-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-pyrazol-1-yl-2-(trifluoromethyl)phenyl]methanone Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C(C(F)(F)F)=CC=1N1C=CC=N1 AWLHGHTYQYATNQ-UHFFFAOYSA-N 0.000 claims description 2
GNUHIOVLLGPJCN-UHFFFAOYSA-N [2-chloro-4-(1,2,4-triazol-1-yl)phenyl]-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C(Cl)=CC=1N1C=NC=N1 GNUHIOVLLGPJCN-UHFFFAOYSA-N 0.000 claims description 2
ZOALAJPEYKKZTO-UHFFFAOYSA-N [2-chloro-4-(1-methylpyrazol-3-yl)phenyl]-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound CN1C=CC(C=2C=C(Cl)C(C(=O)N3C4=CC=CC=C4CN4C=CC=C4C3)=CC=2)=N1 ZOALAJPEYKKZTO-UHFFFAOYSA-N 0.000 claims description 2
XEMZNTKLIKDCEY-UHFFFAOYSA-N [2-chloro-4-(1h-1,2,4-triazol-5-yl)phenyl]-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C(Cl)=CC=1C1=NC=NN1 XEMZNTKLIKDCEY-UHFFFAOYSA-N 0.000 claims description 2
HQYVSTLOMUPNAJ-UHFFFAOYSA-N [2-chloro-4-(3-methyl-1,2,4-triazol-1-yl)phenyl]-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound N1=C(C)N=CN1C(C=C1Cl)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 HQYVSTLOMUPNAJ-UHFFFAOYSA-N 0.000 claims description 2
JXKQHDZUZGKDGO-UHFFFAOYSA-N [2-chloro-4-(3-methylpyrazol-1-yl)phenyl]-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound N1=C(C)C=CN1C(C=C1Cl)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 JXKQHDZUZGKDGO-UHFFFAOYSA-N 0.000 claims description 2
CNTDFFHQKBTDDT-UHFFFAOYSA-N [2-chloro-4-(3-methylpyrazol-1-yl)phenyl]-[9-[(dimethylamino)methyl]-6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl]methanone Chemical compound C12=CC=CC=C2CN2C(CN(C)C)=CC=C2CN1C(=O)C(C(=C1)Cl)=CC=C1N1C=CC(C)=N1 CNTDFFHQKBTDDT-UHFFFAOYSA-N 0.000 claims description 2
BNRIICCFBXHNNB-UHFFFAOYSA-N [2-chloro-4-(4-methylimidazol-1-yl)phenyl]-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound C1=NC(C)=CN1C(C=C1Cl)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 BNRIICCFBXHNNB-UHFFFAOYSA-N 0.000 claims description 2
AOODETMDIQQGIO-UHFFFAOYSA-N [2-chloro-4-[3-(trifluoromethyl)pyrazol-1-yl]phenyl]-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound N1=C(C(F)(F)F)C=CN1C(C=C1Cl)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 AOODETMDIQQGIO-UHFFFAOYSA-N 0.000 claims description 2
FJWYRBIBXUCMOQ-UHFFFAOYSA-N [4-(1-butylpyrazol-3-yl)phenyl]-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound CCCCN1C=CC(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)=N1 FJWYRBIBXUCMOQ-UHFFFAOYSA-N 0.000 claims description 2
HXBSWLVZOHGNHL-UHFFFAOYSA-N [4-[1-(2,4-dichlorobenzoyl)pyrazol-3-yl]phenyl]-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)methanone Chemical compound ClC1=CC(Cl)=CC=C1C(=O)N1N=C(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C=C1 HXBSWLVZOHGNHL-UHFFFAOYSA-N 0.000 claims description 2
QOKBTDWACCQPEV-UHFFFAOYSA-N [9-[(dimethylamino)methyl]-6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl]-[2-methoxy-4-(3-methylpyrazol-1-yl)phenyl]methanone Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3CN3C(CN(C)C)=CC=C3C2)C(OC)=CC=1N1C=CC(C)=N1 QOKBTDWACCQPEV-UHFFFAOYSA-N 0.000 claims description 2
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
RMBZMOITLBWQKI-UHFFFAOYSA-N cyclopropyl-[3-[4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]pyrazol-1-yl]methanone Chemical compound C1=CC(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)=NN1C(=O)C1CC1 RMBZMOITLBWQKI-UHFFFAOYSA-N 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
XMCIDBZYUCGHPL-UHFFFAOYSA-N methyl 2-chloro-4-(2-methyl-1,3-dihydropyrazol-3-yl)benzoate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1C1N(C)NC=C1 XMCIDBZYUCGHPL-UHFFFAOYSA-N 0.000 claims description 2
BXSFODFSBQHNDM-UHFFFAOYSA-N methyl 2-chloro-4-(3-methylpyrazol-1-yl)benzoate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1N1N=C(C)C=C1 BXSFODFSBQHNDM-UHFFFAOYSA-N 0.000 claims description 2
JXDDDANKAGTDAA-UHFFFAOYSA-N methyl 2-chloro-4-[3-(dimethylamino)prop-1-ynyl]benzoate Chemical compound COC(=O)C1=CC=C(C#CCN(C)C)C=C1Cl JXDDDANKAGTDAA-UHFFFAOYSA-N 0.000 claims description 2
GLZBUNHGODEJPT-UHFFFAOYSA-N methyl 2-chloro-4-cyanobenzoate Chemical compound COC(=O)C1=CC=C(C#N)C=C1Cl GLZBUNHGODEJPT-UHFFFAOYSA-N 0.000 claims description 2
WAVWSBNVGLPPDX-UHFFFAOYSA-N methyl 2-methoxy-4-(3-methylpyrazol-1-yl)benzoate Chemical compound C1=C(OC)C(C(=O)OC)=CC=C1N1N=C(C)C=C1 WAVWSBNVGLPPDX-UHFFFAOYSA-N 0.000 claims description 2
QHQSPBOTJSKHPU-UHFFFAOYSA-N methyl 4-hydrazinyl-2-methoxybenzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(NN)C=C1OC QHQSPBOTJSKHPU-UHFFFAOYSA-N 0.000 claims description 2
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 7
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 3
229920002554 vinyl polymer Polymers 0.000 claims 3
QVSKPOGUURMZEN-UHFFFAOYSA-N 1-[2-chloro-4-(2-methyl-1,2,4-triazol-3-yl)phenyl]-2-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)ethane-1,2-dione Chemical compound CN1N=CN=C1C(C=C1Cl)=CC=C1C(=O)C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 QVSKPOGUURMZEN-UHFFFAOYSA-N 0.000 claims 1
PKABUCAIFGKGAN-UHFFFAOYSA-N 1-[2-chloro-4-(5-methyl-1h-1,2,4-triazol-3-yl)phenyl]-2-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl)ethane-1,2-dione Chemical compound N1C(C)=NC(C=2C=C(Cl)C(C(=O)C(=O)N3C4=CC=CC=C4CN4C=CC=C4C3)=CC=2)=N1 PKABUCAIFGKGAN-UHFFFAOYSA-N 0.000 claims 1
QRGCELUZUJYYFW-UHFFFAOYSA-N 1-[3-[4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]pyrazol-1-yl]ethanone Chemical compound CC(=O)N1C=CC(C=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)=N1 QRGCELUZUJYYFW-UHFFFAOYSA-N 0.000 claims 1
ZACOHTBOHFCQIE-UHFFFAOYSA-N 1-[4-(4,10-dihydropyrazolo[5,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1C(=O)N1C2=CC=CC=C2CN2N=CC=C2C1 ZACOHTBOHFCQIE-UHFFFAOYSA-N 0.000 claims 1
KMKSCFGGYAIFPZ-UHFFFAOYSA-N 1-[4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]-3-(dimethylamino)prop-2-en-1-one Chemical compound C1=CC(C(=O)C=CN(C)C)=CC=C1C(=O)N1C2=CC=CC=C2CN2C=CC=C2C1 KMKSCFGGYAIFPZ-UHFFFAOYSA-N 0.000 claims 1
CZNKGHOHUYTBKK-UHFFFAOYSA-N 2-methoxy-4-(3-methylpyrazol-1-yl)benzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(N2N=C(C)C=C2)=C1 CZNKGHOHUYTBKK-UHFFFAOYSA-N 0.000 claims 1
KQMYATMVMYUOGC-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-(4-imidazol-1-ylphenyl)methanone Chemical compound C1C2=CC=CN2CC2=CC=CC=C2N1C(=O)C(C=C1)=CC=C1N1C=CN=C1 KQMYATMVMYUOGC-UHFFFAOYSA-N 0.000 claims 1
BPJFXRBPXNGTAI-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-(4-pyrazol-1-ylphenyl)methanone Chemical compound C1C2=CC=CN2CC2=CC=CC=C2N1C(=O)C(C=C1)=CC=C1N1C=CC=N1 BPJFXRBPXNGTAI-UHFFFAOYSA-N 0.000 claims 1
VKBOUDPLTDGHDT-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-(3,5-dimethylpyrazol-1-yl)phenyl]methanone Chemical compound N1=C(C)C=C(C)N1C1=CC=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C=C1 VKBOUDPLTDGHDT-UHFFFAOYSA-N 0.000 claims 1
ZACVIYHEWUMBSW-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-[1-(thiophene-2-carbonyl)pyrazol-3-yl]phenyl]methanone Chemical compound C1C2=CC=CN2CC2=CC=CC=C2N1C(=O)C(C=C1)=CC=C1C(=N1)C=CN1C(=O)C1=CC=CS1 ZACVIYHEWUMBSW-UHFFFAOYSA-N 0.000 claims 1
BJQWKPUIFULUQT-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[4-[3-(trifluoromethyl)pyrazol-1-yl]phenyl]methanone Chemical compound N1=C(C(F)(F)F)C=CN1C1=CC=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C=C1 BJQWKPUIFULUQT-UHFFFAOYSA-N 0.000 claims 1
ZOPZYYBHDGGLSD-UHFFFAOYSA-N 6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepin-5-yl-[6-(1-methylpyrazol-4-yl)pyridin-3-yl]methanone Chemical compound C1=NN(C)C=C1C1=CC=C(C(=O)N2C3=CC=CC=C3CN3C=CC=C3C2)C=N1 ZOPZYYBHDGGLSD-UHFFFAOYSA-N 0.000 claims 1
HWBYVOXCQHVWCI-UHFFFAOYSA-N 6-(1-methylpyrazol-4-yl)pyridine-3-carboxylic acid Chemical compound C1=NN(C)C=C1C1=CC=C(C(O)=O)C=N1 HWBYVOXCQHVWCI-UHFFFAOYSA-N 0.000 claims 1
DYGYAUXYIMNPKK-UHFFFAOYSA-N Cc1ccn(n1)-c1ccc(C(=O)C2N3NN=NC3=CNc3ccccc23)c(Cl)c1 Chemical compound Cc1ccn(n1)-c1ccc(C(=O)C2N3NN=NC3=CNc3ccccc23)c(Cl)c1 DYGYAUXYIMNPKK-UHFFFAOYSA-N 0.000 claims 1
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KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 1
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JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
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150000003254 radicals Chemical class 0.000 description 1
238000011552 rat model Methods 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
238000012216 screening Methods 0.000 description 1
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XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
239000002002 slurry Substances 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
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AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
238000000527 sonication Methods 0.000 description 1
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101150035983 str1 gene Proteins 0.000 description 1
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239000001959 sucrose esters of fatty acids Substances 0.000 description 1
235000010965 sucrose esters of fatty acids Nutrition 0.000 description 1
229940032085 sucrose monolaurate Drugs 0.000 description 1
229940035023 sucrose monostearate Drugs 0.000 description 1
150000005846 sugar alcohols Polymers 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
150000005691 triesters Chemical class 0.000 description 1
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
PVNIQBQSYATKKL-UHFFFAOYSA-N tripalmitin Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PVNIQBQSYATKKL-UHFFFAOYSA-N 0.000 description 1
235000019165 vitamin E Nutrition 0.000 description 1
229940046009 vitamin E Drugs 0.000 description 1
239000011709 vitamin E Substances 0.000 description 1
108010047303 von Willebrand Factor Proteins 0.000 description 1
102100036537 von Willebrand factor Human genes 0.000 description 1
229960001134 von willebrand factor Drugs 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
- A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
- 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
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus

Landscapes

Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Diabetes (AREA)
Epidemiology (AREA)
Hematology (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicinal Preparation (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

JP2001526180A 1999-09-27 2000-09-26 バソプレッシンアゴニスト処方および製法 Pending JP2003510280A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US40616599A	1999-09-27	1999-09-27
US09/406,165		1999-09-27
PCT/US2000/026380 WO2001022969A2 (fr)	1999-09-27	2000-09-26	Preparation d'agoniste de la vasopressine et procede de preparation

Publications (1)

Publication Number	Publication Date
JP2003510280A true JP2003510280A (ja)	2003-03-18

Family

ID=23606805

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP2001526180A Pending JP2003510280A (ja)	1999-09-27	2000-09-26	バソプレッシンアゴニスト処方および製法

Country Status (7)

Country	Link
EP (1)	EP1216045A2 (fr)
JP (1)	JP2003510280A (fr)
CN (1)	CN1391476A (fr)
AU (1)	AU7615200A (fr)
CA (1)	CA2385971A1 (fr)
MX (1)	MXPA02003191A (fr)
WO (1)	WO2001022969A2 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7138393B2 (en)	1998-07-24	2006-11-21	Wyeth	Biologically active vasopressin agonist metabolites
US20030105144A1 (en) *	2001-04-17	2003-06-05	Ping Gao	Stabilized oral pharmaceutical composition
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2000
- 2000-09-26 WO PCT/US2000/026380 patent/WO2001022969A2/fr not_active Ceased
- 2000-09-26 CA CA002385971A patent/CA2385971A1/fr not_active Abandoned
- 2000-09-26 JP JP2001526180A patent/JP2003510280A/ja active Pending
- 2000-09-26 MX MXPA02003191A patent/MXPA02003191A/es unknown
- 2000-09-26 AU AU76152/00A patent/AU7615200A/en not_active Abandoned
- 2000-09-26 EP EP00965432A patent/EP1216045A2/fr not_active Withdrawn
- 2000-09-26 CN CN00816009A patent/CN1391476A/zh active Pending

Also Published As

Publication number	Publication date
WO2001022969A3 (fr)	2001-12-20
MXPA02003191A (es)	2002-09-30
WO2001022969A2 (fr)	2001-04-05
EP1216045A2 (fr)	2002-06-26
CN1391476A (zh)	2003-01-15
CA2385971A1 (fr)	2001-04-05
AU7615200A (en)	2001-04-30

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