CN116178337A - 苯并二氮杂䓬类化合物及其作为Rho激酶抑制剂的应用 - Google Patents
苯并二氮杂䓬类化合物及其作为Rho激酶抑制剂的应用 Download PDFInfo
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- CN116178337A CN116178337A CN202211486877.7A CN202211486877A CN116178337A CN 116178337 A CN116178337 A CN 116178337A CN 202211486877 A CN202211486877 A CN 202211486877A CN 116178337 A CN116178337 A CN 116178337A
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- alkyl
- substituted
- hydroxy
- hydrogen
- membered
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- 239000003590 rho kinase inhibitor Substances 0.000 title claims abstract description 5
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 88
- 238000002360 preparation method Methods 0.000 claims abstract description 39
- 239000003814 drug Substances 0.000 claims abstract description 17
- 230000000694 effects Effects 0.000 claims abstract description 16
- -1 pyrrolopyridinyl Chemical group 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 67
- 239000000203 mixture Substances 0.000 claims description 48
- 125000004429 atom Chemical group 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 24
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
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- 239000012453 solvate Substances 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
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- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
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- 239000011737 fluorine Substances 0.000 claims description 11
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- 108010041788 rho-Associated Kinases Proteins 0.000 claims description 9
- 125000006568 (C4-C7) heterocycloalkyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 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 5
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- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 2
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- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 abstract description 3
- 230000008901 benefit Effects 0.000 abstract description 3
- 229940043355 kinase inhibitor Drugs 0.000 abstract description 3
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- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 21
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 16
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- 238000005481 NMR spectroscopy Methods 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 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 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 12
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 11
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
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- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2021114049526 | 2021-11-24 | ||
| CN202111404952 | 2021-11-24 |
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| Publication Number | Publication Date |
|---|---|
| CN116178337A true CN116178337A (zh) | 2023-05-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211486877.7A Pending CN116178337A (zh) | 2021-11-24 | 2022-11-24 | 苯并二氮杂䓬类化合物及其作为Rho激酶抑制剂的应用 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN116178337A (fr) |
| WO (1) | WO2023093787A1 (fr) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006044753A2 (fr) * | 2004-10-19 | 2006-04-27 | Smithkline Beecham Corporation | Composes chimiques |
| WO2010114894A1 (fr) * | 2009-03-31 | 2010-10-07 | Arqule, Inc. | Composés hétérocycliques substitués |
| CN102753179A (zh) * | 2009-11-17 | 2012-10-24 | 密执安大学评议会 | 具有治疗性能的1,4-苯并二氮杂*-2,5-二酮和相关化合物 |
| CN102753544A (zh) * | 2009-11-17 | 2012-10-24 | 密执安大学评议会 | 具有治疗性能的1，4-苯并二氮杂*-2，5-二酮和相关化合物 |
-
2022
- 2022-11-24 WO PCT/CN2022/133916 patent/WO2023093787A1/fr unknown
- 2022-11-24 CN CN202211486877.7A patent/CN116178337A/zh active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006044753A2 (fr) * | 2004-10-19 | 2006-04-27 | Smithkline Beecham Corporation | Composes chimiques |
| WO2010114894A1 (fr) * | 2009-03-31 | 2010-10-07 | Arqule, Inc. | Composés hétérocycliques substitués |
| CN102753179A (zh) * | 2009-11-17 | 2012-10-24 | 密执安大学评议会 | 具有治疗性能的1,4-苯并二氮杂*-2,5-二酮和相关化合物 |
| CN102753544A (zh) * | 2009-11-17 | 2012-10-24 | 密执安大学评议会 | 具有治疗性能的1，4-苯并二氮杂*-2，5-二酮和相关化合物 |
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| Publication number | Publication date |
|---|---|
| WO2023093787A1 (fr) | 2023-06-01 |
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