CA2450262A1 - 2,5-diarylpyrazines, 2,5-diarylpyridines and 2,5-diarylpyrimidines as crf1 receptor modulators - Google Patents
2,5-diarylpyrazines, 2,5-diarylpyridines and 2,5-diarylpyrimidines as crf1 receptor modulators Download PDFInfo
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- CA2450262A1 CA2450262A1 CA002450262A CA2450262A CA2450262A1 CA 2450262 A1 CA2450262 A1 CA 2450262A1 CA 002450262 A CA002450262 A CA 002450262A CA 2450262 A CA2450262 A CA 2450262A CA 2450262 A1 CA2450262 A1 CA 2450262A1
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- Prior art keywords
- phenyl
- amino
- mono
- compound
- methoxy
- Prior art date
- 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.)
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- 108091005471 CRHR1 Proteins 0.000 title claims abstract description 21
- 150000001875 compounds Chemical class 0.000 claims abstract description 245
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 claims abstract description 48
- 238000000034 method Methods 0.000 claims abstract description 48
- 230000027455 binding Effects 0.000 claims abstract description 23
- 239000000523 sample Substances 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 12
- 230000036506 anxiety Effects 0.000 claims abstract description 10
- -1 tri-substituted, 1- naphthyl Chemical group 0.000 claims description 289
- 150000003839 salts Chemical class 0.000 claims description 72
- 229910052736 halogen Inorganic materials 0.000 claims description 68
- 150000002367 halogens Chemical class 0.000 claims description 67
- 239000000203 mixture Substances 0.000 claims description 60
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 58
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 52
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 51
- 125000005843 halogen group Chemical group 0.000 claims description 48
- 125000004432 carbon atom Chemical group C* 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 37
- 210000004027 cell Anatomy 0.000 claims description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
- 150000002431 hydrogen Chemical class 0.000 claims description 30
- 238000000338 in vitro Methods 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 125000004076 pyridyl group Chemical group 0.000 claims description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 125000004043 oxo group Chemical group O=* 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 241001465754 Metazoa Species 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 16
- 125000002883 imidazolyl group Chemical group 0.000 claims description 15
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 15
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 14
- 125000002541 furyl group Chemical group 0.000 claims description 14
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 14
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 14
- 238000001525 receptor binding assay Methods 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 239000012472 biological sample Substances 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 10
- 125000002971 oxazolyl group Chemical group 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 125000000335 thiazolyl group Chemical group 0.000 claims description 10
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
- 125000001425 triazolyl group Chemical group 0.000 claims description 9
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical class 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 238000001727 in vivo Methods 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 210000001124 body fluid Anatomy 0.000 claims description 5
- 239000010839 body fluid Substances 0.000 claims description 5
- 238000011534 incubation Methods 0.000 claims description 5
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 4
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 4
- 210000002569 neuron Anatomy 0.000 claims description 4
- 239000006188 syrup Substances 0.000 claims description 4
- 235000020357 syrup Nutrition 0.000 claims description 4
- WBGBGXMECPELHI-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-(5-fluoro-2-methoxyphenyl)pyrazine Chemical compound CCC1=NC(C=2C(=CC=C(F)C=2)OC)=C(CC)N=C1C1=CC=C(OC)C=C1OC WBGBGXMECPELHI-UHFFFAOYSA-N 0.000 claims description 3
- LEUCFGXBIMXSTR-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-5-[2-methoxy-4-(trifluoromethoxy)phenyl]-3,6-dimethylpyrazine Chemical compound COC1=CC(OC)=CC=C1C1=NC(C)=C(C=2C(=CC(OC(F)(F)F)=CC=2)OC)N=C1C LEUCFGXBIMXSTR-UHFFFAOYSA-N 0.000 claims description 3
- JSXKXOSIJYZLNF-UHFFFAOYSA-N 5-(5-fluoro-2-methoxyphenyl)-4-methoxy-2-(2-methoxy-4,6-dimethylphenyl)-6-methylpyrimidine Chemical compound COC1=CC=C(F)C=C1C1=C(C)N=C(C=2C(=CC(C)=CC=2C)OC)N=C1OC JSXKXOSIJYZLNF-UHFFFAOYSA-N 0.000 claims description 3
- 238000000376 autoradiography Methods 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 3
- KMMOUEUBVQKIOZ-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-5-(2,5-dimethylphenyl)-3,6-diethylpyrazine Chemical compound CCC1=NC(C=2C(=CC=C(C)C=2)C)=C(CC)N=C1C1=CC=C(OC)C=C1OC KMMOUEUBVQKIOZ-UHFFFAOYSA-N 0.000 claims description 2
- FWFQNYFIVKWSFP-UHFFFAOYSA-N 3-(3,5-diethylpyrazol-1-yl)-2-methoxy-6-[2-methoxy-4-(trifluoromethoxy)phenyl]-5-methylpyridine Chemical compound N1=C(CC)C=C(CC)N1C1=CC(C)=C(C=2C(=CC(OC(F)(F)F)=CC=2)OC)N=C1OC FWFQNYFIVKWSFP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 125000005432 dialkylcarboxamide group Chemical group 0.000 claims description 2
- 239000012530 fluid Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 25
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 14
- 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims 12
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 4
- 238000005406 washing Methods 0.000 claims 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 3
- LIUBIORPMLRDJF-UHFFFAOYSA-N 1-[4-[5-(2,5-dimethylphenyl)-3,6-diethylpyrazin-2-yl]-3,5-dimethoxyphenyl]ethanol Chemical compound CCC1=NC(C=2C(=CC(=CC=2OC)C(C)O)OC)=C(CC)N=C1C1=CC(C)=CC=C1C LIUBIORPMLRDJF-UHFFFAOYSA-N 0.000 claims 1
- WUZIDBVQKLRIPB-UHFFFAOYSA-N 1-[4-[5-(2,5-dimethylphenyl)-3,6-diethylpyrazin-2-yl]-3,5-dimethoxyphenyl]ethanone Chemical compound CCC1=NC(C=2C(=CC(=CC=2OC)C(C)=O)OC)=C(CC)N=C1C1=CC(C)=CC=C1C WUZIDBVQKLRIPB-UHFFFAOYSA-N 0.000 claims 1
- BGZZRIMFHBIIEI-UHFFFAOYSA-N 2,5-bis(2,4-dimethoxyphenyl)-3,6-diethylpyrazine Chemical compound CCC1=NC(C=2C(=CC(OC)=CC=2)OC)=C(CC)N=C1C1=CC=C(OC)C=C1OC BGZZRIMFHBIIEI-UHFFFAOYSA-N 0.000 claims 1
- DGDWIDICUIAHMN-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-(2,3,5-trichlorophenyl)pyrazine Chemical compound CCC1=NC(C=2C(=C(Cl)C=C(Cl)C=2)Cl)=C(CC)N=C1C1=CC=C(OC)C=C1OC DGDWIDICUIAHMN-UHFFFAOYSA-N 0.000 claims 1
- ZMTFJCIBWVYKMK-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-(2,4,6-trimethylphenyl)pyrazine Chemical compound CCC1=NC(C=2C(=CC(C)=CC=2C)C)=C(CC)N=C1C1=CC=C(OC)C=C1OC ZMTFJCIBWVYKMK-UHFFFAOYSA-N 0.000 claims 1
- FHNRZIJAXCKDNH-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-(2-methoxy-5-propan-2-ylphenyl)pyrazine Chemical compound CCC1=NC(C=2C(=CC=C(C=2)C(C)C)OC)=C(CC)N=C1C1=CC=C(OC)C=C1OC FHNRZIJAXCKDNH-UHFFFAOYSA-N 0.000 claims 1
- HHLZPPDELXXHLI-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-(2-methylphenyl)pyrazine Chemical compound CCC1=NC(C=2C(=CC(OC)=CC=2)OC)=C(CC)N=C1C1=CC=CC=C1C HHLZPPDELXXHLI-UHFFFAOYSA-N 0.000 claims 1
- AKDXVUVTVXZOFF-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-(3-methylphenyl)pyrazine Chemical compound CCC1=NC(C=2C(=CC(OC)=CC=2)OC)=C(CC)N=C1C1=CC=CC(C)=C1 AKDXVUVTVXZOFF-UHFFFAOYSA-N 0.000 claims 1
- HULSIAJKZKUTPU-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-(4-fluoro-3-methylphenyl)pyrazine Chemical compound CCC1=NC(C=2C(=CC(OC)=CC=2)OC)=C(CC)N=C1C1=CC=C(F)C(C)=C1 HULSIAJKZKUTPU-UHFFFAOYSA-N 0.000 claims 1
- XJYPDMJBVJECPV-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-[2-(trifluoromethyl)phenyl]pyrazine Chemical compound CCC1=NC(C=2C(=CC=CC=2)C(F)(F)F)=C(CC)N=C1C1=CC=C(OC)C=C1OC XJYPDMJBVJECPV-UHFFFAOYSA-N 0.000 claims 1
- QKYNPRQCZBBACO-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-[3-(trifluoromethoxy)phenyl]pyrazine Chemical compound CCC1=NC(C=2C(=CC(OC)=CC=2)OC)=C(CC)N=C1C1=CC=CC(OC(F)(F)F)=C1 QKYNPRQCZBBACO-UHFFFAOYSA-N 0.000 claims 1
- QFLCTLQRAGZVPR-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-[3-(trifluoromethyl)phenyl]pyrazine Chemical compound CCC1=NC(C=2C(=CC(OC)=CC=2)OC)=C(CC)N=C1C1=CC=CC(C(F)(F)F)=C1 QFLCTLQRAGZVPR-UHFFFAOYSA-N 0.000 claims 1
- FTLCVJIYNXJAKB-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-naphthalen-1-ylpyrazine Chemical compound CCC1=NC(C=2C3=CC=CC=C3C=CC=2)=C(CC)N=C1C1=CC=C(OC)C=C1OC FTLCVJIYNXJAKB-UHFFFAOYSA-N 0.000 claims 1
- BVCPGUGHWQTKEJ-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-naphthalen-2-ylpyrazine Chemical compound CCC=1N=C(C=2C=C3C=CC=CC3=CC=2)C(CC)=NC=1C1=CC=C(OC)C=C1OC BVCPGUGHWQTKEJ-UHFFFAOYSA-N 0.000 claims 1
- BGHCMPVFVKWWBZ-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-phenylpyrazine Chemical compound CCC1=NC(C=2C(=CC(OC)=CC=2)OC)=C(CC)N=C1C1=CC=CC=C1 BGHCMPVFVKWWBZ-UHFFFAOYSA-N 0.000 claims 1
- ULBLIKCTKCWWID-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-dimethyl-5-(2-methylphenyl)pyrazine Chemical compound COC1=CC(OC)=CC=C1C1=NC(C)=C(C=2C(=CC=CC=2)C)N=C1C ULBLIKCTKCWWID-UHFFFAOYSA-N 0.000 claims 1
- NMYQXTOJTJXABZ-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-5-(2,3-dimethylphenyl)-3,6-diethylpyrazine Chemical compound CCC1=NC(C=2C(=CC(OC)=CC=2)OC)=C(CC)N=C1C1=CC=CC(C)=C1C NMYQXTOJTJXABZ-UHFFFAOYSA-N 0.000 claims 1
- LVZNFDXIXYQITO-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-5-(2,5-dimethoxyphenyl)-3,6-diethylpyrazine Chemical compound CCC1=NC(C=2C(=CC=C(OC)C=2)OC)=C(CC)N=C1C1=CC=C(OC)C=C1OC LVZNFDXIXYQITO-UHFFFAOYSA-N 0.000 claims 1
- VILHKICPLHVTHQ-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-5-(2,6-dimethylphenyl)-3,6-diethylpyrazine Chemical compound CCC1=NC(C=2C(=CC=CC=2C)C)=C(CC)N=C1C1=CC=C(OC)C=C1OC VILHKICPLHVTHQ-UHFFFAOYSA-N 0.000 claims 1
- JTJFDQBQZILVDR-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-5-(3,5-dimethylphenyl)-3,6-diethylpyrazine Chemical compound CCC1=NC(C=2C(=CC(OC)=CC=2)OC)=C(CC)N=C1C1=CC(C)=CC(C)=C1 JTJFDQBQZILVDR-UHFFFAOYSA-N 0.000 claims 1
- QJAMUCWIAHNPRS-UHFFFAOYSA-N 2-(2,5-dichlorophenyl)-5-(2,4-dimethoxyphenyl)-3,6-diethylpyrazine Chemical compound CCC1=NC(C=2C(=CC(OC)=CC=2)OC)=C(CC)N=C1C1=CC(Cl)=CC=C1Cl QJAMUCWIAHNPRS-UHFFFAOYSA-N 0.000 claims 1
- GGPSFFARPDXADE-UHFFFAOYSA-N 2-(2,5-dimethylphenyl)-3,6-diethyl-5-[4-(1-fluoroethyl)-2,6-dimethoxyphenyl]pyrazine Chemical compound CCC1=NC(C=2C(=CC(=CC=2OC)C(C)F)OC)=C(CC)N=C1C1=CC(C)=CC=C1C GGPSFFARPDXADE-UHFFFAOYSA-N 0.000 claims 1
- GVJILNWFSKAYCX-UHFFFAOYSA-N 2-(2,5-dimethylphenyl)-3,6-diethyl-5-[4-(2-fluoropropan-2-yl)-2,6-dimethoxyphenyl]pyrazine Chemical compound CCC1=NC(C=2C(=CC(=CC=2OC)C(C)(C)F)OC)=C(CC)N=C1C1=CC(C)=CC=C1C GVJILNWFSKAYCX-UHFFFAOYSA-N 0.000 claims 1
- LHNUBEVQAMLATC-UHFFFAOYSA-N 2-(2,5-dimethylphenyl)-5-[4-(1,3-dioxolan-2-yl)-2,6-dimethoxyphenyl]-3,6-diethylpyrazine Chemical compound CCC1=NC(C=2C(=CC(=CC=2OC)C2OCCO2)OC)=C(CC)N=C1C1=CC(C)=CC=C1C LHNUBEVQAMLATC-UHFFFAOYSA-N 0.000 claims 1
- OTAJFFMNPOIMMD-UHFFFAOYSA-N 2-(5-chloro-2-methoxyphenyl)-5-(2,4-dimethoxyphenyl)-3,6-diethylpyrazine Chemical compound CCC1=NC(C=2C(=CC=C(Cl)C=2)OC)=C(CC)N=C1C1=CC=C(OC)C=C1OC OTAJFFMNPOIMMD-UHFFFAOYSA-N 0.000 claims 1
- CDCSWCQJUWIEQB-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-5-(2,4-dimethoxyphenyl)-3,6-diethylpyrazine Chemical compound CCC1=NC(C=2C(=CC(OC)=CC=2)OC)=C(CC)N=C1C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CDCSWCQJUWIEQB-UHFFFAOYSA-N 0.000 claims 1
- TYYCKFPMBRRBJO-UHFFFAOYSA-N 2-[4-(difluoromethyl)-2,6-dimethoxyphenyl]-5-(2,5-dimethylphenyl)-3,6-diethylpyrazine Chemical compound CCC1=NC(C=2C(=CC(=CC=2OC)C(F)F)OC)=C(CC)N=C1C1=CC(C)=CC=C1C TYYCKFPMBRRBJO-UHFFFAOYSA-N 0.000 claims 1
- AVFGIQIAGRLQIT-UHFFFAOYSA-N 2-[4-[5-(2,5-dimethylphenyl)-3,6-diethylpyrazin-2-yl]-3,5-dimethoxyphenyl]propan-2-ol Chemical compound CCC1=NC(C=2C(=CC(=CC=2OC)C(C)(C)O)OC)=C(CC)N=C1C1=CC(C)=CC=C1C AVFGIQIAGRLQIT-UHFFFAOYSA-N 0.000 claims 1
- BOJORVHSOBCQLB-UHFFFAOYSA-N 2-methoxy-6-[2-methoxy-4-(trifluoromethoxy)phenyl]-5-methyl-3-(5-propyltetrazol-1-yl)pyridine Chemical compound CCCC1=NN=NN1C1=CC(C)=C(C=2C(=CC(OC(F)(F)F)=CC=2)OC)N=C1OC BOJORVHSOBCQLB-UHFFFAOYSA-N 0.000 claims 1
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- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29748301P | 2001-06-12 | 2001-06-12 | |
| US60/297,483 | 2001-06-12 | ||
| PCT/US2002/016518 WO2002100838A1 (en) | 2001-06-12 | 2002-05-22 | 2,5-diarylpyrazines, 2,5-diarylpyridines and 2,5-diarylpyrimidines as crf1 receptor modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2450262A1 true CA2450262A1 (en) | 2002-12-19 |
Family
ID=23146501
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002450262A Abandoned CA2450262A1 (en) | 2001-06-12 | 2002-05-22 | 2,5-diarylpyrazines, 2,5-diarylpyridines and 2,5-diarylpyrimidines as crf1 receptor modulators |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US6887875B2 (OSRAM) |
| EP (1) | EP1399428A1 (OSRAM) |
| JP (1) | JP2005500286A (OSRAM) |
| AP (1) | AP2003002924A0 (OSRAM) |
| BG (1) | BG108427A (OSRAM) |
| CA (1) | CA2450262A1 (OSRAM) |
| EC (1) | ECSP034898A (OSRAM) |
| HR (1) | HRP20031096A2 (OSRAM) |
| HU (1) | HUP0400179A3 (OSRAM) |
| IL (1) | IL159058A0 (OSRAM) |
| IS (1) | IS7060A (OSRAM) |
| MX (1) | MXPA03011391A (OSRAM) |
| PL (1) | PL367476A1 (OSRAM) |
| RU (1) | RU2003136151A (OSRAM) |
| TN (1) | TNSN03133A1 (OSRAM) |
| WO (1) | WO2002100838A1 (OSRAM) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL146531A0 (en) * | 2000-03-16 | 2002-07-25 | Neurogen Corp | 5-substituted arylpyrimidines |
| US6964965B2 (en) | 2002-04-26 | 2005-11-15 | Pharmacia & Upjohn | Substituted pyrazine derivatives |
| ATE325115T1 (de) | 2002-08-19 | 2006-06-15 | Glaxo Group Ltd | Pyrimidinderivate als selektive cox-2-inhibitoren |
| GB0221443D0 (en) | 2002-09-16 | 2002-10-23 | Glaxo Group Ltd | Pyridine derivates |
| GB0225548D0 (en) | 2002-11-01 | 2002-12-11 | Glaxo Group Ltd | Compounds |
| AU2003278542A1 (en) * | 2002-11-21 | 2004-06-15 | Pharmacia & Upjohn Company Llc | Pyrazine compounds as crf modulators |
| JP2007512275A (ja) | 2003-11-24 | 2007-05-17 | エフ.ホフマン−ラ ロシュ アーゲー | ピラゾリルおよびイミダゾリルピリミジン |
| US20080132522A1 (en) * | 2004-07-14 | 2008-06-05 | Basf Aktiengesellschaft | 2-Substituted Pyrimidines, Method for Their Production and Their Use for Controlling Pathogenic Fungi |
| TW200637556A (en) * | 2005-01-31 | 2006-11-01 | Basf Ag | Substituted 5-phenyl pyrimidines I in therapy |
| KR20080040692A (ko) * | 2005-08-02 | 2008-05-08 | 렉시컨 파마슈티컬스 인코퍼레이티드 | 단백질 키나제 억제제로서의 2-아미노아릴 피리딘 |
| TW200908984A (en) * | 2007-08-07 | 2009-03-01 | Piramal Life Sciences Ltd | Pyridyl derivatives, their preparation and use |
| US7932256B2 (en) * | 2008-07-31 | 2011-04-26 | Bristol-Myers Squibb Company | (S)-4-(1-cyclopropyl-2-methoxyethyl)-6-(6-(difluoromethoxy)-2,5-dimethylpyridin-3-ylamino)-5-oxo-4,5-dihydropyrazine-2-carbonitrile: a pyrazinone modulator of corticotropin-releasing factor receptor activity |
| WO2011051478A1 (en) * | 2009-10-30 | 2011-05-05 | Domain Therapeutics | Novel oxime derivatives and their use as allosteric modulators of metabotropic glutamate receptors |
| US9357781B2 (en) | 2013-05-03 | 2016-06-07 | Inscent, Inc. | Honeybee repellents and uses thereof |
| US9351494B2 (en) | 2013-05-03 | 2016-05-31 | Inscent, Inc. | Honeybee repellents and uses thereof |
| CN105254576A (zh) * | 2014-02-26 | 2016-01-20 | 中国科学院长春应用化学研究所 | 一种谷氨酸二酮哌嗪的制备方法 |
| KR102708681B1 (ko) | 2018-02-13 | 2024-09-26 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| CN118221646A (zh) | 2018-07-13 | 2024-06-21 | 吉利德科学公司 | Pd-1/pd-l1抑制剂 |
| JP2022074173A (ja) * | 2019-03-18 | 2022-05-18 | 住友化学株式会社 | 2,5-ジクロロピラジンの製造方法 |
| CN112142716B (zh) * | 2020-10-29 | 2021-08-31 | 山东新时代药业有限公司 | 一种5元杂芳基取代的吡嗪衍生物及其应用 |
| CN113429354A (zh) * | 2021-07-22 | 2021-09-24 | 广东嘉博制药有限公司 | 一种盐酸甲氧明聚合物杂质及其制备方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1463813A (fr) * | 1964-02-26 | 1966-07-22 | Ciba Geigy | Nouvelles amino-phénylcétones et procédé pour leur préparation |
| US3660404A (en) * | 1969-02-24 | 1972-05-02 | Du Pont | U.v.-absorbing ortho-hydroxyphenyl substituted bipyrimidyls |
| DE2064380C3 (de) * | 1970-12-30 | 1981-01-22 | Hoechst Ag, 6000 Frankfurt | Lichtempfindliches Gemisch |
| JPS625970A (ja) | 1985-03-15 | 1987-01-12 | Terumo Corp | ピラジン誘導体およびこれを含有する血小板凝集抑制剤 |
| DE68926635T2 (de) * | 1988-04-25 | 1997-01-02 | Dainippon Ink & Chemicals | 2,5-Disubstituierte Pyrazin-Derivate, Pyrimidin-Derivate und sie enthaltende Flüssigkristalle |
| JPH02209873A (ja) * | 1989-02-08 | 1990-08-21 | Dainippon Ink & Chem Inc | 光学活性2,5―ジ置換ピリミジン誘導体 |
| JP2770385B2 (ja) * | 1989-03-16 | 1998-07-02 | セイコーエプソン株式会社 | ピリミジン誘導体 |
| WO1995010506A1 (en) * | 1993-10-12 | 1995-04-20 | The Du Pont Merck Pharmaceutical Company | 1n-alkyl-n-arylpyrimidinamines and derivatives thereof |
| JPH0948760A (ja) * | 1995-08-03 | 1997-02-18 | Dainippon Ink & Chem Inc | ピリミジン化合物 |
| JP4044175B2 (ja) * | 1996-07-26 | 2008-02-06 | 株式会社半導体エネルギー研究所 | 光学活性化合物及び該化合物を含有する反強誘電性液晶組成物 |
| US6686486B1 (en) * | 1997-05-07 | 2004-02-03 | Padma Marwah | Process for effecting allylic oxidation |
| SE9702651D0 (sv) * | 1997-07-09 | 1997-07-09 | Astra Pharma Prod | Novel compounds |
| WO1999038829A1 (en) * | 1998-01-28 | 1999-08-05 | Shionogi & Co., Ltd. | Novel tricyclic compound |
| CO5210940A1 (es) * | 1999-05-04 | 2002-10-30 | Novartis Ag | Compuestos plaguicidas derivados de pirimidina y composiciones que los contienen |
| NZ520484A (en) * | 2000-02-16 | 2005-03-24 | Neurogen Corp | Substituted arylpyrazines that are modulators of CRF (corticotropin releasing factor) receptor and methods of treatment using them |
-
2002
- 2002-05-22 HR HR20031096A patent/HRP20031096A2/xx not_active Application Discontinuation
- 2002-05-22 JP JP2003503606A patent/JP2005500286A/ja active Pending
- 2002-05-22 RU RU2003136151/04A patent/RU2003136151A/ru not_active Application Discontinuation
- 2002-05-22 EP EP02737167A patent/EP1399428A1/en not_active Withdrawn
- 2002-05-22 CA CA002450262A patent/CA2450262A1/en not_active Abandoned
- 2002-05-22 HU HU0400179A patent/HUP0400179A3/hu unknown
- 2002-05-22 IL IL15905802A patent/IL159058A0/xx unknown
- 2002-05-22 WO PCT/US2002/016518 patent/WO2002100838A1/en not_active Ceased
- 2002-05-22 AP APAP/P/2003/002924A patent/AP2003002924A0/en unknown
- 2002-05-22 US US10/154,482 patent/US6887875B2/en not_active Expired - Fee Related
- 2002-05-22 PL PL02367476A patent/PL367476A1/xx not_active Application Discontinuation
- 2002-05-22 MX MXPA03011391A patent/MXPA03011391A/es unknown
-
2003
- 2003-07-08 TN TNPCT/US2002/016518A patent/TNSN03133A1/en unknown
- 2003-11-28 IS IS7060A patent/IS7060A/is unknown
- 2003-12-08 BG BG108427A patent/BG108427A/xx unknown
- 2003-12-12 EC EC2003004898A patent/ECSP034898A/es unknown
-
2005
- 2005-04-04 US US11/098,885 patent/US20050176721A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0400179A2 (hu) | 2004-08-30 |
| US6887875B2 (en) | 2005-05-03 |
| IS7060A (is) | 2003-11-28 |
| RU2003136151A (ru) | 2005-05-20 |
| MXPA03011391A (es) | 2004-07-01 |
| TNSN03133A1 (en) | 2005-12-23 |
| JP2005500286A (ja) | 2005-01-06 |
| BG108427A (en) | 2005-01-31 |
| US20050176721A1 (en) | 2005-08-11 |
| PL367476A1 (en) | 2005-02-21 |
| US20030119844A1 (en) | 2003-06-26 |
| AP2003002924A0 (en) | 2003-12-31 |
| IL159058A0 (en) | 2004-05-12 |
| WO2002100838A1 (en) | 2002-12-19 |
| EP1399428A1 (en) | 2004-03-24 |
| HUP0400179A3 (en) | 2004-10-28 |
| HRP20031096A2 (en) | 2005-08-31 |
| ECSP034898A (es) | 2004-01-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |