BG106968A - Заместени арилпиразини - Google Patents
Заместени арилпиразини Download PDFInfo
- Publication number
- BG106968A BG106968A BG106968A BG10696802A BG106968A BG 106968 A BG106968 A BG 106968A BG 106968 A BG106968 A BG 106968A BG 10696802 A BG10696802 A BG 10696802A BG 106968 A BG106968 A BG 106968A
- Authority
- BG
- Bulgaria
- Prior art keywords
- alkyl
- compound
- whose name
- group
- ethylpropyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract description 559
- 238000000034 method Methods 0.000 claims abstract description 115
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 62
- 208000035475 disorder Diseases 0.000 claims abstract description 31
- 201000010099 disease Diseases 0.000 claims abstract description 26
- 238000011282 treatment Methods 0.000 claims abstract description 23
- 108091005471 CRHR1 Proteins 0.000 claims abstract description 15
- 241000282414 Homo sapiens Species 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 471
- -1 cyano, nitro, amino Chemical group 0.000 claims description 366
- 229910052736 halogen Inorganic materials 0.000 claims description 134
- 150000002367 halogens Chemical class 0.000 claims description 121
- 125000003545 alkoxy group Chemical group 0.000 claims description 115
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 110
- 125000004432 carbon atom Chemical group C* 0.000 claims description 76
- 125000001188 haloalkyl group Chemical group 0.000 claims description 74
- 229910052739 hydrogen Inorganic materials 0.000 claims description 74
- 239000000203 mixture Substances 0.000 claims description 74
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 73
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 68
- 239000001257 hydrogen Substances 0.000 claims description 58
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 55
- 125000001424 substituent group Chemical group 0.000 claims description 55
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 claims description 51
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 42
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 40
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 36
- 230000000694 effects Effects 0.000 claims description 34
- 229910052799 carbon Inorganic materials 0.000 claims description 33
- 238000000338 in vitro Methods 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 33
- 230000027455 binding Effects 0.000 claims description 32
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 31
- 102000005962 receptors Human genes 0.000 claims description 31
- 108020003175 receptors Proteins 0.000 claims description 31
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
- 125000001624 naphthyl group Chemical group 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 210000004027 cell Anatomy 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 208000015114 central nervous system disease Diseases 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 21
- 229920006395 saturated elastomer Polymers 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 208000019901 Anxiety disease Diseases 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 208000030814 Eating disease Diseases 0.000 claims description 13
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- 235000014632 disordered eating Nutrition 0.000 claims description 13
- 125000004043 oxo group Chemical group O=* 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 238000003556 assay Methods 0.000 claims description 12
- 108010052164 Sodium Channels Proteins 0.000 claims description 11
- 102000018674 Sodium Channels Human genes 0.000 claims description 11
- 230000036506 anxiety Effects 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 208000020925 Bipolar disease Diseases 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 230000006870 function Effects 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 7
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 claims description 7
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 claims description 7
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 6
- 230000037396 body weight Effects 0.000 claims description 6
- 238000002825 functional assay Methods 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 6
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 6
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- BGPJLYIFDLICMR-UHFFFAOYSA-N 1,4,2,3-dioxadithiolan-5-one Chemical compound O=C1OSSO1 BGPJLYIFDLICMR-UHFFFAOYSA-N 0.000 claims description 4
- FWALWHDJIBIZDE-UHFFFAOYSA-N 2-(2,4-dimethylpentan-3-yloxy)-3,6-diethyl-5-[4-methoxy-2-(trifluoromethoxy)phenyl]pyrazine Chemical group N1=C(OC(C(C)C)C(C)C)C(CC)=NC(C=2C(=CC(OC)=CC=2)OC(F)(F)F)=C1CC FWALWHDJIBIZDE-UHFFFAOYSA-N 0.000 claims description 4
- YFIPDLXBDOAVAO-UHFFFAOYSA-N 3-ethyl-6-methoxy-5-[2-methoxy-4-(trifluoromethoxy)phenyl]-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(CC)C(NC(CC)CC)=NC(OC)=C1C1=CC=C(OC(F)(F)F)C=C1OC YFIPDLXBDOAVAO-UHFFFAOYSA-N 0.000 claims description 4
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000005494 pyridonyl group Chemical group 0.000 claims description 4
- VYZPZUJZDAHHRC-UHFFFAOYSA-N 2,5-diethyl-3-(2-ethylbutyl)-6-[2-methoxy-4-(trifluoromethoxy)phenyl]pyrazine Chemical group N1=C(CC)C(CC(CC)CC)=NC(CC)=C1C1=CC=C(OC(F)(F)F)C=C1OC VYZPZUJZDAHHRC-UHFFFAOYSA-N 0.000 claims description 3
- NHYVVBVBDFCLMJ-UHFFFAOYSA-N 2,5-diethyl-3-(4-methoxy-2-methylphenyl)-6-pentan-3-yloxypyrazine Chemical group N1=C(CC)C(OC(CC)CC)=NC(CC)=C1C1=CC=C(OC)C=C1C NHYVVBVBDFCLMJ-UHFFFAOYSA-N 0.000 claims description 3
- LSKYMESYHOSCHL-UHFFFAOYSA-N 2,5-diethyl-3-heptan-4-yloxy-6-[4-methoxy-2-(trifluoromethoxy)phenyl]pyrazine Chemical group N1=C(CC)C(OC(CCC)CCC)=NC(CC)=C1C1=CC=C(OC)C=C1OC(F)(F)F LSKYMESYHOSCHL-UHFFFAOYSA-N 0.000 claims description 3
- KRFAELKVMRDFGF-UHFFFAOYSA-N 2,5-diethyl-3-pentan-3-yloxy-6-(2-propan-2-yloxy-4-propoxyphenyl)pyrazine Chemical group CC(C)OC1=CC(OCCC)=CC=C1C1=NC(CC)=C(OC(CC)CC)N=C1CC KRFAELKVMRDFGF-UHFFFAOYSA-N 0.000 claims description 3
- BXGITYIDSFZVCX-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-hexan-3-yloxypyrazine Chemical group N1=C(CC)C(OC(CC)CCC)=NC(CC)=C1C1=CC=C(OC)C=C1OC BXGITYIDSFZVCX-UHFFFAOYSA-N 0.000 claims description 3
- SYRRAMMZXBNZHX-UHFFFAOYSA-N 2-(2,4-dimethylpentan-3-yloxy)-3,6-diethyl-5-[2-methyl-4-(trifluoromethoxy)phenyl]pyrazine Chemical group N1=C(OC(C(C)C)C(C)C)C(CC)=NC(C=2C(=CC(OC(F)(F)F)=CC=2)C)=C1CC SYRRAMMZXBNZHX-UHFFFAOYSA-N 0.000 claims description 3
- LVXHVVYEVCWZQR-UHFFFAOYSA-N 2-(2,6-dimethoxyphenyl)-3,6-diethyl-5-hexan-3-yloxypyrazine Chemical group N1=C(CC)C(OC(CC)CCC)=NC(CC)=C1C1=C(OC)C=CC=C1OC LVXHVVYEVCWZQR-UHFFFAOYSA-N 0.000 claims description 3
- ACXXNHMWXNDVDI-UHFFFAOYSA-N 2-(4-butoxy-2-chlorophenyl)-3,6-diethyl-5-hexan-3-yloxypyrazine Chemical group ClC1=CC(OCCCC)=CC=C1C1=NC(CC)=C(OC(CC)CCC)N=C1CC ACXXNHMWXNDVDI-UHFFFAOYSA-N 0.000 claims description 3
- CSIRJPCJNLGAJQ-UHFFFAOYSA-N 2-[2,4-bis(trifluoromethyl)phenyl]-3,6-diethyl-5-pentan-3-yloxypyrazine Chemical group N1=C(CC)C(OC(CC)CC)=NC(CC)=C1C1=CC=C(C(F)(F)F)C=C1C(F)(F)F CSIRJPCJNLGAJQ-UHFFFAOYSA-N 0.000 claims description 3
- QPJXHFXRLKYFRR-UHFFFAOYSA-N 2-butan-2-ylsulfanyl-5-(2,4-dimethoxyphenyl)-3,6-diethylpyrazine Chemical compound N1=C(CC)C(SC(C)CC)=NC(CC)=C1C1=CC=C(OC)C=C1OC QPJXHFXRLKYFRR-UHFFFAOYSA-N 0.000 claims description 3
- ZPUQPHBDUCFMOJ-UHFFFAOYSA-N 3,6-diethyl-5-[2-methoxy-6-(trifluoromethoxy)phenyl]-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(CC)C(NC(CC)CC)=NC(CC)=C1C1=C(OC)C=CC=C1OC(F)(F)F ZPUQPHBDUCFMOJ-UHFFFAOYSA-N 0.000 claims description 3
- ZPWOVHNNMBKOFC-UHFFFAOYSA-N 3,6-diethyl-5-[4-methoxy-2-(trifluoromethyl)phenyl]-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(CC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(OC)C=C1C(F)(F)F ZPWOVHNNMBKOFC-UHFFFAOYSA-N 0.000 claims description 3
- LQORDWFDJZSRLW-UHFFFAOYSA-N 3,6-diethyl-5-naphthalen-2-yl-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(CC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(C=CC=C2)C2=C1 LQORDWFDJZSRLW-UHFFFAOYSA-N 0.000 claims description 3
- YXDAZDIDNULNFC-UHFFFAOYSA-N 3-ethyl-6-methoxy-5-[2-methyl-4-(trifluoromethoxy)phenyl]-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(CC)C(NC(CC)CC)=NC(OC)=C1C1=CC=C(OC(F)(F)F)C=C1C YXDAZDIDNULNFC-UHFFFAOYSA-N 0.000 claims description 3
- RLLMOVPGXDDHLP-UHFFFAOYSA-N 3-methoxy-5-(2-methoxy-4-propan-2-yloxyphenyl)-6-methyl-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(OC)C(NC(CC)CC)=NC(C)=C1C1=CC=C(OC(C)C)C=C1OC RLLMOVPGXDDHLP-UHFFFAOYSA-N 0.000 claims description 3
- ADAZQMSUAWEMQU-UHFFFAOYSA-N 4-[3-ethyl-6-methoxy-5-(pentan-3-ylamino)pyrazin-2-yl]-3-methoxyphenol Chemical group N1=C(OC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(O)C=C1OC ADAZQMSUAWEMQU-UHFFFAOYSA-N 0.000 claims description 3
- RIYHNDFRJNCQGN-UHFFFAOYSA-N 5-(2,4-dimethylphenyl)-6-ethyl-3-methoxy-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(OC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(C)C=C1C RIYHNDFRJNCQGN-UHFFFAOYSA-N 0.000 claims description 3
- VDRMLMFCKUCYPK-UHFFFAOYSA-N 5-(2-chloro-4-ethoxyphenyl)-3-methoxy-6-methyl-n-pentan-3-ylpyrazin-2-amine Chemical group ClC1=CC(OCC)=CC=C1C1=NC(OC)=C(NC(CC)CC)N=C1C VDRMLMFCKUCYPK-UHFFFAOYSA-N 0.000 claims description 3
- RAYXWHNXPOYBPJ-UHFFFAOYSA-N 5-(2-chloro-4-pentan-3-yloxyphenyl)-6-ethyl-3-methoxy-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(OC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(OC(CC)CC)C=C1Cl RAYXWHNXPOYBPJ-UHFFFAOYSA-N 0.000 claims description 3
- OXJBBGBLHNIBBX-UHFFFAOYSA-N 5-(2-chloro-4-propan-2-yloxyphenyl)-3-ethyl-6-methoxy-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(CC)C(NC(CC)CC)=NC(OC)=C1C1=CC=C(OC(C)C)C=C1Cl OXJBBGBLHNIBBX-UHFFFAOYSA-N 0.000 claims description 3
- WDEFCCPFEHGDOR-UHFFFAOYSA-N 5-(4-chloro-2,6-dimethoxyphenyl)-3-methoxy-6-methyl-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(OC)C(NC(CC)CC)=NC(C)=C1C1=C(OC)C=C(Cl)C=C1OC WDEFCCPFEHGDOR-UHFFFAOYSA-N 0.000 claims description 3
- GTQYQJWGNJYBNS-UHFFFAOYSA-N 5-(4-chloro-2,6-dimethoxyphenyl)-6-methoxypyrazin-2-amine Chemical group COC1=CC(Cl)=CC(OC)=C1C1=NC=C(N)N=C1OC GTQYQJWGNJYBNS-UHFFFAOYSA-N 0.000 claims description 3
- AAECUKNAQUIPBJ-UHFFFAOYSA-N 5-(4-chloro-2-methoxyphenyl)-3,6-diethyl-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(CC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(Cl)C=C1OC AAECUKNAQUIPBJ-UHFFFAOYSA-N 0.000 claims description 3
- LUBUGXITXCGDFU-UHFFFAOYSA-N 5-(4-chloro-2-methoxyphenyl)-6-ethyl-3-methoxy-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(OC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(Cl)C=C1OC LUBUGXITXCGDFU-UHFFFAOYSA-N 0.000 claims description 3
- IWJRUYQGXUSVDV-UHFFFAOYSA-N 5-(4-chloro-2-methylphenyl)-3,6-diethyl-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(CC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(Cl)C=C1C IWJRUYQGXUSVDV-UHFFFAOYSA-N 0.000 claims description 3
- GHYHREIGFVRCSZ-UHFFFAOYSA-N 5-(4-ethoxy-2-methoxyphenyl)-3-ethyl-6-methoxy-n-pentan-3-ylpyrazin-2-amine Chemical group COC1=CC(OCC)=CC=C1C1=NC(CC)=C(NC(CC)CC)N=C1OC GHYHREIGFVRCSZ-UHFFFAOYSA-N 0.000 claims description 3
- BRMRKRMGSAMLOJ-UHFFFAOYSA-N 5-(4-fluoro-2-methoxyphenyl)-6-methoxy-3-methyl-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(C)C(NC(CC)CC)=NC(OC)=C1C1=CC=C(F)C=C1OC BRMRKRMGSAMLOJ-UHFFFAOYSA-N 0.000 claims description 3
- OSHVTLMVDXKQIN-UHFFFAOYSA-N 5-[2-[2-chloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethyl)phenyl]-6-methoxy-3-methyl-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(C)C(NC(CC)CC)=NC(OC)=C1C1=CC=C(C(F)(F)F)C=C1C1=CC=C(C(F)(F)F)C=C1Cl OSHVTLMVDXKQIN-UHFFFAOYSA-N 0.000 claims description 3
- PVNFMIAFIQALIE-UHFFFAOYSA-N 5-[4-bromo-2-(trifluoromethoxy)phenyl]-3,6-diethyl-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(CC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(Br)C=C1OC(F)(F)F PVNFMIAFIQALIE-UHFFFAOYSA-N 0.000 claims description 3
- CIACCKNDSNVFAP-UHFFFAOYSA-N 5-[4-chloro-2-(trifluoromethyl)phenyl]-3,6-diethyl-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(CC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(Cl)C=C1C(F)(F)F CIACCKNDSNVFAP-UHFFFAOYSA-N 0.000 claims description 3
- FVTAVYVGYCXKBH-UHFFFAOYSA-N 6-ethyl-3-methoxy-5-(2-methoxy-4-propan-2-yloxyphenyl)-n-pentan-3-ylpyrazin-2-amine Chemical group N1=C(OC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(OC(C)C)C=C1OC FVTAVYVGYCXKBH-UHFFFAOYSA-N 0.000 claims description 3
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 238000000159 protein binding assay Methods 0.000 claims description 3
- PMMFSHPEWKGEFS-UHFFFAOYSA-N tert-butyl-[4-(3,6-diethyl-5-pentan-3-yloxypyrazin-2-yl)-3-ethoxyphenoxy]-dimethylsilane Chemical group CCOC1=CC(O[Si](C)(C)C(C)(C)C)=CC=C1C1=NC(CC)=C(OC(CC)CC)N=C1CC PMMFSHPEWKGEFS-UHFFFAOYSA-N 0.000 claims description 3
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- XFFQPEYVHSNGRB-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-3,6-diethyl-5-pentan-3-yloxypyrazine Chemical group N1=C(CC)C(OC(CC)CC)=NC(CC)=C1C1=CC=C(Cl)C=C1Cl XFFQPEYVHSNGRB-UHFFFAOYSA-N 0.000 claims description 2
- WLYPBMBWKYALCG-UHFFFAOYSA-N [2,4-bis(trifluoromethyl)phenyl]boronic acid Chemical group OB(O)C1=CC=C(C(F)(F)F)C=C1C(F)(F)F WLYPBMBWKYALCG-UHFFFAOYSA-N 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 238000012289 standard assay Methods 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 16
- 238000000099 in vitro assay Methods 0.000 claims 13
- 208000013200 Stress disease Diseases 0.000 claims 10
- 238000005406 washing Methods 0.000 claims 4
- XYQKQPCULMKZFH-UHFFFAOYSA-N 2,5-diethyl-3-(2-methoxy-4,6-dimethylphenyl)-6-pentan-3-yloxypyrazine Chemical group N1=C(CC)C(OC(CC)CC)=NC(CC)=C1C1=C(C)C=C(C)C=C1OC XYQKQPCULMKZFH-UHFFFAOYSA-N 0.000 claims 2
- OHXPPNCJBUNNPO-UHFFFAOYSA-N 2,5-diethyl-3-[2-methoxy-4,6-bis(trifluoromethyl)phenyl]-6-pentan-3-yloxypyrazine Chemical group N1=C(CC)C(OC(CC)CC)=NC(CC)=C1C1=C(OC)C=C(C(F)(F)F)C=C1C(F)(F)F OHXPPNCJBUNNPO-UHFFFAOYSA-N 0.000 claims 2
- YSOSXWRQRKKNLC-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-3,6-diethyl-5-pentan-2-yloxypyrazine Chemical group N1=C(CC)C(OC(C)CCC)=NC(CC)=C1C1=CC=C(Cl)C=C1Cl YSOSXWRQRKKNLC-UHFFFAOYSA-N 0.000 claims 2
- VXQWBWRDFSCLLK-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-3,6-dimethyl-5-pentan-3-yloxypyrazine Chemical group N1=C(C)C(OC(CC)CC)=NC(C)=C1C1=CC=C(Cl)C=C1Cl VXQWBWRDFSCLLK-UHFFFAOYSA-N 0.000 claims 2
- NMUBIASTRDUCCV-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-5-[2-(methoxymethyl)pyrrolidin-1-yl]-3,6-dimethylpyrazine Chemical group COCC1CCCN1C1=NC(C)=C(C=2C(=CC(Cl)=CC=2)Cl)N=C1C NMUBIASTRDUCCV-UHFFFAOYSA-N 0.000 claims 2
- SCLSROTZQVKIJB-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-5-[2-(methoxymethyl)pyrrolidin-1-yl]-3,6-dimethylpyrazine Chemical group COCC1CCCN1C1=NC(C)=C(C=2C(=CC(OC)=CC=2)OC)N=C1C SCLSROTZQVKIJB-UHFFFAOYSA-N 0.000 claims 2
- XIZRTKWPFZIEBA-UHFFFAOYSA-N 2-(2,4-dimethylpentan-3-yloxy)-3,6-diethyl-5-(2-ethyl-4-methoxyphenyl)pyrazine Chemical group CCC1=CC(OC)=CC=C1C1=NC(CC)=C(OC(C(C)C)C(C)C)N=C1CC XIZRTKWPFZIEBA-UHFFFAOYSA-N 0.000 claims 2
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- PKIMSBDGZDRTDE-UHFFFAOYSA-N 2-(3,6-diethyl-5-pentan-3-yloxypyrazin-2-yl)-3,5-dimethylphenol Chemical group N1=C(CC)C(OC(CC)CC)=NC(CC)=C1C1=C(C)C=C(C)C=C1O PKIMSBDGZDRTDE-UHFFFAOYSA-N 0.000 claims 2
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- 239000011701 zinc Substances 0.000 description 1
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Classifications
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- 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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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
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- C07D241/18—Oxygen or sulfur atoms
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- C07D241/20—Nitrogen atoms
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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
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
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- Child & Adolescent Psychology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Photoreceptors In Electrophotography (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
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US18293400P | 2000-02-16 | 2000-02-16 | |
US20645500P | 2000-05-22 | 2000-05-22 | |
PCT/US2001/005264 WO2001060806A2 (en) | 2000-02-16 | 2001-02-16 | Substituted arylpyrazines |
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BG110174A BG110174A (en) | 2000-02-16 | 2002-07-31 | Substituted arylpyrazines |
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AT (1) | ATE307121T1 (cs) |
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Families Citing this family (38)
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WO2002024681A2 (en) | 2000-09-20 | 2002-03-28 | Ortho-Mcneil Pharmaceutical, Inc. | Pyrazine derivatives as modulators of tyrosine kinases |
BR0209920A (pt) | 2001-05-22 | 2004-03-30 | Neurogen Corp | Composto ou sal farmaceuticamente aceitável do mesmo, métodos de tratar ansiedade, depressão ou estresse e sìndrome do intestino irritável ou doença de crohn, de detectar receptores de crf1 em uma primeira amostra biológica, de demonstrar a presença ou ausência de receptores de crf1 em uma amostra biológica e de inibir a ligação de crf a um receptor de crf1, composição farmacêutica, e, embalagem |
AP2003002924A0 (en) * | 2001-06-12 | 2003-12-31 | Neurogen Corp | 2,5-diarylpyrazines, 2,5 - diarylpyridines and 2,5 - diarylpyrimidines as CRF1 receptor modulators |
SE0102438D0 (sv) * | 2001-07-05 | 2001-07-05 | Astrazeneca Ab | New compounds |
SE0102439D0 (sv) * | 2001-07-05 | 2001-07-05 | Astrazeneca Ab | New compounds |
US6852737B2 (en) * | 2001-08-06 | 2005-02-08 | Recordati Ireland Limited | Crude and crystalline forms of lercanidipine hydrochloride |
ITMI20011726A1 (it) | 2001-08-06 | 2003-02-06 | Recordati Ind Chimica E Farma | Forme polimorfe della lercanidipina cloridrato |
US6992087B2 (en) | 2001-11-21 | 2006-01-31 | Pfizer Inc | Substituted aryl 1,4-pyrazine derivatives |
MXPA04004714A (es) * | 2001-11-21 | 2004-08-19 | Upjohn Co | Derivados de aril 1,4-pirazina sustituidos. |
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WO2004000318A2 (en) | 2002-06-21 | 2003-12-31 | Cellular Genomics, Inc. | Certain amino-substituted monocycles as kinase modulators |
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EP1539736A1 (en) * | 2002-09-12 | 2005-06-15 | Pharmacia & Upjohn Company LLC | Substituted 1,4-pyrazine derivatives |
EP1565454A1 (en) * | 2002-11-21 | 2005-08-24 | Pharmacia & Upjohn Company LLC | Pyrazine compounds as crf modulators |
SE0203753D0 (sv) * | 2002-12-17 | 2002-12-17 | Astrazeneca Ab | New compounds |
SE0203754D0 (sv) * | 2002-12-17 | 2002-12-17 | Astrazeneca Ab | New compounds |
DK1603570T5 (da) | 2003-02-26 | 2013-12-09 | Sugen Inc | Aminoheteroarylforbindelser som proteinkinaseinhibitorer |
JP2006525993A (ja) | 2003-05-09 | 2006-11-16 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | Crf1受容体拮抗剤である化合物 |
CA2524352A1 (en) | 2003-05-09 | 2004-11-18 | Pharmacia & Upjohn Company Llc | Substituted pyrimidine derivatives |
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BRPI0415863A (pt) * | 2003-10-27 | 2007-01-09 | Astellas Pharma Inc | derivados pirazina e seus usos farmacêuticos |
US20060211710A1 (en) * | 2005-03-17 | 2006-09-21 | Pfizer Inc | Substituted aryl 1,4-pyrazine derivatives |
AR053712A1 (es) * | 2005-04-18 | 2007-05-16 | Neurogen Corp | Heteroarilos sustituidos, antagonistas de cb1 (receptor 1 canabinoide) |
PL1959955T3 (pl) * | 2005-12-05 | 2011-04-29 | Pfizer Prod Inc | Sposób traktowania nieprawidłowego wzrostu komórek |
AU2006323025B2 (en) * | 2005-12-05 | 2012-07-05 | Pfizer Products Inc. | Polymorphs of a c-Met/HGFR inhibitor |
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MX369857B (es) | 2014-02-14 | 2019-11-25 | Takeda Pharmaceuticals Co | Pirazinas moduladoras de receptor 6 acoplado a la proteina g (gpr6). |
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JP6916279B2 (ja) | 2016-07-12 | 2021-08-11 | レヴォリューション・メディスンズ,インコーポレイテッド | アロステリックshp2阻害剤としての2,5−二置換3−メチルピラジンおよび2,5,6−三置換3−メチルピラジン |
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EP3724189B1 (en) | 2017-12-15 | 2023-10-04 | Revolution Medicines, Inc. | Polycyclic compounds as allosteric shp2 inhibitors |
JP2021523933A (ja) * | 2018-04-20 | 2021-09-09 | バージニア・テック・インテレクチュアル・プロパティーズ・インコーポレイテッドVirginia Tech Intellectual Properties, Inc. | ミトコンドリア脱共役剤として有用なイミダゾピリジン |
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DE2425355A1 (de) | 1974-05-25 | 1975-12-04 | Basf Ag | Verfahren zur herstellung von pyrazinen |
EG12387A (en) * | 1975-04-21 | 1978-12-31 | Merck & Co Inc | Process for preparing of piperazinyl pyrazines |
FR2398738A1 (fr) * | 1977-06-22 | 1979-02-23 | Lilly Co Eli | Preparation de benzoylurees |
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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 |
JPH0739398B2 (ja) * | 1986-10-04 | 1995-05-01 | 宇部興産株式会社 | 液晶性ピラジン誘導体 |
NZ227684A (en) * | 1988-01-30 | 1991-07-26 | Merck Sharp & Dohme | Pyrazine, pyridazine, and pyrimidine derivatives and pharmaceutical compositions |
JPH0348666A (ja) | 1989-07-17 | 1991-03-01 | Rasa Kogyo Kk | 芳香族ジアミン化合物の製造方法 |
DE3940477A1 (de) * | 1989-12-07 | 1991-06-13 | Bayer Ag | Hetaryl-substituierte pyridinylpyrimidin-derivate |
GB2272216A (en) * | 1992-11-04 | 1994-05-11 | Merck Patent Gmbh | Liquid crystalline di-, tri- and tetra-fluorinated phenylpyrazines |
WO1995010506A1 (en) | 1993-10-12 | 1995-04-20 | The Du Pont Merck Pharmaceutical Company | 1n-alkyl-n-arylpyrimidinamines and derivatives thereof |
AU7095496A (en) * | 1995-09-26 | 1997-04-17 | Nippon Soda Co., Ltd. | Pyrazole compounds, process for preparing the same, and agrohorticultural bactericide |
WO1998011075A1 (en) | 1996-09-16 | 1998-03-19 | Du Pont Pharmaceuticals Company | Pyrazinones and triazinones and their derivatives thereof |
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BE1011077A3 (fr) | 1997-03-28 | 1999-04-06 | Univ Catholique Louvain | Composition pharmaceutique, cosmetique et/ou alimentaire aux proprietes anti-oxydantes. |
CN1231440C (zh) | 1998-01-28 | 2005-12-14 | 盐野义制药株式会社 | 新的三环化合物 |
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WO2000045800A2 (en) | 1999-02-02 | 2000-08-10 | K.U. Leuven Research & Development | Immunosurpressive effects of pteridine derivatives |
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