OA12178A - Substituted arylpyrazines. - Google Patents
Substituted arylpyrazines. Download PDFInfo
- Publication number
- OA12178A OA12178A OA1200200251A OA1200200251A OA12178A OA 12178 A OA12178 A OA 12178A OA 1200200251 A OA1200200251 A OA 1200200251A OA 1200200251 A OA1200200251 A OA 1200200251A OA 12178 A OA12178 A OA 12178A
- Authority
- OA
- OAPI
- Prior art keywords
- compound according
- alkyl
- named
- amine
- phenyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract description 366
- 238000000034 method Methods 0.000 claims abstract description 59
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 51
- 208000035475 disorder Diseases 0.000 claims abstract description 31
- 201000010099 disease Diseases 0.000 claims abstract description 17
- 241000282414 Homo sapiens Species 0.000 claims abstract description 12
- 108091005471 CRHR1 Proteins 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 261
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 149
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 116
- -1 cyano, nitro, amino Chemical group 0.000 claims description 108
- 229910052736 halogen Inorganic materials 0.000 claims description 93
- 150000002367 halogens Chemical group 0.000 claims description 84
- 239000000203 mixture Substances 0.000 claims description 74
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 68
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 58
- 125000004432 carbon atom Chemical group C* 0.000 claims description 55
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 claims description 55
- 125000001188 haloalkyl group Chemical group 0.000 claims description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 47
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 238000000338 in vitro Methods 0.000 claims description 31
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 claims description 30
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 150000001412 amines Chemical class 0.000 claims description 26
- 102000005962 receptors Human genes 0.000 claims description 26
- 108020003175 receptors Proteins 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 238000003556 assay Methods 0.000 claims description 22
- 230000000694 effects Effects 0.000 claims description 21
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 208000015114 central nervous system disease Diseases 0.000 claims description 16
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 229920006395 saturated elastomer Polymers 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 230000027455 binding Effects 0.000 claims description 12
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 11
- 208000019901 Anxiety disease Diseases 0.000 claims description 10
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 10
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 9
- 108010052164 Sodium Channels Proteins 0.000 claims description 9
- 102000018674 Sodium Channels Human genes 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 238000000159 protein binding assay Methods 0.000 claims description 9
- 238000001525 receptor binding assay Methods 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 208000030814 Eating disease Diseases 0.000 claims description 7
- 235000014632 disordered eating Nutrition 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 4
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 4
- 229910052727 yttrium Inorganic materials 0.000 claims description 4
- BGPJLYIFDLICMR-UHFFFAOYSA-N 1,4,2,3-dioxadithiolan-5-one Chemical compound O=C1OSSO1 BGPJLYIFDLICMR-UHFFFAOYSA-N 0.000 claims description 3
- 208000020925 Bipolar disease Diseases 0.000 claims description 3
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- 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 2
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 2
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 102100029469 WD repeat and HMG-box DNA-binding protein 1 Human genes 0.000 claims description 2
- 101710097421 WD repeat and HMG-box DNA-binding protein 1 Proteins 0.000 claims description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 6
- 102100025878 C1q-related factor Human genes 0.000 claims 4
- AHFINSWGYAZBOZ-UHFFFAOYSA-N 4-chloro-2-(trifluoromethyl)benzaldehyde Chemical group FC(F)(F)C1=CC(Cl)=CC=C1C=O AHFINSWGYAZBOZ-UHFFFAOYSA-N 0.000 claims 2
- 125000004122 cyclic group Chemical group 0.000 claims 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- NHYVVBVBDFCLMJ-UHFFFAOYSA-N 2,5-diethyl-3-(4-methoxy-2-methylphenyl)-6-pentan-3-yloxypyrazine Chemical compound N1=C(CC)C(OC(CC)CC)=NC(CC)=C1C1=CC=C(OC)C=C1C NHYVVBVBDFCLMJ-UHFFFAOYSA-N 0.000 claims 1
- KRFAELKVMRDFGF-UHFFFAOYSA-N 2,5-diethyl-3-pentan-3-yloxy-6-(2-propan-2-yloxy-4-propoxyphenyl)pyrazine Chemical compound CC(C)OC1=CC(OCCC)=CC=C1C1=NC(CC)=C(OC(CC)CC)N=C1CC KRFAELKVMRDFGF-UHFFFAOYSA-N 0.000 claims 1
- YSOSXWRQRKKNLC-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-3,6-diethyl-5-pentan-2-yloxypyrazine Chemical compound N1=C(CC)C(OC(C)CCC)=NC(CC)=C1C1=CC=C(Cl)C=C1Cl YSOSXWRQRKKNLC-UHFFFAOYSA-N 0.000 claims 1
- BXGITYIDSFZVCX-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3,6-diethyl-5-hexan-3-yloxypyrazine Chemical compound N1=C(CC)C(OC(CC)CCC)=NC(CC)=C1C1=CC=C(OC)C=C1OC BXGITYIDSFZVCX-UHFFFAOYSA-N 0.000 claims 1
- ACXXNHMWXNDVDI-UHFFFAOYSA-N 2-(4-butoxy-2-chlorophenyl)-3,6-diethyl-5-hexan-3-yloxypyrazine Chemical compound ClC1=CC(OCCCC)=CC=C1C1=NC(CC)=C(OC(CC)CCC)N=C1CC ACXXNHMWXNDVDI-UHFFFAOYSA-N 0.000 claims 1
- ZPUQPHBDUCFMOJ-UHFFFAOYSA-N 3,6-diethyl-5-[2-methoxy-6-(trifluoromethoxy)phenyl]-n-pentan-3-ylpyrazin-2-amine Chemical compound N1=C(CC)C(NC(CC)CC)=NC(CC)=C1C1=C(OC)C=CC=C1OC(F)(F)F ZPUQPHBDUCFMOJ-UHFFFAOYSA-N 0.000 claims 1
- QIZHOWDQYOYIOX-UHFFFAOYSA-N 5-(2,4-dimethylphenyl)-6-methoxy-3-methyl-n-pentan-3-ylpyrazin-2-amine Chemical compound N1=C(C)C(NC(CC)CC)=NC(OC)=C1C1=CC=C(C)C=C1C QIZHOWDQYOYIOX-UHFFFAOYSA-N 0.000 claims 1
- PCNGNNSUPCYPDC-UHFFFAOYSA-N 5-(2-chloro-4-methylphenyl)-3,6-diethyl-n-pentan-3-ylpyrazin-2-amine Chemical compound N1=C(CC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(C)C=C1Cl PCNGNNSUPCYPDC-UHFFFAOYSA-N 0.000 claims 1
- CIACCKNDSNVFAP-UHFFFAOYSA-N 5-[4-chloro-2-(trifluoromethyl)phenyl]-3,6-diethyl-n-pentan-3-ylpyrazin-2-amine Chemical compound N1=C(CC)C(NC(CC)CC)=NC(CC)=C1C1=CC=C(Cl)C=C1C(F)(F)F CIACCKNDSNVFAP-UHFFFAOYSA-N 0.000 claims 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 claims 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 claims 1
- OLLFMCQYCAMBHM-UHFFFAOYSA-N N-methyl-5-pentan-3-yloxypyrazin-2-amine Chemical compound CNC1=NC=C(N=C1)OC(CC)CC OLLFMCQYCAMBHM-UHFFFAOYSA-N 0.000 claims 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims 1
- IQWVEGXQPJETDK-UHFFFAOYSA-N n-(cyclopropylmethyl)-5-(2,4-dichlorophenyl)-3,6-diethyl-n-propylpyrazin-2-amine Chemical compound N=1C(CC)=C(C=2C(=CC(Cl)=CC=2)Cl)N=C(CC)C=1N(CCC)CC1CC1 IQWVEGXQPJETDK-UHFFFAOYSA-N 0.000 claims 1
- 229960005419 nitrogen Drugs 0.000 claims 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 16
- 208000019022 Mood disease Diseases 0.000 abstract description 6
- 208000017194 Affective disease Diseases 0.000 abstract description 4
- 208000012902 Nervous system disease Diseases 0.000 abstract description 4
- 208000025966 Neurological disease Diseases 0.000 abstract description 4
- 230000001154 acute effect Effects 0.000 abstract description 3
- 230000001684 chronic effect Effects 0.000 abstract description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 68
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 64
- 239000000243 solution Substances 0.000 description 59
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 47
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 47
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 28
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 28
- 239000003921 oil Substances 0.000 description 26
- 235000019198 oils Nutrition 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 25
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 24
- 150000003839 salts Chemical class 0.000 description 24
- 229910052938 sodium sulfate Inorganic materials 0.000 description 24
- 235000011152 sodium sulphate Nutrition 0.000 description 24
- 239000000047 product Substances 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000000284 extract Substances 0.000 description 21
- 125000004429 atom Chemical group 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 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 description 11
- 125000005843 halogen group Chemical group 0.000 description 11
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 229910052708 sodium Inorganic materials 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 101150041968 CDC13 gene Proteins 0.000 description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 231100000252 nontoxic Toxicity 0.000 description 7
- 230000003000 nontoxic effect Effects 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
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- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
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- 238000010626 work up procedure Methods 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- MMSLSKDMIZOHRX-WYDAWZGFSA-N α-helical crf(9-41) Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(N)=O MMSLSKDMIZOHRX-WYDAWZGFSA-N 0.000 description 1
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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- C07D241/00—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
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
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- C07D241/20—Nitrogen atoms
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- 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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- 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 (2)
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US18293400P | 2000-02-16 | 2000-02-16 | |
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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 |
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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 |
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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 |
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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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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 |
EP3982949A4 (en) * | 2019-06-14 | 2023-10-11 | Disarm Therapeutics, Inc. | MRSA1 INHIBITORS |
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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 |
US4293552A (en) * | 1978-02-27 | 1981-10-06 | Eli Lilly And Company | Novel 1-(mono-o-substituted benzoyl)-3-(substituted pyrazinyl) ureas |
US4211870A (en) * | 1979-04-06 | 1980-07-08 | Eli Lilly And Company | Preparation of substituted 2-aminopyrazines |
JPS59144772A (ja) * | 1983-02-08 | 1984-08-18 | Ube Ind Ltd | 液晶性ピラジン誘導体およびその製法 |
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 |
MA26473A1 (fr) * | 1997-03-01 | 2004-12-20 | Glaxo Group Ltd | Composes pharmacologiquement actifs. |
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 |
GB9818881D0 (en) | 1998-08-28 | 1998-10-21 | Glaxo Group Ltd | Compounds |
WO2000045800A2 (en) | 1999-02-02 | 2000-08-10 | K.U. Leuven Research & Development | Immunosurpressive effects of pteridine derivatives |
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