MX2011005100A - Compuestos pirazina como inhibidores de fosfodiesterasa 10. - Google Patents
Compuestos pirazina como inhibidores de fosfodiesterasa 10.Info
- Publication number
- MX2011005100A MX2011005100A MX2011005100A MX2011005100A MX2011005100A MX 2011005100 A MX2011005100 A MX 2011005100A MX 2011005100 A MX2011005100 A MX 2011005100A MX 2011005100 A MX2011005100 A MX 2011005100A MX 2011005100 A MX2011005100 A MX 2011005100A
- Authority
- MX
- Mexico
- Prior art keywords
- benzo
- pyrazin
- phenyl
- yloxy
- imidazol
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title claims description 31
- 150000003216 pyrazines Chemical class 0.000 title abstract description 4
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title description 6
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 177
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 53
- 201000010099 disease Diseases 0.000 claims abstract description 40
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims abstract description 23
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 20
- 208000020925 Bipolar disease Diseases 0.000 claims abstract description 14
- 208000035475 disorder Diseases 0.000 claims abstract description 13
- -1 tetrahydrofuranoyl Chemical group 0.000 claims description 438
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 366
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 157
- 229920006395 saturated elastomer Polymers 0.000 claims description 139
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 122
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 112
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 109
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 97
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 90
- 229910052801 chlorine Inorganic materials 0.000 claims description 87
- 229910052731 fluorine Inorganic materials 0.000 claims description 86
- 229910052794 bromium Inorganic materials 0.000 claims description 78
- 229910052757 nitrogen Inorganic materials 0.000 claims description 60
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 59
- 125000004429 atom Chemical group 0.000 claims description 58
- 229910052799 carbon Inorganic materials 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- 229910052717 sulfur Inorganic materials 0.000 claims description 32
- MPVDXIMFBOLMNW-UHFFFAOYSA-N chembl1615565 Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1N=NC1=CC=CC=C1 MPVDXIMFBOLMNW-UHFFFAOYSA-N 0.000 claims description 27
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 125000002950 monocyclic group Chemical group 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 206010012289 Dementia Diseases 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 17
- 125000005605 benzo group Chemical group 0.000 claims description 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 17
- 125000004434 sulfur atom Chemical group 0.000 claims description 17
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 16
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000002619 bicyclic group Chemical group 0.000 claims description 14
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 14
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- UHGULLIUJBCTEF-UHFFFAOYSA-N 2-aminobenzothiazole Chemical compound C1=CC=C2SC(N)=NC2=C1 UHGULLIUJBCTEF-UHFFFAOYSA-N 0.000 claims description 13
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 208000018737 Parkinson disease Diseases 0.000 claims description 11
- 208000028017 Psychotic disease Diseases 0.000 claims description 11
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 10
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 10
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 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 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 206010008748 Chorea Diseases 0.000 claims description 7
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 229910052701 rubidium Inorganic materials 0.000 claims description 7
- DEPDDPLQZYCHOH-UHFFFAOYSA-N 1h-imidazol-2-amine Chemical compound NC1=NC=CN1 DEPDDPLQZYCHOH-UHFFFAOYSA-N 0.000 claims description 6
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 6
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 6
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 6
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 6
- 125000003725 azepanyl group Chemical group 0.000 claims description 6
- 125000002393 azetidinyl group Chemical group 0.000 claims description 6
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 claims description 6
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 6
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 6
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 6
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 6
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000003551 oxepanyl group Chemical group 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- DATJETPTDKFEEF-UHFFFAOYSA-N pyrrolidine-3-carbonitrile Chemical compound N#CC1CCNC1 DATJETPTDKFEEF-UHFFFAOYSA-N 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 208000011117 substance-related disease Diseases 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 6
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 229910052727 yttrium Inorganic materials 0.000 claims description 6
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 5
- GQPNNKHTDDJYMP-UHFFFAOYSA-N 4-(3-chloropyrazin-2-yl)oxybenzaldehyde Chemical compound ClC1=NC=CN=C1OC1=CC=C(C=O)C=C1 GQPNNKHTDDJYMP-UHFFFAOYSA-N 0.000 claims description 5
- 206010010219 Compulsions Diseases 0.000 claims description 5
- 206010026749 Mania Diseases 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 206010013663 drug dependence Diseases 0.000 claims description 5
- DOERLFMEMVFBQS-UHFFFAOYSA-N n-[4-(3-chloropyrazin-2-yl)oxyphenyl]-6-fluoro-1,3-benzothiazol-2-amine Chemical compound S1C2=CC(F)=CC=C2N=C1NC(C=C1)=CC=C1OC1=NC=CN=C1Cl DOERLFMEMVFBQS-UHFFFAOYSA-N 0.000 claims description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- NIMQYXHSYCEJLU-UHFFFAOYSA-N 4-(3-morpholin-4-ylpyrazin-2-yl)oxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OC1=NC=CN=C1N1CCOCC1 NIMQYXHSYCEJLU-UHFFFAOYSA-N 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- NYXHUSNUGHZSKK-UHFFFAOYSA-N COC1CCN(CC1)C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O Chemical compound COC1CCN(CC1)C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O NYXHUSNUGHZSKK-UHFFFAOYSA-N 0.000 claims description 4
- 208000019022 Mood disease Diseases 0.000 claims description 4
- LWEHAYWSXSNTAN-UHFFFAOYSA-N OC1CC(CCC1)C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O Chemical compound OC1CC(CCC1)C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O LWEHAYWSXSNTAN-UHFFFAOYSA-N 0.000 claims description 4
- YNKHISLAJZLSNR-UHFFFAOYSA-N OC1CN(CC1)C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O Chemical compound OC1CN(CC1)C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O YNKHISLAJZLSNR-UHFFFAOYSA-N 0.000 claims description 4
- 206010034719 Personality change Diseases 0.000 claims description 4
- 150000001720 carbohydrates Chemical group 0.000 claims description 4
- PQANGXXSEABURG-UHFFFAOYSA-N cyclohex-2-en-1-ol Chemical compound OC1CCCC=C1 PQANGXXSEABURG-UHFFFAOYSA-N 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- RLZJFTOYCVIYLE-UHFFFAOYSA-N oxane-4-carbonitrile Chemical compound N#CC1CCOCC1 RLZJFTOYCVIYLE-UHFFFAOYSA-N 0.000 claims description 4
- BKUFYUPSQXPJGX-UHFFFAOYSA-N C1(CCCC1)C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O Chemical compound C1(CCCC1)C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O BKUFYUPSQXPJGX-UHFFFAOYSA-N 0.000 claims description 3
- OBFWKHFOQNLCHV-UHFFFAOYSA-N COC1=NC=CC=C1C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O Chemical compound COC1=NC=CC=C1C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O OBFWKHFOQNLCHV-UHFFFAOYSA-N 0.000 claims description 3
- NLGQVZJXELIMRV-UHFFFAOYSA-N COCC1N(CCC1)C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O Chemical compound COCC1N(CCC1)C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O NLGQVZJXELIMRV-UHFFFAOYSA-N 0.000 claims description 3
- KSDGDEIZWGGUDZ-UHFFFAOYSA-N [1-[3-[4-(1,3-benzothiazol-2-ylamino)phenoxy]pyrazin-2-yl]piperidin-2-yl]methanol Chemical compound OCC1CCCCN1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=NC2=CC=CC=C2S1 KSDGDEIZWGGUDZ-UHFFFAOYSA-N 0.000 claims description 3
- UESDQIHAOCLDAK-UHFFFAOYSA-N [4-(3-morpholin-4-ylpyrazin-2-yl)oxyphenyl]-(1-propan-2-ylbenzimidazol-2-yl)methanone Chemical compound N=1C2=CC=CC=C2N(C(C)C)C=1C(=O)C(C=C1)=CC=C1OC1=NC=CN=C1N1CCOCC1 UESDQIHAOCLDAK-UHFFFAOYSA-N 0.000 claims description 3
- XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 0.000 claims description 3
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 claims description 3
- KRRMOUBLHUGKFX-KRWDZBQOSA-N n-[4-[3-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]pyrazin-2-yl]oxyphenyl]-1,3-benzothiazol-2-amine Chemical compound COC[C@@H]1CCCN1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=NC2=CC=CC=C2S1 KRRMOUBLHUGKFX-KRWDZBQOSA-N 0.000 claims description 3
- 150000002829 nitrogen Chemical class 0.000 claims description 3
- YNCIDBYSTGADKV-UHFFFAOYSA-N (1-methylbenzimidazol-2-yl)-[4-(3-morpholin-4-ylpyrazin-2-yl)oxyphenyl]methanone Chemical compound N=1C2=CC=CC=C2N(C)C=1C(=O)C(C=C1)=CC=C1OC1=NC=CN=C1N1CCOCC1 YNCIDBYSTGADKV-UHFFFAOYSA-N 0.000 claims description 2
- GCQAVHNIIDWDIK-UHFFFAOYSA-N (1-methylbenzimidazol-2-yl)-[4-[3-(2-methylpyridin-3-yl)pyrazin-2-yl]oxyphenyl]methanone Chemical compound CC1=NC=CC=C1C1=NC=CN=C1OC1=CC=C(C(=O)C=2N(C3=CC=CC=C3N=2)C)C=C1 GCQAVHNIIDWDIK-UHFFFAOYSA-N 0.000 claims description 2
- JZSMZKJZDCZCGJ-UHFFFAOYSA-N (1-methylbenzimidazol-2-yl)-[4-[3-(oxan-4-yl)pyrazin-2-yl]oxyphenyl]methanone Chemical compound N=1C2=CC=CC=C2N(C)C=1C(=O)C(C=C1)=CC=C1OC1=NC=CN=C1C1CCOCC1 JZSMZKJZDCZCGJ-UHFFFAOYSA-N 0.000 claims description 2
- LIUKTCWPZUWMKH-NVXWUHKLSA-N (1r,3r)-3-[3-[4-(1,3-benzothiazol-2-ylamino)phenoxy]pyrazin-2-yl]cyclohexan-1-ol Chemical compound C1[C@H](O)CCC[C@H]1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=NC2=CC=CC=C2S1 LIUKTCWPZUWMKH-NVXWUHKLSA-N 0.000 claims description 2
- BLLKHCJAOCXHCW-HNNXBMFYSA-N (3s)-3-[3-[4-(1,3-benzothiazol-2-ylamino)phenoxy]pyrazin-2-yl]cyclohexan-1-one Chemical compound C1C(=O)CCC[C@@H]1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=NC2=CC=CC=C2S1 BLLKHCJAOCXHCW-HNNXBMFYSA-N 0.000 claims description 2
- AFWSQFMTRFITGY-UHFFFAOYSA-N (5-fluoro-1-methylbenzimidazol-2-yl)-[4-[3-(oxan-4-yl)pyrazin-2-yl]oxyphenyl]methanone Chemical compound N=1C2=CC(F)=CC=C2N(C)C=1C(=O)C(C=C1)=CC=C1OC1=NC=CN=C1C1CCOCC1 AFWSQFMTRFITGY-UHFFFAOYSA-N 0.000 claims description 2
- WOMJZGSOHCMFTN-UHFFFAOYSA-N (6-fluoro-1h-benzimidazol-2-yl)-[4-[3-(2-methoxypyridin-3-yl)pyrazin-2-yl]oxyphenyl]methanone Chemical compound COC1=NC=CC=C1C1=NC=CN=C1OC1=CC=C(C(=O)C=2NC3=CC=C(F)C=C3N=2)C=C1 WOMJZGSOHCMFTN-UHFFFAOYSA-N 0.000 claims description 2
- DVBCTQVDMKFPPK-UHFFFAOYSA-N 1,3-benzothiazol-2-yl-[4-(3-morpholin-4-ylpyrazin-2-yl)oxyphenyl]methanone Chemical compound N=1C2=CC=CC=C2SC=1C(=O)C(C=C1)=CC=C1OC1=NC=CN=C1N1CCOCC1 DVBCTQVDMKFPPK-UHFFFAOYSA-N 0.000 claims description 2
- PODKIINFHOBJKF-UHFFFAOYSA-N 1-[3-[4-(1,3-benzothiazol-2-ylamino)phenoxy]pyrazin-2-yl]-4-methylpiperidin-4-ol Chemical compound C1CC(C)(O)CCN1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=NC2=CC=CC=C2S1 PODKIINFHOBJKF-UHFFFAOYSA-N 0.000 claims description 2
- KFCTWWLEMAKQQT-UHFFFAOYSA-N 1-[3-[4-(1,3-benzothiazol-2-ylamino)phenoxy]pyrazin-2-yl]azetidine-3-carbonitrile Chemical compound C1C(C#N)CN1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=NC2=CC=CC=C2S1 KFCTWWLEMAKQQT-UHFFFAOYSA-N 0.000 claims description 2
- CHAZKGHHVDIGDH-UHFFFAOYSA-N 1-[4-[3-[4-(1,3-benzothiazol-2-ylamino)phenoxy]pyrazin-2-yl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=NC2=CC=CC=C2S1 CHAZKGHHVDIGDH-UHFFFAOYSA-N 0.000 claims description 2
- NFJWUVZWQQNUEZ-UHFFFAOYSA-N 1-[4-[3-[4-(1,3-benzothiazol-2-ylamino)phenoxy]pyrazin-2-yl]piperidin-1-yl]-2-fluoropropan-1-one Chemical compound C1CN(C(=O)C(F)C)CCC1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=NC2=CC=CC=C2S1 NFJWUVZWQQNUEZ-UHFFFAOYSA-N 0.000 claims description 2
- CKKWDWPXKBMQAE-UHFFFAOYSA-N 1-[4-[3-[6-(1,3-benzothiazol-2-ylamino)pyridin-3-yl]oxypyrazin-2-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NC=CN=C1OC(C=N1)=CC=C1NC1=NC2=CC=CC=C2S1 CKKWDWPXKBMQAE-UHFFFAOYSA-N 0.000 claims description 2
- FSOBJGLZSZGYOL-UHFFFAOYSA-N 1h-benzimidazol-2-yl-[4-[3-(1,4-oxazepan-4-yl)pyrazin-2-yl]oxyphenyl]methanone Chemical compound N=1C2=CC=CC=C2NC=1C(=O)C(C=C1)=CC=C1OC1=NC=CN=C1N1CCCOCC1 FSOBJGLZSZGYOL-UHFFFAOYSA-N 0.000 claims description 2
- WKXMBUVKQCWZQC-UHFFFAOYSA-N 1h-benzimidazol-2-yl-[4-[3-(2-methylpropoxy)pyrazin-2-yl]oxyphenyl]methanone Chemical compound CC(C)COC1=NC=CN=C1OC1=CC=C(C(=O)C=2NC3=CC=CC=C3N=2)C=C1 WKXMBUVKQCWZQC-UHFFFAOYSA-N 0.000 claims description 2
- SGVADHZEXLKTJV-UHFFFAOYSA-N 1h-imidazo[4,5-b]pyridin-2-yl-[4-(3-morpholin-4-ylpyrazin-2-yl)oxyphenyl]methanone Chemical compound N=1C2=NC=CC=C2NC=1C(=O)C(C=C1)=CC=C1OC1=NC=CN=C1N1CCOCC1 SGVADHZEXLKTJV-UHFFFAOYSA-N 0.000 claims description 2
- VQBSHRMJYCLXMB-UHFFFAOYSA-N 2-[4-[3-[4-(1,3-benzothiazol-2-ylamino)phenoxy]pyrazin-2-yl]piperazin-1-yl]ethanol Chemical compound C1CN(CCO)CCN1C1=NC=CN=C1OC(C=C1)=CC=C1NC1=NC2=CC=CC=C2S1 VQBSHRMJYCLXMB-UHFFFAOYSA-N 0.000 claims description 2
- WXGATHRIMCDRGO-UHFFFAOYSA-N 4-(3-pyridin-4-ylpyrazin-2-yl)oxybenzaldehyde Chemical compound N1=CC=C(C=C1)C=1C(=NC=CN=1)OC1=CC=C(C=C1)C=O WXGATHRIMCDRGO-UHFFFAOYSA-N 0.000 claims description 2
- MVMCMVVKUMPLEH-UHFFFAOYSA-N 4-[3-(2-pyrrolidin-1-ylethoxy)pyrazin-2-yl]oxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OC1=NC=CN=C1OCCN1CCCC1 MVMCMVVKUMPLEH-UHFFFAOYSA-N 0.000 claims description 2
- CBMYTZVXJPYTMK-UHFFFAOYSA-N 4-[3-(4,4-difluorocyclohexen-1-yl)pyrazin-2-yl]oxybenzaldehyde Chemical compound FC1(CC=C(CC1)C=1C(=NC=CN1)OC1=CC=C(C=C1)C=O)F CBMYTZVXJPYTMK-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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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
- C07D403/14—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 three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
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- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
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| US16621209P | 2009-04-02 | 2009-04-02 | |
| PCT/US2009/064637 WO2010057121A1 (en) | 2008-11-14 | 2009-11-16 | Pyrazine compounds as phosphodiesterase 10 inhibitors |
Publications (1)
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| MX2011005100A true MX2011005100A (es) | 2011-05-30 |
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| MX2011005100A MX2011005100A (es) | 2008-11-14 | 2009-11-16 | Compuestos pirazina como inhibidores de fosfodiesterasa 10. |
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| US9156812B2 (en) | 2008-06-04 | 2015-10-13 | Bristol-Myers Squibb Company | Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine |
| US8637500B2 (en) * | 2008-12-17 | 2014-01-28 | Amgen Inc. | Aminopyridine and carboxypyridine compounds as phosphodiesterase 10 inhibitors |
| KR101730665B1 (ko) | 2009-02-05 | 2017-04-26 | 다케다 야쿠힌 고교 가부시키가이샤 | 피리다지논 화합물 |
| WO2010132442A1 (en) * | 2009-05-12 | 2010-11-18 | Albany Molecular Reserch, Inc. | 7-([1,2,4,]triazolo[1,5,-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4- tetrahydroisoquinoline and use thereof |
| MX2011011900A (es) | 2009-05-12 | 2012-01-20 | Squibb Bristol Myers Co | Formas cristalinas de (s)-7-([1,2,4]triazolo[1,5-a]piridin-6-il)-4 -(3,4-diclorofenil)-1,2,3,4-tetrahidroisoquinolina y usos de las misma. |
| PH12012501661A1 (en) | 2010-02-19 | 2012-10-22 | Boehringer Ingelheim Int | Tricyclic pyridine derivatives, medicaments containing such compounds, their use and process for their preparation |
| TWI546302B (zh) | 2010-06-24 | 2016-08-21 | 武田藥品工業股份有限公司 | 稠合雜環化合物 |
| JP5760085B2 (ja) * | 2010-08-04 | 2015-08-05 | 武田薬品工業株式会社 | 縮合複素環化合物 |
| US8883788B2 (en) | 2010-08-04 | 2014-11-11 | Takeda Pharmaceutical Company Limited | Fused heterocyclic ring compound |
| EP2604597B1 (en) | 2010-08-10 | 2017-01-04 | Takeda Pharmaceutical Company Limited | Heterocyclic compound and use thereof inhibitor of phosphodiesterase 10a |
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