JP2016505557A5 - - Google Patents
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- Publication number
- JP2016505557A5 JP2016505557A5 JP2015545985A JP2015545985A JP2016505557A5 JP 2016505557 A5 JP2016505557 A5 JP 2016505557A5 JP 2015545985 A JP2015545985 A JP 2015545985A JP 2015545985 A JP2015545985 A JP 2015545985A JP 2016505557 A5 JP2016505557 A5 JP 2016505557A5
- Authority
- JP
- Japan
- Prior art keywords
- cyclopropylmethoxy
- difluoro
- azetidin
- pyrazine
- carbonyl
- 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.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims description 19
- PPFSTWQTUYTVGT-UHFFFAOYSA-N 4-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]thiomorpholine-3-carboxamide Chemical compound NC(=O)C1CSCCN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 PPFSTWQTUYTVGT-UHFFFAOYSA-N 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 150000001408 amides Chemical class 0.000 claims description 3
- -1 oxomorpholinyl Chemical group 0.000 claims 23
- 125000000623 heterocyclic group Chemical group 0.000 claims 9
- 206010016654 Fibrosis Diseases 0.000 claims 6
- 206010064930 age-related macular degeneration Diseases 0.000 claims 6
- 208000019425 cirrhosis of liver Diseases 0.000 claims 6
- 125000000217 alkyl group Chemical group 0.000 claims 4
- ISHAPNLCSAGSSW-UHFFFAOYSA-N 1-[5-cyclopropyl-6-(cyclopropylmethoxy)pyrazine-2-carbonyl]-4,4-dimethylpyrrolidine-2-carboxamide Chemical compound C1C(C)(C)CC(C(N)=O)N1C(=O)C(N=C1OCC2CC2)=CN=C1C1CC1 ISHAPNLCSAGSSW-UHFFFAOYSA-N 0.000 claims 3
- CUDKBOBOHWXOKN-UHFFFAOYSA-N 1-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]-4,4-dimethylpyrrolidine-2-carboxamide Chemical compound C1C(C)(C)CC(C(N)=O)N1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 CUDKBOBOHWXOKN-UHFFFAOYSA-N 0.000 claims 3
- 208000007788 Acute Liver Failure Diseases 0.000 claims 3
- 206010000804 Acute hepatic failure Diseases 0.000 claims 3
- 201000001320 Atherosclerosis Diseases 0.000 claims 3
- 208000031229 Cardiomyopathies Diseases 0.000 claims 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 3
- 208000008069 Geographic Atrophy Diseases 0.000 claims 3
- 208000010412 Glaucoma Diseases 0.000 claims 3
- 206010051920 Glomerulonephropathy Diseases 0.000 claims 3
- 206010019280 Heart failures Diseases 0.000 claims 3
- 206010061218 Inflammation Diseases 0.000 claims 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 3
- 208000002260 Keloid Diseases 0.000 claims 3
- 206010023330 Keloid scar Diseases 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 206010069385 Ocular ischaemic syndrome Diseases 0.000 claims 3
- 208000002193 Pain Diseases 0.000 claims 3
- 206010037660 Pyrexia Diseases 0.000 claims 3
- 206010038933 Retinopathy of prematurity Diseases 0.000 claims 3
- 201000009594 Systemic Scleroderma Diseases 0.000 claims 3
- 206010042953 Systemic sclerosis Diseases 0.000 claims 3
- 206010052779 Transplant rejections Diseases 0.000 claims 3
- 206010046851 Uveitis Diseases 0.000 claims 3
- 208000027418 Wounds and injury Diseases 0.000 claims 3
- 231100000836 acute liver failure Toxicity 0.000 claims 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 3
- 210000000988 bone and bone Anatomy 0.000 claims 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 3
- 230000002490 cerebral effect Effects 0.000 claims 3
- 230000001684 chronic effect Effects 0.000 claims 3
- 230000007882 cirrhosis Effects 0.000 claims 3
- 230000006378 damage Effects 0.000 claims 3
- 206010012601 diabetes mellitus Diseases 0.000 claims 3
- 208000033679 diabetic kidney disease Diseases 0.000 claims 3
- 230000004761 fibrosis Effects 0.000 claims 3
- 208000007565 gingivitis Diseases 0.000 claims 3
- 230000001969 hypertrophic effect Effects 0.000 claims 3
- 230000004054 inflammatory process Effects 0.000 claims 3
- 208000014674 injury Diseases 0.000 claims 3
- 208000028867 ischemia Diseases 0.000 claims 3
- 230000000302 ischemic effect Effects 0.000 claims 3
- 210000001117 keloid Anatomy 0.000 claims 3
- 208000017169 kidney disease Diseases 0.000 claims 3
- 208000002780 macular degeneration Diseases 0.000 claims 3
- 208000010125 myocardial infarction Diseases 0.000 claims 3
- 208000031225 myocardial ischemia Diseases 0.000 claims 3
- 230000004770 neurodegeneration Effects 0.000 claims 3
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 3
- 230000010412 perfusion Effects 0.000 claims 3
- 230000002265 prevention Effects 0.000 claims 3
- 208000005069 pulmonary fibrosis Diseases 0.000 claims 3
- 201000002793 renal fibrosis Diseases 0.000 claims 3
- 208000004644 retinal vein occlusion Diseases 0.000 claims 3
- 231100000241 scar Toxicity 0.000 claims 3
- 230000009885 systemic effect Effects 0.000 claims 3
- 230000001052 transient effect Effects 0.000 claims 3
- SLGNYEOMLKBLIK-NSHDSACASA-N (2s)-1-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]-4,4-difluoropyrrolidine-2-carboxamide Chemical compound NC(=O)[C@@H]1CC(F)(F)CN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 SLGNYEOMLKBLIK-NSHDSACASA-N 0.000 claims 2
- CUBFMUJIDHGHON-UHFFFAOYSA-N 6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)-n-(1-methoxy-2-methylpropan-2-yl)-n-methylpyrazine-2-carboxamide Chemical compound C1CC1COC1=NC(C(=O)N(C)C(C)(C)COC)=CN=C1N1CC(F)(F)C1 CUBFMUJIDHGHON-UHFFFAOYSA-N 0.000 claims 2
- PNKHMUYUQJQQQU-UHFFFAOYSA-N [5-cyclopropyl-6-(cyclopropylmethoxy)pyrazin-2-yl]-(2,2-dimethylpyrrolidin-1-yl)methanone Chemical compound CC1(C)CCCN1C(=O)C(N=C1OCC2CC2)=CN=C1C1CC1 PNKHMUYUQJQQQU-UHFFFAOYSA-N 0.000 claims 2
- MAXRHXDLGBYMAD-UHFFFAOYSA-N [6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazin-2-yl]-(2,2-dimethylpyrrolidin-1-yl)methanone Chemical compound CC1(C)CCCN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 MAXRHXDLGBYMAD-UHFFFAOYSA-N 0.000 claims 2
- RADWJJYFOOUQDK-UHFFFAOYSA-N [6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazin-2-yl]-(3,3-dimethylmorpholin-4-yl)methanone Chemical compound CC1(C)COCCN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 RADWJJYFOOUQDK-UHFFFAOYSA-N 0.000 claims 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 150000003857 carboxamides Chemical class 0.000 claims 2
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 125000002757 morpholinyl group Chemical group 0.000 claims 2
- CNGJPRQBRBBAAX-UHFFFAOYSA-N n-tert-butyl-6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)-n-(2-methoxyethyl)pyrazine-2-carboxamide Chemical compound C1CC1COC1=NC(C(=O)N(CCOC)C(C)(C)C)=CN=C1N1CC(F)(F)C1 CNGJPRQBRBBAAX-UHFFFAOYSA-N 0.000 claims 2
- ICKCVIQXRDRPTI-UHFFFAOYSA-N n-tert-butyl-6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)-n-methylpyrazine-2-carboxamide Chemical compound C1CC1COC1=NC(C(=O)N(C)C(C)(C)C)=CN=C1N1CC(F)(F)C1 ICKCVIQXRDRPTI-UHFFFAOYSA-N 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- VPJDFQXEQISZLA-CQSZACIVSA-N (2r)-1-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]-n,n-dimethylpyrrolidine-2-carbothioamide Chemical compound CN(C)C(=S)[C@H]1CCCN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 VPJDFQXEQISZLA-CQSZACIVSA-N 0.000 claims 1
- XMKGBINAXSPRKN-LBPRGKRZSA-N (2s)-1-[5-cyclopropyl-6-(cyclopropylmethoxy)pyrazine-2-carbonyl]-4,4-difluoropyrrolidine-2-carboxamide Chemical compound NC(=O)[C@@H]1CC(F)(F)CN1C(=O)C(N=C1OCC2CC2)=CN=C1C1CC1 XMKGBINAXSPRKN-LBPRGKRZSA-N 0.000 claims 1
- AZAQQPJXYPDQCS-WHUIICBVSA-N (2s)-1-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]-4-hydroxy-4-methylpyrrolidine-2-carboxamide Chemical compound C1C(C)(O)C[C@@H](C(N)=O)N1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 AZAQQPJXYPDQCS-WHUIICBVSA-N 0.000 claims 1
- LNRDCWSMLNFCKY-UHFFFAOYSA-N 1-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]piperidine-2-carboxamide Chemical compound NC(=O)C1CCCCN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 LNRDCWSMLNFCKY-UHFFFAOYSA-N 0.000 claims 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 1
- LGYNIFWIKSEESD-UHFFFAOYSA-N 2-ethylhexanal Chemical compound CCCCC(CC)C=O LGYNIFWIKSEESD-UHFFFAOYSA-N 0.000 claims 1
- DNODHRHZHANYEO-UHFFFAOYSA-N 4-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]morpholin-2-one Chemical compound C1C(F)(F)CN1C1=NC=C(C(=O)N2CC(=O)OCC2)N=C1OCC1CC1 DNODHRHZHANYEO-UHFFFAOYSA-N 0.000 claims 1
- GXMVBYITSSGQER-UHFFFAOYSA-N 5-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]-5-azaspiro[2.4]heptane-6-carboxamide Chemical compound C1N(C(=O)C=2N=C(OCC3CC3)C(N3CC(F)(F)C3)=NC=2)C(C(=O)N)CC21CC2 GXMVBYITSSGQER-UHFFFAOYSA-N 0.000 claims 1
- KZMJZRATNJTRNA-UHFFFAOYSA-N 5-cyclopropyl-6-(cyclopropylmethoxy)-n-(1-methoxy-2-methylpropan-2-yl)-n-methylpyrazine-2-carboxamide Chemical compound C1CC1COC1=NC(C(=O)N(C)C(C)(C)COC)=CN=C1C1CC1 KZMJZRATNJTRNA-UHFFFAOYSA-N 0.000 claims 1
- DQGNFQJJQBUCMP-UHFFFAOYSA-N 6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)-n-ethyl-n-propan-2-ylpyrazine-2-carboxamide Chemical compound C1CC1COC1=NC(C(=O)N(C(C)C)CC)=CN=C1N1CC(F)(F)C1 DQGNFQJJQBUCMP-UHFFFAOYSA-N 0.000 claims 1
- UODCOTAUGKQESU-ZDUSSCGKSA-N [(3s)-1-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]pyrrolidin-3-yl] acetate Chemical compound C1[C@@H](OC(=O)C)CCN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 UODCOTAUGKQESU-ZDUSSCGKSA-N 0.000 claims 1
- URASPVATSWONFK-UHFFFAOYSA-N [1-[5-cyclopropyl-6-(cyclopropylmethoxy)pyrazine-2-carbonyl]-3-methylpyrrolidin-3-yl] acetate Chemical compound C1C(OC(=O)C)(C)CCN1C(=O)C(N=C1OCC2CC2)=CN=C1C1CC1 URASPVATSWONFK-UHFFFAOYSA-N 0.000 claims 1
- FFOXXHDQUUDKOV-UHFFFAOYSA-N [1-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]-3-methylpyrrolidin-3-yl] acetate Chemical compound C1C(OC(=O)C)(C)CCN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 FFOXXHDQUUDKOV-UHFFFAOYSA-N 0.000 claims 1
- PHCZFHXFRVWXOW-UHFFFAOYSA-N [5-cyclopropyl-6-(cyclopropylmethoxy)pyrazin-2-yl]-(3,3,4,4-tetrafluoropyrrolidin-1-yl)methanone Chemical compound C1C(F)(F)C(F)(F)CN1C(=O)C(N=C1OCC2CC2)=CN=C1C1CC1 PHCZFHXFRVWXOW-UHFFFAOYSA-N 0.000 claims 1
- NZLXQSVAQWMGCX-UHFFFAOYSA-N [5-cyclopropyl-6-(cyclopropylmethoxy)pyrazin-2-yl]-(7-oxa-4-azaspiro[2.5]octan-4-yl)methanone Chemical compound C=1N=C(C2CC2)C(OCC2CC2)=NC=1C(=O)N1CCOCC11CC1 NZLXQSVAQWMGCX-UHFFFAOYSA-N 0.000 claims 1
- MJOBLMCVCVMOJT-LLVKDONJSA-N [5-cyclopropyl-6-(cyclopropylmethoxy)pyrazin-2-yl]-[(2r)-2-methylpyrrolidin-1-yl]methanone Chemical compound C[C@@H]1CCCN1C(=O)C(N=C1OCC2CC2)=CN=C1C1CC1 MJOBLMCVCVMOJT-LLVKDONJSA-N 0.000 claims 1
- ULZLYINESXARHU-UHFFFAOYSA-N [6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazin-2-yl]-(2,2-dimethylmorpholin-4-yl)methanone Chemical compound C1COC(C)(C)CN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 ULZLYINESXARHU-UHFFFAOYSA-N 0.000 claims 1
- WHEVZVDNKRTZHA-UHFFFAOYSA-N [6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazin-2-yl]-(2-oxa-7-azaspiro[3.4]octan-7-yl)methanone Chemical compound C1C(F)(F)CN1C1=NC=C(C(=O)N2CC3(COC3)CC2)N=C1OCC1CC1 WHEVZVDNKRTZHA-UHFFFAOYSA-N 0.000 claims 1
- NPOSXWDUCSOJAX-UHFFFAOYSA-N [6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazin-2-yl]-(3,3,4,4-tetrafluoropyrrolidin-1-yl)methanone Chemical compound C1C(F)(F)CN1C1=NC=C(C(=O)N2CC(F)(F)C(F)(F)C2)N=C1OCC1CC1 NPOSXWDUCSOJAX-UHFFFAOYSA-N 0.000 claims 1
- JTBMTLQPRDBTQC-UHFFFAOYSA-N [6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazin-2-yl]-(3,3-difluoropyrrolidin-1-yl)methanone Chemical compound C1C(F)(F)CN1C1=NC=C(C(=O)N2CC(F)(F)CC2)N=C1OCC1CC1 JTBMTLQPRDBTQC-UHFFFAOYSA-N 0.000 claims 1
- RNHDQIQNRFAOIU-UHFFFAOYSA-N [6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazin-2-yl]-(7-oxa-4-azaspiro[2.5]octan-4-yl)methanone Chemical compound C1C(F)(F)CN1C1=NC=C(C(=O)N2C3(CC3)COCC2)N=C1OCC1CC1 RNHDQIQNRFAOIU-UHFFFAOYSA-N 0.000 claims 1
- ZXJWVSDWNJTBJK-LLVKDONJSA-N [6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazin-2-yl]-[(2r)-2-methylpyrrolidin-1-yl]methanone Chemical compound C[C@@H]1CCCN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 ZXJWVSDWNJTBJK-LLVKDONJSA-N 0.000 claims 1
- ZXJWVSDWNJTBJK-NSHDSACASA-N [6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazin-2-yl]-[(2s)-2-methylpyrrolidin-1-yl]methanone Chemical compound C[C@H]1CCCN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 ZXJWVSDWNJTBJK-NSHDSACASA-N 0.000 claims 1
- FZQXJJYOPAWXBR-UHFFFAOYSA-N [6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazin-2-yl]-[4-(2-hydroxyethyl)piperazin-1-yl]methanone Chemical compound C1CN(CCO)CCN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 FZQXJJYOPAWXBR-UHFFFAOYSA-N 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims 1
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 239000007822 coupling agent Substances 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- FRWMYAZAWIIHDG-UHFFFAOYSA-N ethyl 2-[tert-butyl-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]amino]acetate Chemical compound C1CC1COC1=NC(C(=O)N(CC(=O)OCC)C(C)(C)C)=CN=C1N1CC(F)(F)C1 FRWMYAZAWIIHDG-UHFFFAOYSA-N 0.000 claims 1
- 125000004438 haloalkoxy group Chemical group 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- GRZKZDYFLDPNBM-CYBMUJFWSA-N methyl (2r)-1-[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]pyrrolidine-2-carboxylate Chemical compound COC(=O)[C@H]1CCCN1C(=O)C(N=C1OCC2CC2)=CN=C1N1CC(F)(F)C1 GRZKZDYFLDPNBM-CYBMUJFWSA-N 0.000 claims 1
- PIZOYHRQRIQRPT-AWEZNQCLSA-N methyl (2s)-1-[5-cyclopropyl-6-(cyclopropylmethoxy)pyrazine-2-carbonyl]pyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCN1C(=O)C(N=C1OCC2CC2)=CN=C1C1CC1 PIZOYHRQRIQRPT-AWEZNQCLSA-N 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- FIAAIGAANUVTAQ-UHFFFAOYSA-N n-tert-butyl-5-(3,3-difluoroazetidin-1-yl)-n-methyl-6-(2,2,2-trifluoroethoxy)pyrazine-2-carboxamide Chemical compound FC(F)(F)COC1=NC(C(=O)N(C)C(C)(C)C)=CN=C1N1CC(F)(F)C1 FIAAIGAANUVTAQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 1
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- WTBJIFNMKOKRJX-UHFFFAOYSA-N thiomorpholine-3-carboxamide Chemical compound NC(=O)C1CSCCN1 WTBJIFNMKOKRJX-UHFFFAOYSA-N 0.000 description 2
- XNLYSROZAAXKJP-UHFFFAOYSA-N 6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carboxylic acid Chemical compound C1CC1COC1=NC(C(=O)O)=CN=C1N1CC(F)(F)C1 XNLYSROZAAXKJP-UHFFFAOYSA-N 0.000 description 1
- 0 O=C(c1nc(OCC2CC2)c(N(C2)CC2(F)F)nc1)N1*CSCC1 Chemical compound O=C(c1nc(OCC2CC2)c(N(C2)CC2(F)F)nc1)N1*CSCC1 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12196024 | 2012-12-07 | ||
| EP12196024.9 | 2012-12-07 | ||
| PCT/EP2013/075444 WO2014086807A1 (en) | 2012-12-07 | 2013-12-04 | Novel pyrazine derivatives as cb2 receptor agonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016505557A JP2016505557A (ja) | 2016-02-25 |
| JP2016505557A5 true JP2016505557A5 (cg-RX-API-DMAC7.html) | 2018-02-08 |
| JP6322646B2 JP6322646B2 (ja) | 2018-05-09 |
Family
ID=47290805
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015545985A Active JP6322646B2 (ja) | 2012-12-07 | 2013-12-04 | Ｃｂ２受容体アゴニストとしての新規ピラジン誘導体 |
Country Status (32)
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2964646B1 (en) | 2013-03-07 | 2017-04-19 | F. Hoffmann-La Roche AG | Novel pyrazol derivatives |
| CA2899168A1 (en) | 2013-03-26 | 2014-10-02 | F. Hoffmann-La Roche Ag | Novel pyridine derivatives |
| ES2635632T3 (es) | 2013-05-02 | 2017-10-04 | F. Hoffmann-La Roche Ag | Derivados de pirrolo[2,3-d]pirimidina como agonistas del receptor CB2 |
| PT2991987T (pt) | 2013-05-02 | 2018-07-13 | Hoffmann La Roche | Derivados de purina como agonistas do recetor cb2 |
| CA2915766C (en) | 2013-09-06 | 2023-09-26 | F. Hoffmann-La Roche Ag | Triazolo[4,5-d]pyrimidine derivatives and their use as cannabinoid receptor 2 agonists |
| EA030116B1 (ru) * | 2014-04-04 | 2018-06-29 | Ф. Хоффманн-Ля Рош Аг | Пиридин-2-амиды, пригодные в качестве агонистов cb2 |
| DK3386951T3 (en) * | 2015-12-09 | 2020-04-27 | Hoffmann La Roche | Phenylderivater som cannabinoidreceptor-2-agonister |
| EP3642200B1 (en) | 2017-06-20 | 2023-05-03 | F. Hoffmann-La Roche AG | Pyridine derivatives |
| JP7478672B2 (ja) | 2018-06-27 | 2024-05-07 | エフ． ホフマン－ラ ロシュ アーゲー | カンナビノイド受容体２の阻害剤としての新規なアゼチジン置換ピリジン及びピラジン化合物 |
| CN112074513B (zh) | 2018-06-27 | 2024-06-14 | 豪夫迈·罗氏有限公司 | 作为优先大麻素2激动剂的吡啶和吡嗪衍生物 |
| EP3813888B1 (en) | 2018-06-27 | 2025-11-26 | F. Hoffmann-La Roche AG | Radiolabeled cannabinoid receptor 2 ligand |
| MA53002A (fr) * | 2018-06-27 | 2021-05-05 | Eth Zuerich | Nouveaux composés de pyridine et de pyrazine en tant qu'inhibiteurs du récepteur cannabinoïde 2 |
| WO2022128050A1 (en) | 2020-12-14 | 2022-06-23 | Symrise Ag | Medicament for fighting inflammation and pain |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7629346B2 (en) * | 2006-06-19 | 2009-12-08 | Hoffmann-La Roche Inc. | Pyrazinecarboxamide derivatives as CB1 antagonists |
| MX2009003316A (es) * | 2006-10-04 | 2009-04-09 | Hoffmann La Roche | Derivados de pirazina-2-carboxamida como moduladores receptores de cb2. |
| WO2012031817A1 (en) | 2010-09-09 | 2012-03-15 | F. Hoffmann-La Roche Ag | Determination of abca1 protein levels in cells |
| US9321727B2 (en) | 2011-06-10 | 2016-04-26 | Hoffmann-La Roche Inc. | Pyridine derivatives as agonists of the CB2 receptor |
| US9403808B2 (en) * | 2011-10-28 | 2016-08-02 | Hoffmann-La Roche Inc. | Pyrazine derivatives |
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2013
- 2013-12-04 KR KR1020157014961A patent/KR20150092156A/ko not_active Withdrawn
- 2013-12-04 CA CA2885418A patent/CA2885418A1/en not_active Abandoned
- 2013-12-04 WO PCT/EP2013/075444 patent/WO2014086807A1/en not_active Ceased
- 2013-12-04 SI SI201330591A patent/SI2928882T1/sl unknown
- 2013-12-04 ES ES13799545.2T patent/ES2621958T3/es active Active
- 2013-12-04 AU AU2013354115A patent/AU2013354115B2/en not_active Ceased
- 2013-12-04 DK DK13799545.2T patent/DK2928882T3/en active
- 2013-12-04 PL PL13799545T patent/PL2928882T3/pl unknown
- 2013-12-04 SG SG11201504011UA patent/SG11201504011UA/en unknown
- 2013-12-04 LT LTEP13799545.2T patent/LT2928882T/lt unknown
- 2013-12-04 EP EP13799545.2A patent/EP2928882B1/en not_active Not-in-force
- 2013-12-04 HU HUE13799545A patent/HUE030836T2/en unknown
- 2013-12-04 UA UAA201506212A patent/UA116894C2/uk unknown
- 2013-12-04 US US14/648,399 patent/US9512141B2/en not_active Expired - Fee Related
- 2013-12-04 IN IN3145DEN2015 patent/IN2015DN03145A/en unknown
- 2013-12-04 CN CN201380063228.9A patent/CN104837830B/zh not_active Expired - Fee Related
- 2013-12-04 BR BR112015009603A patent/BR112015009603A2/pt not_active Application Discontinuation
- 2013-12-04 EA EA201590827A patent/EA025840B1/ru not_active IP Right Cessation
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- 2013-12-04 JP JP2015545985A patent/JP6322646B2/ja active Active
- 2013-12-04 PT PT137995452T patent/PT2928882T/pt unknown
- 2013-12-04 PE PE2015000736A patent/PE20151060A1/es not_active Application Discontinuation
- 2013-12-04 MA MA38217A patent/MA38217B1/fr unknown
- 2013-12-04 HR HRP20170572TT patent/HRP20170572T1/hr unknown
- 2013-12-05 AR ARP130104504A patent/AR093804A1/es unknown
- 2013-12-06 TW TW102144989A patent/TW201427960A/zh unknown
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2015
- 2015-03-26 IL IL237982A patent/IL237982A/en not_active IP Right Cessation
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- 2015-05-14 PH PH12015501072A patent/PH12015501072A1/en unknown
- 2015-05-15 CL CL2015001318A patent/CL2015001318A1/es unknown
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