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 (enExample) | 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 |
|---|---|---|---|---|
| JP6514119B2 (ja) | 2013-03-07 | 2019-05-15 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 新規ピラゾール誘導体 |
| NO2978755T3 (enExample) | 2013-03-26 | 2018-06-02 | ||
| PE20151977A1 (es) | 2013-05-02 | 2016-01-07 | Hoffmann La Roche | Nuevos derivados de purina |
| KR20160002857A (ko) | 2013-05-02 | 2016-01-08 | 에프. 호프만-라 로슈 아게 | CB2 수용체 작용제로서의 피롤로[2,3-d]피리미딘 유도체 |
| KR20220140651A (ko) | 2013-09-06 | 2022-10-18 | 에프. 호프만-라 로슈 아게 | 신규의 트라이아졸로[4,5-d]피리미딘 유도체 |
| CA2943013A1 (en) * | 2014-04-04 | 2015-10-08 | F. Hoffmann-La Roche Ag | Pyridine-2-amides useful as cb2 agonists |
| DK3386951T3 (en) * | 2015-12-09 | 2020-04-27 | Hoffmann La Roche | Phenylderivater som cannabinoidreceptor-2-agonister |
| JP7300398B2 (ja) | 2017-06-20 | 2023-06-29 | エフ． ホフマン－ラ ロシュ アーゲー | ピリジン誘導体 |
| EP3995155A1 (en) | 2018-06-27 | 2022-05-11 | F. Hoffmann-La Roche AG | Radiolabeled cannabinoid receptor 2 ligand |
| 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 |
| BR112020025013A2 (pt) * | 2018-06-27 | 2021-03-23 | F. Hoffmann-La Roche Ag | novos compostos de piridina e pirazina como inibidores do receptor 2 de canabinoide |
| EP3814328A1 (en) | 2018-06-27 | 2021-05-05 | F. Hoffmann-La Roche AG | Novel azetidine-substituted pyridine and pyrazine compounds as inhibitors of cannabinoid receptor 2 |
| WO2022128050A1 (en) | 2020-12-14 | 2022-06-23 | Symrise Ag | Medicament for fighting inflammation and pain |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US7629346B2 (en) * | 2006-06-19 | 2009-12-08 | Hoffmann-La Roche Inc. | Pyrazinecarboxamide derivatives as CB1 antagonists |
| EP2076499B1 (en) * | 2006-10-04 | 2010-05-12 | F.Hoffmann-La Roche Ag | Pyrazine-2-carboxamide derivatives as cb2 receptor modulators |
| 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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