TWI616430B - Atx調節劑 - Google Patents
Atx調節劑 Download PDFInfo
- Publication number
- TWI616430B TWI616430B TW102126996A TW102126996A TWI616430B TW I616430 B TWI616430 B TW I616430B TW 102126996 A TW102126996 A TW 102126996A TW 102126996 A TW102126996 A TW 102126996A TW I616430 B TWI616430 B TW I616430B
- Authority
- TW
- Taiwan
- Prior art keywords
- cis
- trifluoromethyl
- oxy
- naphthalene
- ethyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract description 201
- 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 claims abstract description 94
- 230000000694 effects Effects 0.000 claims abstract description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 369
- -1 nitro, hydroxyl Chemical group 0.000 claims description 265
- 229910052757 nitrogen Inorganic materials 0.000 claims description 196
- 125000000623 heterocyclic group Chemical group 0.000 claims description 131
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 118
- 239000001257 hydrogen Substances 0.000 claims description 106
- 229910052739 hydrogen Inorganic materials 0.000 claims description 106
- 125000001072 heteroaryl group Chemical group 0.000 claims description 93
- 125000005843 halogen group Chemical group 0.000 claims description 90
- 101000864057 Homo sapiens Serine/threonine-protein kinase SMG1 Proteins 0.000 claims description 89
- 101000897035 Homo sapiens Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 claims description 88
- 101001114134 Gloydius halys Neutral phospholipase A2 agkistrodotoxin Proteins 0.000 claims description 87
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 76
- 150000002431 hydrogen Chemical class 0.000 claims description 76
- 125000003118 aryl group Chemical group 0.000 claims description 74
- 150000003839 salts Chemical class 0.000 claims description 71
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 70
- 125000003545 alkoxy group Chemical group 0.000 claims description 60
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 59
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 53
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 53
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 53
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 50
- 150000001412 amines Chemical class 0.000 claims description 49
- 125000004122 cyclic group Chemical group 0.000 claims description 44
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 44
- 229910052717 sulfur Inorganic materials 0.000 claims description 42
- 229910052760 oxygen Inorganic materials 0.000 claims description 41
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 40
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 39
- 239000002253 acid Substances 0.000 claims description 37
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims description 34
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 33
- 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 33
- 125000005347 halocycloalkyl group Chemical group 0.000 claims description 33
- 125000005842 heteroatom Chemical group 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 125000002950 monocyclic group Chemical group 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
- 229910052799 carbon Inorganic materials 0.000 claims description 30
- 201000006417 multiple sclerosis Diseases 0.000 claims description 28
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 27
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 23
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 22
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims description 22
- 125000006769 halocycloalkoxy group Chemical group 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims description 21
- 241000124008 Mammalia Species 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
- 208000002193 Pain Diseases 0.000 claims description 19
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 claims description 19
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 16
- 125000000304 alkynyl group Chemical group 0.000 claims description 15
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 14
- 239000003112 inhibitor Substances 0.000 claims description 14
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 12
- DMUXSGAKEXSNGN-UHFFFAOYSA-N 2-ethyloctanoic acid Chemical compound CCCCCCC(CC)C(O)=O DMUXSGAKEXSNGN-UHFFFAOYSA-N 0.000 claims description 12
- 150000001721 carbon Chemical group 0.000 claims description 12
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 11
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 11
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 11
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 11
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 11
- 208000024891 symptom Diseases 0.000 claims description 11
- DYWSVUBJGFTOQC-UHFFFAOYSA-N xi-2-Ethylheptanoic acid Chemical compound CCCCCC(CC)C(O)=O DYWSVUBJGFTOQC-UHFFFAOYSA-N 0.000 claims description 11
- 208000000094 Chronic Pain Diseases 0.000 claims description 10
- 125000005257 alkyl acyl group Chemical group 0.000 claims description 10
- OWIUPIRUAQMTTK-UHFFFAOYSA-N carbazic acid Chemical compound NNC(O)=O OWIUPIRUAQMTTK-UHFFFAOYSA-N 0.000 claims description 10
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 9
- 206010065390 Inflammatory pain Diseases 0.000 claims description 8
- 208000004296 neuralgia Diseases 0.000 claims description 8
- 208000021722 neuropathic pain Diseases 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- FVGQYNFQNOHFPX-UEDWGHLCSA-N CC[C@H]1CC[C@H](CC1)Oc1ccc2ccc(CN3CCC(CC3)C(O)=O)cc2c1Cl Chemical compound CC[C@H]1CC[C@H](CC1)Oc1ccc2ccc(CN3CCC(CC3)C(O)=O)cc2c1Cl FVGQYNFQNOHFPX-UEDWGHLCSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 6
- 230000004968 inflammatory condition Effects 0.000 claims description 6
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 5
- HNYWATKKFFNQFM-UHFFFAOYSA-N 9-[7-(4-methylcyclohexyl)oxy-8-(trifluoromethyl)naphthalene-2-carbonyl]-9-azabicyclo[3.3.1]nonane-3-carboxylic acid Chemical compound C1CC(C)CCC1OC1=CC=C(C=CC(=C2)C(=O)N3C4CCCC3CC(C4)C(O)=O)C2=C1C(F)(F)F HNYWATKKFFNQFM-UHFFFAOYSA-N 0.000 claims description 5
- SZBVQLXGZWYFCQ-UHFFFAOYSA-N 9-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalene-2-carbonyl]-9-azabicyclo[3.3.1]nonane-3-carboxylic acid Chemical compound C1C(C(=O)O)CC2CCCC1N2C(=O)C(C=C1C=2C(F)(F)F)=CC=C1C=CC=2OC1CCC(C(F)(F)F)CC1 SZBVQLXGZWYFCQ-UHFFFAOYSA-N 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- PDZVLUXDLFYWRZ-QKUVIELKSA-N C(#N)C=1C(=CC=C2C=CC(=CC12)C(C)N1CCC(CC1)C(=O)O)O[C@@H]1CC[C@@H](CC1)C(F)(F)F Chemical compound C(#N)C=1C(=CC=C2C=CC(=CC12)C(C)N1CCC(CC1)C(=O)O)O[C@@H]1CC[C@@H](CC1)C(F)(F)F PDZVLUXDLFYWRZ-QKUVIELKSA-N 0.000 claims description 5
- PHGBDEFQUNIVAZ-DHDVMJEDSA-N C(#N)C=1C(=CC=C2C=CC(=CC12)CN1C2CC(CC1CC2)C(=O)O)O[C@@H]2CC[C@@H](CC2)CC Chemical compound C(#N)C=1C(=CC=C2C=CC(=CC12)CN1C2CC(CC1CC2)C(=O)O)O[C@@H]2CC[C@@H](CC2)CC PHGBDEFQUNIVAZ-DHDVMJEDSA-N 0.000 claims description 5
- CERDYVGRKLJTIJ-OXRXSKLMSA-N CC(N1C2CCCC1CC(C2)C(O)=O)c1ccc2ccc(O[C@@H]3CC[C@H](C)CC3)c(c2c1)C(F)(F)F Chemical compound CC(N1C2CCCC1CC(C2)C(O)=O)c1ccc2ccc(O[C@@H]3CC[C@H](C)CC3)c(c2c1)C(F)(F)F CERDYVGRKLJTIJ-OXRXSKLMSA-N 0.000 claims description 5
- BYCIMQOIBDDRAS-BIOKIISNSA-N CC(N1C2CCCC1CC(C2)C(O)=O)c1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(c2c1)C(F)(F)F Chemical compound CC(N1C2CCCC1CC(C2)C(O)=O)c1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(c2c1)C(F)(F)F BYCIMQOIBDDRAS-BIOKIISNSA-N 0.000 claims description 5
- PNKVNDXYIUZDLT-ALHDYUKWSA-N CC1([C@H](C[C@H]1N[C@H](C)C1=CC2=C(C(=CC=C2C=C1)O[C@@H]1CC[C@@H](CC1)C(F)(F)F)C(F)(F)F)C(=O)O)C Chemical compound CC1([C@H](C[C@H]1N[C@H](C)C1=CC2=C(C(=CC=C2C=C1)O[C@@H]1CC[C@@H](CC1)C(F)(F)F)C(F)(F)F)C(=O)O)C PNKVNDXYIUZDLT-ALHDYUKWSA-N 0.000 claims description 5
- YAROUYNUUZPDRJ-UWUNEBHHSA-N C[C@H]1CC[C@H](CC1)OC1=CC=C2C=CC(=CC2=C1C(F)(F)F)CN1CCOCC1 Chemical compound C[C@H]1CC[C@H](CC1)OC1=CC=C2C=CC(=CC2=C1C(F)(F)F)CN1CCOCC1 YAROUYNUUZPDRJ-UWUNEBHHSA-N 0.000 claims description 5
- RZPPKCWFXKPGOK-XBZZPOKOSA-N OC(=O)C1CC2CCCC(C1)N2Cc1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(c2c1)C(F)(F)F Chemical compound OC(=O)C1CC2CCCC(C1)N2Cc1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(c2c1)C(F)(F)F RZPPKCWFXKPGOK-XBZZPOKOSA-N 0.000 claims description 5
- 239000003246 corticosteroid Substances 0.000 claims description 5
- 229960001334 corticosteroids Drugs 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- 230000036210 malignancy Effects 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- QUTQICJBWHIKGL-UHFFFAOYSA-N 9-[[8-chloro-7-(4-methylcyclohexyl)oxynaphthalen-2-yl]methyl]-9-azabicyclo[3.3.1]nonane-3-carboxylic acid Chemical compound C1CC(C)CCC1OC1=CC=C(C=CC(CN2C3CCCC2CC(C3)C(O)=O)=C2)C2=C1Cl QUTQICJBWHIKGL-UHFFFAOYSA-N 0.000 claims description 4
- GOWHVDFAACWISF-IAJZFSITSA-N C(#N)C=1C(=CC=C2C=CC(=CC12)C(C)N1C2CC(CC1CCC2)C(=O)O)O[C@@H]2CC[C@@H](CC2)CC Chemical compound C(#N)C=1C(=CC=C2C=CC(=CC12)C(C)N1C2CC(CC1CCC2)C(=O)O)O[C@@H]2CC[C@@H](CC2)CC GOWHVDFAACWISF-IAJZFSITSA-N 0.000 claims description 4
- JLLYPSZJBPXWLP-DABZEWERSA-N C(#N)C=1C(=CC=C2C=CC(=CC12)C(CC)N1C2CC(CC1CCC2)C(=O)O)O[C@@H]2CC[C@@H](CC2)C(F)(F)F Chemical compound C(#N)C=1C(=CC=C2C=CC(=CC12)C(CC)N1C2CC(CC1CCC2)C(=O)O)O[C@@H]2CC[C@@H](CC2)C(F)(F)F JLLYPSZJBPXWLP-DABZEWERSA-N 0.000 claims description 4
- TVBVJNRYMZQZLO-JSOYUDEYSA-N CC(N1C2CCC1CC(C2)C(O)=O)c1ccc2ccc(O[C@@H]3CC[C@H](C)CC3)c(c2c1)C(F)(F)F Chemical compound CC(N1C2CCC1CC(C2)C(O)=O)c1ccc2ccc(O[C@@H]3CC[C@H](C)CC3)c(c2c1)C(F)(F)F TVBVJNRYMZQZLO-JSOYUDEYSA-N 0.000 claims description 4
- VKHCIMALUGZBCD-CPGABTQKSA-N CC(N1C2CCC1CC(C2)C(O)=O)c1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(C(F)F)c2c1 Chemical compound CC(N1C2CCC1CC(C2)C(O)=O)c1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(C(F)F)c2c1 VKHCIMALUGZBCD-CPGABTQKSA-N 0.000 claims description 4
- WVQIEUMHCNWAJP-YOYDSGEPSA-N CC(N1C2CCCC1CC(C2)C(O)=O)c1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(C#N)c2c1 Chemical compound CC(N1C2CCCC1CC(C2)C(O)=O)c1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(C#N)c2c1 WVQIEUMHCNWAJP-YOYDSGEPSA-N 0.000 claims description 4
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- QMLOEANIZOVIHW-VFNMEIJHSA-N CCC(N1CCC(CC1)C(O)=O)c1ccc2ccc(O[C@@H]3CC[C@H](CC)CC3)c(C#N)c2c1 Chemical compound CCC(N1CCC(CC1)C(O)=O)c1ccc2ccc(O[C@@H]3CC[C@H](CC)CC3)c(C#N)c2c1 QMLOEANIZOVIHW-VFNMEIJHSA-N 0.000 claims description 4
- YYZLWLFEPLDZKT-RLAPIPATSA-N CCC(N1CCC(CC1)C(O)=O)c1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(Cl)c2c1 Chemical compound CCC(N1CCC(CC1)C(O)=O)c1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(Cl)c2c1 YYZLWLFEPLDZKT-RLAPIPATSA-N 0.000 claims description 4
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- PZASAAIJIFDWSB-RQDPYJAVSA-N FC([C@H]1CC[C@H](CC1)OC1=CC=C2C=CC(=CC2=C1C(F)(F)F)[C@@H](C)N1C2CC(CC1CC2)C(=O)O)(F)F Chemical compound FC([C@H]1CC[C@H](CC1)OC1=CC=C2C=CC(=CC2=C1C(F)(F)F)[C@@H](C)N1C2CC(CC1CC2)C(=O)O)(F)F PZASAAIJIFDWSB-RQDPYJAVSA-N 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 239000002955 immunomodulating agent Substances 0.000 claims description 4
- 229940121354 immunomodulator Drugs 0.000 claims description 4
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Classifications
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- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic 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
- C07D401/02—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
- C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D471/08—Bridged systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
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- C—CHEMISTRY; METALLURGY
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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| IN2014DN09346A (https=) | 2012-06-13 | 2015-07-17 | Hoffmann La Roche | |
| MX363388B (es) * | 2012-07-27 | 2019-03-20 | Biogen Ma Inc | Agentes moduladores de autotaxina. |
| EA027809B1 (ru) | 2012-07-27 | 2017-09-29 | Биоген Айдек Ма Инк. | Соединения, которые являются s1p-модулирующими агентами и/или atx-модулирующими агентами |
| US9555050B2 (en) | 2012-07-27 | 2017-01-31 | Biogen Ma Inc. | ATX modulating agents |
| WO2014025709A1 (en) | 2012-08-06 | 2014-02-13 | Biogen Idec Ma Inc. | Compounds that are s1p modulating agents and/or atx modulating agents |
| WO2014025708A1 (en) | 2012-08-06 | 2014-02-13 | Biogen Idec Ma Inc. | Compounds that are s1p modulating agents and/or atx modulating agents |
| KR102179599B1 (ko) | 2012-09-25 | 2020-11-19 | 에프. 호프만-라 로슈 아게 | 이환형 유도체 |
| AR095079A1 (es) | 2013-03-12 | 2015-09-16 | Hoffmann La Roche | Derivados de octahidro-pirrolo[3,4-c]-pirrol y piridina-fenilo |
| CN105764905B (zh) | 2013-11-26 | 2019-06-07 | 豪夫迈·罗氏有限公司 | 新的八氢-环丁二烯并[1,2-c;3,4-c’]二吡咯-2基 |
| CN106103446B (zh) | 2014-03-26 | 2019-07-30 | 豪夫迈·罗氏有限公司 | 作为自分泌运动因子(atx)和溶血磷脂酸(lpa)生产抑制剂的二环化合物 |
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| GB201501870D0 (en) | 2015-02-04 | 2015-03-18 | Cancer Rec Tech Ltd | Autotaxin inhibitors |
| GB201502020D0 (en) | 2015-02-06 | 2015-03-25 | Cancer Rec Tech Ltd | Autotaxin inhibitory compounds |
| MA41898A (fr) | 2015-04-10 | 2018-02-13 | Hoffmann La Roche | Dérivés de quinazolinone bicyclique |
| AU2016270373A1 (en) | 2015-06-05 | 2018-01-04 | Vertex Pharmaceuticals Incorporated | Triazoles for the treatment of demyelinating diseases |
| CA2992889A1 (en) | 2015-09-04 | 2017-03-09 | F. Hoffmann-La Roche Ag | Phenoxymethyl derivatives |
| RU2018112230A (ru) | 2015-09-24 | 2019-10-30 | Ф. Хоффманн-Ля Рош Аг | Бициклические соединения в качестве ингибиторов atx |
| CR20180057A (es) | 2015-09-24 | 2018-04-02 | Hoffmann La Roche | Nuevos compuestos biciclicos como inhibidores duales de atx/ca. |
| KR20180054830A (ko) | 2015-09-24 | 2018-05-24 | 에프. 호프만-라 로슈 아게 | 오토탁신(atx) 억제제로서의 이환형 화합물 |
| AU2016328365B2 (en) | 2015-09-24 | 2020-04-23 | F. Hoffmann-La Roche Ag | New bicyclic compounds as dual ATX/CA inhibitors |
| WO2018106646A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Aminotriazoles for the treatment of demyelinating diseases |
| WO2018106641A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Pyrazoles for the treatment of demyelinating diseases |
| WO2018106643A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Heterocyclic azoles for the treatment of demyelinating diseases |
| SG11201908560SA (en) | 2017-03-16 | 2019-10-30 | Hoffmann La Roche | Heterocyclic compounds useful as dual atx/ca inhibitors |
| WO2018167113A1 (en) | 2017-03-16 | 2018-09-20 | F. Hoffmann-La Roche Ag | New bicyclic compounds as atx inhibitors |
| EP3638672A1 (en) | 2017-06-13 | 2020-04-22 | GlaxoSmithKline Intellectual Property Development Limited | Chemical compounds as h-pgds inhibitors |
| WO2020156459A1 (zh) | 2019-02-01 | 2020-08-06 | 湖北生物医药产业技术研究院有限公司 | 吡咯并嘧啶衍生物及其用途 |
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| US7629468B2 (en) * | 2000-10-02 | 2009-12-08 | Janssen Pharmaceutica Nv | Metabotropic glutamate receptor antagonists |
| US20100056506A1 (en) * | 2006-05-01 | 2010-03-04 | Pfizer Products Inc. | Substituted 2-amino-fused heterocyclic compounds |
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