ES2829636T3 - Pirazolo[3,4-b]piridin-6-carboxamidas N-sulfoniladas y método de uso - Google Patents
Pirazolo[3,4-b]piridin-6-carboxamidas N-sulfoniladas y método de uso Download PDFInfo
- Publication number
- ES2829636T3 ES2829636T3 ES16788232T ES16788232T ES2829636T3 ES 2829636 T3 ES2829636 T3 ES 2829636T3 ES 16788232 T ES16788232 T ES 16788232T ES 16788232 T ES16788232 T ES 16788232T ES 2829636 T3 ES2829636 T3 ES 2829636T3
- Authority
- ES
- Spain
- Prior art keywords
- carboxamide
- pyridine
- phenyl
- cyclobutyl
- methanesulfonyl
- 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.)
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- 238000000034 method Methods 0.000 title description 88
- JKFBIZUZFKODCG-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyridine-6-carboxamide Chemical class N1C(C(=O)N)=CC=C2C=NN=C21 JKFBIZUZFKODCG-UHFFFAOYSA-N 0.000 title description 19
- -1 -N3 Chemical group 0.000 claims abstract description 993
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 300
- 150000001875 compounds Chemical class 0.000 claims abstract description 169
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 142
- 150000003839 salts Chemical class 0.000 claims abstract description 117
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 91
- 239000001257 hydrogen Substances 0.000 claims abstract description 91
- 125000005466 alkylenyl group Chemical group 0.000 claims abstract description 88
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 51
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 43
- 125000001424 substituent group Chemical group 0.000 claims abstract description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 38
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims abstract description 38
- AMWPZASLDLLQFT-JJNLEZRASA-N [(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl n-(2-aminoacetyl)sulfamate Chemical compound O[C@@H]1[C@H](O)[C@@H](COS(=O)(=O)NC(=O)CN)O[C@H]1N1C2=NC=NC(N)=C2N=C1 AMWPZASLDLLQFT-JJNLEZRASA-N 0.000 claims abstract description 30
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 28
- 150000002367 halogens Chemical class 0.000 claims abstract description 27
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 26
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 24
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 22
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 20
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 17
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 11
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims abstract description 10
- 229910052702 rhenium Inorganic materials 0.000 claims abstract description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 4
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 4
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 4
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims abstract 31
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 623
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 349
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 338
- 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 316
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 180
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 172
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 141
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 117
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 107
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 103
- KECCPKLXQUOWMI-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(CO)CO KECCPKLXQUOWMI-UHFFFAOYSA-N 0.000 claims description 64
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 62
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 59
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 52
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 51
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 47
- 239000003814 drug Substances 0.000 claims description 47
- 125000002950 monocyclic group Chemical group 0.000 claims description 41
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 35
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 29
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 29
- 238000011282 treatment Methods 0.000 claims description 27
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 25
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 20
- 229940124597 therapeutic agent Drugs 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 18
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 17
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 16
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 14
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 13
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 12
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 12
- 239000003623 enhancer Substances 0.000 claims description 12
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 11
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 11
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 11
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 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 7
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims description 6
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 5
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 5
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 4
- 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 claims description 4
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 4
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
- ANMVTDVBEDVFRB-UHFFFAOYSA-N 1-propan-2-ylpyrazole Chemical compound CC(C)N1C=CC=N1 ANMVTDVBEDVFRB-UHFFFAOYSA-N 0.000 claims description 2
- WMKYKQWKLILFBM-UHFFFAOYSA-N 2h-pyridine-1-carboxylic acid Chemical compound OC(=O)N1CC=CC=C1 WMKYKQWKLILFBM-UHFFFAOYSA-N 0.000 claims description 2
- PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 claims description 2
- 125000000062 cyclohexylmethoxy group Chemical group [H]C([H])(O*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims description 2
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 claims description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 claims description 2
- GZNHBQOHAWURQU-UHFFFAOYSA-N C(C1CCN(CC1)C1=CN(N=C1C1CCC1)C1=CC=CC=C1)N1CCCC1 Chemical compound C(C1CCN(CC1)C1=CN(N=C1C1CCC1)C1=CC=CC=C1)N1CCCC1 GZNHBQOHAWURQU-UHFFFAOYSA-N 0.000 claims 3
- LCQBXGRVYNIISR-UHFFFAOYSA-N FC1(CCN(CC1)C1=C2C(=NC(=C1)C(=O)NS(=O)(=O)C)N(N=C2C(C)C)C1=CC=C(C=C1)F)COC Chemical compound FC1(CCN(CC1)C1=C2C(=NC(=C1)C(=O)NS(=O)(=O)C)N(N=C2C(C)C)C1=CC=C(C=C1)F)COC LCQBXGRVYNIISR-UHFFFAOYSA-N 0.000 claims 1
- LATNQRFKPCZWQN-CRAIPNDOSA-N F[C@@H]1CN(CC[C@H]1O)C1=C2C(=NC(=C1)C(=O)NS(=O)(=O)C)N(N=C2C(C)C)C1=CC=C(C=C1)F Chemical compound F[C@@H]1CN(CC[C@H]1O)C1=C2C(=NC(=C1)C(=O)NS(=O)(=O)C)N(N=C2C(C)C)C1=CC=C(C=C1)F LATNQRFKPCZWQN-CRAIPNDOSA-N 0.000 claims 1
- RDJVGBVLLKJFCC-UHFFFAOYSA-N N1(CCCCC1)C1CCN(CC1)C1=C2C(=NC(=C1)C(=O)NS(=O)(=O)C1CC1)N(N=C2C1CCC1)C1=CC=CC=C1 Chemical compound N1(CCCCC1)C1CCN(CC1)C1=C2C(=NC(=C1)C(=O)NS(=O)(=O)C1CC1)N(N=C2C1CCC1)C1=CC=CC=C1 RDJVGBVLLKJFCC-UHFFFAOYSA-N 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 31
- 125000003342 alkenyl group Chemical group 0.000 abstract description 6
- HEYSFDAMRDTCJM-UUOKFMHZSA-N [(2r,3s,4r,5r)-5-(2-amino-6-oxo-3h-purin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methyl phosphono hydrogen phosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H]1O HEYSFDAMRDTCJM-UUOKFMHZSA-N 0.000 abstract 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
- 150000003857 carboxamides Chemical class 0.000 description 143
- 239000000203 mixture Substances 0.000 description 53
- 102220020717 rs397508657 Human genes 0.000 description 52
- 230000035772 mutation Effects 0.000 description 50
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 48
- 235000002639 sodium chloride Nutrition 0.000 description 44
- 201000010099 disease Diseases 0.000 description 35
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 29
- 150000002431 hydrogen Chemical group 0.000 description 29
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 29
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 125000003386 piperidinyl group Chemical group 0.000 description 25
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
- 108090000623 proteins and genes Proteins 0.000 description 23
- 230000000694 effects Effects 0.000 description 22
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 21
- 125000004193 piperazinyl group Chemical group 0.000 description 21
- 125000004076 pyridyl group Chemical group 0.000 description 21
- 102220000269 rs62514893 Human genes 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 18
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 18
- 229940079593 drug Drugs 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 17
- 125000000217 alkyl group Chemical group 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 16
- 125000002757 morpholinyl group Chemical group 0.000 description 16
- 125000004429 atom Chemical group 0.000 description 15
- 125000002393 azetidinyl group Chemical group 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 239000003643 water by type Substances 0.000 description 15
- 125000003373 pyrazinyl group Chemical group 0.000 description 14
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 208000021386 Sjogren Syndrome Diseases 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 230000001684 chronic effect Effects 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 13
- 125000005842 heteroatom Chemical group 0.000 description 13
- 125000000714 pyrimidinyl group Chemical group 0.000 description 13
- 230000032258 transport Effects 0.000 description 13
- LTUFGCFAPCJOFQ-UHFFFAOYSA-N 2h-pyran-3-carboxamide Chemical compound NC(=O)C1=CC=COC1 LTUFGCFAPCJOFQ-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 239000005711 Benzoic acid Substances 0.000 description 11
- 235000010233 benzoic acid Nutrition 0.000 description 11
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
- 125000003566 oxetanyl group Chemical group 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 11
- 108091006146 Channels Proteins 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 230000000414 obstructive effect Effects 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 10
- 229910052717 sulfur Inorganic materials 0.000 description 10
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 10
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 235000019439 ethyl acetate Nutrition 0.000 description 9
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 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 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- ZKWFSTHEYLJLEL-UHFFFAOYSA-N morpholine-4-carboxamide Chemical compound NC(=O)N1CCOCC1 ZKWFSTHEYLJLEL-UHFFFAOYSA-N 0.000 description 8
- 125000002098 pyridazinyl group Chemical group 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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| US201662309794P | 2016-03-17 | 2016-03-17 | |
| PCT/IB2016/056029 WO2017060874A1 (en) | 2015-10-09 | 2016-10-07 | N-sulfonylated pyrazolo[3,4-b]pyridin-6-carboxamides and method of use |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT3183254T (pt) | 2014-08-21 | 2019-08-29 | Boehringer Ingelheim Int | Novos compostos de espiro[3h-indole-3,2¿-pirrolidin]-2(1h)-ona e derivados como inibidores de mdm2-p53 |
| TWI737635B (zh) | 2015-10-09 | 2021-09-01 | 德商百靈佳殷格翰國際股份有限公司 | 作為mdm2－p53抑制劑之新穎螺﹝3h－吲哚－3，2´－吡咯啶﹞－2（1h）－酮化合物及其衍生物 |
| SI3359541T1 (sl) | 2015-10-09 | 2021-01-29 | Abbvie Overseas S.A R.L. | N-sulfonirani pirazolo(3,4 b)piridin-6-karboksamidi in postopki uporabe |
| US10138227B2 (en) | 2016-06-03 | 2018-11-27 | Abbvie S.Á.R.L. | Heteroaryl substituted pyridines and methods of use |
| US10399940B2 (en) | 2016-10-07 | 2019-09-03 | Abbvie S.Á.R.L. | Substituted pyrrolidines and methods of use |
| US9981910B2 (en) | 2016-10-07 | 2018-05-29 | Abbvie S.Á.R.L. | Substituted pyrrolidines and methods of use |
| EP3558982A1 (en) | 2016-12-20 | 2019-10-30 | AbbVie S.À.R.L. | Deuterated cftr modulators and methods of use |
| TW201831471A (zh) | 2017-02-24 | 2018-09-01 | 盧森堡商艾伯維公司 | 囊腫纖化症跨膜傳導調節蛋白的調節劑及其使用方法 |
| US10988454B2 (en) | 2017-09-14 | 2021-04-27 | Abbvie Overseas S.À.R.L. | Modulators of the cystic fibrosis transmembrane conductance regulator protein and methods of use |
| WO2019193062A1 (en) | 2018-04-03 | 2019-10-10 | Abbvie S.Á.R.L | Substituted pyrrolidines and their use |
| GB201905711D0 (en) * | 2019-04-24 | 2019-06-05 | Galapagos Nv | Novel compounds and pharmaceutical compositions thereof for the treatment of kidney diseases |
| US11345691B2 (en) | 2019-06-03 | 2022-05-31 | AbbVie Global Enterprises Ltd. | Prodrug modulators of the cystic fibrosis transmembrane conductance regulator protein and methods of use |
| US20220267300A1 (en) * | 2019-06-12 | 2022-08-25 | NodThera Limited | Sulfonamide derivatives and uses thereof |
| US11236067B2 (en) | 2019-07-12 | 2022-02-01 | Orphomed, Inc. | Compound for treating cystic fibrosis |
| CN114206892A (zh) * | 2019-08-09 | 2022-03-18 | 爱杜西亚药品有限公司 | (2-乙酰氨基)硫代-β-D-吡喃半乳糖苷衍生物 |
| KR102836833B1 (ko) * | 2019-12-10 | 2025-07-22 | 에프. 호프만-라 로슈 아게 | 신규 메틸퀴나졸리논 유도체 |
| WO2021242505A1 (en) | 2020-05-08 | 2021-12-02 | Halia Therapeutics, Inc. | Inhibitors of nek7 kinase |
| MX2022015495A (es) | 2020-06-08 | 2023-03-14 | Halia Therapeutics Inc | Inhibidores de cinasa relacionada con el gen a nunca en mitosis (nek7). |
| CR20230120A (es) | 2020-08-07 | 2023-09-01 | Vertex Pharma | Moduladores del regulador de la conductancia transmembrana de la fibrosis quística |
| EP4199914A4 (en) | 2020-08-20 | 2024-09-04 | The Board of Trustees of the Leland Stanford Junior University | METHODS OF TREATMENT OF RESPIRATORY DISEASES CHARACTERIZED BY HYPERSECRETION OF MUCUS |
| US12324802B2 (en) | 2020-11-18 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| WO2022150174A1 (en) | 2021-01-06 | 2022-07-14 | AbbVie Global Enterprises Ltd. | Modulators of the cystic fibrosis transmembrane conductance regulator protein and methods of use |
| WO2022150173A1 (en) | 2021-01-06 | 2022-07-14 | AbbVie Global Enterprises Ltd. | Modulators of the cystic fibrosis transmembrane conductance regulator protein and methods of use |
| IL314449A (en) | 2022-02-03 | 2024-09-01 | Vertex Pharma | Methods of treatment for cystic fibrosis |
| IL314691A (en) | 2022-02-03 | 2024-10-01 | Vertex Pharma | PREPARATION METHODS AND CRYSTALLINE FORMS OF (6A,12A)-17-AMINO-12-METHYL-6,15-BIS(TRIFLUOROMETHYL)-13,19-DIOXA-3,4,18-TRIAZATRICYCLO[ 12.3.112.3.1. NONADECA-1(18),2,4,14,16-PENTAEN-6-OL |
| CA3251045A1 (en) | 2022-02-08 | 2023-08-17 | Vertex Pharmaceuticals Incorporated | MODULATORS OF THE TRANSMEMBRANE CONDUCTANCE REGULATOR IN CYSTIC FIBROSIS |
| US20250332151A1 (en) | 2022-05-16 | 2025-10-30 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| CN115806532A (zh) * | 2022-08-31 | 2023-03-17 | 大连百傲化学股份有限公司 | 一种mit中杂质的制备方法 |
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| CN115960100B (zh) * | 2022-12-28 | 2023-08-18 | 北京康立生医药技术开发有限公司 | 一种治疗胃肠道间质瘤药物皮咪特昔布的合成方法 |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3833598A (en) * | 1972-12-29 | 1974-09-03 | Squibb & Sons Inc | Amino derivatives of pyrazolopyridine-6-carboxylic acids and esters |
| GB0217431D0 (en) | 2002-07-27 | 2002-09-04 | Astrazeneca Ab | Novel compounds |
| CA2559629A1 (en) * | 2004-03-16 | 2005-09-29 | Glaxo Group Limited | Pyrazolo[3,4-b]pyridine compound, and its use as a pde4 inhibitor |
| AU2005251745A1 (en) | 2004-06-04 | 2005-12-22 | The Regents Of The University Of California | Compounds having activity in increasing ion transport by mutant-CFTR and uses thereof |
| PT1773816E (pt) | 2004-06-24 | 2015-04-29 | Vertex Pharma | Moduladores de transportadores de cassete de ligação de atp |
| US8354427B2 (en) | 2004-06-24 | 2013-01-15 | Vertex Pharmaceutical Incorporated | Modulators of ATP-binding cassette transporters |
| WO2006004188A1 (en) * | 2004-07-05 | 2006-01-12 | Astellas Pharma Inc. | Pyrazolopyridine derivatives |
| US8362031B2 (en) * | 2004-08-20 | 2013-01-29 | University Of Kansas | Lonidamine analogues and treatment of polycystic kidney disease |
| CN101687883B (zh) | 2007-05-25 | 2012-05-23 | 沃泰克斯药物股份有限公司 | 囊性纤维化跨膜传导调节因子的调节剂 |
| JP2011503103A (ja) * | 2007-11-07 | 2011-01-27 | フォールドアールエックス ファーマシューティカルズ インコーポレーティッド | タンパク質輸送の調節方法 |
| CN101939054B (zh) | 2007-12-10 | 2014-10-29 | 诺华股份有限公司 | 有机化合物 |
| WO2009076593A1 (en) | 2007-12-13 | 2009-06-18 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| RU2518479C2 (ru) | 2008-10-23 | 2014-06-10 | Вертекс Фармасьютикалз Инкорпорейтед | Твердые формы n-(7-азабицикло[2.2.1]гептан-7-ил-)-2-(трифторметил)фенил)-4-оксо-5-(трифторметил)-1,4-дигидрохинолин-3-карбоксамида |
| WO2010078103A1 (en) | 2008-12-30 | 2010-07-08 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
| US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| PT2616444E (pt) * | 2010-09-14 | 2015-12-09 | Inst Biochemii I Biofizyki Pan | Compostos como moduladores de uma proteína cftr mutante e seu uso para tratar doenças associadas à disfunção da proteína cftr |
| PL2624695T3 (pl) | 2010-10-08 | 2016-03-31 | Nivalis Therapeutics Inc | Nowe podstawione związki chinolinowe jako inhibitory reduktazy S-nitrozoglutationu |
| WO2013038381A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine/pyrazine amide derivatives |
| EP2755652B1 (en) | 2011-09-16 | 2021-06-02 | Novartis AG | N-substituted heterocyclyl carboxamides |
| ES2558457T3 (es) | 2011-09-16 | 2016-02-04 | Novartis Ag | Compuestos heterocíclicos para el tratamiento de fibrosis quística |
| WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| AU2012312520A1 (en) | 2011-09-20 | 2014-05-08 | The University Of North Carolina At Chapel Hill | Regulation of sodium channels by PLUNC proteins |
| CA2853439A1 (en) * | 2011-10-31 | 2013-05-10 | Xenon Pharmaceuticals Inc. | Benzenesulfonamide compounds and their use as therapeutic agents |
| WO2014081820A1 (en) * | 2012-11-20 | 2014-05-30 | Discoverybiomed, Inc. | Small molecule cftr correctors |
| LU92578B1 (fr) | 2013-05-07 | 2014-12-15 | Galapagos Nv | Nouveaux composés et compostions pharmaceutiques de ceux-ci pour le traitement de la mucoviscidose |
| PE20160286A1 (es) | 2013-08-08 | 2016-05-22 | Galapagos Nv | DERIVADOS DE TIENO [2,3-c] PIRANO Y SUS COMPOSICIONES FARMACEUTICAS PARA EL TRATAMIENTO DE LA FIBROSIS QUISTICA |
| KR20160118345A (ko) * | 2014-02-06 | 2016-10-11 | 애브비 인코포레이티드 | 6-헤테로아릴옥시- 및 6-아릴옥시-퀴놀린-2-카복사미드 및 이의 용도 |
| EP3116870A1 (en) | 2014-03-13 | 2017-01-18 | Proteostasis Therapeutics, Inc. | Compounds, compositions, and methods for increasing cftr activity |
| WO2015138909A1 (en) | 2014-03-13 | 2015-09-17 | Proteostasis Therapeutics, Inc. | Compounds, compositions, and methods for increasing cftr activity |
| SG10201803472QA (en) | 2014-10-31 | 2018-06-28 | Abbvie Sarl | Substituted chromanes and method of use |
| AU2015339196A1 (en) | 2014-10-31 | 2017-05-11 | Abbvie S.A.R.L. | Substituted tetrahydropyrans and method of use |
| BR112018007165A2 (pt) * | 2015-10-09 | 2019-01-22 | AbbVie S.à.r.l. | novos compostos para tratamento da fibrose cística |
| SI3359541T1 (sl) * | 2015-10-09 | 2021-01-29 | Abbvie Overseas S.A R.L. | N-sulfonirani pirazolo(3,4 b)piridin-6-karboksamidi in postopki uporabe |
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