BR112020005102A2 - moduladores da proteína reguladora de condutância transmembranar de fibrose cística e métodos de uso - Google Patents
moduladores da proteína reguladora de condutância transmembranar de fibrose cística e métodos de uso Download PDFInfo
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- BR112020005102A2 BR112020005102A2 BR112020005102-0A BR112020005102A BR112020005102A2 BR 112020005102 A2 BR112020005102 A2 BR 112020005102A2 BR 112020005102 A BR112020005102 A BR 112020005102A BR 112020005102 A2 BR112020005102 A2 BR 112020005102A2
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- BR
- Brazil
- Prior art keywords
- sulfonyl
- carboxamide
- cyclopropane
- pyridin3yl
- oxy
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- 201000003883 Cystic fibrosis Diseases 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title claims abstract description 26
- 102000034356 gene-regulatory proteins Human genes 0.000 title description 5
- 108091006104 gene-regulatory proteins Proteins 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 113
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- -1 C (O) N (R7) 2 Proteins 0.000 claims description 1769
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 550
- 150000003857 carboxamides Chemical class 0.000 claims description 469
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 claims description 332
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 289
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 274
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 243
- 125000001424 substituent group Chemical group 0.000 claims description 210
- 125000000623 heterocyclic group Chemical group 0.000 claims description 205
- 229910052801 chlorine Inorganic materials 0.000 claims description 192
- 229910052794 bromium Inorganic materials 0.000 claims description 182
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 178
- 125000001072 heteroaryl group Chemical group 0.000 claims description 177
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 151
- 229910052731 fluorine Inorganic materials 0.000 claims description 147
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 claims description 130
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 120
- 229910052740 iodine Inorganic materials 0.000 claims description 117
- 125000003118 aryl group Chemical group 0.000 claims description 116
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 108
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 93
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 92
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 84
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 68
- 101100079984 Caenorhabditis elegans nhr-9 gene Proteins 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 57
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 55
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 50
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 41
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 41
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 37
- 125000004076 pyridyl group Chemical group 0.000 claims description 37
- 239000003814 drug Substances 0.000 claims description 33
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 29
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 26
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 24
- 229940124597 therapeutic agent Drugs 0.000 claims description 23
- 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims description 22
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 101100240519 Caenorhabditis elegans nhr-13 gene Proteins 0.000 claims description 16
- 101100240520 Caenorhabditis elegans nhr-14 gene Proteins 0.000 claims description 16
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims description 16
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims description 16
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 15
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 12
- 239000003623 enhancer Substances 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 8
- 101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 8
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 7
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 5
- 101100240518 Caenorhabditis elegans nhr-12 gene Proteins 0.000 claims description 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 claims description 4
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 4
- QKGKJMXEFGLWKC-UHFFFAOYSA-N 2-[[1-(2,4-dichlorophenyl)cyclopropanecarbonyl]sulfamoyl]benzoic acid Chemical compound ClC1=C(C=CC(=C1)Cl)C1(CC1)C(=O)NS(=O)(=O)C1=C(C(=O)O)C=CC=C1 QKGKJMXEFGLWKC-UHFFFAOYSA-N 0.000 claims description 4
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 4
- UPWNQNXUCATZCA-UHFFFAOYSA-N N-(benzenesulfonyl)-1-(2,4-dichlorophenyl)cyclopropane-1-carboxamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC(=O)C1(CC1)C1=C(C=C(C=C1)Cl)Cl UPWNQNXUCATZCA-UHFFFAOYSA-N 0.000 claims description 4
- OIFOMFAGTXKCKA-UHFFFAOYSA-N N-(benzenesulfonyl)-1-(3,4-dichlorophenyl)cyclopropane-1-carboxamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC(=O)C1(CC1)C1=CC(=C(C=C1)Cl)Cl OIFOMFAGTXKCKA-UHFFFAOYSA-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
- 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 claims description 4
- 229940095102 methyl benzoate Drugs 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 claims description 2
- MTMHAZRINSGABW-UHFFFAOYSA-N N-(benzenesulfonyl)-1-(2-chlorophenyl)cyclopropane-1-carboxamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC(=O)C1(CC1)C1=C(C=CC=C1)Cl MTMHAZRINSGABW-UHFFFAOYSA-N 0.000 claims description 2
- NLJDKUUWQLOMIZ-UHFFFAOYSA-N N-(benzenesulfonyl)-1-(2-fluorophenyl)cyclopropane-1-carboxamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC(=O)C1(CC1)C1=C(C=CC=C1)F NLJDKUUWQLOMIZ-UHFFFAOYSA-N 0.000 claims description 2
- QQEMJOZMMUHOEI-UHFFFAOYSA-N N-(benzenesulfonyl)-1-(3-bromophenyl)cyclopropane-1-carboxamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC(=O)C1(CC1)C1=CC(=CC=C1)Br QQEMJOZMMUHOEI-UHFFFAOYSA-N 0.000 claims description 2
- NSSUPAJAKKVQFZ-UHFFFAOYSA-N N-(benzenesulfonyl)-1-(4-chlorophenyl)cyclobutane-1-carboxamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC(=O)C1(CCC1)C1=CC=C(C=C1)Cl NSSUPAJAKKVQFZ-UHFFFAOYSA-N 0.000 claims description 2
- LZWMAWYJBXNQMA-UHFFFAOYSA-N N-(benzenesulfonyl)-1-(4-chlorophenyl)cyclopropane-1-carboxamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC(=O)C1(CC1)C1=CC=C(C=C1)Cl LZWMAWYJBXNQMA-UHFFFAOYSA-N 0.000 claims description 2
- OTRRIPLGWXVIDR-UHFFFAOYSA-N N-(benzenesulfonyl)-1-(4-fluorophenyl)cyclopropane-1-carboxamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC(=O)C1(CC1)C1=CC=C(C=C1)F OTRRIPLGWXVIDR-UHFFFAOYSA-N 0.000 claims description 2
- DOMOCWIXODDDNN-UHFFFAOYSA-N N-(benzenesulfonyl)-1-(4-methoxyphenyl)cyclopropane-1-carboxamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC(=O)C1(CC1)C1=CC=C(C=C1)OC DOMOCWIXODDDNN-UHFFFAOYSA-N 0.000 claims description 2
- FFJZBEITUIJFQC-UHFFFAOYSA-N N-(benzenesulfonyl)-1-(4-methylphenyl)cyclopropane-1-carboxamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC(=O)C1(CC1)C1=CC=C(C=C1)C FFJZBEITUIJFQC-UHFFFAOYSA-N 0.000 claims description 2
- POQCJFVOLGMWFI-UHFFFAOYSA-N N-(benzenesulfonyl)-1-phenylcyclopropane-1-carboxamide Chemical compound O=C(NS(=O)(=O)c1ccccc1)C1(CC1)c1ccccc1 POQCJFVOLGMWFI-UHFFFAOYSA-N 0.000 claims description 2
- XZZDGHPLBMGRHW-UHFFFAOYSA-N N-(benzenesulfonyl)-2,2-dimethyl-1-phenylcyclopropane-1-carboxamide Chemical compound C1(=CC=CC=C1)S(=O)(=O)NC(=O)C1(C(C1)(C)C)C1=CC=CC=C1 XZZDGHPLBMGRHW-UHFFFAOYSA-N 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- XIHCPFKWEQVFCI-UHFFFAOYSA-N N-quinolin-5-ylsulfonylcyclopropanecarboxamide Chemical compound N1=CC=CC=2C(=CC=CC1=2)S(=O)(=O)NC(=O)C1CC1 XIHCPFKWEQVFCI-UHFFFAOYSA-N 0.000 claims 155
- MGGQGCLRCDNGSH-UHFFFAOYSA-N CC1=NC=2C=CC=C(C=2C=C1)S(=O)(=O)NC(=O)C1CC1 Chemical compound CC1=NC=2C=CC=C(C=2C=C1)S(=O)(=O)NC(=O)C1CC1 MGGQGCLRCDNGSH-UHFFFAOYSA-N 0.000 claims 90
- GFFMUNUTBUASGW-UHFFFAOYSA-N N1CCCC=2C(=CC=CC1=2)S(=O)(=O)NC(=O)C1CC1 Chemical compound N1CCCC=2C(=CC=CC1=2)S(=O)(=O)NC(=O)C1CC1 GFFMUNUTBUASGW-UHFFFAOYSA-N 0.000 claims 37
- MRYBBUALPJZKAH-UHFFFAOYSA-N N1C=CC=2C(=CC=CC1=2)S(=O)(=O)NC(=O)C1CC1 Chemical compound N1C=CC=2C(=CC=CC1=2)S(=O)(=O)NC(=O)C1CC1 MRYBBUALPJZKAH-UHFFFAOYSA-N 0.000 claims 35
- NPXXJHWJZRUMGM-UHFFFAOYSA-N O=C(C1CC1)NS(C1=CC=CC2=C1C=NN2)(=O)=O Chemical compound O=C(C1CC1)NS(C1=CC=CC2=C1C=NN2)(=O)=O NPXXJHWJZRUMGM-UHFFFAOYSA-N 0.000 claims 9
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims 2
- NGKHKQQEIAUCDW-UHFFFAOYSA-N 1-cyclopropylsulfonylnaphthalene Chemical compound O=S(=O)(C1CC1)c1cccc2ccccc12 NGKHKQQEIAUCDW-UHFFFAOYSA-N 0.000 claims 2
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- GCBXAQLZTBLSGE-UHFFFAOYSA-N 1-phenylcyclopropane-1-carboxamide Chemical compound C=1C=CC=CC=1C1(C(=O)N)CC1 GCBXAQLZTBLSGE-UHFFFAOYSA-N 0.000 claims 1
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- KAHOGKUPAQBWJU-UHFFFAOYSA-N CN1C(C(S(NC(C2CCC2)=O)(=O)=O)=CC=C2)=C2N=C1 Chemical compound CN1C(C(S(NC(C2CCC2)=O)(=O)=O)=CC=C2)=C2N=C1 KAHOGKUPAQBWJU-UHFFFAOYSA-N 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- WDOYWJXXSGMIOV-UHFFFAOYSA-N n-(4-methylphenyl)sulfonylcyclopropanecarboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)C1CC1 WDOYWJXXSGMIOV-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/45—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the singly-bound nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfonamides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
- C07D213/71—Sulfur atoms to which a second hetero atom is attached
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
- C07D235/28—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Sanitary Thin Papers (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pyridine Compounds (AREA)
- Indole Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Quinoline Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Furan Compounds (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762558430P | 2017-09-14 | 2017-09-14 | |
| US62/558,430 | 2017-09-14 | ||
| US201762608846P | 2017-12-21 | 2017-12-21 | |
| US62/608,846 | 2017-12-21 | ||
| PCT/IB2018/057020 WO2019053634A1 (en) | 2017-09-14 | 2018-09-13 | MODULATORS OF THE TRANSMEMBRANE CONDUCTANCE REGULATORY PROTEIN OF CYSTIC FIBROSIS AND METHODS OF USE |
Publications (1)
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|---|---|
| BR112020005102A2 true BR112020005102A2 (pt) | 2020-09-24 |
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| BR112020005102-0A BR112020005102A2 (pt) | 2017-09-14 | 2018-09-13 | moduladores da proteína reguladora de condutância transmembranar de fibrose cística e métodos de uso |
Country Status (34)
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW202140422A (zh) | 2014-10-06 | 2021-11-01 | 美商維泰克斯製藥公司 | 囊腫纖維化症跨膜傳導調節蛋白之調節劑 |
| GEP20217329B (en) | 2016-09-30 | 2021-12-10 | Vertex Pharma | Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator |
| EA202192783A1 (ru) | 2016-12-09 | 2022-02-24 | Вертекс Фармасьютикалз Инкорпорейтед | Модулятор регулятора трансмембранной проводимости при муковисцидозе, фармацевтические композиции, способы лечения и способ получения указанного модулятора |
| MA54105A (fr) | 2017-06-08 | 2021-09-15 | Vertex Pharma | Méthodes de traitement de la fibrose kystique |
| IL272032B2 (en) | 2017-07-17 | 2026-04-01 | Vertex Pharma | Combination therapy for the treatment of cystic fibrosis including N-(1,3-DIMETHYLPYRAZOL-4-YL)SULFONYL-6-[3-(3,3,3-TRIFLUORO-2,2- DIMETHYL-PROPOXY)PYRAZOL-1-YL]-2-[(4S)-2,2,4- TRIMETHYLPYRROLIDIN-1-YL]PYRIDINE-3-CARBOXAMIDE and |
| MA49752A (fr) | 2017-08-02 | 2021-04-21 | Vertex Pharma | Procédés de préparation de composés de pyrrolidine |
| 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 |
| KR102717072B1 (ko) | 2017-10-18 | 2024-10-15 | 인사이트 코포레이션 | Pi3k-감마 저해제로서의 3차 하이드록시기로 치환된 축합된 이미다졸 유도체 |
| CA3078893A1 (en) | 2017-10-19 | 2019-04-25 | Vertex Pharmaceuticals Incorporated | Crystalline forms and compositions of cftr modulators |
| KR102716244B1 (ko) | 2017-12-08 | 2024-10-14 | 버텍스 파마슈티칼스 인코포레이티드 | 낭포성 섬유증 막횡단 전도 조절자의 조정제의 제조 방법 |
| TWI810243B (zh) | 2018-02-05 | 2023-08-01 | 美商維泰克斯製藥公司 | 用於治療囊腫纖化症之醫藥組合物 |
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