NO332932B1 - Benzensulfonamidderivater, anvendelse derav og sammensetning inneholdende et slikt derivat - Google Patents
Benzensulfonamidderivater, anvendelse derav og sammensetning inneholdende et slikt derivatInfo
- Publication number
- NO332932B1 NO332932B1 NO20054878A NO20054878A NO332932B1 NO 332932 B1 NO332932 B1 NO 332932B1 NO 20054878 A NO20054878 A NO 20054878A NO 20054878 A NO20054878 A NO 20054878A NO 332932 B1 NO332932 B1 NO 332932B1
- Authority
- NO
- Norway
- Prior art keywords
- hydrogen
- dichlorophenoxy
- cyano
- hydroxy
- benzonitrile
- Prior art date
Links
- 150000008331 benzenesulfonamides Chemical class 0.000 title claims abstract description 19
- 239000000203 mixture Substances 0.000 title claims description 59
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
- 201000010099 disease Diseases 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 208000006673 asthma Diseases 0.000 claims abstract description 10
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 61
- 239000001257 hydrogen Substances 0.000 claims description 61
- -1 nitro, cyano, tetrazolyl Chemical group 0.000 claims description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 46
- 239000000460 chlorine Substances 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 150000002431 hydrogen Chemical group 0.000 claims description 15
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 239000011737 fluorine Substances 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 239000011630 iodine Substances 0.000 claims description 6
- 208000026935 allergic disease Diseases 0.000 claims description 4
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 230000004957 immunoregulator effect Effects 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- OGOWXUSOQDTJOW-UHFFFAOYSA-N n-(1-azabicyclo[2.2.2]octan-3-yl)-2-(3,5-dichlorophenyl)sulfanyl-5-nitrobenzenesulfonamide Chemical compound C1N(CC2)CCC2C1NS(=O)(=O)C1=CC([N+](=O)[O-])=CC=C1SC1=CC(Cl)=CC(Cl)=C1 OGOWXUSOQDTJOW-UHFFFAOYSA-N 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 206010037391 Pulmonary granuloma Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 206010039083 rhinitis Diseases 0.000 claims description 3
- UOUQMAUKVKOFQE-FQEVSTJZSA-N (2s)-1-[1-[5-cyano-2-(3,5-dichlorophenoxy)phenyl]sulfonylpiperidin-4-yl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C1CCN(S(=O)(=O)C=2C(=CC=C(C=2)C#N)OC=2C=C(Cl)C=C(Cl)C=2)CC1 UOUQMAUKVKOFQE-FQEVSTJZSA-N 0.000 claims description 2
- RJKTVYBEKJWZDB-UHFFFAOYSA-N 3-[(1-benzyl-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrol-5-yl)sulfonyl]-4-(3,5-dichlorophenoxy)benzonitrile Chemical compound ClC1=CC(Cl)=CC(OC=2C(=CC(=CC=2)C#N)S(=O)(=O)N2CC3N(CC=4C=CC=CC=4)CCC3C2)=C1 RJKTVYBEKJWZDB-UHFFFAOYSA-N 0.000 claims description 2
- VUQUOGIUBXJSJR-AHWVRZQESA-N 3-[4-[(3s,4s)-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxypyrrolidin-1-yl]piperidin-1-yl]sulfonyl-4-(3,5-dichlorophenoxy)benzonitrile Chemical compound C1[C@H](O)[C@@H](O[Si](C)(C)C(C)(C)C)CN1C1CCN(S(=O)(=O)C=2C(=CC=C(C=2)C#N)OC=2C=C(Cl)C=C(Cl)C=2)CC1 VUQUOGIUBXJSJR-AHWVRZQESA-N 0.000 claims description 2
- LMYYBIFKCFVCMN-WDSOQIARSA-N 4-(3,5-dichlorophenoxy)-3-[(3s)-3-[(3s,4s)-3,4-dihydroxypyrrolidin-1-yl]pyrrolidin-1-yl]sulfonylbenzonitrile Chemical compound C1[C@H](O)[C@@H](O)CN1[C@@H]1CN(S(=O)(=O)C=2C(=CC=C(C=2)C#N)OC=2C=C(Cl)C=C(Cl)C=2)CC1 LMYYBIFKCFVCMN-WDSOQIARSA-N 0.000 claims description 2
- SKAFTGCTEWPJFZ-UHFFFAOYSA-N 4-(3,5-dichlorophenoxy)-3-[2-[(3-hydroxypyrrolidin-1-yl)methyl]piperidin-1-yl]sulfonylbenzonitrile Chemical compound C1C(O)CCN1CC1N(S(=O)(=O)C=2C(=CC=C(C=2)C#N)OC=2C=C(Cl)C=C(Cl)C=2)CCCC1 SKAFTGCTEWPJFZ-UHFFFAOYSA-N 0.000 claims description 2
- SQLAWHDQGJYLEE-UHFFFAOYSA-N 4-(3,5-dichlorophenoxy)-3-[3-[(2,5-dioxopyrrolidin-1-yl)methyl]-4-pyrrolidin-1-ylpiperidin-1-yl]sulfonylbenzonitrile Chemical compound ClC1=CC(Cl)=CC(OC=2C(=CC(=CC=2)C#N)S(=O)(=O)N2CC(CN3C(CCC3=O)=O)C(CC2)N2CCCC2)=C1 SQLAWHDQGJYLEE-UHFFFAOYSA-N 0.000 claims description 2
- IQXPWEGYBXICGU-UHFFFAOYSA-N 4-(3,5-dichlorophenoxy)-3-[3-[(2,5-dioxopyrrolidin-1-yl)methyl]piperazin-1-yl]sulfonylbenzonitrile Chemical compound ClC1=CC(Cl)=CC(OC=2C(=CC(=CC=2)C#N)S(=O)(=O)N2CC(CN3C(CCC3=O)=O)NCC2)=C1 IQXPWEGYBXICGU-UHFFFAOYSA-N 0.000 claims description 2
- NZMQPWWKJLZBCA-DEOSSOPVSA-N 4-(3,5-dichlorophenoxy)-3-[4-[(2s)-2-(2-hydroxypropan-2-yl)pyrrolidin-1-yl]piperidin-1-yl]sulfonylbenzonitrile Chemical compound CC(C)(O)[C@@H]1CCCN1C1CCN(S(=O)(=O)C=2C(=CC=C(C=2)C#N)OC=2C=C(Cl)C=C(Cl)C=2)CC1 NZMQPWWKJLZBCA-DEOSSOPVSA-N 0.000 claims description 2
- YELUWQMRLNJXBO-FQEVSTJZSA-N 4-(3,5-dichlorophenoxy)-3-[4-[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]piperidin-1-yl]sulfonylbenzonitrile Chemical compound OC[C@@H]1CCCN1C1CCN(S(=O)(=O)C=2C(=CC=C(C=2)C#N)OC=2C=C(Cl)C=C(Cl)C=2)CC1 YELUWQMRLNJXBO-FQEVSTJZSA-N 0.000 claims description 2
- STGIKTRYXLHYCS-PMACEKPBSA-N 4-(3,5-dichlorophenoxy)-3-[4-[(3s,4s)-3,4-dihydroxypyrrolidin-1-yl]piperidin-1-yl]sulfonylbenzonitrile Chemical compound C1[C@H](O)[C@@H](O)CN1C1CCN(S(=O)(=O)C=2C(=CC=C(C=2)C#N)OC=2C=C(Cl)C=C(Cl)C=2)CC1 STGIKTRYXLHYCS-PMACEKPBSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- FRPPDBUZVCMUAE-ICSRJNTNSA-N methyl (2s,4s)-1-[5-cyano-2-(3,5-dichlorophenoxy)phenyl]sulfonyl-4-pyrrolidin-1-ylpyrrolidine-2-carboxylate Chemical compound C([C@H](C[C@H]1C(=O)OC)N2CCCC2)N1S(=O)(=O)C1=CC(C#N)=CC=C1OC1=CC(Cl)=CC(Cl)=C1 FRPPDBUZVCMUAE-ICSRJNTNSA-N 0.000 claims description 2
- RVYZTFQAFBFWBI-SFHVURJKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-cyano-2-(3,5-dichlorophenoxy)benzenesulfonamide Chemical compound ClC1=CC(Cl)=CC(OC=2C(=CC(=CC=2)C#N)S(=O)(=O)N[C@@H]2C3CCN(CC3)C2)=C1 RVYZTFQAFBFWBI-SFHVURJKSA-N 0.000 claims description 2
- RVYZTFQAFBFWBI-GOSISDBHSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-5-cyano-2-(3,5-dichlorophenoxy)benzenesulfonamide Chemical compound ClC1=CC(Cl)=CC(OC=2C(=CC(=CC=2)C#N)S(=O)(=O)N[C@H]2C3CCN(CC3)C2)=C1 RVYZTFQAFBFWBI-GOSISDBHSA-N 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- LDJDHSINBFNMFS-UHFFFAOYSA-N n-[2,4-dimethoxy-5-[(2-piperidin-1-ylphenyl)methylsulfamoyl]phenyl]acetamide Chemical compound C1=C(NC(C)=O)C(OC)=CC(OC)=C1S(=O)(=O)NCC1=CC=CC=C1N1CCCCC1 LDJDHSINBFNMFS-UHFFFAOYSA-N 0.000 claims 2
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 1
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- 150000001875 compounds Chemical class 0.000 description 102
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
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- 238000006243 chemical reaction Methods 0.000 description 38
- 210000004027 cell Anatomy 0.000 description 37
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
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- VJEHAGIRIFQFGS-UHFFFAOYSA-N tert-butyl [[cyano(phenyl)methyl]amino] carbonate Chemical compound CC(C)(C)OC(=O)ONC(C#N)C1=CC=CC=C1 VJEHAGIRIFQFGS-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- 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
- A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
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- 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
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- 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
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D207/12—Oxygen or sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C—CHEMISTRY; METALLURGY
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members 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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-
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/404—2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/48—Sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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JP2004217654A (ja) * | 2002-12-27 | 2004-08-05 | Japan Tobacco Inc | 縮合n含有へテロ環化合物及びその医薬用途 |
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JP2011147872A (ja) | 2010-01-21 | 2011-08-04 | Kansai Kanaami Kk | 積層焼結フィルター |
EP2547655B1 (en) | 2010-03-17 | 2016-03-09 | Axikin Pharmaceuticals, Inc. | Arylsulfonamide ccr3 antagonists |
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2004
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- 2009-07-16 US US12/504,606 patent/US20090286771A1/en not_active Abandoned
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