DE60221569T2 - Acrylsulfonamidderivate zur verwendung als ccr3-antagonisten bei der behandlung von inflammatorischen und immunologischen erkrankungen - Google Patents
Acrylsulfonamidderivate zur verwendung als ccr3-antagonisten bei der behandlung von inflammatorischen und immunologischen erkrankungen Download PDFInfo
- Publication number
- DE60221569T2 DE60221569T2 DE60221569T DE60221569T DE60221569T2 DE 60221569 T2 DE60221569 T2 DE 60221569T2 DE 60221569 T DE60221569 T DE 60221569T DE 60221569 T DE60221569 T DE 60221569T DE 60221569 T2 DE60221569 T2 DE 60221569T2
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- Prior art keywords
- branched
- straight
- hydrogen
- ring
- alkyl
- Prior art date
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- Expired - Lifetime
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- 238000011282 treatment Methods 0.000 title claims description 15
- 230000002757 inflammatory effect Effects 0.000 title claims description 6
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 title claims 2
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 title claims 2
- 239000005557 antagonist Substances 0.000 title description 2
- 208000026278 immune system disease Diseases 0.000 title description 2
- BKQNPNCFOHHRBB-UHFFFAOYSA-N 1-oxoprop-2-ene-1-sulfonamide Chemical class NS(=O)(=O)C(=O)C=C BKQNPNCFOHHRBB-UHFFFAOYSA-N 0.000 title 1
- 208000027866 inflammatory disease Diseases 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims description 219
- 239000001257 hydrogen Substances 0.000 claims description 218
- 239000000203 mixture Substances 0.000 claims description 193
- 150000002431 hydrogen Chemical class 0.000 claims description 118
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 100
- -1 cyano, carboxy Chemical group 0.000 claims description 98
- 229920006395 saturated elastomer Polymers 0.000 claims description 92
- 125000000217 alkyl group Chemical group 0.000 claims description 86
- 239000000460 chlorine Substances 0.000 claims description 85
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 74
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 67
- 229910052736 halogen Inorganic materials 0.000 claims description 64
- 150000002367 halogens Chemical class 0.000 claims description 59
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 51
- 229910052717 sulfur Inorganic materials 0.000 claims description 44
- UOTCXIMRODXHSV-UHFFFAOYSA-N [2,3-dihydroxy-4-(2-methylsulfonyloxyethylazaniumyl)butyl]-(2-methylsulfonyloxyethyl)azanium;dichloride Chemical compound [Cl-].[Cl-].CS(=O)(=O)OCC[NH2+]CC(O)C(O)C[NH2+]CCOS(C)(=O)=O UOTCXIMRODXHSV-UHFFFAOYSA-N 0.000 claims description 42
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 37
- 229910052760 oxygen Inorganic materials 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 36
- 229910052801 chlorine Inorganic materials 0.000 claims description 33
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 30
- HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 26
- 125000005842 heteroatom Chemical group 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
- 239000011737 fluorine Substances 0.000 claims description 25
- 229910052731 fluorine Inorganic materials 0.000 claims description 25
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 23
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 22
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 20
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 16
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 208000006673 asthma Diseases 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 9
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 210000004072 lung Anatomy 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 7
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- 230000001363 autoimmune Effects 0.000 claims description 6
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 6
- 238000011321 prophylaxis Methods 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- 208000026935 allergic disease Diseases 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 4
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- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 208000023328 Basedow disease Diseases 0.000 claims description 4
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 4
- 206010018691 Granuloma Diseases 0.000 claims description 4
- 208000015023 Graves' disease Diseases 0.000 claims description 4
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 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 4
- 125000006263 dimethyl aminosulfonyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])S(*)(=O)=O 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000004957 immunoregulator effect Effects 0.000 claims description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 206010039083 rhinitis Diseases 0.000 claims description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000003944 tolyl group Chemical group 0.000 claims description 4
- CXMDVJPSBFHFAZ-UHFFFAOYSA-N 1-[2-(3,5-dibromophenoxy)-5-nitrophenyl]sulfonylpiperazine Chemical compound C1CNCCN1S(=O)(=O)C1=CC([N+](=O)[O-])=CC=C1OC1=CC(Br)=CC(Br)=C1 CXMDVJPSBFHFAZ-UHFFFAOYSA-N 0.000 claims description 3
- MWURPJRFLFHBRA-UHFFFAOYSA-N 1-[2-(3,5-dichloro-2-fluorophenoxy)-5-nitrophenyl]sulfonylpiperazine Chemical compound C1CNCCN1S(=O)(=O)C1=CC([N+](=O)[O-])=CC=C1OC1=CC(Cl)=CC(Cl)=C1F MWURPJRFLFHBRA-UHFFFAOYSA-N 0.000 claims description 3
- YOUXJSFJQJOEAR-UHFFFAOYSA-N 1-[2-(3,5-dichlorophenoxy)-5-nitrophenyl]sulfonyl-1,4-diazepane Chemical compound C1CCNCCN1S(=O)(=O)C1=CC([N+](=O)[O-])=CC=C1OC1=CC(Cl)=CC(Cl)=C1 YOUXJSFJQJOEAR-UHFFFAOYSA-N 0.000 claims description 3
- PZXBCZDWOYKAFB-UHFFFAOYSA-N 1-[2-(3,5-dichlorophenoxy)-5-nitrophenyl]sulfonyl-3,5-dimethylpiperazine Chemical compound C1C(C)NC(C)CN1S(=O)(=O)C1=CC([N+]([O-])=O)=CC=C1OC1=CC(Cl)=CC(Cl)=C1 PZXBCZDWOYKAFB-UHFFFAOYSA-N 0.000 claims description 3
- LPTOUQBSQLGFOP-UHFFFAOYSA-N 1-[2-(3,5-dichlorophenoxy)-5-nitrophenyl]sulfonyl-3-pyrrolidin-1-ylpyrrolidine Chemical compound C1CC(N2CCCC2)CN1S(=O)(=O)C1=CC([N+](=O)[O-])=CC=C1OC1=CC(Cl)=CC(Cl)=C1 LPTOUQBSQLGFOP-UHFFFAOYSA-N 0.000 claims description 3
- DJXLHVLRWFRMAX-UHFFFAOYSA-N 1-[2-(3,5-dichlorophenoxy)-5-nitrophenyl]sulfonyl-n,n-diethylpyrrolidin-3-amine Chemical compound C1C(N(CC)CC)CCN1S(=O)(=O)C1=CC([N+]([O-])=O)=CC=C1OC1=CC(Cl)=CC(Cl)=C1 DJXLHVLRWFRMAX-UHFFFAOYSA-N 0.000 claims description 3
- GKHAHZQMENAZHG-UHFFFAOYSA-N 1-[2-(3,5-dichlorophenoxy)-5-nitrophenyl]sulfonylpiperazine Chemical compound C1CNCCN1S(=O)(=O)C1=CC([N+](=O)[O-])=CC=C1OC1=CC(Cl)=CC(Cl)=C1 GKHAHZQMENAZHG-UHFFFAOYSA-N 0.000 claims description 3
- UZEKJXMJLMPEHG-UHFFFAOYSA-N 1-[2-(3,5-dichlorophenoxy)-5-nitrophenyl]sulfonylpiperazine-2-carboxylic acid Chemical compound OC(=O)C1CNCCN1S(=O)(=O)C1=CC([N+]([O-])=O)=CC=C1OC1=CC(Cl)=CC(Cl)=C1 UZEKJXMJLMPEHG-UHFFFAOYSA-N 0.000 claims description 3
- UNTKZXYTPPOUHO-UHFFFAOYSA-N 1-[2-(3,5-dichlorophenyl)sulfanyl-5-nitrophenyl]sulfonyl-4-pyrrolidin-1-ylpiperidine Chemical compound C1CC(N2CCCC2)CCN1S(=O)(=O)C1=CC([N+](=O)[O-])=CC=C1SC1=CC(Cl)=CC(Cl)=C1 UNTKZXYTPPOUHO-UHFFFAOYSA-N 0.000 claims description 3
- UGKSLSUMQNVYAW-UHFFFAOYSA-N 1-[2-(3,5-dimethylphenoxy)-5-nitrophenyl]sulfonyl-1,4-diazepane Chemical compound CC1=CC(C)=CC(OC=2C(=CC(=CC=2)[N+]([O-])=O)S(=O)(=O)N2CCNCCC2)=C1 UGKSLSUMQNVYAW-UHFFFAOYSA-N 0.000 claims description 3
- POXBXXTZUWRVJJ-UHFFFAOYSA-N 1-[2-(3,5-dimethylphenoxy)-5-nitrophenyl]sulfonyl-4-ethylpiperazine Chemical compound C1CN(CC)CCN1S(=O)(=O)C1=CC([N+]([O-])=O)=CC=C1OC1=CC(C)=CC(C)=C1 POXBXXTZUWRVJJ-UHFFFAOYSA-N 0.000 claims description 3
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- FLIQFYMILMDSAW-UHFFFAOYSA-N 1-[5-chloro-2-(3,5-dimethylphenoxy)phenyl]sulfonyl-4-ethylpiperazine Chemical compound C1CN(CC)CCN1S(=O)(=O)C1=CC(Cl)=CC=C1OC1=CC(C)=CC(C)=C1 FLIQFYMILMDSAW-UHFFFAOYSA-N 0.000 claims description 3
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- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000008275 solid aerosol Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical group OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- JIBQUVFMGQWASR-UHFFFAOYSA-N tert-butyl 4-[2-(3,5-dichlorophenoxy)-5-(dimethylcarbamoyl)phenyl]sulfonylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1S(=O)(=O)C1=CC(C(=O)N(C)C)=CC=C1OC1=CC(Cl)=CC(Cl)=C1 JIBQUVFMGQWASR-UHFFFAOYSA-N 0.000 description 1
- IXBWTTXRCGKKEH-UHFFFAOYSA-N tert-butyl 4-[2-(3,5-dimethylphenoxy)-4-nitrophenyl]sulfonylpiperazine-1-carboxylate Chemical compound CC1=CC(C)=CC(OC=2C(=CC=C(C=2)[N+]([O-])=O)S(=O)(=O)N2CCN(CC2)C(=O)OC(C)(C)C)=C1 IXBWTTXRCGKKEH-UHFFFAOYSA-N 0.000 description 1
- OQLBYUIGUZLKLN-UHFFFAOYSA-N tert-butyl 4-[2-(3,5-dimethylphenoxy)-5-(2h-tetrazol-5-yl)phenyl]sulfonylpiperazine-1-carboxylate Chemical compound CC1=CC(C)=CC(OC=2C(=CC(=CC=2)C=2NN=NN=2)S(=O)(=O)N2CCN(CC2)C(=O)OC(C)(C)C)=C1 OQLBYUIGUZLKLN-UHFFFAOYSA-N 0.000 description 1
- UZHKEWQMAAUIJX-UHFFFAOYSA-N tert-butyl 4-[2-(3,5-dimethylphenoxy)-5-(hydroxymethyl)phenyl]sulfonylpiperazine-1-carboxylate Chemical compound CC1=CC(C)=CC(OC=2C(=CC(CO)=CC=2)S(=O)(=O)N2CCN(CC2)C(=O)OC(C)(C)C)=C1 UZHKEWQMAAUIJX-UHFFFAOYSA-N 0.000 description 1
- PKZPQJBANHGRNN-UHFFFAOYSA-N tert-butyl 4-[2-(3,5-dimethylphenoxy)-5-methoxycarbonylphenyl]sulfonylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1S(=O)(=O)C1=CC(C(=O)OC)=CC=C1OC1=CC(C)=CC(C)=C1 PKZPQJBANHGRNN-UHFFFAOYSA-N 0.000 description 1
- NPRGXPRWUYOUGX-UHFFFAOYSA-N tert-butyl 4-[3-bromo-5-(3,5-dimethylphenoxy)phenyl]sulfonylpiperazine-1-carboxylate Chemical compound CC1=CC(C)=CC(OC=2C=C(C=C(Br)C=2)S(=O)(=O)N2CCN(CC2)C(=O)OC(C)(C)C)=C1 NPRGXPRWUYOUGX-UHFFFAOYSA-N 0.000 description 1
- HXKOCZAITVMTQI-UHFFFAOYSA-N tert-butyl 4-[5-cyano-2-(3,5-dichlorophenoxy)phenyl]sulfonyl-1,4-diazepane-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCCN1S(=O)(=O)C1=CC(C#N)=CC=C1OC1=CC(Cl)=CC(Cl)=C1 HXKOCZAITVMTQI-UHFFFAOYSA-N 0.000 description 1
- XKXIQBVKMABYQJ-UHFFFAOYSA-M tert-butyl carbonate Chemical compound CC(C)(C)OC([O-])=O XKXIQBVKMABYQJ-UHFFFAOYSA-M 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 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
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
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- 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
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- 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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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/64—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton
- C07C323/67—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton containing sulfur atoms of sulfonamide groups, bound to the carbon skeleton
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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
- C07D207/02—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
- 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
- C07D207/14—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
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
- C07D207/48—Sulfur atoms
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
- C07D211/28—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms to which a second hetero atom is attached
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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- C07D211/58—Nitrogen atoms attached in position 4
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/96—Sulfur atom
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- 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
- C07D213/65—One oxygen atom attached in position 3 or 5
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- 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
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- C07D213/62—Oxygen or sulfur atoms
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- 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
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| SG175277A1 (en) * | 2009-04-22 | 2011-11-28 | Axikin Pharmaceuticals Inc | Arylsulfonamide ccr3 antagonists |
| NZ595823A (en) | 2009-04-22 | 2014-03-28 | Axikin Pharmaceuticals Inc | 2,5-disubstituted arylsulfonamide ccr3 antagonists |
| WO2010129351A1 (en) | 2009-04-28 | 2010-11-11 | Schepens Eye Research Institute | Method to identify and treat age-related macular degeneration |
| EP2448581B1 (en) * | 2009-06-29 | 2016-12-07 | Agios Pharmaceuticals, Inc. | Therapeutic compositions and related methods of use |
| PT2448582T (pt) | 2009-06-29 | 2017-07-10 | Agios Pharmaceuticals Inc | Compostos e composições terapêuticas |
| ES2542404T3 (es) | 2010-03-02 | 2015-08-05 | Axikin Pharmaceuticals, Inc. | Antagonistas de CCR3 de tipo arilsulfonamida enriquecidos isotópicamente |
| CA2793391A1 (en) * | 2010-03-17 | 2011-09-22 | Axikin Pharmaceuticals, Inc. | Arylsulfonamide ccr3 antagonists |
| JP5860045B2 (ja) | 2010-07-09 | 2016-02-16 | ファイザー・リミテッドPfizer Limited | 化合物 |
| ES2532356T3 (es) | 2010-07-09 | 2015-03-26 | Pfizer Limited | N-sulfonilbenzamidas como inhibidores de los canales de sodio dependientes de voltaje |
| CN103298786B (zh) * | 2010-10-11 | 2016-01-20 | 埃克希金医药品有限公司 | 芳基磺酰胺盐ccr3拮抗剂 |
| JP5837091B2 (ja) | 2010-12-17 | 2015-12-24 | アジオス ファーマシューティカルズ, インコーポレイテッド | ピルビン酸キナーゼm2(pkm2)調節剤としての新規n−(4−(アゼチジン−1−カルボニル)フェニル)−(ヘテロ−)アリールスルホンアミド誘導体 |
| US9328077B2 (en) | 2010-12-21 | 2016-05-03 | Agios Pharmaceuticals, Inc | Bicyclic PKM2 activators |
| TWI549947B (zh) | 2010-12-29 | 2016-09-21 | 阿吉歐斯製藥公司 | 治療化合物及組成物 |
| CN108451955B (zh) | 2011-05-03 | 2022-02-01 | 安吉奥斯医药品有限公司 | 用于治疗的丙酮酸激酶活化剂 |
| WO2012151440A1 (en) | 2011-05-03 | 2012-11-08 | Agios Pharmaceuticals, Inc. | Pyruvate kinase activators for use for increasing lifetime of the red blood cells and treating anemia |
| AR093763A1 (es) | 2012-09-07 | 2015-06-24 | Axikin Pharmaceuticals Inc | Antagonistas de ccr3 de arilsulfonamida isotopicamente enriquecidas |
| WO2014139144A1 (en) | 2013-03-15 | 2014-09-18 | Agios Pharmaceuticals, Inc. | Therapeutic compounds and compositions |
| SMT202300344T1 (it) | 2015-06-11 | 2023-11-13 | Agios Pharmaceuticals Inc | Metodi di utilizzo degli attivatori della piruvato chinasi |
| US12221463B2 (en) | 2020-08-07 | 2025-02-11 | The Board Of Regents Of The University Of Oklahoma | Method of promoting wound healing by inhibiting CCR3 |
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| DE4404749A1 (de) * | 1994-02-15 | 1995-08-17 | Bayer Ag | ABS-Polymer-Zusammensetzungen mit gleichmäßiger matter Oberfläche |
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| CA2329777A1 (en) * | 1998-04-27 | 1999-11-04 | Dashyant Dhanak | Ccr-3 receptor antagonists |
| US6440966B1 (en) * | 1999-01-13 | 2002-08-27 | Warner-Lambert Company | Benzenesulfonamide derivatives and their use as MEK inhibitors |
| AU5473800A (en) | 1999-06-11 | 2001-01-02 | Merck & Co., Inc. | Cyclopentyl modulators of chemokine receptor activity |
| US6432981B1 (en) | 1999-06-11 | 2002-08-13 | Merck & Co., Inc. | Cyclopentyl modulators of chemokine receptor activity |
| WO2001032604A1 (en) * | 1999-11-05 | 2001-05-10 | University College London | Activators of soluble guanylate cyclase |
| DE10008420A1 (de) | 2000-02-23 | 2001-08-30 | Bayer Ag | Polymerzusammensetzungen mit verbesserter Eigenschaftskonstanz |
| DE10008419A1 (de) | 2000-02-23 | 2001-08-30 | Bayer Ag | Polymerzusammensetzungen mit verbesserter Eigenschaftskonstanz |
| JP2003081937A (ja) | 2001-09-07 | 2003-03-19 | Bayer Ag | ベンゼンスルホンアミド誘導体 |
| DE10145773A1 (de) | 2001-09-17 | 2003-04-03 | Bayer Ag | ABS-Zusammensetzungen mit verbesserten Eigenschaftskombinationen |
| RU2380356C2 (ru) * | 2003-03-24 | 2010-01-27 | Актимис Фармасьютикалз, Инк. | Производные 2-фенокси и 2-фенилсульфонамида с ссr3 антагонистической активностью для лечения астмы и других воспалительных или иммунологических заболеваний |
-
2001
- 2001-09-07 JP JP2001272327A patent/JP2003081937A/ja active Pending
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2002
- 2002-08-29 AR ARP020103259A patent/AR037235A1/es not_active Application Discontinuation
- 2002-09-04 US US10/489,029 patent/US7700586B2/en not_active Expired - Fee Related
- 2002-09-04 EP EP07013793A patent/EP1849469B1/en not_active Expired - Lifetime
- 2002-09-04 DE DE60221569T patent/DE60221569T2/de not_active Expired - Lifetime
- 2002-09-04 CA CA002459432A patent/CA2459432C/en not_active Expired - Fee Related
- 2002-09-04 JP JP2003526406A patent/JP4517047B2/ja not_active Expired - Fee Related
- 2002-09-04 ES ES07013793T patent/ES2354378T3/es not_active Expired - Lifetime
- 2002-09-04 EP EP02772265A patent/EP1461038B9/en not_active Expired - Lifetime
- 2002-09-04 WO PCT/EP2002/009873 patent/WO2003022277A1/en not_active Ceased
- 2002-09-04 DE DE60238149T patent/DE60238149D1/de not_active Expired - Lifetime
- 2002-09-04 ES ES02772265T patent/ES2294167T3/es not_active Expired - Lifetime
- 2002-09-05 GT GT200200178A patent/GT200200178A/es unknown
- 2002-09-05 TW TW091120389A patent/TWI262187B/zh not_active IP Right Cessation
- 2002-09-06 MY MYPI20023349A patent/MY133303A/en unknown
- 2002-09-06 HN HN2002000247A patent/HN2002000247A/es unknown
- 2002-09-06 PE PE2002000882A patent/PE20030440A1/es not_active Application Discontinuation
- 2002-09-06 SV SV2002001225A patent/SV2004001225A/es not_active Application Discontinuation
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2010
- 2010-04-19 US US12/763,072 patent/US8242118B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20100204213A1 (en) | 2010-08-12 |
| CA2459432C (en) | 2009-05-26 |
| EP1461038B9 (en) | 2009-09-23 |
| EP1849469B1 (en) | 2010-10-27 |
| US7700586B2 (en) | 2010-04-20 |
| HN2002000247A (es) | 2003-11-24 |
| SV2004001225A (es) | 2004-02-24 |
| CA2459432A1 (en) | 2003-03-20 |
| EP1461038A1 (en) | 2004-09-29 |
| GT200200178A (es) | 2003-05-23 |
| JP2003081937A (ja) | 2003-03-19 |
| JP2005519024A (ja) | 2005-06-30 |
| EP1461038B1 (en) | 2007-08-01 |
| US8242118B2 (en) | 2012-08-14 |
| DE60238149D1 (de) | 2010-12-09 |
| ES2354378T3 (es) | 2011-03-14 |
| HK1109867A1 (en) | 2008-06-27 |
| WO2003022277A1 (en) | 2003-03-20 |
| PE20030440A1 (es) | 2003-06-26 |
| TWI262187B (en) | 2006-09-21 |
| AR037235A1 (es) | 2004-11-03 |
| US20050070582A1 (en) | 2005-03-31 |
| DE60221569D1 (de) | 2007-09-13 |
| ES2294167T3 (es) | 2008-04-01 |
| EP1849469A1 (en) | 2007-10-31 |
| MY133303A (en) | 2007-11-30 |
| JP4517047B2 (ja) | 2010-08-04 |
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Owner name: AXIKIN PHARMACEUTICALS, INC., SAN DIEGO, CALIF, US |