WO2005113542B1 - Inhibiteurs sulfonamido n-cycliques de gamma-secretase - Google Patents
Inhibiteurs sulfonamido n-cycliques de gamma-secretaseInfo
- Publication number
- WO2005113542B1 WO2005113542B1 PCT/US2005/017985 US2005017985W WO2005113542B1 WO 2005113542 B1 WO2005113542 B1 WO 2005113542B1 US 2005017985 W US2005017985 W US 2005017985W WO 2005113542 B1 WO2005113542 B1 WO 2005113542B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- alkyl
- chloro
- benzenesulfonyl
- independently
- alkoxy
- Prior art date
Links
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 title 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 230000002401 inhibitory effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 36
- 206010001897 Alzheimer's disease Diseases 0.000 claims abstract 8
- 206010057668 Cognitive disease Diseases 0.000 claims abstract 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 83
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 62
- 125000003545 alkoxy group Chemical group 0.000 claims 51
- 125000005843 halogen group Chemical group 0.000 claims 45
- 125000000217 alkyl group Chemical group 0.000 claims 40
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 31
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 29
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 20
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 18
- 125000004043 oxo group Chemical group O=* 0.000 claims 17
- -1 1 ,2,3,4-tetrahydroquinoxalinyl Chemical group 0.000 claims 16
- 150000003839 salts Chemical class 0.000 claims 12
- 239000011780 sodium chloride Substances 0.000 claims 12
- 206010012289 Dementia Diseases 0.000 claims 10
- 125000003386 piperidinyl group Chemical group 0.000 claims 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims 5
- 125000002541 furyl group Chemical group 0.000 claims 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 5
- 125000004076 pyridyl group Chemical group 0.000 claims 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 5
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 5
- 208000005145 Cerebral Amyloid Angiopathy Diseases 0.000 claims 4
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- 125000004652 decahydroisoquinolinyl group Chemical group C1(NCCC2CCCCC12)* 0.000 claims 4
- 230000003412 degenerative Effects 0.000 claims 4
- 125000001153 fluoro group Chemical group F* 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims 3
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- OJJBZIOUOASLBF-UHFFFAOYSA-N 2-[2-(4-chlorophenyl)sulfonyl-3,4-dihydro-1H-isoquinolin-1-yl]acetic acid Chemical compound C1CC2=CC=CC=C2C(CC(=O)O)N1S(=O)(=O)C1=CC=C(Cl)C=C1 OJJBZIOUOASLBF-UHFFFAOYSA-N 0.000 claims 2
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 206010064930 Age-related macular degeneration Diseases 0.000 claims 2
- 201000010374 Down syndrome Diseases 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- 206010018987 Haemorrhage Diseases 0.000 claims 2
- 210000004558 Lewy Bodies Anatomy 0.000 claims 2
- 208000002780 Macular Degeneration Diseases 0.000 claims 2
- 206010061536 Parkinson's disease Diseases 0.000 claims 2
- 206010044688 Trisomy 21 Diseases 0.000 claims 2
- 125000005037 alkyl phenyl group Chemical group 0.000 claims 2
- 125000002785 azepinyl group Chemical group 0.000 claims 2
- 230000001054 cortical Effects 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 2
- 239000001301 oxygen Substances 0.000 claims 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims 2
- 230000000306 recurrent Effects 0.000 claims 2
- 125000003003 spiro group Chemical group 0.000 claims 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- 239000011593 sulfur Substances 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 230000002792 vascular Effects 0.000 claims 2
- HIWROFGCKQGFKO-PHIMTYICSA-N (2R,6S)-1-(4-chlorophenyl)sulfonyl-2,6-dimethylpiperidine Chemical compound C[C@H]1CCC[C@@H](C)N1S(=O)(=O)C1=CC=C(Cl)C=C1 HIWROFGCKQGFKO-PHIMTYICSA-N 0.000 claims 1
- YXIQNXLOGZKSTQ-AWEZNQCLSA-N (2S)-1-(4-chlorophenyl)sulfonyl-2-(pyrrolidin-1-ylmethyl)pyrrolidine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1[C@H](CN2CCCC2)CCC1 YXIQNXLOGZKSTQ-AWEZNQCLSA-N 0.000 claims 1
- SHFVMXYJQFRLHJ-SECBINFHSA-N (3R)-1-(4-chlorophenyl)sulfonyl-3-methylpiperazine Chemical compound C1CN[C@H](C)CN1S(=O)(=O)C1=CC=C(Cl)C=C1 SHFVMXYJQFRLHJ-SECBINFHSA-N 0.000 claims 1
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical group C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims 1
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims 1
- 125000005960 1,4-diazepanyl group Chemical group 0.000 claims 1
- YYQLDNIWEVJMJZ-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-1,4-diazepane Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCNCCC1 YYQLDNIWEVJMJZ-UHFFFAOYSA-N 0.000 claims 1
- RYCKLNAISBDCNU-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-2,3-dihydroindole-2-carboxamide Chemical compound NC(=O)C1CC2=CC=CC=C2N1S(=O)(=O)C1=CC=C(Cl)C=C1 RYCKLNAISBDCNU-UHFFFAOYSA-N 0.000 claims 1
- XGKYOUXSJHGVPI-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-2,5-dihydropyrrole Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CC=CC1 XGKYOUXSJHGVPI-UHFFFAOYSA-N 0.000 claims 1
- NWSLSBSZJKJVGX-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-2-phenylaziridine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C(C=2C=CC=CC=2)C1 NWSLSBSZJKJVGX-UHFFFAOYSA-N 0.000 claims 1
- RVZVLUTVLOPNCZ-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-3,4-dihydro-2H-quinolin-8-amine Chemical compound C1=2C(N)=CC=CC=2CCCN1S(=O)(=O)C1=CC=C(Cl)C=C1 RVZVLUTVLOPNCZ-UHFFFAOYSA-N 0.000 claims 1
- RMRCIUGTXUYGNZ-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-3,4-dihydro-2H-quinoline Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C2=CC=CC=C2CCC1 RMRCIUGTXUYGNZ-UHFFFAOYSA-N 0.000 claims 1
- GBIZPDOONVSETD-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-4-(1-phenylethyl)piperazine Chemical compound C=1C=CC=CC=1C(C)N(CC1)CCN1S(=O)(=O)C1=CC=C(Cl)C=C1 GBIZPDOONVSETD-UHFFFAOYSA-N 0.000 claims 1
- YNPKENGKFDXEJF-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-4-(3,4-dichlorophenyl)piperazine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCN(C=2C=C(Cl)C(Cl)=CC=2)CC1 YNPKENGKFDXEJF-UHFFFAOYSA-N 0.000 claims 1
- CAKCNYHZZMERMW-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-6-ethoxy-2,2,4-trimethylquinoline Chemical compound CC1(C)C=C(C)C2=CC(OCC)=CC=C2N1S(=O)(=O)C1=CC=C(Cl)C=C1 CAKCNYHZZMERMW-UHFFFAOYSA-N 0.000 claims 1
- KYCATQZSRHNATO-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-6-fluoro-2-methyl-3,4-dihydro-2H-quinoline Chemical compound CC1CCC2=CC(F)=CC=C2N1S(=O)(=O)C1=CC=C(Cl)C=C1 KYCATQZSRHNATO-UHFFFAOYSA-N 0.000 claims 1
- VFOJKDAOSUABGE-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-N,N-diethylpiperidine-3-carboxamide Chemical compound C1C(C(=O)N(CC)CC)CCCN1S(=O)(=O)C1=CC=C(Cl)C=C1 VFOJKDAOSUABGE-UHFFFAOYSA-N 0.000 claims 1
- PNLUMVHBVKSUGP-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-N-methyl-2,3-dihydroindole-2-carboxamide Chemical compound CNC(=O)C1CC2=CC=CC=C2N1S(=O)(=O)C1=CC=C(Cl)C=C1 PNLUMVHBVKSUGP-UHFFFAOYSA-N 0.000 claims 1
- DZFXLKMJEOGJLV-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonylpiperidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CCCN1S(=O)(=O)C1=CC=C(Cl)C=C1 DZFXLKMJEOGJLV-UHFFFAOYSA-N 0.000 claims 1
- WQUWIRWFTDFGFT-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1S(=O)(=O)C1=CC=C(Cl)C=C1 WQUWIRWFTDFGFT-UHFFFAOYSA-N 0.000 claims 1
- DSSHPQBPVDVEJM-UHFFFAOYSA-N 2-(4-chlorophenyl)sulfonyl-3,4-dihydro-1H-isoquinoline Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CC2=CC=CC=C2CC1 DSSHPQBPVDVEJM-UHFFFAOYSA-N 0.000 claims 1
- YFZIGQRZCMIXGX-UHFFFAOYSA-N 2-(4-chlorophenyl)sulfonyl-4-iodopyrazole-3-carboxylic acid Chemical compound OC(=O)C1=C(I)C=NN1S(=O)(=O)C1=CC=C(Cl)C=C1 YFZIGQRZCMIXGX-UHFFFAOYSA-N 0.000 claims 1
- ZOHPZUFNTLHVCM-UHFFFAOYSA-N 2-(4-chlorophenyl)sulfonyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1S(=O)(=O)C1=CC=C(Cl)C=C1 ZOHPZUFNTLHVCM-UHFFFAOYSA-N 0.000 claims 1
- LSXOEZYWLVMKTQ-UHFFFAOYSA-N 2-(4-chlorophenyl)sulfonyl-6-methoxy-1,3,4,9-tetrahydropyrido[3,4-b]indole Chemical group C1CC=2C3=CC(OC)=CC=C3NC=2CN1S(=O)(=O)C1=CC=C(Cl)C=C1 LSXOEZYWLVMKTQ-UHFFFAOYSA-N 0.000 claims 1
- LONVBICBOKMNMU-UHFFFAOYSA-N 2-[2-[4-(4-chlorophenyl)sulfonylpiperazin-1-yl]ethoxy]ethanol Chemical compound C1CN(CCOCCO)CCN1S(=O)(=O)C1=CC=C(Cl)C=C1 LONVBICBOKMNMU-UHFFFAOYSA-N 0.000 claims 1
- INBZGITWJSYRLQ-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)sulfonylpiperazin-1-yl]-1-pyrrolidin-1-ylethanone Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCN(CC(=O)N2CCCC2)CC1 INBZGITWJSYRLQ-UHFFFAOYSA-N 0.000 claims 1
- OAZGEVMZMDOIIH-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)sulfonylpiperazin-1-yl]benzonitrile Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCN(C=2C(=CC=CC=2)C#N)CC1 OAZGEVMZMDOIIH-UHFFFAOYSA-N 0.000 claims 1
- HJDMFRUBGVKLQZ-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)sulfonylpiperazin-1-yl]ethanol Chemical compound C1CN(CCO)CCN1S(=O)(=O)C1=CC=C(Cl)C=C1 HJDMFRUBGVKLQZ-UHFFFAOYSA-N 0.000 claims 1
- ZCYCZDZSEDMTRV-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)sulfonylpiperazin-1-yl]pyrimidine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCN(C=2N=CC=CN=2)CC1 ZCYCZDZSEDMTRV-UHFFFAOYSA-N 0.000 claims 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims 1
- AEEXYHPSEOAWJQ-UHFFFAOYSA-N 3-(4-chlorophenyl)sulfonyl-1,3-thiazolidine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CSCC1 AEEXYHPSEOAWJQ-UHFFFAOYSA-N 0.000 claims 1
- DJPSCONZKNJHKI-UHFFFAOYSA-N 4-(4-chlorophenyl)sulfonyl-1,3-dihydroquinoxalin-2-one Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C2=CC=CC=C2NC(=O)C1 DJPSCONZKNJHKI-UHFFFAOYSA-N 0.000 claims 1
- BCTUAFHOTKWIPY-UHFFFAOYSA-N 4-(4-chlorophenyl)sulfonyl-1-(4-methoxyphenyl)-2-methylpiperazine Chemical compound C1=CC(OC)=CC=C1N1C(C)CN(S(=O)(=O)C=2C=CC(Cl)=CC=2)CC1 BCTUAFHOTKWIPY-UHFFFAOYSA-N 0.000 claims 1
- UUHJXJKUAAIMSI-UHFFFAOYSA-N 4-(4-chlorophenyl)sulfonyl-2-methyl-1-(3-methylphenyl)piperazine Chemical compound CC1CN(S(=O)(=O)C=2C=CC(Cl)=CC=2)CCN1C1=CC=CC(C)=C1 UUHJXJKUAAIMSI-UHFFFAOYSA-N 0.000 claims 1
- UEJJKAIZUNTNJX-UHFFFAOYSA-N 4-(4-chlorophenyl)sulfonyl-2-methyl-1-(4-methylphenyl)piperazine Chemical compound CC1CN(S(=O)(=O)C=2C=CC(Cl)=CC=2)CCN1C1=CC=C(C)C=C1 UEJJKAIZUNTNJX-UHFFFAOYSA-N 0.000 claims 1
- XSJYUNRKEQZUEJ-UHFFFAOYSA-N 4-(4-chlorophenyl)sulfonyl-2-methyl-1-phenylpiperazine Chemical compound CC1CN(S(=O)(=O)C=2C=CC(Cl)=CC=2)CCN1C1=CC=CC=C1 XSJYUNRKEQZUEJ-UHFFFAOYSA-N 0.000 claims 1
- ALKLDHFMJPCTQN-UHFFFAOYSA-N 4-(4-chlorophenyl)sulfonyl-3-methyl-1,3-dihydroquinoxalin-2-one Chemical compound C12=CC=CC=C2NC(=O)C(C)N1S(=O)(=O)C1=CC=C(Cl)C=C1 ALKLDHFMJPCTQN-UHFFFAOYSA-N 0.000 claims 1
- ZDKPGCVIAFEFJW-UHFFFAOYSA-N 4-(4-chlorophenyl)sulfonyl-3-methyl-2,3-dihydro-1,4-benzoxazine Chemical compound CC1COC2=CC=CC=C2N1S(=O)(=O)C1=CC=C(Cl)C=C1 ZDKPGCVIAFEFJW-UHFFFAOYSA-N 0.000 claims 1
- CHRUFZISMPINDK-UHFFFAOYSA-N 4-(4-chlorophenyl)sulfonyl-3-phenyl-2,3-dihydro-1,4-benzoxazine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C2=CC=CC=C2OCC1C1=CC=CC=C1 CHRUFZISMPINDK-UHFFFAOYSA-N 0.000 claims 1
- DSDGQZJWZACMPK-UHFFFAOYSA-N 4-(4-chlorophenyl)sulfonylmorpholine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCOCC1 DSDGQZJWZACMPK-UHFFFAOYSA-N 0.000 claims 1
- FDOUWHOQTJKHEX-UHFFFAOYSA-N 4-benzyl-1-(4-chlorophenyl)sulfonylpiperidine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCC(CC=2C=CC=CC=2)CC1 FDOUWHOQTJKHEX-UHFFFAOYSA-N 0.000 claims 1
- YOYWBKVLJVPZAW-UHFFFAOYSA-N 4-bromo-1-(4-chlorophenyl)sulfonyl-3-methylpyrazole Chemical compound C1=C(Br)C(C)=NN1S(=O)(=O)C1=CC=C(Cl)C=C1 YOYWBKVLJVPZAW-UHFFFAOYSA-N 0.000 claims 1
- MVTOXTXHQLHTHR-UHFFFAOYSA-N 4-bromo-1-(4-chlorophenyl)sulfonylpiperidine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCC(Br)CC1 MVTOXTXHQLHTHR-UHFFFAOYSA-N 0.000 claims 1
- JPYQFYIEOUVJDU-UHFFFAOYSA-N Beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 claims 1
- AMFDHQASTRREMO-UHFFFAOYSA-N N-benzyl-1-(4-chlorophenyl)sulfonyl-N-methyl-2,3-dihydroindole-2-carboxamide Chemical compound C1C2=CC=CC=C2N(S(=O)(=O)C=2C=CC(Cl)=CC=2)C1C(=O)N(C)CC1=CC=CC=C1 AMFDHQASTRREMO-UHFFFAOYSA-N 0.000 claims 1
- VHFXBTVPDDZDCI-QFIPXVFZSA-N [(2S)-1-(4-chlorophenyl)sulfonylpyrrolidin-2-yl]-diphenylmethanol Chemical compound C([C@H]1C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1S(=O)(=O)C1=CC=C(Cl)C=C1 VHFXBTVPDDZDCI-QFIPXVFZSA-N 0.000 claims 1
- YFZBTCGWNKVJMK-UHFFFAOYSA-N [1-(4-chlorophenyl)sulfonyl-2,3-dihydroindol-2-yl]-pyrrolidin-1-ylmethanone Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C2=CC=CC=C2CC1C(=O)N1CCCC1 YFZBTCGWNKVJMK-UHFFFAOYSA-N 0.000 claims 1
- FROBWHAKIVORQG-UHFFFAOYSA-N [1-(4-chlorophenyl)sulfonylpiperidin-3-yl]methanol Chemical compound C1C(CO)CCCN1S(=O)(=O)C1=CC=C(Cl)C=C1 FROBWHAKIVORQG-UHFFFAOYSA-N 0.000 claims 1
- BXRIJNFJSWTNQJ-UHFFFAOYSA-N [4-(4-chlorophenyl)sulfonylpiperazin-1-yl]-(furan-2-yl)methanone Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCN(C(=O)C=2OC=CC=2)CC1 BXRIJNFJSWTNQJ-UHFFFAOYSA-N 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 230000000240 adjuvant Effects 0.000 claims 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims 1
- 125000003725 azepanyl group Chemical group 0.000 claims 1
- DUNFAKCGESYTTD-QGZVFWFLSA-N benzyl (2R)-1-(4-chlorophenyl)sulfonylpyrrolidine-2-carboxylate Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1[C@@H](C(=O)OCC=2C=CC=CC=2)CCC1 DUNFAKCGESYTTD-QGZVFWFLSA-N 0.000 claims 1
- LMADGGQXMBPYTQ-UHFFFAOYSA-N benzyl 4-(4-chlorophenyl)sulfonylpiperazine-1-carboxylate Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCN(C(=O)OCC=2C=CC=CC=2)CC1 LMADGGQXMBPYTQ-UHFFFAOYSA-N 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- MSZJEPVVQWJCIF-UHFFFAOYSA-N butylazanide Chemical compound CCCC[NH-] MSZJEPVVQWJCIF-UHFFFAOYSA-N 0.000 claims 1
- 125000002704 decyl group Chemical group [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])C([H])([H])C([H])([H])* 0.000 claims 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- NRTBMOKCKFTCAV-UHFFFAOYSA-N ethyl 4-(4-chlorophenyl)sulfonylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1S(=O)(=O)C1=CC=C(Cl)C=C1 NRTBMOKCKFTCAV-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- XRMLOZSMCSUBTL-UHFFFAOYSA-N phenylazanide Chemical compound [NH-]C1=CC=CC=C1 XRMLOZSMCSUBTL-UHFFFAOYSA-N 0.000 claims 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- XVOBINBTLCYECZ-UHFFFAOYSA-N tert-butyl 4-(4-chlorophenyl)sulfonylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1S(=O)(=O)C1=CC=C(Cl)C=C1 XVOBINBTLCYECZ-UHFFFAOYSA-N 0.000 claims 1
Abstract
L'invention concerne des composés sulfonamido N-cycliques qui s'utilisent dans le traitement ou la prévention des troubles cognitifs, tels que la maladie d'Alzheimer. Des composés revêtant un intérêt particulier sont représentés par la formule (I), dans laquelle R4, R5, R6, R7 et R8 sont tels que décrits dans le descriptif. Par ailleurs, l'invention concerne des compositions pharmaceutiques qui contiennent les composés représentés par la formule (I), ainsi que des méthodes de traitement des troubles cognitifs, y compris la maladie d'Alzheimer, au moyen des composés de la formule (I).
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002567343A CA2567343A1 (fr) | 2004-05-20 | 2005-05-20 | Inhibiteurs sulfonamido n-cycliques de gamma-secretase |
| EP05754201A EP1758884A2 (fr) | 2004-05-20 | 2005-05-20 | Inhibiteurs sulfonamido n-cycliques de gamma-secretase |
| JP2007527530A JP2007538106A (ja) | 2004-05-20 | 2005-05-20 | γセクレターゼのＮ−環式スルホンアミド阻害剤 |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US57286204P | 2004-05-20 | 2004-05-20 | |
| US60/572,862 | 2004-05-20 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2005113542A2 WO2005113542A2 (fr) | 2005-12-01 |
| WO2005113542A3 WO2005113542A3 (fr) | 2006-03-02 |
| WO2005113542B1 true WO2005113542B1 (fr) | 2006-04-20 |
Family
ID=34968952
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2005/017985 WO2005113542A2 (fr) | 2004-05-20 | 2005-05-20 | Inhibiteurs sulfonamido n-cycliques de gamma-secretase |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20060035884A1 (fr) |
| EP (1) | EP1758884A2 (fr) |
| JP (1) | JP2007538106A (fr) |
| CA (1) | CA2567343A1 (fr) |
| WO (1) | WO2005113542A2 (fr) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0302573D0 (sv) | 2003-09-26 | 2003-09-26 | Astrazeneca Ab | Benzimidazole derivatives, compositions containing them, preparation thereof and uses thereof |
| FR2869904B1 (fr) * | 2004-05-07 | 2006-07-28 | Fournier S A Sa Lab | Modulateurs des recepteurs lxr |
| WO2006004880A2 (fr) * | 2004-06-30 | 2006-01-12 | Schering Corporation | Amines heterocycliques a substitution n-arylsulfonyle inhibant la gamma secretase |
| RU2374234C2 (ru) | 2004-09-24 | 2009-11-27 | Астразенека Аб | Бензимидазольные производные, содержащие их композиции, их получение и применение |
| CA2598610C (fr) * | 2005-03-03 | 2011-05-31 | F. Hoffmann-La Roche Ag | Derives d'amide d'acide 1-sulfonyl-piperidine-3-carboxylique en tant qu'inhibiteurs de la 11-beta-hydroxysteroide dehydrogenase pour le traitement du diabete sucre de type ii |
| EP1943250A1 (fr) * | 2005-09-09 | 2008-07-16 | Euro-Celtique S.A. | Composes fondus et spirocycle ainsi que l'utilisation de ceux-ci |
| TW200736255A (en) * | 2005-12-01 | 2007-10-01 | Elan Pharm Inc | 5-(Substituted)-pyrazolopiperidines |
| AU2006326540A1 (en) | 2005-12-14 | 2007-06-21 | Amgen Inc. | Diaza heterocyclic sulfonamide derivatives and their uses |
| GB0526257D0 (en) | 2005-12-22 | 2006-02-01 | Novartis Ag | Organic compounds |
| PA8713501A1 (es) | 2006-02-07 | 2009-09-17 | Wyeth Corp | INHIBIDORES DE 11-BETA HIDROXIESTEROIDE DEHIDROGENASA - 11ßHSD1 |
| CA2640229A1 (fr) * | 2006-02-08 | 2007-08-16 | Wyeth | Derives de sulfonamide utilises pour traiter une infection par le virus de l'hepatite c |
| EP1990335A4 (fr) * | 2006-03-02 | 2009-11-11 | Astellas Pharma Inc | Inhibiteur de la 17 beta hsd de type 5 |
| TW200745049A (en) | 2006-03-23 | 2007-12-16 | Astrazeneca Ab | New crystalline forms |
| TW200808769A (en) | 2006-04-18 | 2008-02-16 | Astrazeneca Ab | Therapeutic compounds |
| UY30377A1 (es) * | 2006-06-02 | 2008-01-02 | Elan Pharm Inc | Inhibidores triciclicos fusionados de sulfonamida de gama-secretasa |
| ATE509956T1 (de) * | 2006-06-08 | 2011-06-15 | Helmholtz Zentrum Muenchen | Spezifische proteaseinhibitoren und ihre verwendung in der krebstherapie |
| KR20090079914A (ko) * | 2006-09-29 | 2009-07-22 | 그뤼넨탈 게엠베하 | 치환된 설폰아미드 유도체 |
| AU2008216842A1 (en) * | 2007-02-12 | 2008-08-21 | Merck Sharp & Dohme Corp. | Piperidine derivatives |
| GB0813144D0 (en) | 2008-07-17 | 2008-08-27 | Glaxo Group Ltd | Novel compounds |
| GB0813142D0 (en) | 2008-07-17 | 2008-08-27 | Glaxo Group Ltd | Novel compounds |
| EP2676956A1 (fr) * | 2008-08-01 | 2013-12-25 | Purdue Pharma L.P. | Composés de tétrahydro-pyridinyle et de dihydropyrrolyle et leur utilisation |
| EA201170421A1 (ru) * | 2008-09-05 | 2012-01-30 | Элан Фармасьютикалз, Инк. | N-сульфонамидопиразолильные полициклические соединения |
| WO2011073276A1 (fr) * | 2009-12-16 | 2011-06-23 | Evotec Ag | Dérivés d'arylsulfonamides de benzoxazine en tant que modulateurs de kv.1.3 |
| WO2011073273A1 (fr) * | 2009-12-16 | 2011-06-23 | Evotec Ag | Dérivés d'arylsulfonamides de benzoxazine en tant que modulateurs de kv.1.3 |
| GB201000685D0 (en) | 2010-01-15 | 2010-03-03 | Glaxo Group Ltd | Novel compounds |
| WO2014083384A1 (fr) * | 2012-11-28 | 2014-06-05 | Stichting Dienst Landbouwkundig Onderzoek | Composés de benzènesulfonamide pour l'embryogenèse somatique dans des plantes |
| US9975852B2 (en) | 2013-03-04 | 2018-05-22 | Health Sciences North Research Institute | Quinoline sulfonyl derivatives and uses thereof |
| WO2015038644A2 (fr) | 2013-09-10 | 2015-03-19 | Debrabander Jef | Thérapie ciblant des protéines polypose adénomateuse familiale (apc) tronquées |
| CN104557726B (zh) * | 2013-10-19 | 2019-05-24 | 广东东阳光药业有限公司 | 芳杂环类衍生物及其在药物上的应用 |
| CN104557664B (zh) * | 2013-10-19 | 2020-01-21 | 广东东阳光药业有限公司 | 芳杂环类衍生物及其在药物上的应用 |
| CN104725295B (zh) | 2013-12-20 | 2019-05-24 | 广东东阳光药业有限公司 | 芳杂环类衍生物及其在药物上的应用 |
| CN105085367B (zh) * | 2014-05-03 | 2019-05-21 | 广东东阳光药业有限公司 | 取代的杂芳基化合物及其组合物和用途 |
| US10082496B2 (en) | 2014-09-10 | 2018-09-25 | Board Of Regents Of The University Of Texas System | Targeting emopamil binding protein (EBP) with small molecules that induce an abnormal feedback response by lowering endogenous cholesterol biosynthesis |
| WO2016107541A1 (fr) * | 2014-12-29 | 2016-07-07 | 成都先导药物开发有限公司 | Composé de pyrrole-amide, son procédé de préparation et son utilisation |
| WO2016107544A1 (fr) * | 2014-12-29 | 2016-07-07 | 成都先导药物开发有限公司 | Composé intermédiaire pour la préparation d'un composé pyrrole amide et son procédé de préparation et d'utilisation |
| CN105732458B (zh) * | 2014-12-29 | 2019-06-07 | 成都先导药物开发有限公司 | 吡咯酰胺类化合物及其制备方法与用途 |
| CN105801464B (zh) * | 2014-12-29 | 2019-05-28 | 成都先导药物开发有限公司 | 吡咯酰胺类化合物及其制备方法与用途 |
| EP3474667A4 (fr) | 2016-06-23 | 2019-11-27 | St. Jude Children's Research Hospital, Inc. | Modulateurs à petites molécules des pantothénate kinases |
| TW201825458A (zh) | 2016-09-20 | 2018-07-16 | 英商葛蘭素史克智慧財產（第二）有限公司 | Ｔｒｐｖ４拮抗劑 |
| CA3036933A1 (fr) | 2016-09-20 | 2018-03-29 | Glaxosmithkline Intellectual Property (No.2) Limited | Antagonistes de trpv4 |
| WO2018055527A1 (fr) | 2016-09-20 | 2018-03-29 | Glaxosmithkline Intellectual Property (No.2) Limited | Antagonistes de trpv4 |
| WO2019133632A1 (fr) * | 2017-12-27 | 2019-07-04 | St. Jude Children's Research Hospital | Méthodes de traitement de troubles associés à castor |
| BR112020012875A2 (pt) | 2017-12-27 | 2021-01-05 | St. Jude Children¿S Research Hospital, Inc. | Moduladores de pequenas moléculas das pantotenato quinases |
| KR102068299B1 (ko) * | 2018-12-21 | 2020-01-20 | 한국기초과학지원연구원 | Cyp4a 저해 화합물을 유효성분으로 포함하는 대사질환의 예방 또는 치료용 조성물 |
| CN109925510A (zh) * | 2019-04-11 | 2019-06-25 | 北京卓凯生物技术有限公司 | Rac1活性抑制剂在制备治疗阿尔茨海默病的药物中的应用 |
| GB201918410D0 (en) * | 2019-12-13 | 2020-01-29 | Z Factor Ltd | Compounds and their use for the treatment of alpha1-antitrypsin deficiency |
| EP3868376A1 (fr) * | 2020-02-21 | 2021-08-25 | Institut national de recherche pour l'agriculture, l'alimentation et l'environnement | Procédé de traitement d'infections bactériennes et composition pharmaceutique pour le traitement d'infections bactériennes |
| GB202108543D0 (en) * | 2021-06-15 | 2021-07-28 | Z Factor Ltd | Compounds and their use for the treatment of alpha1-antitrypsin deficiency |
| GB202108544D0 (en) * | 2021-06-15 | 2021-07-28 | Z Factor Ltd | Compounds and their use for the treatment of alpha1-antitrypsin deficiency |
| GB202108542D0 (en) * | 2021-06-15 | 2021-07-28 | Z Factor Ltd | Compounds and their use for the treatment of alpha1-antitrypsin deficiency |
| EP4450494A1 (fr) * | 2023-04-20 | 2024-10-23 | Consejo Superior De Investigaciones Científicas | Dérivés d'indole en tant qu'inhibiteurs d'histone désacétylase (hdac) pour le traitement du cancer |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW575561B (en) * | 1999-03-25 | 2004-02-11 | Hoffmann La Roche | 1-arenesulfonyl-2-aryl-pyrrolidine and piperidine derivatives |
| US6589978B2 (en) * | 2000-06-30 | 2003-07-08 | Hoffman-La Roche Inc. | 1-sulfonyl pyrrolidine derivatives |
| WO2003014075A2 (fr) * | 2001-08-03 | 2003-02-20 | Schering Corporation | Nouveaux inhibiteurs de gamma-secretase |
| TW200302717A (en) * | 2002-02-06 | 2003-08-16 | Schering Corp | Novel gamma secretase inhibitors |
| WO2003093245A1 (fr) * | 2002-05-03 | 2003-11-13 | Elan Pharmaceuticals, Inc. | Derives d'acetamide sulfonylquinoxalone et composes associes en tant qu'antagonistes de la bradykinine |
| EP1664010A1 (fr) * | 2003-08-29 | 2006-06-07 | Vernalis (R&D) Limited | Antagoniste des canaux calcium type n, de type sulfonamides |
-
2005
- 2005-05-20 US US11/133,738 patent/US20060035884A1/en not_active Abandoned
- 2005-05-20 CA CA002567343A patent/CA2567343A1/fr not_active Abandoned
- 2005-05-20 WO PCT/US2005/017985 patent/WO2005113542A2/fr not_active Application Discontinuation
- 2005-05-20 JP JP2007527530A patent/JP2007538106A/ja active Pending
- 2005-05-20 EP EP05754201A patent/EP1758884A2/fr not_active Withdrawn
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2005113542B1 (fr) | Inhibiteurs sulfonamido n-cycliques de gamma-secretase | |
| RU2382778C2 (ru) | Производные индола в качестве антагонистов гистаминовых рецепторов | |
| RU2487127C2 (ru) | Хиральные цис-имидазолины | |
| ES2562183T3 (es) | Benzonaftiridinaminas como inhibidores de la autotaxina | |
| RU2007118538A (ru) | Производные хинолина | |
| ES2577829T3 (es) | Derivados de aminopirimidina como moduladores de la LRRK2 | |
| RU2010130095A (ru) | Активаторы глюкокиназы и фармацевтические композиции, содержащие их в качестве активного ингредиента | |
| RU2004113451A (ru) | Производные бензимидазолидинона в качестве агентов мускариновых рецепторов | |
| EA200601849A1 (ru) | 4-фениламинохиназолин-6-ил-амиды | |
| HRP20140030T1 (hr) | Derivati prolina kao inhibitori katepsina | |
| RU2422442C2 (ru) | Производные индол-3-ил-карбонил-пиперидина и пиперазина | |
| RU2005105682A (ru) | Новые бензодиоксолы | |
| KR20050096956A (ko) | 피라졸 유도체 | |
| HRP20141259T1 (hr) | Supstituirani izokinolinoni i kinazolinoni | |
| ES2585044T3 (es) | Derivados de pirazinona bicíclicos | |
| RU2014120210A (ru) | (гетеро)арилциклопропиламины в качестве ингибиторов lsd1 | |
| PE20040687A1 (es) | Quinolinas sustituidas como antagonistas del receptor ccr5 | |
| MX2011010203A (es) | Derivados de piperidina y piperazina como inhibidores de autotaxina. | |
| JP2006522746A5 (fr) | ||
| HRP20140252T1 (hr) | Derivati imidazola kao inhibitori kazeinske kinaze | |
| AR051215A1 (es) | Derivados de quinazolina | |
| PE20081238A1 (es) | Piperidinas sustituidas como antagonistas de hdm2 | |
| JP2006522744A5 (fr) | ||
| MY133992A (en) | Muscarinic antagonists | |
| AR058984A1 (es) | Derivados de ciclohexil piperazinil metanona |