📜3,5-二氯苄基溴置于sodium Hydroxide体系中,化学反应生成 3,5-二氯苯乙酸 参考文献:Pybus Et Al.,Annals Of Applied Biology,1959,Vol. 47,P. 593,595 标题:Pybus Et Al.,Annals Of Applied Biology,1959,Vol. 47,P. 593,595
专利号:EP-0946499-B1 优先权日:1996-11-22 标 题 :N-(aryl/heteroaryl/alkylacetyl) amino acid amides, pharmaceutical compositions comprising same, and methods for inhibiting beta-amyloid peptide release and/or its synthesis by use of such compounds 发明人:WU JING; TUNG JAY S; NISSEN JEFFREY S; MABRY THOMAS E; LATIMER LEE H; EID CLARK NORMAN; AUDIA JAMES E 权利人:ELAN PHARM INC; LILLY CO ELI 摘要:Disclosed are compounds which inhibit beta -amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits beta -amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions. Said compounds are represented by formula (I), wherein R<1> is selected from the group consisting of: a) alkyl, alkenyl, alkaryl, alkcycloalkyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic; b) a substituted phenyl group of formula (II), wherein R is alkylene of from 1 to 8 carbon atoms, m is an integer equal to 0 or 1, and c) 1- or 2-naphthyl substituted at the 5, 6, 7 and/or 8 positions, R<2> is selected from the group consisting of hydrogen, alkyl of from 1 to 4 carbon atoms, alkylalkoxy of from 1 to 4 carbon atoms, alkylthioalkoxy of from 1 to 4 carbon atoms; and R<3> and R<3'> are independently selected from the group consisting of: (a) hydrogen, (b) alkyl, (c) -(R<7>)n(W)p, wherein R<7> is an alkylene group, W is selected from the group consisting of (i) formula (A); (ii) heteroaryl; and (iii) N-heterocyclic, and n is an integer equal to 0 or 1, and p is an integer equal to 1 to 3; (d) -CH( phi )CH2C(O)O-Q where Q is selected from the group consisting of alkyl, aryl, heteroaryl and heterocyclic; X' is hydrogen, hydroxy or fluoro; X'' is hydrogen, hydroxy or fluoro, or X' and X'' together form an oxo group, Z is selected from the group consisting of a bond covalently linking R<1> to -CX'X''-, oxygen and sulfur.
专利号:US-6849650-B2 优先权日:1998-02-27 标 题:Heterocyclic compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds 发明人:THORSETT EUGENE D; PORTER WARREN J; NISSEN JEFFREY S; LATIMER LEE H; AUDIA JAMES E; DROSTE JAMES 权利人:ATHENA NEUROSCIENCES INC; LILLY CO ELI 摘要:Disclosed are compounds which inhibit β-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits β-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.
专利号:EP-0951464-B1 优先权日:1996-11-22 标题:N-(aryl/heteroarylacetyl) amino acid esters, pharmaceutical compositions comprising same, and methods for inhibiting beta-amyloid peptide release and/or its synthesis by use of such compounds 发明人:WU JING; THORSETT EUGENE D; NISSEN JEFFREY S; MABRY THOMAS E; LATIMER LEE H; JOHN VARGHESE; FANG LAWRENCE Y; AUDIA JAMES E 权利人:ELAN PHARM INC; LILLY CO ELI 摘要:Disclosed are compounds which inhibit beta -amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits beta -amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.
专利号:EP-0951466-B1 优先权日:1996-12-23 标题:Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting beta-amyloid peptide release and/or its synthesis by use of such compounds 发明人:WU JING; TUNG JAY S; THORSETT EUGENE D; PLEISS MICHAEL A; NISSEN JEFFREY S; NEITZ JEFFREY; LATIMER LEE H; JOHN VARGHESE; FREEDMAN STEPHEN; BRITTON THOMAS C; AUDIA JAMES E; REEL JON K; MABRY THOMAS E; DRESSMAN BRUCE A; CWI CYNTHIA L; DROSTE JAMES J; HENRY STEVEN S; MCDANIEL STACEY L; SCOTT WILLIAM L; STUCKY RUSSELL D 权利人:ELAN PHARM INC; LILLY CO ELI 摘要:Disclosed are compounds for Formula (I) wherein the substituents are as defined in the claims which inhibit β-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits β-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.
专利号:US-6262302-B1 优先权日:1996-11-22 标题:N-(aryl/heteroaryl/alkylacetyl) amino acid amides, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds 发明人:WU JING; TUNG JAY S; NISSEN JEFFREY S; MABRY THOMAS E; LATIMER LEE H; EID CLARK N; AUDIA JAMES E 权利人:ELAN PHARM INC; LILLY CO ELI 摘要:Disclosed are compounds which inhibit beta-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed pharmaceutical compositions comprising a compound which inhibits beta-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.
专利号:US-6333351-B1 优先权日:1996-11-22 标题:N-(aryl/heteroarylacetyl) amino acid esters, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds 发明人:WU JING; THORSETT EUGENE D; NISSEN JEFFREY S; MABRY THOMAS E; LATIMER LEE H; JOHN VARGHESE; FANG LAWRENCE Y; AUDIA JAMES E 权利人:ATHENA NEUROSCIENCES INC; LILLY CO ELI 摘要:Disclosed are compounds which inhibit beta-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed pharmaceutical compositions comprising a compound which inhibits beta-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.
参考文献:10.1126/sciadv.abf8711 摘要:Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Díaz RE, Young ID, Carvalho Martins L, Smith DH, Schulze-Gahmen U, Owens TW, Deshpande I, Merz GE, Thwin AC, Biel JT, Peters JK, Moritz M, Herrera N, Kratochvil HT; QCRG Structural Biology Consortium, Aimon A, Bennett JM, Brandao Neto J, Cohen AE, Dias A, Douangamath A, Dunnett L, Fedorov O, Ferla MP, Fuchs MR, Gorrie-Stone TJ, Holton JM, Johnson MG, Krojer T, Meigs G, Powell AJ, Rack JGM, Rangel VL, Russi S, Skyner RE, Smith CA, Soares AS, Wierman JL, Zhu K, O'Brien P, Jura N, Ashworth A, Irwin JJ, Thompson MC, Gestwicki JE, von Delft F, Shoichet BK, Fraser JS, Ahel I. Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking. Sci Adv. 2021 Apr;7(16).