From peptides to non-peptide peptidomimetics: Design and synthesis of new piperidine inhibitors of aspartic peptidases

被引：58

作者：

Bursavich, MG

West, CW

Rich, DH

机构：

[1] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA

[2] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA

来源：

ORGANIC LETTERS | 2001年 / 3卷 / 15期

关键词：

D O I：

10.1021/ol016092u

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] The 3-alkoxy-4-arylpiperidine inhibitors of aspartic peptidases are shown to be a new type of non-peptide peptidomimetic inhibitor. These piperidines can be designed from peptide derived inhibitors by use of a structure generating program but only after the enzyme active site conformation has been modified in a mechanistically related fashion. New enantioselective syntheses of 3-alkoxy-4-arylpiperidine analogues are described.

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页码：2317 / 2320

页数：4

相关论文

共 35 条

[1] Molecular recognition of protein-ligand complexes: Applications to drug design [J].

Babine, RE ;

Bender, SL .

CHEMICAL REVIEWS, 1997, 97 (05) :1359-1472

[2]

Bohacek RS, 1996, MED RES REV, V16, P3, DOI 10.1002/(SICI)1098-1128(199601)16:1<3::AID-MED1>3.3.CO

[3]

2-D

[4] Design and synthesis of unsymmetrical peptidyl urea inhibitors of aspartic peptidases [J].

Dales, NA ;

Bohacek, RS ;

Satyshur, KA ;

Rich, DH .

ORGANIC LETTERS, 2001, 3 (15) :2313-2316

[5] Conformational selection of inhibitors and substrates by proteolytic enzymes: Implications for drug design and polypeptide processing [J].

Fairlie, DP ;

Tyndall, JDA ;

Reid, RC ;

Wong, AK ;

Abbenante, G ;

Scanlon, MJ ;

March, DR ;

Bergman, DA ;

Chai, CLL ;

Burkett, BA .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (07) :1271-1281

[6]

Farmer P. S., 1980, DRUG DESIGN, V10, P119

[7] Purification and crystallization of rhizopuspepsin: The use of nickel chelation chromatography to select for catalytically active species [J].

Flentke, GR ;

Glinski, J ;

Satyshur, K ;

Rich, DH .

PROTEIN EXPRESSION AND PURIFICATION, 1999, 16 (02) :213-220

[8] Nonpeptidic ligands for peptide and protein receptors [J].

Freidinger, RM .

CURRENT OPINION IN CHEMICAL BIOLOGY, 1999, 3 (04) :395-406

[9] Piperidine-renin inhibitors compounds with improved physicochemical properties [J].

Güller, R ;

Binggeli, A ;

Breu, V ;

Bur, D ;

Fischli, W ;

Hirth, G ;

Jenny, C ;

Kansy, M ;

Montavon, F ;

Müller, M ;

Oefner, C ;

Stadler, H ;

Vieira, E ;

Wilhelm, M ;

Wostl, W ;

Märki, HP .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (10) :1403-1408

[10]

Hagen S, 2000, ADV MED CH, V5, P159, DOI 10.1016/S1067-5698(00)80006-1

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