Novel tetrahydropyran-based peptidomimetics from a bioisosteric transformation of a tripeptide. Evidence of their activity at melanocortin receptors

被引：12

作者：

Mazur, AW ^{[1
]}

Kulesza, A ^{[1
]}

Mishra, RK ^{[1
]}

Cross-Doersen, D ^{[1
]}

Russell, AF ^{[1
]}

Ebetino, FH ^{[1
]}

机构：

[1] Procter & Gamble Pharmaceut, Hlth Care Res Ctr, Mason, OH 45040 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2003年 / 11卷 / 14期

关键词：

D O I：

10.1016/S0968-0896(03)00274-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have prepared novel peptidomimetics based on a 2,4,6-trisubstituted tetrahydropyran. This scaffold was constructed in an isosteric transformation using conceptual constraints imposed on a tripeptide moiety involving O-i'-C-1(+1)gamma and O-i'-Ni+2 formal cyclization modes. A series of regioselective transformations commencing with a substituted dihydropyran-4-one readily provided the required analogues. Specific tetrahydropyrane analogues modeled on PheArgTrp as a truncated version of the melanocortin receptor message sequence, showed activity at the melanocortin receptors MC4R and MC1R. Thus, the 2,4,6-trisubstituted tetrahydropyran scaffold has provided a potentially useful peptidomimetic lead, and conceptual cyclization of peptide moieties can offer a valuable design strategy in peptidomimetic research. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：3053 / 3063

页数：11

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