Generation of a new class of hNK2 receptor ligands using the 'fragment approach'

被引：5

作者：

D'Andrea, P

Porcelloni, M

Madami, A

Patacchini, R

Altamura, M

Fattori, D

机构：

[1] Menarini Ric SpA, I-00040 Pomezia, Rome, Italy

[2] Menarini Ric SpA, I-50131 Florence, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 03期

关键词：

NK2; fragment approach;

D O I：

10.1016/j.bmcl.2004.11.045

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The so called 'fragment approach' was applied in the search for new leads as selective hNK(2) antagonists. A first round of structural space exploration through the use of bond rigidity as scaffold to support the fragments, afforded 27a as 200 nM hNK(2) ligand. Further refinement gave MEN 14933 as a 16 nM hNK(2) ligand, selective versus hNK(1), of a novel class. Conformational analysis was used to study results and plan future work. (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：585 / 588

页数：4

相关论文

共 11 条

[1] Activation method to prepare a highly reactive acylsulfonamide ''safety-catch'' linker for solid-phase synthesis [J].

Backes, BJ ;

Virgilio, AA ;

Ellman, JA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (12) :3055-3056

[2] Molecular recognition: the fragment approach in lead generation [J].

Fattori, D .

DRUG DISCOVERY TODAY, 2004, 9 (05) :229-238

[3] Small molecule antagonists of the tachykinin NK2 receptor [J].

Fattori, D ;

Altamura, M ;

Maggi, CA .

MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2004, 4 (03) :331-340

[4] Molecular complexity and its impact on the probability of finding leads for drug discovery [J].

Hann, MM ;

Leach, AR ;

Harper, G .

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 2001, 41 (03) :856-864

[5] MELDOLA LECTURE - THE ROLE OF AROMATIC INTERACTIONS IN MOLECULAR RECOGNITION [J].

HUNTER, CA .

CHEMICAL SOCIETY REVIEWS, 1994, 23 (02) :101-109

[6] A GENERAL-METHOD FOR THE SOLID-PHASE SYNTHESIS OF UREAS [J].

HUTCHINS, SM ;

CHAPMAN, KT .

TETRAHEDRON LETTERS, 1994, 35 (24) :4055-4058

[7] TACHYKININ RECEPTORS AND TACHYKININ RECEPTOR ANTAGONISTS [J].

MAGGI, CA ;

PATACCHINI, R ;

ROVERO, P ;

GIACHETTI, A .

JOURNAL OF AUTONOMIC PHARMACOLOGY, 1993, 13 (01) :23-93

[8] Pharmacophore and receptor models for neurokinin receptors [J].

Poulsen, A ;

Bjornholm, B ;

Gundertofte, K ;

Pogozheva, ID ;

Liljefors, T .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2003, 17 (11) :765-783

[9]

REIJTO PA, 1998, PAC S BIOCOMPUT, P362

[10] Nonleadlikeness and leadlikeness in biochemical screening [J].

Rishton, GM .

DRUG DISCOVERY TODAY, 2003, 8 (02) :86-96