Hit-to-lead studies: The discovery of potent, orally bioavailable thiazolopyrimidine CXCR2 receptor antagonists

被引：46

作者：

Baxter, A ^{[1
]}

Cooper, A ^{[1
]}

Kinchin, E ^{[1
]}

Moakes, K ^{[1
]}

Unitt, J ^{[1
]}

Wallace, A ^{[1
]}

机构：

[1] AstraZeneca R&D Charnwood, Loughborough LE11 5RH, Leics, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 04期

关键词：

CXCR2; antagonist; hit-to-lead;

D O I：

10.1016/j.bmcl.2005.10.091

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A Hit-to-Lead optimisation programme was carried out on a high throughput screening hit, the thiazolopyrimidine 1, resulting in the discovery of the potent, orally bioavailable CXCR2 antagonist 29. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：960 / 963

页数：4

共 8 条

[1]

AUSTEN R, Patent No. 0009511

[2] SYNTHESIS OF DERIVATIVES OF THIAZOLO 4,5-D!PYRIMIDINE .2. [J].

BAKER, JA ;

CHATFIEL.PV .

JOURNAL OF THE CHEMICAL SOCIETY C-ORGANIC, 1970, (18) :2478-&

[3] Hit-to-lead studies: The discovery of potent, orally bioavailable triazolethiol CXCR2 receptor antagonists [J].

Baxter, A ;

Bennion, C ;

Bent, J ;

Boden, K ;

Brough, S ;

Cooper, A ;

Kinchin, E ;

Kindon, N ;

McInally, T ;

Mortimore, M ;

Roberts, B ;

Unitt, J .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (16) :2625-2628

[4] STUDIES IN THE 5-HALO-2-THIOURACIL SERIES .1. AN IMPROVED METHOD OF DEBENZYLATION OF 5-IODO-2-BENZYLTHIOURACIL AND HOMOLOGS [J].

LANZILOTTI, AE ;

ZIEGLER, JB ;

SHABICA, AC .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1954, 76 (14) :3666-3667

[5] Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings [J].

Lipinski, CA ;

Lombardo, F ;

Dominy, BW ;

Feeney, PJ .

ADVANCED DRUG DELIVERY REVIEWS, 1997, 23 (1-3) :3-25

[6]

MICHNE WF, 1996, PHARM NEWS, V3, P19

[7]

Teague SJ, 1999, ANGEW CHEM INT EDIT, V38, P3743, DOI 10.1002/(SICI)1521-3773(19991216)38:24<3743::AID-ANIE3743>3.0.CO

[8]

2-U

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