CDP840. A prototype of a novel class of orally active anti-inflammatory phosphodiesterase 4 inhibitors

被引：46

作者：

Alexander, RP

Warrellow, GJ

Eaton, MAW

Boyd, EC

Head, JC

Porter, JR

Brown, JA

Reuberson, JT

Hutchinson, B

Turner, P

Boyce, B

Barnes, D

Mason, B

Cannell, A

Taylor, RJ

Zomaya, A

Millican, A

Leonard, J

Morphy, R

Wales, M

Perry, M

Allen, RA

Gozzard, N

Hughes, B

Higgs, G

机构：

[1] Celltech R&D Ltd, Dept Med Chem, Slough SL1 3WE, Berks, England

[2] Celltech R&D Ltd, Dept Biol, Slough SL1 3WE, Berks, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(02)00202-0

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery, synthesis and biological activity of a series of triarylethane phosphodiesterase 4 inhibitors is described. Structure-activity relationship studies are presented for CDP840 29), a potent, chiral, selective inhibitor of PDE 4 (IC50 4nM). CDP840 is non-emetic in the ferret at 30 mg kg(-1) (po), active in models of inflammation and reverses ozone-induced bronchial hyperreactivity in the guinea pig. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：1451 / 1456

页数：6

共 21 条

[1]

ALEXANDER RP, 1995, Patent No. 9517386

[2]

BEELEY, 1993, Patent No. 9325517

[3]

BOYD EC, 1994, Patent No. 09410118

[4] The effects of phosphodiesterase type 4 inhibitors on tumour necrosis factor-α and leukotriene B4 in a novel human whole blood assay [J].

Brideau, C ;

Van Staden, C ;

Styhler, A ;

Rodger, IW ;

Chan, CC .

BRITISH JOURNAL OF PHARMACOLOGY, 1999, 126 (04) :979-988

[5]

CHRISTENSEN SB, 1994, ANNU REP MED CHEM, V29, P185

[6]

Francis SH, 2001, PROG NUCLEIC ACID RE, V65, P1

[7]

GIEMBYCZ MA, 1993, CLIN EXP ALLERGY, V22, P19

[8] The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects [J].

Harbinson, PL ;

MacLeod, D ;

Hawksworth, R ;

OToole, S ;

Sullivan, PJ ;

Heath, P ;

Kilfeather, S ;

Page, CP ;

Costello, J ;

Holgate, ST ;

Lee, TH .

EUROPEAN RESPIRATORY JOURNAL, 1997, 10 (05) :1008-1014

[9] Inhibition of bronchospasm and ozone-induced airway hyperresponsiveness in the guinea-pig by CDP840, a novel phosphodiesterase type 4 inhibitor [J].

Holbrook, M ;

Gozzard, N ;

James, T ;

Higgs, G ;

Hughes, B .

BRITISH JOURNAL OF PHARMACOLOGY, 1996, 118 (05) :1192-1200

[10]

HOROWSKI R, 1985, CURR THER RES CLIN E, V38, P23

← 1 2 3 →