RPR203494 a pyrimidine analogue of the p38 inhibitor RPR200765A with an improved in vitro potency

被引:49
作者
Collis, AJ [1 ]
Foster, ML [1 ]
Halley, F [1 ]
Maslen, C [1 ]
McLay, IM [1 ]
Page, KM [1 ]
Redford, EJ [1 ]
Souness, JE [1 ]
Wilsher, NE [1 ]
机构
[1] Dagenham Res Ctr, Aventis Pharma, Dagenham RM10 7XS, Essex, England
关键词
D O I
10.1016/S0960-894X(01)00034-8
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Following the discovery of RPR200765, a series of pyrimidine analogues have been prepared as backups. Amongst them, RPR203494 was identified with a better in vitro profile than RPR200765A. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:693 / 696
页数:4
相关论文
共 10 条
  • [1] Pyrimidinylimidazole inhibitors of CSBP/P37 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes
    Adams, JL
    Boehm, JC
    Kassis, S
    Gorycki, PD
    Webb, EF
    Hall, R
    Sorenson, M
    Lee, JC
    Ayrton, A
    Griswold, DE
    Gallagher, TF
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (22) : 3111 - 3116
  • [2] Badger AM, 2000, ARTHRITIS RHEUM, V43, P175, DOI 10.1002/1529-0131(200001)43:1<175::AID-ANR22>3.0.CO
  • [3] 2-S
  • [4] Computational methods for the prediction of 'drug-likeness'
    Clark, DE
    Pickett, SD
    [J]. DRUG DISCOVERY TODAY, 2000, 5 (02) : 49 - 58
  • [5] COOK DC, UNPUB ORG PROCESS RE
  • [6] LEE JC, 1994, NATURE, V372, P736
  • [7] Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
    Lipinski, CA
    Lombardo, F
    Dominy, BW
    Feeney, PJ
    [J]. ADVANCED DRUG DELIVERY REVIEWS, 1997, 23 (1-3) : 3 - 25
  • [8] Design and synthesis of potent, selective, and orally bioavailable tetrasubstituted imidazole inhibitors of p38 mitogen-activated protein kinase
    Liverton, NJ
    Butcher, JW
    Claiborne, CF
    Claremon, DA
    Libby, BE
    Nguyen, KT
    Pitzenberger, SM
    Selnick, HG
    Smith, GR
    Tebben, A
    Vacca, JP
    Varga, SL
    Agarwal, L
    Dancheck, K
    Forsyth, AJ
    Fletcher, DS
    Frantz, B
    Hanlon, WA
    Harper, CF
    Hofsess, SJ
    Kostura, M
    Lin, J
    Luell, S
    O'Neill, EA
    Orevillo, CJ
    Pang, M
    Parsons, J
    Rolando, A
    Sahly, Y
    Visco, DM
    O'Keefe, SJ
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (12) : 2180 - 2190
  • [9] The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy
    McLay, IM
    Halley, F
    Souness, JE
    McKenna, J
    Benning, V
    Birrell, M
    Burton, B
    Belvisi, M
    Collis, A
    Constan, A
    Foster, M
    Hele, D
    Jayyosi, Z
    Kelley, M
    Maslen, C
    Miller, G
    Ouldelhkim, MC
    Page, K
    Phipps, S
    Pollock, K
    Porter, B
    Ratcliffe, AI
    Redford, EJ
    Webber, S
    Slater, B
    Thybaud, V
    Wilsher, N
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2001, 9 (02) : 537 - 554
  • [10] Muller-Ladner U, 1996, Curr Opin Rheumatol, V8, P210