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N-4,6-嘧啶-N-烷基-N'-苯基脲作为淋巴细胞特异性酪氨酸激酶口服活性抑制剂的研发

Development of N-4,6-pyrimidine-N-alkyl-N'-phenyl ureas as orally active inhibitors of lymphocyte specific tyrosine kinase.

作者信息

Maier Jennifer A, Brugel Todd A, Sabat Mark, Golebiowski Adam, Laufersweiler Matthew J, VanRens John C, Hopkins Corey R, De Biswanath, Hsieh Lily C, Brown Kimberly K, Easwaran Vijayasurian, Janusz Michael J

机构信息

Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Rd. Mason, OH 45040, USA.

出版信息

Bioorg Med Chem Lett. 2006 Jul 15;16(14):3646-50. doi: 10.1016/j.bmcl.2006.04.072. Epub 2006 May 8.

DOI:10.1016/j.bmcl.2006.04.072
PMID:16682201
Abstract

A new class of lymphocyte specific tyrosine kinase (lck) inhibitors based on an N-4,6-pyrimidine-N-alkyl-N'-phenyl urea scaffold is described. Many of these compounds showed low-nanomolar inhibition of lck kinase activity as well as IL-2 synthesis from Jurkat cells. One of these analogs, 7i, was shown to be orally efficacious by in vivo testing in a rat adjuvant-induced arthritis study.

摘要

描述了一类基于N-4,6-嘧啶-N-烷基-N'-苯基脲支架的新型淋巴细胞特异性酪氨酸激酶（lck）抑制剂。这些化合物中的许多对lck激酶活性以及Jurkat细胞中白细胞介素-2的合成表现出低纳摩尔抑制作用。其中一种类似物7i，在大鼠佐剂诱导的关节炎研究中的体内试验表明口服有效。

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