6-chloro-N4,2-dimethyl-pyrimidine-4,5-diamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-chloro-N4,2-dimethyl-pyrimidine-4,5-diamine
• 英文别名: 6-chloro-N,2-dimethylpyrimidine-4,5-diamine；6-chloro-2,N⁴-dimethyl-pyrimidine-4,5-diyldiamine；6-Chlor-2,N⁴-dimethyl-pyrimidin-4,5-diyldiamin；5-Amino-4-chloro-2-methyl-6-methylaminopyrimidine；6-chloro-4-N,2-dimethylpyrimidine-4,5-diamine
• 化学式: C₆H₉ClN₄
• 分子量: 172.617
• InChiKey: FGRYRJUMFNOCKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-N4,2-dimethyl-pyrimidine-4,5-diamine 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 乙醇 、 水 、 丙酮 、 乙腈 为溶剂， 反应 35.0h， 生成 8-(2-chlorophenyl)-6-(4-ethylpiperazin-1-yl)-2,9-dimethyl-purine hydrochloride
  参考文献：
  名称：

  Selective Cannabinoid Receptor Type 2 (CB2) Agonists: Optimization of a Series of Purines Leading to the Identification of a Clinical Candidate for the Treatment of Osteoarthritic Pain

  摘要：

  A focused screening strategy identified thienopyrimidine 12 as a cannabinoid receptor type 2 agonist (hCB2) with moderate selectivity over the hCB1 receptor. This initial hit suffered from poor in vitro metabolic stability and high in vivo clearance. Structure-activity relationships describe the optimization and modification to a new more polar series of purine CB2 agonists. Examples from this novel scaffold were found to be highly potent and fully efficacious agonists of the human CB2 receptor with excellent selectivity against CBI, often having no CBI agonist activity at the highest concentration measured (>100 mu M). Compound 26 is a centrally penetrant molecule which possesses good biopharmaceutical properties, is highly water-soluble, and demonstrates robust oral activity in rodent models of joint pain. In addition, the peripherally restricted molecule 22 also demonstrated significant efficacy in the same analgesic model of rodent inflammatory pain.

  DOI：

  10.1021/jm400305d
• 作为产物：
  描述：

  2-甲基-4,6-二氯-5-氨基嘧啶 、 甲胺 在 N,N-二异丙基乙胺 作用下， 以 水 、 异丙醇 为溶剂， 反应 4.0h， 以77%的产率得到6-chloro-N4,2-dimethyl-pyrimidine-4,5-diamine
  参考文献：
  名称：

  Selective Cannabinoid Receptor Type 2 (CB2) Agonists: Optimization of a Series of Purines Leading to the Identification of a Clinical Candidate for the Treatment of Osteoarthritic Pain

  摘要：

  A focused screening strategy identified thienopyrimidine 12 as a cannabinoid receptor type 2 agonist (hCB2) with moderate selectivity over the hCB1 receptor. This initial hit suffered from poor in vitro metabolic stability and high in vivo clearance. Structure-activity relationships describe the optimization and modification to a new more polar series of purine CB2 agonists. Examples from this novel scaffold were found to be highly potent and fully efficacious agonists of the human CB2 receptor with excellent selectivity against CBI, often having no CBI agonist activity at the highest concentration measured (>100 mu M). Compound 26 is a centrally penetrant molecule which possesses good biopharmaceutical properties, is highly water-soluble, and demonstrates robust oral activity in rodent models of joint pain. In addition, the peripherally restricted molecule 22 also demonstrated significant efficacy in the same analgesic model of rodent inflammatory pain.

  DOI：

  10.1021/jm400305d

文献信息

• Piperazinyl derivatives of purines and isosteres thereof as hypoglycemic
  申请人：Merck & Co., Inc.

  公开号：US05057517A1

  公开（公告）日：1991-10-15

  There are disclosed certain 6-piperazinopurines and heteroaromatic derivatives thereof which have oral hypoglycemic acitivity and with such ability to lower blood sugar are useful in the treatment of type II diabetes and/or obesity with associated insulin resistance. Processes for the preparation of such compounds and compositions containing such compounds as the active ingredient thereof are also disclosed.

  本文披露了某些6-哌嗪嘌呤和其杂环衍生物，具有口服降糖活性，并具有降低血糖的能力，可用于治疗II型糖尿病和/或伴随胰岛素抵抗的肥胖症。本文还披露了制备这些化合物的方法以及含有这些化合物作为其活性成分的组合物。
• Piperazinyl derivates of purines and isosteres thereof as hypoglycemic agents
  申请人：Merck & Co., Inc.

  公开号：EP0300726A1

  公开（公告）日：1989-01-25

  There are disclosed certain 6-piperazino-­purine and heteroaromatic derivatives thereof which have oral hypoglycemic activity and with such ability to lower blood sugar are useful in the treatment of type II diabetes and/or obesity with associated insulin resistance. Processes for the preparation of such compounds and compositions containing such compounds as the active ingredient thereof are also disclosed.

  已公开的某些 6-哌嗪基嘌呤及其杂芳香族衍生物具有口服降血糖活性，这种降血糖能力可用于治疗 II 型糖尿病和/或伴有胰岛素抵抗的肥胖症。 此外，还公开了制备此类化合物的工艺和含有此类化合物作为其活性成分的组合物。
• Conditioning of Skeletal Muscles in Adult and Old Mice for Protection From Contraction-Induced Injury
  作者：S. V. Brooks、J. A. Opiteck、J. A. Faulkner

  DOI：10.1093/gerona/56.4.b163

  日期：2001.4.1

  The purpose of this study was to design a conditioning program that protected muscles in both adult and old mice from a protocol of contractions that previously caused a significant number of damaged fibers and a deficit in force, Hind-limb dorsiflexor muscles of adult (7 months) and old (22 months) female B6D2F1 mice were exposed once a week to a protocol of repeated forced stretches while maximally activated in vivo. By week 4, muscles of adult, but not old, mice showed no force deficit. Conditioning was continued for 6 weeks, when both age groups showed no force deficit for two consecutive weeks. Three days after the sixth contraction protocol, when morphological damage and force deficits are most severe, the numbers of damaged fibers in muscles of adult and old mice were not different from those in uninjured control muscles and the force deficits were reduced dramatically compared with unconditioned muscles. We conclude that muscles of both adult and old mice conditioned successfully, but muscles of old mice conditioned more slowly than those of adult mice.
• Discovery and optimization of novel purines as potent and selective CB2 agonists
  作者：Sean P. Hollinshead、Peter C. Astles、Mark G. Chambers、Michael P. Johnson、John Palmer、Michael W. Tidwell

  DOI：10.1016/j.bmcl.2012.06.035

  日期：2012.8

  A focused screening strategy identified thienopyrimidine 1 as a hCB2 cannabinoid receptor agonist with moderate selectivity over the hCB1 receptor. This initial hit suffered from poor in vitro metabolic stability and high in vivo clearance. Structure-activity relationships describe the optimization and modification to a less lipophilic purine core. Examples from this novel series were found to be highly potent and fully efficacious agonists of the human CB2 receptor with excellent selectivity against CB1. Compound 10 possesses good biopharmaceutical properties, is highly water soluble and demonstrates robust oral activity in rodent models of joint pain. (c) 2012 Elsevier Ltd. All rights reserved.
• US5057517A
  申请人：——

  公开号：US5057517A

  公开（公告）日：1991-10-15