S-2-((S)-3-(4-氯苯基)-N'-((4-氯苯基)磺酰基)-4-苯基-4,5-二氢-1H-吡唑-1-甲脒基)-3-(甲基-d)丁酰胺-d（十八氘代JD5037）的合成
Synthesis of S-2-((S)-3-(4-chlorophenyl)-N'-((4-chlorophenyl)sulfonyl)-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboximidamido)-3-(methyl-d )butanamide-d , octadeuterated JD5037.
作者信息
Iyer Malliga R, Cinar Resat, Coffey Nathan J, Chorvat Robert J, Kunos George
机构信息
Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA.
Jenrin Discovery LLC, Chadds Ford, PA, USA.
出版信息
J Labelled Comp Radiopharm. 2017 Aug;60(10):460-465. doi: 10.1002/jlcr.3521. Epub 2017 Aug 2.
Abstract
JD5037 (1) is a potent and selective, peripherally acting inverse agonist of the cannabinoid (CB R) receptor. Peripheral CB receptor antagonists/inverse agonists have great potential in the treatment of metabolic disorders like type 2 diabetes, obesity, and nonalcoholic steatohepatitis. We report the synthesis of octadeuterated [ H ]-JD5037 (S, S) (8) along with its (S, R) diastereomer (13) from commercially available L-valine-d starting material. The [ H ]-JD5037 compound will be used to quantitate unlabeled JD5037 during clinical ADME studies and will be used as an LC-MS/MS bioanalytical standard.
摘要
JD5037 (1) 是一种强效且具有选择性的外周作用大麻素 (CB R) 受体反向激动剂。外周CB受体拮抗剂/反向激动剂在治疗2型糖尿病、肥胖症和非酒精性脂肪性肝炎等代谢紊乱疾病方面具有巨大潜力。我们报道了从市售L-缬氨酸-d起始原料合成十八氘代的 [H]-JD5037 (S, S) (8) 及其非对映异构体 (S, R) (13)。[H]-JD5037化合物将用于临床药物代谢动力学和药物处置研究中对未标记的JD5037进行定量，并将用作液相色谱-串联质谱生物分析标准品。
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