title: Synthesis and biological evaluation of cyclopentyl-triazolol-pyrimidine (CPTP) based P2Y12 antagonists.
abstract: In this Letter we describe SAR investigation on the cyclopentyl-triazolol-pyrimidine scaffold in pursuit of new oral P2Y12 inhibitors. Different synthetic routes were developed for variations at the cyclopentyl core. Optimization finally led to compound 2d which was advanced into preclinical development based on better potency and safety profile in comparison to ticagrelor.
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China. Electronic address: tuwy@shhrp.com.
authors: Wangyang
authors: W
authors: Tu
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Jiang
authors: J
authors: Fan
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Haitang
authors: H
authors: Zhang
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Guoji
authors: G
authors: Xu
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Zhiwei
authors: Z
authors: Liu
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Jian
authors: J
authors: Qu
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Fanglong
authors: F
authors: Yang
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Lei
authors: L
authors: Zhang
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Tianyu
authors: T
authors: Luan
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Jijun
authors: J
authors: Yuan
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Aishen
authors: A
authors: Gong
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Jun
authors: J
authors: Feng
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Piaoyang
authors: P
authors: Sun
authors: Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
authors: Qing
authors: Q
authors: Dong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003517:Cyclopentanes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects; D053657:Platelet-Rich Plasma / Q000187:drug effects; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D003517:Cyclopentanes; D058921:Purinergic P2Y Receptor Antagonists; D011743:Pyrimidines; D058925:Receptors, Purinergic P2Y12; D014230:Triazoles; C030986:pyrimidine
keywords: Anti-platelet; Excessive bleeding; P2Y(12) receptor antagonist; Ticagrelor