BR101549

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: BR101549
• 英文别名: Ethyl [2-butyl-6-oxo-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]methyl}-4-(propan-2-yl)-1,6-dihydropyrimidin-5-yl]acetate；ethyl 2-[2-butyl-6-oxo-1-[[4-[2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]-4-propan-2-ylpyrimidin-5-yl]acetate
• 化学式: C₃₀H₃₄N₄O₅
• 分子量: 530.624
• InChiKey: AGTBDYUKVYUOHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  BR101549 在 氯化亚砜 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 butyl 2-[2-butyl-6-oxo-1-[[4-[2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]-4-propan-2-ylpyrimidin-5-yl]acetate
  参考文献：
  名称：

  Identification of BR101549 as a lead candidate of non-TZD PPARγ agonist for the treatment of type 2 diabetes: Proof-of-concept evaluation and SAR

  摘要：

  The new class of PPARgamma non-TZD agonist originally derived from the backbone of anti-hypertensive Fimasartan, BR101549, was identified as a potential lead for anti-diabetic drug development. The X-ray crys-tallography of BR101549 with PPARgamma ligand binding domain (LBD) revealed unique binding characteristics versus traditional TZD full agonists. The lead candidate, BR101549, has been found activating PPARgamma to the level of Pioglitazone in vitro and indeed has demonstrated its effects on blood glucose control in mouse proof-of-concept evaluation. The attempts to improve its metabolic stability profile through follow-up SAR including deuterium incorporation have been also described.

  DOI：

  10.1016/j.bmcl.2018.12.043
• 作为产物：
  描述：

  戊腈 在 盐酸 、 羟胺 、 lithium hydride 作用下， 以 乙醇 、 水 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 BR101549
  参考文献：
  名称：

  Discovery of the bifunctional modulator of angiotensin II type 1 receptor (AT1R) and PPARγ derived from the AT1R antagonist, Fimasartan

  摘要：

  Inspired by the well-known PPAR gamma partial agonism of angiotensin II type 1 receptor (AT1R) antagonists exemplified by an antihypertensive drug, Telmisartan, efforts to identify compounds with the dual activities have been pursued in order to control the two major metabolic disorders, hypertension and hyperglycemia simultaneously. Lead compound 18 derived from the AT1R antagonist, Fimasartan, has successfully presented the possibility to control the medical conditions by a single molecule.

  DOI：

  10.1016/j.bmcl.2018.08.036

文献信息

• Discovery of BR102375, a new class of non-TZD PPARγ full agonist for the treatment of type 2 diabetes
  作者：Wonken Choung、Deokmo Yang、Hakdo Kim、Hyukjoon Choi、Bo Ram Lee、Min Park、Su Min Jang、Jae Soo Lim、Woo Sik Kim、Kyung-Hee Kim、Jungwook Chin、Kyungjin Jung、Geumwoo Lee、Eunmi Hong、Tae-ho Jang、Jeongmin Joo、Hayoung Hwang、Jayhyuk Myung、Seong Heon Kim

  DOI：10.1016/j.bmcl.2019.06.027

  日期：2019.8

  As a potential treatment of type 2 diabetes, a novel PPAR gamma non-TZD full agonist, compound 18 (BR102375) was identified from the original lead BR101549 by the SAR efforts of the labile metabolite control through bioisosteres approach. In vitro assessments of BR102375 demonstrated its activating potential of PPAR gamma comparable to Pioglitazone as well as the induction of related gene expressions. Further in vivo evaluation of BR102375 in diabetic rodent models successfully proved its glucose lowering effect as a potential antidiabetic agent, but the anticipated suppression of weight gain was not evident. The X-ray co-crystal analysis of BR102375-PPAR gamma LBD unexpectedly revealed binding modes totally different from those of BR101549, which was found, instead, closely resembled to those of TZD full agonists.
• [EN] PYRIMIDINONE DERIVATIVE COMPOUND AND USE THEREOF<br/>[FR] COMPOSÉ DÉRIVÉ DE PYRIMIDINONE ET SON UTILISATION<br/>[KO] 피리미디논 유도체 화합물 및 이의 용도
  申请人：BORYUNG PHARM

  公开号：WO2019039818A1

  公开（公告）日：2019-02-28

  본 발명은 피리미디논 유도체, 이의 광학 이성질체 또는 이의 약제학적으로 허용가능한 염을 제공한다. 본 발명의 화합물은 고혈압 및/또는 당뇨병의 치료, 예방 또는 개선 활성을 나타낸다.