Butanoic acid, 4-chloro-3-methyl-4-oxo-, methyl ester, (3R)- | 83509-05-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: Butanoic acid, 4-chloro-3-methyl-4-oxo-, methyl ester, (3R)-
• 英文别名: methyl (3R)-4-chloro-3-methyl-4-oxobutanoate
• CAS: 83509-05-1
• 化学式: C₆H₉ClO₃
• 分子量: 164.589
• InChiKey: WRCFPABNOIMFKO-SCSAIBSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Butanoic acid, 4-chloro-3-methyl-4-oxo-, methyl ester, (3R)- 在 sodium hydroxide 、 9-borabicyclo[3.3.1]nonane dimer 、 草酰氯 、 sodium hexamethyldisilazane 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium tri-t-butoxyaluminum hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 62.5h， 生成 (S)-3-Methyl-5-oxo-pentanoic acid ((R)-1-naphthalen-1-yl-ethyl)-amide
  参考文献：
  名称：

  冈比亚酸A–D，有效的抗真菌聚醚的绝对构型，从海洋鞭毛藻Gambierdiscus toxicus中分离出来

  摘要：

  通过改进的Mosher方法，NMR分析和手性荧光HPLC结合测定，确定了从海洋鞭毛鞭毛冈比亚鞭毛虫中分离出来的强效抗真菌聚醚化合物甘地酸A–D的绝对构型。

  DOI：

  10.1016/s0040-4020(00)00753-5
• 作为产物：
  描述：

  (R)-(+)-甲基丁二酸 在 氢氧化钾 、 sodium hydroxide 、 草酰氯 作用下， 以 乙醚 为溶剂， 反应 53.0h， 生成 Butanoic acid, 4-chloro-3-methyl-4-oxo-, methyl ester, (3R)-
  参考文献：
  名称：

  Derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline: effect of changes at postions 2 and 5 of the hexanoic acid portion

  摘要：

  Several derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline (1) were synthesized and tested for converting enzyme inhibition activity and blood pressure lowering effects in rats. One compound, 5(S)-benzamido-2(R)-methyl-4-oxo-6-phenylhexanoyl-L-proline (2a), had and I50 against angiotensin converting enzyme of 1.0 x 10(-9) M and is the most potent inhibitor prepared thus far in this class of compounds. Testing of 2a orally at 30 mg/kg for inhibition of the angiotensin I induced blood pressure increase in conscious normotensive rats gave 100% inhibition that required 143 min before the angiotensin I blood pressure response returned to 70% of the pretreatment control response. In the conscious renal hypertensive rat, 2a given orally at a dose of 3 mg/kg caused a lowering of blood pressure that reached its maximum of 40 mmHg 8 h following drug administration.

  DOI：

  10.1021/jm00353a005

文献信息

• HETEROCYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20150133451A1

  公开（公告）日：2015-05-14

  The present invention provides a heterocyclic compound having an IRAK-4 inhibitory action, which is useful for the prophylaxis or treatment of inflammatory disease, autoimmune disease, osteoarticular degenerative disease, neoplastic disease and the like, and a medicament containing thereof. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  本发明提供了一种具有IRAK-4抑制作用的杂环化合物，该化合物对于预防或治疗炎症性疾病、自身免疫疾病、骨关节退行性疾病、肿瘤性疾病等具有用处，并且包含该化合物的药物。本发明涉及一种由下式（I）表示的化合物： 其中每个符号如规范中定义的那样，或其盐。
• Enzymatic Formation of a Skipped Methyl‐Substituted Octaprenyl Side Chain of Longestin (KS‐505a): Involvement of Homo‐IPP as a Common Extender Unit
  作者：Taro Ozaki、Sandip S. Shinde、Lei Gao、Ryo Okuizumi、Chengwei Liu、Yasushi Ogasawara、Xiaoguang Lei、Tohru Dairi、Atsushi Minami、Hideaki Oikawa

  DOI：10.1002/anie.201802116

  日期：2018.5.28

  Longestin (KS‐505a), a specific inhibitor of phosphodiesterase, is a meroterpenoid that consists of a unique octacyclic terpene skeleton with branched methyl groups at unusual positions (C1 and C12). Biochemical analysis of Lon23, a methyltransferase involved in the biosynthesis of longestin, demonstrated that it methylates homoisopentenyl diphosphate (homo‐IPP) to afford (3Z)‐3‐methyl IPP. This compound

  Longestin（KS‐505a）是磷酸二酯酶的特异性抑制剂，是一种类萜，由独特的八环萜烯骨架组成，在异常位置（C1和C12）带有分支甲基。Lon23（一种参与Longestin生物合成的甲基转移酶）的生化分析表明，它可以将均异戊烯基二磷酸（homo-IPP）甲基化以提供（3 Z）-3-甲基IPP。该化合物与IPP一起被Lon22（香叶基香叶基香叶基二磷酸（GGPP）合酶同系物）选择性地接受为扩展单元，从而生成二甲基化GGPP（dmGGPP）。dmGGPP的绝对配置确定为（4 R，12 R）降解和手性GC分析。这些发现使我们能够为不寻常的同萜类长汀的生物合成途径的关键步骤提出酶促序列。
• Convenient synthesis of antisepsis agent TAK-242 by novel optical resolution through diastereomeric N-acylated sulfonamide derivative
  作者：Atsuko Nishiguchi、Tomomi Ikemoto、Kiminori Tomimatsu

  DOI：10.1016/j.tet.2007.02.127

  日期：2007.5

  A convenient synthesis method of antisepsis agent TAK-242 ((R)-1) through diastereomeric resolution was developed. By condensation of racemate rac-1 with chiral acid (S)-O-acetylmanderic acid (6a), the desired diastereomer 5a was isolated with 98% de in 39% yield by simple crystallization. Deacylation of 5a with aq NaOH followed by recrystallization provided (R)-1 with 99% ee in 20% yield from rac-1

  通过非对映异构体拆分，开发了一种简便的防腐剂TAK-242（（R）-1）的合成方法。通过使外消旋体rac - 1与手性酸（S）-O-乙酰基扁桃酸（6a）缩合，通过简单的结晶以39％的收率分离出所需的非对映异构体5a，收率为98％。用NaOH水溶液对5a进行脱酰，然后重结晶，得到具有99％ee的（R）-1，从rac - 1产率为20％。
• [EN] LACTAM COMPOUNDS USEFUL AS PROTEIN KINASE INHIBITORS<br/>[FR] COMPOSES A BASE DE LACTAME UTILES EN TANT QU'INHIBITEURS DE LA PROTEINE KINASE
  申请人：MILLENNIUM PHARM INC

  公开号：WO2006041773A3

  公开（公告）日：2006-05-18
• Derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline: effect of changes at postions 2 and 5 of the hexanoic acid portion
  作者：Ronald G. Almquist、Jac Crase、Clive Jennings-White、Robert F. Meyer、Milton L. Hoefle、Ronald D. Smith、Arnold D. Essenburg、Harvey R. Kaplan

  DOI：10.1021/jm00353a005

  日期：1982.11

  Several derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline (1) were synthesized and tested for converting enzyme inhibition activity and blood pressure lowering effects in rats. One compound, 5(S)-benzamido-2(R)-methyl-4-oxo-6-phenylhexanoyl-L-proline (2a), had and I50 against angiotensin converting enzyme of 1.0 x 10(-9) M and is the most potent inhibitor prepared thus far in this class of compounds. Testing of 2a orally at 30 mg/kg for inhibition of the angiotensin I induced blood pressure increase in conscious normotensive rats gave 100% inhibition that required 143 min before the angiotensin I blood pressure response returned to 70% of the pretreatment control response. In the conscious renal hypertensive rat, 2a given orally at a dose of 3 mg/kg caused a lowering of blood pressure that reached its maximum of 40 mmHg 8 h following drug administration.