1-Methyl-1,3-cyclohexancarbolacton | 64326-18-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 1-Methyl-1,3-cyclohexancarbolacton
• 英文别名: 1-methyl-6-oxa-bicyclo[3.2.1]octan-7-one；1-Methyl-6-oxabicyclo[3.2.1]octan-7-one
• CAS: 64326-18-7
• 化学式: C₈H₁₂O₂
• 分子量: 140.182
• InChiKey: BBHHJKGNHOCKBQ-UHFFFAOYSA-N

物化性质

• 熔点：
  39-40 °C(Solv: hexane (110-54-3))
• 沸点：
  102-104 °C(Press: 10 Torr)
• 密度：
  1.119±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-Methyl-1,3-cyclohexancarbolacton 在 氯化亚砜 、 zinc(II) chloride 作用下， 反应 12.0h， 生成 3-chloro-1-methylcyclohexanecarboxylic acid chloride
  参考文献：
  名称：

  Ismailov, A. G.; Rustamov, M. A.; Akhmedov, A. A., Journal of Organic Chemistry USSR (English Translation), 1980, p. 64 - 69

  摘要：

  DOI：
• 作为产物：
  描述：

  3-chloro-1-methylcyclohexanecarboxylic acid 生成 1-Methyl-1,3-cyclohexancarbolacton
  参考文献：
  名称：

  Ismailov, A. G.; Rustamov, M. A.; Akhmedov, A. A., Journal of Organic Chemistry USSR (English Translation), 1980, p. 64 - 69

  摘要：

  DOI：

文献信息

• Thiazolidine derivatives and production thereof
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04461902A1

  公开（公告）日：1984-07-24

  A thiazolidine derivative of the general formula, ##STR1## is a cyclohexane ring having an oxo or hydroxyl group as a substituent on any of the methylene groups constituting the ring and R is a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, is a novel compound and is useful as, for example, remedies for diabetes, hyperlipemia and so on of mammals including human beings.

  一种通式为##STR1##的噻唑啉衍生物，其中环己烷环上的任意亚甲基基团上有氧代或羟基取代基，R为氢原子或1至4个碳原子的低碳基团，是一种新化合物，可用作哺乳动物（包括人类）的糖尿病、高脂血症等疾病的治疗药物等。
• Isoxazole o-linked carbamoyl cyclohexyl acids as LPA antagonists
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US11180488B2

  公开（公告）日：2021-11-23

  The present invention provides compounds of Formula (Ia) or (Ib) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X1, X2, X3, and X4 are each independently CR6 or N; provided that no more than two of X1, X2, X3, or X4 are N; L is C1-4 alkylene substituted with 0 to 4 R7; R1 is (—CH2)aR9; a is an integer of 0 or 1; R2 is each independently halo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, alkoxyalkyl, haloalkoxyallcyl, or haloalkoxy; n is an integer of 0, 1, or 2; R3 is hydrogen, C1-6 alkyl, C1-6 deuterated alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy, and the alkyl, by itself or as part of other moiety, is optionally substituted with deuterium partially or fully; R4 is C1-10 alkyl, C1-10 deuterated alkyl, C1-10 haloalkyl, C1-10 alkenyl, C3-8 cycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, —(C1-6 alkylene)-(C3-8 cycloalkyl), —(C1-6 alkylene)-(6 to 10-membered aryl), —(C1-6 alkylene)-(3 to 8-membered heterocyclyl), or —(C1-6 alkylene)-(5 to 6-membered heteroaryl); wherein each of the alkyl, alkylene, alkenyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R8; or alternatively, R3 and R4, taken together with the N atom to which they are attached, form a 4 to 9-membered heterocyclic ring moiety which is substituted with 0 to 3 R; R5 and R6 are each independently hydrogen, halo, cyano, hydroxyl, amino, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R7 is halo, oxo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R8 are each independently deuterium, halo, hydroxyl, amino, cyano, C1-6 alkyl, C1-6 deuterated alkyl, C2-6 alkenyl, C2-6 alkynyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl; or alternatively, two R8, taken together with the atoms to which they are attached, form a 3 to 6-membered carbocyclic ring or a 3 to 6-membered heterocyclic ring each of which is independently substituted with 0 to 3 R12; R9 is selected from —CN, —C(O)OR10, —C(O)NR11aR11b, —CO—NH—CO—Re, —CO—NH—SO2—Re, —CO—NH—SO—Re, —SO2—OH, —SO2—NH—CO—Re, —P(O)(OH)2, tetrazol-5-yl, —CH2—CO—NH—CO—Re, —CH2—CO—NH—SO2—Re, CH2—CO—NH—SO—Re, —CH2—SO2—OH, —CH2—SO2—NH—CO—Re, —CH2—P(O)(OH)2, tetrazol-5-ylmethylene; Re is C1-6 alkyl, C3-6 cycloalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl; R10 is hydrogen or C1-10 alkyl; and R11a and R11b are each independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; and R12 is halo, cyano, hydroxyl, amino, C1-6alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl. These compounds are selective LPA receptor inhibitors.

  本发明提供了式(Ia)或(Ib)化合物或其立体异构体、同分异构体或药学上可接受的盐或溶液，其中X1、X2、X3和X4各自独立地为CR6或N；条件是X1、X2、X3或X4中不超过两个为N；L为被0至4个R7取代的C1-4亚烷基；R1为(-CH2)aR9；a为0或1的整数；R2 各自独立地为卤代、氰基、羟基、氨基、C1-6 烷基、C3-6 环烷基、C4-6 杂环烷基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基、烷氧基烷基、卤代烷氧基杂环烷基或卤代烷氧基；n 为 0、1 或 2 的整数；R3 是氢、C1-6 烷基、C1-6 氚代烷基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基或卤代烷氧基，且烷基本身或作为其他分子的一部分可任选被氘部分或全部取代；R4 是 C1-10 烷基、C1-10 氚代烷基、C1-10 卤代烷基、C1-10 烯基、C3-8 环烷基、6-10 元芳基、3-8 元杂环基、-(C1-6 亚烷基)-(C3-8 环烷基)、-(C1-6 亚烷基)-(6-10 元芳基)、-(C1-6 亚烷基)-(3-8 元杂环基)或-(C1-6 亚烷基)-(5-6 元杂芳基)；其中，每个烷基、亚烷基、烯基、环烷基、芳基、杂环基和杂芳基本身或作为其他分子的一部分，独立地被 0 至 3 个 R8 取代；R5 和 R6 各自独立地为氢、卤代、氰基、羟基、氨基、C1-6 烷基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基或卤代烷氧基；R7 是卤代、氧代、氰基、羟基、氨基、C1-6 烷基、C3-6 环烷基、C4-6 杂环烷基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基或卤代烷氧基；R8 各自独立地为氘、卤素、羟基、氨基、氰基、C1-6 烷基、C1-6 氚代烷基、C2-6 烯基、C2-6 炔基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基、卤代烷氧基、苯基或 5-6 元杂芳基；或者，两个 R8 与它们所连接的原子一起形成一个 3 至 6 元碳环或一个 3 至 6 元杂环，其中每个环独立地被 0 至 3 个 R12 取代；R9 选自-CN、-C(O)OR10、-C(O)NR11aR11b、-CO-NH-CO-Re、-CO-NH-SO2-Re、-CO-NH-SO-Re、-SO2-OH、-SO2-NH-CO-Re、-P(O)(OH)2、四氮唑-5-基，-CH2-CO-NH-CO-Re，-CH2-CO-NH-SO2-Re，CH2-CO-NH-SO-Re，-CH2-SO2-OH，-CH2-SO2-NH-CO-Re，-CH2-P(O)(OH)2，四氮唑-5-基亚甲基；Re 是 C1-6 烷基、C3-6 环烷基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基或卤代烷氧基烷基；R10 是氢或 C1-10 烷基；R11a 和 R11b 各自独立地是氢、C1-6 烷基、C3-6 环烷基、C4-6 杂环烷基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基或卤代烷氧基；R12 是卤素、氰基、羟基、氨基、C1-6-烷基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基、卤代烷氧基、苯基或 5 至 6 元杂芳基。这些化合物是选择性 LPA 受体抑制剂。
• 10.1021/jacs.4c04043
  作者：Zhuang, Zhe、Sheng, Tao、Qiao, Jennifer X.、Yeung, Kap-Sun、Yu, Jin-Quan

  DOI：10.1021/jacs.4c04043

  日期：——

  carboxylic acids and cycloalkane acetic acids was observed, giving either fused or bridged γ-lactones that are difficult to access by other methods. δ-C–H lactonization was only favored in the presence of tertiary δ-C–H bonds. The synthetic utility of this methodology was demonstrated by the late-stage functionalization of amino acids, drug molecules, and natural products, as well as a two-step total synthesis

  位点选择性C(sp 3 )–H氧化在有机合成和药物发现中具有重要意义。游离羧酸的γ-C(sp 3 )–H内酯化提供了从丰富且廉价的羧酸制备具有生物学重要意义的内酯支架的最直接的方法；然而，具有广泛底物范围的这种转化的多功能催化剂仍然难以捉摸。在此，我们报道了一种简单但广泛适用且可扩展的游离脂肪酸γ-内酯化反应，该反应由铜催化剂与廉价的Selectflu作为氧化剂相结合实现。该内酯化反应表现出与叔键、苄基键、烯丙基键、亚甲基键和伯键 γ-C-H 键的相容性，可生成多种结构多样的内酯，例如螺内酯、稠合内酯和桥连内酯。值得注意的是，观察到环烷羧酸和环烷乙酸的独特γ-亚甲基C-H内酯化，得到稠合或桥联的γ-内酯，这是其他方法难以获得的。仅当存在叔δ-C-H键时，才利于δ-C-H内酯化。该方法的合成效用通过氨基酸、药物分子和天然产物的后期功能化以及(异)薄荷内酯的两步全合成（迄今为止报道的最短合成）得到证明。
• ISMAILOV A. G.; PYCTAMOB M. A.; AXMEDOV A. A., ZH. ORGAN. XIMII, 1980, 16, HO 1, 68-73
  作者：ISMAILOV A. G.、 PYCTAMOB M. A.、 AXMEDOV A. A.

  DOI：——

  日期：——
• ISMAJLOV A. G.; GASHIMOV G. A.; PYCTAMOB M. A., AZEHRB. KIMJA ZH., AZERB. XIM. ZH., 1979, HO 6, 58-61
  作者：ISMAJLOV A. G.、 GASHIMOV G. A.、 PYCTAMOB M. A.

  DOI：——

  日期：——