2-(3-hydroxycyclohexyl)acetic acid | 86576-85-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(3-hydroxycyclohexyl)acetic acid
• CAS: 86576-85-4
• 化学式: C₈H₁₄O₃
• 分子量: 158.197
• InChiKey: KEPYKFNXJFNSDL-UHFFFAOYSA-N

物化性质

• 沸点：
  326.4±15.0 °C(Predicted)
• 密度：
  1.166±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-hydroxycyclohexyl)acetic acid 在 氯化亚砜 、 三苯基膦 、 lithium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 1.5h， 生成 (±)-trans-2-(3-(4-(4-(((cyclopentyl(methyl)carbamoyl)oxy)methyl)-3-methylisoxazol-5-yl)phenoxy)cyclohexyl)acetic acid
  参考文献：
  名称：

  发现用于治疗肺纤维化疾病的氧环己酸溶血磷脂酸受体 1 (LPA1) 拮抗剂 BMS-986278

  摘要：

  氧环己酸 BMS-986278 ( 33 ) 是一种有效的溶血磷脂酸受体 1 (LPA 1 ) 拮抗剂，人类 LPA 1 K b为 6.9 nM。讨论了从 LPA 1拮抗剂临床化合物 BMS-986020 ( 1 )开始的构效关系 (SAR) 研究，最终发现了33。详细的体外和体内临床前药理学概况33，以及它的药代动力学/代谢特征，进行了描述。基于其在啮齿动物慢性肺纤维化模型中的体内功效以及在多个临床前物种中优异的整体 ADME（吸收、分布、代谢、排泄）特性，33 项已进入临床试验，包括正在进行的 2 期临床试验。肺纤维化 (NCT04308681)。

  DOI：

  10.1021/acs.jmedchem.1c01256
• 作为产物：
  描述：

  3-羟基苯乙酸 在 Rh on carbon 氢气 作用下， 以 sodium hydroxide 为溶剂， 60.0 ℃ 、101.32 kPa 条件下， 反应 3.0h， 以99%的产率得到2-(3-hydroxycyclohexyl)acetic acid
  参考文献：
  名称：

  一些2,4-二氧杂-和2,4-二氧杂-3-硅双环[3.3.1]壬烷的合成与构象

  摘要：

  通过13 C和1 H NMR光谱确定的标题化合物的构象表明，双环[3.3.1]壬烷中的2-和4-亚甲基被醚氧原子取代会严重破坏cc的构象：在2-oxabicyclocyclo [ 3.3.1]-壬烷的cc和bc构象异构体大约相等，而在2,4-二恶双环[3.3.1]壬烷中，bc的构象占优势。的2,4-二氧杂-3- silabicyclo [3.3.1]壬烷还主要发生在矿井BC构象。与碳环双环[3.3.1]壬烷一样，两翼都被强烈展平。描述了立体选择性合成的3α-甲基双环[3.3.1]壬烷，这项研究中的重要模型化合物。

  DOI：

  10.1016/0040-4020(82)80072-0

文献信息

• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2015180612A1

  公开（公告）日：2015-12-03

  Disclosed are novel retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.

  揭示了新型视黄醇相关孤儿受体γ（RORγ）调节剂及其在通过RORγ介导的疾病治疗中的应用。
• [EN] ISOXAZOLE O-LINKED CARBAMOYL CYCLOHEXYL ACIDS AS LPA ANTAGONISTS<br/>[FR] ACIDES CARBAMOYLE CYCLOHEXYLIQUES À LIAISON O ISOXAZOLE UTILISÉS EN TANT QU'ANTAGONISTES DE LPA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2019126084A1

  公开（公告）日：2019-06-27

  The present invention provides compounds of Formula (Ia) or (Ib) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein 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, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxy, alkoxyalkyi, haloalkoxyallcyl, or haloalkoxy; n is an integer of 0, 1, or 2; R3 is hydrogen, C1-6 alkyl, C1-6 deuterated alkyl, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyi, 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 haloalkyi, 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, C1-6 alkyl, 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)的化合物或其立体异构体、互变异构体或药学上可接受的盐或溶剂，其中X1、X2、X3和X4分别独立地为CR6或N；但X1、X2、X3或X4中不超过两个为N；L为C1-4烷基，其上取代有0至4个R7；R1为(-CH2)aR9；a为0或1的整数；R2分别为卤素、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、卤代烷氧基烷基或卤代烷氧基；n为0、1或2的整数；R3为氢、C1-6烷基、C1-6氘代烷基、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，烷基本身或作为其他基团的一部分，可以部分或完全地被氘取代；R4为C1-10烷基、C1-10氘代烷基、C1-10卤代烷基、C1-10烯基、C3-8环烷基、6至10成员芳基、3至8成员杂环烷基、-(C1-6烷基)-(C3-8环烷基)、-(C1-6烷基)-(6至10成员芳基)、-(C1-6烷基)-(3至8成员杂环烷基)或-(C1-6烷基)-(5至6成员杂芳基)；其中烷基、烷基烯烃、烷烃、芳基、杂环烷基和杂芳基中的每一个，本身或作为其他基团的一部分，可以独立地被0至3个R8取代；或者，R3和R4，与它们连接的N原子一起，形成一个取代有0至3个R的4至9成员杂环基团；R5和R6分别独立地为氢、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、烷氧基或卤代烷氧基；R7为卤素、氧、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分别独立地为氘、卤素、羟基、氨基、氰基、C1-6烷基、C1-6氘代烷基、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至6成员杂芳基；或者，两个R8，与它们连接的原子一起，形成一个取代有0至3个R12的3至6成员碳环基或3至6成员杂环基；R9从-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、四唑-5-基亚甲基中选择；Re为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；R10为氢或C1-10烷基；R11a和R11b分别独立地为氢、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、烷氧基或卤代烷氧基；R12为卤素、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、烷氧基或卤代烷氧基、苯基或5至6成员杂芳基。这些化合物是选择性的LPA受体抑制剂。
• BENZOYL-PIPERIDINE DERIVATIVES AS DUAL MODULATORS OF THE 5-HT2A AND D3 RECEPTORS
  申请人：Gobbi Luca

  公开号：US20090042943A1

  公开（公告）日：2009-02-12

  The present invention relates to compounds of formula (I) wherein R 1 and A are as defined in the specification as dual modulators of the serotonin 5-HT 2a and dopamine D 3 receptors, their manufacture, pharmaceutical compositions containing them and their use as medicaments. Compounds of general formula (I) have high affinity for the dopamine D 3 and serotonin (5-Hydroxytryptamine; 5-HT) 5-HT 2A receptors and are effective in the treatment of psychotic disorders, as well as other diseases such as depression and anxiety, drug dependence, dementias and memory impairment.

  本发明涉及以下式（I）的化合物 其中R 1 和A如说明书中定义的作为血清素5-HT 2a 和多巴胺D 3 受体的双调节剂，它们的制备，含有它们的药物组合物以及它们作为药物的用途。一般式（I）的化合物对多巴胺D 3 和血清素（5-羟色胺；5-HT）5-HT 2A 受体具有高亲和力，并且在治疗精神分裂症等疾病以及抑郁症、焦虑症、药物依赖、痴呆症和记忆障碍等其他疾病中具有有效性。
• 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。
• Some Reactions of Δ²-Cyclohexenone, Including the Synthesis of Bicyclo(2,2,2)-octanedione-2,6
  作者：Paul D. Bartlett、G. Forrest Woods

  DOI：10.1021/ja01868a014

  日期：1940.11