5,5-difluoro-1-oxaspiro[2.3]hexane | 1197420-24-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 环氧化物
• 英文名称: 5,5-difluoro-1-oxaspiro[2.3]hexane
• CAS: 1197420-24-8
• 化学式: C₅H₆F₂O
• 分子量: 120.099
• InChiKey: RNALRSYAWLFJMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5,5-difluoro-1-oxaspiro[2.3]hexane 在 sodium dihydrogenphosphate dihydrate 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 130.0 ℃ 、344.75 kPa 条件下， 反应 5.0h， 生成 1-((4-amino-2-methoxyphenoxy)methyl)-3,3-difluorocyclobutanol
  参考文献：
  名称：

  6-（4-氯苯基）-3-（4-（（（3,3-二氟-1-羟基环丁基）甲氧基）-3-甲氧基苯基）噻吩并[3,2 - d ]嘧啶-4（3 ）的合成及抗肥胖性H）-一（BMS-814580）：一种高效的黑色素浓缩激素受体1（MCHR1）抑制剂

  摘要：

  描述了衍生自化合物2b的一系列环状叔醇在体外和体内的有效MCHR1拮抗活性。随后的药代动力学和药效学研究确定BMS-814580（化合物10）为高效抗肥胖药，具有相对干净的体外和体内安全性。

  DOI：

  10.1021/acs.jmedchem.6b00676
• 作为产物：
  描述：

  3,3-二氟环丁烷羧酸 在 lithium aluminium tetrahydride 、 草酰氯 、 双氧水 、 N,N-二甲基甲酰胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 42.5h， 生成 5,5-difluoro-1-oxaspiro[2.3]hexane
  参考文献：
  名称：

  6-（4-氯苯基）-3-（4-（（（3,3-二氟-1-羟基环丁基）甲氧基）-3-甲氧基苯基）噻吩并[3,2 - d ]嘧啶-4（3 ）的合成及抗肥胖性H）-一（BMS-814580）：一种高效的黑色素浓缩激素受体1（MCHR1）抑制剂

  摘要：

  描述了衍生自化合物2b的一系列环状叔醇在体外和体内的有效MCHR1拮抗活性。随后的药代动力学和药效学研究确定BMS-814580（化合物10）为高效抗肥胖药，具有相对干净的体外和体内安全性。

  DOI：

  10.1021/acs.jmedchem.6b00676

文献信息

• [EN] MAP4K4 INHIBITORS<br/>[FR] INHIBITEURS DE MAP4K4
  申请人：IMPERIAL INNOVATIONS LTD

  公开号：WO2019073253A1

  公开（公告）日：2019-04-18

  This invention relates to pyrrolopyrimidine comprising compounds that may be useful as inhibitors of Mitogen-activated Protein Kinase Kinase Kinase Kinase-4 (MAP4K4). The invention also relates to the use of these pyrrolopyrimidine comprising compounds, for example in a method of treatment. There are also provided processes for producing compounds of the present invention and method of their use. In particular, the present invention relates to compounds of formula (I).

  这项发明涉及含有吡咯吡嘧啶的化合物，这些化合物可能作为丝裂原活化蛋白激酶激酶激酶激酶-4（MAP4K4）的抑制剂而有用。该发明还涉及利用这些含有吡咯吡嘧啶的化合物，例如在治疗方法中的使用。还提供了生产本发明化合物的方法以及它们的使用方法。具体而言，本发明涉及式（I）的化合物。
• [EN] PYRROLONE MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR D'HORMONE CONCENTRANT LA MÉLANINE 1 DE TYPE PYRROLONE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010042674A1

  公开（公告）日：2010-04-15

  The present application provides compounds, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I wherein R1, Formula Ia, R4, R5, Formula Ib, R3, R3a, W, D, R2a, R2b and R2c are defined herein. Additionally, the present application provides pharmaceutical compositions containing at least one compound according to Formula I and optionally at least one additional therapeutic agent. Finally, the present application provides methods for treating a patient suffering from an MCHR-1 modulated disease or disorder such as, for example, obesity, diabetes, depression, anxiety or intestinal inflammation, by administration of a therapeutically effective dose of a compound according to Formula I.

  本申请提供了根据公式I提供的化合物，包括所有立体异构体、溶剂合物、前药和药用可接受形式，其中R1、公式Ia、R4、R5、公式Ib、R3、R3a、W、D、R2a、R2b和R2c在此处定义。此外，本申请提供了含有至少一种根据公式I的化合物和可选至少一种额外治疗剂的药物组合物。最后，本申请提供了治疗患有MCHR-1调节性疾病或紊乱的患者的方法，例如肥胖、糖尿病、抑郁症、焦虑或肠道炎症，通过给予根据公式I的化合物的治疗有效剂量。
• [EN] SPIROHEPTANE SALICYLAMIDES AND RELATED COMPOUNDS AS INHIBITORS OF ROCK<br/>[FR] SALICYLAMIDES DE SPIROHEPTANE ET COMPOSÉS ASSOCIÉS UTILISÉS COMME INHIBITEURS DE ROCK
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2017123860A1

  公开（公告）日：2017-07-20

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically-acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective ROCK inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating cardiovascular, smooth muscle, oncologic, neuropathologic, autoimmune, fibrotic, and/or inflammatory disorders using the same.

  本发明提供了式(I)的化合物：或立体异构体、互变异构体或药用可接受的盐，其中所有变量如本文所述定义。这些化合物是选择性的ROCK抑制剂。本发明还涉及包含这些化合物的药物组合物以及使用同一化合物治疗心血管、平滑肌、肿瘤学、神经病理学、自身免疫、纤维化和/或炎症性疾病的方法。
• [EN] AZOLOTRIAZINONE MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR-1 D'HORMONE DE MÉLANO-CONCENTRATION D'AZOLOTRIAZINONE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010042682A1

  公开（公告）日：2010-04-15

  The present application provides compounds that are useful as MCHR1 antagonists, especially for the treatment of obesity, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I, wherein R1, is selected from the group consisting of monocyclic aryl or monocyclic heteroaryl; W is selected from the group consisting of a direct bond, -O-, and -N(R6)-; provided that if W is a direct bond, D is a cyclic amine that is attached to A via the nitrogen atom of the cyclic amine; D is selected from the group consisting of a direct bond, substituted or unsubstituted C1 to C4 alkyl, substituted or unsubstituted C3 to C7 cycloalkyl, cycloalkylalkyl, and 4- to 6-membered cyclic amines, provided that if D is a direct bond, R2a, R2b, and R2c must be selected from H, alkyl, or cycloalkyl; E and G are independently N or CH provided that both are not N; R1 is substituted or unsubstituted phenyl or substituted or unsubstituted monocyclic heteroaryl; R2a, R2b, and R2c are independently selected from the group consisting of hydrogen, halo, cyano, hydroxyl, -NR5R5a, -SO2R34, -CO2R35 -NR5CO2R21, -NR5COR21, substituted or unsubstituted C1 to C4 alkyl, substituted or unsubstituted C3 to C7 cycloalkyl, substituted or unsubstituted 4- to 6-membered cyclic amines wherein said cyclic amine is optionally substituted with -OH, carbonylamino, alkoxycarbonylamino, or at least one of R2a, R2b, and R2c is a prodrug moiety selected from amino acid esters or phosphoric acid esters wherein said amino acid ester has the formula -OC(O)CH(NH2)R31, wherein R31 is H or C1 to C4 alkyl; or any two of R2a, Rb, or R2c, may be taken together to form a ring; R3 and R3a are each independently selected from the group consisting of hydrogen, hydroxyl, lower alkoxy, halo, CN, substituted or unsubstituted C1 to C4 alkyl, perfluoroalkyl, substituted or unsubstituted C3 to C7 cycloalkyl, cycloalkoxy, amino, alkylamino, dialkylamino, and aminoalkyl, wherein R3 or R3a and D may optionally be taken together with the atoms to which they are attached to form a 5- to 7-membered ring; R5 and R5a are the same or different and are independently selected from the group consisting of hydrogen, substituted or unsubstituted lower alkyl, hydroxyalkyl, hydroxyalkylcycloalkyl, substituted or unsubstituted heterocycloalkyl, acyl, alkoxycarbonyl, carboxyalkyl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted cycloalkylalkyl, wherein the R5 and R5a groups and the N atom to which they are attached may form a ring; R21 and R31 are each H or C1 to C4 alkyl; R34 is alkyl; R35 is H or alkyl; and R6 is selected from the group consisting of H, C1 to C4 alkyl and C3 to C7 cycloalkyl.

  本申请提供了作为MCHR1拮抗剂有用的化合物，特别用于肥胖症的治疗，包括所有立体异构体、溶剂化合物、前药和根据式I的药学上可接受的形式，其中R1从单环芳基或单环杂芳基组成的群体中选择；W从直接键、-O-和-N(R6)-组成的群体中选择；条件是如果W是直接键，则D是通过环胺的氮原子连接到A的环胺；D从直接键、取代或未取代的C1到C4烷基、取代或未取代的C3到C7环烷基、环烷基烷基和4-到6-成员环胺组成的群体中选择，条件是如果D是直接键，则R2a、R2b和R2c必须从H、烷基或环烷基中选择；E和G独立地是N或CH，条件是两者都不是N；R1是取代或未取代的苯基或取代或未取代的单环杂芳基；R2a、R2b和R2c独立地从氢、卤素、氰基、羟基、-NR5R5a、-SO2R34、-CO2R35 -NR5CO2R21、-NR5COR21、取代或未取代的C1到C4烷基、取代或未取代的C3到C7环烷基、取代或未取代的4-到6-成员环胺中选择，其中所述环胺可以选择地取代为-OH、羰基氨基、烷氧羰基氨基，或R2a、R2b和R2c中的至少一个是选择自氨基酸酯或磷酸酯的前药基团，其中所述氨基酸酯具有式-OC(O)CH(NH2)R31，其中R31为H或C1到C4烷基；或R2a、Rb或R2c中的任意两个可以结合形成环；R3和R3a各自独立地从氢、羟基、较低烷氧基、卤素、CN、取代或未取代的C1到C4烷基、全氟烷基、取代或未取代的C3到C7环烷基、环烷氧基、氨基、烷基氨基、二烷基氨基和氨基烷基中选择，其中R3或R3a和D可以选择地结合形成5-到7-成员环；R5和R5a相同或不同，独立地从氢、取代或未取代的较低烷基、羟基烷基、羟基烷基环烷基、取代或未取代的杂环烷基、酰基、烷氧羰基、羧基烷基、取代或未取代的环烷基和取代或未取代的环烷基烷基中选择，其中R5和R5a基团和它们连接的N原子可以形成环；R21和R31各自为H或C1到C4烷基；R34为烷基；R35为H或烷基；R6从H、C1到C4烷基和C3到C7环烷基中选择。
• HYDROXY SUBSTITUTED THIENO PYRIMIDINONES AS MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS
  申请人：Washburn William N.

  公开号：US20090298794A1

  公开（公告）日：2009-12-03

  The present invention provides compounds having the following Formula IA and IB, which are useful as MCHR1 antagonists, and includes prodrugs and pharmaceutically acceptable salts thereof:

  本发明提供了具有以下化学式IA和IB的化合物，这些化合物可作为MCHR1拮抗剂使用，并包括其前药和药用盐：