2-咪唑并[1,2-a]嘧啶-7-丙烷-2-醇 | 461451-35-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并[1，2-a]嘧啶
• 中文名称: 2-咪唑并[1,2-a]嘧啶-7-丙烷-2-醇
• 英文名称: 2-(imidazo[1,2-a]pyrimidin-7-yl)propan-2-ol
• 英文别名: 2-Imidazo[1,2-a]pyrimidin-7-yl-propan-2-ol；2-imidazo[1,2-a]pyrimidin-7-ylpropan-2-ol
• CAS: 461451-35-4
• 化学式: C₉H₁₁N₃O
• mdl: MFCD09031440
• 分子量: 177.206
• InChiKey: WIFLLVVTSRUGNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  50.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-咪唑并[1,2-a]嘧啶-7-丙烷-2-醇 在 溴 、 sodium acetate 、 potassium bromide 作用下， 以 甲醇 为溶剂， 生成 2-(3-bromoimidazo[1,2-a]pyrimidin-7-yl)propan-2-ol
  参考文献：
  名称：

  Efficient Synthesis of a GABA_A α_2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach

  摘要：

  A practical synthesis of 2- [3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo [1,2-a] pyrimidin-7-yl] -propan-2-ol (1), an oral GABA(A) alpha(2/3)-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.

  DOI：

  10.1021/jo050741o
• 作为产物：
  描述：

  3-羟基-3-甲基-2-丁酮 在 4-二甲氨基吡啶 、 乙醇 、 三氟化硼乙醚 、 sodium methylate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 30.45h， 生成 2-咪唑并[1,2-a]嘧啶-7-丙烷-2-醇
  参考文献：
  名称：

  Efficient Synthesis of a GABA_A α_2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach

  摘要：

  A practical synthesis of 2- [3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo [1,2-a] pyrimidin-7-yl] -propan-2-ol (1), an oral GABA(A) alpha(2/3)-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.

  DOI：

  10.1021/jo050741o

文献信息

• [EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF DISEASES<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES ASSOCIÉES POUR LE TRAITEMENT DE MALADIES
  申请人：GALAPAGOS NV

  公开号：WO2020239658A1

  公开（公告）日：2020-12-03

  The present invention discloses compounds according to Formula (I), wherein R1a, R1b, R1c, R2a, W1, W2, X1, X2, X3, Y, and Z are as defined herein. The present invention relates to compounds, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of inflammatory diseases, autoinflammatory diseases, autoimmune diseases, proliferative diseases, fibrotic diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformation, diseases involving impairment of bone turnover, diseases associated with hypersecretion of IL-6, diseases associated with hypersecretion of TNFα, interferons, IL-12 and/or IL-23, respiratory diseases, endocrine and/or metabolic diseases, cardiovascular diseases, dermatological diseases, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.

  本发明公开了根据式（I）的化合物，其中R1a、R1b、R1c、R2a、W1、W2、X1、X2、X3、Y和Z如本文所定义。本发明涉及化合物、其生产方法、包括其在内的制药组合物，以及使用这些化合物进行预防和/或治疗炎症性疾病、自身炎症性疾病、自身免疫性疾病、增生性疾病、纤维化疾病、移植排斥、涉及软骨周转障碍的疾病、先天软骨畸形、涉及骨周转障碍的疾病、与IL-6过度分泌有关的疾病、与TNFα、干扰素、IL-12和/或IL-23过度分泌有关的疾病、呼吸系统疾病、内分泌和/或代谢性疾病、心血管疾病、皮肤病和/或异常血管生成相关疾病的治疗方法，通过给予本发明的化合物。
• Imidazo-pyrimidine derivatives as ligands for gaba receptors
  申请人：——

  公开号：US20020193385A1

  公开（公告）日：2002-12-19

  A class of 3-phenylimidazo[1,2-&agr;]pyrimidine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a —NH— linkage, and further substituted on the phenyl ring by alkyl, trifluoromethyl, alkoxy or one or two halogen atoms, especially fluoro, are selective ligands for GABA A receptors, in particular having good affinity for the &agr;2 and/or &agr;3 and/or &agr;5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

  一类3-苯基咪唑[1,2-&agr;]嘧啶衍生物，苯环的间位被取代，取代基可以是直接连接或通过氧原子或-NH-键桥接的取代芳基或杂环芳基，苯环上进一步被取代为烷基，三氟甲基，烷氧基或一个或两个卤素原子，特别是氟，是GABAA受体的选择性配体，特别是对其中的&agr;2和/或&agr;3和/或&agr;5亚基具有良好的亲和力，因此对于治疗和/或预防中枢神经系统的不良症状，包括焦虑，惊厥和认知障碍具有益处。
• Imidazo-pyrimidine derivatives as ligands for GABA receptors
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US07030128B2

  公开（公告）日：2006-04-18

  A class of imidazo[1,2-α]pyrimidine derivatives, substituted at the 3-position by an optionally substituted five-membered or six-membered heteroaromatic ring, are selective ligands for GABAA receptors, in particular having good affinity for the α2 and/or α3 and/or α5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

  一类在3位取代了一个选择性取代的五元或六元杂环芳香环的咪唑[1,2-α]嘧啶衍生物是GABAA受体的选择性配体，尤其对其中的α2和/或α3和/或α5亚基具有良好的亲和力，因此对于治疗和/或预防中枢神经系统的不良症状，包括焦虑、抽搐和认知障碍具有益处。
• IMIDAZO-PYRIMIDINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP1381606B1

  公开（公告）日：2005-07-20
• Efficient Synthesis of a GABA_A α_2,3-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach
  作者：Mark S. Jensen、R. Scott Hoerrner、Wenjie Li、Dorian P. Nelson、Gary J. Javadi、Peter G. Dormer、Dongwei Cai、Robert D. Larsen

  DOI：10.1021/jo050741o

  日期：2005.7.1

  A practical synthesis of 2- [3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo [1,2-a] pyrimidin-7-yl] -propan-2-ol (1), an oral GABA(A) alpha(2/3)-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.