8a-Pyridin-2-ylmethyl-2-(2,2,2-trifluoro-ethyl)-tetrahydro-imidazo[1,5-a]pyrazine-1,3-dione | 218952-63-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 8a-Pyridin-2-ylmethyl-2-(2,2,2-trifluoro-ethyl)-tetrahydro-imidazo[1,5-a]pyrazine-1,3-dione
• 英文别名: 8a-Pyridin-2-ylmethyl-2-(2,2,2-trifluoro-ethyl)-tetrahydro-imidazol[1.5-a]pyrazine-1,3-dione；8a-(pyridin-2-ylmethyl)-2-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1,3-dione
• CAS: 218952-63-7
• 化学式: C₁₄H₁₅F₃N₄O₂
• 分子量: 328.294
• InChiKey: UCZGQLWFDZVBER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8a-Pyridin-2-ylmethyl-2-(2,2,2-trifluoro-ethyl)-tetrahydro-imidazo[1,5-a]pyrazine-1,3-dione 在 D-酒石酸 作用下， 以 水 、 丙酮 为溶剂， 反应 48.0h， 生成 1,3-dioxo-8a-(S)-pyridin-2-ylmethyl-2-(2,2,2-trifluoro-ethyl)-hexahydro-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Combinations of &bgr;3 agonists and growth hormone secretagogues

  摘要：

  这项发明涉及包括β3肾上腺素受体激动剂在内的药物组合物，其中包括(4-(2-(2-(6-氨基吡啶-3-基)-2(R)-羟乙基氨基)乙氧基)苯乙酸)和生长激素或生长激素促分泌剂，以及这些化合物或其前药的药用可接受盐。该发明还涉及使用这些组合物治疗动物中的肥胖、糖尿病、高血压和衰弱，特别是在人类中的方法。

  公开号：

  US06657063B1
• 作为产物：
  描述：

  1,3-dioxo-8a-(S)-pyridin-2-ylmethyl-2-(2,2,2-trifluoro-ethyl)-hexahydro-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester 以78%的产率得到8a-Pyridin-2-ylmethyl-2-(2,2,2-trifluoro-ethyl)-tetrahydro-imidazo[1,5-a]pyrazine-1,3-dione
  参考文献：
  名称：

  Combinations of &bgr;3 agonists and growth hormone secretagogues

  摘要：

  这项发明涉及包括β3肾上腺素受体激动剂在内的药物组合物，其中包括(4-(2-(2-(6-氨基吡啶-3-基)-2(R)-羟乙基氨基)乙氧基)苯乙酸)和生长激素或生长激素促分泌剂，以及这些化合物或其前药的药用可接受盐。该发明还涉及使用这些组合物治疗动物中的肥胖、糖尿病、高血压和衰弱，特别是在人类中的方法。

  公开号：

  US06657063B1

文献信息

• Process and intermediates for growth hormone secretagogues
  申请人：Pfizer Inc.

  公开号：US06297380B1

  公开（公告）日：2001-10-02

  This invention relates to a process for preparing compounds of the Formula I, wherein R1, R2 and Pt are as defined in the specification, which are intermediates in the synthesis of certain growth hormone secretagogue compounds. This invention further relates to processes for preparing the growth hormone secretagogues. The invention also relates to the compound of Formula I wherein R1 is H, R2 is 2,2,2-trifluoromethyl and Pt is Boc.

  本发明涉及一种制备公式I中化合物的过程，其中R1、R2和Pt如规范中所定义，这些化合物是某些生长激素分泌素化合物合成的中间体。本发明还涉及制备生长激素分泌素的过程。本发明还涉及公式I中R1为H，R2为2,2,2-三氟甲基，Pt为Boc的化合物。
• Melanocortin receptor ligands
  申请人：——

  公开号：US20020072604A1

  公开（公告）日：2002-06-13

  A compound of the formula 1 wherein R 3 , R 4 , R 6 , R 7 , X 4 , Q and HET are as defined above, useful for the treatment or prevention of disorders, diseases or conditions responsive to the activation of melanocortin receptor.

  一种化合物，其化学式为1，其中R3、R4、R6、R7、X4、Q和HET的定义如上所述，用于治疗或预防对黑色素细胞激素受体激活敏感的疾病、疾病或病情。
• Dipeptide derivatives
  申请人：——

  公开号：US20010041703A1

  公开（公告）日：2001-11-15

  This invention is directed to compounds of the formula 1 and the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the Specification, which are growth hormone secretogogues and which increase the level of endogenous growth hormone. The compounds of this invention are useful for the treatment and prevention of osteoporosis and/or frailty, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintenance of skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis and/or frailty when used in combination with: a bisphosphonate compound such as alendronate; estrogen, premarin, and optionally progesterone; an estrogen agonist or antagonist; or calcitonin, and pharmaceutical compositions useful therefor. Further, the present invention is directed to pharmaceutical compositions useful for increasing the endogenous production or release of growth hormone in a human or other animal which comprises an effective amount of a compound of the present invention and a growth hormone secretagogue selected from GHRP-6, Hexarelin, GHRP-1, growth hormone releasing factor (GRF), IGF-1, IGF-2 or B-H-T920. The invention is also directed to intermediates useful in the preparation of compounds of Formula I.

  本发明涉及公式1的化合物及其药学上可接受的盐，其中取代基如规范中所定义，这些化合物是生长激素分泌促进剂，可以增加内源性生长激素的水平。本发明的化合物可用于治疗和预防骨质疏松和/或衰弱、充血性心力衰竭、与衰老有关的衰弱、肥胖症；加速骨折修复、减轻重大手术后的蛋白质分解反应、减少慢性疾病引起的消瘦和蛋白质流失、加速伤口愈合或加速烧伤患者或接受重大手术的患者的恢复；改善肌肉力量、运动能力、皮肤厚度维持、代谢稳态或肾脏稳态。本发明的化合物在与双磷酸盐化合物（如阿伦膦酸）、雌激素、预马林和可选孕激素、雌激素激动剂或拮抗剂或降钙素联合使用时，也可用于治疗骨质疏松和/或衰弱，以及用于该用途的药物组合物。此外，本发明还涉及用于增加人类或其他动物内源性生长激素的产生或释放的药物组合物，该组合物包括本发明化合物的有效量和从GHRP-6、Hexarelin、GHRP-1、生长激素释放因子（GRF）、IGF-1、IGF-2或B-H-T920中选择的生长激素分泌促进剂。本发明还涉及用于制备公式I化合物的中间体。
• Process and hydantoin intermediates for the synthesis of growth hormone secretagogues
  申请人：Pfizer Products Inc.

  公开号：EP1004583A2

  公开（公告）日：2000-05-31

  This invention relates to a process for preparing compounds of the Formula wherein R1, R2 and Pt are as defined in the specification, which are intermediates in the synthesis of certain growth hormone secretagogue compounds. This invention further relates to processes for preparing the growth hormone secretagogues. The invention also relates to the compound of Formula I wherein R1 is H, R2 is 2,2,2-trifluoromethyl and Pt is Boc.

  本发明涉及一种制备式化合物的工艺。 其中 R1、R2 和 Pt 如说明书中所定义，它们是合成某些生长激素促泌剂化合物的中间体。本发明还涉及制备生长激素促泌剂的工艺。本发明还涉及式 I 的化合物，其中 R1 是 H，R2 是 2,2,2-三氟甲基，Pt 是 Boc。
• Growth hormone secretagogues
  申请人：Pfizer Products Inc.

  公开号：EP0995748A1

  公开（公告）日：2000-04-26

  This invention is directed to compounds of the formula and the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the specification, which are growth hormone secretogogues and which increase the level of endogenous growth hormone. The compounds of this invention are useful for the treatment and prevention of osteoporosis, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintanence of skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis when used in combination with: a bisphosphonate compound such as alendronate; estrogen, premarin, and optionally progesterone; a β3 adrenergic receptor agonist; an estrogen agonist or antagonist; or calcitonin, and pharmaceutical compositions useful therefor. Further, the present invention is directed to pharmaceutical compositions useful for increasing the endogenous production or release of growth hormone in a human or other animal which comprises an effective amount of a compound of the present invention and a growth hormone secretagogue selected from GHRP-6, Hexarelin, GHRP-1, growth hormone releasing factor (GRF), IGF-1, IGF-2 or B-HT920.

  本发明涉及式 及其药学上可接受的盐类，其中的取代基如说明书中所定义，它们是生长激素促泌剂，能提高内源性生长激素的水平。本发明的化合物可用于治疗和预防骨质疏松症、充血性心力衰竭、衰老引起的虚弱、肥胖；加速骨折修复，减轻大手术后蛋白质分解反应，减少慢性病引起的恶病质和蛋白质丢失，加速伤口愈合，或加速烧伤病人或接受大手术病人的康复；改善肌肉力量、活动能力、保持皮肤厚度、新陈代谢平衡或肾脏平衡。本发明的化合物与下列物质结合使用时，还可用于治疗骨质疏松症：双膦酸盐化合物，如阿仑膦酸盐；雌激素、前列腺素，以及可选的孕酮；β3肾上腺素能受体激动剂；雌激素激动剂或拮抗剂；或降钙素，以及对其有用的药物组合物。此外，本发明还涉及用于增加人或其他动物生长激素的内源性产生或释放的药物组合物，该组合物包含有效量的本发明化合物和选自 GHRP-6、Hexarelin、GHRP-1、生长激素释放因子（GRF）、IGF-1、IGF-2 或 B-HT920 的生长激素分泌物。