2-amino-N-((R)-1-((S)-3a-benzyl-2-ethyl-3-oxo-2,3,3a,4,6,7-hexahydropyrazolo[4,3-c]pyridin-5-yl)-3-(benzyloxy)-1-oxopropan-2-yl)-2-methylpropanamide | 193273-84-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-amino-N-((R)-1-((S)-3a-benzyl-2-ethyl-3-oxo-2,3,3a,4,6,7-hexahydropyrazolo[4,3-c]pyridin-5-yl)-3-(benzyloxy)-1-oxopropan-2-yl)-2-methylpropanamide
• 英文别名: N-[(2R)-1-[(3aS)-3a-benzyl-2-ethyl-3-oxo-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]-1-oxo-3-phenylmethoxypropan-2-yl]-2-amino-2-methylpropanamide
• CAS: 193273-84-6
• 化学式: C₂₉H₃₇N₅O₄
• 分子量: 519.6
• InChiKey: UBEBVVBBTDUZKB-BTYSJIOQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  6

文献信息

• [EN] GROWTH-HORMONE SECRETAGOGUES<br/>[FR] COMPOSES SECRETAGOGUES D'HORMONE DE CROISSANCE
  申请人：PFIZER INC.

  公开号：WO1997024369A1

  公开（公告）日：1997-07-10

  (EN) This invention is directed to compounds of formula (I) and the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the Specification, which are growth hormone secretagogues 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, maintenance 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; 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. The invention is also directed to intermediates useful in the preparation of compounds of formula (I).(FR) L'invention concerne des composés représentés par la formule (I), ainsi que leurs sels acceptables sur le plan pharmaceutique, dans laquelle les substituants sont tels qu'ils sont définis dans la description, qui sont des sécrétagogues de l'hormone de croissance et qui augmentent le niveau de l'hormone de croissance endogène. Ces composés sont utiles pour traiter et prévenir l'ostéoporose, l'insuffisance cardiaque congestive, la fragilité associée au vieillissement, l'obésité, pour accélérer la réparation des fractures osseuses, atténuer la réaction catabolique protéique après une opération lourde, limiter la cachexie et la perte protéique dues à une maladie chronique, accélérer la cicatrisation des lésions ou la covalescence de patients brûlés ou de patients ayant subi une intervention de chirurgie lourde, améliorer la résistance musculaire, la mobilité, le maintien de l'épaisseur de la peau, l'homéostasie métabolique ou l'homéostasie rénale. Ces composés sont également utiles pour traiter l'ostéoporose quand on les utilise en combinaison avec un composé bisphophate, tel qu'alendronate, des oestrogènes, prémarine et, éventuellement, progestérone, un agoniste ou un antagoniste d'oestrogène, ou calcitonine, ainsi qu'avec des compositions pharmaceutiques utiles à cet effet. L'invention concerne, de plus, des compositions pharmaceutiques utiles pour augmenter la production endogène ou la libération d'hormone de croissance chez l'homme ou chez l'animal, et comprenant une dose efficace d'un composé de l'invention et un sécrétagogue d'hormone de croissance sélectionné parmi GHRP-6, Hexareline, GHRP-1, le facteur de libération de l'hormone de croissance (GRF), IGF-1, IGF-2 ou B-HT920. L'invention concerne également des intermédiaires utiles pour préparer les composés représentés par la formule (I).

  本发明涉及公式（I）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素，可增加内源性生长激素的水平。本发明的化合物对于治疗和预防骨质疏松症、充血性心力衰竭、与衰老有关的虚弱、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丢失、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、皮肤厚度的维护、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，如阿伦膦酸盐；雌激素，前马林，可选孕激素；雌激素激动剂或拮抗剂；或降钙素结合使用时，也可用于治疗骨质疏松症，以及用于此目的的药物组合物。此外，本发明还涉及在人类或其他动物中增加内源性生长激素产生或释放的药物组合物，该组合物包括本发明的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-HT920中选择的生长激素分泌素。本发明还涉及用于制备公式（I）化合物的中间体。
• Growth-hormone secretagogues
  申请人：——

  公开号：US20020049196A1

  公开（公告）日：2002-04-25

  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, 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 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-HT920. 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，是生长激素分泌素，能够增加内源性生长激素的水平。本发明的化合物用于治疗和预防骨质疏松症、充血性心力衰竭、与衰老有关的虚弱、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、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（如阿仑膦酸盐）、雌激素、孕马血浆、以及可选的孕激素搭配使用时，也有用于治疗骨质疏松症的作用，或与降钙素一起使用，以及药学组合物的使用方法。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产生或释放的药学组合物，该组合物包括本发明化合物的有效量和选择自GHRP-6、Hexarelin、GHRP-1、生长激素释放因子（GRF）、IGF-1、IGF-2或B-HT920的生长激素分泌素。本发明还涉及用于制备公式I化合物的中间体。
• GHRELIN RECEPTOR AGONIST FOR TREATMENT OF DYSCRASIA
  申请人：RaQualia Pharma Inc

  公开号：EP2540721A1

  公开（公告）日：2013-01-02

  The present invention relates to use of a compound of the present invention or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the compound or the salt, for the manufacture of a medicament for the treatment of cachexia. The invention also relates to a method for the treatment of cachexia, comprising administering the compound of the present invention or a pharmaceutical composition comprising the same to a human or an animal. The invention further relates to use of said compound, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the compound or the salt, in combination with one or more second active agents. Moreover, the invention relates to a pharmaceutical composition and a kit comprising the compound of the present invention or a pharmaceutically acceptable salt thereof, for the treatment of said disease.

  本发明涉及使用本发明化合物或其药学上可接受的盐，或包含本发明化合物或盐的药物组合物制造治疗恶病质的药物。本发明还涉及一种治疗恶病质的方法，包括向人或动物施用本发明化合物或包含本发明化合物的药物组合物。本发明还涉及将所述化合物或其药学上可接受的盐，或包含该化合物或盐的药物组合物与一种或多种第二活性剂结合使用。此外，本发明还涉及一种药物组合物和一种包含本发明化合物或其药学上可接受的盐的试剂盒，用于治疗所述疾病。
• Ghrelin receptor agonist for treatment of cachexia
  申请人：Shimada Kaoru

  公开号：US10975070B2

  公开（公告）日：2021-04-13

  The present invention relates to use of a compound of the present invention or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the compound or the salt, for the manufacture of a medicament for the treatment of cachexia. The invention also relates to a method for the treatment of cachexia, comprising administering the compound of the present invention or a pharmaceutical composition comprising the same to a human or an animal. The invention further relates to use of said compound, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the compound or the salt, in combination with one or more second active agents. Moreover, the invention relates to a pharmaceutical composition and a kit comprising the compound of the present invention or a pharmaceutically acceptable salt thereof, for the treatment of said disease.

  本发明涉及使用本发明化合物或其药学上可接受的盐，或包含本发明化合物或盐的药物组合物制造治疗恶病质的药物。本发明还涉及一种治疗恶病质的方法，包括向人或动物施用本发明化合物或包含本发明化合物的药物组合物。本发明还涉及将所述化合物或其药学上可接受的盐，或包含该化合物或盐的药物组合物与一种或多种第二活性剂结合使用。此外，本发明还涉及一种药物组合物和一种包含本发明化合物或其药学上可接受的盐的试剂盒，用于治疗所述疾病。
• GROWTH-HORMONE SECRETAGOGUES
  申请人：PFIZER INC.

  公开号：EP0869968B1

  公开（公告）日：2007-05-02