(S)-4-氨基-5-(4,4-二甲基环己基氨基)-5-氧代戊酸 | 163000-63-3

• 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
• 中文名称: (S)-4-氨基-5-(4,4-二甲基环己基氨基)-5-氧代戊酸
• 英文名称: Neboglamine
• 英文别名: (S)-4-amino-5-(4,4-dimethylcyclohexylamino)-5-oxopentanoic acid；(S)-4-amino-N-(4,4-dimethyl-cyclohexyl)glutamic acid；(S)-4-amino-N-(4,4-dimethylcyclohexyl)glutamic acid；(4S)-4-amino-5-[(4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid
• CAS: 163000-63-3
• 化学式: C₁₃H₂₄N₂O₃
• 分子量: 256.345
• InChiKey: VCRGLZYPNNAVRP-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  92.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  螺谷胺 、 (S)-4-氨基-5-(4,4-二甲基环己基氨基)-5-氧代戊酸 在 氯甲酸乙酯 、 三乙胺 作用下， 生成 (4S)-4-[[(4R)-5-(8-azaspiro[4.5]decan-8-yl)-4-[(3,5-dichlorobenzoyl)amino]-5-oxopentanoyl]amino]-5-[(4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid
  参考文献：
  名称：

  Structure−Antigastrin Activity Relationships of New Spiroglumide Amido Acid Derivatives

  摘要：

  A series of new spiroglumide amido acid derivatives was synthesized and evaluated for their ability to inhibit the binding of cholecystokinin (CCK) to guinea pig brain cortex (CCKB receptors) and peripheral rat pancreatic acini (CCKA receptors), as well as to inhibit in vitro the gastrin-induced Ca2+ increase in rabbit gastric parietal cells. Appropriate chemical manipulations of the structure of spiroglumide (CR 2194), i.e., (R)-4-(3,5-dichlorobenzamido)-5-(8-azaspiro[4,5]decan-8-yl)-5-oxopentanoic acid, led to potent and selective antagonists of CCKB/gastrin receptors. Structure-activity relationships are discussed. Some of these new derivatives, as, for example, compound 54 (CR 2622), i.e., (S)-4-[[(R)-4'-[(3,5-dichlorobenzoyl)amino]-5'-(8-azaspiro[4.5] decan-8-yl)-5'-oxo-pentanonyl]amino]-5-(1-naphthylamino)-5- oxopentanoic acid, exhibit activity 70-170 times greater than that of spiroglumide, depending upon the model used (IC50 = 2 x 10(-8) vs 140 x 10(-8) mol in binding inhibition of [H-3]-N-Me-N-Leu-CCK-8 in guinea pig brain cortex and IC50 = 0.7 x 10(-8) vs 122.3 x 10(-8) mol in inhibition of gastrin-induced Ca2+ mobilization in parietal cells of rabbit, respectively). Computer-assisted conformational analysis studies were carried out in order to compare the chemical structure of both the agonist (pentagastrin) and the antagonist (54).

  DOI：

  10.1021/jm950372w
• 作为产物：
  描述：

  以55的产率得到(S)-4-氨基-5-(4,4-二甲基环己基氨基)-5-氧代戊酸
  参考文献：
  名称：

  Derivatives of glutamic and aspartic acids, a method of preparing them,

  摘要：

  通式(I)和(II)所代表的化合物，其中r为1或2，R.sub.2和R.sub.3独立地选择自H、CH.sub.3、C.sub.2 H.sub.5和CHO，但要求R.sub.2和R.sub.3不能同时为CHO，而R.sub.1从以下选取：氨基烷基金刚烷基、单环氨基烷基、双环氨基螺环基、双环氨基基(正融合)、双环氨基基、氮杂环烷基、氮杂双环基(正融合)、双环氮杂螺环基、氮杂双环基和氮杂环烷基，以及线性或支链氨基烷基。

  公开号：

  US05723494A1

文献信息

• Conjugates of glutamate and NMDA receptor channel blockers without excito-toxic effects
  申请人：Tschollar,, Werner

  公开号：EP1903028A1

  公开（公告）日：2008-03-26

  Methods for delivering therapeutic amounts of glutamate to the CNS while simultaneously protecting against its excito-toxic effects are provided. By administering a blood-brain barrier-permeable Conjugate Compound, which comprises glutamate linked to an N-methyl-D-aspartate receptor antagonist, glutamate is released within the CNS for beneficial effect without causing excito-toxicity. Examples of such Conjugate Compounds are provided and their cognition-enhancing effect without engendering excito-toxicity in both normal and cognition-impaired animals is demonstrated.

  本研究提供了向中枢神经系统输送治疗量谷氨酸的方法，同时防止其兴奋毒性效应。通过施用可透过血脑屏障的共轭化合物（其中包括与 N-甲基-D-天冬氨酸受体拮抗剂相连的谷氨酸），谷氨酸可在中枢神经系统内释放，从而产生有益效果，同时不会导致兴奋毒性。本文提供了此类共轭化合物的实例，并证明了它们在正常动物和认知障碍动物中的认知增强效果，而不会产生兴奋毒性。
• USE OF NEBOGLAMINE (CR 2249) AS AN ANTIPSYCHOTIC AND NEUROPROTECTIVE
  申请人：ROTTAPHARM S.P.A.

  公开号：EP1755583A1

  公开（公告）日：2007-02-28
• USE OF NEBOGLAMINE FOR THE TREATMENT OF SCHIZOPHRENIA
  申请人：ROTTAPHARM S.P.A.

  公开号：EP1755583B1

  公开（公告）日：2010-04-14
• USE OF NEBOGLAMINE IN THE TREATMENT OF TOXICODEPENDENCY
  申请人：ROTTAPHARM S.P.A.

  公开号：EP1940376A2

  公开（公告）日：2008-07-09
• Use of Neboglamine (Cr 2249) as an Antipsychotic and Neuroprotective
  申请人：Makovec Francesco

  公开号：US20070249715A1

  公开（公告）日：2007-10-25

  Use of neboglamine, (S)-4-amino-N-(4,4-dimethylcyclohexyl)glutamic acid (CR 2249) (CAS Registry Number 163000-63-3), of the racemate thereof or of a pharmaceutically acceptable salt thereof for the preparation of a medicament for the treatment of schizophrenia.