(S)-2-[(azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid benzyl ester | 141595-75-7

• 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: (S)-2-[(azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid benzyl ester
• 英文别名: N-(hexahydro-1H-azepin-1-ylcarbonyl)-L-Leucine benzyl ester；benzyl (2S)-2-(azepane-1-carbonylamino)-4-methylpentanoate
• CAS: 141595-75-7
• 化学式: C₂₀H₃₀N₂O₃
• 分子量: 346.47
• InChiKey: UWTMQVHYHCWLMN-SFHVURJKSA-N

物化性质

• 沸点：
  526.1±29.0 °C(Predicted)
• 密度：
  1.085±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-[(azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid benzyl ester 在 palladium on activated charcoal 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 (S)-Azepane-1-carboxylic acid (1-{2-[(4-benzyloxy-phenyl)-(3-methyl-but-2enyl)-amino]-1,1-dimethyl-ethylcarbamoyl}-3-methyl-butyl)-amide
  参考文献：
  名称：

  Synthesis of a Series of 4-Benzyloxyaniline Analogues as Neuronal N-Type Calcium Channel Blockers with Improved Anticonvulsant and Analgesic Properties

  摘要：

  In this article, the rationale for the design, synthesis, and biological evaluation of a series of N-type voltage-sensitive calcium channel (VSCC) blockers is described. N-Type VSCC blockers, such as ziconotide, have shown utility in several models of stroke and pain. Modification of the previously reported lead, 1a, led to several 4-(4-benzyloxylphenyl)piperidine structures with potent in vitro and in vivo activities. In this series, the most interesting compound, (S)-2-amino- 1-{4-[(4-benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-piperidin-1-yl}-4-methyl-pentan-1-one (11), blocked N-type calcium channels (IC50 = 0.67 mu M in the IMR32 assay) and was efficacious in the audiogenic DBA/2 seizure mouse model (ED50 = 6 mg/kg, iv) as well as the antiwrithing model (ED50 = 6 mg/kg, iv). Whole-cell voltage-clamp electrophysiology experiments demonstrated that compound 11 blocked N-type Ca2+ channels and Na+ channels in superior cervical ganglion neurons at similar concentrations. Compound 11, which showed superior in vivo efficacy, stands out as an interesting lead for further development of neurotherapeutic agents in this series.

  DOI：

  10.1021/jm9902739
• 作为产物：
  描述：

  L-Leucin-benzylester-isocyanat 生成 (S)-2-[(azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid benzyl ester
  参考文献：
  名称：

  Peptide compound and its preparation

  摘要：

  公开了具有以下结构的新型肽（I"）##STR1##其中R.sup.1是氢或酰基，R.sup.2.sub.c是较低的烷基，R.sup.3.sub.c是可选的N-取代吲哚甲基，R.sup.4是氢，较低的烷基，C.sub.6-10 ar(lower)alkyl，氨基（较低）烷基，受保护的氨基（较低）烷基，羧基（较低）烷基，受保护的羧基（较低）烷基，或者可选地取代的杂环（较低）烷基，R.sup.5是羧基，受保护的羧基，羧基（较低）烷基或受保护的羧基（较低）烷基，R.sup.7是氢或较低的烷基，A是--O--，--NH--，较低的烷基氨基或较低的亚烷基，或其药用可接受盐。此外，描述了这类肽的制备方法。这些肽被用于治疗由内皮素介导的疾病，如高血压。

  公开号：

  US05284828A1

文献信息

• Substituted diarylalkyl amides as calcium channel antagonists
  申请人：——

  公开号：US06458781B1

  公开（公告）日：2002-10-01

  The present invention provides compounds that block calcium channels and have the Formula I: The present invention also provides pharmaceutical compositions containing the compounds of Formula I and methods of using them to treat stroke, cerebral ischemia, head trauma, and epilepsy.

  本发明提供了阻断钙通道并具有化学式I的化合物。 本发明还提供了含有化学式I化合物的药物组合物，以及使用它们治疗中风、脑缺血、头部创伤和癫痫的方法。
• Aniline derivatives as calcium channel blockers
  申请人：Warner-Lambert Company

  公开号：US06251918B1

  公开（公告）日：2001-06-26

  The present invention provides compounds that block calcium channels having formula (I). The present invention also provides methods of using the compounds of formula (I) to treat stroke, cerebral ischemia, head trauma, or epilepsy and to pharmaceutical compositions that contain the compounds of formula (I).

  本发明提供了一种阻断钙通道的化合物，其化学式为(I)。本发明还提供了使用化合物(I)治疗中风、脑缺血、头部创伤或癫痫的方法，以及含有化合物(I)的药物组合物。
• Reduced dipeptide analogues as calcium channel antagonists
  申请人：Warner-Lambert Company

  公开号：US06316440B1

  公开（公告）日：2001-11-13

  The present invention provides novel N-type calcium channel blockers, compositions comprising them, and methods of their use. The compounds of the invention are useful in the treatment of stroke, cerebral ischemia, pain, epilepsy, and head trauma. The novel compounds provided by this invention have Formula (1), wherein R1 is H or methyl; R2 is H, azepanylcarbonyl, C1-C7 alkyl, —(CH2)n-phenyl, wherein the phenyl is unsubstituted or substituted with C1-C4 alkyl, C1-C4 alkoxy, or halo; R3 is C1-C5 alkyl; X is —NR4R5 or —OR7; R4 and R5 are independently H, C1-C5 alkyl; or R4 and R5 together with the nitrogen to which they are both bound form formulae (a); (b); (c); (d) or (e); R6 is —(CH2)n-phenyl, wherein the phenyl is unsubstituted or substituted with C1-C4 alkyl, C1-C4 alkoxy, or halo; A and B are independently —CO— or —CH2—, provided that A and B are not both —CO—; R7 is C1-C5 alkyl; Z is —CH2—, —O—, —S—, or —N(R8)—; R8 is H or C1-C6 alkyl; and n is 1 or 2.

  本发明提供了新型N-型钙通道阻滞剂，包含它们的组合物，以及它们的使用方法。本发明的化合物在中风、脑缺血、疼痛、癫痫和头部创伤的治疗中是有用的。本发明提供的新型化合物具有式（1），其中R1为H或甲基；R2为H，氮杂环己酰基，C1-C7烷基，—（CH2）n-苯基，其中苯基未取代或取代为C1-C4烷基，C1-C4烷氧基或卤素；R3为C1-C5烷基；X为—NR4R5或—OR7；R4和R5独立地为H，C1-C5烷基；或R4和R5与它们共价结合的氮原子一起形成式（a）、（b）、（c）、（d）或（e）；R6为—（ ）n-苯基，其中苯基未取代或取代为C1-C4烷基，C1-C4烷氧基或卤素；A和B独立地为—CO—或— —，但A和B不能同时为—CO—；R7为C1-C5烷基；Z为— —，—O—，—S—或—N(R8)—；R8为H或C1-C6烷基；n为1或2。
• [EN] SUBSTITUTED DIARYLALKYL AMIDES AS CALCIUM CHANNEL ANTAGONISTS<br/>[FR] AMIDES DE DIARYLALKYLE SUBSTITUES EN TANT QU'ANTAGONISTES DE CANAUX CALCIQUES
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1999055688A1

  公开（公告）日：1999-11-04

  (EN) The present invention provides compounds that block calcium channels and have Formula (I). The present invention also provides pharmaceutical compositions containing the compounds of Formula (I) and methods of using them to treat stroke, cerebral ischemia, head trauma, and epilepsy.(FR) L'invention concerne des composés de formule (I) inhibant les canaux calciques. L'invention concerne également des compositions pharmaceutiques renfermant les composés de formule (I) et leurs procédés d'utilisation pour traiter les accidents cérébrovasculaires, l'ischémie cérébrale, des traumatismes crâniens et l'épilepsie.

  本发明提供了一种阻断钙通道的化合物，其具有公式（I）。本发明还提供了含有公式（I）化合物的药物组合物以及使用它们治疗中风、脑缺血、头部创伤和癫痫的方法。
• [EN] ANILINE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS<br/>[FR] DERIVES D'ANILINE UTILISES EN TANT QU'INHIBITEURS CALCIQUES
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1999007689A1

  公开（公告）日：1999-02-18

  (EN) The present invention provides compounds that block calcium channels having formula (I). The present invention also privides methods of using the compounds of formula (I) to treat stroke, cerebral ischemia, head trauma, or epilepsy and to pharmaceutical compositions that contain the compounds of formula (I).(FR) L'invention concerne des composés inhibiteurs calciques, de formule (I). Elle se rapporte également à des procédés d'utilisation desdits composés de formule (I) pour le traitement de l'attaque, de l'ischémie cérébrale, du traumatisme crânien ou de l'épilepsie, et à des compositions pharmaceutiques contenant les composés de formule (I).

  本发明提供了具有式（I）的阻断钙通道的化合物。本发明还提供了使用式（I）的化合物治疗中风、脑缺血、头部创伤或癫痫的方法，以及含有式（I）的药物组合物。