(2S)-3-cyclohexylmethoxy-2-t-butoxycarbonylaminopropanoic acid | 219626-93-4

• 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: (2S)-3-cyclohexylmethoxy-2-t-butoxycarbonylaminopropanoic acid
• 英文别名: N-(tert-butoxycarbonyl)-O-cyclohexylmethyl-L-serine；(2S)-2-t-butoxycarbonylamino-3-cyclohexylmethoxypropanoic acid；(2S)-3-(cyclohexylmethoxy)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 219626-93-4
• 化学式: C₁₅H₂₇NO₅
• 分子量: 301.383
• InChiKey: OAXCWEOFDZKYGX-LBPRGKRZSA-N

物化性质

• 沸点：
  450.2±40.0 °C(Predicted)
• 密度：
  1.102±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-甲基-4-甲氧基苄胺 、 (2S)-3-cyclohexylmethoxy-2-t-butoxycarbonylaminopropanoic acid 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2S)-N-methyl-N-(4-methoxybenzyl)-3-cyclohexylmethoxy-2-t-butoxycarbonyl-aminopropanamide
  参考文献：
  名称：

  Structure–Activity Study and Analgesic Efficacy of Amino Acid Derivatives as N-Type Calcium Channel Blockers

  摘要：

  The synthesis and structure activity relationship (SAR) study of a novel series of N-type calcium channel blockers are described. L-Cysteine derivative 2a was found to be a potent and selective N-type calcium channel blocker with IC50 0.63 muM on IMR-32 assay. Compound 2a showed analgesic efficacy in the rat formalin-induced pain model by intrathecal and oral administration. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00414-0
• 作为产物：
  描述：

  N-BOC-O-苄基-L-丝氨酸 在 rhodium on alumina 氢气 作用下， 以 异丙醇 为溶剂， 以86%的产率得到(2S)-3-cyclohexylmethoxy-2-t-butoxycarbonylaminopropanoic acid
  参考文献：
  名称：

  基于L氨基酸的N型钙通道阻滞剂的结构活性研究。

  摘要：

  描述了基于L-氨基酸的N型钙通道阻滞剂的合成及其构效关系（SAR）。评价合成的化合物对N型和L型钙通道的抑制活性，重点是降低由于阻断L型钙通道而引起的心血管副作用的选择性。在筛选我们的化合物库的过程中，N-（叔丁氧羰基）-L-天冬氨酸衍生物1a被确定为一系列新的N型钙通道阻滞剂的初始铅化合物，该抑制剂可抑制钙流入IMR- 32个人类神经母细胞瘤细胞，IC（50）为3.4 microM。在使用IMR-32细胞的电生理实验中，化合物1a也显示出N型钙通道电流的阻滞作用（在10 microM处抑制34％，n = 3）。作为1a氨基酸残基转化的结果，发现包含N-（叔丁氧羰基）-L-半胱氨酸的化合物12a是有效的N型钙通道阻滞剂，IC（50）为0.61 microM 。因此，选择L-半胱氨酸作为进一步修饰的潜在结构基序。以S-环己基甲基-L-半胱氨酸为中心支架优化L-半胱氨酸的C和N端可产生有效和选

  DOI：

  10.1016/s0968-0896(02)00558-8

文献信息

• Amino acid derivatives and drugs containing the same as the active ingredient
  申请人：Ono Pharmaceutical Co., Ltd

  公开号：US06605608B1

  公开（公告）日：2003-08-12

  The present invention relates to the compounds of the formula (I) and salts thereof (all the symbols are the same meanings as described in the specification). The compounds of the formula (I) possess inhibitory activity of N-type calcium channel, so they are useful as drug for prevention and/or treatment of cerebral infarct, transient ischemic attack, encephalomyelopathy after cardiac operation, spinal angiopathy, hypertension with stress, neurosis, epilepsy, asthma and pollakiuria etc. or agent for the treatment of pain.

  本发明涉及式(I)的化合物及其盐（所有符号的含义与说明书中描述的相同）。式(I)的化合物具有N-型钙通道的抑制活性，因此它们可用作预防和/或治疗脑梗死、短暂性缺血性发作、心脏手术后脑脊髓病、脊髓血管病、应激性高血压、神经症、癫痫、哮喘和尿频等疾病的药物，或用作治疗疼痛的药剂。
• Amino acid derivatives
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US20030013725A1

  公开（公告）日：2003-01-16

  A compound of the formula (1): 1 [wherein R 1 is (substituted) alkyl, alkoxy, phenyl, hetero ring etc.; A is bond, CO, SO 2 ; R 2 is H, (substituted) alkyl etc.; D is alkylene etc.; E is COO, OCO, O, S, SO, SO 2 etc.; R 3 is (substituted) alkyl, carbocyclic ring, hetero ring; J is O, NR 16 (R 16 is H, substituted alkyl); R 4 is (substituted) alkyl, carbocyclic ring, hetero ring.] or non-toxic salt thereof, and an N-type calcium channel blocker comprising it as an active ingredient. The compounds of the formula (I) possess an inhibitory action on N-type calcium channel, so they are useful as agent for the prevention and/or treatment of cerebral infarct, transient ischemic attack, encephalomyelopathy after cardiac operation, spinal angiopathy, hypertension with stress, neurosis or epilepsy etc. or agent for the treatment of pain.

  化合物的式子（1）：1[其中R1是（取代）烷基，烷氧基，苯基，杂环等；A是键，CO，SO2；R2是H，（取代）烷基等；D是烷基等；E是COO，OCO，O，S，SO，SO2等；R3是（取代）烷基，环烷基，杂环；J是O，NR16（R16是H，取代烷基）；R4是（取代）烷基，环烷基，杂环。或其非毒性盐，以及作为活性成分的N型钙通道阻滞剂。式（I）的化合物具有对N型钙通道的抑制作用，因此它们可用作预防和/或治疗脑梗死、短暂性脑缺血发作、心脏手术后脑脊髓病、脊髓血管病、应激性高血压、神经症或癫痫等的药物或治疗疼痛的药物。
• Amino acid derivatives and pharmaceutical composition comprising, as active ingredients, them
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US20030232806A1

  公开（公告）日：2003-12-18

  The present invention relates to the compounds of the formula (I) and salts thereof (all the symbols are the same meanings as described in the specification). 1 The compounds of the formula (I) possess inhibitory activity of N-type calcium channel, so they are useful as drug for prevention and/or treatment of cerebral infarct, transient ischemic attack, encephalomyelopathy after cardiac operation, spinal angiopathy, hypertension with stress, neurosis, epilepsy, asthma and pollakiuria etc. or agent for the treatment of pain

  本发明涉及化合物(I)及其盐（其中所有符号的含义与说明书中描述的相同）。化合物(I)具有N型钙通道的抑制活性，因此它们可用作预防和/或治疗脑梗死、短暂性脑缺血发作、心脏手术后脑脊髓病、脊髓血管病、应激性高血压、神经症、癫痫、哮喘和尿频等疾病的药物，或用作治疗疼痛的药剂。
• AMINO ACID DERIVATIVES
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：EP0997147A1

  公开（公告）日：2000-05-03

  A compound of the formula (I): [wherein R1 is (substituted) alkyl, alkoxy, phenyl, hetero ring etc.; A is bond, CO, SO2; R2 is H, (substituted) alkyl etc.; D is alkylene etc.; E is COO, OCO, O, S, SO, SO2 etc.; R3 is (substituted) alkyl, carbocyclic ring, hetero ring; J is O, NR16 (R16 is H, substituted alkyl); R4 is (substituted) alkyl, carbocyclic ring, hetero ring.] or non-toxic salt thereof, and an N-type calcium channel blocker comprising it as an active ingredient. The compounds of the formula (I) possess an inhibitory action on N-type calcium channel, so they are useful as agent for the prevention and/or treatment of cerebral infarct, transient ischemic attack, encephalomyelopathy after cardiac operation, spinal angiopathy, hypertension with stress, neurosis or epilepsy etc. or agent for the treatment of pain.

  式 (I) 的化合物： [其中 R1 是（取代）烷基、烷氧基、苯基、杂环等；A 是键、CO、SO2；R2 是 H、（取代）烷基等；D 是亚烷基等；E 是 COO、OCO、O、S、SO、SO2 等。R3是（取代的）烷基、碳环、杂环；J是O、NR16（R16是H、取代的烷基）；R4是（取代的）烷基、碳环、杂环]或其无毒盐，以及包含其作为活性成分的N型钙通道阻滞剂。 式（I）化合物对 N 型钙通道具有抑制作用，因此可作为预防和/或治疗脑梗塞、短暂性脑缺血发作、心脏手术后脑脊髓病变、脊髓血管病变、应激性高血压、神经官能症或癫痫等疾病的药物或治疗疼痛的药物。
• AMINO ACID DERIVATIVES AND DRUGS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1090912A1

  公开（公告）日：2001-04-11

  Compounds represented by general formula (I) and salts thereof, wherein each symbol is as defined in the specification. Because of inhibiting the N type calcium channel, the compounds of general formula (I) are useful as preventives and/or remedies for brain infarction, transient ischemic attack, cerebrospinal failure following heart operation, spinal vascular failure, stress hypertension, neurosis, epilepsy, asthma, frequent urination, etc. or analgesics.

  通式(I)代表的化合物及其盐类，其中各符号如说明书中所定义。由于能抑制 N 型钙通道，通式（I）化合物可作为脑梗塞、短暂性脑缺血发作、心脏手术后脑脊髓衰竭、脊髓血管衰竭、应激性高血压、神经官能症、癫痫、哮喘、尿频等疾病的预防和/或治疗药物或镇痛剂。