tert-butyl (R)-3-[tert-butoxycarbonyl-[(R)-1-(naphthalen-1-yl)ethyl]amino]pyrrolidine-1-carboxylate | 870858-89-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: tert-butyl (R)-3-[tert-butoxycarbonyl-[(R)-1-(naphthalen-1-yl)ethyl]amino]pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (3R)-3-[(2-methylpropan-2-yl)oxycarbonyl-[(1R)-1-naphthalen-1-ylethyl]amino]pyrrolidine-1-carboxylate
• CAS: 870858-89-2
• 化学式: C₂₆H₃₆N₂O₄
• 分子量: 440.583
• InChiKey: IPJDRKYCYNZRIU-UYAOXDASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (R)-3-[tert-butoxycarbonyl-[(R)-1-(naphthalen-1-yl)ethyl]amino]pyrrolidine-1-carboxylate 在 盐酸 、 palladium diacetate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 氯仿 、 甲苯 为溶剂， 生成
  参考文献：
  名称：

  发现用于治疗甲状旁腺功能亢进症的下一代钙敏感受体激动剂evocalcet

  摘要：

  钙敏感受体（CaSR）在检测细胞外钙离子和调节甲状旁腺细胞分泌的甲状旁腺激素中起重要作用，并且该受体是治疗甲状旁腺功能亢进症的合适靶标。盐酸西那卡塞是一种代表性的CaSR激动剂，广泛用于甲状旁腺功能亢进症。但是，它对临床使用存在一些问题，例如恶心/呕吐和对CYP2D6的强抑制作用。我们试图改善cinacalcet的这些问题，从而使新药物成为可取的CaSR激动剂。通过cinacalcet的优化可鉴定出吡咯烷化合物，并成功地导致了evocalcet作为口服变构CaSR激动剂的发现。Evocalcet具有高度有利的特性，例如CaSR激动活性和良好的DMPK特性，

  DOI：

  10.1016/j.bmcl.2018.04.055
• 作为产物：
  描述：

  N-(tert-butoxycarbonyl)-3-(1-(R)-α-naphthylethyl)-aminopyrrolidine 、 三光气 、 叔丁醇 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以31%的产率得到tert-butyl (S)-3-[tert-butoxycarbonyl-[(R)-1-(naphthalen-1-yl)ethyl]amino]pyrrolidine-1-carboxylate
  参考文献：
  名称：

  发现用于治疗甲状旁腺功能亢进症的下一代钙敏感受体激动剂evocalcet

  摘要：

  钙敏感受体（CaSR）在检测细胞外钙离子和调节甲状旁腺细胞分泌的甲状旁腺激素中起重要作用，并且该受体是治疗甲状旁腺功能亢进症的合适靶标。盐酸西那卡塞是一种代表性的CaSR激动剂，广泛用于甲状旁腺功能亢进症。但是，它对临床使用存在一些问题，例如恶心/呕吐和对CYP2D6的强抑制作用。我们试图改善cinacalcet的这些问题，从而使新药物成为可取的CaSR激动剂。通过cinacalcet的优化可鉴定出吡咯烷化合物，并成功地导致了evocalcet作为口服变构CaSR激动剂的发现。Evocalcet具有高度有利的特性，例如CaSR激动活性和良好的DMPK特性，

  DOI：

  10.1016/j.bmcl.2018.04.055

文献信息

• NOVEL CRYSTALLINE ARYLALKYLAMINE COMPOUND AND PROCESS FOR PRODUCING THE SAME
  申请人：MITSUBISHI TANABE PHARMA CORPORATION

  公开号：US20160200679A1

  公开（公告）日：2016-07-14

  The present invention provides novel crystal forms of arylalkylamine compounds. Specifically, the novel crystal forms of 4-(3S-(1R-(1-naphthyl)ethylamino)pyrrolidin-1-yl)phenylacetic acid have excellent stability and therefore are useful as pharmaceutical ingredients. The present invention also provides industrially advantageous processes for producing the arylalkylamine compounds.

  本发明提供了新型芳基烷基胺化合物的晶体形式。具体地，4-(3S-(1R-(1-萘基)乙基氨基)吡咯烷-1-基)苯乙酸的新型晶体形式具有优异的稳定性，因此可以作为药用成分。本发明还提供了工业上有利的生产芳基烷基胺化合物的方法。
• Arylalkylamine Compound and Process for Preparing the Same
  申请人：Miyazaki Hiroshi

  公开号：US20070225296A1

  公开（公告）日：2007-09-27

  The present invention relates to an arylalkylamine compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof, a process for preparing the same, and use of the above-mentioned compound as an activating compound (CaSR agonist) of a Ca sensing receptor, a pharmaceutical composition containing the above-mentioned compound as an effective ingredient, etc. The symbols in the formula represent the following meanings: Ar: optionally substituted aryl or optionally substituted heteroaryl here, the cyclic portion of the heteroaryl is bicyclic heterocyclic ring in which 5- to 6-membered monocyclic heterocyclic ring containing 1 or 2 hetero atom(s) and benzene ring are fused; R 1 : a group selected from the group consisting of optionally substituted cyclic hydrocarbon group, and optionally substituted heterocyclic group; n: an integer of 1 to 3; X: single bonding arm, —CH 2 —, —CO—, —(CH 2 ) m —CO—, —CH(R 2 )—CO—, —(CH 2 ) p —Y—(C(R 3 )(R 4 )) q —CO—, —NH—CO— or —N(R 5 )—CO—; in the above-mentioned respective definitions of the X, the bonding arm described at the left end represents a bond with R 1 ; m is an integer of 1 to 3; p is an integer of 0 to 2; q is an integer of 0 to 2; Y: —O— or —SO 2 —; R 2 : phenyl or lower alkyl; R 3 , R 4 : each independently represents hydrogen atom or lower alkyl; R 5 : lower alkyl; provided that the ring portion of the group represented by R 1 is neither naphthylidine nor partially saturated group thereof, and, when X is —CH 2 — or —CO—, R 1 is not naphthyl.

  本发明涉及一种由以下公式[I]表示的芳基烷基胺化合物或其药学上可接受的盐，其制备方法，以及上述化合物作为钙感受受体的激活化合物（CaSR激动剂），以及含有上述化合物作为有效成分的制药组合物等的用途。公式中的符号表示以下含义：Ar：此处为可选取代的芳基或可选取代的杂环芳基，其中杂环的环部分是一个含有1或2个杂原子的5-至6元单环杂环，与苯环融合；R1：选自可选取代的环烃基团和可选取代的杂环基团的群；n：1至3的整数；X：单键臂、—CH2—、—CO—、—（CH2）m—CO—、—CH（R2）—CO—、—（CH2）p—Y—（C（R3）（R4））q—CO—、—NH—CO—或—N（R5）—CO—；在上述各定义的X中，左端所描述的键臂表示与R1的键；m为1至3的整数；p为0至2的整数；q为0至2的整数；Y：—O—或—SO2—；R2：苯基或低碳烷基；R3、R4：各自独立地表示氢原子或低碳烷基；R5：低碳烷基；前提是由R1表示的基团的环部分既不是萘亚甲基也不是其部分饱和基团，且当X为—CH2—或—CO—时，R1不是萘基。
• ARYLALKYLAMINE COMPOUND AND PROCESS FOR PREPARING THE SAME
  申请人：MIYAZAKI Hiroshi

  公开号：US20100249049A1

  公开（公告）日：2010-09-30

  The present invention relates to an arylalkylamine compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof, a process for preparing the same, and use of the above-mentioned compound as an activating compound (CaSR agonist) of a Ca sensing receptor, a pharmaceutical composition containing the above-mentioned compound as an effective ingredient, etc. The symbols in the formula represent the following meanings: Ar: optionally substituted aryl or optionally substituted heteroaryl here, the cyclic portion of the heteroaryl is bicyclic heterocyclic ring in which 5- to 6-membered monocyclic heterocyclic ring containing 1 or 2 hetero atom(s) and benzene ring are fused; R 1 : a group selected from the group consisting of optionally substituted cyclic hydrocarbon group, and optionally substituted heterocyclic group; n: an integer of 1 to 3; X: single bonding arm, —CH 2 —, —CO—, —(CH 2 ) m —CO—, —CH(R 2 )—CO—, —(CH 2 ) p —Y—(C(R 3 )(R 4 )) q —CO—, —NH—CO— or —N(R 5 )—CO—; in the above-mentioned respective definitions of the X, the bonding arm described at the left end represents a bond with R 1 ; m is an integer of 1 to 3; p is an integer of 0 to 2; q is an integer of 0 to 2; Y: —O— or —SO 2 —; R 2 : phenyl or lower alkyl; R 3 , R 4 : each independently represents hydrogen atom or lower alkyl; R 5 : lower alkyl; provided that the ring portion of the group represented by R 1 is neither naphthylidine nor partially saturated group thereof, and, when X is —CH 2 — or —CO—, R 1 is not naphthyl.

  本发明涉及一种由下式[I]表示的芳基烷基胺化合物或其药学上可接受的盐，制备该化合物的方法，以及上述化合物作为钙感受受体（CaSR激动剂）的激活化合物、包含上述化合物作为有效成分的药物组合物等的用途。式中符号表示以下含义：Ar：可选取的取代芳基或可选取的取代杂环芳基，在此，所述杂环的环状部分是由1或2个杂原子的5-6元单环杂环与苯环融合而成的双环杂环；R1：选自可选取的取代环烃基团和可选取的取代杂环基团的群；n：为1至3的整数；X：单键连接臂，-CH2-，-CO-，-(CH2)m-CO-，-CH(R2)-CO-，-(CH2)p-Y-(C(R3)(R4))q-CO-，-NH-CO-或-N(R5)-CO-；在上述X的各自定义中，左端所述连接臂表示与R1的键合；m为1至3的整数；p为0至2的整数；q为0至2的整数；Y：-O-或-SO2-；R2：苯基或低碳烷基；R3，R4：各自独立地表示氢原子或低碳烷基；R5：低碳烷基；所述R1表示的基的环部分既不是萘亚甲基基团，也不是其部分饱和基团，当X为-CH2-或-CO-时，R1不是萘基。
• Arylalkylamine compound and process for preparing the same
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：US08778628B2

  公开（公告）日：2014-07-15

  An arylalkylamine compound is represented by the following formula [I-e] or a pharmaceutically acceptable salt thereof.

  一种芳基烷基胺化合物可由以下公式[I-e]或其药学上可接受的盐所代表。
• NOVEL CRYSTALLINE ARYLALKYLAMINE COMPOUND AND METHOD FOR PRODUCING SAME
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：EP3042893A1

  公开（公告）日：2016-07-13

  The present invention provides novel crystal forms of arylalkylamine compounds. Specifically, the novel crystal forms of 4-(3S-(1R-(1-naphthyl)ethylamino)pyrrolidin-1-yl)phenylacetic acid have excellent stability and therefore are useful as pharmaceutical ingredients. The present invention also provides industrially advantageous processes for producing the arylalkylamine compounds.

  本发明提供了芳基烷基胺化合物的新型晶体形式。具体来说，新型晶体形式包括 4-(3S-(1R-(1-萘基)乙氨基)吡咯烷-1-基)苯乙酸的新型晶体具有极佳的稳定性，因此可用作药物成分。本发明还提供了具有工业优势的芳基烷基胺化合物生产工艺。