rimcazole | 75859-04-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: rimcazole
• 英文别名: 9-[3-[(3S,5R)-3,5-dimethylpiperazin-1-yl]propyl]carbazole
• CAS: 75859-04-0
• 化学式: C₂₁H₂₇N₃
• 分子量: 321.465
• InChiKey: GUDVQJXODNJRIJ-CALCHBBNSA-N

物化性质

• 沸点：
  499.1±45.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  2

制备方法与用途

Rimcazole（BW 234U）是一种有效的抗精神病药物，同时也是σ受体的竞争性拮抗剂。这种化合物适用于研究急性精神分裂症相关症状。

反应信息

• 作为反应物：
  描述：

  rimcazole 在 palladium on activated charcoal 氢气 、 硝酸 、 sodium cyanoborohydride 作用下， 以 甲醇 、 乙醇 、 水 、 溶剂黄146 、 乙腈 为溶剂， 25.0 ℃ 、206.84 kPa 条件下， 反应 7.5h， 生成 9-[3-((3R,5S)-3,4,5-Trimethyl-piperazin-1-yl)-propyl]-9H-carbazol-3-ylamine
  参考文献：
  名称：

  Isothiocyanate Derivatives of 9-[3-(cis-3,5-Dimethyl-1-piperazinyl)propyl]- carbazole (Rimcazole):  Irreversible Ligands for the Dopamine Transporter

  摘要：

  Cocaine has been reported to bind to the dopamine transporter in a biphasic fashion, and it has been hypothesized that the low-affinity component may play a modulatory role in cocaine's psychomotor stimulant effects. In an effort to gain further insight into the roles of the two sites, we have prepared a series of irreversible ligands based on rimcazole (9-[3-(cis-3,5-dimethyl-1-piperazinyl)propyl]carbazole, 2), a compound that has been postulated to bind only to the low-affinity site. The alkylating moiety (isothiocyanate) is attached to the distal nitrogen of the piperazine ring via alkyl chains of varying lengths or directly attached to one of the aromatic groups. It was found that substitution on the piperazine nitrogen caused an initial decrease in affinity that was recovered as the alkyl chain length increased. Importantly, the analogue 16, with the highest affinity for the dopamine transporter (DAT), binds in a monophasic and irreversible manner, as evidenced by the greatly diminished binding of [H-3]WIN 35,428 in tissue that had been preincubated with the Ligand and then thoroughly washed using centrifugation. The dose-dependent reduction in B-max was accompanied by a concentration-related decrease in K-D values. This shift in K-D to a lower value suggests that the preincubation with 16 produced a preferential irreversible binding to the low-affinity [H-3]WIN 35,428 site on the dopamine transporter. These Ligands may prove to be important tools with which to study the significance of the low-affinity site on the DAT. Since rimcazole does not share the behavioral profile of cocaine, and in fact appears to play a modulatory role, these compounds may provide leads for a novel cocaine-abuse treatment.

  DOI：

  10.1021/jm9705519
• 作为产物：
  描述：

  N-[3-[cis-3,5-dimethyl-4-(methanesulfonyl)piperazin-1-yl]propyl]carbazole 在 lithium diisopropyl amide 、 氧气 、 水 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.25h， 以73%的产率得到rimcazole
  参考文献：
  名称：

  甲烷磺酰胺选择性脱保护为胺

  摘要：

  甲烷磺酰胺即使在其他传统的磺酰胺存在下，也能通过去质子化和用O 2（g）氧化而脱保护为其母体胺。

  DOI：

  10.1021/ol100086j

文献信息

• Pyrrazole derivatives as sigma receptors antagonists
  申请人：LABORATORIOS DEL DR. ESTEVE, S.A.

  公开号：EP1829873A1

  公开（公告）日：2007-09-05

  The present invention relates to compounds of formula (I), methods for their preparation, medicaments comprising these compounds as well their use in the manufacture of a medicament for the treatment of humans and animals.

  本发明涉及式(I)的化合物， 其制备方法，包含这些化合物的药物，以及它们在制造用于治疗人类和动物的药物中的应用。
• [EN] QUATERNARY AMINE COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF<br/>[FR] COMPOSÉS D'AMINE QUATERNAIRE ET CONJUGUÉS ANTICORPS-MÉDICAMENT DE CEUX-CI
  申请人：GENENTECH INC

  公开号：WO2016090050A1

  公开（公告）日：2016-06-09

  This invention relates to antibody-drug conjugates represented by Formula (I) Ab- (L-D)p, Ab is an antibody; p is 1-8; L-D is a chemical moiety represented by the following formula -Str-(Pep)-Sp-D; Str is a stretcher unit covalently attached to Ab; Pep is a linker; D is anti-tumor agent represented by the following formula wherein R<20>and R<30>are each independently Ct-C6alkyl, and R<10>is a non-hydrogen substituent; or R<30>is C1-C6alkyl, and R<10>and R<20>together with the N form a substituted C3-C7heterocycloalkyl ring; or R<3>° is absent, and R<10>and R<20>together with the N form a substituted heteroaryl ring; Sp-D is a spacer moiety of fomula: This invention also relates to a method of treating cancer, use of antibody-drug conjugates of Formula (I) in therapy, and use of antibody-drug conjugates of Formula (I) in manufacturing a medicament for treating cancer. This invention also relates to method of preparing antibody-drug conjugates of Formula (I).

  这项发明涉及由公式（I）Ab-（L-D）p表示的抗体药物偶联物，其中Ab是抗体；p为1-8；L-D是由以下公式表示的化学基团-Str-(Pep)-Sp-D；Str是共价连接到Ab的延伸单元；Pep是连接剂；D是由以下公式表示的抗肿瘤剂，其中R20和R30分别独立为C1-C6烷基，R10是非氢取代基；或R30为C1-C6烷基，且R10和R20与N一起形成取代的C3-C7杂环烷基环；或R3°不存在，且R10和R20与N一起形成取代的杂芳基环；Sp-D是公式的间隔基团：这项发明还涉及一种治疗癌症的方法，使用公式（I）的抗体药物偶联物进行治疗，以及使用公式（I）的抗体药物偶联物制造治疗癌症药物的用途。这项发明还涉及制备公式（I）的抗体药物偶联物的方法。
• [EN] 1-(4-(2-((1-(3,4-DIFLUOROPHENYL)-1H-PYRAZOL-3-YL)METHOXY)ETHYL) PIPERAZIN-1-YL)ETHANONE SALTS<br/>[FR] SELS DE 1-(4-(2-((1-(3,4-DIFLUOROPHÉNYL)-1H-PYRAZOL-3-YL)MÉTHOXY)ÉTHYL) PIPÉRAZIN-1-YL)ÉTHANONE
  申请人：ESTEVE LABOR DR

  公开号：WO2017037166A1

  公开（公告）日：2017-03-09

  The present invention relates to 1 -(4-(2-((1 -(3,4-difluorophenyl)-1 H-pyrazol-3-yl)methoxy)ethyl)piperazin-1 -yl)ethanone salts, specifically to the hydrochloride and to the maleate, to pharmaceutical compositions comprising them, and to their use in therapy and/or prophylaxis of sigma receptor associated diseases.

  本发明涉及1-(4-(2-((1-(3,4-二氟苯基)-1H-吡唑-3-基)甲氧基)乙基)哌嗪-1-基)乙酰胺盐，特别是盐酸盐和马来酸盐，涉及含有它们的药物组合物，以及它们在治疗和/或预防与σ受体相关疾病中的用途。
• [EN] INDENE DERIVATIVES, THEIR PREPARATION AND USE AS MEDICAMENTS<br/>[FR] DÉRIVÉS D'INDÈNE, LEUR PRÉPARATION ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS
  申请人：ESTEVE LABOR DR

  公开号：WO2014006071A1

  公开（公告）日：2014-01-09

  The present invention relates to new indene derivatives having a great affinity for sigma receptors, especially sigma-1 receptors, as well as to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments.

  本发明涉及新的茚衍生物，特别是对sigma受体，尤其是sigma-1受体具有较大亲和力的茚衍生物，以及它们的制备过程、包含它们的组合物，以及它们作为药物的使用。
• Indene derivatives, their preparation and use as medicaments
  申请人：Laboratorios del. Dr. Esteve, S.A.

  公开号：EP2682391A1

  公开（公告）日：2014-01-08

  The present invention relates to new indene derivatives having a great affinity for sigma receptors, especially sigma-1 receptors, as well as to the process for the preparation thereof, to compositions comprising them, and to their use as medicaments.

  本发明涉及新的茚衍生物，这些衍生物对sigma受体，特别是sigma-1受体具有很高的亲和力，以及它们的制备过程，包含它们的组合物，以及它们作为药物的使用。