TMAVA | 87597-00-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: TMAVA
• 英文别名: 4-Carboxy-N,N,N-trimethylbutan-1-aminium；4-carboxybutyl(trimethyl)azanium
• CAS: 87597-00-0
• 化学式: C₈H₁₈NO₂
• 分子量: 160.236
• InChiKey: CDLVFVFTRQPQFU-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,4-dichloro-3-(2,4-dimethyl-quinolin-8-yloxymethyl)-N-[1-(piperazine-1-carbonyl)-cyclopentyl]-benzenesulfonamide 、 TMAVA 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 [5-[4-[1-[[2,4-Dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]cyclopentanecarbonyl]piperazin-1-yl]-5-oxopentyl]-trimethylazanium
  参考文献：
  名称：

  Design and Synthesis of Novel Sulfonamide-Containing Bradykinin hB₂ Receptor Antagonists. 2. Synthesis and Structure−Activity Relationships of α,α-Cycloalkylglycine Sulfonamides

  摘要：

  Recently we reported on the design and synthesis of a novel class of selective nonpeptide bradykinin (BK) B-2 receptor antagonists (J. Med. Chem. 2006, 3602-3613). This work led to the discovery of MEN 15442, an antagonist with subnanomolar affinity for the human B2 receptor (hB2R), which also displayed significant and prolonged activity in vivo (for up to 210 min) against BK-induced bronchoconstriction in the guinea-pig at a dose of 300 nmol/kg (it), while demonstrating only a slight effect on BK-induced hypotension. Here we describe the further optimization of this series of compounds aimed at maximizing the effect on bronchoconstriction and minimizing the effect on hypotension, with a view to developing topically delivered drugs for airway diseases. The work led to the discovery of MEN 16132, a compound which, after intratracheal or aerosol administration, inhibited, in a dose-dependent manner, BK-induced bronchoconstricton in the airways, while showing minimal systemic activity. This compound was selected as a preclinical candidate for the topical treatment of airway diseases involving kinin B2 receptor stimulation.

  DOI：

  10.1021/jm061143k
• 作为产物：
  描述：

  硫酸二甲酯 、 5-氨基颉草酸 在 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 TMAVA
  参考文献：
  名称：

  Design and Synthesis of Novel Sulfonamide-Containing Bradykinin hB₂ Receptor Antagonists. 2. Synthesis and Structure−Activity Relationships of α,α-Cycloalkylglycine Sulfonamides

  摘要：

  Recently we reported on the design and synthesis of a novel class of selective nonpeptide bradykinin (BK) B-2 receptor antagonists (J. Med. Chem. 2006, 3602-3613). This work led to the discovery of MEN 15442, an antagonist with subnanomolar affinity for the human B2 receptor (hB2R), which also displayed significant and prolonged activity in vivo (for up to 210 min) against BK-induced bronchoconstriction in the guinea-pig at a dose of 300 nmol/kg (it), while demonstrating only a slight effect on BK-induced hypotension. Here we describe the further optimization of this series of compounds aimed at maximizing the effect on bronchoconstriction and minimizing the effect on hypotension, with a view to developing topically delivered drugs for airway diseases. The work led to the discovery of MEN 16132, a compound which, after intratracheal or aerosol administration, inhibited, in a dose-dependent manner, BK-induced bronchoconstricton in the airways, while showing minimal systemic activity. This compound was selected as a preclinical candidate for the topical treatment of airway diseases involving kinin B2 receptor stimulation.

  DOI：

  10.1021/jm061143k

文献信息

• [EN] MACROCYCLIC PANTETHEINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS MACROCYCLIQUES DE LA PANTÉTHÉINE ET LEURS UTILISATIONS
  申请人：COMET THERAPEUTICS INC

  公开号：WO2021108579A1

  公开（公告）日：2021-06-03

  The present disclosure relates to compounds of Formulae (I) or (II): and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.

  本公开涉及式(I)或(II)的化合物，以及其药学上可接受的盐或溶剂化合物。本公开还涉及包含这些化合物的药物组合物，以及这些化合物和药物组合物的治疗和诊断用途。
• TMAVA拮抗剂的用途以及用于诊断脂肪肝或心力衰竭的系统
  申请人：郑乐民

  公开号：CN113058037A

  公开（公告）日：2021-07-02

  本公开涉及N，N，N‑三甲基‑5‑氨基戊酸拮抗剂在制备治疗脂肪肝和/或心力衰竭的药物中的用途以及一种用于诊断脂肪肝和/或心力衰竭的系统。本公开为脂肪肝和/或心力衰竭提供了新的治疗方案，通过拮抗TMAVA，可以降低患者血浆和肝脏中的甘油三酯和游离脂肪酸的水平，同时，还能消除TMAVA对γ‑异丙基甜菜碱羟化酶活性的抑制作用，避免内源性肉碱合成减少导致的游离脂肪酸线粒体β‑氧化作用变弱，从而可见减少脂肪酸在肝脏和心脏处的异位堆积，对脂肪肝和/或心力衰竭的治疗效果明显。
• Preparation of polysaccharide betainate type compounds, compounds obtained, their use and compositions comprising them
  申请人：——

  公开号：US20030147818A1

  公开（公告）日：2003-08-07

  A process for preparing compounds from the polysaccharide betainate family, novel compounds so obtained, and their use in cosmetics or in dermatology, as well as the compositions, such as cosmetic or dermatological compositions, comprising said novel compounds.

  一种制备甜菜酸多糖家族化合物的工艺、由此获得的新型化合物及其在化妆品或皮肤病学中的用途，以及包含上述新型化合物的组合物，如化妆品或皮肤病学组合物。
• Design and synthesis of novel sulfonamide-containing bradykinin hB2 receptor antagonists. Synthesis and structure-relationships of α,α-tetrahydropyranylglycine
  作者：Christopher I. Fincham、Alessandro Bressan、Piero D’Andrea、Alessandro Ettorre、Sandro Giuliani、Sandro Mauro、Stefania Meini、Marielle Paris、Laura Quartara、Cristina Rossi、Antonella Squarcia、Claudio Valenti、Fattori Daniela、Carlo Alberto Maggi

  DOI：10.1016/j.bmc.2012.01.036

  日期：2012.3

  A series of alpha,alpha-cycloalkylglycine sulfonamide compounds of general formula 1 has previously been identified by our group as selective human B-2(hB(2)) receptor antagonists. Here we report the in vitro and in vivo BK antagonist activity of a further evolution of the series, consisting in compounds of the general formula 2, containing either an alkyl piperazine or a 4-alkyl piperidine ring bearing various positively charged groups (R'). These studies unexpectedly revealed quite a flat nanomolar/subnanomolar SAR for the binding affinity, while differences were seen in the in vitro functional activities. We propose that variations in the residence time may explain these results. (C) 2012 Elsevier Ltd. All rights reserved.
• Préparation de composés de type bétainates de polysaccharides, composés obtenus, leur utilisation et les compositions les comprenant
  申请人：L'ORÉAL

  公开号：EP1312616B1

  公开（公告）日：2008-01-23