LH708 | 1616758-14-5

• 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: LH708
• 英文别名: L-cystine bis(N'-methylpiperazide)；LH-708；(2R)-2-amino-3-[[(2R)-2-amino-3-(4-methylpiperazin-1-yl)-3-oxopropyl]disulfanyl]-1-(4-methylpiperazin-1-yl)propan-1-one
• CAS: 1616758-14-5
• 化学式: C₁₆H₃₂N₆O₂S₂
• 分子量: 404.601
• InChiKey: OTZBBNVLKDUVJM-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N,N'-bis(tert-butoxycarbonyl)-L-cystine bis(N'-methylpiperazide) 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 LH708
  参考文献：
  名称：

  设计，合成和评估作为胱氨酸尿症的l-胱氨酸结晶抑制剂的l-胱氨酸二酰胺

  摘要：

  为了克服的化学和代谢稳定性的问题升-cystine二甲酯（CDME）和升-cystine甲酯（CME），一系列的升带或不带二酰胺-cystine Ñ α -methylation被设计，合成并评价了它们的l-胱氨酸结晶的抑制活性。升-Cystine二酰胺2A -我不Ñ α -methylation被发现是有效的抑制剂升-cystine结晶而Ñ α的-methylation升-cystine二酰胺导致衍生物3b的-我没有1-胱氨酸结晶的任何抑制活性。计算建模表明Ñ α -methylation导致显著降低在结合升-cystine二酰胺向升-cystine晶体表面。间的升-cystine二酰胺2A -我，升-cystine bismorpholide（CDMOR，LH707，2克）和升-cystine双（N' -methylpiperazide）（CDNMP，LH708，2H）是最有效的抑制剂升-cystine结晶。

  DOI：

  10.1016/j.bmcl.2018.03.024

文献信息

• Cystine Diamide Analogs for the Prevention of Cystine Stone Formation in Cystinuria
  申请人：Rutgers, The State University of New Jersey

  公开号：US20140187546A1

  公开（公告）日：2014-07-03

  Cystine analogs that improve the solubility of L-cystine in urine for treatment of cystinuria and which have the structure: and pharmaceutically acceptable salts, solvates and prodrugs thereof, wherein each R and R′ pair are independently selected from (i) or (ii); (i) R and R′ are independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alcohol, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, and substituted or unsubstituted heteroaryl, or (ii) R and R′ together form a substituted or unsubstituted heterocyclic ring structure, or a substituted or unsubstituted heteroaryl ring structure; X is hydrogen, or an alkyl; and Y is O or S.

  改善L-半胱氨酸在尿液中的溶解度以治疗囊胱氨酸尿症的半胱氨酸类似物，其结构为：以及其药用可接受的盐、溶剂化合物和前药，其中每个R和R′对均独立地从(i)或(ii)中选择；(i) R和R′均独立地从氢、取代或未取代的烷基、取代或未取代的烯基、取代或未取代的醇、取代或未取代的芳基、取代或未取代的环烷基、取代或未取代的杂环基和取代或未取代的杂芳基中选择，或(ii) R和R′共同形成取代或未取代的杂环戒结构或取代或未取代的杂芳环结构；X为氢或烷基；Y为O或S。
• Cystine diamide analogs for the prevention of cystine stone formation in cystinuria
  申请人：Rutgers, The State University of New Jersey

  公开号：US10836737B2

  公开（公告）日：2020-11-17

  Cystine analogs that improve the solubility of L-cystine in urine for treatment of cystinuria and which have the structure: and pharmaceutically acceptable salts, solvates and prodrugs thereof, wherein each R and R′ pair are independently selected from (i) or (ii); (i) R and R′ are independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alcohol, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, and substituted or unsubstituted heteroaryl, or (ii) R and R′ together form a substituted or unsubstituted heterocyclic ring structure, or a substituted or unsubstituted heteroaryl ring structure; X is hydrogen, or an alkyl; and Y is O or S.

  可改善 L-胱氨酸在尿液中的溶解度，用于治疗胱氨酸尿症的胱氨酸类似物，其结构如下： 1： 及其药学上可接受的盐、溶液剂和原药，其中 每对 R 和 R′独立选自(i)或(ii)； (i) R 和 R′独立地选自氢、取代或未取代的烷基、取代或未取代的烯基、取代或未取代的醇基、取代或未取代的芳基、取代或未取代的环烷基、取代或未取代的杂环基和取代或未取代的杂芳基，或 (ii) R 和 R′共同形成取代或未取代的杂环环结构，或取代或未取代的杂芳基环结构； X 是氢或烷基；Y 是 O 或 S。
• <scp>l</scp>-Cystine Diamides as <scp>l</scp>-Cystine Crystallization Inhibitors for Cystinuria
  作者：Longqin Hu、Yanhui Yang、Herve Aloysius、Haifa Albanyan、Min Yang、Jian-Jie Liang、Anthony Yu、Alexander Shtukenberg、Laura N. Poloni、Vladyslav Kholodovych、Jay A. Tischfield、David S. Goldfarb、Michael D. Ward、Amrik Sahota

  DOI：10.1021/acs.jmedchem.6b00647

  日期：2016.8.11

  L-Cystine bismorpholide (la) and L-cystine bis(N'-methylpiperazide) (1b) were seven and twenty-four times more effective than L-cystine dimethyl ester (CDME) in increasing the metastable supersaturation range of L-cystine, respectively, effectively inhibiting L-cystine crystallization. This behavior can be attributed to inhibition of crystal growth at microscopic length scale, as revealed by atomic force microscopy. Both 1a and 1b are more stable than CDME, and 1b was effective in vivo in a knockout mouse model of cystinuria.
• CYSTINE DIAMIDE ANALOGS FOR THE PREVENTION OF CYSTINE STONE FORMATION IN CYSTINURIA
  申请人：Rutgers, The State University of New Jersey

  公开号：US20160362386A1

  公开（公告）日：2016-12-15

  Cystine analogs that improve the solubility of L-cystine in urine for treatment of cystinuria and which have the structure: and pharmaceutically acceptable salts, solvates and prodrugs thereof, wherein each R and R′ pair are independently selected from (i) or (ii); (i) R and R′ are independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alcohol, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic, and substituted or unsubstituted heteroaryl, or (ii) R and R′ together form a substituted or unsubstituted heterocyclic ring structure, or a substituted or unsubstituted heteroaryl ring structure; X is hydrogen, or an alkyl; and Y is O or S.
• US9428453B2
  申请人：——

  公开号：US9428453B2

  公开（公告）日：2016-08-30