右尼古地平 | 120054-86-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 右尼古地平
• 英文名称: Dexniguldipine
• 英文别名: 5-O-[3-(4,4-diphenylpiperidin-1-yl)propyl] 3-O-methyl (4R)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 120054-86-6
• 化学式: C36H39N3O6
• 分子量: 609.7
• InChiKey: SVJMLYUFVDMUHP-MGBGTMOVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  、 （R）-（-）-盐酸尼古地平 、 4-羟乙基哌嗪乙磺酸 、 、 硫酸软骨素钠盐 、 、 Tetrasodium;1-methylnonane-1,3,5,7-tetracarboxylate 、 以 二甲基亚砜 为溶剂， 反应 24.27h， 生成 右尼古地平
  参考文献：
  名称：

  Hydrophilic microparticles and methods to prepare same

  摘要：

  本发明涉及一种材料及其制备方法。该材料可被描述为亲水性微粒子，包括一簇有机物质和其表面的一层聚电解质。本发明建立了一种改进的方法，利用多离子亲水性聚合物制备水不溶性有机物质的水溶胶分散体，通过该方法可以在去除药物的稳定剂和/或溶解介质后，维持悬浮液的稳定性。该改进的方法可用于制备各种水不溶性有机物质。

  公开号：

  US06048550A1

文献信息

• [EN] ALKYNE-, AZIDE- AND TRIAZOLE-CONTAINING FLAVONOIDS AS MODULATORS FOR MULTIDRUG RESISTANCE IN CANCERS<br/>[FR] FLAVONOÏDES CONTENANT DE L'ALCYNE, DE L'AZIDE ET DU TRIAZOLE UTILISÉS COMME MODULATEURS DE RÉSISTANCE MULTIPLE AUX MÉDICAMENTS DANS LES CANCERS
  申请人：UNIV HONG KONG POLYTECHNIC

  公开号：WO2013127361A1

  公开（公告）日：2013-09-06

  A triazole bridged flavonoid dimer compound library was efficiently constructed via the cycloaddition reaction of a series of flavonoid-containing azides (Az 1-15) and alkynes (Ac 1-17). These triazole bridged flavonoid dimers and their precursor alkyne- and azide-continaing flavonoids were screened for their ability to modulate multidrug resistance (MDR) in P-gp-overexpressed cell line (LCC6MDR), MRPl-overexpressed cell line (2008/MRPl) and BCRP-overexpressed cell line (HEK293/R2 and MCF7-MX100). Generally, they displayed very promising MDR reversal activity against P-gp-, MRPl- and BCRP-mediated drug resistance. Moreover, they showed different levels of selectivity for various transporters. Overall, they can be divided into mono-selective, dual-selective and multi-selective modulators for the P-gp, MRPl and BCRP transporters. The EC50 values for reversing paclitaxel resistance (141 - 340 nM) of LCC6MDR cells, DOX (78 - 590 nM) and vincristine (82 - 550 nM) resistance of 2008/MRPl cells and topotecan resistance (0.9 - 135 nM) of HEK293/R2 and MCF7-MX100 cells were at nanomolar range. Importantly, a number of compounds displayed EC50 at or below 10 nM in BCRP-overexpressed cell lines, indicating that these bivalent triazoles more selectively inhibit BCRP transporter than the P-gp and MRPl transporters. Most of the dimers are notably safe MDR chemosensitizers as indicated by their high therapeutic index values.

  通过对一系列含有三唑基的黄酮类化合物（Az 1-15）和炔烃（Ac 1-17）进行环加成反应，高效构建了一个三唑桥联的黄酮二聚体化合物库。对这些三唑桥联的黄酮二聚体及其前体炔烃和三唑基的黄酮类化合物进行了筛选，以评估它们对P-gp过表达细胞系（LCC6MDR）、MRP1过表达细胞系（2008/MRP1）和BCRP过表达细胞系（HEK293/R2和MCF7-MX100）调节多药耐药性（MDR）的能力。总体而言，它们显示出对P-gp、MRP1和BCRP介导的药物耐药性具有非常有前景的MDR逆转活性。此外，它们对各种转运蛋白显示出不同程度的选择性。总体而言，它们可以分为对P-gp、MRP1和BCRP转运蛋白具有单选择性、双选择性和多选择性调节剂。逆转LCC6MDR细胞对紫杉醇耐药性（141-340 nM）、2008/MRP1细胞对阿霉素（78-590 nM）和长春碱（82-550 nM）耐药性以及HEK293/R2和MCF7-MX100细胞对托泊替康耐药性（0.9-135 nM）的EC50值在纳摩尔范围内。重要的是，许多化合物在BCRP过表达的细胞系中显示出EC50在或低于10 nM，表明这些双价三唑更具选择性地抑制BCRP转运蛋白而不是P-gp和MRP1转运蛋白。大多数二聚体根据其高治疗指数值显示出明显安全的MDR化疗敏感化剂特性。
• [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] FLAVONOID DIMERS AND THEIR USE<br/>[FR] DIMÈRES FLAVONOÏDES ET LEURS APPLICATIONS
  申请人：UNIV MCGILL

  公开号：WO2011137516A1

  公开（公告）日：2011-11-10

  This invention relates to bis-flavonoid compounds of formula Flavonoid-Linker-Y-Linker-Flavonoid, their synthesis and use for inhibiting multidrug resistance in chemotherapy and protozoan infection.

  这项发明涉及到公式为黄酮素-连接子-Y-连接子-黄酮素的双黄酮类化合物，它们的合成以及在化疗和原虫感染中抑制多药耐药性的用途。
• [EN] CONJUGATES OF AN ELECTRON-DONATING NITROGEN OR TERTIARY AMINE COMPRISING COMPOUNDS<br/>[FR] CONJUGUÉS D'AZOTE DONNEUR D'ÉLECTRONS OU DE COMPOSÉS COMPRENANT UNE AMINE TERTIAIRE
  申请人：ASCENDIS PHARMA AS

  公开号：WO2020254602A1

  公开（公告）日：2020-12-24

  The present invention relates to conjugates of an electron-donating heteroaromatic nitrogen or tertiary amine comprising drugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising said conjugates and the use of said conjugates as medicaments.

  本发明涉及包含药物和其药用盐的电子给体杂环氮或三级胺的共轭物，包括含有该共轭物的药物组合物以及将该共轭物用作药物的用途。
• [EN] TOPICAL COMPOSITIONS AND METHODS FOR TREATMENT<br/>[FR] COMPOSITIONS TOPIQUES ET MÉTHODES DE TRAITEMENT
  申请人：ATOSSA GENETICS INC

  公开号：WO2019051370A1

  公开（公告）日：2019-03-14

  The present disclosure provides novel topical compositions comprising endoxifen and salts and solvates thereof and methods for making the compositions. Certain compounds have been combined to make a stable topical compositions comprising endoxifen. The present disclosure also provides methods for treatment of hormone-dependent breast and hormone-dependent reproductive tract disorders.

  本公开提供了包含恩多西芬及其盐和溶剂化物的新型局部组合物，并提供了制备该组合物的方法。某些化合物已被组合以制备稳定的局部组合物，其中包括恩多西芬。本公开还提供了治疗激素依赖性乳腺癌和激素依赖性生殖道疾病的方法。