(2R)-3-azido-2-hydroxypropyl p-toluenesulfonate | 136459-46-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R)-3-azido-2-hydroxypropyl p-toluenesulfonate
• 英文别名: [(2R)-3-azido-2-hydroxypropyl] 4-methylbenzenesulfonate
• CAS: 136459-46-6
• 化学式: C₁₀H₁₃N₃O₄S
• 分子量: 271.297
• InChiKey: GSOZMIFQWCNBHZ-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R)-3-azido-2-hydroxypropyl p-toluenesulfonate 、 2-(1-methylethoxy)phenyl-1-piperazine 在 三乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 30.0h， 以50%的产率得到(S)-α-(azidomethyl)-4-[2-(1-methylethoxy)phenyl]-1-piperazineethanol
  参考文献：
  名称：

  Design, synthesis and biological evaluation of pyridine-phenylpiperazines: A novel series of potent and selective α1a-adrenergic receptor antagonist

  摘要：

  Beginning from the screening hit and literature alpha(1)-adrenergic compounds, a hybridized basic skeleton A was proposed as the pharmacophore for potent and selective alpha(1a)-AR antagonists. Introduction of a hydroxy group to increase the flexibility afforded B which served as the screening model and resulted in the identification of the second-generation lead 1. Using the Topliss approach, a number of potent and selective alpha(1a)-AR antagonists were discovered. In all cases, binding affinity and selectivity at the alpha(1a)-AR of S-hydroxy enantiomers were higher than the R-hydroxy enantiomers. As compared to the des-hydroxy analogues, the S-hydroxy enantiomers displayed comparable potency and better selectivity at alpha(1a)-AR. The S-hydroxy enantiomer 17 (K-i = 0.79 nM; alpha(1b)/alpha(1a) = 800; alpha(1d)/alpha(1a) = 104) was slightly less potent but much more selective at alpha(1a)-AR than tamsulosin (K-i = 0.13 nM, alpha(1b)/alpha(1a) = 15, alpha(1d)/alpha(1a) = 1.4). Compound 17 displayed higher selectivity in inhibiting rat prostate contraction over rat aorta contraction and also exhibited a higher degree of uroselectivity than tamsulosin in the anesthetized dog model. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00151-6
• 作为产物：
  描述：

  (R)-(-)-对甲基苯磺酸-2,2-二甲基-1,3-二氧戊环基-4-甲酯 在 ruthenium trichloride 盐酸 、 sodium periodate 、 氯化亚砜 、 sodium azide 、 三乙胺 作用下， 以 四氯化碳 、 二氯甲烷 、 水 、 丙酮 、 乙腈 为溶剂， 反应 3.17h， 生成 (2R)-3-azido-2-hydroxypropyl p-toluenesulfonate
  参考文献：
  名称：

  Lohray; Rajesh; Bhushan, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2002, vol. 41, # 3, p. 586 - 592

  摘要：

  DOI：

文献信息

• Ring-opening of glycidyl derivatives by silanes mediated by Ti(O-il-Pr)4 or Al(O-i-Pr)3: Access to versatile C3 building blocks.
  作者：Kun I. Sutowardoyo、Denis Sinou

  DOI：10.1016/s0957-4166(00)82168-0

  日期：1991.1

  Ring-opening of chiral glycidol or glycidyl tosylate by Me3SiN3 or Me3SiCN catalyzed by Ti(O-i-Pr)4 or Al(O-i-Pr)3 occured in a regiospecific manner and with very high stereoselectivity, leading to new trifunctionalized chiral building blocks. The enantiomeric excess of the ring-opened products was 90−95 %, as determined by 1H NMR of the Mosher ester derivatives, indicating that there was not significant

  Ti（O- i- Pr）4或Al（O- i- Pr）3催化的Me 3 SiN 3或Me 3 SiCN催化手性缩水甘油或甲苯磺酸缩水甘油酯的开环反应是区域特异性的，并且立体选择性很高，导致新的三功能手性构建基块。通过Mosher酯衍生物的1 H NMR测定，开环产物的对映体过量为90-95％，这表明在开环过程中光学纯度没有明显降低。该方法用于在94％ee（丙醇类似物的前体）中一锅合成（R）-1-叠氮基-3-萘氧基-2-羟基丙烷。
• [EN] PHTALIMIDO ARYLPIPERAZINES AS ALPHA 1A RECEPTOR ANTAGONISTS USEFUL IN THE TREATMENT OF BENIGN PROSTATIC HYPERPLASIA<br/>[FR] PHTALIMIDO-ARYLPIPERAZINES UTILES DANS LE TRAITEMENT DE L'HYPERPLASIE PROSTATIQUE BENIGNE EN TANT QU'ANTAGONISTES DU RECEPTEUR ALPHA IA
  申请人：ORTHO-McNEIL PHARMACEUTICAL, INC.

  公开号：WO1999042445A1

  公开（公告）日：1999-08-26

  (EN) This invention relates to a series of heterocyclic substituted piperazines of Formula (I), pharmaceutical compositions containing them and intermediates used in their manufacture. The compounds of the invention selectively inhibit binding to the $g(a)-1a adrenergic receptor, a receptor which has been implicated in benign prostatic hyperplasia. As such the compounds are potentially useful in the treatment of this disease.(FR) L'invention concerne une série de pipérazines hétérocycliques substituées représentées par la formule I: (I), ainsi que des compositions pharmaceutiques contenant ces pipérazines et des intermédiaires utilisé dans la préparation de ces dernières. Ces composés inhibent de manière sélective la liaison au récepteur adrénergique $g(a)-1a, un récepteur dont on a démontré le rôle dans l'hyperplasie prostatique bénigne. Ces composés présentent par conséquent une utilité potentielle pour le traitement de cette pathologie.

  该发明涉及一系列Formula (I)的杂环取代哌嗪、包含它们的制药组合物和用于其制造的中间体。该发明的化合物选择性地抑制与$g(a)-1a肾上腺素能受体的结合，该受体已被证明在良性前列腺增生中起作用。因此，这些化合物在治疗该疾病方面具有潜在的用途。
• Phthalimido arylpiperazines as alpha 1A receptor antagonists useful in the treatment of benign prostatic hyperplasia
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1346983A2

  公开（公告）日：2003-09-24

  This invention relates to a series of heterocyclic substituted piperazines of Formula (I), pharmaceutical compositions containing them and intermediates used in their manufacture. The compounds of the invention selectively inhibit binding to the α-1a adrenergic receptor, a receptor which has been implicated in benign prostatic hyperplasia. As such the compounds are potentially useful in the treatment of this disease.

  本发明涉及一系列式（I）的杂环取代哌嗪类化合物、含有这些化合物的药物组合物以及用于制造这些化合物的中间体。本发明的化合物可选择性地抑制与 α-1a 肾上腺素能受体的结合，该受体与良性前列腺增生症有关。因此，本发明化合物可用于治疗这种疾病。
• Novel phthalimido arylpiperazines useful in the treatment of benign prostatic hyperplasia
  申请人：——

  公开号：US20020077476A1

  公开（公告）日：2002-06-20

  This invention relates to a series of heterocyclic substituted piperazines of Formula I 1 pharmaceutical compositions containing them and intermediates used in their manufacture. The compounds of the invention selectively inhibit binding to the &agr;-1 a adrenergic receptor, a receptor which has been implicated in benign prostatic hyperplasia. As such the compounds are potentially useful in the treatment of this disease.

  本发明涉及一系列式 I 的杂环取代的哌嗪类化合物 1 含有这些化合物的药物组合物以及用于制造这些化合物的中间体。本发明的化合物可选择性地抑制与 &agr;-1 a 肾上腺素能受体（一种与良性前列腺增生有关的受体）的结合。因此，本发明化合物可用于治疗这种疾病。
• Design, Synthesis, and Structure−Activity Relationships of Phthalimide-Phenylpiperazines:  A Novel Series of Potent and Selective α₁_a-Adrenergic Receptor Antagonists
  作者：Gee-Hong Kuo、Catherine Prouty、William V. Murray、Virginia Pulito、Linda Jolliffe、Peter Cheung、Sally Varga、Mary Evangelisto、Jian Wang

  DOI：10.1021/jm9905918

  日期：2000.6.1

  Beginning from the screening hit and literature alpha(1)-adrenergic compounds, a hybridized basic skeleton A was proposed as the pharmacophore for potent and selective alpha(1a)-AR antagonists. Introduction of a hydroxy group to increase the flexibility afforded B which served as the screening model and resulted in the identification of the second-generation lead 1. Using the Topliss approach, a number of potent and selective alpha(1a)-AR antagonists were discovered. In all cases, binding affinity and selectivity at the alpha(1a)-AR of S-hydroxy enantiomers were higher than those of the R-hydroxy enantiomers. As compared to the des-hydroxy analogues, the S-hydroxy enantiomers had slightly lower binding affinity at alpha(1a)-AR but gained more than 2-fold selectivity for alpha(1a)-AR over alpha(1b)-AR, and 2- to 6-fold selectivity for alpha(1a)-AR over alpha(1d)-AR. They also had less cross activities against a panel of 25-35 peripheral and CNS receptors. The S-hydroxy enantiomers 23 and 24 (K-i = 0.29 nM, 0.33 nM; alpha(1b)/alpha(1a) >5690, >6060; alpha(1d)/alpha(1a) = 186, 158, respectively) were slightly less potent but much more selective at alpha(1a)-AR than tamsulosin (K-i = 0.13 nM, alpha(1d)/alpha(1a)= 14.8, alpha(1d)/alpha(1a) = 1.4). In the functional assay, the S-hydroxy enantiomers 20, 23, and 24 were less potent than tamsulosin in inhibiting contractions of rat prostate tissue but more selective in the inhibition of tissue contractions of rat prostate versus rat aorta. Compound 24 was selected as the development candidate for the treatment of BPH.