ethyl 4-(4-fluorophenylsulfonyl)-1-(prop-2-ynyl)piperidine-4-carbox-ylate | 226396-64-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: ethyl 4-(4-fluorophenylsulfonyl)-1-(prop-2-ynyl)piperidine-4-carbox-ylate
• 英文别名: Ethyl 4-(4-fluorophenyl)sulfonyl-1-prop-2-ynylpiperidine-4-carboxylate
• CAS: 226396-64-1
• 化学式: C₁₇H₂₀FNO₄S
• 分子量: 353.415
• InChiKey: UBLHDADGSYAUDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-fluorophenylsulfonyl)-1-(prop-2-ynyl)piperidine-4-carbox-ylate 在 甲醇 、 氢氧化钾 、 caesium carbonate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 乙酰氯 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 29.25h， 生成 SC 276
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of β- and α-Piperidine Sulfone Hydroxamic Acid Matrix Metalloproteinase Inhibitors with Oral Antitumor Efficacy

  摘要：

  alpha-Piperidine-beta-sulfone hydroxamate derivatives were explored that are potent for matrix metalloproteinases (MMP)-2, -9, and -13 and are sparing of MMP-1. The investigation of the beta-sulfones subsequently led to the discovery of hitherto unknown alpha-sulfone hydroxamates that are superior to the corresponding beta-sulfones in potency for target MMPs, selectivity vs MMP-1, and exposure when dosed orally. alpha-Tiperidine-alpha-sulfone, hydroxamate 35f (SC-276) was advanced through antitumor and antiangiogenesis assays and was selected for development. Compound 35f demonstrates excellent antitumor activity vs MX-1 breast tumor in mice when dosed orally as monotherapy or in combination with paclitaxel.

  DOI：

  10.1021/jm0500875
• 作为产物：
  描述：

  1,4-哌啶二羧酸,4-[(4-氟苯基)硫代]-,1-(1,1-二甲基乙基)4-乙基酯 在 盐酸 、 苯酐 、 过氧化脲素 、 potassium carbonate 作用下， 以 醋酸异丙酯 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.17h， 生成 ethyl 4-(4-fluorophenylsulfonyl)-1-(prop-2-ynyl)piperidine-4-carbox-ylate
  参考文献：
  名称：

  含碳硼烷的基质金属蛋白酶 (MMP) 配体作为硼中子俘获疗法 (BNCT) 的候选者。

  摘要：

  基于先前报道的强效选择性砜异羟肟酸酯抑制剂 SC-76276、SC-78080 (SD-2590) 和 SC-77964，已经设计并合成了有效的 MMP 抑制剂，通过点击化学添加富硼碳硼烷簇靶向已知上调明胶酶的肿瘤细胞。与 MMP-2 对接表明结合涉及异羟肟酸锌结合基团、砜部分与肽骨架残基 Leu82 和 Leu83 的关键 H 键，以及与深 P1' 口袋的疏水相互作用。两种三唑区域异构体中更有效的一种的 IC 50与 MMP-2 相比为 3.7 nM，IC 50与 MMP-9 相比为 46 nM。

  DOI：

  10.1002/cmdc.202000470

文献信息

• [EN] CARBORANE HYDROXAMIC ACID MATRIX METALLOPROTEINASE INHIBITORS AND AGENTS FOR BORON NEUTRON CAPTURE THERAPY<br/>[FR] INHIBITEURS DE MÉTALLOPROTÉINASE MATRICIELLE D'ACIDE HYDROXAMIQUE CARBORANE ET AGENTS POUR UNE THÉRAPIE PAR CAPTURE DE NEUTRONS PAR LE BORE
  申请人：UNIV LOYOLA CHICAGO

  公开号：WO2020006384A1

  公开（公告）日：2020-01-02

  Disclosed herein are novel carborane hydroxamic acid matrix metalloproteinase ("MMP") inhibitors and agents bearing borane-containing moieties and methods for their use in treating or preventing a disease, such as cancer and rheumatoid arthritis. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salt thereof: Formula (I) wherein the substituents are as described.

  本文披露了新型碳硼烷羟肟酸基金属蛋白酶抑制剂和含硼基团的药物，以及它们在治疗或预防疾病（如癌症和类风湿性关节炎）中的使用方法。具体来说，本文披露了化合物的结构式（I）及其药用盐：结构式（I）中的取代基如所述。
• Orally Active MMP-1 Sparing α-Tetrahydropyranyl and α-Piperidinyl Sulfone Matrix Metalloproteinase (MMP) Inhibitors with Efficacy in Cancer, Arthritis, and Cardiovascular Disease
  作者：Daniel P. Becker、Thomas E. Barta、Louis J. Bedell、Terri L. Boehm、Brian R. Bond、Jeffery Carroll、Chris P. Carron、Gary A. DeCrescenzo、Alan M. Easton、John N. Freskos、Chris L. Funckes-Shippy、Marcia Heron、Susan Hockerman、Carol Pearcy Howard、James R. Kiefer、Madeleine H. Li、Karl J. Mathis、Joseph J. McDonald、Pramod P. Mehta、Grace E. Munie、Teresa Sunyer、Craig A. Swearingen、Clara I. Villamil、Dean Welsch、Jennifer M. Williams、Ying Yu、Jun Yao

  DOI：10.1021/jm100669j

  日期：2010.9.23

  alpha-Sulfone-alpha-piperidine and alpha-tetrahydropyranyl hydroxamates were explored that are potent inhibitors of MMP's-2, -9, and -13 that spare MMP-1, with oral efficacy in inhibiting tumor growth in mice and left-ventricular hypertrophy in rats and in the bovine cartilage degradation ex vivo explant system. alpha-Piperidine 19v (SC-78080/SD-2590) was selected for development toward the initial indication of cancer, while alpha-piperidine and alpha-tetrahydropyranyl hydroxamates 19w (SC-77964) and 9l (SC-77774), respectively, were identified as backup compounds.
• CARBORANE HYDROXAMIC ACID MATRIX METALLOPROTEINASE INHIBITORS AND AGENTS FOR BORON NEUTRON CAPTURE THERAPY
  申请人：LOYOLA UNIVERSITY OF CHICAGO

  公开号：US20210290763A1

  公开（公告）日：2021-09-23

  Disclosed herein are novel carborane hydroxamic acid matrix metalloproteinase (“MMP”) inhibitors and agents bearing borane-containing moieties and methods for their use in treating or preventing a disease, such as cancer and rheumatoid arthritis. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salt thereof: Formula (I) wherein the substituents are as described.