3-(4-chloro-3-iodo-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]-pyridine-5-carboxylic acid tert-butyl ester | 1049809-51-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(4-chloro-3-iodo-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]-pyridine-5-carboxylic acid tert-butyl ester
• 英文别名: 3-(4-Chloro-3-iodo-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester；tert-butyl 3-(4-chloro-3-iodophenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxylate
• CAS: 1049809-51-9
• 化学式: C₁₇H₁₉ClIN₃O₂
• 分子量: 459.714
• InChiKey: UFXIOSQJAPITHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-chloro-3-iodo-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]-pyridine-5-carboxylic acid tert-butyl ester 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 caesium carbonate 、 戴斯-马丁氧化剂 、 溶剂黄146 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 N-(4-chloro-benzyl)-N-(4-{2-chloro-5-[1-(3-morpholin-4-yl-propyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]phenylethynyl}-benzyl)-2,2,2-trifluoro-acetamide
  参考文献：
  名称：

  Pyrazole-based arylalkyne Cathepsin S inhibitors. Part III: Modification of P4 region

  摘要：

  Novel classes of tetrahydropyrido-pyrazole thioether amines and arylalkynes that display potency against human Cathepsin S have been previously reported. Here, key pharmacophoric elements of these two classes are merged, and SAR investigations of the P4 region are described, in conjunction with re-optimization of the P5 and P1/P1'/P3 regions. Identification of meta-substituted arylalkynes with good potency and improved solubility is described. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.014
• 作为产物：
  描述：

  Tert-butyl 3-(4-chloro-3-iodobenzoyl)-4-oxopiperidine-1-carboxylate 在 肼 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 3-(4-chloro-3-iodo-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]-pyridine-5-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Practical Synthesis of a Cathepsin S Inhibitor: Route Identification, Purification Strategies, and Serendipitous Discovery of a Crystalline Salt Form

  摘要：

  A "redox economical" strategy resulted in it concise, modular synthesis Of Compound 1, it potent Cathepsin S inhibitor. Starting from three building blocks, crude drug substance was prepared in a two-step sequence in high yield. Efficient purification of the crude drug Substance wits accomplished via the formation of an unusual monoethyl oxalate salt.

  DOI：

  10.1021/jo902650b

文献信息

• CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S
  申请人：Ameriks Michael K.

  公开号：US20080200454A1

  公开（公告）日：2008-08-21

  Carbon-linked tetrahydro-pyrazolo-pyridine compounds are described, which are useful as cathepsin S modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by cathepsin S activity, such as psoriasis, pain, multiple sclerosis, atherosclerosis, and rheumatoid arthritis.

  描述了与碳相连的四氢吡唑吡啶化合物，这些化合物可作为cathepsin S调节剂。这些化合物可用于制备药物组合物和治疗疾病状态、疾病和病况的方法，这些疾病状态、疾病和病况是由cathepsin S活性介导的，如银屑病、疼痛、多发性硬化症、动脉粥样硬化和类风湿性关节炎。
• [EN] PROCESSES FOR THE PREPARATION OF CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S<br/>[FR] PROCÉDÉS POUR LA PRÉPARATION DE MODULATEURS CONSTITUÉS DE CATHEPSINE S DE TÉTRAHYDRO-PYRAZOLO-PYRIDINE À LIAISON CARBONE
  申请人：SUNESIS PHARMACEUTICALS INC

  公开号：WO2009102937A1

  公开（公告）日：2009-08-20

  Method of making carbon-linked tetrahydro-pyrazolo-pyridine compounds of the following Formula (I) and pharmaceutically acceptable salts thereof: comprising reacting a compound of formula (IX) with a compound of formula (X) to form a compound of Formula (I); wherein: R1 and R2 taken together with the nitrogen to which they are attached form a morpholine ring, unsubstituted or substituted with one or two methyl substituents; R3 is H or OH; R4 is -SO2CH3, -CONH2, or -COCONH2; R5 is H or methyl; R6 is a benzyl group, unsubstituted or substituted with one or two substituents independently selected from the group consisting of C1-4alkyl, CF3, halo, OH, -OC1-4alkyl, -OCF3, -OCHF2, NRddRee, -CO2C1-4alkyl, -SC1-4alkyl, and -SO2C1-4alkyl; where Rdd and Ree are each independently H or C1-4alkyl; R7 is H, fluoro, or chloro; and LG1 is iodide, bromide, or trifluoromethanesulfonate. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by cathepsin S activity, such as psoriasis, pain, multiple sclerosis, atherosclerosis, and rheumatoid arthritis.

  制备以下化合物Formula (I)及其药用可接受盐的碳连接四氢吡唑吡啶化合物的方法：将Formula (IX)的化合物与Formula (X)的化合物反应以形成Formula (I)的化合物；其中：R1和R2与它们连接的氮一起形成吗啉环，未取代或取代为一个或两个甲基取代基；R3为H或OH；R4为-SO2CH3，-CONH2或-COCONH2；R5为H或甲基；R6为苄基，未取代或取代为一个或两个从C1-4烷基，CF3，卤素，OH，-OC1-4烷基，-O ，-OCHF2，NRddRee，-CO2C1-4烷基，-SC1-4烷基和-SO2C1-4烷基组成的取代基中独立选择的取代基；其中Rdd和Ree各自独立为H或C1-4烷基；R7为H，氟或氯；LG1为碘化物，溴化物或三氟甲磺酸盐。这些化合物可用于药物组合物和治疗由S蛋白酶活性介导的疾病状态、紊乱和病况的方法，如牛皮癣、疼痛、多发性硬化症、动脉粥样硬化和类风湿性关节炎。
• Pyrazole-based cathepsin S inhibitors with arylalkynes as P1 binding elements
  作者：Michael K. Ameriks、Frank U. Axe、Scott D. Bembenek、James P. Edwards、Yin Gu、Lars Karlsson、Mike Randal、Siquan Sun、Robin L. Thurmond、Jian Zhu

  DOI：10.1016/j.bmcl.2009.09.014

  日期：2009.11

  A crystal structure of 1 bound to a Cys25Ser mutant of cathepsin S helped to elucidate the binding mode of a previously disclosed series of pyrazole-based CatS inhibitors and facilitated the design of a new class of arylalkyne analogs. Optimization of the alkyne and tetrahydropyridine portions of the pharmacophore provided potent CatS inhibitors (IC(50) = 40-300 nM), and an X-ray structure of 32 revealed that the arylalkyne moiety binds in the S1 pocket of the enzyme. (c) 2009 Elsevier Ltd. All rights reserved.
• [EN] CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S<br/>[FR] MODULATEURS DE CATHEPSINE S À LA TÉTRAHYDRO-PYRAZOLO-PYRIDINE LIÉS AU CARBONE
  申请人：SUNESIS PHARMACEUTICALS INC

  公开号：WO2008100618A2

  公开（公告）日：2008-08-21

  [EN] Carbon-linked tetrahydro-pyrazolo-pyridine compounds are described, which are useful as cathepsin S modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by cathepsin S activity, such as psoriasis, pain, multiple sclerosis, atherosclerosis, and rheumatoid arthritis.
  [FR] L'invention concerne des composés de tétrahydro-pyrazolo-pyridine liés au carbone qui sont utiles en tant que modulateurs de cathepsine S. De tels composés peuvent être utilisés dans des compositions pharmaceutiques et des procédés pour le traitement de maladies, de troubles et d'états provoqués par l'activité de la cathepsine S, tels que le psoriasis, la douleur, la sclérose multiple, l'athérosclérose, et l'arthrite rhumatoïde.