6-氯-2-甲基烟酰氯化物 | 62366-52-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 6-氯-2-甲基烟酰氯化物
• 英文名称: 6-Chloro-2-methylpyridine-3-carbonyl chloride
• CAS: 62366-52-3
• 化学式: C₇H₅Cl₂NO
• 分子量: 190.029
• InChiKey: GOEBQWNZXWEQIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-氯-2-甲基烟酰氯化物 、 叔丁醇 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以0.022 g的产率得到tert-butyl 6-chloro-2-methylnicotinate
  参考文献：
  名称：

  Small Molecule Antagonist of Leukocyte Function Associated Antigen-1 (LFA-1): Structure−Activity Relationships Leading to the Identification of 6-((5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl)nicotinic Acid (BMS-688521)

  摘要：

  Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18 or alpha(L)beta(2), belongs to the beta(2) integrin subfamily and is constitutively expressed on all leukocytes. The major ligands of LFA-1 include three intercellular adhesion molecules 1, 2, and 3 (ICAM 1, 2, and 3). The interactions between LFA-1 and the ICAMs are critical for cell adhesion, and preclinical animal studies and clinical data from the humanized anti-LFA-1 antibody efalizumab have provided proof-of-concept for LFA-1 as an immunological target. This article will detail the structure activity relationships (SAR) leading to a novel second generation series of highly potent spirocyclic hydantoin antagonists of LFA-1. With significantly enhanced in vitro and ex vivo potency relative to our first clinical compound (1), as well as demonstrated in vivo activity and an acceptable pharmacokinetic and safety profile, 6-((5S,9R)-9-(4-cyanophenyl)-3-(3, 5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro-[4.4]nonan-7-yl)nicotinic acid (2e) was selected to advance into clinical trials.

  DOI：

  10.1021/jm100348u
• 作为产物：
  描述：

  6-氯-2-甲基烟酸 在 氯化亚砜 作用下， 反应 3.0h， 生成 6-氯-2-甲基烟酰氯化物
  参考文献：
  名称：

  Small Molecule Antagonist of Leukocyte Function Associated Antigen-1 (LFA-1): Structure−Activity Relationships Leading to the Identification of 6-((5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl)nicotinic Acid (BMS-688521)

  摘要：

  Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18 or alpha(L)beta(2), belongs to the beta(2) integrin subfamily and is constitutively expressed on all leukocytes. The major ligands of LFA-1 include three intercellular adhesion molecules 1, 2, and 3 (ICAM 1, 2, and 3). The interactions between LFA-1 and the ICAMs are critical for cell adhesion, and preclinical animal studies and clinical data from the humanized anti-LFA-1 antibody efalizumab have provided proof-of-concept for LFA-1 as an immunological target. This article will detail the structure activity relationships (SAR) leading to a novel second generation series of highly potent spirocyclic hydantoin antagonists of LFA-1. With significantly enhanced in vitro and ex vivo potency relative to our first clinical compound (1), as well as demonstrated in vivo activity and an acceptable pharmacokinetic and safety profile, 6-((5S,9R)-9-(4-cyanophenyl)-3-(3, 5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro-[4.4]nonan-7-yl)nicotinic acid (2e) was selected to advance into clinical trials.

  DOI：

  10.1021/jm100348u

文献信息

• Bisamide Inhibitors of Hedgehog Signaling
  申请人：Goldsmith Richard A.

  公开号：US20080269215A1

  公开（公告）日：2008-10-30

  The invention provides inhibitors of hedgehog signaling that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula I: wherein ring A, ring B, R 1 , R 2 , R 3 , R 4 , R 5 , m and n are as defined herein.

  该发明提供了对刺猬信号通路的抑制剂，可用作治疗恶性肿瘤的治疗剂，其中化合物具有一般式I：其中环A、环B、R1、R2、R3、R4、R5、m和n的定义如本文所述。
• BISAMIDE INHIBITORS OF HEDGEHOG SIGNALING
  申请人：Genentech, Inc.

  公开号：EP1957461A1

  公开（公告）日：2008-08-20
• US8101610B2
  申请人：——

  公开号：US8101610B2

  公开（公告）日：2012-01-24
• [EN] BISAMIDE INHIBITORS OF HEDGEHOG SIGNALING<br/>[FR] INHIBITEURS À BASE DE BISAMIDE DU SIGNAL HEDGEHOG
  申请人：GENENTECH INC

  公开号：WO2007059157A1

  公开（公告）日：2007-05-24

  [EN] The invention provides inhibitors of hedgehog signaling that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula (I), wherein ring A, ring B, R₁, R₂, R₃, R₄, R₅, m and n are as defined herein.
  [FR] La présente invention concerne des inhibiteurs du signal hedgehog qui sont utiles comme agents thérapeutiques pour traiter des malignités, dans lesquels les composés présentent la formule générale (I), le noyau A, le noyau B, R₁, R₂, R₃, R₄, R₅, m et n étant tels que définis ici.
• Small Molecule Antagonist of Leukocyte Function Associated Antigen-1 (LFA-1): Structure−Activity Relationships Leading to the Identification of 6-((5<i>S</i>,9<i>R</i>)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl)nicotinic Acid (BMS-688521)
  作者：Scott H. Watterson、Zili Xiao、Dharmpal S. Dodd、David R. Tortolani、Wayne Vaccaro、Dominique Potin、Michele Launay、Dawn K. Stetsko、Stacey Skala、Patric M. Davis、Deborah Lee、Xiaoxia Yang、Kim W. McIntyre、Praveen Balimane、Karishma Patel、Zheng Yang、Punit Marathe、Pathanjali Kadiyala、Andrew J. Tebben、Steven Sheriff、ChiehYing Y. Chang、Theresa Ziemba、Huiping Zhang、Bang-Chi Chen、Albert J. DelMonte、Nelly Aranibar、Murray McKinnon、Joel C. Barrish、Suzanne J. Suchard、T. G. Murali Dhar

  DOI：10.1021/jm100348u

  日期：2010.5.13

  Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18 or alpha(L)beta(2), belongs to the beta(2) integrin subfamily and is constitutively expressed on all leukocytes. The major ligands of LFA-1 include three intercellular adhesion molecules 1, 2, and 3 (ICAM 1, 2, and 3). The interactions between LFA-1 and the ICAMs are critical for cell adhesion, and preclinical animal studies and clinical data from the humanized anti-LFA-1 antibody efalizumab have provided proof-of-concept for LFA-1 as an immunological target. This article will detail the structure activity relationships (SAR) leading to a novel second generation series of highly potent spirocyclic hydantoin antagonists of LFA-1. With significantly enhanced in vitro and ex vivo potency relative to our first clinical compound (1), as well as demonstrated in vivo activity and an acceptable pharmacokinetic and safety profile, 6-((5S,9R)-9-(4-cyanophenyl)-3-(3, 5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro-[4.4]nonan-7-yl)nicotinic acid (2e) was selected to advance into clinical trials.