5-cyclopropyl-3-nitro-4-(piperazin-1-yl)pyridin-2-amine | 1095382-31-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-cyclopropyl-3-nitro-4-(piperazin-1-yl)pyridin-2-amine
• 英文别名: 5-Cyclopropyl-3-nitro-4-piperazin-1-ylpyridin-2-amine
• CAS: 1095382-31-2
• 化学式: C₁₂H₁₇N₅O₂
• 分子量: 263.299
• InChiKey: NPHHZLDPRXLLTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(2-氯乙酰胺基)噻唑 、 5-cyclopropyl-3-nitro-4-(piperazin-1-yl)pyridin-2-amine 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以78%的产率得到2-(4-(2-amino-5-cyclopropyl-3-nitropyridin-4-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide
  参考文献：
  名称：

  Imidazo[4,5-b]pyridine Derivatives As Inhibitors of Aurora Kinases: Lead Optimization Studies toward the Identification of an Orally Bioavailable Preclinical Development Candidate

  摘要：

  Lead optimization studies using 7 as the starting point led to a new class of imidazo[4,5-b]pyridine-based inhibitors of Aurora kinases that possessed the 1-benzylpiperazinyl motif at the 7-position, and displayed favorable in vitro properties. Cocrystallization of Aurora-A with 40c (CCT137444) provided a clear understanding into the interactions of this novel class of inhibitors with the Aurora kinases. Subsequent physicochemical property refinement by the incorporation of solubilizing groups led to the identification of 3-((4-(6-bromo-2-(4-(4-methylpiperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-yl)methyl)-5-methylisoxazole (51, CCT137690) which is a potent inhibitor of Aurora kinases (Aurora-A IC(50) = 0.015 +/- 0.003 muM, Aurora-B IC(50) = 0.025 muM, Aurora-C IC(50) = 0.019 muM). Compound 51 is highly orally bioavailable, and in in vivo efficacy studies it inhibited the growth of SW620 colon carcinoma xenografts following oral administration with no observed toxicities as defined by body weight loss.

  DOI：

  10.1021/jm100262j
• 作为产物：
  描述：

  tert-butyl 4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazine-1-carboxylate 在 palladium diacetate potassium phosphate 、 三氟乙酸 、 三环己基膦 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 3.75h， 生成 5-cyclopropyl-3-nitro-4-(piperazin-1-yl)pyridin-2-amine
  参考文献：
  名称：

  WO2009/1021

  摘要：

  公开号：

文献信息

• [EN] IMIDAZOPYRIDINE DERIVATIVES USEFUL AS ENZYME INHIBITORS FOR THE TREATMENT OF CELL PROLIFERATIVE AND AUTOIMMUNE DISEASES<br/>[FR] DÉRIVÉS D'IMIDAZOPYRIDINE UTILES COMME INHIBITEURS D'ENZYMES POUR LE TRAITEMENT DE MALADIES DE PROLIFÉRATION DES CELLULES ET AUTO-IMMUNES
  申请人：CHROMA THERAPEUTICS LTD

  公开号：WO2009001021A1

  公开（公告）日：2008-12-31

  [EN] The 62 specific compounds disclosed in the description, which fall within the general structural formula (I) below, are inhibitors of aurora kinase enzymes: wherein X is -N-, -CH2-N-, -CH2-CH-, or -CH-; R1 is a radical of formula (IA) wherein Z is -CH2-, -NH-, -O-, -S(O)- -S-, -S(O)2 or a divalent monocyclic carbocyclic or heterocyclic radical having 3-7 ring atoms; AIk is an optionally substituted divalent C1-C6 alkylene radical; A is hydrogen or an optionally substituted monocyclic carbocyclic or heterocyclic ring having 5-7 ring atoms; r, s and t are independently 0 or 1, provided that when A is hydrogen then at least one of r and s is 1; R2 is halogen, -CN, -CF3, -OCH3, or cyclopropyl; and R3 is a radical of formula (IB) wherein Q is hydrogen or an optionally substituted phenyl or monocyclic heterocyclic ring with 5 or 6 ring atoms; Z1 is -S-, -S(O)-, -S(O)2-, -O-, -SO2NH-, -NHSO2-, NHC(=O)NH, -NH(C=S)NH-, Or -N(R4)- wherein R4 is hydrogen, C1-C3 alkyl, cycloalkyl, or benzyl; and AIk1 and AIk2 are, independently, optionally substituted divalent C1-C3 alkylene radicals; and m, n and p are independently O or 1.
  [FR] Les 62 composés spécifiques divulgués dans la description qui tombent dans la définition de la formule structurale générale (I) ci-après sont des inhibiteurs des enzymes Aurora kinases : dans laquelle X représente -N-, -CH2-N-, -CH2-CH- ou -CH- ; R1 est un radical de formule (IA) dans laquelle Z représente -CH2-, -NH-, -O-, -S(O)- -S-, -S(O)2 ou un radical carbocyclique ou hétérocyclique monocyclique divalent ayant 3-7 atomes de cycle ; Alk est un radical alkylène en C1-C6 divalent, facultativement substitué ; A représente hydrogène ou un noyau carbocyclique ou hétérocyclique monocyclique, facultativement substitué, ayant 5-7 atomes de carbone ; r, s et t sont indépendamment 0 ou 1, à la condition que, lorsque A représente hydrogène, alors au moins l'un parmi r et s est 1 ; R2 représente halogène, -CN, -CF3, -OCH3 ou cyclopropyle ; et R3 est un radical de formule (IB) dans laquelle Q représente hydrogène ou un noyau phényle ou monocyclique hétérocyclique facultativement substitué, ayant 5 ou 6 atomes de cycle ; Z1 représente -S-, -S(O)-, -S(O)2-, -O-, -SO2NH-, -NHSO2-, NHC(=O)NH, -NH(C=S)NH- ou -N(R4)- dans laquelle R4 représente hydrogène, alkyle en C1-C3, cycloalkyle ou benzyle ; et Alk1 et Alk2 sont, indépendamment, des radicaux alkylène en C1-C3 divalents facultativement substitués ; et m, n et p sont indépendamment 0 ou 1.
• WO2009/1021
  申请人：——

  公开号：——

  公开（公告）日：——
• Imidazo[4,5-<i>b</i>]pyridine Derivatives As Inhibitors of Aurora Kinases: Lead Optimization Studies toward the Identification of an Orally Bioavailable Preclinical Development Candidate
  作者：Vassilios Bavetsias、Jonathan M. Large、Chongbo Sun、Nathalie Bouloc、Magda Kosmopoulou、Mizio Matteucci、Nicola E. Wilsher、Vanessa Martins、Jóhannes Reynisson、Butrus Atrash、Amir Faisal、Frederique Urban、Melanie Valenti、Alexis de Haven Brandon、Gary Box、Florence I. Raynaud、Paul Workman、Suzanne A. Eccles、Richard Bayliss、Julian Blagg、Spiros Linardopoulos、Edward McDonald

  DOI：10.1021/jm100262j

  日期：2010.7.22

  Lead optimization studies using 7 as the starting point led to a new class of imidazo[4,5-b]pyridine-based inhibitors of Aurora kinases that possessed the 1-benzylpiperazinyl motif at the 7-position, and displayed favorable in vitro properties. Cocrystallization of Aurora-A with 40c (CCT137444) provided a clear understanding into the interactions of this novel class of inhibitors with the Aurora kinases. Subsequent physicochemical property refinement by the incorporation of solubilizing groups led to the identification of 3-((4-(6-bromo-2-(4-(4-methylpiperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-yl)methyl)-5-methylisoxazole (51, CCT137690) which is a potent inhibitor of Aurora kinases (Aurora-A IC(50) = 0.015 +/- 0.003 muM, Aurora-B IC(50) = 0.025 muM, Aurora-C IC(50) = 0.019 muM). Compound 51 is highly orally bioavailable, and in in vivo efficacy studies it inhibited the growth of SW620 colon carcinoma xenografts following oral administration with no observed toxicities as defined by body weight loss.