4-溴-N-[1-[7-氯-3,4-二氢-4-氧代-3-(苯基甲基)-2-喹唑啉基]丙基]-N-[3-(二甲基氨基)丙基]-苯甲酰胺 | 336115-72-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-溴-N-[1-[7-氯-3,4-二氢-4-氧代-3-(苯基甲基)-2-喹唑啉基]丙基]-N-[3-(二甲基氨基)丙基]-苯甲酰胺
• 中文别名: 丁酰胺,3-羰基-N-(5,6,7,9-四氢-1,2,3,10-四甲氧基-9-羰基苯并[a]庚搭烯-7-基)-,(S)-(9CI)
• 英文名称: CK0106023
• 英文别名: N-[1-(3benzyl-7-chloro-4-oxoquinazolin-2-yl)propyl]-4-bromo-N-[3(dimethylamino)propyl]benzamide；Benzamide, 4-bromo-N-(1-(7-chloro-3,4-dihydro-4-oxo-3-(phenylmethyl)-2-quinazolinyl)propyl)-N-(3-(dimethylamino)propyl)-；N-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)propyl]-4-bromo-N-[3-(dimethylamino)propyl]benzamide
• CAS: 336115-72-1
• 化学式: C₃₀H₃₂BrClN₄O₂
• 分子量: 595.967
• InChiKey: PZVLDHUUSWUATQ-UHFFFAOYSA-N

物化性质

• 沸点：
  717.0±70.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  56.2
• 氢给体数：
  0
• 氢受体数：
  4

制备方法与用途

这是一种强效、特异性的allosteric抑制剂，针对KSP马达结构域ATP酶活性，其Ki值为12纳摩尔。

文献信息

• COMBINATIONS OF PYRAZOLE DERIVATIVES FOR THE INHIBITION OF CDKS AND GSK'S
  申请人：Lyons John Francis

  公开号：US20100021420A1

  公开（公告）日：2010-01-28

  A combination comprising (a) a compound of formula (0): or salts or tautomers or N-oxides or solvates thereof; wherein X is R 1 -A-NR 4 — or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO 2 , C═O, NR 9 (C═O) or 0(C═O) wherein R 9 is hydrogen or C 1-4 hydrocarbyl optionally substituted by hydroxy or C 1-4 alkoxy; Y is a bond or an alkylene chain of 1 to 3 carbon atoms; R 1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or an optionally substituted C 1-8 hydrocarbyl group wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO 2 ; R 2 is hydrogen; halogen; C 1-4 alkoxy; or a C 1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C 1-4 alkoxy; R 3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R 4 is hydrogen or a C 1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C 1-4 alkoxy; and (b) a compound of formula (I′″) or salts, tautomers, solvates and N-oxides thereof: wherein R 1 is 2,6-dichlorophenyl; R 2a and R 2b are both hydrogen; and R 3 is a group: formula (A) where R 4 is C 1-4 alkyl.

  一个组合物，包括（a）式（0）的化合物：或其盐或互变异构体或N-氧化物或溶剂合物；其中X为R1-A-NR4-或5-或6-成员的碳环或杂环环；A为键，SO2，C═O，NR9（C═O）或0（C═O），其中R9为氢或C1-4烃基，可选择地被羟基或C1-4烷氧基取代；Y为键或1至3个碳原子的烷基链；R1为氢；具有3至12个环成员的碳环或杂环基；或可选择地被卤代、羟基或C1-4烷氧基取代的C1-8烃基，其中烃基的1或2个碳原子可选择地被从O、S、NH、SO、SO2中选择的原子或基团取代；R2为氢；卤素；C1-4烷氧基；或可选择地被卤代、羟基或C1-4烷氧基取代的C1-4烃基；R3选自氢和具有3至12个环成员的碳环或杂环基；和R4为氢或可选择地被卤代、羟基或C1-4烷氧基取代的C1-4烃基；和（b）式（I′″）的化合物或其盐、互变异构体、溶剂合物和N-氧化物：其中R1为2,6-二氯苯基；R2a和R2b均为氢；和R3为一个基团：式（A），其中R4为C1-4烷基。
• PHARMACEUTICAL COMBINATIONS OF 1-CYCLOPROPYL-3- [3-(5-M0RPHOOLIN-4-YL-METHYL-1H-BENZOIMIDAZOL-2-YL)- LH-1-PYRAZOL-4-YL]- UREA
  申请人：Curry Jayne Elizabeth

  公开号：US20100055094A1

  公开（公告）日：2010-03-04

  The invention provides combinations of an ancillary compound and a compound which is a salt of 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea selected from the lactate and citrate salts and mixtures thereof. Also provided are crystalline forms of the salts, methods for making the salts and their uses in treating cancers. The invention further provides combinations of an ancillary compound and a compound of the formula (I) as defined in PCT/GB2004/002824 (WO 2005/002552) or a compound of the formula (I′) or a salt, solvate, tautomer or N-oxide thereof, wherein R 1 , E, A and M are as defined in the claims.

  该发明提供了一种辅助化合物和一种盐化合物的组合物，所述盐化合物为1-环丙基-3-[3-(5-吗啉-4-基甲基-1H-苯并咪唑-2-基)-1H-吡唑-4-基]-脲的盐，所述盐选自乳酸盐和柠檬酸盐及其混合物。还提供了所述盐的晶型形式，制备所述盐的方法以及它们在治疗癌症中的用途。该发明进一步提供了一种辅助化合物和根据PCT/GB2004/002824（WO 2005/002552）中定义的式（I）或式（I'）的化合物的组合物，或者其盐、溶剂化合物、互变异构体或N-氧化物，其中R1、E、A和M如权利要求中所定义。
• Methods and compositions utilizing quinazolinones
  申请人：Finer Jeffrey T.

  公开号：US20080182864A1

  公开（公告）日：2008-07-31

  Quinazolinones of formulae (a, b, c and d) are disclosed. They are useful for treating cellular proliferative diseases and disorders associated with KSP kinesin activity.

  公开了式（a、b、c和d）的喹唑啉酮。它们可用于治疗与KSP肌动蛋白活性相关的细胞增殖性疾病和疾病。
• PHARMACEUTICAL COMBINATIONS
  申请人：Lyons John Francis

  公开号：US20090263398A1

  公开（公告）日：2009-10-22

  The invention provides a combination comprising an ancillary compound and a compound having the formula (0): or salts or tautomers or N-oxides or solvates thereof; wherein X is a group R 1 -A-NR 4 — or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO 2 , C═O, NR 9 (C═O) or 0(C═O) wherein R 9 is hydrogen or C 1-4 hydrocarbyl optionally substituted by hydroxy or C 1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R 1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C 1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen, hydroxy, C 1-4 hydrocarbyloxy, amino, mono- or di-C 1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO 2 ; R 2 is hydrogen; halogen; C 1-4 alkoxy; or a C 1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C 1-4 alkoxy; R 3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C 1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C 1-4 alkoxy.

  本发明提供一种组合物，包括一个辅助化合物和一个具有以下公式（0）或其盐或异构体或N-氧化物或溶剂化物的化合物；其中X是一个R1-A-NR4-基团或一个5-或6-环碳或杂环基团；A是一个键，SO2，C═O，NR9（C═O）或0（C═O），其中R9是氢或C1-4烃基，可选地被羟基或C1-4烷氧基取代；Y是一个键或长度为1、2或3个碳原子的烷基链；R1是氢；一个具有3至12个环成员的碳环或杂环基团；或一个C1-8烃基，可选地被一个或多个卤素、羟基、C1-4烷氧基、氨基、单或双C1-4烷基氨基和具有3至12个环成员的碳环或杂环基团的取代基所取代，其中烃基的1或2个碳原子可以可选地被O、S、NH、SO或SO2中的一个原子或基团取代；R2是氢；卤素；C1-4烷氧基；或一个C1-4烃基，可选地被卤素、羟基或C1-4烷氧基取代；R3选择自氢和具有3至12个环成员的碳环或杂环基团；R4是氢或一个C1-4烃基，可选地被卤素、羟基或C1-4烷氧基取代。
• METHODS AND COMPOSTIONS UTILIZIING QUINAZOLINONES
  申请人：Finer Jeffrey T.

  公开号：US20100210670A1

  公开（公告）日：2010-08-19

  Quinazolinones of formulae (a, b, c and d) are disclosed. They are useful for treating cellular proliferative diseases and disorders associated with KSP kinesin activity.

  公开了化学式为(a、b、c和d)的喹嗪酮类化合物。它们可用于治疗与KSP肌动蛋白活性相关的细胞增殖性疾病和疾病。