2-amino-5-methoxy-4-(3-(pyrrolidin-1-yl)propoxy)benzamide hydrochloride | 199327-74-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-amino-5-methoxy-4-(3-(pyrrolidin-1-yl)propoxy)benzamide hydrochloride
• 英文别名: 2-amino-5-methoxy-4-(3-pyrrolidin-1-ylpropoxy)benzamide hydrochloride；2-amino-5-methoxy-4-(3-pyrrolidin-1-ylpropoxy)benzamide;hydrochloride
• CAS: 199327-74-7
• 化学式: C₁₅H₂₃N₃O₃*ClH
• 分子量: 329.827
• InChiKey: DCVHRHNUNDARMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.66
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  90.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-5-methoxy-4-(3-(pyrrolidin-1-yl)propoxy)benzamide hydrochloride 在 sodium acetate 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以83%的产率得到6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]-3,4-dihydroquinazolin-4-one
  参考文献：
  名称：

  Quinazoline derivatives with anti-tumour activity

  摘要：

  这项发明涉及式I的喹唑啉衍生物，其中m、R1、n、R2和R3中的每一个具有描述中定义的任意含义；它们的制备方法，含有它们的药物组合物以及它们在制造用作抗侵袭剂的药物的过程中在固体肿瘤疾病的控制和/或治疗中的使用。

  公开号：

  US20040048881A1
• 作为产物：
  描述：

  5-methoxy-2-nitro4-(3-(pyrrolidin-1-yl)propoxy)benzamide 在 盐酸 、 铁粉 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 2-amino-5-methoxy-4-(3-(pyrrolidin-1-yl)propoxy)benzamide hydrochloride
  参考文献：
  名称：

  QUINAZOLINE DERIVATIVES AS ANGIOGENESIS INHIBITORS

  摘要：

  公开号：

  EP1154774B1

文献信息

• Oxindole derivatives
  申请人：Zeneca Limited

  公开号：US06265411B1

  公开（公告）日：2001-07-24

  The invention relates to compounds of formula (I), wherein: R2 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino, nitro, C2-4alkanoyl, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylthio, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, overscore (N)}—C1-4alkylcarbamoyl, overscore (N)},overscore (N)}-di(C1-4alkyl)carbamoyl, aminosulphonyl, overscore (N)}—C1-4alkylaminosulphonyl, overscore (N)},overscore (N)}-di(C1-4alkyl)aminosulphonyl, C1-4alkylsulphonylamino, or a group R4X1 wherein X1 represents a direct bond, C2-4alkanoyl, —CONR5R6—, —SO2NR7R8— or —SO2R9— (wherein R5 and R7, each independently represents hydrogen or C1-2alkyl and R6, R8 and R9 each independently represents C1-4alkyl and wherein R4 is linked to R6, R8 or R9) and R4 represents an optionally substituted group selected from phenyl and a 5 or 6-membered heterocyclic group; n is an integer from 0 to 4, R1 represents hydrogen, C1-4alkyl, C1-4alkoxymethyl, di(C1-4alkoxy)methyl or C1-4alkanoyl; m is an integer from 0 to 4; and R3 represents hydroxy, halogeno, nitro, trifluoromethyl, C1-3alkyl, cyano, amino or R10X2 (wherein X2 represents a direct bond, —CH2—, or a single or double heteroatom linker group including —S—, —SO— and —NR15— (wherein R15 represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl), and R10 is an alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R10 is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF and FGF, properties of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

  本发明涉及公式(I)的化合物，其中：R2代表羟基，卤素，C1-3烷基，C1-3烷氧基，C1-3烷氧酰基，三氟甲基，氰基，氨基，硝基，C2-4烷氧酰基，C1-4烷氧酰氨基，C1-4烷氧羰基，C1-4烷基亚硫酰基，C1-4烷基亚磺酰基，C1-4烷基亚磺酰基，碳酸酰基，N}-C1-4烷基碳酸酰基，N},N}-二(C1-4烷基)碳酸酰基，氨基磺酰基，N}-C1-4烷基氨基磺酰基，N},N}-二(C1-4烷基)氨基磺酰基，C1-4烷基亚磺酰氨基，或R4X1基团，其中X1代表直接键，C2-4烷氧酰基，-CONR5R6-，-SO2NR7R8-或-SO2R9-（其中R5和R7，每个独立地代表氢或C1-2烷基，R6，R8和R9每个独立地代表C1-4烷基，R4连接到R6，R8或R9），R4代表可选地取代的基团，选自苯基和5或6成员的杂环组；n是0到4的整数，R1代表氢，C1-4烷基，C1-4烷氧甲基，二(C1-4烷氧基)甲基或C1-4烷氧酰基；m是0到4的整数；R3代表羟基，卤素，硝基，三氟甲基，C1-3烷基，氰基，氨基或R10X2（其中X2代表直接键，-CH2-，或包括-S-，-SO-和-NR15-的单个或双杂原子连接基团（其中R15代表氢，C1-3烷基或C1-3烷氧基C2-3烷基），R10是可选地取代的烯基或炔基链，例如羟基，氨基，硝基，烷基，环烷基，烷氧基烷基，或从吡啶酮，苯基和杂环环中选择的可选地取代的基团，该烷基，烯基或炔基链可具有杂原子连接基团，或R10是可选地取代的基团，选自吡啶酮，苯基和杂环环。公式(I)的化合物及其药用盐抑制VEGF和FGF的活性，这些活性在包括癌症和类风湿性关节炎在内的多种疾病状态的治疗中具有重要价值。
• Quinazoline derivatives
  申请人：——

  公开号：US20040044015A1

  公开（公告）日：2004-03-04

  The invention concerns quinazoline derivatives of Formula (I) wherein each of m, R 1 , n, R 2 and R 3 have any of the meanings defined in the description; process for the preparation, pharmaceutical compositions them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.

  这项发明涉及式（I）的喹唑啉衍生物，其中m、R1、n、R2和R3中的每一个具有描述中定义的任意含义；制备过程，药物组合物及其在制备用作抗侵袭剂的药物中的使用，用于包含和/或治疗固体肿瘤疾病。
• [EN] QUINAZOLINE DERIVATIVES AS ANGIOGENESIS INHIBITORS<br/>[FR] DERIVES DE QUINAZOLINE UTILISES COMME INHIBITEURS DE L'ANGIOGENESE
  申请人：ASTRAZENECA UK LTD

  公开号：WO2000047212A1

  公开（公告）日：2000-08-17

  The invention relates to the use of compounds of formula (I), wherein ring C is an 8, 9, 10, 12 or 13-membered bicyclic or tricyclic moiety which optionally may contain 1-3 heteroatoms selected independently from O, N and S; Z is -O-, -NH-, -S-, -CH2- or a direct bond; n is 0-5; m is 0-3; R2 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C¿1-3?alkyl, C1-3alkoxy, C1-3alkylsulphanyl, -NR?3R4¿ (wherein R?3 and R4¿, which may be the same or different, each represents hydrogen or C¿1-3?alkyl), or R?5X1¿- (wherein X?1 and R5¿ are as defined herein; R1 represents hydrogen, oxo, halogeno, hydroxy, C¿1-4?alkoxy, C1-4alkyl, C1-4alkoxymethyl, C1-4alkanoyl, C1-4haloalkyl, cyano, amino, C2-5alkenyl, C2-5alkynyl, C1-3alkanoyloxy, nitro, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylsulphanyl, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, N-C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, aminosulphonyl, N-C1-4alkylaminosulphonyl, N,N-di(C1-4alkyl)aminosulphonyl, N-(C1-4alkylsulphonyl)amino, N-(C1-4alkylsulphonyl)-N-(C1-4alkyl)amino, N,N-di(C1-4alkylsulphonyl)amino, a C3-7alkylene chain joined to two ring C carbon atoms, C1-4alkanoylaminoC1-4alkyl, carboxy or a group R?56X10¿ (wherein X?10 and R56¿ are as defined herein); and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula (I). The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

  本发明涉及使用式(I)的化合物，其中环C是一个含有1-3个杂原子（独立选择自O、N和S）的8、9、10、12或13元的双环或三环基团；Z是-O-、-NH-、-S-、-CH2-或直接键；n为0-5；m为0-3；R2代表氢、羟基、卤代、氰基、硝基、三氟甲基、C1-3烷基、C1-3烷氧基、C1-3烷基硫基、-NR3R4（其中R3和R4，可能相同或不同，每个代表氢或C1-3烷基），或R5X1-（其中X1和R5如上定义）；R1代表氢、氧代、卤代、羟基、C1-4烷氧基、C1-4烷基、C1-4烷氧甲基、C1-4烷酰基、C1-4卤代烷基、氰基、氨基、C2-5烯基、C2-5炔基、C1-3烷酰氧基、硝基、C1-4烷酰胺基、C1-4烷氧羰基、C1-4烷基硫基、C1-4烷基亚砜基、C1-4烷基磺酰基、氨基甲酰基、N-C1-4烷基氨基甲酰基、N,N-二(C1-4烷基)氨基甲酰基、氨基磺酰基、N-C1-4烷基氨基磺酰基、N,N-二(C1-4烷基)氨基磺酰基、N-(C1-4烷基磺酰基)氨基、N-(C1-4烷基磺酰基)-N-(C1-4烷基)氨基、N,N-二(C1-4烷基磺酰基)氨基、与两个环C碳原子连接的C3-7烷基链、C1-4烷酰胺基C1-4烷基、羧基或R56X10基团（其中X10和R56如上定义）；以及其盐，在制备用于在温血动物中产生抗血管生成和/或血管通透性降低效应的药物中使用，制备这种化合物的过程，包含式(I)的化合物或其药学上可接受的盐作为活性成分的制药组合物和式(I)的化合物。式(I)的化合物及其药学上可接受的盐抑制VEGF的效果，这是治疗包括癌症和类风湿性关节炎在内的许多疾病状态的有价值的属性。
• Quinazoline compounds with therapeutic use
  申请人：Moore Corine Nelly

  公开号：US20050009850A1

  公开（公告）日：2005-01-13

  The invention concerns the use of the quinazoline derivatives of Formula (I) wherein each of m, R 1 , Z, n and R 3 have any of the meanings defined in the description in the manufacture of a medicament for use in the prevention or treatment of T cell mediated diseases or medical conditions in a warm-blooded animal.

  本发明涉及在温血动物中预防或治疗T细胞介导的疾病或医疗状况的药物制剂的制造中使用式（I）的喹唑啉衍生物，其中m，R1，Z，n和R3中的每一个都具有描述中定义的任何含义。
• Quinazoline derivatives as angiogenesis inhibitors
  申请人：Stokes SE Elaine

  公开号：US20060004017A1

  公开（公告）日：2006-01-05

  The invention relates to the use of compounds of formula (I), wherein ring C is an 8, 9, 10, 12 or 13-membered bicyclic or tricyclic moiety which optionally may contain 1-3 heteroatoms selected independently from O, N and S; Z is —O—, —NH—, —S—, —CH 2 — or a direct bond; n is 0-5; m is 0-3; R 2 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylsulphanyl, —NR 3 R 4 (wherein R 3 and R 4 , which may be the same or different, each represents hydrogen or C 1-3 alkyl), or R 5 X t — (wherein X 1 and R 5 are as defined herein; R 1 represents hydrogen, oxo, halogeno, hydroxy, C 1-4 alkoxy, C 1-4 alkyl, C 1-4 alkoxymethyl, C 1-4 alkanoyl, C 1-4 haloalkyl, cyano, amino, C 2-5 alkenyl, C 2-5 alkynyl, C 1-3 alkanoyloxy, nitro, C 1-4 alkanoylamino, C 1-4 alkoxycarbonyl, C 1-4 alkylsulphanyl, C 1-4 alkylsulphinyl, C 1-4 alkylsulphonyl, carbamoyl, N —C 1-4 alkylcarbamoyl, N,N -di(C 1-4 alkyl)carbamoyl, aminosulphonyl, N —C 1-4 alkylaminosulphonyl, N,N -di(C 1-4 alkyl)aminosulphonyl, N -(C 1-4 alkylsulphonyl)amino, N —(C 1-4 alkylsulphonyl)— N —(C 1-4 alkyl)amino, N,N -di(C 1-4 alkylsulphonyl)amino, a C 3-7 alkylene chain joined to two ring C carbon atoms, C 1-4 alkanoylaminoC 1-4 alkyl, carboxy or a group R 56 X 10 (wherein X 10 and R 56 are as defined herein); and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula (I). The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

  本发明涉及使用公式（I）的化合物，其中环C是一个包含1-3个独立选择的杂原子O、N和S的8、9、10、12或13元双环或三环基团；Z是-O-、-NH-、-S-、-CH2-或直接键；n为0-5；m为0-3；R2表示氢、羟基、卤代、氰基、硝基、三氟甲基、C1-3烷基、C1-3烷氧基、C1-3烷基硫基、-NR3R4（其中R3和R4，可以相同，也可以不同，分别表示氢或C1-3烷基），或R5Xt-（其中X1和R5如上定义）；R1表示氢、酮、卤代、羟基、C1-4烷氧基、C1-4烷基、C1-4烷氧甲基、C1-4酰基、C1-4卤代烷基、氰基、氨基、C2-5烯基、C2-5炔基、C1-3酰氧基、硝基、C1-4酰胺基、C1-4烷氧羰基、C1-4烷基硫基、C1-4烷基亚硫基、C1-4烷基磺酰基、氨基甲酰基、N-C1-4烷基氨基甲酰基、N，N-二（C1-4烷基）氨基甲酰基、氨基磺酰基、N-C1-4烷基氨基磺酰基、N，N-二（C1-4烷基）氨基磺酰基、N-（C1-4烷基磺酰基）氨基、N-（C1-4烷基磺酰基）-N-（C1-4烷基）氨基、N，N-二（C1-4烷基磺酰基）氨基、连接两个环C碳原子的C3-7烷基链、C1-4酰胺基C1-4烷基、羧基或R56X10基团（其中X10和R56如上定义）；以及其盐，在制造用于产生在温血动物中的抗血管生成和/或血管通透性减少效应的药物中使用，制备这种化合物的方法，含有公式（I）的化合物或其药学上可接受的盐作为活性成分的制药组合物和公式（I）的化合物。公式（I）的化合物及其药学上可接受的盐抑制VEGF的效果，在治疗包括癌症和类风湿性关节炎在内的多种疾病状态中具有价值。