公开(公告)号：EP2993173A1

公开(公告)日：2016-03-09

申请号：EP15188487.1

申请日：2011-03-29

申请人： AJINOMOTO CO., INC.

发明人： KATAOKA, Noriyasu ,  KODAMA, Riho ,  TATARA, Akinori

IPC分类号： C07D239/96 ,  A61K31/517 ,  A61P1/04 ,  A61P3/10 ,  A61P9/00 ,  A61P9/10 ,  A61P11/06 ,  A61P17/06 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  A61P35/04 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00

CPC分类号： C07D239/96

摘要： Provided is a crystal of a salt of the compound represented by formula (I), which is excellent in its solubility in water. In particular, also provided is a crystal of hydrochloride, hydrobromate, sulfate, nitrate, p-toluenesulfonate or methanesulfonate of the compound represented by formula (I).

公开(公告)号：EP2103601B1

公开(公告)日：2012-03-14

申请号：EP07832344.1

申请日：2007-11-22

申请人： Ajinomoto Co., Inc.

发明人： KATAOKA, Noriyasu ,  OKADO, Kotaro ,  YAMADA, Tatsuhiro ,  FUJITA, Koichi ,  SUZUKI, Tamotsu ,  OKUZUMI, Tatsuya ,  SUGIKI, Masayuki ,  TATARA, Akinori

IPC分类号： C07D239/96 ,  C07C233/51 ,  C07C237/40 ,  C07C265/12 ,  C07C271/22 ,  C07C271/28 ,  C07C275/42

CPC分类号： C07D239/96 ,  C07C233/47 ,  C07C233/87 ,  C07C237/40 ,  C07C237/42 ,  C07C265/12 ,  C07C271/22 ,  C07C271/28 ,  C07C275/42 ,  Y02P20/55

摘要： A process for the production of phenylalanine derivatives having quinazolinedione rings as represented by the general formula (1) or pharmaceutically acceptable salts thereof: (1) which comprises the following steps (a), (b) and (c): the step (a) of reacting an acylphenylalanine derivative represented by the general formula (2): (2) with a carbonyl-introducing agent and a specific anthranilic acid derivative to form a corresponding carboxy asymmetric urea derivative, the step (b) of converting the carboxy asymmetric urea derivative into a corresponding quinazolinedione in the presence of a carboxyl-activating agent, and the optional step (c) comprising the N-alkylation step of replacing the hydrogen atom attached to the nitrogen atom constituting the quinazoline- dione ring by an alkyl group with an N-alkylating agent and/or the deblocking step of deblocking R3' (a group corresponding to R3) when R3' is in a protected state. According to the process, phenylalanine derivatives having quinazolinedione skeletons can be produced in high yield favorable for industrialization.

公开(公告)号：EP2103601A1

公开(公告)日：2009-09-23

申请号：EP07832344.1

申请日：2007-11-22

申请人： Ajinomoto Co., Inc.

发明人： KATAOKA, Noriyasu ,  OKADO, Kotaro ,  YAMADA, Tatsuhiro ,  FUJITA, Koichi ,  SUZUKI, Tamotsu ,  OKUZUMI, Tatsuya ,  SUGIKI, Masayuki ,  TATARA, Akinori

IPC分类号： C07D239/96 ,  C07C233/51 ,  C07C237/40 ,  C07C265/12 ,  C07C271/22 ,  C07C271/28 ,  C07C275/42

CPC分类号： C07D239/96 ,  C07C233/47 ,  C07C233/87 ,  C07C237/40 ,  C07C237/42 ,  C07C265/12 ,  C07C271/22 ,  C07C271/28 ,  C07C275/42 ,  Y02P20/55

摘要： A method for preparing a phenylalanine derivative having a quinazoline-dione ring represented by the following formula (1) or a pharmaceutically acceptable salt thereof, comprising the following steps (a), (b) and (c):

(a) reacting an acyl phenylalanine derivative represented by the following formula (2):

with a carbonyl group-introducing reagent and a specific anthranilic acid derivative to thus form the corresponding carboxy-asymmetric urea derivative;
(b) converting the carboxy-asymmetric urea derivative into the corresponding quinazoline-dione derivative in the presence of a carboxyl group-activating agent:
(c) if desired, substituting an N-alkyl group for the hydrogen atom bonded to the nitrogen atom present in the quinazoline-dione ring of the quinazoline-dione derivative using an N-alkylation agent and then deprotecting the resulting product, when the substituent R3' which is a group corresponding to R3 is protected. According to this method, there can be obtained a phenylalanine derivative having a quinazoline-dione skeleton in a industrially favorably high yield.

摘要翻译： 一种用于制备苯丙氨酸衍生物具有由下式表示的喹唑啉二酮环（1）或其药学上可接受的盐，其包括以下步骤（a），（b）和（c）中的方法：（A）反应成酰基 由下式（2）表示的苯丙氨酸衍生物：与羰基导入试剂和特定的邻氨基苯甲酸衍生物，以形成因此对应羧基不对称脲衍生物; （B）将所述羧基不对称脲衍生物为相应的喹唑啉二酮衍生物在羧基活化剂的存在下：如果需要清除（c）中，用N-烷基为键合到本氮原子上的氢原子 在使用N-烷基化剂，然后脱保护得到的产物，当取代基R3“是对应于R3基团被保护的喹唑啉二酮衍生物的喹唑啉二酮环。 。根据该方法，可以得到在工业上有利地高收率具有喹唑啉二酮骨架苯基丙氨酸衍生物。