公开(公告)号：EP1568690A1

公开(公告)日：2005-08-31

申请号：EP04030775.3

申请日：1998-04-22

申请人： Euro-Celtique S.A.

发明人： Wang, Yan ,  Cai, Sui Xiong ,  Lan, Nancy C. ,  Ilyin, Victor I. ,  Keana, John F. W. ,  Weber, Eckard

IPC分类号： C07D211/06 ,  C07D213/02 ,  C07D215/02 ,  C07D239/02 ,  C07D309/02 ,  A61K31/35 ,  A61K31/44 ,  A61K31/445 ,  A61K31/47 ,  A61K31/505 ,  C07D213/64

CPC分类号： C07D213/643 ,  C07C281/14 ,  C07C323/48 ,  C07C337/08 ,  C07D209/14 ,  C07D211/46 ,  C07D213/68 ,  C07D215/12 ,  C07D215/20 ,  C07D239/34 ,  C07D307/91 ,  C07D309/12 ,  C07D317/50 ,  C07D317/62 ,  C07D317/64 ,  C07D319/18

摘要： This invention is related to carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones represented by formula (I), or a pharmaceutically acceptable salt or prodrug thereof, wherein: Y is oxygen or sulfur; R 1 , R 21 , R 22 and R 23 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl; or R 22 and R 23 , together with the N, form a heterocycle; A 1 and A 2 are independently aryl, heteroaryl, saturated or partially unsaturated carbocycle or saturated or partially unsaturated heterocycle, any of which is optionally substituted; X is one or O, S, NR 24 , CR 25 R 26 , C(O), NR 24 C(O), C(O)NR 24 , SO, SO 2 or a covalent bond; where R 24 , R 25 and R 26 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl. The invention is also directed to the use of carbocycle and heterocycle substituted semicarbazones and thiosemicarbazones for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyiotrophic lateral sclerosis (ALS), for the treatment and prevention of otoneurotoxicity and eye diseases involving glutamate toxicity and for the treatment, prevention or amelioration of pain, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy and urinary incontinence.

摘要翻译： 本发明涉及碳环和杂环取代的缩氨基脲和缩氨基硫脲，式（I）表示的，或者其药学上可接受的盐或其前药，worin：Y是氧或硫; R1，R21，R22和R23独立地是氢，烷基，环烷基，烯基，炔基，卤代烷基，芳基，氨基烷基，羟基烷基，烷氧基烷基或羧基烷基; 或R22和R23与N一起形成杂环; A1和A2为unabhängig芳基，杂芳基，饱和或部分不饱和的羰周期或饱和或部分不饱和杂环，任何的所有其任选substituiertem; X是一种或O，S，NR24，CR25R26，C（O），NR24C（O），C（O）NR24，SO，SO 2或共价键; 其中R24，R25和R26独立地是氢，烷基，环烷基，烯基，炔基，卤代烷基，芳基，氨基烷基，羟基烷基，烷氧基烷基或羧基烷基。 因此，本发明涉及使用碳氮化周期和杂环substituiertem缩氨基脲和缩氨基硫脲的对神经元损伤的以下全局和局部缺血的治疗，用于治疗或预防的神经退行性病症：诸如amyiotrophic侧索硬化症（ALS），用于治疗和预防 的otoneurotoxicity和眼部疾病涉及谷氨酸毒性以及用于治疗，预防或改善疼痛，如抗惊厥药，和抗躁狂抑制剂，局部麻醉剂，抗心律不齐和糖尿病性神经病变和尿失禁的治疗或预防。