UOLKER Majkl Dzh. A. (CA),УОЛКЕР Майкл Дж. А. (CA),PLUVE Bertran M. K. (CA),ПЛУВЬЕ Бертран М. К. (CA),NORTEN Dzhulian S. (GB),НОРТЕН Джулиан С. (GB),FERNANDES Filipp (GB),ФЕРНАНДЕС Филипп (GB),UOLKER MAJKL DZH. A.,УОЛКЕР Майкл Дж. А.,PLUVE BERTRAN M. K.,ПЛУВЬЕ Бертран М. К.,NORTEN DZHULIAN S.,НОРТЕН Джулиан С.,FERNANDES FILIPP,ФЕРНАНДЕС Филипп
申请号：
RU2013110225/04
公开号：
RU0002577541C2
申请日:
2011.08.09
申请国别(地区):
RU
年份:
2016
代理人:
摘要：
FIELD: chemistry.SUBSTANCE: present invention relates to a novel crystalline Polymorph of N-{2-[(2E)-2-(mezitilimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a]isoquinoline-3(4H)-yl]ethyl}urea. Said compound can be used in treating asthma, allergic asthma, bronchitis, chronic obstructive pulmonary disease (COPD) or respiratory distress syndrome. Crystalline structure of said Polymorph has x-ray powder diffraction diffractogram containing characteristic peaks in units 2θ, at 10.1°, 12.9°, 15.3° and 17.6°, and following structural parameters, obtained by single crystal analysisTemperature123 (2) KWave length 0.71073 ÅCrystalline circuittriclinicSpatial groupP-1Dimensions of elementary cella = 8.1246 (4) Åα = 91.583(4)°.b = 11.4573 (5) Åβ = 90,299(4)°.c = 13.2398 (6) Åγ = 99.628(4)°.volume1214.56 (10) Å 3Z 2At that, at least 95 % of polymorph is in thermodynamically stable polymorphic form. Invention also relates to method of producing said crystalline polymorph. Method involves (a) combining N-{2-[(2E)-2-(mezitilimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a] isoquinoline-3(4H)-yl]ethyl}urea with solvent to form mixture, (b) heating mixture at temperature in range of 45-121 °C during time, suitable for formation of said polymorph, and slow cooling to temperature in range of 30-40 °C, under conditions suitable for formation of said polymorph； and (c) filtering and drying. Method may further include stage of mixture filtration after step (a). As solvent DMSO, ethanol, methanol, isopropyl alcohol, hexanes, pentane, ethyl acetate, dichloromethane or chloroform can be used.EFFECT: said mixture is retained at or above temperature of about 50 °C for about 24-96 hours.19 cl, 22 dwg, 15 tbl, 13 exНастоящее изобретение относится к новому кристаллическому полиморфу N-{2-[(2Е)-2-(мезитилимино)-9,10-диметокси-4-оксо-6,7-дигидро-2Н-пиримидо[6,1-а]изохинолин-3(4Н)-ил]этил}мочевины. Указанное соединение может быть использовано при лечении астмы, аллергической ас
