申请人:Hoffman-La Roche Inc.
公开号:US04316839A1
公开(公告)日:1982-02-23
Imidazodiazepine derivatives of the formula ##STR1## wherein A together with the two carbon atoms denoted as .alpha. and .beta. is selected from the group consisting of ##STR2## the dotted line represents the double bond present in groups (a) and (b), D is >C.dbd.O or >C.dbd.S, R.sup.1 is selected from the group consisting of cyano, lower alkanoyl and a group of the formula --COOR.sup.4, R.sup.4 is selected from the group consisting of methyl, ethyl, isopropyl and 2-hydroxyethyl, R.sup.5 is selected from the group consisting of hydrogen, trifluoromethyl and halogen and R.sup.6 is selected from the group consisting of hydrogen, trifluoromethyl, halogen and lower alkyl and either R.sup.2 is hydrogen and R.sup.3 is hydrogen or lower alkyl or R.sup.2 and R.sup.3 together are trimethylene or propenylene and the carbon atom denoted as .gamma. has the S- or R,S-configuration, and pharmaceutically acceptable salts thereof are presented and have utility for antagonizing the central-depressant, muscle relaxant, ataxic, blood pressure-lowering and respiratory-depressant properties of 1,4-benzodiazepines which have tranquillizing activity. They can be used, for example, as antidotes in the case of intoxications in which excessive intake of 1,4-benzodiazepines which have tranquillizing participates, or for shortening an anaesthesia induced by such 1,4-benzodiazepines. They can also be used for suppressing the activities on the central nervous system of 1,4-benzodiazepines used in other fields of indication, for example of schistosomicidally-active 1,4-benzodiazepines such as (+)-5-(o-chlorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazepin-2 -one. Also presented are processes to produce the imidazodiazepine derivatives and intermediates therefor.
咪唑二氮杂环己烯衍生物的公式为##STR1##其中A与两个碳原子α和β一起从##STR2##中选择,虚线代表(a)和(b)中存在的双键,D为>C.dbd.O或>C.dbd.S,R.sup.1从氰基,较低的烷酰基和公式--COOR.sup.4的基团中选择,R.sup.4从甲基,乙基,异丙基和2-羟乙基中选择,R.sup.5从氢,三氟甲基和卤素中选择,R.sup.6从氢,三氟甲基,卤素和较低烷基中选择,R.sup.2为氢,R.sup.3为氢或较低烷基,或者R.sup.2和R.sup.3一起为三甲亚基或丙烯亚基,所述的碳原子γ具有S-或R,S-构型,及其药学上可接受的盐,用于对抗具有镇静活性的1,4-苯二氮杂环己烷的中枢抑制、肌肉松弛、共济失调、降低血压和呼吸抑制特性。它们可以用作例如,在过量摄入具有镇静活性的1,4-苯二氮杂环己烷的中毒情况下的解毒剂,或者缩短由这些1,4-苯二氮杂环己烷引起的麻醉。它们还可用于抑制其他适应领域中使用的1,4-苯二氮杂环己烷对中枢神经系统的活性,例如对于片尾蚴活性的1,4-苯二氮杂环己烷,如(+)-5-(邻氯苯基)-1,3-二氢-3-甲基-7-硝基-2H-1,4-苯二氮杂环己烷-2-酮。还提供了生产咪唑二氮杂环己烯衍生物及其中间体的方法。