Patent ES-8602800-A1 (ES)
Title: Spiro(2H-1,4-benzodioxepin-3(5H)4'-piperidine and 3'-pyrrolidino) compounds, a process for preparing the same and their use as medicaments.
IPC: C07D409/04
Filed: 1985-03-01
Abstract: Spiro-benzodioxepin cpds. of formula (I) and their salts and optical and geometrical isomers are new. In (I) R1 is 3- or 4C brnached or straight chain alkyl or alkenyl or 4C alkynyl terminally mono- or di- substd. by Ar1 and/or Ar2 or R1 is (CH2)3-CHOH-Ar1, (CH2)3-CH(OAr1)-Ar2, (CH2)2OCH(R5)2, (CH2)2SCH(R5)2, (CH2)2NHCH(R5)2, 3-(2-Ar1-1,3-dioxolan-2-yl) propyl, -CO-(CH2)2-R10, 3-(9-fluorenyl)propyl, or 3-(9,10-dihydro-anthracen-9-yl) propyl, Ar1 is Y-substd. phenyl. - Ar2 is Z-substd. phenyl Y and Z are H, Cl, F, Br, I, NO2, CF3, 1-4C n-alkyl, 1-4C n-alkoxy, acyl or NH2 each R5 is independently Ar2 or Ar2 R10 is -CH(Ar1)(Ar2) n is 0 or 1 R2 is H when n is 0, or is H or 1-3C n-alkyl when n is 1 R3 and R4 are H or 1-3C n-alkyl m is 0, 1 or 2 X is Cl, F, Br, I, NO2, CF3, NR6R7, CONR6R7, 1-6C straight or branched alkyl, CN, OR6, SR7, SO3R7, COR8, NHCOR8, SO2R9 or SOR9 R6 and R7 are H or 1-6C n-alkyl R8 is 1-6C straight or banched alkyl and R9 is 1-6C n-alkyl provided that when m is 2, the X substits. can be the same only when X is Cl, F, Br, I, 1-6C alkyl or OR6. - (I) are antihypertensive agents which compare favourably with alpha-methyl dopa. They may be administered by any suitable dopa. They may be administered by any suitable route, pref. orally. Daily dose is 0.1-50 mg/kg. (Dwg.0/2) EPAB- EP-102034 B A compound of the formula (I) wherein m is zero, 1 or 2 n is 1 R1 is (a) a C1-C5 branched or straight chain alkyl group or hydrogen (b) a terminally substituted C1-C5 branched or straight chain alkyl group, or a terminally substituted 3-butenyl group, wherein the terminal substituents are one of two substituents independently selected from the group consisting of formulae (i)-(iii), gps. of formulae (c)-(k) a C1-C3 branched or straight chain alkylene group terminally substituted by one substituent selected from the group consisting of C3-C5 cyclic alkyl group, -OH, -CN, -NR12R13 or of formulae (iv)-(xi) and gps. of formulae (m)-(r) where R2 is hydrogen or a C1-C3 straight chain alkyl group R3 is hydrogen or a C1-C3 straight chain alkyl group R4 is hydrogen or a C1-C3 straight chain alkyl group each R5 substituent is independently selected from the group consisting of formulae (xii)-(xiii) X is Cl, F, Br, I, -NO2, -CF3, -NR6R7, -C(O)-NR6R7, C1-C6 branched or straight chain alkyl, -CN, -O-R4, -SR7, -SO3R7, -C(O)-R8, -NHCOR8, -SO2R9 or -SOR9 where R6 is hydrogen or a C1-C6 straight chain alkyl group R7 is hydrogen or a C1-C6 straight chain alkyl group R8 is C1-C6 branched or straight chain alkyl group R9 is a C1-C6 straight chain alkyl group provided that when m=2, the X-substituents can be the same only when X is selected from the group consisting of Cl, F, Br, I, C1-C6 branched or straight chain alkyl or -O-R6 Y and Z are the same or different and are independently selected from the group consisting of H, Cl, F, Br, I, -NO2, -CF3, C1-C4 straight chain alkyl, alkoxy containing C1-C4 straight chain alkyl, acyl or -NH2 R10 is a gp. (xiv) R12 and R13 are the same or different and are independently selected from the group consisting of hydrogen, methyl and ethyl with the exception of the compounds of formula (I) wherein R1 is C1-C5-branched or straight chain alkyl which is terminally substituted by an optionally substituted phenyl group and the pharmaceuti - EP-102034 B A compound of the formula (I) wherein m is zero, 1 or 2 n is 1 R1 is (a) a C1-C5 branched or straight chain alkyl group or hydrogen (b) a terminally substituted C1-C5 branched or straight chain alkyl group, or a terminally substituted 3-butenyl group, wherein the terminal substituents are one of two substituents independently selected from the group consisting of formulae (i)-(iii), gps. of formulae (c)-(k) a C1-C3 branched or straight chain alkylene group terminally substituted by one substituent selected from the group consisting of C3-C5 cyclic alkyl group, -OH, -CN, -NR12R13 or of formulae (iv)-(xi) and gps. of formulae (m)-(r) where R2 is hydrogen or a C1-C3 straight chain alkyl group R3 is hydrogen or a C1-C3 straight chain alkyl group R4 is hydrogen or a C1-C3 straight chain alkyl group each R5 substituent is independently selected from the group consisting of formulae (xii)-(xiii) X is Cl, F, Br, I, -NO2, -CF3, -NR6R7, -C(O)-NR6R7, C1-C6 branched or straight chain alkyl, -CN, -O-R4, -SR7, -SO3R7, -C(O)-R8, -NHCOR8, -SO2R9 or -SOR9 where R6 is hydrogen or a C1-C6 straight chain alkyl group R7 is hydrogen or a C1-C6 straight chain alkyl group R8 is C1-C6 branched or straight chain alkyl group R9 is a C1-C6 straight chain alkyl group provided that when m =2, the X-substituents can be the same only when X is selected from the group consisting of Cl, F, Br, I, C1-C6 branched or straight chain alkyl or -O-R6 Y and Z are the same or different and are independently selected from the group consisting of H, Cl, F, Br, I, -NO2, -CF3, C1-C4 straight chain alkyl, alkoxy containing C1-C4 straight chain alkyl, acyl or -NH2 R10 is a gp. (xiv) R12 and R13 are the same or different and are independently selected from the group consisting of hydrogen, methyl and ethyl with the exception of the compounds of formula (I) wherein R1 is C1-C5-branched or straight chain alkyl which is terminally substituted by an optionally substituted phenyl group and the pharmaceuti