US 5,310,927 A · Benzofuran derivatives

Abstract

The invention provides compounds of formula (I): ##STR1## or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein R.sup.1 represents a hydrogen atom or a halogen atom or a group selected from C.sub.1-6 alkyl, C.sub.2-6 alkenyl, fluoroC.sub.1-6 alkyl, C.sub.1-6 alkoxy, --CHO, --CO.sub.2 H or --COR.sup.2 ; Ar represents the group ##STR2## Het represents an N-linked imidazolyl group optionally substituted by one, two or three substituents. The compounds may be used in the treatment or prophylaxis of hypertension and diseases associated with cognitive disorders.

A compound of formula (I):

##STR27## or a physiologically acceptable salt, solvate or metabolically labile ester thereof wherein
R.sup.1 represents a hydrogen atom or a halogen atom or a group selected from C.sub.1-6 alkyl, C.sub.2-6 alkenyl, fluoroC.sub.1-6 alkyl, C.sub.1-6 alkoxy, --CHO, --CO.sub.2 H or --COR.sup.2 ;
Ar represents the group ##STR28## R.sup.2 represents a group selected from C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.1-6 alkoxy or the group --NR.sup.10 R.sup.11,
R.sup.3 represents a group selected from --SO.sub.3 R.sup.15, --PO(OR.sup.15).sub.2, --PO(OR.sup.16 R.sup.16, --SO.sub.2 NHR.sup.16, --CONHNHSO.sub.2 CF.sub.3, --SO.sub.2 NH-heteroaryl, --CH.sub.2 SO.sub.2 NH-heteroaryl, --SO.sub.2 NHCOR.sup.17, --CH.sub.2 SO.sub.2 NHCOR.sup.17, --CONHSO.sub.2 R.sup.17, --CH.sub.2 CONHSO.sub.2 R.sup.17, --NHSO.sub.2 NHCOR.sup.17, --NHCONHSO.sub.2 R.sup.17. --SO.sub.2 NHCONHR.sup.17, --CONHSO.sub.2 NHR.sup.17, ##STR29## wherein `heteroaryl` represents a 5 membered aromatic ring containing from 1 to 3 nitrogen atoms said aromatic ring being optionally substituted by 1 or 2 substituents selected from a halogen atom or a group selected from hydroxy, --SH, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, --CF.sub.3, --NO.sub.2, --CO.sub.2 H, C.sub.1-5 acyloxy, --NH.sub.2, C.sub.1-4 alkylamino or diC.sub.1-4 alkylamino;
R.sup.4 and R.sup.5 which may be the same or different each independently represent a hydrogen atom or a halogen atom or a C.sub.1-6 alkyl group;
Het represents an N-linked imidazolyl group optionally substituted at the 2-position by a C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.1-6 alkylthio, C.sub.1-6 alkoxy, C.sub.3-7 cycloalkyl or C.sub.3-7 cycloalkylC.sub.1-4 alkyl group, the imidazolyl group optionally being substituted at the 4-and 5-positions by one or two further substituents selected from a halogen atom or a group selected from cyano, nitro, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, fluoroC.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub. 1-4 alkyl, (CH.sub.2).sub.m R.sup.6, --(CH.sub.2).sub.n COR.sup.7 or --(CH.sub.2).sub.p NR.sup.8 COR.sup.9 ;
R.sup.6 represents a hydroxy or cl-6alkoxy group;
R.sup.7 represents a hydrogen atom or a group selected from hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, phenyl, phenoxy or the group --NR.sup.10 R.sup.11 ;.
R.sup.8 represents a hydrogen atom or a C.sub.1-6 alkyl group;
R.sup.9 represents a hydrogen atom or a group selected from C.sub.1-6 alkyl,
C.sub.1-6 alkoxy, phenyl, phenoxy or the group --NR.sup.10 R.sup.11 ;
R.sup.10 and R.sup.11, which may be the same or different, each independently represent a hydrogen atom or a C.sub.1-4 alkyl group;
R.sup.15 represents a hydrogen atom or the group --CH(R.sup.16)OC(O)R.sup.21 ;
R.sup.16 represents a hydrogen atom or a group selected from C.sub.1-6 alkyl, phenyl or benzyl;
R.sup.17 represents a group selected from aryl, heteroaryl (as defined above), C.sub.3-7 cycloalkyl, perfluoroC.sub.1-4 alkyl or C.sub.1-4 alkyl optionally substituted by a halogen atom or a group selected from hydroxy, --SH, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, --CF.sub.3, --NO.sub.2, --CO.sub.2 H, --C.sub.1-5 acyloxy, --NH.sub.2, C.sub.1-4 alkylamino, diC.sub.1-4 alkylamino, --PO.sub.3 H or --PO(OH)C.sub.1-4 alkoxy, wherein `aryl` represents a phenyl or naphthalenyl group optionally substituted by 1 or 2 substituents selected from a halogen atom or a group selected from C.sub.1-4 alkyl, C.sub.1-4 alkoxy, --NO.sub.2, --CF.sub.3, C.sub.1-4 alkylthio, hydroxy or --NH.sub.2 ;
R.sup.18 represents a hydrogen atom or a group selected from C.sub.1-6 alkyl, phenyl or benzyl;
R.sup.19 represents a hydrogen atom or a group selected from C.sub.1-6 alkyl, C.sub.2-4 alkenyl or C.sub.1-4 alkoxyC.sub.1-4 alkyl;
R.sup.20 represents a group selected from --CN, --NO.sub.2 or --CO.sub.2 R.sup.16 ;
R.sup.21 represents a group selected from C.sub.1-6 alkyl, aryl (as defined above) or --CH.sub.2 -aryl (as defined above);
R.sup.22 represents a group selected from --CO.sub.2 R , --SO.sub.3 R.sup.15, --NHSO.sub.2 CF.sub.3, --PO(OR.sup.15).sub.2, --SO.sub.2 NHR.sup.18 or a Clinked tetrazolyl group;
m represents an integer from 1 to 4, preferably 1 or 2, especially 1;
n represents an integer from 0 to 4, preferably 0, 1 or 2, especially 0 or 1;
and
p represents an integer from 1 to 4, preferably 1 or 2.

21 more elements

Benzofuran derivatives

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Benzofuran derivatives

Life of this patent

Abstract

Claims16