Certain aminoguanidine compounds, pharmaceutical compositions containing them and their use in treating gastrointestinal motility disorders and disorders associated with cephalic pain
First Claim
1. A compound of the formula ##STR27## wherein R1 hydrogen;
- C1-6 alkyl;
(C1-6 alkyl)carbonyl;
or benzoyl;
R5 is hydrogen;
halo;
C1-6 alkyl;
hydroxy;
nitro;
amino;
C1-4 alkylamino;
C1-10 alkylcarbonylamino;
C2-6 alkoxy-carbonyl;
SO2 NRa Rb ;
cyano;
trimethylsilyl;
C1-6 alkyl monosubstituted by --SO2 -(C1-6 alkyl), --SO2 NRa Rb, --CONRa Rb, --NH--SO2 --(C1-6 alkyl), --N (C1-6 alkyl)--SO2 --(C1-6 alkyl), --NRa Rb, C2-6 alkoxycarbonyl or --PO(C1-4 alkyl)2 ;
carboxy;
CONRa Rb ;
--PO(C1-4 alkyl)2 ;
--OCONRc Rd ;
C1-6 alkoxy;
C1-6 alkoxy monosubstitutedby hydroxy, C1-4 alkoxy, NRa R'"'"'b, CONRa Rb, CSNRa Rb,(C1-6 alkyl)carbonyloxy or benzoyloxy;
C2-6 alkenyloxy;
pyridyl-carbonyloxy;
(C1-6 alkyl)carbonyloxy;
or benzoyloxy;
and wherever they appear in the above definition ofR5, each of Ra and Rb, independently, is hydrogen or C1-6 alkyl;
R'"'"'b is hydrogen or C1-6 alkyl; and
each of Rc and Rd, independently, is C1-6 alkyl;
R7 is hydrogen, halo, C1-6 alkyl or C1-6 alkoxy;
X--Y is --CR8 ═
N-- or---H(R8)--NH-- where R8 is hydrogen or C1-6 alkyl; and
B is a radical of formula (a) or (b), ##STR28## where n is 1 or 2;
A1 is C═
O or CH2 ;
X1 is S;
NR11 where R11 is hydrogen;
or CR12 R13 where each of R12 and R13, independently, is hydrogen or C1-4 alkyl;
R10 is hydrogen;
C1-12 alkyl;
C1-6 alkyl monosubstituted by hydroxy, aryl, aryloxy, adamantyl, a heterocyclic radical, --NH--SO2 -aryl or --NR15 --COR16 where R15 is hydrogen or C1-4 alkyl and R16 is C1-6 alkyl, C5-7 cycloalkyl, C5-7 cycloalkyl-C1-4 alkyl, aryl or aryl(C1-4 alkyl);
C5-7 cycloalkyl;
adamantyl;
(C1-10 alkyl)-carbonyl;
benzoyl;
phenyl(C1-4 alkyl)carbonyl;
or --CONHR14 where R14 is C1-10 alkyl or C5-7 cycloalkyl;
and wherever "aryl" appears as is or in the significances "aryloxy", "--NH--SO2 -aryl" or "aryl(C1-4 alkyl)" in the above definition, it is phenyl or phenyl mono- or disubstituted by fluoro, chloro, methyl or methoxy; and
wherever the term "a heterocyclic radical" appears in the above definition, it is pyridyl, imidazolyl, benzimidazolyl, pyrrolidinyl, piperidino, pyrazinyl, perhydroindolyl or a radical of formula (d) ##STR29## where E is --CH2 CH2 --,--CH2 N(R17)-- where R17 is hydrogen or C1-4 alkyl;
or --(CH2)3 --where one or two hydrogens therein can be replaced by C1-6 alkyl; and
E1 is --CO--or --CH2 --;
andX2 is --SR20 where R20 is C1-6 alkyl;
or --NR3 R'"'"'10 where either R3 is hydrogen or C1-6 alkyl and R'"'"'10 has one of the significances indicated above for R10 ;
or R3 andR'"'"'10 together with the nitrogen atom to which they are attached form a heterocyclic radical as defined above;
with the proviso that where B is a radical of formula (b), only one of R10 and R'"'"'10 can be other than hydrogen and X2 can be --SR20 only when R10 is hydrogen;
which compound is in free base or pharmaceutically acceptable salt form.
2 Assignments
0 Petitions
Accused Products
Abstract
Compounds of formula
A--X--Y--NH--B
wherein A is derived from optionally substituted benzothiophene, indole, 4-aza-and 7-aza-benzothiophene or-indole, A bearing in position 5 hydrogen, halogen, optionally substituted alkyl, hydroxy, nitro, amino, alkylamino, acylamino, alkoxycarbonyl, sulfamoyl, cyano, trimethylsilyl, carboxy, carbamoyl, phosphate, oxycarbamoyl, heterocyclic radical or ether or ester group, X-Y is --CR8 ═N-- or CH(R8)--NH-- wherein R8 is -H or alkyl and attached at position 3 of A, and B is a heterocyclic radical or a residue ##STR1## wherein R10 is H, optionally substituted alkyl, cycloalkyl, aryl, adamantyl, acyl or carbamoyl and X2 is alkylthio or NR3 R10 wherein R3 is H or alkyl or R3 and R10 together with the nitrogen atom to which they are attached form a heterocyclic radical, in free form or in salt form, have pharmacological activity, e.g. for treating gastrointestinal disorders.
-
Citations
17 Claims
-
1. A compound of the formula ##STR27## wherein R1 hydrogen;
- C1-6 alkyl;
(C1-6 alkyl)carbonyl;
or benzoyl;R5 is hydrogen;
halo;
C1-6 alkyl;
hydroxy;
nitro;
amino;
C1-4 alkylamino;
C1-10 alkylcarbonylamino;
C2-6 alkoxy-carbonyl;
SO2 NRa Rb ;
cyano;
trimethylsilyl;
C1-6 alkyl monosubstituted by --SO2 -(C1-6 alkyl), --SO2 NRa Rb, --CONRa Rb, --NH--SO2 --(C1-6 alkyl), --N (C1-6 alkyl)--SO2 --(C1-6 alkyl), --NRa Rb, C2-6 alkoxycarbonyl or --PO(C1-4 alkyl)2 ;
carboxy;
CONRa Rb ;
--PO(C1-4 alkyl)2 ;--OCONRc Rd ;
C1-6 alkoxy;
C1-6 alkoxy monosubstitutedby hydroxy, C1-4 alkoxy, NRa R'"'"'b, CONRa Rb, CSNRa Rb, (C1-6 alkyl)carbonyloxy or benzoyloxy; C2-6 alkenyloxy;
pyridyl-carbonyloxy;(C1-6 alkyl)carbonyloxy;
or benzoyloxy;and wherever they appear in the above definition of R5, each of Ra and Rb, independently, is hydrogen or C1-6 alkyl;
R'"'"'b is hydrogen or C1-6 alkyl; and
each of Rc and Rd, independently, is C1-6 alkyl;R7 is hydrogen, halo, C1-6 alkyl or C1-6 alkoxy; X--Y is --CR8 ═
N-- or---H(R8)--NH-- where R8 is hydrogen or C1-6 alkyl; andB is a radical of formula (a) or (b), ##STR28## where n is 1 or 2; A1 is C═
O or CH2 ;X1 is S;
NR11 where R11 is hydrogen;
or CR12 R13 where each of R12 and R13, independently, is hydrogen or C1-4 alkyl;R10 is hydrogen;
C1-12 alkyl;
C1-6 alkyl monosubstituted by hydroxy, aryl, aryloxy, adamantyl, a heterocyclic radical, --NH--SO2 -aryl or --NR15 --COR16 where R15 is hydrogen or C1-4 alkyl and R16 is C1-6 alkyl, C5-7 cycloalkyl, C5-7 cycloalkyl-C1-4 alkyl, aryl or aryl(C1-4 alkyl);
C5-7 cycloalkyl;
adamantyl;
(C1-10 alkyl)-carbonyl;
benzoyl;
phenyl(C1-4 alkyl)carbonyl;
or --CONHR14 where R14 is C1-10 alkyl or C5-7 cycloalkyl;and wherever "aryl" appears as is or in the significances "aryloxy", "--NH--SO2 -aryl" or "aryl(C1-4 alkyl)" in the above definition, it is phenyl or phenyl mono- or disubstituted by fluoro, chloro, methyl or methoxy; and
wherever the term "a heterocyclic radical" appears in the above definition, it is pyridyl, imidazolyl, benzimidazolyl, pyrrolidinyl, piperidino, pyrazinyl, perhydroindolyl or a radical of formula (d) ##STR29## where E is --CH2 CH2 --,--CH2 N(R17)-- where R17 is hydrogen or C1-4 alkyl;
or --(CH2)3 --where one or two hydrogens therein can be replaced by C1-6 alkyl; and
E1 is --CO--or --CH2 --;and X2 is --SR20 where R20 is C1-6 alkyl;
or --NR3 R'"'"'10 where either R3 is hydrogen or C1-6 alkyl and R'"'"'10 has one of the significances indicated above for R10 ;
or R3 andR'"'"'10 together with the nitrogen atom to which they are attached form a heterocyclic radical as defined above; with the proviso that where B is a radical of formula (b), only one of R10 and R'"'"'10 can be other than hydrogen and X2 can be --SR20 only when R10 is hydrogen;
which compound is in free base or pharmaceutically acceptable salt form. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
- C1-6 alkyl;
Specification