US 5,962,448 A · Pyrroloazepine derivatives

Abstract

A pyrroloazepine compound having the following formula (I): wherein the ring P represented by ##STR1## is a pyrrole ring having the following structure: ##STR2## wherein R.sub.1 represents C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.8 cycloalkyl-alkyl, C.sub.6 -C.sub.14 aryl or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted; and R.sub.2 represents H or C.sub.1 -C.sub.8 alkyl, which is optionally substituted; the dashed line indicates the presence or absence of a bond; and, when the bond is present, Z.sub.2 is not present and Z.sub.1 represents H, but, when the bond is absent, Z.sub.1 and Z.sub.2 are both H; Z.sub.1 represents H and Z.sub.2 represents a group OR.sub.3, in which R.sub.3 represents H, C.sub.1 -C.sub.8 alkyl, or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted; Z.sub.1 and Z.sub.2 both represent groups SR.sub.4, in which R.sub.4 represents C.sub.1 -C.sub.8 alkyl or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted; or Z.sub.1 and Z.sub.2 are combined together to represent O, a group NOR.sub.5, in which R.sub.5 represents H, or C.sub.1 -C.sub.8 alkyl or C.sub.2 -C.sub.3 alkylenedithio, which are optionally substituted; A represents alkylene, alkenylene or alkynylene; and Y represents a group in which W is CH, C.dbd. or N, m is for 0 or 1, n is for 1, 2 or 3, G is O, S, C.dbd.O, sulfinyl, sulfonyl, alkylene, alkenylene or acetal; E.sub.1 and E.sub.2 is H or C.sub.1 -C.sub.8 alkyl; and D represents an aromatic hydrocarbon or an aromatic heterocyclic ring. The compound (I) has strong serotonin-2 receptor antagonistic action and low toxicity and less side effects, and is therapeutically useful in the treatment of circulatory diseases and/or conditions related thereto.

A compound of the formula (I) or a salt thereof:

##STR149## wherein the ring P represented by ##STR150## is a pyrrole ring having the following structure:
##STR151## wherein R.sub.1 is C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.8 cycloalkyl-alkyl, C.sub.7 -C.sub.22 aralkyl or a C.sub.6 -C.sub.14 aryl, which are optionally substituted by halogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
and R.sub.2 is a hydrogen atom or C.sub.1 -C.sub.8 alkyl, which is optionally substituted by halogen;
the dashed line indicates the presence or absence of a bond;
and, when the bond indicated by the dashed line is present, Z.sub.2 is not present and Z.sub.1 represents a hydrogen atom, but, when the bond indicated by the dashed line is absent, Z.sub.1 and Z.sub.2 both are hydrogen atoms:
Z.sub.1 is a hydrogen atom and Z.sub.2 is a group OR.sub.3, in which R.sub.3 is a hydrogen atom, C.sub.1 -C.sub.8 alkyl or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted by halogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
Z.sub.1 and Z.sub.2 both represent groups SR.sub.4, in which R.sub.4 is C.sub.1 -C.sub.8 alkyl, C.sub.7 -C.sub.22 aralkyl or C.sub.6 -C.sub.14 aryl, which are optionally substituted by halogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy:
or Z.sub.1 and Z.sub.2 are combined together to represent an oxygen atom, a group NOR.sub.5, in which R.sub.5 is a hydrogen atom, C.sub.1 -C.sub.8 alkyl or C.sub.6 -C.sub.14 aryl, which are optionally substituted by halogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
or a group of the formula:
##STR152## in which L is an ethylene or trimethylene, which are optionally substituted by halogen. C.sub.1 -C.sub.4 alkyl, C.sub.6 -C.sub.14 aryl, C.sub.7 -C.sub.22 aralkyl or C.sub.1 -C.sub.4 alkylidene;
A is alkylene, alkenylene or alkynylene;
and
Y is a group of the formula:
##STR153## in which W is CH, C.dbd. or a nitrogen atom;
and, when W is CH, m is 0 or 1, n is 1 or 2, G is an oxygen atom, or a sulfur atom, carbonyl, sulfinyl, sulfonyl, alkylene, alkenylene, or a group of the formula:
##STR154## in which R.sub.6 is a C.sub.6 -C.sub.14 aryl group, which is optionally substituted by halogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
a group of the formula:
##STR155## in which R.sub.7 is hydroxyl, C.sub.1 -C.sub.4 alkoxy or C.sub.7 -C.sub.22 aralkoxy, or cyclic or acyclic acetal;
when W is C.dbd., m is 1, n is 1 or 2, G is a group of the formula:
##STR156## in which the double bond is coupled with W and R.sub.8 is C.sub.1 -C.sub.8 alkyl, C.sub.6 -C.sub.14 aryl or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted with halogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
when W is a nitrogen atom, m is 0 or 1, n is 2 or 3, and G is carbonyl, sulfonyl, alkylene, alkenylene or a group --CHR.sub.9 --, in which R.sub.9 is C.sub.1 -C.sub.8 alkyl, C.sub.6 -C.sub.14 aryl or C.sub.7 -C.sub.22 aralkyl, which are optionally substituted by halogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy:
E.sub.1 and E.sub.2 each independently is a hydrogen atom or C.sub.1 -C.sub.8 alkyl, which is optionally substituted by halogen C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
and
D represents C.sub.6 -C.sub.28 aromatic hydrocarbon, which is optionally substituted by halogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.6 -C.sub.14 aryl, C.sub.7 -C.sub.22 aralkyl, C.sub.7 -C.sub.22 aralkyloxy, cyano, nitro, carboxyl, alkoxycarbonyl, lower alkylsulfonylamino, carbamoyl or hydroxy;
or D represents an aromatic heterocyclic group, which is monocyclic or bicyclic and which optionally contains three or less of the same or different oxygen, sulfur or nitrogen atoms, and which aromatic heterocyclic group is optionally substituted by the same substituents as defined for said C.sub.6 -C.sub.28 aromatic hydrocarbon.

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Pyrroloazepine derivatives

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Pyrroloazepine derivatives

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Abstract

Claims31