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US 6,271,223 B1Granted
Pyrrolothiazine and pyrrolothiazepine compounds having serotonin-2 receptor antagonistic and alpha-1-blocking action
AssigneeSuntory Limited
InventorsAkira Mizuno, Makoto Shibata, Tomoe Kamei, Harukazu Fukami, Norio Inomata
Life of this patent
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Abstract
A pyrrolesulfonamide derivative having the following formula (I): is provided wherein P, A, Y, l, Z1 and Z2 are as described herein, wherein the derivative has strong serotonin-2 receptor antagonistic action, low toxicity and fewer side effects, and its use as a therapeutic for circulatory diseases such as ischemic heart diseases, cerebrovascular disturbances and peripheral circulatory disturbances.
Claims11
A pyrrolesulfonamide derivative or a salt thereof, said pyrrolesulfonamide derivative being represented by the following formula (I):
- wherein
- the ring P represented by
- means a pyrrole ring represented by the following structure:
- in which R represents an alkyl group, a cycloalkyl group, a cycloalkyl-alkyl group or a substituted or unsubstitued aralkyl group;
- the dashed line indicates the presence or absence of a bond;
- and, when the bond indicated by the dashed line is present, Z2 is not present and Z1 represents a hydrogen atom but, when the bond indicated by the dashed line is absent, Z1 represents a hydrogen atom and Z2 represents a hydroxyl group;
- or Z1 and Z2 are combined together to represent an oxygen atom or a group NOR1 in which R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted aryl group;
- l represents 0 or 1;
- A represents a substituted or unsubstituted alkylene group, a substituted or unsubstituted alkenylene group or a substituted or unsubstituted alkynylene group;
- and
- Y represents a group
- in which W represents CH, C═ or a nitrogen atom;
- and, when W represents CH, m stands for 0 or 1, B represents a carbonyl group, a sulfonyl group, an alkylene group, an alkenylene group, a group —C(OH)R2— in which R2 represents a substituted or unsubstituted aryl group, a group —CHR3— in which R3 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted cyclic or acyclic acetal group;
- when W represents C═, m stands for 1, B represents a group
- in which the double bond is coupled with W and R4 represents a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group;
- when W represents a nitrogen atom, n stands for 0 or 1, and B represents a carbonyl group, a sulfonyl group, an alkylene group, an alkenylene group or a group —CHR5— in which R5 represents a substituted or unsubstituted aryl group;
- E1 and E2 each independently represents a hydrogen atom or a lower alkyl group;
- and D represents a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted aromatic heterocyclic group.
15 more elements
A process for the preparation of a pyrrolesulfonamide derivative represented by the following formula (Ia):
- wherein
- the ring P represented by
- means a pyrrole ring represented by the following structure:
- in which R represents an alkyl group, a cycloalkyl-alkyl group or a substituted or unsubstituted aralkyl group;
- the dashed line indicates the presence or absence of a bond;
- and, when the bond indicated by the dashed line is present, Z2 is not present and Z1 represents a hydrogen atom but, when the bond indicated by the dashed line is absent, Z1 represents a hydrogen atom and Z2 represents a hydroxyl group;
- or Z1 and Z2 are combined together to represent an oxygen atom or a group NOR1 in which R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted aryl group;
- l represents 0 or 1;
- A represents a substituted or unsubstituted alkylene group, a substituted or unsubstituted alkenylene group or a substituted or unsubstituted alkynylene group;
- and
- Y represents a group
- in which W represents CH, C═ or a nitrogen atom;
- and, when w represents CH, m stands for 0 or 1, B represents a carbonyl group, a sulfonyl group, an alkylene group, an alkenylene group, a group —C(OH)R2— in which R2 represents a substituted or unsubstituted aryl group, a group —CHR3— in which R3 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted cyclic or acyclic acetal group;
- when W represents C═, m stands for 1, B represents a group
- in which the double bond is coupled with W and R4 represents a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group;
- when W represents a nitrogen atom, m stands for 0 or 1, and B represents a carbonyl group, a sulfonyl group, an alkylene group, an alkenylene group or a group —CHR5— in which R5 represents a substituted or unsubstituted aryl group;
- E1 and E2 each independently represents a hydrogen atom or a lower alkyl group;
- and D represents a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted aromatic heterocyclic group;
- wherein the process comprises:
- reacting a compound, which is represented by the following formula (III):
- X—A—X′ (III)
- wherein A has the same meaning as defined above and X and X′ represent the same or different eliminative groups, to a compound represented by the following formula (II)
- wherein the ring P and l have the same meanings as defined above, thereby obtaining a compound represented by the following formula (IV):
- wherein A, the ring P, X and l have the same meanings as defined above;
- and then
- reacting a nitrogen-containing compound represented by the following formula (V):
- H—Y (V)
- wherein Y has the same meaning as defined above.
25 more elements
Dependencies are inferred from the claim text.