Claims
- 1. A benzene-condensed heterocyclic derivative of the formula (I): wherein R1 is —X—(CH2)nCOOR3 wherein X is —O—, —S—, or —CH2—, R3 is hydrogen, C1-C5 lower alkyl, or an atom or group which gives a pharmaceutically acceptable salt, and n is an integer of 1 to 3;R2 is —NR4—CR5R6—CHR7—whereinR4 is —(CH2)m—Y—R8 wherein m is an integer of 1 to 4, Y is 1) —O—, 2) —CH2—, 3) —S(O)p— and p is an integer of 0 to 2, 4) —CO—, 5) —CH(OH)—, 6) —NR9SO2—, 7) —NR9CO—, 8) —CONR9, 9) —NR9—, 10) —O—N═CR9—, wherein R9 is a) hydrogen, b) C1-C5 alkyl, c) phenyl or substituted phenyl, d) C1-C5 alkyl substituted with a phenyl or with a substituted phenyl group, or 11) the group represented by the formula (IIa) and (IIb) R8 is 1) phenyl, thienyl, furyl, naphthyl or C3-C8 cycloalkyl, 2) substituted phenyl, substituted thienyl, substituted furyl or substituted naphthyl, 3) C1-C5 alkyl which is substituted with one or two substituents selected from the group consisting of phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted furyl, naphthyl, substituted naphthyl, C3-C8 cycloalkyl and phenoxy; 4) C2-C5 alkenyl which is substituted with one or two substituents selected from the group consisting of phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted furyl, naphthyl, substituted naphthyl, C3-C8 cycloalkyl and phenoxy; 5) C3-C5 alkynyl which is substituted with one or two substituents selected from the group consisting of phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted furyl, naphthyl, substituted naphthyl, C3-C8 cycloalkyl and phenoxy; 6) C2-C8 alkoxyalkyl which is substituted with one or two substituents selected from the group consisting of phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted furyl, naphthyl, substituted naphthyl, C3-C8 cycloalkyl and phenoxy; 7) C1-C5 hydroxyalkyl which is substituted with one or two substituents selected from the group consisting of phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted furyl, naphthyl, substituted naphthyl, C3-C8 cycloalkyl and phenoxy; 8) C2-C8 alkylthioalkyl which is substituted with one or two substituents selected from the group consisting of phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted, naphthyl, substituted naphthyl, C3-C8 cycloalkyl and phenoxy; 9) C1-C5 aminoalkyl which is substituted with one or two substituents selected from the group consisting of phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted furyl, naphthyl, substituted naphthyl, C3-C8 cycloalkyl and phenoxy; 10) —CH2—C(O)—R10 wherein R10 is phenyl or substituted phenyl or C1-C5 alkyl substituted with one or two phenyl groups or substituted phenyl; R5 is 1) hydrogen, 2) C1-C5 alkyl, 3) C1-C5 hydroxyalkyl or acetoxyalkyl, 4) C1-C5 alkyl substituted with one or two phenyl groups or substituted phenyl; or 5) C2-C8 alkoxyalkyl substituted with one or two phenyl groups or substituted phenyl groups; and R6 and R7 represent hydrogen or R6 and R7 are covalently bonded to represent a double bond, with the proviso that when X is CH2, Y is not CH2.
- 2. The compound according to claim 1, wherein X is —O—.
- 3. The compound according to claim 1, wherein Y is —O— or —CH2—.
- 4. The compound according to claim 1, wherein Y is —S(O)p—.
- 5. The compound according to claim 1, wherein Y is —NR9SO2— or —NR9CO—.
- 6. The compound according to claim 1, wherein Y is —NR9— or —CONR9—.
- 7. The benzene-condensed heterocylic derivative according to claim 1, wherein when R8 is a substituted phenyl, wherein the phenyl group is substituted with at least one substituent selected from the group consisting of C1-C5alkyl, phenyl, hydroxy, C1-C5 alkyloxy, phenoxy, halogen, trifluoromethyl, cyano, nitro, amino and C1-C5 alkylamino.
- 8. A thromboxane A2 receptor antagonist comprising the compound according to claim 1 as an active ingredient.
- 9. A pharmaceutical composition comprising the compound according to claim 1 as an active ingredient.
- 10. A pharmaceutical composition for therapy or prevention of hypertension, thrombosis, ischemic heart diseases, cerebral circulatory diseases, peripheral circulatory diseases, arteriosclerosis, platelet function disorder, hyperlipidemia, nephritis or asthma comprising the compound of claim 1.
- 11. A method for antagonizing activity of a thromboxane A2 receptor comprising contacting said thromboxane A2 receptor with a compound according to claim 1.
- 12. A method for preventing or treating a disease resulting from excessive thromboxane A2 activity resulting in abnormal platelet activation, thrombus formation or vasoconstriction comprising administering to a subject suffering from said disease an effective amount of the composition of claim 9 for inhibiting platelet activation, thrombus formation or vasoconstriction.
- 13. A method according to claim 12, wherein said disease is selected from the group consisting of hypertension, thrombosis, ischemic heart diseases, cerebral circulatory diseases, peripheral circulatory diseases, arteriosclerosis, platelet function disorder, hyperlipidemia, nephritis and asthma.
Priority Claims (1)
Number |
Date |
Country |
Kind |
7-788 |
Jan 1995 |
JP |
|
Parent Case Info
This application is a divisional of Ser. No. 08/700,477 filed Jun. 26, 1997 now U.S. Pat. No. 6,043,264.
US Referenced Citations (6)
Foreign Referenced Citations (4)
Number |
Date |
Country |
165810 |
Dec 1985 |
EP |
337766 |
Oct 1989 |
EP |
0548949 A2 |
Jun 1993 |
EP |
05081187 AL |
Feb 1994 |
EP |
Non-Patent Literature Citations (1)
Entry |
FitzGerald, “Prostaglandins and Related Compounds”, Cecil Textbook of Medicine, 20th Edition, vol. 2, pp. 1187-1194 (1996). |