Claims
- 1. A naphthyloxyacetic acid derivative of the general formula (I) wherein A is (i) hydrogen; (ii) -(C1-4 alkylene)-OH; or (iii) -(C1-4 alkylene)-CN; E is (i) single bond or (ii) C1-6 alkylene; G is —S—, —SO— or —SO2—, L is (i) C1-6 alkylene, (ii) —(CH2)m—CH═CH—(CH2)n— in which m is 0 or an integer of 1-3, n is 0 or an integer of 1-3 or (iii) —(CH2)x—CH(OH)—(CH2)y— in which x is an integer of 1-3, y is 0 or an integer of 1-3; in which each phenyl group is optionally substituted by 1-3 of C1-4 alkyl, C1-4 alkoxy, halogen, nitro or trifluoromethyl; in the formula is single bond or double bond; with the proviso that,(1) when G is —SO— or —SO2—, M is neither in which each phenyl group is optionally substituted by 1-3 of C1-4 alkyl, C1-4 alkoxy, halogen, nitro or trifluoromethyl,(2) when m in L is 0, G is —SO— or —SO2—, (3) when n in L is 0, M is in which each phenyl group is optionally substituted by 1-3 of C1-4 alkyl, C1-4 alkoxy, halogen, nitro or trifluoromethyl,(4) when y in L is 0, M is in which each phenyl group may be substituted by 1-3 of C1-4 alkyl, C 1-4 alkoxy, halogen, nitro or trifluoromethyl, and(5) when A is hydrogen, L is —(CH2)m—CH═CH—CH2)n— in which m is 0 or an integer of 1-3 and n is 0 or an integer of 1-3 or —(CH2)x-CH(OH)—(CH2)y— in which x is an integer of 1-3 and y 0 or an integer of 1-3 or non-toxic salt thereof, non-toxic acid addition salt thereof or their hydrate.
- 2. A compound according to claim 1, wherein A is -(C1-alkylene)-OH.
- 3. A compound according to claim 1, wherein A is hydrogen.
- 4. A compound according to claim 5, wherein L is —(CH2)m—CH═CH— (CH2)n or —(CH2)x—CH(OH)—(CH2)y—.
- 5. A compound according to claim 4, wherein G is —S—.
- 6. A pharmaceutical composition which comprises a carrier and an effective amount of naphthyloxyacetic acid derivative of the formula (1) depicted in claim 1, non-toxic salt thereof, non-toxic acid addition salt thereof or their hydrate.
- 7. A prostaglandin E2 antagonist or agonist which comprises a naphthyloxyacetic acid derivative of the formula (I) depicted in claim 1, non-toxic salt thereof, non-toxic acid addition salt thereof or their hydrate.
- 8. A compound according to claim 1, which is(1) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-phenoxy-2RS-propanol, (2) 1-[2-(5-hydroxy-1-naphthyl)ethylsulfinyl]-3-phenoxy-2RS-propanol, (3) 1-[2-(5-hydroxy-1-naphthylethylsulfonyl]-3-phenoxy-2RS-propanol, (4) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-phenoxy-2R-propanol, (5) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-phenoxy-2S-propanol, (6) 1-(5-hydroxy-1-naphthyl)methylthio-3-phenoxy-2RS-propanol, (7) 1-5-hydroxy-1-naphthyl)methylsulfinyl-3-phenoxy-2RS-propanol, (8) 1-(5-hydroxy-1-naphthyl)methylsulfonyl-3-phenoxy-2RS-propanol, (9) 2-[3-(5-hydroxy-1-naphthylpropylthio]-1-phenyl-1RS-ethanol, (10) 2-[3-(5-hydroxy-1-naphthyl)propylsulfinyl]-1-phenyl-1RS-ethanol, (11) 2-[3-(5-hydroxy-1-naphthylpropylsulfonyl]-1-phenyl-1RS-ethanol, (12) 1-(5-hydroxy-1-naphthyl)thio-3-phenoxy-2RS-propanol, (13) 1-(5-hydroxy-1-naphthyl)sulfinyl-3-phenoxy-2RS-propanol, (14) 1-(5-hydroxy-1-naphthyl)sulfonyl-3-phenoxy-2RS-propanol, (15) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-(4-chlorophenoxy)-2RS-propanol, (16) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-(4-methylphenoxy)-2RS-propanol, (17) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-(4-methoxyphenoxy)-2RS-propanol, (18) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-diphenylmethoxy-2RS-propanol, (19) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-[1-phenyl-1-(4-chlorophenyl)-methoxy]-2RS-propanol, (20) 1-[2-(5-hydroxy-1-naphthyl)ethylthio]-3-phenyltbio-2RS-propanol, (21) 1-(5-hydroxy-1-naphthyl)methylthio-3-diphenylmethoxy-2RS-propanol, (22) 1-(5-hydroxy-1-naphthyl)methylthio-3-[1-phenyl-1-(4-chlorophenyl)-methoxy]-2RS- propanol, (23) 2-{5-[2-(2RS-hydroxy-3-(1-phenyl-1-(4-chlorophenyl)methoxy)propylthio)-ethyl]-1-naphthyloxy}ethanol, or (24) 1-{2-[5-hydroxy-1-(1,2,3,4-tetrahydronaphthyl)]ethylthio}-3-phenoxy-2RS-propanol.
- 9. The compound of claim 1, wherein A is —(C1-4 alkylene)-CN.
- 10. A compound according to claim 4, wherein G is —SO—.
- 11. A compound according to claim 4, wherein G is —SO2—.
- 12. A compound according to claim 5 which is(1) 1-cyanomethoxy-5-[2-2RS-hydroxy-3-phenoxypropylthio)-ethyl]napthylene, (2) 1-cyanomethoxy-5-{2-[2RS-hydroxy-3-(4-chlorophenoxy)propylthio]ethyl}-napthalene, (3) 1-cyanomethoxy-5-{2-[2RS-hydroxy-3-(4-methylphenoxy)propylthio]ethyl}naphthalene, (4) 1-cyanomethoxy-5-{2-[2RS-hydroxy-3-(4-methoxyphenoxy)-propylthio]ethyl}naphthalene, (5) 1-cyanomethoxy-5-[2-(2RS-hydroxy-3-diphenylmethoxypropylthio)-ethyl]naphthalene, (6) 1-cyanomethoxy-5-[2-(2RS-hydroxy-3-phenylthiopropylthio)-ethyl]naphthalene, (7) 1-cyanomethoxy-5-[(2RS-hydroxy-3-diphenylmethoxy)propylthiomethyl]-naphthalene, and (8) 1-cyanomethoxy-5-[2-(2RS-hydroxy-3-phenoxypropylthio)ethyl]-5,6,7,8-tetrahydronaphthalene.
Parent Case Info
This application is a divisional of U.S. patent application Ser No. 09/000,102 now U.S. Pat. No. 6,018,068, filed Jan. 26, 1998, which is a 371 of PCT/JP96/01833, filed Jul. 2, 1996 now WO97/05091.
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