Claims
- 1. A compound of Formula I
- 2. A compound of claim 1 wherein W is O; R0 is hydrogen; R1 is located at the 5-position and R2 is located at the 3-position; and R1 and R2 are each independently hydrogen, —(C1-C6)alkyl, halogen or CN.
- 3. A compound of claim 2 wherein R3 is hydrogen, —(C1-C4)alkyl or halogen; R4 is (a) —(C1-C10)alkyl substituted with zero to three substituents independently selected from F, hydroxy, oxo, aryl, heteroaryl, —(C3-C8)cycloalkyl, or heterocycloalkyl, (b) —(C3-C8)cycloalkyl, (c) heterocycloalkyl, (d) —C(O)Rc, (e) —ORb, (f) NRaC(O)Rd, (g) —NRaC(O)NRcRd or (h) —NRaS(O)2Rd;
or R3 and R4 are taken together along with the carbon atoms to which they are attached to form a carbocyclic ring of formula —(CH2)i— or a heterocyclic ring of formula —(CH2)k—Q—(CH2)i— wherein Q is —O—, —S—or —NRe—; i is 3, 4, 5 or 6; k is 0, 1, 2, 3, 4 or 5; and I is 0, 1, 2, 3, 4 or 5; and wherein the carbocyclic ring and the heterocyclic ring are each substituted with zero to four substituents independently selected from (a) —(C1-C4)alkyl, (b) —ORb, (c) oxo, (d) —CN, (e) phenyl or (f) —NRaRg; provided that when the substituent R4 is —(C1C10)alkyl substituted with zero to three substituents, the oxo group is substituted on a carbon atom other than the C1 carbon atom in —(C1-C10)alkyl.
- 4. A compound of claim 3 wherein R5 is —OH, —OC(O)Rf or —F; Rf is-(C1-C10)alkyl substituted with zero to three substituents independently selected from Group VI; R6 is hydrogen, halogen or-(C1-C4)alkyl; R7 is hydrogen or methyl; and R8 and R9 are each independently hydrogen, —(C1-C6)alkyl or halogen.
- 5. A compound of claim 4 wherein R4 is —(C0-C2)alkyl-(C3-C6)cycloalkyl, —(C1-C10)alkyl, or —(C0-C2)alkyl-aryl; and R10 is —C(O)OH, —C(O)OCH3 or —C(O)OCH2CH3.
- 6. A compound of claim 5 wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is —CH2-phenyl-4-F; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH.
- 7. A compound of claim 4 wherein R4 is —CH(OH)-aryl, —CH(OH)-heteroaryl, —CH(OH)—(CO—C2)alkyl-(C3-C8)cycloalkyl or —CH(OH)—(CO—C2)alkyl-heterocycloalkyl; and R10 is —C(O)OH, —C(O)OCH3 or-C(O)OCH2CH3.
- 8. A compound of claim 7 selected from the group consisting of:
a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is —CH(OH)-phenyl-4-F; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is —CH(OH)-phenyl-4-F; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OCH3; a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is —CH(OH)—CH2-cyclopentyl; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is —CH(OH)—CH2-cyclobutyl; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is —CH(OH)-phenyl-4-F; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is —CH(OH)-cyclopentyl; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH; and a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is —CH(OH)-cyclobutyl; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH.
- 9. A compound of claim 4 wherein R4 is —C(O)-aryl, —C(O)-heteroaryl, —C(O)—(C0-C2)alkyl-(C3-C8)cycloalkyl or —C(O)—(C0-C2)alkyl-heterocycloalkyl; and R10 is —C(O)OH, —C(O)OCH3 or —C(O)OCH2CH3.
- 10. A compound of claim 9 selected from the group consisting of:
a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is —C(O)-phenyl-4-F; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is —C(O)-phenyl-4-F; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OCH3; a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is —C(O)—CH2-cyclopentyl; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is CH3; R2 is CH3; R3 is hydrogen; R4 is —C(O)—CH2-cyclobutyl; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is —C(O)-cyclobutyl; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is —C(O)-cyclopentyl; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH; and a compound wherein R1 is Cl; R2 is CH3; R3 is hydrogen; R4 is —C(O)-phenyl-4-F; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH.
- 11. A compound of claim 3 wherein R3 and R4 are taken together along with the carbon atoms to which they are attached to form a carbocyclic ring of formula —(CH2)i— or a heterocyclic ring of formula —(CH2)k—Q—(CH2)i— wherein Q is —O—, —S—, or —NRe—; i is 3, 4, 5or6; k is 0, 1, 2, 3, 4or 5; and I is 0, 1, 2, 3, 4 or 5; and wherein the carbocyclic ring and the heterocyclic ring are each substituted with zero to four substituents independently selected from (a) —(C1-C4)alkyl, (b) —ORb, (c) oxo, (d) —CN, (e) phenyl or (f) —NRaRg.
- 12. A compound of claim 11 wherein R3 and R4 are taken together along with the carbon atoms to which they are attached to form a carbocyclic ring of formula —(CH2)i— wherein i is 3 and the carbocyclic ring is optionally substituted with zero to three substituents independently selected from the group consisting of oxo and methyl; or a heterocyclic ring of formula —(CH2)k—Q—(CH21— wherein Q is —NRa, Ra is hydrogen or-(C1-C6)alkyl; and k is 1; I is 1; and the heterocyclic ring is optionally substituted with one or two substituents independently selected from the group consisting of oxo and methyl.
- 13. A compound of claim 12 wherein R1 and R2 are each independently —CH3 or —Cl; R3 is hydrogen; R5 is —OH; R6, R7, R8 and R9 are each hydrogen; and R10 is —C(O)OH, —C(O)OCH3 or —C(O)OCH2CH3.
- 14. A compound of claim 13 selected from the group consisting of:
a compound wherein R1 is CH3, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form an indanyl, and R10 is —C(O)OH; a compound wherein R1 is Cl, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form an indanyl, and R10 is —C(O)OH; a compound wherein R1 is Cl, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form a 2-methyl-1-oxo-2,3-dihydro-1H-isoindolyl, and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form a 2-methyl-1-oxo-2,3-dihydro-1H-isoindolyl, and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form a 2-methyl-1-oxo-indanyl, and R10 is —C(O)OH; and a compound wherein R1 is CH3, R2 is CH3, R3 and R4 are taken together along with the carbon atoms to which they are attached to form a 2,2-dimethyl-1-oxo-indanyl, and R10 is —C(O)OH.
- 15. A compound of formula A
- 16. A compound of claim 15 selected from the group consisting of:
a compound wherein R1 is Cl; R2 is Cl; R4 is —SO2—NH-cyclopropyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —SO2—NH-cyclobutyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is CH3; R4 is —SO2—NH-cyclobutyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is CH3, R4 is —SO2—NH-cyclobutyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is CH3, R4 is —SO2—NH-cyclopropyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is CH3; R4 is —SO2—NH-cyclopropyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —SO2—NH—CH(CH3)2; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —SO2—NH-(CH2)3—CH3; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —SO2—NH-(CH2)6—CH3; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —SO2—NH-(4-fluoro-phenyl); R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is CH3, R4 is —SO2—NH-cyclohexyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; and a compound wherein R1 is Cl, R2 is Cl, R4 is —SO2—NH-cyclohexyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH.
- 17. A compound of claim 15 selected from the group consisting of:
N-[3,5-dichloro-4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[3,5-dichloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; and N-[4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid.
- 18. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of Formula A, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 15.
- 19. A compound of formula A
- 20. A compound of claim 19 selected from the group consisting of:
a compound wherein R1 is CH3; R2 is CH3; R4 is —C(O)N(CH3)-cyclobutyl; R3 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is CH3; R2 is CH3; R4 is —C(O)N(CH3)-cyclobutyl; R8 and R9 are each hydrogen; and R10 is —C(O)OCH3; a compound wherein R1 is Cl; R2 is CH3; R4 is —C(O)N(CH3)-cyclobutyl; R8 and R9 are each hydrogen; and R1 is —C(O)OH; a compound wherein R1 is Cl; R2 is CH3; R4 is —C(O)NH—CH(CH(CH3)2)2; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —C(O)NH—CH(CH(CH3)2)2; R3 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —C(O)NH—CH(CH3)-cyclohexyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is CH3; R2 is CH3; R4is —C(O)N(CH3)-cyclopentyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is CH3; R2 is CH3; R4is —C(O)N(CH3)—CH(CH3)2, R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —C(O)NH-(4-fluoro-phenyl); R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —C(O)NH—CH2-cyclohexyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —C(O)N(CH3)—CH2-cyclohexyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —C(O)N(CH3)-cyclohexyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —C(O)N(CH3)-cyclopentyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —C(O)N(CH3)-cycloheptyl; R8 and R9 are each hydrogen; and R10 is —C(O)OH; a compound wherein R1 is Cl; R2 is Cl; R4 is —C(O)N(CH3)—CH(CH(CH3)2)2; R8 and R9 are each hydrogen; and Rt° is —C(O)OH; and a compound wherein R1 is Cl; R2 is Cl; R4 is —C(O)N(CH3)—CH(CH3)-cyclohexyl; R3 and R9 are each hydrogen; and R10 is —C(O)OH.
- 21. A compound of claim 19 selected from the group consisting of:
N-{4-[3-(cyclobutyl-methyl-carbamoyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid; N-{3-chloro-4-[4-hydroxy-3-(1-isopropyl-2-methyl-propylcarbamoyl)-phenoxy]-5-methyl-phenyl}-malonamic acid; and N-{3,5-dichloro-4-[3-((1S)-cyclohexyl-ethylcarbamoyl)-4-hydroxy-phenoxy]-phenyl}-malonamic acid.
- 22. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of Formula A, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 19.
- 23. A compound of formula A
- 24. A compound of claim 23 selected from the group consisting of:
a compound wherein R1 is Cl, R2 is CH3, R4 is —SO2—CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OCH3; a compound wherein R1 is Cl, R2 is CH3, R4 is —SO2—CH2-cyclobutyl, R3 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is Cl, R2 is CH3, R4 is —SO2—CH2-cyclobutyl, R8 is hydrogen, R9 is methyl and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is Cl, R4 is —SO2—CH2-cyclobutyl, R3 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is H, R4 is —SO2—CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is Cl, R2 is CH3, R4 is —SO2—CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OCH2CH3; a compound wherein R1 is Cl, R2 is CH3, R4 is —SO2—CH2-cyclopropyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is Cl, R2 is Cl, R4 is —SO2—CH2-cyclopropyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is CH3, R4 is —SO2—CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OCH2CH3; a compound wherein R1 is CH3, R2 is CH3, R4 is —SO2—CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OCH3; a compound wherein R1 is CH3, R2 is CH3, R4 is —SO2—CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is CH3, R4 is —SO2—CH2-cyclobutyl, R8 is hydrogen, R9 is methyl and R10 is —C(O)OH; a compound wherein R1 is Cl, R2 is Cl, R4 is —SO2—CH2-cyclobutyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is CH3, R4 is —SO2—CH2-cyclopentyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is CH3, R4 is —SO2—CH2-cyclobutyl, R8 is methyl, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is Cl, R2 is CH3, R4 is —SO2—CH2-cyclohexyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is Cl, R2 is CH3, R4 is —SO2—CH2-cyclobutyl, R8 is methyl, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is Cl, R2 is CH3, R4 is —SO2—CH2-cyclopentyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is CH3, R4 is —SO2—CH2-cyclohexyl, R3 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; a compound wherein R1 is CH3, R2 is CH3, R4 is —SO2-cyclopentyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OH; and a compound wherein R1 is Cl, R is CH3, R4 is —SO2-cyclopentyl, R8 is hydrogen, R9 is hydrogen and R10 is —C(O)OH.
- 25. A compound of claim 23 selected from the group consisting of:
N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[3,5-dichloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-[3,5-dichloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-2-methyl-malonamic acid; N-[3-chloro-4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-2-methyl-malonamic acid; N-[3-chloro-4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid methyl ester; N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid ethyl ester; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid ethyl ester; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid methyl ester; N-[3-chloro-4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; and N-[4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid.
- 26. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of Formula A, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 23.
- 27. A compound selected from the group consisting of:
N-{4-[3-(cyclobutyl-methyl-carbamoyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid; N-{3-chloro-4-[4-hydroxy-3-(1-isopropyl-2-methyl-propylcarbamoyl)-phenoxy]-5-methyl-phenyl}-malonamic acid; N-{3,5-dichloro-4-[3-((1 S)-cyclohexyl-ethylcarbamoyl)-4-hydroxy-phenoxy]-phenyl}-malonamic acid; N-[3,5-dichloro-4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[3,5-dichloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-[4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[3,5-dichloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-[3,5-dichloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-2-methyl-malonamic acid; N-[3-chloro-4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-2-methyl-malonamic acid; N-[3-chloro-4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-{4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid; N-{3-chloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-5-methyl-phenyl}-malonamic acid; N-{4-[3-(4-fluoro-benzoyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid; N-[4-(3-cyclopentylacetyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-(4-{3-[(4-fluoro-phenyl)-hydroxy-methyl]-4-hydroxy-phenoxy}-3,5-dimethyl-phenyl)-malonamic acid; N-{4-[3-(2-cyclopentyl-1-hydroxy-ethyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid; N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid methyl ester; N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid ethyl ester; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid ethyl ester; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid methyl ester; N-[3-chloro-4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-{3-chloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-5-methyl-phenyl}-malonamic acid; N-{3-chloro-4-[3-(4-fluoro-benzenesulfonyl)4-hydroxy-phenoxy]-5-methyl-phenyl}-malonamic acid methyl ester; N-{3,5-dichloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-phenyl}-malonamic acid methyl ester; N-{3,5-dichloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-phenyl}-malonamic acid ethyl ester; N-{4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-2-methyl-malonamic acid methyl ester; N-{4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-2-methyl-malonamic acid; N-{3-chloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-5-methyl-phenyl}-2-methyl-malonamic acid methyl ester; N-{3-chloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-5-methyl-phenyl}-2-methyl-malonamic acid; N-{3,5-dichloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-phenyl}-2-methyl-malonamic acid methyl ester; and N-{3,5-dichloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-phenyl}-2-methyl-malonamic acid; or an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug.
- 28. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of claim 27, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug.
- 29. A method of claim 28 wherein the condition is obesity.
- 30. A method of claim 28 wherein the condition is diabetes.
- 31. A method of claim 29 which further comprises administering an anorectic agent.
- 32. A method of claim 31 wherein the anorectic agent is selected from the group consisting of phentermine, sibutramine, fenfluramine, dexfenfluramine and bromocriptine.
- 33. A method of claim 29 which further comprises administering a lipase inhibitor.
- 34. A method of claim 33 wherein the lipase inhibitor is selected from the group consisting of lipstatin, tetrahydrolipstatin (orlistat), FL-386, WAY-121898, Bay-N-3176, valilactone, esterastin, ebelactone A, ebelactone B and RHC 80267, stereoisomers thereof, and pharmaceutically acceptable salts of said compounds and stereoisomers.
- 35. A pharmaceutical composition comprising a compound of claim 27, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug.
- 36. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of Formula I, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 1.
- 37. A method of claim 36 wherein the condition is obesity.
- 38. A method of claim 36 wherein the condition is diabetes.
- 39. A pharmaceutical composition comprising a compound of Formula I, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 1.
- 40. A method of treating hair loss in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of
- 41. A method of claim 40 which comprises administering a compound of Formula I wherein W is O; R0 is hydrogen; R1 is located at the 5-position and R2 is located at the 3-position; and R1 and R2 are each independently hydrogen, —(C1-C6)alkyl, halogen or CN.
- 42. A method of claim 41 which comprises administering a compound of Formula I wherein R3 is hydrogen, —(C1-C4)alkyl or halogen; R4 is (a) —(C1-C10)alkyl substituted with zero to three substituents independently selected from F, hydroxy, oxo, aryl, heteroaryl, —(C3-C8)cycloalkyl, or heterocycloalkyl, (b) —S(O)2NRcRd, (c) —C(O)NRcRd, (d) —S(O)2Rc, (e) —(C3-C8)cycloalkyl, (f) heterocycloalkyl, (g) —C(O)Rc, (h) ORb, (i) SRr, (j) —S(O)Rc, (k) —NRaC(O)Rd, (I) —NRaC(O)NRcRd or (m) —NRaS(O)2Rd;
or R3 and R4 are taken together along with the carbon atoms to which they are attached to form a carbocyclic ring of formula —(CH2)i— or a heterocyclic ring of formula —(CH2)k—Q—(CH21— wherein Q is —O—, —S—or —NRe—; i is 3, 4, 5 or 6; k is 0, 1, 2, 3, 4 or 5; and I is 0, 1, 2, 3, 4 or 5; and wherein the carbocyclic ring and the heterocyclic ring are each substituted with zero to four substituents independently selected from (a) —(C1-C4)alkyl, (b) —ORb, (c) oxo, (d) —CN, (e) phenyl or (f) —NRaRg; provided that when the substituent R4 is —(C1C10)alkyl substituted with zero to three substituents, the oxo group is substituted on a carbon atom other than the C1 carbon atom in —(C1-C10)alkyl.
- 43. A method of claim 42 which comprises administering a compound of Formula I wherein R5 is —OH, —OC(O)Rf or —F; and Rf is —(C1-C10)alkyl substituted with zero to three substituents independently selected from Group VI; R6 is hydrogen, halogen or —(C1-C4)alkyl; R7 is hydrogen or methyl; and R8 and R9 are each independently hydrogen, —(C1-C6)alkyl or halogen.
- 44. A method of claim 43 which comprises administering a compound of Formula I wherein R4 is (a) —(C1-C10)alkyl substituted with zero to three substituents independently selected from F, hydroxy, oxo, aryl, heteroaryl, —(C3-C8)cycloalkyl, or heterocycloalkyl, (b) —S(O)2NRcRd, (c) —C(O)NRcRd, (d)—S(O)2Rc, (e) —(C3-C8)cycloalkyl, (f) heterocycloalkyl or (g) —C(O)Rc; and R10 is —C(O)OH, —C(O)OCH3 or —C(O)OCH2CH3 or a pharmaceutically acceptable salt or prodrug thereof.
- 45. A method of claim 44 which comprises administering a compound selected from the group consisting of:
N-{4-[3-(cyclobutyl-methyl-carbamoyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid; N-{3-chloro-4-[4-hydroxy-3-( 1-isopropyl-2-methyl-propylcarbamoyl)-phenoxy]-5-methyl-phenyl}-malonamic acid; N-{3,5-dichloro-4-[3-((1 S)-cyclohexyl-ethylcarbamoyl)-4-hydroxy-phenoxy]-phenyl}-malonamic acid; N-[3,5-dichloro-4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[3,5-dichloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[4-(3-cyclobutylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-[4-(3-cyclopropylsulfamoyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[3,5-dichloro-4-(3-cyclopropylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-[3,5-dichloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-phenyl]-malonamic acid; N-[4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-2-methyl-malonamic acid; N-[3-chloro-4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-2-methyl-malonamic acid; N-[3-chloro-4-(3-cyclopentylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[4-(3-cyclohexylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-{4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid; N-{3-chloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-5-methyl-phenyl}-malonamic acid; N-{4-[3-(4-fluoro-benzoyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid; N-[4-(3-cyclopentylacetyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-(4-{3-[(4-fluoro-phenyl)-hydroxy-methyl]-4-hydroxy-phenoxy}-3,5-dimethyl-phenyl)-malonamic acid; N-{4-[3-(2-cyclopentyl-1-hydroxy-ethyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid; N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid methyl ester; N-[3-chloro-4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid ethyl ester; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid ethyl ester; N-[4-(3-cyclobutylmethanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid methyl ester; N-[3-chloro-4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-5-methyl-phenyl]-malonamic acid; N-[4-(3-cyclopentanesulfonyl-4-hydroxy-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid; N-{3-chloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-5-methyl-phenyl}-malonamic acid; N-{3-chloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-5-methyl-phenyl}-malonamic acid methyl ester; N-{3,5-dichloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-phenyl}-malonamic acid methyl ester; N-{3,5-dichloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-phenyl}-malonamic acid ethyl ester; N-{4-[3-(4-fluoro-benzenesulfonyl)4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-2-methyl-malonamic acid methyl ester; N-{4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-2-methyl-malonamic acid; N-{3-chloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-5-methyl-phenyl}-2-methyl-malonamic acid methyl ester; N-{3-chloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-5-methyl-phenyl}-2-methyl-malonamic acid; N-{3,5-dichloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-phenyl}-2-methyl-malonamic acid methyl ester; and N-{3,5-dichloro-4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-phenyl}-2-methyl-malonamic acid; N-{4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid; and N-{4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid methyl ester; or an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug.
- 46. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, comprising:
administering to a patient having or at risk of having a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, a therapeutically effective amount of
1) a compound of Formula I, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 1; and 2) an additional compound useful for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss.
- 47. A method of claim 46 wherein the condition is obesity.
- 48. A method of claim 47 wherein the additional compound is a lipase inhibitor.
- 49. A method of claim 48 wherein the lipase inhibitor is selected from the group consisting of lipstatin, tetrahydrolipstatin (orlistat), FL-386, WAY-121898, Bay-N-3176, valilactone, esterastin, ebelactone A, ebelactone B and RHC 80267, stereoisomers thereof, and pharmaceutically acceptable salts of said compounds and stereoisomers.
- 50. A method of claim 47 wherein the additional compound is an anorectic agent.
- 51. A method of claim 50 wherein the anorectic agent is selected from the group consisting of phentermine, sibutramine, fenfluramine, dexfenfluramine and bromocriptine.
- 52. A kit for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, the kit comprising:
a) a first pharmaceutical composition comprising a compound of Formula I, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 1; b) a second pharmaceutical composition comprising an additional compound useful for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss; and c) a container.
- 53. A pharmaceutical composition comprising a compound of Formula I, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, as defined in claim 1; and an additional compound useful to treat a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss.
- 54. A composition of claim 53 wherein the condition is obesity.
- 55. A composition of claim 54 wherein the additional compound is a lipase inhibitor.
- 56. A composition of claim 55 wherein the lipase inhibitor is selected from the group consisting of lipstatin, tetrahydrolipstatin (orlistat), FL-386, WAY-121898, Bay-N-3176, valilactone, esterastin, ebelactone A, ebelactone B and RHC 80267, stereoisomers thereof, and pharmaceutically acceptable salts of said compounds and stereoisomers.
- 57. A composition of claim 54 wherein the additional compound is an anorectic agent.
- 58. A composition of claim 57 wherein the anorectic agent is selected from the group consisting of phentermine, sibutramine, fenfluramine, dexfenfluramine and bromocriptine.
- 59. A method of treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, comprising:
administering to a patient having or at risk of having a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, a therapeutically effective amount of
1) a compound of claim 27, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug; and 2) an additional compound useful for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss.
- 60. A method of claim 59 wherein the condition is obesity.
- 61. A method of claim 60 wherein the additional compound is a lipase inhibitor.
- 62. A method of claim 61 wherein the lipase inhibitor is selected from the group consisting of lipstatin, tetrahydrolipstatin (orlistat), FL-386, WAY-121898, Bay-N-3176, valilactone, esterastin, ebelactone A, ebelactone B and RHC 80267, stereoisomers thereof, and pharmaceutically acceptable salts of said compounds and stereoisomers.
- 63. A method of claim 60 wherein the additional compound is an anorectic agent.
- 64. A method of claim 63 wherein the anorectic agent is selected from the group consisting of phentermine, sibutramine, fenfluramine, dexfenfluramine and bromocriptine.
- 65. A kit for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss, the kit comprising:
a) a first pharmaceutical composition comprising a compound of claim 27, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug; b) a second pharmaceutical composition comprising an additional compound useful for treating a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss; and c) a container.
- 66. A pharmaceutical composition comprising a compound of claim 27, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug; and an additional compound useful to treat a condition selected from the group consisting of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorder, thyroid disease, hypothyroidism, thyroid cancer, diabetes, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss.
- 67. A composition of claim 66 wherein the condition is obesity.
- 68. A composition of claim 67 wherein the additional compound is a lipase inhibitor.
- 69. A composition of claim 68 wherein the lipase inhibitor is selected from the group consisting of lipstatin, tetrahydrolipstatin (orlistat), FL-386, WAY-121898, Bay-N-3176, valilactone, esterastin, ebelactone A, ebelactone B and RHC 80267, stereoisomers thereof, and pharmaceutically acceptable salts of said compounds and stereoisomers.
- 70. A composition of claim 67 wherein the additional compound is an anorectic agent.
- 71. A composition of claim 68 wherein the anorectic agent is selected from the group consisting of phentermine, sibutramine, fenfluramine, dexfenfluramine and bromocriptine.
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application claims priority of U.S. Provisional Application No. 60/193,618, filed Mar. 31, 2000.
Provisional Applications (1)
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Number |
Date |
Country |
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60193618 |
Mar 2000 |
US |
Patent Application
20010051657
