초록 ▼

and prodrugs thereof, geometric and optical isomers thereof, and pharmaceutically acceptable salts of such compounds, prodrugs and isomers, wherein R.sup.1 -R.sup.8 and X are as described herein. Pharmaceutical compositions containing such compounds, prodrugs, isomers or pharmaceutically acceptable

and prodrugs thereof, geometric and optical isomers thereof, and pharmaceutically acceptable salts of such compounds, prodrugs and isomers, wherein R.sup.1 -R.sup.8 and X are as described herein. Pharmaceutical compositions containing such compounds, prodrugs, isomers or pharmaceutically acceptable salts thereof, and methods, pharmaceutical compositions and kits for treating obesity, hyperlipidemia, thyroid disease, hypothyroidism and related disorders and diseases such as diabetes mellitus, atherosclerosis, hypertension, coronary heart disease, hypercholesteremia, depression and osteoporosis are also provided.

대표청구항 ▼

[What is claimed is:] [1.] rodrug thereof, a geometric or optical isomer thereof, or a pharmaceutically acceptable salt of said compound, said prodrug, or said isomer, wherein:R.sup.1 and R.sup.2 are independently halogen, C.sub.1-8 alkyl, --CN or C.sub.1-8 perfluoroalkyl; provided that at least one

[What is claimed is:] [1.] rodrug thereof, a geometric or optical isomer thereof, or a pharmaceutically acceptable salt of said compound, said prodrug, or said isomer, wherein:R.sup.1 and R.sup.2 are independently halogen, C.sub.1-8 alkyl, --CN or C.sub.1-8 perfluoroalkyl; provided that at least one of R.sup.1 and R.sup.2 is --CN;R.sup.3 is hydrogen or C.sub.1-8 alkyl;R.sup.4 is halogen, C.sub.1-8 perfluoroalkyl, C.sub.1-8 alkyl, C.sub.1-8 alkanoyl, hydroxy-(C.sub.1-8 alkyl), aryl optionally substituted with Y and Z, aryl-(C.sub.1-8 alkyl), carbocyclic aroyl optionally substituted with Y and Z, C.sub.3-10 cycloalkyl optionally substituted with Y and Z, or C.sub.3-10 cycloalkyl-(C.sub.1-8 alkyl);or R.sup.4 is the radical rein: R.sup.9 is hydrogen, C.sub.1-8 alkyl, aryl optionally substituted with Y and Z, aryl-(C.sub.1-8 alkyl), C.sub.3-10 cycloalkyl optionally substituted with Y and Z, or (C.sub.3-10 cycloalkyl-(C.sub.1-8 alkyl); R.sup.10 is --OR.sup.14 ; R.sup.11 is hydrogen or C.sub.1-8 alkyl; or R.sup.10 and R.sup.11 may be taken together with the carbon atom to which they are attached to form a carbonyl group;R.sup.5 is hydroxy, esterified hydroxy or etherified hydroxy;R.sup.6 is hydrogen, halogen, C.sub.1-8 alkyl or C.sub.1-8 perfluoroalkyl;R.sup.7 is hydrogen, C.sub.1-8 alkyl or C.sub.1-8 perfluoroalkyl;R.sup.8 is --OR.sup.12 or --NR.sup.12 R.sup.13 ;R.sup.12 and R.sup.13 are each independently hydrogen or C.sub.1-8 alkyl;R.sup.14 is hydrogen, C.sub.1-8 alkyl or C.sub.1-8 acyl;X is O, S(O).sub.a, C.dbd.O or NR.sup.15 ;a is 0, 1 or 2;R.sup.15 is hydrogen or C.sub.1-8 alkyl;Y and Z for each occurrence are independently (a) hydrogen, (b) halogen, (c) trifluoromethyl, (d) --OCF.sub.3, (e) --CN, (f) C.sub.1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, --OCF.sub.3, --CF.sub.3 and phenyl, (g) C.sub.1-6 alkoxy, (h) aryl optionally substituted with one or more substituents independently selected from the group consisting of halogen, --OCF.sub.3, --CF.sub.3, C.sub.1-4 alkyl and C.sub.1-4 alkoxy, (i) --C(O).sub.2 R.sup.16, (j) --C(O)NR.sup.16 R.sup.17, (k) --C(O)R.sup.16, (l) --NR.sup.16 C(O)NR.sup.16 R.sup.17 or (m) --NR.sup.16 C(O)R.sup.17 ; or Y and Z for any occurrence may be taken together to form (a) a carbocycle of the formula --(CH.sub.2).sub.b, or (b) a heterocycle selected from the group consisting of --O(CH.sub.2).sub.c O--, (CH.sub.2).sub.d NH-- and --CH.dbd.CHNH--;b is 3, 4, 5, 6 or 7;c and d are each independently 2, 3, 4, 5 or 6;R.sup.16 and R.sup.17 for each occurrence are independently hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, --(C.sub.1-6 alkyl)-C.sub.1-6 alkoxy, aryl optionally substituted with Y and Z, het optionally substituted with Y and Z, --(C.sub.1-4 alkyl)-aryl optionally substituted with Y and Z, --(C.sub.1-4 alkyl)-heterocycle optionally substituted with Y and Z, --(C.sub.1-4 alkyl)-hydroxy, --(C.sub.1-4 alkyl)-halo, --(C.sub.1-4 alkyl)-poly-halo, --(C.sub.1-4 alkyl)-CONR.sup.18 R.sup.19 or C.sub.3-10 cycloalkyl;het for each occurrence is a heterocyclic ring selected from the group consisting of 4-, 5-, 6-, 7- and 8-membered partially and fully saturated, and unsaturated, heterocyclic rings containing from one to four heteroatoms independently selected from the group consisting of N, O and S, and including any bicyclic group in which said heterocyclic ring is fused to a benzene ring or a heterocyclic ring selected from the group consisting of 4-, 5-, 6-, 7- and 8-membered partially and fully saturated, and unsaturated, heterocyclic rings containing from one to four heteroatoms independently selected from the group consisting of N, O and S; andR.sup.18 and R.sup.19 for each occurrence are independently hydrogen, C.sub.1-6 alkyl, C.sub.3-10 cycloalkyl or aryl optionally substituted with Y and Z.