COMPOSITIONS AND METHODS FOR THE TREATMENT OF METABOLIC DISORDERS

摘要

The present invention relates to treatment and/or prevention of one or more metabolic disorders utilizing fatostatin A and/or a derivative and/or analog thereof. In other aspects, the compound for treatment and/or prevention of one or more metabolic disorders utilizes an A-B-C tripartite structure, wherein A, B, and C are identical or non-identical structures and are described in detail herein. In specific aspects, the metabolic disorder includes obesity or diabetes, for example.

主权项

1. A compound comprising the general formula: wherein R1 is hydrogen, methyl, ethyl, or propyl; R2, R3, and R4 are the same or different and are selected from the group consisting of: a) hydroxy; b) substituted or unsubstituted C1-10 alkyl; c) substituted or unsubstituted C2-10 alkenyl; d) substituted or unsubstituted C2-10 alkynyl; e) substituted or unsubstituted C3-6 cycloalkyl; f) substituted or unsubstituted aryl; g) substituted or unsubstituted heteroaryl; wherein said substitutions in b), c), d), e), f), and/or g) are optionally further substituted with 1-5 groups selected from the group consisting of:
1) hydroxy;2) —(C═O)Ra;3) —(C═O)ORa;4) —(C═O)H;5) —(C═O)OH;6) —O(CH2)nCOORa, wherein n=1-10;7) halo;8) cyano;9) carboxy;10) amino;11) mono-substituted amino;12) di-substituted amino;13) amido;14) mono-substituted amido;15) di-substituted amido; and16) any combination thereof,wherein in 2), 3), or 6) Ra is a C1-10 alkyl, C2-10 alkenl, C2-10 alkynyl, C3-6 cycloalkyl, aryl, or heteroaryl; h) —(C═O)Ra; i) —(C═O)ORa; j) —(C═O)H; k) —(C═O)OH; l) —O(CH2)nCOORa, wherein n=1-10, wherein in h), i), or l), Ra is a C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-6 cycloalkyl, aryl or heteroaryl; m) halo; n) cyano; o) carboxy; p) amino; q) mono-substituted amino; r) di-substituted amino, s) amido; t) mono-substituted amido; and u) di-substituted amido;
wherein one or more of said mono-substituted amino, di-substituted amino, mono-substituted amido, and di-substituted amido have a substitution selected from the group consisting of C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-6 cycloalkyl, aryl, heteroaryl, sulfoxide, sulfone, sulfonate, alkyl sulfonate, sulfonic acid, and any combination thereof,
wherein in u) said alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heteroaryl are optionally further substituted with 1-5 groups selected from the group consisting of:
i) hydroxy;ii) —(C═O)Ra;iii) —(C═O)ORa;iv) —(C═O)H;v) —(C═O)OH;vi) —O(CH2)nCOORa, wherein n=1-10,wherein in ii), iii), or vi) Ra is a C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-6 cycloalkyl, aryl or heteroaryl;vii) halo;viii) cyano;ix) carboxy;x) amino;xi) mono-substituted amino;xii) di-substituted amino;xiii) amido;xiv) mono-substituted amido;xv) di-substituted amido; andxvi) any combination thereof; R5 is a substituted alkyl, aryl heteroaryl or —SO2R wherein R is a substituted alkyl, aryl or heteroaryl; and, Y1 is nitrogen, Y2 and Y3 are the same or different and are sulfur or methylene.