Melanin-concentrating hormone receptor antagonists and methods of use
This invention relates generally to N-benzylamino cyclic thioureas, pharmaceutical compositions containing them, and their use as antagonists of melanin-concentrating hormone receptor (MCH receptor).
1. A composition of matter comprising a compound having the following structural formula:
wherein,
R 1 and R 2 are selected from H, a hydrocarbyl having up to 20 carbon atoms, and a hydrocarbyl having up to 20 carbon atoms and substituted with a group selected from hydroxy, alkoxy, amino, substituted amino, thio, alkylthio, guanidino, ureido and heterocyclyl;
R 3 is selected from a hydrocarbyl having up to 20 carbon atoms, and a hydrocarbyl having up to 20 carbon atoms and substituted with a group selected from halo, haloalkyl, hydroxy, alkyl, alkoxy, alkylenedioxy, amino, substituted amino, aminoalkyl, thio, alkylthio, guanidino, ureido, heterocyclyl, heteroaryl, and heteroarylthio;
R 4 is a substituted amino, —NR 6 R 7 , wherein R 6 and R 7 are selected from H and a hydrocarbyl having up to 20 carbon atoms; R 6 and R 7 , with inclusion of N, may combine to form a heterocyclic ring such as indolinyl having the formula
R 5 is selected from O, S, NH, N-alkyl, N-alkenyl, N-alkynyl, N-cycloalkyl, N-aryl and N-aralkyl,
n is 1 to 3; and
wherein the composition is further characterized by at least one additional limitation selected from group consisting of:
one or more methylene groups of a hydrocarbyl group of R3 being replaced by an oxygen atom;
R 1 being selected from alkyl and aminoalkyl;
R 1 being selected from (S)-Methyl, (R)-Methyl or (S)-Propyl;
R 1 being (S)-Aminopropyl;
R 2 being selected from (R)-Aminomethyl-(imino)-propyl, (S)-Aminomethyl-(imino)-propyl or (S)-Methylthiomethyl;
R 3 being selected from alkyl, aralkyl or substituted aralkyl;
R 3 being 3-bromophenethyl;
R 3 being 3,5 bis-(trifluoromethyl)phenethyl;
R 4 being aralkylamino;
R 4 being benzylamino;
R 6 and R 7 with inclusion of n, being heterocyclyl; and
—NR 6 R 7 being isoindolinyl having the formula
2. A composition according to claim 1 , wherein R1, R2, R3, R6 or R7 comprises a straight chain hydrocarbyl.
3. A composition according to claim 1 , wherein R1, R2, R3, R6 or R7 comprises a branched chain hydrocarbyl.
4. A composition according to claim 1 , wherein R1, R2, R3, R6 or R7 comprises a saturated hydrocarbyl.
5. A composition according to claim 1 , wherein R1, R2, R3, R6 or R7 comprises an unsaturated hydrocarbyl.
6. A composition according to claim 1 , wherein R1, R2, R3, R6 or R7 comprises a cyclic hydrocarbyl.
7. A composition according to claim 1 , wherein R1, R2, R3, R6 or R7 comprises an acyclic hydrocarbyl.
8. A composition according to claim 1 , wherein R1, R2, R3, R6 or R7 comprises a chiral hydrocarbyl.
9. A composition according to claim 1 , wherein R1, R2, R3, R6 or R7 comprises an achiral hydrocarbyl.
10. A composition according to claim 1 , wherein R1, R2, R3, R6 or R7 comprises a substituted hydrocarbyl.