312638-87-2Relevant articles and documents
PHARMACOLOGICAL CHAPERONES FOR TREATING OBESITY
-
Page/Page column 2/18, (2008/06/13)
The invention relates to methods of enhancing normal melanocortin-4 receptor (MC4R) activity, and to enhancing activity of an MC4R having a mutation which affects protein folding and/or processing of the MC4R. The invention provides a method of treating an individual having a condition in which increased activity of an MC4R at the cell surface would be beneficial, for example in obesity, by administering an effective amount of a pharmacological chaperone for the MC4R. The invention provides MC4R pharmacological chaperones which enhance the activity of MC4R. The invention further provides a method of screening to identify pharmacological chaperones which enhance folding of an MC4R in the endoplasmic reticulum (ER), in order to enhance the activity of the MC4R at the cell surface.
Melanocortin receptor ligands
-
Page/Page column 9, (2008/06/13)
The present invention relates to compounds which comprise a 4-substituted piperidine ring linked to a substituted or unsubstituted hydrocarbyl ring. The compounds, including all enatiomeric and diasteriomeric forms and pharmaceutically acceptable salts thereof, have the formula: wherein preferably R is substituted aryl, W1 is a carbocyclic unit, and W2 is a heteroatom comprising unit.
Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium-3-ylcarbonyl]-(1R)-1- (4-chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl) piperidin-1-yl]-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist
Sebhat, Iyassu K.,Martin, William J.,Ye, Zhixiong,Barakat, Khaled,Mosley, Ralph T.,Johnston, David B. R.,Bakshi, Raman,Palucki, Brenda,Weinberg, David H.,MacNeil, Tanya,Kalyani, Rubana N.,Tang, Rui,Stearns, Ralph A.,Miller, Randy R.,Tamvakopoulos, Constantin,Strack, Alison M.,McGowan, Erin,Cashen, Doreen E.,Drisko, Jennifer E.,Hom, Gary J.,Howard, Andrew D.,MacIntyre, D. Euan,Van der Ploeg, Lex H. T.,Patchett, Arthur A.,Nargund, Ravi P.
, p. 4589 - 4593 (2007/10/03)
Synthetic and natural peptides that act as nonselective melanocortin receptor agonists have been found to be anorexigenic and to stimulate erectile activity. We report the design and development of 1, a potent, selective (1184-fold vs MC3R, 350-fold vs MC5R), small-molecule agonist of the MC4 receptor. Pharmacological testing confirms the food intake lowering effects of MC4R agonism and suggests another role for the receptor in the stimulation of erectile activity.