Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtype-4 receptor agonist.

[1]  T. Baillie,et al.  Metabolic activation of a 1,3-disubstituted piperazine derivative: evidence for a novel ring contraction to an imidazoline. , 2005, Chemical research in toxicology.

[2]  J. Metzger,et al.  Discovery of (2S)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4 receptor agonist. , 2005, Bioorganic & medicinal chemistry letters.

[3]  D. Macintyre,et al.  Melanocortin receptors and erectile function. , 2004, European urology.

[4]  Pierre Bougnères,et al.  A homozygous null mutation delineates the role of the melanocortin-4 receptor in humans. , 2004, The Journal of clinical endocrinology and metabolism.

[5]  C. Haskell-Luevano,et al.  Melanocortin ligands: 30 years of structure–activity relationship (SAR) studies , 2004, Medicinal research reviews.

[6]  P. Molinoff,et al.  Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra® , 2004, International Journal of Impotence Research.

[7]  P. Molinoff,et al.  Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction , 2004, International Journal of Impotence Research.

[8]  J. Flier.  Obesity Wars Molecular Progress Confronts an Expanding Epidemic , 2004, Cell.

[9]  C. Fotsch,et al.  Synthesis of novel melanocortin 4 receptor agonists and antagonists containing a succinamide core. , 2004, Bioorganic & medicinal chemistry letters.

[10]  R. Ruel,et al.  β-Alanine dipeptides as MC4R agonists , 2003 .

[11]  F. Ujjainwalla,et al.  Design and syntheses of melanocortin subtype-4 receptor agonists: evolution of the pyridazinone archetype. , 2003, Bioorganic & medicinal chemistry letters.

[12]  C. Vaisse,et al.  The human MC4R promoter: characterization and role in obesity. , 2003, Diabetes.

[13]  Teresa Y. Phillips,et al.  Aryl piperazine melanocortin MC4 receptor agonists. , 2003, Bioorganic & medicinal chemistry letters.

[14]  C. Harmon,et al.  Recent developments in our understanding of melanocortin system in the regulation of food intake , 2003, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[15]  A. Daal,et al.  Melanocortins and their receptors and antagonists. , 2003, Current drug targets.

[16]  V. Hruby,et al.  Ac-nle-c[asp-his-dphe-arg-trp-lys]-nh2 induces penile erection via brain and spinal melanocortin receptors , 2003, Neuroscience.

[17]  I. Gantz,et al.  The melanocortin system. , 2003, American journal of physiology. Endocrinology and metabolism.

[18]  M. Pelleymounter,et al.  The role of melanocortin peptides and receptors in regulation of energy balance. , 2003, Current pharmaceutical design.

[19]  L. Illum.  Nasal drug delivery: new developments and strategies. , 2002, Drug discovery today.

[20]  C. Saper,et al.  The Need to Feed Homeostatic and Hedonic Control of Eating , 2002, Neuron.

[21]  D. Johnston,et al.  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. , 2002, Journal of medicinal chemistry.

[22]  Christopher P Austin,et al.  A role for the melanocortin 4 receptor in sexual function , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. Bednarek,et al.  Selective, high affinity peptide antagonists of alpha-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro. , 2001, Journal of medicinal chemistry.

[24]  L. Rossetti,et al.  Central melanocortin receptors regulate insulin action. , 2001, The Journal of clinical investigation.

[25]  C. Marazano,et al.  An enantioselective synthesis of isoquinuclidines from 3-substituted chiral pyridinium salts , 2001 .

[26]  R. Cone,et al.  The central melanocortin system can directly regulate serum insulin levels. , 2000, Endocrinology.

[27]  J. Friedman,et al.  Obesity in the new millennium , 2000, Nature.

[28]  J. Metzger,et al.  Role of the melanocortin-4 receptor in metabolic rate and food intake in mice , 2000, Transgenic Research.

[29]  S. O’Rahilly,et al.  Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. , 2000, The Journal of clinical investigation.

[30]  S. Heymsfield,et al.  Identification and functional analysis of novel human melanocortin-4 receptor variants. , 1999, Diabetes.

[31]  M. Bednarek,et al.  Structure-function studies on the cyclic peptide MT-II, lactam derivative of α-melanotropin☆ ☆ Throughout this report, the numbering of the amino acid residues in α-MSH has been retained for all linear and cyclic peptides. , 1999, Peptides.

[32]  V. Katta,et al.  Biochemical, biophysical, and pharmacological characterization of bacterially expressed human agouti-related protein. , 1998, Biochemistry.

[33]  Y. Langlois,et al.  New synthetic approaches to the oxahydrindane subunit of avermectins , 1997 .

[34]  R. Cone,et al.  Targeted Disruption of the Melanocortin-4 Receptor Results in Obesity in Mice , 1997, Cell.

[35]  Victor J. Hruby,et al.  Role of melanocortinergic neurons in feeding and the agouti obesity syndrome , 1997, Nature.

[36]  T. Hoye,et al.  Applications of MTPA (Mosher) Amides of Secondary Amines: Assignment of Absolute Configuration in Chiral Cyclic Amines , 1996 .

[37]  T. Hoye,et al.  MTPA (Mosher) amides of cyclic secondary amines: Conformational aspects and a useful method for assignment of amine configuration , 1996 .

[38]  Richard P. Woychik,et al.  Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor , 1994, Nature.

[39]  M. Mortrud,et al.  Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. , 1994, Molecular endocrinology.

[40]  S. Freedman,et al.  Synthesis and biological activity of 1,2,4-oxadiazole derivatives: highly potent and efficacious agonists for cortical muscarinic receptors. , 1990, Journal of medicinal chemistry.

[41]  C. Kouklovsky,et al.  .alpha.,.beta.-Unsaturated oxazolines, a powerful tool in asymmetric Diels-Alder cycloadditions , 1990 .

[42]  Jayne Marks.  From the Publisher , 2004, International Journal of Impotence Research.

[43]  M. Bednarek,et al.  Chapter 4. Melanocortin-4 receptor agonists and antagonists: Chemistry and potential therapeutic utilities , 2003 .

[44]  K. Flegal,et al.  Increasing prevalence of overweight among US adults. The National Health and Nutrition Examination Surveys, 1960 to 1991. , 1994, JAMA.

[45]  M. Mahon,et al.  Synthesis of 5-homoshikimic acid and some fluorinated derivatives as potential inhibitors of 5-enolpyruvylshikimate-3-phosphate synthase , 1992 .

[46]  B. Gillet,et al.  Synthesis of chiral isoquinuclidines and determination of their absolute configuration , 1988 .

[47]  H. Grill,et al.  Printed in U.S.A. Copyright © 2000 by The Endocrine Society The Role of the Dorsal Vagal Complex and the Vagus Nerve in Feeding Effects of Melanocortin-3/4 Receptor Stimulation* , 2022 .

[48]  J. Born,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society The Melanocortin Melanocyte-Stimulating Hormone/Adrenocorticotropin 4–10 Decreases Body Fat in Humans* , 2022 .