Palatin Technologies Incorporated

Ramesh Rajpurohit

Shubh D Sharma

Yi-Qun Shi

Annette M Shadiack

Zhijun Wu

Kevin D Burris

Wei Yang

Papireddy Purma

Margarita Bastos

Hui-Zhi Cai

Yiqun Shi

Bolun Hu

A melanocortin-4 receptor agonist cyclic peptide of the formula where R, R, R, R, R, R, R, R, R, x, y and z are as defined in the specification, and a method of treating sexual dysfunction, including male erectile dysfunction and female sexual dysfunction, and other melanocortin 4 receptor responsive conditions and disorders.

N-alkylated cyclic peptide melanocortin agonists

A melanocortin receptor-specific compound of the general formula of structure I: where X, R, R, R, R, R, R, Rand Rare as defined in the specification, which compound binds with high affinity to one or more melanocortin receptors and is optionally an agonist, an antagonist, an inverse agonist or an antagonist of an inverse agonist, and may be employed for treatment of one or melanocortin receptor-associated conditions or disorders, and methods for the use of the compounds of the invention.

Melanocortin receptor-specific compounds

The invention relates to a method of deriving a peptidomimetic of a biologically active metallopeptide, wherein the peptidomimetic includes at least one non-peptide ring structure defining a template space superimposable on a corresponding defined template space of the metallopeptide, and where the peptidomimetic further includes at least two elements independently including an amino acid residue, amino acid side chain moiety or derivative thereof, the elements defining and occupying a similar descriptor space as corresponding elements of the metallopeptide. The invention further relates to peptidomimetics with a template space heterocyclic ring structure, including 5-, 6- and 8-membered and 5-5- and 6-5-bicyclic fused ring structure melanocortin receptor-specific peptidomimetics.

Peptidomimetics of biologically active metallopeptides

A peptide of the structural formula: or a pharmaceutically acceptable salt thereof, wherein R, R, R, R, R, R, m and n are as defined. Further provided are methods for treatment of sexual dysfunction, including erectile dysfunction and female sexual dysfunction, and combination drugs and method of use thereof, including a peptide of the invention and one or more second sexual dysfunction pharmaceutical agents.

Peptide compositions for treatment of sexual dysfunction

A method of modulating energy homeostasis in a mammal without eliciting a sexual response by administration of a therapeutically effective amount of a pharmaceutical composition including a melanocortin receptor compound of the formula: where Ris a bond or a linker unit including from one to six backbone atoms and an unsubstituted naphthalene group, and L, R, Rand Rare as defined in the specification.

Naphthalene-containing melanocortin receptor-specific small molecule

Melanocortin receptor-specific compounds of the general formulas and pharmaceutically acceptable salts thereof, where J is a substituted or unsubstituted monocyclic or bicyclic ring structure, L is a linker, W is a heteroatom unit with at least one cationic center, hydrogen bond donor or hydrogen bond acceptor, Q includes a substituted or unsubstituted aromatic carbocyclic ring, R, R, y and z are as defined in the specification, and the carbon atom marked with an asterisk can have any stereochemical configuration, and optionally with one or two additional ring substituents as defined, which compounds bind to one or more melanocortin receptors and are optionally an agonist, a partial agonist, an antagonist, an inverse agonist or an antagonist of an inverse agonist, and may be employed for treatment of one or more melanocortin receptor-associated conditions or disorders, and methods for the use of the compounds of the invention.

Substituted melanocortin receptor-specific piperazine compounds

A substituted piperazine compound having the structure I: or the structure IX: or an enantomeric, stereoisomeric or diastereomeric form of the foregoing, and pharmaceutically acceptable salts thereof, where J, L, Q, W, A, R, R, z and y are as defined in the specification, and the carbon atoms marked with an asterisk can have any stereochemical configuration, which compounds bind to one or more melanocortin receptors and may be employed in pharmaceutical preparations for treatment of one or more melanocortin receptor-associated conditions or disorders, and methods for the use of the compounds of the invention.

Melanocortin receptor-specific pyrrolidine compounds having the structure: and stereoisomer and pharmaceutically acceptable salts thereof, where R, R, and Rare as described in the specification, preferably where Ris a D-amino acid with at least one substituted or unsubstituted phenyl or naphthyl aromatic ring, and where Roptionally further includes an amine capping group or from one to three additional amino acid residues, optionally with an amine capping group, which compounds are agonists, antagonists or mixed agonists and antagonists at one or more melanocortin receptors, and having utility in the treatment of melanocortin receptor-related disorders and conditions. Methods of synthesis of compounds of structure (I), pharmaceutical compositions containing a compound of structure (I) and methods relating to the use thereof are also disclosed.

Pyrrolidine melanocortin-specific compounds

Linear and cyclic peptides are provided specific to one or melanocortin receptors, and which exhibit agonist, antagonist, or mixed agonist-antagonist activity. In one embodiment, a linear peptide of the following general formula is provided: 

Linear and cyclic melanocortin receptor-specific peptides

Metallopeptide compositions are provided for treatment of sexual dysfunction in mammals, including male sexual dysfunction, such as erectile dysfunction, and female sexual dysfunction. The metallopeptides include at least one, and preferably two, aromatic amino acid side chain moieties, and are further characterized in that the metallopeptides preferably do not bind or significantly bind to a melanocortin receptor.

Metallopeptide compositions for treatment of sexual dysfunction

Metallopeptides with a sequence of a biologically active alpha-melanocyte stimulating hormone (&#x3b1;-MSH), gamma-melanocyte stimulating hormone (&#x3b3;-MSH), or bombesin sequence of length n residues, wherein a residue including a nitrogen atom and sulfur atom each available for complexation to a metal ion is inserted at any position from between the two and three position to the C-terminus side of the n position, or alternatively is substituted for the residue at any position from the three position to the n position, with a metal ion complexed thereto, with any proline (Pro) residue which is either of the two residues on the immediately adjacent N-terminus side of the inserted or substituent residue comprising a nitrogen atom and sulfur atom available for complexation to a metal ion is substituted with a homolog.

Metallopeptide compounds

Melanocortin receptor-specific piperazine or ketopiperazine compounds having the structure: and stereoisomer and pharmaceutically acceptable salts thereof, where X is CHor C&#x2550;O, R, R, and Rare as described in the specification, preferably where Ris a D-amino acid with at least one substituted or unsubstituted phenyl or naphthyl aromatic ring, and where Roptionally further includes an amine capping group, a second amino acid residue or a second amino acid residue with an amine capping group, which compounds are agonists, antagonists or mixed agonists and antagonists at one or more melanocortin receptors, and having utility in the treatment of melanocortin receptor-related disorders and conditions. Methods of synthesis of compounds of structure (I), pharmaceutical compositions containing a compound of structure (I) and methods relating to the use thereof are also disclosed.

Piperazine melanocortin-specific compounds

The invention provides methods for identification and determination of target-specific sites in peptides and proteins, including a method for determining the primary sequence of a secondary structure within a known parent polypeptide that binds to the target of interest. In one embodiment of the invention, a residue or mimetic containing a nitrogen atom and a sulfur atom available for binding to a metal ion is serially substituted for single residues in or inserted between adjacent residues in a known primary sequence of a peptide or protein. The resulting sequence is complexed with a metal ion thereby forming a metallopeptide. The resulting metallopeptides are then used in binding or functional assays related to the target of interest, and the metallopeptide(s) which result in significant or substantially decreased or changed binding or functionality are determined to identify the primary sequence involved in such binding or functionality.

Knockout identification of target-specific sites in peptides

A highly selective melanocortin-4 receptor antagonist cyclic hexapeptide of the formula where R, R, R, R, R, R, x, y and z are as defined in the specification, and a method of treating body weight disorders, including cachexia, sarcopenia and wasting syndrome or disease, and treating inflammation and immune disorders.

Growing community of inventors

Hillsboro, NJ, United States of America

Ramesh Rajpurohit