Arena Pharmaceuticals, Inc.

Cara Therapeutics, Inc.

Neurocrine Biosciences, Inc.

Other

Ssp Co. Ltd

Tripos, Inc.

Cera Therapeutics, Inc.

Derek T Chalmers

Chen Wang Liaw

Dominic P Behan

Claudio Daniel Schteingart

Guangcheng Jiang

Javier Sueiras-Diaz

Roberta Vezza Alexander

Robert H Spencer

Frédérique Menzaghi

Zhiyong Luo

Joseph F Russo

William J Thomsen

Robert Zhiyong Luo

Ruoping Chen

Qian Liu

Kevin P Lowitz

Robert C Glen

Richard J Foster

Michael S Lawless

Julian R Smith

James N Leonard

Dimitri Emil Grigoriadis

David J Unett

Tilman Oltersdorf

Timothy W Lovenberg

Errol B DeSouza

Daniel T Connolly

Susumo Sato

Yaron Hakak

Tadayuki Koda

Jeremy G Richman

Sonja Strah-Pleynet

Nigel R A Beeley

Michael E Lewis

I-Lin Lin

Nigel R Beeley

Huong T Dang

Dominique Maciejewski-Lenior

Daniel Ortuño

I Lin-Lin

Michael R Lerner

Bryan J Choi

The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low PCYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: The compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.

Synthetic peptide amides and dimers thereof

The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low PCYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I: These compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.

Synthetic peptide amides

The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low PCYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I: Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.

The invention relates to methods of use of synthetic peptide amides that are ligands of the kappa opioid receptor in the treatment and prevention of kappa opioid receptor-associated diseases and conditions; and particularly to uses of these agonists in the prophylaxis, inhibition and treatment of pain, inflammation and pruritis associated with a variety of diseases, disorders and conditions. Inflammatory conditions preventable or treatable by the methods of the invention include diseases and conditions associated with elevated levels of a proinflammatory cytokines, such as TNF-&#x3b1;, IL-1&#x3b2;, IL-6, MMP-1 and MMP-3. Such diseases and conditions include cardiovascular inflammation, neurological inflammation, skeletal inflammation, muscular inflammation, gastrointestinal inflammation, ocular inflammation, otic inflammation, inflammation due to insect bites and inflammation due to wound healing; atherosclerosis, ischemia, restenosis and vasculitis; of asthma, Sjogren's syndrome, pulmonary inflammation, chronic airway inflammation and chronic obstructive pulmonary disease (COPD), allergy, psoriasis, psoriatic arthritis, eczema, scleroderma, atopic dermatitis and systemic lupus erythematosus, arthritis, synovitis, osteomyelitis, rheumatoid arthritis, osteoarthritis and ankylosing spondylitis; septicemia and septic shock, diabetes, glucose intolerance, insulin resistance and obesity, colitis, ulcerative colitis, Crohn's disease, IBD and IBS, and the inflammatory diseases and conditions due to tumor proliferation, tumor metastasis or transplantation rejection.

Uses of kappa opioid synthetic peptide amides

Synthetic peptide amides for pain

The invention relates to methods of use of synthetic peptide amides that are ligands of the kappa opioid receptor in the treatment and prevention of kappa opioid receptor-associated diseases and conditions; and particularly to uses of these agonists in the prophylaxis, inhibition and treatment of pain, inflammation and pruritis associated with a variety of diseases, disorders and conditions. Inflammatory conditions preventable or treatable by the methods of the invention include diseases and conditions associated with elevated levels of a proinflammatory cytokines, such as TNF-&#x3b1;, IL-&#x3b2;, IL-6, MMP-1 and MMP-3. Such diseases and conditions include cardiovascular inflammation, neurological inflammation, skeletal inflammation, muscular inflammation, gastrointestinal inflammation, ocular inflammation, otic inflammation, inflammation due to insect bites and inflammation due to wound healing; atherosclerosis, ischemia, restenosis and vasculitis; of asthma, Sjogren's syndrome, pulmonary inflammation, chronic airway inflammation and chronic obstructive pulmonary disease (COPD), allergy, psoriasis, psoriatic arthritis, eczema, scleroderma, atopic dermatitis and systemic lupus erythematosus, arthritis, synovitis, osteomyelitis, rheumatoid arthritis, osteoarthritis and ankylosing spondylitis; septicemia and septic shock, diabetes, glucose intolerance, insulin resistance and obesity, colitis, ulcerative colitis, Crohn's disease, IBD and IBS, and the inflammatory diseases and conditions due to tumor proliferation, tumor metastasis or transplantation rejection.

The invention relates to synthetic peptide amides that are ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low PCYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: wherein Xaa is a D-amino acid and G is selected from the following three groups:  The compounds are useful in the prophylaxis and treatment of pain, pruritis and inflammation associated with a variety of diseases and conditions.

Synthetic peptide amides and dimeric forms thereof

The invention disclosed in this patent document relates to transmembrane receptors, more particularly to a human G protein-coupled receptor for which the endogenous ligand is unknown ('orphan GPCR receptors'), and most particularly to mutated (non-endogenous) versions of the human GPCRs for evidence of constitutive activity.

Constitutively activated human G protein coupled receptors

The invention relates to synthetic peptide amides that are ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low PCYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: wherein Xaa is a D-amino acid and G is selected from the following three groups: The compounds are useful in the prophylaxis and treatment of pain, pruritus and inflammation associated with a variety of diseases and conditions.

Uses of synthetic peptide amides

Methods for elevating and stabilizing prolactin levels in a mammal including methods of treating disorders and conditions associated with reduced serum levels of prolactin are provided. Also provided are methods of using certain synthetic tetrapeptide amides which are peripherally selective kappa opioid receptor agonists to elevate or stabilize serum prolactin levels.

Method for elevating prolactin in mammals

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Riverside, CT, United States of America

Derek T Chalmers