Cara Therapeutics, Inc.

Ferring B.v.

Cera Therapeutics, Inc.

Guangcheng Jiang

Javier Sueiras-Diaz

Claudio Daniel Schteingart

Roberta Vezza Alexander

Derek T Chalmers

Robert H Spencer

Frédérique Menzaghi

Zhiyong Luo

Robert Zhiyong Luo

Kazimierz Wisniewski

Graeme Semple

Jacek Stalewski

Jean E Rivier

Anders Nilsson

Pierre Riviere

Sudarkodi Alagarsamy

Aleksandr K Rabinovich

Dipak Kalita

Kesavan Balakumaran

Vikas Gajare

Venkat Aravinda Potula

Atmakuri Venkata Dhanunjaya Rao

Mohosin Layek

Javier J Sueiras-Diaz

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.

This disclosure relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof: in which m, p, A, Ar, Ar, Ar, R, R, and Rare defined in the specification. The compounds of formula (I) can be used as CGRP antagonists and can be used to treat migraine.

CGRP antagonist peptides

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

The present invention relates to a liquid (or solution)-phase manufacturing process for preparing the decapeptide Degareiix, its amino-protected precursor, and other useful intermediates. The invention further relates to polypeptides useful in the solution-phase manufacturing process and to the purification of Degareiix itself. The manufacturing process comprises the step of cleaving the &#x3b5;-amino protecting group P&#x3b5; from a Degareiix precursor according to formula {P)(P&#x3b5;)Ac-AA-AA-NHin an organic solvent comprising the precursor and a cleaving agent dissolved therein: wherein Pis a hydroxyl-protecting group or hydrogen, preferably hydrogen. 

Process for the manufacture of Degarelix and its intermediates

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.

Novel GLP-2 analogs with improved pharmacokinetic properties are described as well as their use in the treatment of disease.

Peptidic GLP-2 agonists

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 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.

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San Diego, CA, United States of America

Guangcheng Jiang