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: 2. The synthetic peptide amide of wherein XaaXaais D-Phe-D-Phe claim 1 , Xaais D-Leu or D-Nle and Xaais selected from the group consisting of (B)D-Arg claim 1 , D-Lys claim 1 , (B)D-Har claim 1 , ζ-(B)D-Hlys claim 1 , D-Dap claim 1 , ε-(B)D-Lys claim 1 , ε-(B)-D-Lys claim 1 , D-Amf claim 1 , amidino-D-Amf claim 1 , γ-(B)D-Dbu and δ-(B)α-(B′)D-Orn.3. The synthetic peptide amide of wherein Xaais selected from the group consisting of D-Lys claim 2 , (B)D-Har claim 2 , ε-(B)D-Lys and ε-(B)-D-Lys.4. The synthetic peptide amide of wherein W is null claim 1 , Y is N and Z is C.5. The synthetic peptide amide of wherein the Y and Z-containing ring moiety is a six-membered saturated ring comprising a single ring heteroatom.6. The synthetic peptide amide of wherein Y and Z are both N and are the only ring heteroatoms in the Y and Z-containing ring moiety.7. The synthetic peptide amide of wherein Rand Rtaken together with zero claim 1 , one or two ring atoms of the Y and Z-containing ring moiety comprise a monocyclic or bicyclic 4-9 membered heterocyclic ring moiety.8. The synthetic peptide amide of wherein Rand Rtaken together with one ring atom of the Y and Z-containing ring moiety comprise a 4- to 8-membered heterocyclic ring moiety which with the Y and Z-containing ring moiety forms a spiro structure and W is null.9. The synthetic peptide amide of wherein e is zero and Rand Rare bonded directly to the same ring atom claim 1 , Ris H claim 1 , OH claim 1 , —NH claim 1 , —COOH claim 1 , —CHCOOH claim 1 , C-Calkyl claim 1 , amidino claim 1 , C-Calkyl-substituted amidino claim 1 , dihydroimidazole claim 1 , D-Pro claim 1 , D-Pro amide claim 1 , or CONHand Ris H claim 1 , —COOH claim 1 , ...

SUBSTITUTED IMIDAZOHETEROCYCLE DERIVATIVES

The present invention provides substituted imidazoheterocycles having the general structure of formula I: 2. A compound according to claim 1 , wherein Y is selected from the group consisting of —NR— claim 1 , —CRRNR— and —NRCRR—; Z is selected from the group consisting of a bond claim 1 , —(CH)— and —CO—; and X is —(CO)R.3. A compound according to claim 1 , wherein Y is selected from the group consisting of —O— claim 1 , —OCRR— and —CRRO—; Z is selected from the group consisting of a bond claim 1 , —(CH)— and —CO—; and X is —(CO)R.4. A compound according to claim 1 , wherein Y is selected from the group consisting of —CRR— and —(CRR)—; Z is selected from the group consisting of a bond claim 1 , —(CH)— and —CO—; and X is —(CO)R.64. A compound according to any of - claims 1 , wherein Z is a bond and Ris —NRR; wherein{'sub': '5', 'Ris —H;'}{'sub': 6', '10', '11', '12', '10', '11', '13, 'Ris selected from the group consisting of —CRRR, —CRRCOR;'}{'sub': '10', 'Ris —H;'}{'sub': 11', '1', '8', '3', '10', '11', '1', '4', '3', '6', '1', '6', '2', '2', '10', '8', '9, 'Ris selected from the group consisting of —H, C-CalkylC-Ccycloalkyl, aryl, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl; wherein the alkyl, cycloalkyl, aryl and heterocyclyl of Rare optionally substituted with one to three substituents independently selected from the group consisting of C-Calkyl, C-Ccycloalkyl, aryl, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl, halo, —OH, C-Calkoxy, —NH, —CN, —NO, oxo, —COOR, and —CONRR;'}{'sub': 12', '1', '6', '1', '6, 'Ris selected from the group consisting of C-Calkyl and C-Chydroxyalkyl; and'}{'sub': 13', '8', '9, 'Ris —NRR.'}76. A pharmaceutical composition comprising a compound according to any of - claims 1 , and a pharmaceutically acceptable diluent claims 1 , excipient or carrier.8. A method of prophylaxis or treatment of a cannabinoid receptor-associated disease or condition in a mammal claim 1 , the method comprising administering to the mammal an effective ...

COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING SWEET TASTE

The present invention provides edible compositions comprising a sweet taste modulator of the present invention, food products comprising such edible compositions and methods of preparing such food products. The present invention also provides methods of reducing the amount of sugar in a food product, methods of reducing the caloric intake in a diet, and methods of enhancing sweet taste in a food product.

COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING SWEET TASTE

The present invention provides edible compositions comprising a sweet taste modulator of the present invention, food products comprising such edible compositions and methods of preparing such food products. The present invention also provides methods of reducing the amount of sugar in a food product, methods of reducing the caloric intake in a diet, and methods of enhancing sweet taste in a food product. 2. The method of claim 1 , wherein the compound is a compound according to Formula (I) claim 1 , wherein claim 1 , as valence and stability permit:{'sub': 1', '1', '3', '1', '3', '1', '3, 'claim-text': {'sub': 1', '3', '1', '3', '1', '3', '3', '2', '2', '2, 'wherein said C-Calkyl, C-Calkenyl, and C-Calkynyl, are optionally substituted with —SO—Ror —COR;'}, 'Ris absent, H, C-Calkyl, C-Calkenyl, or C-Calkynyl,'}{'sub': 2', '1', '3', '1', '3', '1', '3, 'each Ris individually H, C-Calkyl, C-Calkenyl, or C-Calkynyl;'}{'sub': 3', '1', '3', '1', '3', '1', '3, 'each Ris individually absent, H, C-Calkyl, C-Calkenyl, or C-Calkynyl;'}M is absent, H, or O;X is absent, H, F, or O;Y is absent, H, or O; andZ is absent, H, or O.3. The method of claim 2 , wherein the compound is a compound according to Formula (I) claim 2 , wherein claim 2 , as valence and stability permit:{'sub': 1', '1', '3, 'claim-text': {'sub': 1', '3', '3', '2', '2', '2, 'wherein said C-Calkyl is optionally substituted with —SO—Ror —COR;'}, 'Ris absent, H, or C-Calkyl,'}{'sub': 2', '1', '3, 'each Ris individually H or C-Calkyl;'}{'sub': 3', '1', '3, 'each Ris individually absent, H, or C-Calkyl;'}M is absent, H, or O;X is absent, H, F, or O;Y is absent, H, or O; andZ is absent, H, or O.4. The method of claim 3 , wherein the compound is a compound according to Formula (I) claim 3 , wherein claim 3 , as valence and stability permit:{'sub': 1', '1', '3, 'claim-text': {'sub': 1', '3', '3', '2', '2, 'wherein said C-Calkyl is optionally substituted with —SO—Ror —COH;'}, 'Ris absent, H, or C-Calkyl,'}{'sub': 2', '1', ...

USES OF KAPPA OPIOID SYNTHETIC PEPTIDE AMIDES

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-α, IL-1β, 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. 2. The method according to claim 1 , wherein the kappa opioid receptor-associated disease or condition is an inflammatory disease or condition.3. The method according to claim 2 , wherein the inflammatory disease or condition is selected from the group consisting of cardiovascular inflammation claim 2 , neurological inflammation claim 2 , skeletal inflammation claim 2 , muscular inflammation claim 2 , gastrointestinal ...

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: 210-. (canceled)12. The method of claim 11 , wherein XaaXaais D-Phe-D-Phe claim 11 , Xaais D-Leu or D-Nle and Xaais selected from the group consisting of (B)D-Arg claim 11 , D-Lys claim 11 , (B)D-Har claim 11 , ζ-(B)D-Hlys claim 11 , D-Dap claim 11 , ε-(B)D-Lys claim 11 , ε-(B)-D-Lys claim 11 , D-Amf claim 11 , amidino-D-Amf claim 11 , γ-(B)D-Dbu and δ-(B)α-(B′)D-Orn.1420-. (canceled)21. The method of claim 1 , wherein the pruritis is selected from the group consisting of pruritis in atopic dermatitis claim 1 , kidney dialysis-associated puritis claim 1 , ocular pruritis claim 1 , otitic pruritis claim 1 , insect bite pruritis and opioid-induced pruritis.22. The method of claim 13 , wherein the pruritis is pruritis in atopic dermatitis.23. The method of claim 13 , wherein the pruritis is kidney-dialysis associated pruritis.24. The method of claim 13 , wherein the pruritis is uremic prurutis.25. The method of claim 13 , wherein the pruritis is ocular pruritis.26. The method of claim 25 , wherein the ocular pruritis is due to conjunctivitis.27. The method of claim 13 , wherein the pruritis is otic pruritis.28. The method of claim 13 , wherein the pruritis is insect bite pruritis.29. The method of claim 13 , wherein the pruritis is opioid-induced pruritis.30. The method of claim 29 , wherein the opioid-induced pruritis is morphine-induced pruritis.31. The method of claim 13 , wherein the pruritis is pruritis in cholestasis.32. The method of claim 31 , wherein the pruritis in cholestasis is selected from the group consisting of pruritis in primary biliary cirrhosis claim 31 , pruritis in intrahepatic cholestasis of pregnancy and pruritis in chronic cholestatic liver disease.33. ...

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: 28-. (canceled)9. The synthetic peptide amide of wherein e is zero and Rand Rare bonded directly to the same ring atom claim 1 , Ris H claim 1 , OH claim 1 , —NH claim 1 , —COOH claim 1 , —CHCOOH claim 1 , D-Pro claim 1 , D-Pro amide claim 1 , or CONHand Ris H claim 1 , —COOH claim 1 , or C-Calkyl.10. (canceled)12. (canceled)1418-. (canceled)19. A pharmaceutical composition comprising the synthetic peptide amide according to and a pharmaceutically acceptable excipient or carrier.20. A method of treating or preventing a kappa opioid receptor-associated disease or condition in a mammal claim 1 , the method comprising administering to the mammal a composition comprising an effective amount of a synthetic peptide amide according to . This application is a continuation of U.S. patent application Ser. No. 15/170,201 filed Jun. 1, 2016, now U.S. Pat. No. 10,138,270, which is a continuation of U.S. patent application Ser. No. 14/585,438 filed Dec. 30, 2014, now U.S. Pat. No. 9,359,399, which is a continuation of U.S. patent application Ser. No. 13/543,022 filed Jul. 6, 2012, now U.S. Pat. No. 8,951,970, which is a continuation of U.S. patent application Ser. No. 12/786,686 filed May 25, 2010, now U.S. Pat. No. 8,217,007, which is a continuation of U.S. patent application Ser. No. 12/176,279 filed Jul. 18, 2008, now U.S. Pat. No. 7,727,963, which is a continuation of U.S. patent application Ser. No. 11/938,771 filed Nov. 12, 2007, now U.S. Pat. No. 7,402,564, which claims priority to U.S. provisional application Ser. No. 60/928,550, filed May 10, 2007, and to U.S. provisional application Ser. No. 60/858,109, filed Nov. 10, 2006, each of which are expressly incorporated by reference ...

USES OF KAPPA OPIOID SYNTHETIC PEPTIDE AMIDES

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-α, IL-1β, 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. 2. The method according to claim 1 , wherein the kappa opioid receptor-associated disease or condition is an inflammatory disease or condition.3. The method according to claim 2 , wherein the inflammatory disease or condition is selected from the group consisting of cardiovascular inflammation claim 2 , neurological inflammation claim 2 , skeletal inflammation claim 2 , muscular inflammation claim 2 , gastrointestinal ...

Oxidized derivatives of gdf-11 fragments

Substituted imidazoheterocycles

The present invention provides substituted imidazoheterocyclic compounds having the structure of formula I Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis and treatment of cannabinoid receptor-associated diseases and conditions, such as pain, inflammation and pruritis.

Substituted tetrahydroquinazoline compounds as kras inhibitors

The present disclosure relates to novel compounds that inhibits KRAS G12C, pharmaceutical compositions containing such compounds, and their use in prevention and treatment of cancer and related diseases and conditions.

Compounds, compositions, and methods for modulating sweet taste

The present disclosure provides edible compositions comprising a sweet taste modulator or bitter taste blocker of the present disclosure, food products comprising such edible compositions and methods of preparing such food products. The present disclosure also provides methods of reducing the amount of sugar in a food product, methods of reducing the caloric intake in a diet, and methods of enhancing sweet taste or blocking a bitter taste in a food product.

Compounds, compositions, and methods for modulating sweet taste

Substituted imidazoheterocycles

The present invention provides substituted imidazoheterocyclic compounds having the structure of formula I Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis and treatment of cannabinoid receptor-associated diseases and conditions, such as pain, inflammation and pruritis.

Compounds, compositions, and methods for modulating sweet taste

The present disclosure provides edible compositions comprising a sweet taste modulator or bitter taste blocker of the present disclosure, food products comprising such edible compositions and methods of preparing such food products. The present disclosure also provides methods of reducing the amount of sugar in a food product, methods of reducing the caloric intake in a diet, and methods of enhancing sweet taste or blocking a bitter taste in a food product.

Oxidized derivatives of gdf-11 fragments.

Se proporcionan péptidos (y derivados de los mismos), composiciones tópicas y métodos de reducción de signos del envejecimiento y/o mejora de la salud de integumentos humanos. Los péptidos se derivan de factor de diferenciación de crecimiento 11 (GDF-11) humano y normalmente tienen una o más modificaciones químicas de los residuos de aminoácidos. Las modificaciones preferidas de fragmentos de GDF-11 incluyen la oxidación de metionina.

Bicyclic pyrazolo-heterocycles

The present invention provides substituted pyrazolo-heterocycles having the general structure of formula I (I). The structures of rings A and B and substituents R a, R b and R c are described in the specification. Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis, treatment and inhibition of cannabinoid receptor- associated diseases and conditions, such as pain, inflammation and pruritis.

Uses of substituted imidazoheterocycles

The present invention provides methods of prevention and treatment of cannabinoid receptor-associated diseases and conditions, wherein the method includes administering a substituted imidazoheterocyclic compounds having the structure of formula I or a pharmaceutically acceptable salt, acid salt, hydrate, solvate or stereoisomer of a compound having the structure of formula I. The cannabinoid receptor-associated diseases and conditions preventable or treatable by the methods of the present invention include pain, inflammation and pruritis.

Oxidized derivatives of gdf-11 fragments

Se proporcionan péptidos (y derivados de los mismos), composiciones tópicas y métodos para disminuir los signos del envejecimiento y/o mejorar la salud de los tegumentos humanos. Los péptidos se derivan del factor de diferenciación de crecimiento humano 11 (GDF-11) y típicamente tienen una o más modificaciones químicas de los residuos de aminoácidos. Las modificaciones preferidas de los fragmentos de GDF-11 incluyen la oxidación de metionina. (Traducción automática con Google Translate, sin valor legal) Peptides (and derivatives thereof), topical compositions, and methods for diminishing the signs of aging and/or improving the health of human integuments are provided. The peptides are derived from human growth differentiation factor 11 (GDF-11) and typically have one or more chemical modifications of amino acid residues. Preferred modifications of the GDF-11 fragments include methionine oxidation. (Automatic translation with Google Translate, without legal value)

Composição tópica compreendendo derivados oxidados de fragmentos de gdf-11 e método não terapêutico para diminuir o aparecimento de sinais dermatológicos de envelhecimento

derivados oxidados de fragmentos de gdf-11. são proporcionados peptídeos (e seus derivados), composições tópicas e métodos de diminuir os sinais de envelhecimento e/ou melhorar a saúde de tegu-mentos humanos. os peptídeos são derivados do fator de diferenciação de cres-cimento 11 (gdf-11) humano e têm tipicamente uma ou mais modificações quími-cas dos resíduos de aminoácidos. modificações preferenciais de fragmentos de gdf-11 incluem oxidação de metionina.

Substituted quinoline derivatives having sos1 inhibition activities and uses thereof

The present disclosure relates to novel SOS1 inhibitors, pharmaceutical compositions containing such compounds, and their use in prevention and treatment of cancer and related diseases and conditions.

Compounds, compositions, and methods for modulating sweet taste

The present invention provides edible compositions comprising a sweet taste modulator of the present invention, food products comprising such edible compositions and methods of preparing such food products. The present invention also provides methods of reducing the amount of sugar in a food product, methods of reducing the caloric intake in a diet, and methods of enhancing sweet taste in a food product.

Compounds, compositions, and methods for modulating sweet taste

The present invention provides edible compositions comprising a sweet taste modulator or bitter taste blocker of the present invention, food products comprising such edible compositions and methods of preparing such food products. The present invention also provides methods of reducing the amount of sugar in a food product, methods of reducing the caloric intake in a diet, and methods of enhancing sweet taste or blocking a bitter taste in a food product.