CXCR7 antagonists

Compounds having formula I, or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.

Modulators of chemokine receptors

Compounds are provided as chemokine inhibitors having the structure:

Processes and intermediates in the preparation of C5aR antagonists

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds.

Pyrrolidinone carboxamide derivatives as chemerin-R ( CHEMR23 ) modulators

Pyrrolidinone carboxamide compounds of formula (I) are provided that are useful for inhibiting the binding of ligands to the ChemR23 receptor.

FUSED HETEROARYL PYRIDYL AND PHENYL BENZENESUFLONAMIDES AS CCR2 MODULATORS FOR THE TREATMENT OF INFLAMMATION

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists. 123-. (canceled)25. The method of claim 24 , wherein the compound of Formula B is reacted with NaOH and chloromethyl methyl ether to produce the compound of Formula C.27. The method of claim 26 , wherein the reaction is conducted in presence of N claim 26 ,N′-carbonyldiimidazole.29. The method of claim 28 , further comprising reacting 3-amino-5-methylpicolino-nitrile with 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride in pyridine to form the compound of Formula E.30. The method of claim 24 , wherein the solvent used to produce the Grignard reagent is tetrahydrofuran.31. The method of claim 24 , wherein the solvent used in step (b) is tetrahydrofuran.32. The method of claim 24 , wherein step (c) is conducted with an acid.33. The method of claim 32 , wherein the acid is hydrochloric acid.40. The method of claim 39 , wherein the Grignard reagent is formed by reacting 4-iodo-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2 claim 39 ,3-d]pyrimidine with isopropylmagnesium chloride.41. The method of claim 39 , wherein the acid is hydrochloric acid.42. The method of claim 39 , wherein the intermediate D is reacted with O claim 39 , N-dimethyl-hydroxylamine hydrochloride in the presence of N claim 39 ,N′-carbonyldiimidazole. This application is a continuation of U.S. Ser. No. 12/171,782, filed Jul. 11, 2008, which application claims priority to U.S. provisional application Ser. No. 60/949,328, filed Jul. 12, 2007. The disclosures of these priority applications are incorporated by reference herein in their entirety.The present invention described herein was supported at least in part by NIH (U19-AI056690-01). The government has certain rights in the invention.The present ...

Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists.

AZA-ARYL 1H-PYRAZOL-1-YL BENZENE SULFONAMIDES

Compounds are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists. 2. The compound of or salt thereof claim 1 , wherein one of Aor Ais N or N—O claim 1 , and the remaining of A claim 1 , A claim 1 , A claim 1 , A claim 1 , A claim 1 , A claim 1 , A claim 1 , and Aare —CR— claim 1 , where each Ris selected independently.3. The compound of or salt thereof claim 1 , wherein two of claim 1 , AA claim 1 , A claim 1 , Ais N or N—O claim 1 , and the remaining of A claim 1 , A claim 1 , A claim 1 , A claim 1 , A claim 1 , A claim 1 , A claim 1 , and Aare —CR— claim 1 , where each Ris selected independently.6. The compound of or salt thereof claim 5 , where{'sup': '1', 'sub': 2', '3', '3', '2', '3', '3', '3', '2', '2', '3', '2', '2', '3', '2', '3', '2', '3', '3', '2', '3', '3', '2', '3', '2', '3, 'Ris selected from the group consisting of: —CHCH, —CH(CH), —C(CH), —C(CH)CHCH, —C(CHCH)CN, —C(OH)(CH), —OCH, —OCHCH, —OCH(CH), —OC(CH), —OCHCH(CH), —OCF, and morpholino;'}{'sup': '2', 'Ris H, F, or Cl; or'}{'sup': 1', '2, 'sub': 3', '2', '2', '3', '2', '2', '2, 'Rand Rmay together form —OC(CH)CH— or —C(CH)CHCH—;'}{'sup': '3', 'sub': 3', '3, 'Ris H, —CH, or —OCH;'}{'sup': '4', 'Ris H or F;'}{'sup': '5', 'Ris H;'}{'sup': '6', 'sub': 3', '2', '3', '3', '2', '3', '7', '2', '2', '2', '3', '3', '2', '3', '2', '2', '2, 'Ris H, —CH, —CHCH, —CH(CH), —CH, —CHF, —CHF, —CFCH, —CF, —CHOCH, —CHOH, —CHCN, —CN, or —CONH; and'}{'sup': '8', 'sub': 3', '3', '2', '3', '2', '3', '2, 'each Ris independently selected from the group consisting of H, F, Cl, Br, —CH, —OH, —OCH, —OCHCH, —NH, —N(CH), and —CN.'}7. The compound of or salt thereof claim 6 , ...

PYRROLIDINONE CARBOXAMIDE DERIVATIVES

Pyrrolidinone carboxamide compounds are provided that are useful for inhibiting the binding of ligands to the ChemR23 receptor. 3. A compound of claim 1 , wherein Ris methyl.4. A compound of claim 1 , wherein Ris methyl claim 1 , and Ris H or Calkyl.5. A compound of claim 1 , wherein Ris H or Calkyl claim 1 , Ris methyl claim 1 , and Ris H or Calkyl.6. A compound of claim 1 , wherein Ris CF.7. A compound of claim 1 , wherein Ris methyl and Ris CF.9. A compound of claim 8 , wherein Ris selected from the group consisting of —NRRand RRN—Calkyl.10. A compound of claim 9 , wherein Ris RRN—Calkyl.11. A compound of claim 9 , wherein Ris —NRR.12. A compound of claim 8 , wherein Rand Rare each methyl.13. A compound of claim 12 , wherein Ris selected from the group consisting of CF claim 12 , CN and cyclopropyl.14. A compound of claim 8 , wherein Ris mono- or di-(Calkyl)amino-Calkyl claim 8 , and Ris methyl.15. A compound of claim 14 , wherein Ris di(Calkyl)aminomethyl.16. A compound of claim 8 , wherein Rand Rare each methyl.18. A compound of claim 17 , wherein Ris H claim 17 , and Rand Rare each methyl.19. A compound of claim 18 , wherein Ris CF.21. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.221111111111111111111111111111111. The pharmaceutical composition of claim 21 , wherein the compound is a compound provided in claim 21 , B claim 21 , C claim 21 , D claim 21 , E claim 21 , F claim 21 , G claim 21 , H claim 21 , I claim 21 , J claim 21 , K claim 21 , L claim 21 , M claim 21 , N claim 21 , O claim 21 , P claim 21 , Q claim 21 , R claim 21 , S claim 21 , T claim 21 , U claim 21 , V claim 21 , W claim 21 , X claim 21 , Y claim 21 , Z claim 21 , AA claim 21 , BB claim 21 , CC claim 21 , DD claim 21 , EE and FF.23. A method of treating a disease or disorder in a mammal claim 1 , said method comprising administering to said subject a therapeutically effective amount of a compound of claim 1 , for a period of time ...

FUSED HETEROARYL PYRIDYL AND PHENYL BENZENESUFLONAMIDES AS CCR2 MODULATORS FOR THE TREATMENT OF INFLAMMATION

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists. 3. The compound or salt of claim 1 , wherein Xis N.4. The compound of or salt thereof claim 3 , wherein Xand Xare N claim 3 , and Xand Xare CR.5. The compound or salt of claim 4 , where Ris Cl.6. The compound or salt of claim 5 , where Ris —CF.7. The compound or salt of claim 6 , where Ris Cl or methyl.8. The compound or salt of claim 7 , where Ris methyl.9. The compound or salt of claim 4 , wherein Ris Cl claim 4 , Ris CF claim 4 , and Ris Cl.12. A composition comprising a pharmaceutically acceptable carrier and a compound or salt of .13. A method of modulating CCR2 function in a cell claim 1 , comprising contacting the cell with a CCR2 modulating amount of the compound or salt of .14. A method of treating a CCR2-mediated condition or disease comprising administering to a subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt of .15. The method of claim 14 , wherein said CCR2-mediated condition or disease is atherosclerosis.16. The method of claim 14 , wherein said CCR2-mediated condition or disease is restenosis.17. The method of claim 14 , wherein said CCR2-mediated condition or disease is multiple sclerosis.18. The method of claim 14 , wherein said CCR2-mediated condition or disease is selected from the group consisting of inflammatory bowel disease claim 14 , renal fibrosis claim 14 , rheumatoid arthritis claim 14 , obesity and noninsulin-dependent diabetes.19. The method of claim 14 , wherein said CCR2-mediated condition or disease is type 2 diabetes.20. The method of claim 14 , wherein said CCR2-mediated condition or disease is selected from the group consisting of chronic obstructive pulmonary disease claim 14 , idiopathic ...

SOLUBLE C5aR ANTAGONISTS

Compounds are provided to modulate the C5a receptor. The compounds have the following Formula (I): 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein Ris selected from the group consisting of O—(CO)—Calkylene-NRR claim 1 , O—(CO)—Calkylene-NR(CO)—Calkylene-NRR claim 1 , O—P(O)OROR claim 1 , O—CH—O—P(O)ORORand O—(CO)—Carylene-Calkylene-Cheterocyclyl claim 1 , wherein the Cheterocyclyl is selected from the group consisting of piperidinyl claim 1 , piperazinyl claim 1 , pyrrolidinyl claim 1 , morpholinyl and azetidinyl and wherein the piperidinyl claim 1 , piperazinyl claim 1 , pyrrolidinyl claim 1 , morpholinyl and azetidinyl are optionally substituted with 1 to 6 Rgroups.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of —CH—O—P(O)ORORand —P(O)OROR.12. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of —(CO)—Calkylene- NRR claim 1 , —(CO)—O—Calkylene-O—P(O)OROR claim 1 , —P(O)ORO(CO)—Calkyl claim 1 , —P(O)ORNRR claim 1 , —(CO)—O—Calkylene-O—(CO)—Calkenylene-COH claim 1 , —(CO)—Calkylene-NR(CO)—Calkylene- NRRwherein the Calkylene- NRRmay be optionally substituted by with NRR claim 1 , —(CO)—O—Calkylene-O—(CO)—Calkylene-NRR claim 1 , and —(CO)—O—Calkylene-Caryl-O—P(O)ORORwherein the Caryl is optionally substituted with 1 to 5 Rwhich can be the same or different.15. The compound of any one of to claim 1 , to and to claim 1 , which is in the form of a pharmaceutically acceptable salt.16. The compound of wherein the pharmaceutically acceptable salt is selected from the group consisting of ammonium claim 15 , calcium claim 15 , magnesium claim 15 , potassium claim 15 , sodium claim 15 , zinc claim 15 , arginine claim 15 , betaine claim 15 , caffeine claim 15 , choline claim 15 , N claim 15 ,N′-dibenzylethylenediamine claim 15 , diethylamine claim 15 , 2-diethylaminoethanol claim 15 , 2- ...

Aza-aryl 1h-pyrazol-1-yl benzene sulfonamides

Compounds are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists.

MODULATORS OF CHEMOKINE RECEPTORS

Compounds are provided as chemokine inhibitors having the structure: 136.-. (canceled)42. The pharmaceutical composition of claim 41 ,{'sup': 4', '6a', '6b, 'sub': '3', 'wherein Ris H or Y; and Rand Rare each independently selected from H and CHor a pharmaceutically acceptable salt thereof.'}43. The pharmaceutical composition of claim 41 , or a pharmaceutically acceptable salt thereof claim 41 , wherein Ris CH; Ris H or is CH; Ris H or D; Ris H; Ris H claim 41 , F claim 41 , Me or Cl or Br; Ris H or F; Rand Rare each H; and Ris methyl or ethyl; or a pharmaceutically acceptable salt claim 41 , solvate or hydrate claim 41 , thereof.44. The pharmaceutical composition of claim 41 , or a pharmaceutically acceptable salt thereof claim 41 , wherein said compound is substantially free of other isomers at the carbon atom bearing R.45. The pharmaceutical composition of claim 41 , or a pharmaceutically acceptable salt thereof claim 41 , wherein Ris Y.54. The method of claim 53 , wherein said cells expressing CXCR2 are HEK-293 cells or human neutrophils.55. The method of claim 53 , wherein said radioactive CCR1 ligand is CXCL8.56. The method of claim 53 , wherein said reaction mixture comprises an assay buffer comprising 25 mM HEPES claim 53 , 130 mM NaCl claim 53 , 1 mM CaCl claim 53 , and 5 mM MgCl claim 53 , wherein the assay buffer has a pH of 7.1. This application is a continuation of U.S. patent application Ser. No. 15/794,800 filed Oct. 26, 2017, which is a continuation of U.S. patent application Ser. No. 15/353,889 filed Nov. 17, 2016 (now U.S. Pat. No. 9,834,545), which is an application claiming benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 62/257,389 filed Nov. 19, 2015, and U.S. Provisional Application No. 62/277,711 filed Jan. 12, 2016, each of which is herein incorporated by reference in its entirety.NOT APPLICABLENOT APPLICABLEChemokines are chemotactic cytokines that are released by a wide variety of cells to attract macrophages, ...

AZA-ARYL 1H-PYRAZOL-1-YL BENZENE SULFONAMIDES

Compounds are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists. 3. The compound of or salt thereof claim 2 , wherein Ris selected from the group consisting of: —CHCH claim 2 , —CH(CH) claim 2 , —C(CH) claim 2 , —C(CH)CHCH claim 2 , —C(CHCH)CN claim 2 , —C(OH)(CH) claim 2 , —OCH claim 2 , —OCHCH claim 2 , —OCH(CH) claim 2 , —OC(CH) claim 2 , —OCHCH(CH) claim 2 , —OCF claim 2 , and morpholino;{'sup': '2', 'Ris H, F, or Cl; or'}{'sup': '3', 'sub': 3', '3, 'Ris H, —CH, or —OCH;'}{'sup': '4', 'Ris H or F;'}{'sup': '5', 'Ris H;'}{'sup': '6', 'sub': 3', '2', '3', '3', '2', '3', '7', '2', '2', '2', '3', '3', '2', '3', '2', '2', '2, 'Ris H, —CH, —CHCH, —CH(CH), —CH, —CHF, —CHF, —CFCH, —CF, —CHOCH, —CHOH, —CHCN, —CN, or —CONH; and'}{'sup': '8', 'sub': 3', '3', '2', '3', '2', '3', '2, 'each Ris independently selected from the group consisting of H, F, Cl, Br, —CH, —OH, —OCH, —OCHCH, —NH, —N(CH), and —CN.'}4. The compound of or salt thereof claim 2 , wherein{'sup': '1', 'sub': 3', '3, 'Ris —C(CH);'}{'sup': '2', 'Ris H or F;'}{'sup': '3', 'Ris H;'}{'sup': '4', 'Ris H;'}{'sup': '5', 'Ris H; and'}{'sup': '6', 'sub': 3', '2', '2', '3, 'Ris —CH, —CHF, —CHF, or —CF.'}6. The compound of or salt thereof claim 5 , wherein{'sup': '1', 'sub': 2', '3', '3', '2', '3', '3', '3', '2', '2', '3', '2', '2', '3', '2', '3', '2', '3', '3', '2', '3', '3', '2', '3', '2', '3, 'Ris selected from the group consisting of: —CHCH, —CH(CH), —C(CH), —C(CH)CHCH, —C(CHCH)CN, —C(OH)(CH), —OCH, —OCHCH, —OCH(CH), —OC(CH), —OCHCH(CH), —OCF, and morpholino; and'}{'sup': '2', 'Ris H, F, or Cl; or'}{'sup': 1', '2, 'sub': 3', '2', '2', '3', '2', '2', '2, 'Rand ...

AZA-ARYL 1H-PYRAZOL-1-YL BENZENE SULFONAMIDES

Compounds are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists. 119-. (canceled)21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of .23. The sodium salt of the compound of .24. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound or pharmaceutically acceptable salt thereof of .25. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the sodium salt of . This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 61/604,998, filed Feb. 29, 2012, and titled “AZA-ARYL 1H-PYRAZOL-1-7L ENZENE SULFONAMIDES,” which is incorporated, in its entirety, by this reference.The present invention provides compounds and pharmaceutical compositions containing one or more of those compounds or their pharmaceutically acceptable salts, that are effective in inhibiting the binding or function of various chemokines to chemokine receptors. As antagonists or modulators of chemokine receptors, the compounds and compositions have utility in treating various immune disorder conditions and diseases.Chemokines, also known as chemotactic cytokines, are a group of small molecular-weight proteins that are released by a wide variety of cells and have a variety of biological activities. Chemokines attract various types of cells of the immune system, such as macrophages, T cells, eosinophils, basophils and neutrophils, and cause them to migrate from the blood to various lymphoid and none-lymphoid tissues. They mediate infiltration of inflammatory cells to sites of inflammation, and are ...

PROCESSES AND INTERMEDIATES IN THE PREPARATION OF C5aR ANTAGONISTS

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds. 18.-. (canceled).10. A compound of claim 9 , in salt form as a L-DTTA salt.11. A compound of claim 9 , wherein Ris CF.12. A compound of claim 9 , wherein Ris Cl.13. A compound of claim 9 , in salt form as a bis L-DTTA salt.15. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris F claim 14 , and Ris CH.16. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris Cl claim 14 , and Ris H.17. A method in accordance with claim 14 , wherein Ris Cl claim 14 , Ris F claim 14 , and Ris CH.18. A method in accordance with claim 14 , wherein LG is halogen.1920.-. (canceled). This application is a continuation of U.S. patent application Ser. No. 14/867,669 filed Sep. 28, 2015, which application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/057,107, filed Sep. 29, 2014, each of which is incorporated herein by reference.NOT APPLICABLEThe complement system plays a central role in the clearance of immune complexes and in immune responses to infectious agents, foreign antigens, virus infected cells and tumor cells. Inappropriate or excessive activation of the complement system can lead to harmful, and even potentially life-threatening consequences due to severe inflammation and resulting tissue destruction. These consequences are clinically manifested in various disorders including septic shock; myocardial, as well as, intestinal ischemia/reperfusion injury; graft rejection; organ failure; nephritis; pathological inflammation; and autoimmune diseases.The activation of the complement pathway generates biologically active fragments of complement proteins, e.g. C3a, C4a and C5a anaphylatoxins and C5b-9 membrane attack complexes (MAC), all which mediate inflammatory responses by affecting leukocyte chemotaxis; activating macrophages, neutrophils, platelets, mast cells and endothelial cells; and increasing vascular permeability, ...

CXCR7 ANTAGONISTS

Compounds having formula I, 2. The compound of claim 1 , wherein Z is monocyclic or fused-bicyclic heteroaryl claim 1 , having 1-3 heteroatoms as ring members selected from N claim 1 , O and S; and wherein said heteroaryl group is optionally substituted with from 1 to 5 Rsubstituents.3. The compound of claim 1 , wherein Z is monocyclic or fused-bicyclic heteroaryl selected from the group consisting of imidazole claim 1 , pyrazole claim 1 , 1 claim 1 ,2 claim 1 ,3-triazole claim 1 , 1 claim 1 ,2 claim 1 ,4-triazole claim 1 , tetrazole claim 1 , thiazole claim 1 , oxazole claim 1 , oxadiazole claim 1 , pyrimidine claim 1 , pyrazine claim 1 , pyridazine claim 1 , and quinazoline claim 1 , each of which is optionally substituted with from 1-2 Rsubstituents.4. The compound of claim 2 , wherein n is 0.5. The compound of claim 4 , wherein Ris H.6. The compound of claim 1 , wherein each Ris independently selected from the group consisting of H and Calkyl.7. The compound of claim 1 , wherein Ris selected from the group consisting of H claim 1 , CHOH and C(O)NH.10. A compound of claim 8 , wherein Z is a 5-membered heteroaryl group substituted with one Rgroup selected from an optionally substituted aryl claim 8 , heteroaryl claim 8 , cycloalkyl claim 8 , or heterocycloalkyl ring claim 8 , and optionally with up to two additional Rgroups which are selected from halogen claim 8 , Calkyl claim 8 , Chaloalkyl and CHCN.14. The compound of claim 13 , wherein Ris selected from the group consisting of selected from the group consisting of hydrogen claim 13 , halogen claim 13 , cyano claim 13 , Calkyl and —SO— Calkyl.15. The compound of claim 13 , wherein Ris selected from the group consisting of H and Calkyl.16. The compound of claim 13 , wherein Ris selected from the group consisting of hydrogen claim 13 , halogen claim 13 , cyano claim 13 , Calkyl and —SO— Calkyl; and Ris selected from the group consisting of H and Calkyl.17. The compound of claim 1 , selected from the compounds of ...

FREE BASE CRYSTALLINE FORM OF A COMPLEMENT COMPONENT C5a RECEPTOR

Provided herein is a free base crystalline form of a complement component 5a receptor having the formula of Compound 1 12.-. (canceled)3. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by XRPD peaks at 12.4 claim 11 , 15.2 claim 11 , 16.1 claim 11 , 24.4 claim 11 , and 24.7 degrees 2θ (±0.2 degrees 2θ)4. The method of claim 11 , wherein the free base crystalline form of Compound 1 is characterized by an X-ray powder diffraction pattern substantially in accordance with .5. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a differential scanning calorimetry thermogram (DSC) comprising an endothermic peak at around 216° C.6. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a melting point onset of about 213° C. as determined by differential scanning calorimetry thermogram (DSC).7. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a DSC substantially in accordance with .810.-. (canceled)12. The method of claim 11 , wherein the disease or disorder is an inflammatory disease or disorder.13. The method of claim 12 , wherein the disease or disorder is selected from the group consisting of neutropenia claim 12 , sepsis claim 12 , septic shock claim 12 , Alzheimer's disease claim 12 , multiple sclerosis claim 12 , stroke claim 12 , inflammatory bowel disease claim 12 , age-related macular degeneration claim 12 , chronic obstructive pulmonary disorder claim 12 , inflammation associated with burns claim 12 , lung injury claim 12 , osteoarthritis claim 12 , atopic dermatitis claim 12 , chronic urticaria claim 12 , ischemia-reperfusion injury claim 12 , acute respiratory distress syndrome claim 12 , systemic inflammatory response syndrome claim 12 , multiple organ dysfunction syndrome claim 12 , tissue graft rejection claim 12 , cancer and hyperacute ...

CXCR7 ANTAGONISTS

Compounds having formula I, 112.-. (canceled)14. The pharmaceutical composition of claim 13 , wherein Ris selected from the group consisting of selected from the group consisting of hydrogen claim 13 , halogen claim 13 , cyano claim 13 , Calkyl and —SO— Calkyl.15. The pharmaceutical composition of claim 13 , wherein Ris selected from the group consisting of H and Calkyl.16. The pharmaceutical composition of claim 13 , wherein Ris selected from the group consisting of hydrogen claim 13 , halogen claim 13 , cyano claim 13 , Calkyl and —SO— Calkyl; and Ris selected from the group consisting of H and Calkyl.1723.-. (canceled)2527.-. (canceled)29. (canceled) This application is a continuation of U.S. application Ser. No. 14/836,172 filed Aug. 26, 2015, which application is a continuation of U.S. patent application Ser. No. 14/091,641 filed Nov. 27, 2013 (now U.S. Pat. No. 9,169,261), which application claims the benefit of priority to U.S. Provisional Application Ser. No. 61/731,463 filed Nov. 29, 2012, each of which is incorporated herein by reference in its entirety.Not ApplicableThe Sequence Listing written in file-SequenceListing_085236-0099111US-0956502.txt, created on Jan. 28, 2016, 4,447 bytes, machine format IBM-PC, MS-Windows operating system, is hereby incorporated by reference in its entirety for all purposes.The present invention is directed to novel compounds and pharmaceutical compositions that inhibit the binding of the SDF-1 chemokine (also known as the CXCL12 chemokine) or I-TAC (also known as CXCL11) to the chemokine receptor CXCR7. These compounds are useful in preventing tumor cell proliferation, tumor formation, tumor vascularization, metastasis, inflammatory diseases including, but not limited to arthritis, renal inflammatory disorders and multiple sclerosis, conditions of improper vasculatization including, but not limited to wound healing, treatment of HIV infectivity, and treatment of stem cell differentiation and mobilization disorders (see also ...

PROCESSES AND INTERMEDIATES IN THE PREPARATION OF C5aR ANTAGONISTS

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds. 2. A compound of claim 1 , in salt form as a bis L-DTTA salt.6. A method of any of claim 1 , or claim 1 , wherein Ris CF claim 1 , Ris F claim 1 , and Ris CH.7. A method of any of claim 1 , or claim 1 , wherein Ris CF claim 1 , Ris Cl claim 1 , and Ris H.8. A method of any of claim 1 , or claim 1 , wherein Ris Cl claim 1 , Ris F claim 1 , and Ris CH.10. A compound of claim 9 , in salt form as a L-DTTA salt.11. A compound of claim 9 , wherein Ris CF.12. A compound of claim 9 , wherein Ris Cl.13. A compound of claim 9 , in salt form as a bis L-DTTA salt.15. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris F claim 14 , and Ris CH.16. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris Cl claim 14 , and Ris H.17. A method in accordance with claim 14 , wherein Ris Cl claim 14 , Ris F claim 14 , and Ris CH.18. A method in accordance with claim 14 , wherein LG is halogen. This application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/057,107, filed Sep. 29, 2014, the entire content of which is incorporated herein by reference.NOT APPLICABLENOT APPLICABLEThe complement system plays a central role in the clearance of immune complexes and in immune responses to infectious agents, foreign antigens, virus infected cells and tumor cells. Inappropriate or excessive activation of the complement system can lead to harmful, and even potentially life-threatening consequences due to severe inflammation and resulting tissue destruction. These consequences are clinically manifested in various disorders including septic shock; myocardial, as well as, intestinal ischemia/reperfusion injury; graft rejection; organ failure; nephritis; pathological inflammation; and autoimmune diseases.The activation of the complement pathway generates biologically active fragments of complement proteins, e.g. C3a, C4a and C5a anaphylatoxins and ...

CXCR7 ANTAGONISTS

Compounds having formula I, 129.-. (canceled)31. The method of claim 30 , wherein said cells expressing CXCR7 are MCF-7 or MDA-MB435S cells or isolated human monocytes.32. The method of claim 30 , wherein said radioactive CXCR7 ligand is SDF-1 claim 30 , I-TAC claim 30 , or a combination thereof.33. The method of claim 30 , wherein step (a) further comprises a binding buffer.34. The method of claim 33 , wherein the binding buffer comprises 25 mM HEPES claim 33 , 140 mM NaCl claim 33 , 1 mM CaCl claim 33 , 5 mM MgCland 0.2% bovine serum albumin claim 33 , at pH 7.1.35. The method of claim 30 , further comprising washing the PEI-treated GF/B glass filter after step (b) with a wash buffer.36. The method of claim 30 , wherein the wash buffer comprises 25 mM Hepes claim 30 , 140 mM NaCl claim 30 , 1 mM CaCl claim 30 , 5 mM MgCl claim 30 , at pH 7.1.37. The method of claim 30 , wherein said measuring comprises adding scintillation fluid to the aspirated and washed GF/C glass filter.38. The method of claim 30 , wherein Ris selected from the group consisting of selected from the group consisting of hydrogen claim 30 , halogen claim 30 , cyano claim 30 , Calkyl and —SO—Calkyl.39. The method of claim 30 , wherein Ris selected from the group consisting of H and Calkyl.40. The method of claim 30 , wherein Ris selected from the group consisting of hydrogen claim 30 , halogen claim 30 , cyano claim 30 , Calkyl and —SO—Calkyl; and Ris selected from the group consisting of H and Calkyl. This application is a continuation of U.S. application Ser. No. 15/692,739 filed Aug. 31, 2017, which is a continuation of U.S. patent application Ser. No. 14/836,172 filed Aug. 26, 2015 (now U.S. Pat. No. 9,783,544), which is a continuation of U.S. patent application Ser. No. 14/091,641 filed Nov. 27, 2013 (now U.S. Pat. No. 9,169,261), which application claims the benefit of priority to U.S. Provisional Application No. 61/731,463 filed Nov. 29, 2012, each of which is incorporated herein by ...

FREE BASE CRYSTALLINE FORM OF A COMPLEMENT COMPONENT C5a RECEPTOR

Provided herein is a free base crystalline form of a complement component 5a receptor having the formula of Compound 1 Also provided herein are pharmaceutical compositions and methods of treatment using the crystalline free base form of Compound 1 described herein.

Methods of treating generalized pustular psoriasis with an antagonist of ccr6 or cxcr2

The present disclosure provides, inter alia, methods of treating generalized pustular psoriasis (GPP) by administering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C-X-C motif chemokine receptor 2 (CXCR2) antagonist. Also provided herein are methods of modulating dysregulated IL-36 signaling in a subject in need thereof and methods of reducing neutrophil, inflammatory dendritic cell (iDC), and/or CD4 T cell accumulation in a subject in need thereof, said methods, include dministering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C-X-C motif chemokine receptor 2 (CXCR2) antagonist. In some embodiments, the CCR6 and/or CXCR2 antagonist has the formula:

CXCR7 ANTAGONISTS

Compounds having formula I, 2. The compound of claim 1 , wherein Z is monocyclic or fused-bicyclic heteroaryl claim 1 , having 1-3 heteroatoms as ring members selected from N claim 1 , O and S; and wherein said heteroaryl group is optionally substituted with from 1 to 5 Rsubstituents.3. The compound of claim 1 , wherein Z is monocyclic or fused-bicyclic heteroaryl selected from the group consisting of imidazole claim 1 , pyrazole claim 1 , 1 claim 1 ,2 claim 1 ,3-triazole claim 1 , 1 claim 1 ,2 claim 1 ,4-triazole claim 1 , tetrazole claim 1 , thiazole claim 1 , oxazole claim 1 , oxadiazole claim 1 , pyrimidine claim 1 , pyrazine claim 1 , pyridazine claim 1 , and quinazoline claim 1 , each of which is optionally substituted with from 1-2 Rsubstituents.4. The compound of claim 2 , wherein n is 0.5. The compound of claim 4 , wherein Ris H.6. The compound of claim 1 , wherein each Ris independently selected from the group consisting of H and Calkyl.7. The compound of claim 1 , wherein Ris selected from the group consisting of H claim 1 , CHOH and C(O)NH.10. A compound of claim 8 , wherein Z is a 5-membered heteroaryl group substituted with one Rgroup selected from an optionally substituted aryl claim 8 , heteroaryl claim 8 , cycloalkyl claim 8 , or heterocycloalkyl ring claim 8 , and optionally with up to two additional Rgroups which are selected from halogen claim 8 , Calkyl claim 8 , Chaloalkyl and CHCN.14. The compound of claim 13 , wherein Ris selected from the group consisting of selected from the group consisting of hydrogen claim 13 , halogen claim 13 , cyano claim 13 , Calkyl and —SO—Calkyl.15. The compound of claim 13 , wherein Ris selected from the group consisting of H and Calkyl.16. The compound of claim 13 , wherein Ris selected from the group consisting of hydrogen claim 13 , halogen claim 13 , cyano claim 13 , Calkyl and —SO—Calkyl; and Ris selected from the group consisting of H and Calkyl.17. The compound of claim 1 , selected from the compounds of ...

MODULATORS OF CHEMOKINE RECEPTORS

Compounds are provided as chemokine inhibitors having the structure: 116.-. (canceled)17. A method of :{'sup': 4', '6a', '6b, 'sub': '3', 'wherein Ris H or Y; and Rand Rare each independently selected from H and CHor a pharmaceutically acceptable salt, solvate or hydrate, thereof.'}182. A method of claim claim 28 , or any pharmaceutically acceptable salts claim 28 , solvates claim 28 , hydrates claim 28 , N-oxides claim 28 , tautomers or rotamers thereof claim 28 , wherein Ris CH; Ris H or is CH; Ris H or D; Ris H; Ris H claim 28 , F claim 28 , Me or Cl or Br; Ris H or F; Rand Rare each H; and Ris methyl or ethyl; or a pharmaceutically acceptable salt claim 28 , solvate or hydrate claim 28 , thereof.19. A method of claim 28 , or any pharmaceutically acceptable salts claim 28 , solvates claim 28 , hydrates claim 28 , N-oxides claim 28 , tautomers or rotamers thereof claim 28 , wherein said compound is substantially free of other isomers at the carbon atom bearing R.20. A method of claim 28 , or any pharmaceutically acceptable salts claim 28 , solvates claim 28 , hydrates claim 28 , N-oxides claim 28 , tautomers or rotamers thereof claim 28 , wherein Ris Y.2127.-. (canceled)29. A method of claim 28 , wherein the disease or condition is an acute or chronic inflammatory disorder.30. A method of claim 29 , wherein the acute or chronic inflammatory disorder is psoriasis claim 29 , dry eye disease claim 29 , atherosclerosis claim 29 , discoid lupus erythematosus claim 29 , rheumatoid arthritis claim 29 , lupus claim 29 , radiation induced fibrotic lung disease claim 29 , autoimmune bullous dermatosis (AIBD) claim 29 , chronic obstructive pulmonary disease claim 29 , or ozone-induced airway inflammation.31. A method of claim 28 , wherein the disease is a cancer selected from the group consisting of cutaneous T-cell lymphoma claim 28 , non-Hodgkin lymphoma claim 28 , Mycosis fungoides claim 28 , Pagetoid reticulosis claim 28 , Sezary syndrome claim 28 , Granulomatous slack ...

MODULATORS OF CHEMOKINE RECEPTORS

Compounds are provided as chemokine inhibitors having the structure: 5. A compound of claim 1 , or any pharmaceutically acceptable salts claim 1 , solvates claim 1 , hydrates claim 1 , N-oxides claim 1 , tautomers or rotamers thereof claim 1 , wherein B is furanyl or oxazolyl claim 1 , each of which is optionally substituted with Rand R claim 1 , which are independently selected from the group consisting of halogen claim 1 , CN claim 1 , Calkyl claim 1 , Calkoxy and. Chaloalkyl.6. A compound of or any pharmaceutically acceptable salts claim 5 , solvates claim 5 , hydrates claim 5 , N-oxides claim 5 , tautomers or rotamers thereof claim 5 , wherein B is furanyl substituted with Rwhich is CHor Cl and optionally substituted with Rwhich is CH.7. A compound of claim 1 , or any pharmaceutically acceptable salts claim 1 , solvates claim 1 , hydrates claim 1 , N-oxides claim 1 , tautomrers or rotamers thereof claim 1 , wherein Ris H.8. A compound of claim 1 , or any pharmaceutically acceptable salts claim 1 , solvates claim 1 , hydrates claim 1 , N-oxides claim 1 , tautomers or rotamers thereof claim 1 , wherein each of Rand Ris independently selected from the group consisting of H claim 1 , CH claim 1 , Cl and F.11. A compound of claim 1 , or any pharmaceutically acceptable salts claim 1 , solvates claim 1 , hydrates claim 1 , N-oxides claim 1 , tautomers or rotamers thereof claim 1 , wherein each of Rand Ris independently selected from the group consisting of H and Calkyl.14. A compound of claim 1 , or any pharmaceutically acceptable salts claim 1 , solvates claim 1 , hydrates claim 1 , N-oxides claim 1 , tautomers or rotamers thereof claim 1 , wherein Ris H claim 1 , Calkyl or Y claim 1 , wherein the Calkyl is substituted with tetrazolyl or tetrazolonyl claim 1 , wherein the tetrazolyl or tetrazolonyl is optionally substituted with Calkyl claim 1 , Chydroxyalkyl claim 1 , or Calkyl-O—Calkyl wherein Y is selected from the group consisting of pyridinyl claim 1 , pyrazolyl ...

Heteroaryl Sulfonamides and CCR2/CCR9

Compounds are provided that act as potent antagonists of the CCR2 receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR2. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases, and as controls in assays for the identification of CCR2 antagonists. 2. The compound of claim 1 , wherein L is —C(O)—.3. The compound of claim 1 , wherein Xand Xare each independently halogen or Chaloalkyl.4. The compound of claim 1 , wherein X claim 1 , X claim 1 , and Xare each H.5. The compound of claim 1 , wherein Ris hydrogen.6. The compound of claim 1 , wherein Yis unsubstituted Calkyl.7. The compound of claim 1 , wherein Yis hydrogen.8. The compound of claim 1 , wherein Yis —N— or —N+(O)—.9. The compound of claim 1 , wherein Zand Zare —CH—.10. The compound of claim 1 , wherein Zis —N—.11. The compound of claim 1 , wherein Ris hydrogen.12. The compound of claim 1 , wherein Ris hydrogen.16. A composition comprising a pharmaceutically acceptable carrier and the compound or salt of .17. A method of modulating CCR2 function in a cell claim 1 , comprising contacting the cell with a CCR2 modulating amount of the compound of . This application is a continuation of U.S. application Ser. No. 16/272,401, filed Feb. 11, 2019, which is a continuation of U.S. application Ser. No. 15/383,788, filed Dec. 19, 2016, which is a divisional of U.S. application Ser. No. 13/938,119, filed Jul. 9, 2013, which is a continuation of U.S. application Ser. No. 12/309,314, filed Feb. 1, 2011, now U.S. Pat. No. 8,519,135, which issued Aug. 27, 2013, which is a 371 national phase of PCT/US2007/015893, filed Jul. 12, 2007, which is a continuation-in-part of U.S. application Ser. No. 11/486,974, filed Jul. 14, 2006, now U.S. Pat. No. 7,622,583, which issued Nov. 24, 2009. The disclosures of these priority applications are incorporated herein in ...

Heteroaryl sulfonamides and ccr2/ccr9

Compounds are provided that act as potent antagonists of the CCR2 receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR2. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases, and as controls in assays for the identification of CCR2 antagonists.

FUSED HETEROARYL PYRIDYL AND PHENYL BENZENESUFLONAMIDES AS CCR2 MODULATORS FOR THE TREATMENT OF INFLAMMATION

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists. 2. The compound or salt of claim 1 , wherein Xand Xare each independently selected from CR.3. The compound or salt of claim 1 , wherein Xis N; and Xand Xare each N.5. The compound or salt of claim 1 , wherein Ris Cl.6. The compound or salt of claim 5 , wherein Ris —CF.7. The compound or salt of claim 6 , wherein Ris Cl or methyl.8. The compound or salt of claim 7 , wherein Ris methyl.9. The compound or salt of claim 1 , wherein Ris Cl claim 1 , Ris CF claim 1 , and Ris Cl.10. The compound or salt of claim 1 , wherein Ris hydrogen.11. The compound or salt of claim 1 , wherein Ris halogen and Ris Chaloalkyl.14. A composition comprising a pharmaceutically acceptable carrier and a compound or salt of .15. A composition comprising a pharmaceutically acceptable carrier and a compound or salt of .16. A composition comprising a pharmaceutically acceptable carrier and a compound or salt of .17. A method of modulating CCR2 function in a cell in vitro claim 1 , comprising contacting the cell with a CCR2 modulating amount of the compound or salt of .18. A method of modulating CCR2 function in a cell in vitro claim 12 , comprising contacting the cell with a CCR2 modulating amount of the compound or salt of .19. A method of treating a CCR2-mediated condition or disease claim 13 , comprising administering to a subject a therapeutically effective amount of a compound of claim 13 , wherein the CCR2-mediated condition or disease is selected from atherosclerosis claim 13 , restenosis claim 13 , renal fibrosis claim 13 , type 2 diabetes claim 13 , cancer claim 13 , inflammatory bowel disease claim 13 , multiple sclerosis claim 13 , noninsulin-dependent diabetes claim 13 , pulmonary ...

Aza-Aryl 1H-Pyrazol-yl Benzene Sulfonamides

Compounds are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists. 3. The compound of or salt thereof claim 2 , wherein{'sup': '1', 'sub': 2', '3', '3', '2', '3', '3', '3', '2', '2', '3', '2', '2', '3', '2', '3', '2', '3', '3', '2', '3', '3', '2', '3', '2', '3, 'Ris selected from the group consisting of: —CHCH, —CH(CH), —C(CH), —C(CH)CHCH, —C(CHCH)CN, —C(OH)(CH), —OCH, —OCHCH, —OCH(CH), —OC(CH), —OCHCH(CH), —OCF, and morpholino;'}{'sup': '2', 'Ris H, F, or Cl; or'}{'sup': '3', 'sub': 3', '3, 'Ris H, —CH, or —OCH;'}{'sup': '4', 'Ris H or F;'}{'sup': '5', 'Ris H;'}{'sup': '6', 'sub': 3', '2', '3', '3', '2', '3', '7', '2', '2', '2', '3', '3', '2', '3', '2', '2', '2, 'Ris H, —CH, —CHCH, —CH(CH), —CH, —CHF, —CHF, —CFCH, —CF, —CHOCH, —CHOH, —CHCN, —CN, or —CONH; and'}{'sup': '8', 'sub': 3', '3', '2', '3', '2', '3', '2, 'each Ris independently selected from the group consisting of H, F, Cl, Br, —CH, —OH, —OCH, —OCHCH, —NH, —N(CH), and —CN.'}4. The compound of or salt thereof claim 2 , wherein{'sup': '1', 'sub': 3', '3, 'Ris —C(CH);'}{'sup': '2', 'Ris H or F;'}{'sup': '3', 'Ris H;'}{'sup': '4', 'Ris H;'}{'sup': '5', 'Ris H; and'}{'sup': '6', 'sub': 3', '2', '2', '3, 'Ris —CH, —CHF, —CHF, or —CF.'}5. The compound of or salt thereof claim 3 , wherein Ris —C(CH).6. The compound of or salt thereof claim 5 , wherein{'sup': '2', 'Ris H or F;'}{'sup': '3', 'Ris H;'}{'sup': '4', 'Ris H; and'}{'sup': '6', 'sub': 3', '2', '2', '3, 'Ris —CH, —CHF, —CHF, or —CF.'}9. The composition of claim 8 , wherein{'sup': '1', 'sub': 2', '3', '3', '2', '3', '3', '3', '2', '2', '3', '2', '2', '3', '2', '3', '2', '3', '3', '2', '3', '3', '2', '3', ...

METHODS OF TREATING GENERALIZED PUSTULAR PSORIASIS WITH AN ANTAGONIST OF CCR6 OR CXCR2

The present disclosure provides, inter alia, methods of treating generalized pustular psoriasis (GPP) by administering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C—X—C motif chemokine receptor 2 (CXCR2) antagonist. Also provided herein are methods of modulating dysregulated IL-36 signaling in a subject in need thereof and methods of reducing neutrophil, inflammatory dendritic cell (iDC), and/or CD4 T cell accumulation in a subject in need thereof, said methods, include administering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C—X—C motif chemokine receptor 2 (CXCR2) antagonist. In some embodiments, the CCR6 and/or CXCR2 antagonist has the formula: 1. A method of treating a disease or condition selected from the group consisting of generalized pustular psoriasis (GPP) , palmo-plantar psoriasis (PPP) , acute generalized exanthematous pustulosis (AGEP) , hydradenitis suppurativa (HS) , dermatitis herpetiformis , and pemphigus vulgaris in a subject in need thereof , said method comprising administering to the subject an effective amount of an antagonist of Chemokine Receptor 6 (CCR6) and/or C—X—C motif chemokine receptor 2 (CXCR2).2. The method of claim 1 , wherein the disease or condition is generalized pustular psoriasis (GPP).3. The A method of claim 1 , wherein the disease or condition is palmo-plantar psoriasis (PPP).4. The method of claim 1 , wherein the disease or condition is acute generalized exanthematous pustulosis (AGEP).5. The method of claim 1 , wherein the disease or condition is hydradenitis suppurativa (HS).6. The method of claim 1 , wherein the disease or condition is dermatitis herpetiformis.7. The method of claim 1 , wherein the disease or condition is pemphigus vulgaris.8. A method of modulating dysregulated IL-36 signaling in a subject in need thereof claim 1 , said method comprising administering to the subject an effective amount of an antagonist of Chemokine Receptor 6 (CCR6) and/or C—X— ...

SOLUBLE C5aR ANTAGONISTS

Compounds are provided to modulate the C5a receptor. The compounds have the following Formula (I): 213.-. (canceled)15. The compound of claim 1 , which is in the form of a pharmaceutically acceptable salt.16. (canceled)17. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable excipient.18. The pharmaceutical composition of claim 17 , formulated for intravenous claim 17 , transdermal or subcutaneous administration.1921.-. (canceled)22. A method of treating a human suffering from or susceptible to a disease or disorder involving pathologic activation of C5a receptors claim 1 , comprising administering to the mammal a therapeutically effective amount of a compound of .23. The method of claim 22 , wherein the disease or disorder is an inflammatory disease or disorder claim 22 , an autoimmune disease claim 22 , or an oncologic disease or disorder.24. The method of claim 22 , wherein the disease or disorder is a cardiovascular or cerebrovascular disorder.25. (canceled)26. The method of claim 22 , wherein the disease or disorder is selected from the group consisting of neutropenia claim 22 , neutrophilia claim 22 , Wegener's granulomatosis claim 22 , microscopic polyangiitis claim 22 , C3-glomerulopathy claim 22 , C3-glomerulonephritis claim 22 , dense deposit disease claim 22 , membranoproliferative glomerulonephritis claim 22 , Kawasaki disease claim 22 , Hemolytic uremic syndrome claim 22 , atypical hemolytic uremic syndrome (aHUS) claim 22 , tissue graft rejection claim 22 , hyperacute rejection of transplanted organs claim 22 , rheumatoid arthritis claim 22 , systemic lupus erythematosus claim 22 , lupus nephritis claim 22 , lupus glomerulonephritis claim 22 , vasculitis claim 22 , ANCA vasculitis claim 22 , autoimmune hemolytic and thrombocytopenic states claim 22 , immuno vasculitis claim 22 , Graft versus host disease claim 22 , lupus nephropathy claim 22 , Heyman ...

SOLUBLE C5aR ANTAGONISTS

Compounds are provided to modulate the C5a receptor. The compounds have the following Formula (I): 121-. (canceled)23. The method of claim 22 , wherein the disease or disorder is an inflammatory disease or disorder claim 22 , an autoimmune disease claim 22 , or an oncologic disease or disorder.24. The method of claim 22 , wherein the disease or disorder is a cardiovascular or cerebrovascular disorder.25. The method of claim 22 , wherein the disease or disorder is selected from the group consisting of neutropenia claim 22 , neutrophilia claim 22 , Wegener's granulomatosis claim 22 , microscopic polyangiitis claim 22 , C3-glomerulopathy claim 22 , C3-glomerulonephritis claim 22 , dense deposit disease claim 22 , membranoproliferative glomerulonephritis claim 22 , Kawasaki disease claim 22 , sepsis claim 22 , septic shock claim 22 , Hemolytic uremic syndrome claim 22 , atypical hemolytic uremic syndrome (aHUS) claim 22 , Alzheimer's disease claim 22 , multiple sclerosis claim 22 , stroke claim 22 , inflammatory bowel disease claim 22 , chronic obstructive pulmonary disorder claim 22 , inflammation associated with burns claim 22 , lung injury claim 22 , osteoarthritis claim 22 , atopic dermatitis claim 22 , chronic urticaria claim 22 , ischemia-reperfusion injury claim 22 , acute respiratory distress syndrome claim 22 , systemic inflammatory response syndrome claim 22 , multiple organ dysfunction syndrome claim 22 , Uveitis claim 22 , tissue graft rejection claim 22 , hyperacute rejection of transplanted organs claim 22 , myocardial infarction claim 22 , coronary thrombosis claim 22 , vascular occlusion claim 22 , post-surgical vascular reocclusion claim 22 , artherosclerosis claim 22 , polypoidal choroidal vasculopathy claim 22 , traumatic central nervous system injury claim 22 , ischemic heart disease claim 22 , rheumatoid arthritis claim 22 , systemic lupus erythematosus claim 22 , Guillain-Barre syndrome claim 22 , pancreatitis claim 22 , lupus nephritis claim 22 , ...

SOLUBLE C5aR ANTAGONISTS

Compounds are provided to modulate the C5a receptor. The compounds have the following Formula (I): 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein Ris selected from the group consisting of O—(CO)—Calkylene-NRR claim 1 , O—(CO)—Calkylene-NR(CO)—Calkylene-NRR claim 1 , O—P(O)OROR claim 1 , O—CH—O—P(O)ORORand O—(CO)—Carylene-Calkylene-Cheterocyclyl claim 1 , wherein the Cheterocyclyl is selected from the group consisting of piperidinyl claim 1 , piperazinyl claim 1 , pyrrolidinyl claim 1 , morpholinyl and azetidinyl and wherein the piperidinyl claim 1 , piperazinyl claim 1 , pyrrolidinyl claim 1 , morpholinyl and azetidinyl are optionally substituted with 1 to 6 Rgroups.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of —CH—O—P(O)ORORand —P(O)OROR.12. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of —(CO)—Calkylene-NRR claim 1 , —(CO)—O—Calkylene-O—P(O)OROR claim 1 , —P(O)ORO(CO)—Calkyl claim 1 , —P(O)ORNRR claim 1 , —(CO)—O—Calkylene-O—(CO)—Calkenylene-COH claim 1 , —(CO)—Calkylene-NR(CO)—Calkylene-NRRwherein the Calkylene-NRRmay be optionally substituted by with NRR claim 1 , —(CO)—O—Calkylene-O—(CO)—Calkylene-NRR claim 1 , and —(CO)—O—Calkylene-Caryl-O—P(O)ORORwherein the Caryl is optionally substituted with 1 to 5 Rwhich can be the same or different.15. The compound of claim 1 , which is in the form of a pharmaceutically acceptable salt.16. The compound of wherein the pharmaceutically acceptable salt is selected from the group consisting of ammonium claim 15 , calcium claim 15 , magnesium claim 15 , potassium claim 15 , sodium claim 15 , zinc claim 15 , arginine claim 15 , betaine claim 15 , caffeine claim 15 , choline claim 15 , N claim 15 ,N′-dibenzylethylenediamine claim 15 , diethylamine claim 15 , 2-diethyl aminoethanol claim 15 , 2-dimethylaminoethanol claim 15 , ...

PROCESSES AND INTERMEDIATES IN THE PREPARATION OF C5aR ANTAGONISTS

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds.

FUSED HETEROARYL PYRIDYL AND PHENYL BENZENESUFLONAMIDES AS CCR2 MODULATORS FOR THE TREATMENT OF INFLAMMATION

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists. 123-. (canceled)25. The method of claim 24 , wherein R claim 24 , R claim 24 , and Rare each hydrogen.26. The method of claim 24 , wherein Ris halogen and Ris Chaloalkyl.27. The method of claim 24 , wherein Ris Calkyl.28. The method of claim 24 , wherein Ris Cl; Ris CF; and Ris methyl.30. The method of claim 29 , wherein Ris halogen and Ris Chaloalkyl.31. The method of claim 29 , wherein Ris Cl and Ris CF.32. The method of claim 29 , wherein Ris methyl.33. The method of claim 24 , wherein said CCR2-mediated condition or disease is psoriasis.34. The method of claim 24 , wherein said CCR2-mediated condition or disease graft-versus-host disease.35. The method of claim 24 , wherein said CCR2-mediated condition or disease is pulmonary fibrosis.36. The method of claim 24 , wherein said CCR2-mediated condition or disease is transplantation rejection.37. The method of claim 24 , further comprising administering a therapeutically effective amount of a second therapeutic agent.39. The method of claim 38 , wherein said CCR2-mediated condition or disease is psoriasis.40. The method of claim 38 , wherein said CCR2-mediated condition or disease graft-versus-host disease.41. The method of claim 38 , wherein said CCR2-mediated condition or disease is pulmonary fibrosis.42. The method of claim 38 , wherein said CCR2-mediated condition or disease is transplantation rejection.43. The method of claim 38 , further comprising administering a therapeutically effective amount of a second therapeutic agent. This application is a continuation of U.S. Ser. No. 12/171,782, filed Jul. 11, 2008, which application claims priority to U.S. provisional application Ser. No. 60/949,328, filed Jul. 12, ...

PROCESSES AND INTERMEDIATES IN THE PREPARATION OF C5aR ANTAGONISTS

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds. 12.-. (canceled)4. (canceled)6. A method of claim 3 , wherein Ris CF claim 3 , Ris F claim 3 , and Ris CH.7. A method of claim 3 , wherein Ris CF claim 3 , Ris Cl claim 3 , and Ris H.8. A method of claim 3 , wherein Ris Cl claim 3 , Ris F claim 3 , and Ris CH.920.-. (canceled) This application is a continuation of U.S. patent application Ser. No. 16/360,195 filed Mar. 21, 2019, which is a continuation of U.S. patent application Ser. No. 15/659,468 filed Jul. 25, 2017 (now U.S. Pat. No. 10,266,492), which is a divisional of U.S. patent application Ser. No. 14/867,669 filed Sep. 28, 2015 (now U.S. Pat. No. 9,745,268), which application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/057,107, filed Sep. 29, 2014, each of which is incorporated herein by reference.NOT APPLICABLENOT APPLICABLEThe complement system plays a central role in the clearance of immune complexes and in immune responses to infectious agents, foreign antigens, virus infected cells and tumor cells. Inappropriate or excessive activation of the complement system can lead to harmful, and even potentially life-threatening consequences due to severe inflammation and resulting tissue destruction. These consequences are clinically manifested in various disorders including septic shock; myocardial, as well as, intestinal ischemia/reperfusion injury; graft rejection; organ failure; nephritis; pathological inflammation; and autoimmune diseases.The activation of the complement pathway generates biologically active fragments of complement proteins, e.g. C3a, C4a and C5a anaphylatoxins and C5b-9 membrane attack complexes (MAC), all which mediate inflammatory responses by affecting leukocyte chemotaxis; activating macrophages, neutrophils, platelets, mast cells and endothelial cells; and increasing vascular permeability, cytolysis and tissue injury.Complement C5a is one of the most potent ...

chemokine receptor modulators

a presente invenção refere-se a compostos que são fornecidos como inibidores de quimiocina tendo a estrutura: fórmula a The present invention relates to compounds which are provided as chemokine inhibitors having the structure: formula a

Pyrazol-1-yl benzene sulfonamides as ccr9 antagonists

Compounds of formula (I) are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists.

Processes and intermediates in the preparation of c5ar antagonists

Cxcr7 antagonists

Compounds having formula (I) (structurally represented) or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing the compounds in admixture with a pharmaceutically acceptable excipient.

Aza-aryl 1h-pyrazol-1-yl benzene sulfonamides as ccr(9) antagonists

Aza-aryl 1H-pyrazol-1-YL benzene sulfonamides

Compounds are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists.

C5ar soluble antagonists

SE PROPORCIONAN COMPUESTOS PARA MODULAR AL RECEPTOR C5A. LOS COMPUESTOS TIENEN LA SIGUIENTE FÓRMULA (I), INCLUYENDO LOS ESTEREOISÓMEROS Y LAS SALES FARMACÉUTICAMENTE ACEPTABLES DE LOS MISMOS, EN DONDE R1 , R2 Y R3 SON TAL COMO SE DEFINEN EN LA PRESENTE SOLICITUD. TAMBIÉN SE DIVULGAN MÉTODOS ASOCIADOS A LA PREPARACIÓN Y AL USO DE DICHOS COMPUESTOS, ASÍ COMO TAMBIÉN COMPOSICIONES FARMACÉUTICAS QUE COMPRENDEN DICHOS COMPUESTOS. COMPOUNDS ARE PROVIDED TO MODULATE THE C5A RECEIVER. THE COMPOUNDS HAVE THE FOLLOWING FORMULA (I), INCLUDING THE STEREOISOMERS AND THE PHARMACEUTICALLY ACCEPTABLE SALTS OF THE SAME, WHERE R1, R2 AND R3 ARE AS DEFINED IN THIS APPLICATION. METHODS ASSOCIATED WITH THE PREPARATION AND USE OF SUCH COMPOUNDS ARE ALSO DISCLOSED, AS WELL AS PHARMACEUTICAL COMPOSITIONS INCLUDING SUCH COMPOUNDS.

Pyrazol-1-yl benzene sulfonamides as ccr9 antagonists ccr9 -1-

PROCESSES AND INTERMEDIARIES IN THE PREPARATION OF C5AR ANTAGONISTS

"PROCESSOS E INTERMEDIÁRIOS NA PREPARAÇÃO DE ANTAGONISTAS DE C5aR''. São fornecidos métodos e intermediários para a preparação de compostos antagonistas de C5aR selecionados.

Free base crystalline form of a complement component c5a receptor

Provided herein is a free base crystalline form of a complement component 5a receptor having the formula of Compound (1). Also provided herein are pharmaceutical compositions and methods of treatment using the crystalline free base form of Compound (1) described herein.

Processes and intermediates in the preparation of c5ar antagonists

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds.

Fused heteroaryl pyridyl and phenyl benzenesuflonamides as ccr2 modulators for the treatment of inflammation

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists.

Substituted n-cinnamyl benzamides

Substituted benzamide compounds are provided along with methods for the use of those compounds for treating cancer.

PYRAZOL-1-YL BENZENE SULFONAMIDES AS CCR9 ANTAGONISTS, THEIR COMPOSITION AND METHOD OF MODULATE CCR FUNCTION(9) IN A CELL

PIRAZOL-1-IL BENZENO SULFONAMIDAS COMO ANTAGONISTAS DE CCR9. Os compostos de fórmula I são proporcionados os quais atuam como antagonistas potentes do receptor CCR (9). Os testes em animais demonstram que esses compostos são úteis para o tratamento de inflamação, uma doença de marca para CCR (9). Os compostos são geralmente derivados de aril sulfonamida e são úteis em composições farmacêuticas, métodos para o tratamento de doenças mediadas por CCR (9), e como controles em ensaios para a identificação de antagonistas CCR (9). PYRAZOL-1-YL BENZENE SULFONAMIDES AS CCR9 ANTAGONISTS. Compounds of formula I are provided which act as potent CCR receptor antagonists (9). Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for RCC (9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for treating CCR-mediated diseases (9), and as controls in assays for the identification of CCR antagonists (9).

Fused heteroaryl pyridyl and phenyl benzenesulfonamides as CCR2 modulators for the treatment of inflammation

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2- mediated diseases and as controls in assays for the identification of CCR2 antagonists. A compound of the formula (I) or a salt thereof: where: R

CXCR7 antagonists

Un compuesto que tiene la fórmula I**Fórmula** o una sal farmacéuticamente aceptable, hidrato, N-óxido, versión isotópicamente enriquecida o enantioméricamente enriquecida y un rotámero del mismo en la que cada uno de los vértices del anillo Xa, Xb y Xc se selecciona independientemente del grupo que consiste en N, NH, N(R2), CH y C(R2); el subíndice n es 0, 1 o 2; Z se selecciona del grupo que consiste en (i) arilo y heteroarilo monocíclico o bicíclico condensado, en donde el grupo heteroarilo tiene de 1-4 heteroátomos como miembros del anillo seleccionados de N, O y S; y donde dichos grupos arilo y heteroarilo están opcionalmente sustituidos con 1 a 5 sustituyentes R5; (ii) anillo monocíclico de cuatro, cinco, seis o siete miembros seleccionado del grupo que consiste en cicloalcano, y heterocicloalcano, en donde los anillos de heterocicloalcano tienen de 1-3 heteroátomos como miembros de anillo seleccionados de N, O y S; y donde cada uno de dichos anillos Z monocíclicos están opcionalmente sustituidos con 1 a 3 sustituyentes R5; R1 es un miembro seleccionado del grupo que consiste en H y alquilo C1-8, en donde la porción alquilo está opcionalmente sustituida con halógeno, -NRaRb, -ORa, -CO2Ra, y -CONRaRb; cada R2 se selecciona independientemente del grupo que consiste en H, halógeno, CN, alquilo C1-8, haloalquilo C1-8, hidroxialquilo C1-8, -ORa, -CO2Ra, -X-CO2Ra, -NRaRb, -CONRaRb y -X-CONRaRb; R3 es un miembro seleccionado del grupo que consiste en H, alquilo C1-8, haloalquilo C1-8, hidroxialquilo C1-8, - CO2Ra, -X-CO2Ra, -CONRaRb y -X-CONRaRb; cada R4, cuando está presente, es un miembro independientemente seleccionado del grupo que consiste en alquilo C1-8, haloalquilo C1-8, hidroxialquilo C1-8, -ORa, -CO2Ra, -X-CO2Ra, -NRaRb, -CONRaRb y -X-CONRaRb; cada R5 es un miembro independientemente seleccionado del grupo que consiste en halógeno, CN, -X-CN, alquilo C1-8, cicloalquilo C3-8, cicloalquenilo C3-8, espirocicloalquilo C3-5, alquenilo C2-8, alquinilo C2-8, ...

Modulators of chemokine receptors

Compounds are provided as chemokine inhibitors having the structure: Formula (A).

Pyrrolidinone carboxamide derivatives as chemerin-r (chemr23) modulators

Modulators of chemokine receptors

Compounds are provided as chemokine inhibitors having the structure: Formula (A).

HYPEREROYL PYRIDYL AND PHENYL FENIL COMPOUNDS Fused BENZENOSULPHONAMIDS, COMPOSITION, METHOD OF MODULATING CCR2 FUNCTION, USES OF COMPOUNDS AND CRYSTALLINE FORM

compostos de heteroaril piridil e fenil benzenossulfonamidas fundidas, composição, método de modular a função de ccr2, usos dos referidos compostos e forma cristalina". são fornecidos compostos que agem como potentes antagonistas do receptor ccr2. os compostos são geralmente derivados de aril sulfonamida e são úteis em composições farmacêuticas, métodos para o tratamento de doenças mediadas por ccr2 e como controles em ensaios para a identificação de antagonistas de ccr2. um composto da fórmula (i) ou um sal do mesmo: em que r1 e r2 são cada um independentemente hidrogênio, c1-a alquila, -cn, ou c1-a haloalquila, contanto que pelo menos um de r1 ou r2 é diferente do hidrogênio cada r3 é independentemente, r4 é hidrogênio; r5 é halogênio ou c1-a alquila; r6 é hidrogênio; x1 é cr7 , n ou no; x2 e x4 são 15 n ou no; x3 é cr7 ; x6 e x7 são cada um independentemente selecionado a partir de cr7 , n e no; cada r7 é independentemente selecionado a partir do grupo consistindo em hidrogênio, halogênio, cra alquila substituída ou não-substituída, cra alquenila substituída ou não-substituída, cra alquinila substituída ou não-substituída, -cn, =0, -n02 , -or6, -oc(o)r8, -c02r8, -c(o)r8, -c(o)nr0r8,20 -oc(o)nr9r8, -nr1°c(o)r8, -nr1°c(o)nr9r8, -nr9r8, -nr1°c02r8, -sr8,-s(o)r8, -s(o)zr8, -s(0)2nr9r8, -nr10s(o)zr8, c5-1o arila substituída ou nãosubstituída, heteroarila de 5 a 1 o membros substituída ou não-substituída e heterociclila de 3 a 1 o membros substituída ou não-substituída. fused heteroaryl pyridyl and phenyl benzenesulfonamide compounds, composition, method of modulating ccr2 function, uses of said compounds and crystalline form. "Compounds which act as potent ccr2 receptor antagonists are provided. The compounds are generally derived from aryl sulfonamide and are Useful in pharmaceutical compositions, methods for treating ccr2-mediated diseases and as controls in assays for the identification of ccr2 antagonists: a compound of formula (i) or a salt thereof: ...

REPLACED KINOLONES AND METHODS OF USE.

Un compuesto que tiene la fórmula I o sales y N-óxidos farmacéuticamente aceptables del mismo; en el que --- es un doble enlace; A es N o CH; R 1 está ausente; L 1 es -C(O)-; R 2 es -R e ; R 3 es -CH2-R e ; cada R e es independientemente un grupo arilo o heteroarilo de 5-6 miembros que está opcionalmente sustituido con 1-5 sustituyentes seleccionados entre el grupo que consiste en halógeno, -CN, -NO2, - CO2R r , -OC(O)R r , -C(O)NR r R s , -C(O)R r , -S(O)R t , -S(O)2R t , -R t , - C(NOR r )R s , -NR r -C(O)NR r R s , -NH-C(NH2)=NH, -NR t C(NH2)=NH, -NH- C(NH2)=NR t , -NH-C(NHR t )=NH, -NR r S(O)2R t , -NR r S(O)2R t , - NR r S(O)2NR r R s , -N3, -C(NR r V)=NV, -N(V)C(R r )=NV, -X 2 C(NOR r )R s , - X 2 C(NR r Y)=NV, -X2N(Y)C(R r )=NV, -X 2 NR r R s , -X 2 SR r , -X 2 CN, -X 2 NO2, - X 2 CO2R r , -X 2 OC(O)R r , -X 2 CONR r R s , -X 2 C(O)R r , -X 2 OC(O)NR r R s , - X 2 NR s C(O)R r , -X 2 NR s C(O)2R t , -X 2 NR r C(O)NR r R s , -X 2 NH-C(NH2)=NH, - X 2 NR t C(NH2)=NH, -X 2 NH-C(NH2)=NR t , -X 2 NH-C(NHR t )=NH, -X 2 S(O)R t , - X 2 S(O)2R t , -X 2 NR r S(O)2Rt, -X 2 S(O)2NR r R s , -X 2 N3, -OR r , -SR r , -NR r R s , - NR s C(O)R r , -NR 5 C(O)2R t , -S(O)2R t , -S(O)2NR r R s , -X 2 OR r , -O-X 2 OR r , - X 2 NR r R s , -O-X 2 NR r R s y -NR s -X2CO2R r , donde cualquiera de dos sustituyentes situados en átomos adyacentes en R e pueden combinarse para formar un anillo de 5 a 7 miembros que tiene opcionalmente 1-3 heteroátomos seleccionados entre N, O o S; X 2 es alquileno C1-8, heteroalquileno C1-8, alquenileno C2-8, alquinileno C2-8, arileno o heteroarileno; y cada uno de R r y R s se selecciona independientemente entre hidrógeno, alquilo C1-8, haloalquilo C1-8, cicloalquilo C3-6, alquenilo C2-8, alquinilo C2-8, arilo y heteroarilo u opcionalmente, cuando R r y R s se unen al mismo átomo de nitrógeno, pueden combinarse con el átomo de nitrógeno para formar un anillo de cinco o seis miembros que tiene de 0 a 2 heteroátomos más como miembros en el anillo, ...

CXCR7 antagonists

Compounds having formula I,or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.

HYPEREROYL PYRIDYL AND PHENYL BENZENOSULPHONAMIDES FOUNDED AS CCR2 MODULATORS FOR INFLAMMATION TREATMENT

Pyrazol-1-yl benzene sulfonamides as CCR9 antagonists

PYRAZOL-1-YL BENZENE SULFONAMIDES AS CCR9 ANTAGONISTS Abstract Compounds of formula (I) are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulphonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9) mediated diseases, and as controls in assays for the identification of CCR(9) antagonists.

Substituted quinolones and methods of use

Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists.

Pyrazol-1-yl benzene sulfonamides as ccr9 antagonists

Compounds of formula (I) are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists.

Pyrazol-1-yl benzene sulfonamides as ccr9 antagonists

Compounds of formula (I) are provided that act as potent antagonists of the CCR(9) receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR(9). The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR(9)-mediated diseases, and as controls in assays for the identification of CCR(9) antagonists.

Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists.

Substituted quinolones and methods of use

Substituted quinolone compounds and compositions are provided along with methods for the use of those compounds in the treatment of diseases and disorders such as cancer.

METHODS AND INTERMEDIARIES FOR PREPARING C5AR ANTAGONISTS

Methods of treating generalized pustular psoriasis with an antagonist of ccr6 or cxcr2

The present disclosure provides, inter alia, methods of treating generalized pustular psoriasis (GPP) by administering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C-X-C motif chemokine receptor 2 (CXCR2) antagonist. Also provided herein are methods of modulating dysregulated IL-36 signaling in a subject in need thereof and methods of reducing neutrophil, inflammatory dendritic cell (iDC), and/or CD4 T cell accumulation in a subject in need thereof, said methods, include dministering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C-X-C motif chemokine receptor 2 (CXCR2) antagonist. In some embodiments, the CCR6 and/or CXCR2 antagonist has the formula (A):

Methods and intermediates in the preparation of C5AR antagonists

Soluble c5ar antagonists

Compounds are provided to modulate the C5a receptor. The compounds have the following Formula (I) including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Substituierte chinolone und verwendungsverfahren

Aryl sulfonyl (hydroxy) piperidines as ccr6 inhibitors

Compounds of formula (A) are provided which are useful in the treatment of diseases or conditions modulated at least in part by CCR6: Formula (A)

Modulators of chemokine receptors

Modulators of chemokine receptors

Kondensierte heteroarylpyridyl- und phenylbenzensulfonamide als ccr2-modulatoren zur behandlung von entzündungen

Processes and intermediates in the preparation of c5ar antagonists

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds.

Processes and intermediates in the preparation of c5ar antagonists

Methods are provided for preparing a compound having formula (I): including the use of an intermediate compound having the formula (i-3):

Free base crystalline form of a complement component c5a receptor

Provided herein is a free base crystalline form of a complement component 5a receptor having the formula of Compound (1). Also provided herein are pharmaceutical compositions and methods of treatment using the crystalline free base form of Compound (1) described herein.

Modulators of chemokine receptors

Compounds are provided as chemokine inhibitors having the structure:

Methods of treating generalized pustular psoriasis with an antagonist of CCR6 or CXCR2

The present disclosure provides, inter alia, methods of treating generalized pustular psoriasis (GPP) by administering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C-X-C motif chemokine receptor 2 (CXCR2) antagonist. Also provided herein are methods of modulating dysregulated IL-36 signaling in a subject in need thereof and methods of reducing neutrophil, inflammatory dendritic cell (iDC), and/or CD4 T cell accumulation in a subject in need thereof, said methods, include dministering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C-X-C motif chemokine receptor 2 (CXCR2) antagonist. In some embodiments, the CCR6 and/or CXCR2 antagonist has the formula (A):

Free base crystalline form of a complement component c5a receptor

FREE BASE CRYSTALLINE FORM OF A COMPLEMENT COMPONENT C5a RECEPTOR

Provided herein is a free base crystalline form of a complement component 5a receptor having the formula of Compound 1 Also provided herein are pharmaceutical compositions and methods of treatment using the crystalline free base form of Compound 1 described herein.

CXCR7 antagonists

Compounds having formula I,or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.

Processes and intermediates in the preparation of C5aR antagonists

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds.

Compostos e composições farmacêuticas moduladores dos receptores de quimiocina e seus usos

MODULADORES DOS RECEPTORES DE QUIMIOCINA. A presente invenção refere-se a compostos que são fornecidos como inibidores de quimiocina tendo a estrutura: Fórmula A

Forma cristalina de base libre de un receptor del componente c5a de complemento.

En la presente se proporciona una forma cristalina de base libre de un receptor de componente de complemento 5a que tiene la fórmula del compuesto 1 (ver Fórmula) (compuesto 1).En la presente también se proporcionan composiciones farmacéuticas y métodos de tratamiento que utilizan la forma cristalina de base libre del compuesto 1, descrito en la presente.

Aryl sulfonyl (hydroxy) piperidines as ccr6 inhibitors

ANTAGONISTAS C5Ar SOLÚVEIS, COMPOSIÇÕES FARMACEUTICAS E SEUS USOS

A presente invenção refere-se a compostos para modular o receptor de C5a. Os compostos têm a seguinte fórmula (I): incluindo estereoisômeros e seus sais farmaceuticamente aceitáveis, em que R1, R2 e R3 são como aqui definidos. Os métodos associados à preparação e utilização de tais compostos, bem como composições farmacêuticas compreendendo tais compostos, são também divulgados.

Arilsulfonil(hidroxi)piperidinas como inhibidores de ccr6

La presente invencion se refiere a arilsulfonil(hidroxi)piperidinas de formula (A), o una sal, hidrato, solvato N-oxido, forma opticamente enriquecida o rotamero farmaceuticamente aceptable de los mismos. En dichos compuestos, Ar1 es un anillo aromatico o heteroaromatico monociclico de 5 a 6 miembros sustituido con 0-5 miembros seleccionados de haloalquilo de C1-8, hidroxialquilo de C1-8, entre otros; R2 se selecciona de alquinilo de C2-8, haloalquilo de C1-8 o hidroxialquilo de C1-8; Ar2 se selecciona de un anillo aromatico o heteroaromatico monociclico de 5 a 6 miembros o de un anillo biciclico aromatico o heteroaromatico fusionado de 9 a 10 miembros, ambos sustituidos con 0 a 5 R2; R3 y R4 consisten en cicloalquilo de C3-8 o haloalquilo de C1-4; Z es un -O- o -N(Re)-; y el subindice m es 0, 1 o 2. Ademas, los presentes compuestos son utiles en el tratamiento de enfermedades o condiciones moduladas por CCR6.

Aryl sulfonyl (hydroxy) piperidines as ccr6 inhibitors

Compounds of formula (A) are provided which are useful in the treatment of diseases or conditions modulated at least in part by CCR6: Formula (A)

Aryl sulfonyl (hydroxy) piperidines as CCR6 inhibitors

Compounds of formula (A) are provided which are useful in the treatment of diseases or conditions modulated at least in part by CCR6:

Aryl sulfonyl (hydroxy) piperidines as ccr6 inhibitors

Compounds of formula (A) are provided which are useful in the treatment of diseases or conditions modulated at least in part by CCR6: Formula (A)

Arilsulfonil(hidroxi)piperidinas como inhibidores de ccr6

Se proporcionan compuestos de fórmula (A) que son útiles en el tratamiento de enfermedades o condiciones moduladas al menos en parte por CCR6: (A)

Aryl sulfonyl (hydroxy) piperidines as ccr6 inhibitors

Compounds of formula (A) are provided which are useful in the treatment of diseases or conditions modulated at least in part by CCR6: Formula (A)

Aryl Sulfonyl (Hydroxy) Piperidines as CCR6 Inhibitors

Compounds of formula (A) are provided which are useful in the treatment of diseases or conditions modulated at least in part by CCR6:

Arilsulfonil(hidroxi)piperidinas como inhibidores de ccr6.

Se proporcionan compuestos de fórmula (A) que son útiles en el tratamiento de enfermedades o condiciones moduladas al menos en parte por CCR6: (ver Fórmula).

Device for winding magnetic tape into cassette

Arilsulfonil(hidroxi)piperidinas como inhibidores de ccr6

Se proporcionan compuestos de fórmula (A) que son útiles en el tratamiento de enfermedades o condiciones moduladas al menos en parte por CCR6: (A)

Urządzenie do nawijania taśmy magnetycznej do kaset

Urządzenie do nawijania taśmy magnetycznej do kaset, z pneumatycznym podajnikiem i kółkiem podającym taśmę lepną, znamienne tym, że podajnik (31) zamocowany w prowadnicy (34) i wyposażony w komorę (42) zakończoną w górnej części otworami usytuowanymi w taki sposób, że tworzą dwa rzędy środkowe otworów (43) i co najmniej dwa rzędy brzegowe otworów (44), przy czym średnice otworów (43) w rzędach środkowych są od 1,5 do 3 razy większe od średnic otworów (44) rzędów brzegowych i liczba wszystkich rzędów jest większa od 4, a dysza (45) wewnątrz komory (42) ma dwie szczeliny (46) usytuowane pod dwoma środkowymi rzędami otworów (43) w odległości od 2 do 6 średnic tych otworów oraz że na walcowej powierzchni kółka podającego (31) między obrzeżami (36) znajdują się szczelinowe, profilowe nacięcia (37) o kształcie litery V zbiegiem jej ramion zwrócone w kierunku ześlizgu (32) z otworami (38) usytuowanymi w szczelinach , profilowych nacięciach (37) w miejscu zbiegania się ramion litery V, a stosunek powierzchni szczelinowego, profilowego nacięcia (37) do powierzchni otworu (38) jest większy niż 50.

Spinning kit