IMIDAZOPYRAZINE SYK INHIBITORS

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample. 2. At least one chemical entity of claim 1 , wherein Ris chosen from hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , and chloro.3. At least one chemical entity of claim 2 , wherein Ris hydrogen.4. At least one chemical entity of wherein Ris chosen from hydrogen and methyl.5. At least one chemical entity of claim 4 , wherein Ris hydrogen7. At least one chemical entity of claim 1 , wherein Ris phenyl substituted with one or two groups chosen fromhalo,hydroxy,carboxy,cycloalkyl optionally substituted with one or two groups chosen from hydroxy, lower alkoxy, and lower alkyl,heterocycloalkyl optionally substituted with one or two groups chosen from hydroxy, lower alkoxy, lower alkyl, lower alkyl substituted with hydroxy, optionally substituted amino, and oxo,heteroaryl,amino optionally substituted with one or two groups chosen from lower alkyl, lower alkyl substituted with halo, lower alkyl substituted with hydroxy, and lower alkyl substituted with lower alkoxy,{'sub': 6', '7', '6', '7', '6', '7, '—C(O)NRRwherein Rand Rare independently selected from hydrogen, lower alkyl, lower alkyl substituted with hydroxy, lower alkyl substituted with optionally substituted amino, cycloalkyl, aryl, heteroaryl, and heterocycloalkyl, or Rand Rtogether with the nitrogen to which they are bound form a 3- to 7-membered heterocycloalkyl ring optionally substituted with one or two groups chosen from hydroxy, lower alkyl, and lower alkyl substituted with hydroxy,'}{'sub': 2', '6', '7', '6', '7', '6', '7', '6', '7, '—S(O) ...

IMIDAZOPYRIZINE SYK INHIBITORS

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample. 132-. (canceled)34. The method according to claim 33 , wherein the patient is a human.35. The method according to claim 33 , wherein the effective amount of said at least one chemical entity is administered to the patient intravenously claim 33 , intramuscularly claim 33 , parenterally claim 33 , or orally.36. (canceled)37. The method according to claim 33 , wherein the disease responsive to inhibition of Syk activity is cancer.38. The method according to claim 37 , wherein the disease responsive to inhibition of Syk activity is B-cell lymphoma or leukemia.39. The method according to claim 33 , wherein the disease responsive to inhibition of Syk activity is rheumatoid arthritis claim 33 , allergic rhinitis claim 33 , chronic obstructive pulmonary disease (COPD) claim 33 , adult respiratory distress syndrome (ARDs) claim 33 , an allergy-induced inflammatory disease claim 33 , multiple sclerosis claim 33 , autoimmune disease claim 33 , inflammatory disease claim 33 , acute inflammatory reaction claim 33 , allergic disorder claim 33 , or polycystic kidney disease.4052-. (canceled)53. The method according to claim 33 , wherein the disease responsive to inhibition of Syk activity is B-cell lymphoma claim 33 , Hodgkin's lymphoma claim 33 , non-Hodgkin's lymphoma claim 33 , hairy cell leukemia claim 33 , multiple myeloma claim 33 , chronic myelogenous leukemia claim 33 , acute myelogenous leukemia claim 33 , chronic lymphocytic leukemia claim 33 , or acute lymphocytic leukemia.54. The method according to claim 33 ...

IMIDAZOPYRAZINE SYK INHIBITORS

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample. 110-. (canceled)121: A pharmaceutical composition comprising at least one chemical entity of claim , together with at least one pharmaceutically acceptable vehicle chosen from carriers , adjuvants , and excipients.131: A method for treating a patient having a disease responsive to the inhibition of Syk activity , comprising administering to the patient an effective amount of at least one chemical entity according to claim . This application is a Continuation-in-Part of U.S. patent application Ser. No. 12/632,140, filed Dec. 7, 2009, which claims the benefit of provisional U.S. Patent Application 61/120,587, filed Dec. 8, 2008, provisional U.S. Patent Application No. 61/140,514, filed Dec. 23, 2008, and provisional U.S. Patent Application No. 61/240,979, filed Sep. 9, 2009. The contents of the above patent applications are incorporated by reference herein in their entirety.Provided herein are certain imidazopyrazines, compositions, and methods of their manufacture and use.Protein kinases, the largest family of human enzymes, encompass well over 500 proteins. Spleen Tyrosine Kinase (Syk) is a member of the Syk family of tyrosine kinases, and is a regulator of early B-cell development as well as mature B-cell activation, signaling, and survival.Syk is a non-receptor tyrosine kinase that plays critical roles in immunoreceptor- and integrin-mediated signaling in a variety of cell types, including B cells, macrophages, monocytes, mast cells, eosinophils, basophils, neutrophils, dendritic cells, T cells, natural ...

IMIDAZOPYRAZINE SYK INHIBITORS

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample. 152-. (canceled)54. A pharmaceutical composition comprising the compound of claim 53 , or a pharmaceutically acceptable salt thereof claim 53 , and at least one pharmaceutically acceptable vehicle chosen from carriers claim 53 , adjuvants claim 53 , and excipients.55. A method for treating a human having a disease responsive to the inhibition of Syk activity claim 53 , comprising administering to the human an effective amount of the compound according to claim 53 , or a pharmaceutically acceptable salt thereof.56. The method according to claim 55 , wherein an effective amount of the compound is administered to the human intravenously claim 55 , intramuscularly claim 55 , parenterally claim 55 , or orally.57. The method according to claim 55 , wherein the disease responsive to inhibition of Syk activity is cancer.58. The method according to claim 55 , wherein the disease responsive to inhibition of Syk activity is B-cell lymphoma or leukemia.59. The method according to claim 55 , wherein the disease responsive to inhibition of Syk activity is rheumatoid arthritis claim 55 , allergic rhinitis claim 55 , chronic obstructive pulmonary disease (COPD) claim 55 , adult respiratory distress syndrome (ARDs) claim 55 , an allergy-induced inflammatory disease claim 55 , multiple sclerosis claim 55 , an autoimmune disease claim 55 , an inflammatory disease claim 55 , an acute inflammatory reaction claim 55 , an allergic disorder claim 55 , polycystic kidney disease claim 55 , B-cell lymphoma claim 55 , Hodgkin's ...

IMIDAZOPYRAZINE SYK INHIBITORS

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample. 152.-. (canceled)54. The process of claim 53 , wherein the conditions comprise a palladium catalyst.55. The process of claim 54 , wherein the palladium catalyst is tetrakis(tripheyl-phosphine)palladium(0).56. The process of claim 54 , wherein the conditions further comprise a base.57. The process of claim 56 , wherein the conditions further comprise a solvent. This application is a continuation of U.S. application Ser. No. 14/882,278, filed Oct. 13, 2015, which is a continuation of U.S. application Ser. No. 14/300,189, filed Jun. 9, 2014, now U.S. Pat. No. 9,212,191, which is a continuation of U.S. application Ser. No. 13/868,967, filed Apr. 23, 2013, now U.S. Pat. No. 8,765,761, which is a continuation of U.S. application Ser. No. 12/632,140, filed Dec. 7, 2009, now U.S. Pat. No. 8,455,793, which claims the benefit of U.S. Patent Application No. 61/120,587, filed Dec. 8, 2008, U.S. Patent Application No. 61/140,514, filed Dec. 23, 2008, and U.S. Patent Application No. 61/240,979, filed Sep. 9, 2009, each of which are hereby incorporated by reference in their entirety.Provided herein are certain imidazopyrazines, compositions, and methods of their manufacture and use.Protein kinases, the largest family of human enzymes, encompass well over 500 proteins. Spleen Tyrosine Kinase (Syk) is a member of the Syk family of tyrosine kinases, and is a regulator of early B-cell development as well as mature B-cell activation, signaling, and survival.Syk is a non-receptor tyrosine kinase that plays critical roles in ...

IMIDAZOPYRAZINE SYK INHIBITORS

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample. 152-. (canceled)54. The method according to claim 53 , wherein the effective amount of said at least one chemical entity is administered to the human intravenously claim 53 , intramuscularly claim 53 , parenterally claim 53 , or orally.55. The method according to claim 53 , wherein Ris chosen from hydrogen claim 53 , methyl claim 53 , ethyl claim 53 , and chloro.56. The method according to claim 55 , wherein Ris hydrogen.57. The method according to claim 53 , wherein Ris chosen from hydrogen and methyl.58. The method according to claim 57 , wherein Ris hydrogen.59. The method according to claim 53 , wherein Rand Rare both hydrogen.60. The method according to claim 53 , wherein Ris chosen from (1-hydroxyethyl)phenyl claim 53 , 3 claim 53 ,4-dimethoxyphenyl claim 53 , 3-methoxyphenyl claim 53 , 4-ethoxy-3-methoxyphenyl claim 53 , 4-hydroxymethyl-3-methoxyphenyl claim 53 , 3-hydroxymethyl-4-methoxyphenyl claim 53 , 2-fluoro-4-methoxyphenyl claim 53 , 4-(dimethylamino)propoxy-3-methoxyphenyl claim 53 , 4-hydroxypropoxy-3-methoxyphenyl claim 53 , 4-(2-hydroxy-1 claim 53 ,1-dimethylethyl)phenyl claim 53 , 4-(1-hydroxy-1-methylethyl)phenyl claim 53 , 4-methoxy-3-(pyrrolidin-1-yl)phenyl claim 53 , 3-methoxy-4-(pyrrolidin-1-yl)phenyl claim 53 , 3-methoxy-4-(propan-2-yloxy)phenyl claim 53 , 3-methoxy-4-(morpholin-4-yl)phenyl claim 53 , 4-(pyrrolidin-1-yl)phenyl claim 53 , 4-(3-hydroxypyrrolidinyl)phenyl claim 53 , 4-(4-hydroxypiperidinyl)-3-methoxyphenyl claim 53 , 4-(3-hydroxyazetidinyl)-3-methoxyphenyl claim 53 , 4 ...

IMIDAZOPYRAZINE SYK INHIBITORS

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample. 152-. (canceled)54. A pharmaceutical composition comprising the compound of claim 53 , or a pharmaceutically acceptable salt thereof claim 53 , and at least one pharmaceutically acceptable vehicle chosen from carriers claim 53 , adjuvants claim 53 , and excipients.55. A method for treating a human having a disease responsive to the inhibition of Syk activity claim 53 , comprising administering to the human an effective amount of the compound according to claim 53 , or a pharmaceutically acceptable salt thereof.56. The method according to claim 55 , wherein an effective amount of the compound is administered to the human intravenously claim 55 , intramuscularly claim 55 , parenterally claim 55 , or orally.57. The method according to claim 55 , wherein the disease responsive to inhibition of Syk activity is cancer.58. The method according to claim 55 , wherein the disease responsive to inhibition of Syk activity is B-cell lymphoma or leukemia.59. The method according to claim 55 , wherein the disease responsive to inhibition of Syk activity is rheumatoid arthritis claim 55 , allergic rhinitis claim 55 , chronic obstructive pulmonary disease (COPD) claim 55 , adult respiratory distress syndrome (ARDs) claim 55 , an allergy-induced inflammatory disease claim 55 , multiple sclerosis claim 55 , an autoimmune disease claim 55 , an inflammatory disease claim 55 , an acute inflammatory reaction claim 55 , an allergic disorder claim 55 , polycystic kidney disease claim 55 , B-cell lymphoma claim 55 , Hodgkin's ...

INHIBITORS OF SYK IMIDAZOPIRAZINICI

Inhibitors of IRAK4 activity

The present invention relates to compounds which modulate interleukin-1 (IL-1) receptor-associated kinase 4 (IRAK4) and are useful in the prevention or treatment of inflammatory, cell proliferative and immune-related conditions and diseases. Specifically, provided herein are inhibitors of IRAK4 of Formula I and pharmaceutical compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.

Imidazopyrazine syk inhibitors

6-(benzo[d]thiazol-5-yl)-n-(3,4-dimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine

Provided are imidazopyrazine compounds, particularly including 6-(benzo[d]thiazol-5-yl)-N-(3,4-dimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine, structure below, and methods and formulations for their use in inhibiting Spleen Tyrosine Kinase in treating conditions including B-cell lymphomas or leukemias and inflammatory conditions: