You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 29, 2024

Claims for Patent: 8,785,456


✉ Email this page to a colleague

« Back to Dashboard


Summary for Patent: 8,785,456
Title:Substituted isoquinolin-1(2H)-ones, and methods of use thereof
Abstract: Chemical entities that modulate PI3 kinase activity, pharmaceutical compositions containing the chemical entities, and methods of using these chemical entities for treating diseases and conditions associated with P13 kinase activity are described herein.
Inventor(s): Ren; Pingda (San Diego, CA), Liu; Yi (San Diego, CA), Wilson; Troy Edward (San Marino, CA), Li; Liansheng (San Diego, CA), Chan; Katrina (San Diego, CA), Rommel; Christian (La Jolla, CA)
Assignee: Intellikine LLC (La Jolla, CA)
Application Number:13/403,394
Patent Claims:1. A method of inhibiting a phosphatidyl inositol-3 kinase (PI3 kinase) in a subject, comprising administering to the subject an effective amount of a compound of Formula I-1: ##STR00673## or a pharmaceutically acceptable salt thereof, wherein: B is a moiety of Formula II: ##STR00674## wherein: W.sub.c is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl, and q is an integer of 0, 1, 2, 3, or 4; X is a bond or --(CH(R.sup.9)).sub.z--, and z is an integer of 1; Y is --N(R.sup.9)--; W.sub.d is: ##STR00675## R.sup.1 is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, amido, alkoxycarbonyl, sulfonamido, halo, cyano, or nitro; R.sup.2 is alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, heteroarylalkyl, alkoxy, amino, halo, cyano, hydroxy or nitro; R.sup.3 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, alkoxy, amido, amino, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy or nitro; and each instance of R.sup.9 is independently hydrogen, alkyl, or heterocycloalkyl.

2. The method of claim 1, wherein the inhibition takes place in a subject suffering from a disorder, wherein the disorder is a cancer or an inflammatory disease, wherein the cancer is leukemia lymphoma; and wherein the inflammatory disease is asthma, emphysema, allergy, dermatitis, rheumatoid arthritis, psoriasis, lupus erythematosus, graft versus host disease, inflammatory bowel disease, eczema, scleroderma,Crohn's disease, atherosclerosis, encephalomyelitis, or multiple sclerosis.

3. The method of claim 2, wherein the leukemia is B-cell acute lymphoblastic leukemia (B-ALL), acute lymphocytic leukemia, T-cell acute lymphocytic leukemia, adult T-cell leukemia, hairy cell leukemia, myelodysplasia, myeloproliferative disorders, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), myelodysplastic syndrome (MDS), mastocytosis, or mast cell cancer.

4. The method of claim 2, wherein the lymphoma is diffuse large B-cell lymphoma, B-cell immunoblastic lymphoma, small non-cleaved cell lymphoma, human lymphotropic virus-type 1 (HTLV-1) leukemia/lymphoma, adult T-cell lymphoma, AIDS-related lymphoma, Hodgkin disease, or non-Hodgkin lymphomas.

5. The method of claim 2, further comprising administering one or more therapeutic agents selected from chemotherapeutic agents, cytotoxic agents, and radiation.

6. The method of claim 1, wherein the compound is: ##STR00676## ##STR00677## ##STR00678## ##STR00679## ##STR00680## ##STR00681## ##STR00682## or a pharmaceutically acceptable salt thereof.

7. The method of claim 1, wherein the compound is: ##STR00683## ##STR00684## or a pharmaceutically acceptable salt thereof.

8. The method of claim 1, wherein the compound is: ##STR00685## ##STR00686## ##STR00687## or a pharmaceutically acceptable salt thereof.

9. The method of claim 1, wherein the subject is a mammal.

10. The method of claim 9, wherein the mammal is a human.

11. The method of claim 2, wherein the disorder is rheumatoid arthritis, and the amount of the compound is effective to ameliorate one or more symptoms associated with rheumatoid arthritis selected from a reduction in the swelling of the joints, a reduction in serum anti-collagen levels, a reduction in bone resorption, a reduction in cartilage damage, a reduction in pannus, and a reduction in inflammation, and a combination thereof.

12. The method of claim 1, wherein the compound is administered in combination with an mTOR inhibitor.

13. The method of claim 1, wherein the compound is administered in combination with one or more of an agent that inhibits IgE production or activity, 2-(4-(6-cyclohexyloxy-2-naphtyloxy)phenylacetamide)benzoic acid, an mTOR inhibitor, rapamycin, a TORC1 inhibitor, a TORC2 inhibitor, an anti-IgE antibody, corticosteroid, a leukotriene inhibitor, omalizumab, a combination of fluticasone and salmeterol, montelukast, or tiotropium bromide.

14. The method of claim 1, wherein the compound is administered in combination with one or more of a mitotic inhibitor, an alkylating agent, an anti-metabolite, an intercalating antibiotic, a growth factor inhibitor, a cell cycle inhibitor, an enzyme, a topoisomerase inhibitor, an anti-hormone, an angiogenesis inhibitor, or an anti-receptor kinase antibody.

15. The method of claim 1, wherein the compound is administered in combination with one or more of Imatinib mesylate, bortezomib, bicalutamide, gefitinib, alkylating agents, alkyl sulfonates, ethylenimines, altretamine, triethylenemelamine, trietylenephosphoramide, triethylenethiophosphaoramide, trimethylolomelamine, antibiotics, anti-metabolites, denopterin, ancitabine, 6-azauridine, carmofur, dideoxyuridine, doxifluridine, enocitabine, androgens, anti-adrenals, folic acid replenisher, arabinoside, thiotepa, taxanes, anti-hormonal agents, aromatase inhibiting 4(5)-imidazoles, gemcitabine, cisplatin, carboplatin, vincristine, vinorelbine, vinblastin, daunorubicin, doxorubicin, mitoxantrone, anastrozole, or an anti-receptor tyrosine kinase antibody selected from the group consisting of cetuximab, panitumumab, trastuzumab, anti CD20 antibody, rituximab, tositumomab, alemtuzumab, bevacizumab, and gemtuzumab.

16. The method of claim 1, wherein the compound is administered in combination with one or more of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, chloroquine, hydroxychloroquine, azathioprine, cyclophosphamide, methotrexate, cyclosporine, anti-CD20 antibodies, etanercept, infliximab, adalimumab, or interferon beta 1-alpha.

17. The method of claim 1, wherein the B moiety of the compound of Formula I-1 is: ##STR00688## wherein W.sub.c is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; q is an integer of 0 or 1; R.sup.1 is hydrogen, alkyl, or halo; R.sup.2 is alkyl or halo; and R.sup.3 is hydrogen, alkyl, or halo.

18. The method of claim 1, wherein X is --(CH(R.sup.9)).sub.z--, and Y is --NH--.

19. The method of claim 1, wherein R.sup.3 is --H, --CH.sub.3, --CH.sub.2CH.sub.3, --CF.sub.3, --Cl or --F.

20. The method of claim 1, wherein R.sup.3 is --CH.sub.3 or --Cl.

21. The method of claim 17, wherein X is --(CH(R.sup.9)).sub.z--, wherein R.sup.9 is methyl and z is 1; and W.sub.d is ##STR00689##

22. The method of claim 17, wherein R.sup.3 is --CH.sub.3 or --Cl.

23. The method of claim 1, wherein the compound of Formula I-1 is predominately in an (S)-stereochemical configuration.

24. The method of claim 23, wherein the compound of Formula I-1 is the S-enantiomer having an enantiomeric purity greater than 90%.

25. The method of claim 1, wherein the compound has a structure of Formula V-A2: ##STR00690##

26. The method of claim 25, wherein the B moiety of the compound is: ##STR00691## wherein W.sub.c is aryl or cycloalkyl.

27. The method of claim 25, wherein R.sup.3 is methyl or chloro.

28. The method of claim 25, wherein R.sup.3 is chloro.

29. The method of claim 25, wherein the B moiety of the compound is substituted or unsubstituted phenyl.

30. The method of claim 25, wherein the B moiety of the compound is substituted or unsubstituted cycloalkyl.

31. The method of claim 25, wherein the B moiety of the compound is a phenyl that is unsubstituted or substituted with fluoro.

32. The method of claim 25, wherein W.sub.c is aryl or heterocycloalkyl.

33. The method of claim 32, wherein W.sub.c is phenyl.

34. The method of claim 25, wherein W.sub.c is cyclopropyl.

35. The method of claim 25, wherein W.sub.c is substituted by at least one of --CH.sub.3, --CH.sub.2CH.sub.3, --CF.sub.3, --Cl or --F.

36. The method of claim 1, wherein the compound is: ##STR00692## ##STR00693## ##STR00694## or a pharmaceutically acceptable salt thereof.

37. The method of claim 1, wherein the compound has the following structure: ##STR00695## or a pharmaceutically acceptable salt thereof.

38. The method of claim 37, wherein the compound is the S-enantiomer having an enantiomeric purity greater than 90%.

39. The method of claim 1, wherein the compound has the following structure: ##STR00696## or a pharmaceutically acceptable salt thereof.

40. The method of claim 1, wherein the compound is present in a pharmaceutical composition comprising the compound, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

41. The method of claim 2, wherein the subject is a human.

42. The method of claim 2, wherein the disorder is rheumatoid arthritis.

43. The method of claim 2, wherein the disorder is asthma.

44. The method of claim 2, wherein the disorder is cancer selected from leukemia and lymphoma.

45. The method of claim 2, wherein the B moiety of the compound of Formula I-1 is: ##STR00697## wherein W.sub.c is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; q is an integer of 0 or 1; R.sup.1 is hydrogen, alkyl, or halo; R.sup.2 is alkyl or halo; and R.sup.3 is hydrogen, alkyl, or halo.

46. The method of claim 2, wherein X is --(CH(R.sup.9)).sub.z--, and Y is --NH--.

47. The method of claim 2, wherein R.sup.3 is --H, --CH.sub.3, --CH.sub.2CH.sub.3, --CF.sub.3, --Cl or --F.

48. The method of claim 2, wherein R.sup.3 is --CH.sub.3 or --Cl.

49. The method of claim 45, wherein X is --(CH(R.sup.9)).sub.z--, wherein R.sup.9 is methyl and z is 1; and W.sub.d is ##STR00698##

50. The method of claim 45, wherein R.sup.3 is --CH.sub.3 or --Cl.

51. The method of claim 2, wherein the compound of Formula I-1 is predominately in an (S)-stereochemical configuration.

52. The method of claim 51 , wherein the compound of Formula I-1 is the S-enantiomer having an enantiomeric purity greater than 90%.

53. The method of claim 2, wherein the compound has a structure of Formula V-A2: ##STR00699##

54. The method of claim 53, wherein the B moiety of the compound is: ##STR00700## wherein W.sub.c is aryl or cycloalkyl.

55. The method of claim 53, wherein R.sup.3 is methyl or chloro.

56. The method of claim 53, wherein R.sup.3 is chloro.

57. The method of claim 53, wherein the B moiety of the compound is substituted or unsubstituted phenyl.

58. The method of claim 53, wherein the B moiety of the compound is substituted or unsubstituted cycloalkyl.

59. The method of claim 53, wherein the B moiety of the compound is a phenyl that is unsubstituted or substituted with fluoro.

60. The method of claim 53, wherein W.sub.c is aryl or heterocycloalkyl.

61. The method of claim 60, wherein W.sub.c is phenyl.

62. The method of claim 53, wherein W.sub.c is cyclopropyl.

63. The method of claim 53, wherein W.sub.c is substituted by at least one of --CH.sub.3, --CH.sub.2CH.sub.3, --CF.sub.3, --Cl or --F.

64. The method of claim 2, wherein the compound is: ##STR00701## ##STR00702## ##STR00703## ##STR00704## ##STR00705## ##STR00706## ##STR00707## or a pharmaceutically acceptable salt thereof.

65. The method of claim 2, wherein the compound is: ##STR00708## ##STR00709## or a pharmaceutically acceptable salt thereof.

66. The method of claim 2, wherein the compound is: ##STR00710## ##STR00711## ##STR00712## ##STR00713## or a pharmaceutically acceptable salt thereof.

67. The method of claim 2, wherein the compound is: ##STR00714## ##STR00715## ##STR00716## or a pharmaceutically acceptable salt thereof.

68. The method of claim 2, wherein the compound has the following structure: ##STR00717## or a pharmaceutically acceptable salt thereof.

69. The method of claim 68, wherein the compound is the S-enantiomer having an enantiomeric purity greater than 90%.

70. The method of claim 2, wherein the compound has the following structure: ##STR00718## or a pharmaceutically acceptable salt thereof.

71. The method of claim 2, wherein the compound is present in a pharmaceutical composition comprising the compound, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

72. The method of claim 2, wherein the compound is administered in combination with one or more of: a mitotic inhibitor, an alkylating agent, an anti-metabolite, an intercalating antibiotic, a growth factor inhibitor, a cell cycle inhibitor, an enzyme, a topoisomerase inhibitor, an anti-hormone, an angiogenesis inhibitor, or an anti-receptor kinase antibody.

73. The method of claim 2, wherein the compound is administered in combination with an mTOR inhibitor.

74. The method of claim 2, wherein the compound is administered in combination with one or more of: 2-(4-(6-cyclohexyloxy-2-naphtyloxy)phenylacetamide)benzoic acid, an mTOR inhibitor, rapamycin, a TORC1 inhibitor, a TORC2 inhibitor, an anti-IgE antibody, corticosteroid, a leukotriene inhibitor, a combination of fluticasone and salmeterol, and tiotropium bromide.

75. The method of claim 2, wherein the compound is administered in combination with one or more of: Imatinib mesylate, bortezomib, bicalutamide, gefitinib, alkylating agents, alkyl sulfonates, ethylenimines, altretamine, triethylenemelamine, trietylenephosphoramide, triethylenethiophosphaoramide, trimethylolomelamine, antibiotics, anti-metabolites, denopterin, ancitabine, 6-azauridine, carmofur, dideoxyuridine, doxifluridine, enocitabine, androgens, anti-adrenals, folic acid replenisher, arabinoside, thiotepa, taxanes, anti-hormonal agents, aromatase inhibiting 4(5)-imidazoles, gemcitabine, cisplatin, carboplatin, vincristine, vinorelbine, vinblastin, daunorubicin, doxorubicin, mitoxantrone, anastrozole, cetuximab, panitumumab, trastuzumab, rituximab, tositumomab, alemtuzumab, bevacizumab, gemtuzumab, montelukast, and omalizumab.

76. The method of claim 2, wherein the compound is administered in combination with one or more of: non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, chloroquine, hydroxychloroquine, azathioprine, cyclophosphamide, methotrexate, cyclosporine, anti-CD20 antibodies, etanercept, infliximab, adalimumab, and interferon beta 1-alpha.

77. The method of claim 44, further comprising administering one or more therapeutic agents selected from chemotherapeutic agents, cytotoxic agents, and radiation.

78. A method of inhibiting a phosphatidyl inositol-3 kinase (PI3 kinase) in a subject suffering from a cancer, comprising administering to the subject an effective amount of a compound having the following structure: ##STR00719## or a pharmaceutically acceptable salt thereof, wherein the cancer is leukemia or lymphoma.

79. The method of claim 78, wherein the compound is the S-enantiomer having an enantiomeric purity greater than 90%.

80. The method of claim 78, wherein the leukemia is B-cell acute lymphoblastic leukemia (B-ALL), acute lymphocytic leukemia, T-cell acute lymphocytic leukemia, adult T-cell leukemia, hairy cell leukemia, myelodysplasia, myeloproliferative disorders, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), myelodysplastic syndrome (MDS), mastocytosis, mast cell cancer.

81. The method of claim 78, wherein the lymphoma is diffuse large B-cell lymphoma, B-cell immunoblastic lymphoma, small non-cleaved cell lymphoma, human lymphotropic virus-type 1 (HTLV-1) leukemia/lymphoma, AIDS-related lymphoma, adult T-cell lymphoma, Hodgkin disease, or non-Hodgkin lymphomas.

82. The method of claim 78, further comprising administering one or more therapeutic agents selected from chemotherapeutic agents, cytotoxic agents, and radiation.

83. The method of claim 78, wherein the compound is administered in combination with one or more of: a mitotic inhibitor, an alkylating agent, an anti-metabolite, an intercalating antibiotic, a growth factor inhibitor, a cell cycle inhibitor, an enzyme, a topoisomerase inhibitor, an anti-hormone, an angiogenesis inhibitor, or an anti-receptor kinase antibody.

84. The method of claim 78, wherein the compound is administered in combination with one or more of: Imatinib mesylate, bortezomib, bicalutamide, gefitinib, alkylating agents, alkyl sulfonates, ethylenimines, altretamine, triethylenemelamine, trietylenephosphoramide, triethylenethiophosphaoramide, trimethylolomelamine, antibiotics, anti-metabolites, denopterin, ancitabine, 6-azauridine, carmofur, dideoxyuridine, doxifluridine, enocitabine, androgens, anti-adrenals, folic acid replenisher, arabinoside, thiotepa, taxanes, anti-hormonal agents, aromatase inhibiting 4(5)-imidazoles, gemcitabine, cisplatin, carboplatin, vincristine, vinorelbine, vinblastin, daunorubicin, doxorubicin, mitoxantrone, anastrozole, cetuximab, panitumumab, trastuzumab, rituximab, tositumomab, alemtuzumab, bevacizumab, and gemtuzumab.

85. The method of claim 78, wherein the compound is administered in combination with one or more of: bortezomib, alkylating agents, anti-metabolites, denopterin, pteropterin, trimetrexate, ancitabine, 6-azauridine, carmour, dideoxyuridine, doxifluridine, enocitabine, androgens, taxanes, anti-hormonal agents, gemcitabine, cisplatin, carboplatin, vincristine, vinorelbine, vinblastin, mitomycin C, daunorubicin, doxorubicin, mitoxantrone, and anastrozole.

86. A method of inhibiting a phosphatidyl inositol-3 kinase (PI3kinase) in a subject suffering from a cancer, comprising administering to the subject an effective amount of a compound having the following structure: ##STR00720## or a pharmaceutically acceptable salt thereof, wherein the cancer is leukemia or lymphoma.

87. The method of claim 86, wherein the leukemia is B-cell acute lymphoblastic leukemia (B-ALL), acute lymphocytic leukemia, T-cell acute lymphocytic leukemia, adult T-cell leukemia, hairy cell leukemia, myelodysplasia, myeloproliferative disorders, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), myelodysplastic syndrome (MDS), mastocytosis, or mast cell cancer.

88. The method of claim 86, wherein the lymphoma is diffuse large B-cell lymphoma, B-cell immunoblastic lymphoma, small non-cleaved cell lymphoma, human lymphotropic virus-type 1 (HTLV-1) leukemia lymphoma, AIDS-related lymphoma, adult T-cell lymphoma, Hodgkin disease, or non-Hodgkin lymphomas.

89. The method of claim 86, further comprising administering one or more therapeutic agents selected from chemotherapeutic agents, cytotoxic agents, and radiation.

90. The method of claim 86, wherein the compound is administered in combination with one of more of: a mitotic inhibitor, an alkylating agent, an anti-metabolite, an intercalating antibiotic, a growth factor inhibitor, a cell cycle inhibitor, an enzyme, a topoisomerase inhibitor, an anti-hormone, an angiogenesis inhibitor, or an anti-receptor kinase antibody.

91. The method of claim 86, wherein the compound is administered in combination with one or more of: Imatinib mesylate, bortezomib, bicalutamide, gefitinib, alkylating agents, alkyl sulfonates, ethylenimines, altretamine, triethylenemelamine, trietylenephosphoramide, triethylenethiophosphaoramide, trimethylolomelamine, antibiotics, anti-metabolites, denopterin, ancitabine, 6-azauridine, carmofur, dideoxyuridine, doxifluridine, enocitabine, androgens, anti-adrenals, folic acid replenisher, arabinoside, thiotepa, taxanes, anti-hormonal agents, aromatase inhibiting 4(5)-imidazoles, gemcitabine, cisplatin, carboplatin, vincristine, vinorelbine, vinblastin, daunorubicin, doxorubicin, mitoxantrone, anastrozole, cetuximab, panitumumab, trastuzumab, rituximab, tositumomab, alemtuzumab, bevacizumab, and gemtuzumab.

92. The method of claim 86, wherein the compound is administered in combination with one or more of: bortezomib, alkylating agents, anti-metabolites, denopterin, pteropterin, ancitabine, 6-azauridine, carmofur, dideoxyuridine, doxifluridine, enocitabine, androgens, taxanes, anti-hormonal agents, gemcitabine, cisplatin, carboplatin, vincristine, vinorelbine, vinblastin, ifosfamide, mitomycin C, daunorubicin, doxorubicin, mitoxantrone, and anastrozole.

93. A method of inhibiting phosphatidyl inositol-3 kinase (PI3 kinase) in a subject suffering from an inflammatory disease, comprising administering to the subject an effective amount of a compound having the following structure: ##STR00721## or a pharmaceutically acceptable salt thereof, wherein the inflammatory disease is asthma, emphysema, allergy, dermatitis, rheumatoid arthritis, psoriasis, lupus erythematosus, graft versus host disease, inflammatory bowel disease, eczema, scleroderma, Crohn's disease, atherosclerosis, encephalomyelitis, or multiple sclerosis.

94. The method of claim 93, wherein the compound is the S-enantiomer having an enantiomeric purity greater than 90%.

95. The method of claim 93, wherein the inflammatory disease is rheumatoid arthritis.

96. The method of claim 93, wherein the compound is administered in combination with one or more of: non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, chloroquine, hydroxychloroquine, azathioprine, cyclophosphamide, methotrexate, cyclosporine, anti-CD20 antibodies, etanercept, infliximab, adalimumab, and interferon beta 1-alpha.

97. A method of inhibiting a phosphatidyl inositol-3 kinase (PI3 kinase) in a subject: suffering from an inflammatory disease, comprising administering to the subject an effective amount of a compound having the following structures: ##STR00722## or a pharmaceutically acceptable salt thereof, wherein the inflammatory disease is asthma, emphysema, allergy, dermatitis, rheumatoid arthritis, psoriasis, lupus erythematosus, graft versus host disease, inflammatory bowel disease, eczema, scleroderma, Crohn's disease, atherosclerosis, encephalomyelitis, or multiple sclerosis.

98. The method of claim 97, wherein the inflammatory disease is rheumatoid arthritis.

99. The method of claim 97, wherein the compound is administered in combination with one or more of: non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, chloroquine, hydroxychloroquine, azathioprine, cyclophosphamide, methotrexate, cyclosporine, anti-CD20 antibodies, etanercept, infliximab, adalimumab, and interferon beta 1-alpha.

100. A method of inhibiting a phosphatidyl inositol-3 kinase(PI3 kinase) in a subject suffering from a respiratory disease, comprising administering to the subject an effective amount of a compound having the following structure: ##STR00723## or a pharmaceutically salt thereof, wherein the respiratory disease is asthma, chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, or bronchiectasis.

101. The method of claim 100, wherein the compound is the S-enantiomer having an enantiomeric purity greater than 90%.

102. The method of claim 100, wherein the respiratory disease is asthma.

103. The method of claim 100, wherein the compound is administered in combination with one or more of: 2-(4-(6-cyclohexyloxy-2-naphtyloxy)phenylacetamide)benzoic acid, an mTOR inhibitor, rapamycin, a TORC1 inhibitor, a TORC2 inhibitor, an anti-IgE antibody, corticosteroid, a leukotriene inhibitor, a combination of fluticasone and salmeterol, montelukast, and tiotropium bromide.

104. A method of inhibiting a phosphatidyl inositol-3 kinase (PI3 kinase) in a subject suffering from a respiratory disease, comprising administering to the subject an effective amount of a compound having the following structure: ##STR00724## or a pharmaceutically acceptable salt thereof, wherein the respiratory disease is asthma, chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, or bronchiectasis.

105. The method of claim 104, wherein the respiratory disease is asthma.

106. The method of claim 104, wherein the compound is administered in combination with one or more of: 2-(4-(6-cyclohexyloxy-2-naphtyloxy)phenylacetamide)benzoic acid, an mTOR inhibitor, rapamycin, a TORC2 inhibitor, an anti-IgE antibody, corticosteroid, a leukotriene inhibitor, a combination of fluticasone and salmeterol, and tiotropium bromide.

107. The method of claim 104, wherein the compound is administered in combination with montelukast or omalizumab.

108. The method of claim 1, wherein the inhibition takes place in a subject suffering from a disorder, wherein the disorder is an immune disease, wherein the immune disease is acute disseminated encephalomyelitis (ADEM), Addiosn's disease, antiphospholipid antibody syndrome (APS), aplastic anemia, autoimmune hepatitis, coeliac disease, Crohn's disease, Diabetes mellitus (type 1), Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome (GBS), Hashimoto's disease, lupus erythematosus, multiple sclerosis, myasthenia gravis, opoclonus myoclonus syndrome (OMS), optic neuritis, Ord's thyroiditis, oemphigus, polyarthritis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis, Reiter's syndrome, Takayasu's arteritis, temporal arteritis, warm autoimmune hemolytic anemia, Wegener's granulomatosis, alopecia universalis, Chagas's disease, chronic fatigue syndrome, dysautonomia, endometriosis, hidradenitis suppurativea, interstitial cystitis, neuromyotonia, sareoidosis, scleroderma, ulcerative colitis, vitiligo, or vulvodynia.

109. The method of claim 1, wherein the inhibition takes place in a subject suffering front a disorder, wherein the disorder is a respiratory disease, wherein the respiratory disease is asthma, chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, or bronchiectasis.

110. The method of claim 86, wherein the compound is administered in combination with an mTOR inhibitor.

111. The method of claim 86, wherein the compound is administered in combination with one or more of: 2-(4-(6-cyclohexyloxy-2-naphtyloxy)phenylacetamide)benzoic acid, an mTOR inhibitor, rapamycin, a TORC1 inhibitor, a TORC2 inhibitor, an anti-IgE antibody, corticosteroid, a leukotriene inhibitor, a combination of fluticasone and salmeterol, and tiotropium bromide.

112. The method of claim 2, wherein the compound is administered in combination with one or more of nitrogen mustards.

113. The method of claim 112, wherein the nitrogen mustard is chlorambucil, chlornaphazine, cyclophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, or uracil mustard.

114. The method of claim 2, wherein the compound is administered in combination with one or more of nitrosurea.

115. The method of claim 114, wherein the nitrosurea is carmustine, chlorozotocin, fotemustine, lomustine, nimustine, or ranimustine.

116. The method of claim 2, wherein the compound is administered in combination with one or more of anti-estrogens or anti-androgens.

117. The method of claim 2, wherein the compound is administered in combination with one or more of: methotrexate, trimetrexate, 5-fluorouracil (5-FU), fludarabine, thiamiprine, thioguanine, azacitidine, cytarabine, floxuridine, mercaptopurine, pteropterin, onapristone, paclitaxel, docetaxel, tamoxifen, raloxifene, 4-hydroxytamoxifen, trioxifene, keoxifene, toremifene, and mitomycin C.

118. The method of claim 86, wherein the cancer is chronic lymphocytic leukemia.

119. The method of claim 86, wherein the cancer is non-Hodgkin lymphomas.

120. The method of claim 86, wherein the cancer is acute lymphocytic leukemia (ALL).

121. The method of claim 86, wherein the cancer is diffuse large B-cell lymphoma.

122. The method of claim 86, wherein the cancer is myelodysplastic syndrome (MDS).

123. The method of claim 86, wherein the cancer is adult T-cell lymphoma.

124. The method of claim 86, wherein the cancer is acute myelogenous leukemia (AML).

125. The method of claim 86, wherein the cancer is chronic myelogenous leukemia (CML).

126. The method of claim 86, wherein the cancer is myeloproliferative disorders.

127. The method of claim 86, wherein the cancer is mast cell cancer.

128. The method of claim 86, wherein the cancer is Hodgkin disease.

129. The method of claim 86, wherein the cancer is B-cell acute lymphoblastic leukemia.

130. The method of claim 86, wherein the cancer is T-cell acute lymphoblastic leukemia.

131. The method of claim 86, wherein the cancer is multiple myeloma (MM).

132. The method of claim 86, wherein the compound is administered in combination with one or more of nitrogen mustards or rituximab.

133. The method of claim 132, wherein the nitrogen mustard is chlorambucil, chlomaphazine, cyclophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, or uracil mustard.

134. The method of claim 86, wherein the compound is administered in combination with one or more of nitrosureas.

135. The method of claim 134, wherein the nitrosurea is carmustine, chlorozotocin, fotemustine, lomustine, nimustine, or ranimustine.

136. The method of claim 86, wherein the compound is administered in combination with one or more of anti-estrogens or anti-androgens.

137. The method of claim 86, wherein the compound is administered in combination with one or more of: methotrexate, trimetrexate, 5-fluorouracil (5-FU), fludarabine, thiamiprine, thioguanine, azacitidine, cytarabine, floxuridine, mercaptopurine, pteropterin, onapristone, paclitaxel, docetaxel, tamoxifen, raloxifene, 4-hydroxytamoxifen, trioxifene, keoxifene, toremifene, and mitomycin C.

138. The method of claim 132, wherein the nitrogen mustard is chlorambucil.

139. The method of claim 118, wherein the compound is administered in combination with rituximab.

140. The method of claim 118, wherein the compound is administered in combination with one or more nitrogen mustards.

141. The method of claim 119, wherein the compound is administered in combination with rituximab.

142. The method of claim 119, wherein the compound is administered in combination with at least one of nitrogen mustards.

143. The method of claim 68, wherein the compound of Formula I-1 is the S-enantiomer having an enantiomeric purity greater than 95%.

144. The method of claim 68, wherein the compound of Formula I-1 is the S-enantiomer having an enantiomeric purity greater than 80%.

145. The method of claim 68, wherein the compound of Formula I-1 is the S-enantiomer having an enantiomeric purity greater than 55%.

146. The method of claim 39, wherein the subject is a mammal.

147. The method of claim 146, wherein the mammal is a human.

148. The method of claim 97, wherein the inflammatory disease is asthma.

149. The method of claim 97, wherein the inflammatory disease is emphysema.

150. The method of claim 97, wherein the inflammatory disease is allergy.

151. The method of claim 97, wherein the inflammatory disease is dermatitis.

152. The method of claim 97, wherein the inflammatory disease is psoriasis.

153. The method of claim 97, wherein the inflammatory disease is lupus erythematosus.

154. The method of claim 97, wherein the inflammatory disease is graft versus host disease.

155. The method of claim 97, wherein the inflammatory disease is inflammatory bowel disease.

156. The method of claim 97, wherein the inflammatory disease is eczema.

157. The method of claim 97, wherein the inflammatory disease is scleroderma.

158. The method of claim 97, wherein the inflammatory disease is Crohn's disease.

159. The method of claim 97, wherein the inflammatory disease is atherosclerosis.

160. The method of claim 97, wherein the inflammatory disease is encephalomyelitis.

161. The method of claim 97, wherein the inflammatory disease is multiple sclerosis.

162. The method of claim 86, wherein the cancer is hairy cell leukemia.

163. The method of claim 86, wherein the cancer is myelodysplasia.

164. The method of claim 86, wherein the cancer is mastocytosis.

165. The method of claim 86, wherein the cancer is B-cell immunoblastic lymphoma.

166. The method of claim 86, wherein the cancer is small non-cleaved cell lymphoma.

167. The method of claim 86, wherein the cancer is human lymphotropic virus-type 1 (HTLV-1) leukemia/lymphoma.

168. The method of claim 86, wherein the cancer is AIDS-related lymphoma.

169. The method of claim 86, wherein the cancer is adult T-cell leukemia/lymphoma.

170. The method of claim 86, wherein the cancer is adult T-cell leukemia.

Details for Patent 8,785,456

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Genentech, Inc. RITUXAN rituximab Injection 103705 11/26/1997 ⤷  Try a Trial 2028-01-04
Idec Pharmaceuticals Corp. RITUXAN rituximab Injection 103737 02/19/2002 ⤷  Try a Trial 2028-01-04
Janssen Biotech, Inc. REMICADE infliximab For Injection 103772 08/24/1998 ⤷  Try a Trial 2028-01-04
Genentech, Inc. HERCEPTIN trastuzumab For Injection 103792 09/25/1998 ⤷  Try a Trial 2028-01-04
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.