Enantioselective Syntheses of Heteroyohimbine Natural Product Intermediates
US-2016326183-A1 · Nov 10, 2016 · US
US9802888B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-9802888-B2 |
| Application number | US-201414779276-A |
| Country | US |
| Kind code | B2 |
| Filing date | Mar 21, 2014 |
| Priority date | Mar 22, 2013 |
| Publication date | Oct 31, 2017 |
| Grant date | Oct 31, 2017 |
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The present disclosure provides pharmaceutical compositions comprising Stat3 inhibitors and certain pharmaceutically acceptable salts thereof, and methods of use.
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We claim: 1. A pharmaceutical composition comprising a pharmaceutically effective amount of a dosage of 0.05 mg/kg to 4 mg/kg of a compound, or salt, of Formula II and a pharmaceutically acceptable excipient. 2. A method of treating cancer harboring constitutively active Stat3 activity, comprising administering to a subject in need thereof, a therapeutically effective amount of a pharmaceutical composition comprising the composition of claim 1 . 3. The method of claim 2 , wherein the effective dose of the composition of claim 1 is from about 0.08 mg/kg to about 0.5 mg/kg, from about 0.08 to about 0.24 mg/kg, or from about 0.24 to about 0.5 mg/kg, or from about 0.08 to 0.5 mg/kg. 4. The method of claim 2 , wherein the one or more effective doses of the composition of claim 1 are administered orally. 5. The method of claim 2 , wherein the one or more effective doses of the composition of claim 1 are administered subcutaneously, intravenously, or intramuscularly. 6. The method of claim 2 , wherein the cancer is a solid tumor. 7. The method of claim 6 , wherein the solid tumor comprises glioma, breast cancer or pancreatic cancer. 8. The method of claim 2 , wherein the cancer is selected from the group consisting of: lung, breast, prostate, pancreatic, ovarian, bladder, head and neck, thyroid, brain, skin and kidney. 9. The method of claim 2 , wherein the cancer is selected from the group consisting of: brain tumors, gliomas, medulloblastomas, cerebral menangiomas, breast, prostate, pancreatic, ovarian, bladder, head and neck, malignant melanoma, multiple myeloma, lymphomas, including anaplastic large T cell lymphoma, sezary syndrome, EBV-related Burkitt's Lymphoma, HSV Saimiri-dependent (T Cell), cutaneous T cell lymphoma, mycosis fungoides, leukemia, including HTLV-I dependent leukemia, erythroleukemia, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML), chronic myelogenous lekemia (CML), megakaryocytic leukemia, and large granula lymphocyte (LGL) leukemia, thyroid, skin, lung, or kidney cancer, renal cell carcinoma, pancreatic adenocarcinoma, ovarian carcinoma, squamous cell carcinoma of the head and neck, or Hodgkin's Lymphoma. 10. The method of claim 2 , wherein each dose of the composition of claim 1 is between about 0.08 mg/kg and less than about 0.5 mg/kg, and said dose is administered by a delivery route selected from the group consisting of oral, intradermal, intramuscular, intraperitoneal, intravenous, topical, subcutaneous, and epidural routes. 11. The method of claim 6 , whereby tumor progression is inhibited, or reduced, or multi-drug resistance (MDR) is inhibited or reduced.
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