PLATINUM COMPOUNDS, COMPOSITIONS, AND USES THEREOF
The present teachings relate to compounds and compositions for treatment of cancers. In some embodiments, the composition comprises a platinum (IV) complex having at least one reacting group for reacting with a functional group on a protein.
1 . A pharmaceutical composition comprising a compound of Formula IIb:
and a pharmaceutically acceptable salt thereof, wherein:
X and Y are independently selected from NH, alkyl and aryl;
R 1 and R 2 each is Cl, or R 1 and R 2 are joined to form an oxalate;
R 3 is hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of the alkyl, alkenyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups optionally is substituted with one or more groups, each independently selected from halogen, cyano, nitro, hydroxyl, carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl, wherein each of the carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, or heterocyclyl is optionally substituted with one or more groups, each independently selected from halogen, cyano, nitro, hydroxyl, carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl, and
Z is alternatively absent, alkyl, aryl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of the alkyl, alkenyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups optionally is substituted with one or more groups, each independently selected from halogen, cyano, nitro, hydroxyl, carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl, or alkylidene hydrazine wherein each of the carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl or alkylidene hydrazine is optionally substituted with one or more groups, each independently selected from halogen, cyano, nitro, hydroxyl, carboxyl, carbamoyl, ether, alkoxy, aryloxy, amino, amide, carbamate, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heterocyclyl.
2 . The pharmaceutical composition of claim 1 , wherein R 1 and R 2 each is Cl.
3 . The pharmaceutical composition of claim 1 , wherein R 1 and R 2 are joined to form an oxalate.
4 . The pharmaceutical composition of claim 1 , wherein R 3 is alkyl.
5 . The pharmaceutical composition of claim 4 , wherein R 3 is methyl or ethyl.
6 . The pharmaceutical composition of claim 1 , wherein the compound is Compound 8:
7 . The pharmaceutical composition of claim 6 , wherein concentration of Compound 8 is 3-5 mg/mL.
8 . The pharmaceutical composition of claim 7 , wherein concentration of Compound 8 is 5 mg/mL.
9 . The pharmaceutical composition of claim 8 , wherein 10 mL of the pharmaceutical composition is contained in a 50 mL vial.
10 . The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition further comprises a buffer and has a pH of about 2 to about 6.
11 . The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition has a pH of about 4 to about 5.
12 . The pharmaceutical composition of claim 11 , wherein the pharmaceutical composition has a pH of about 4 or about 4.25.
13 . The pharmaceutical composition of claim 10 , wherein the buffer has a concentration of about 0.5 mM to about 100 mM.
14 . The pharmaceutical composition of claim 10 , wherein the buffer is selected from a citrate buffer, an acetate buffer, a lactate buffer, a succinate buffer and a tartrate buffer.
15 . The pharmaceutical composition of claim 14 , wherein the buffer is a citrate buffer comprising sodium citrate and citric acid, or citric acid and sodium hydroxide.
16 . The pharmaceutical composition of claim 6 , wherein the excipient has a weight percent of about 0.5% (w/w) to about 20% (w/w).
17 . The pharmaceutical composition of claim 16 , wherein the excipient comprises one or more excipients selected from mannitol, sucrose, lactose, trehalose, sorbitol, glucose, raffinose, glycine, histidine, polyvinyl pyrollidone and inulin.
18 . The pharmaceutical composition of claim 17 , wherein the excipient is mannitol.
19 . The pharmaceutical composition of claim 18 , wherein the weight percent of mannitol is 2.5% (w/w).
20 . The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is protected from light.
21 . The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is prepared, processed, packaged, or stored at a temperature below about 10° C.
22 . The pharmaceutical composition of claim 21 , wherein the pharmaceutical composition is prepared, processed, packaged, or stored at a temperature of about 2-8° C.
23 . The pharmaceutical composition of claim 21 , wherein the pharmaceutical composition is prepared, processed, or packaged at a temperature of about 2-8° C. and stored below about 20° C.