US 11,980,594 B2
Composition and method for treating a drug-resistant cancer
Chung-Yang Huang, Taipei (TW); and Chia-Chung Hou, Taipei (TW)
Assigned to NOVELWISE PHARMACEUTICAL CORPORATION, Taipei (TW)
Filed by NOVELWISE PHARMACEUTICAL CORPORATION, Taipei (TW)
Filed on May 31, 2022, as Appl. No. 17/828,983.
Claims priority of provisional application 63/194,585, filed on May 28, 2021.
Prior Publication US 2023/0038230 A1, Feb. 9, 2023
Int. Cl. A61K 31/085 (2006.01); A61K 31/495 (2006.01); A61P 35/00 (2006.01)
CPC A61K 31/085 (2013.01) [A61K 31/495 (2013.01); A61P 35/00 (2018.01)] 19 Claims
 
1. A method for treating a TMZ-resistant cancer in a patient, which comprises administering to the patient a therapeutically effective amount of a combination of Temozolomide (TMZ) and a Compound A having the structure of Formula A, or a pharmaceutically acceptable salt or enantiomer thereof:

OG Complex Work Unit Chemistry
wherein
R1 is hydrogen, alkyl, alkenyl, C5-C6 cycloalkyl, 5-membered or 6-membered unsaturated carbocycle or 5-membered or 6-membered heterocycle, or (CH2)mR4;
X is C, —O—, —N— or —S—;
Y is —O—, —NH or —O—C1-C4 alkyl;
n is an integer of 0 to 10;
m is an integer of 0 to 5;
R2 and R3 is independently C1-C6 alkyl;
R4 is C5-C6 cycloalkyl or 5-membered or 6-membered unsaturated carbocycle or heterocycle which may be substituted with halogen, —CF3, —OR7 or —NR7R8, wherein R7 and R8 are independently hydrogen or C1-C6 alkyl;
R5 is OH, NH2 or C5-C8cycloalkyl, 5-membered or 6-membered unsaturated carbocycle or heterocycle wherein the cycloalkyl, carbocycle and heterocycle may be optionally substituted with halogen, NH2, NO2, C1-C6 alkoxy, C1-6 alkylthio, OR7″, NR7R8 or CF3; and
R6 is H, C1-C10 alkyl which may be substituted by hydroxy or C2-C10 alkenyl, or together with R1 being —C2H2—; and
wherein TMZ and the compound A are combined at a relative ratio to effectively overcome TMZ resistance.