Adenosine 2A receptor modulators for use in the treatment of cancer
AssigneeUniversite De Geneve
InventorsLeonardo Scapozza, Aurélie Gouiller, Margot Boujut, Margaux Heritier, David Pejoski, Thibaut De Smedt
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Abstract
The present invention relates to new agents useful for in the treatment of cancers, in particular by immunotherapy, as well as pharmaceutically acceptable salts thereof. In particular, this invention provides new A2AR modulators, pharmaceutical compositions and uses thereof.
Claims16
A method for preventing resistance to anti-cancer immunotherapy and/or treating a cancer in a subject suffering from a cancer or at risk of suffering from resistance to anti-cancer immunotherapy, said method comprising administering a compound of Formula (I) or a pharmaceutical formulation thereof to a subject in need thereof, wherein Formula (I) is:
- wherein R1 is selected from a phenyl optionally substituted by one or more halogen, cyano, hydroxy or C1-C6 alkyl and five or six membered heteroaryl optionally substituted by one or more halogen, cyano, hydroxy or C1-C6 alkyl;
- R2 is selected from H and halogen;
- R3 is selected from H, CN and optionally substituted C1-C6 alkyl;
- R4 is OR, where R is an optionally substituted C1-C6 alkyl or a C1-C6 hydroxyalkyl;
- SR, where R is an optionally substituted C1-C6 alkyl;
- XR(R′);
- an optionally substituted phenyl;
- or an optionally substituted five or six membered heteroaryl, wherein X is selected from O, S, N and R and R′ are independently an optionally substituted C1-C6 alkyl, or XRR′ form together an optionally substituted four to six membered heterocyclic alkyl, wherein the term “substituted” refers to groups substituted with from 1 to 3 substituents selected from the group consisting of halogen, cyano, nitro, hydroxy, amino (—NH2, —NH—, —N—), amide (—NHC(O)—), carbonyl (—C(O)—), alkoxycarbonyl (—C(O)O—), carboxylic acid, ether (—O—), thioether (—S—), sulfoxide (—S(O)—), sulfone (—S(O)2—), and C1-C6 alkyl, wherein said cancer is a solid tumor cancer.
A method for eliciting or increasing an immune response to immunotherapy, said method comprising administering an effective amount of one or more compound of Formula (I) or a pharmaceutical formulation thereof in combination with one or more of treatment selected from adoptive cell therapy, Chimeric Antigen Receptor T cell (CAR-T) therapy, tumor infiltrating lymphocyte (TIL) therapy, anti-cancer vaccine therapy or immunomodulating therapy comprising administering immune checkpoint inhibitors, bispecific T cell engagers, or nanobodies that bind to a single or multiple drug targets, wherein Formula (I) is:
- wherein R1 is selected from a phenyl optionally substituted by one or more halogen, cyano, hydroxy or C1-C6 alkyl and a five or six membered heteroaryl optionally substituted by one or more halogen, cyano, hydroxy or C1-C6 alkyl;
- R2 is selected from H and halogen;
- R3 is selected from H, CN and optionally substituted C1-C6 alkyl;
- R4 is OR, where R is an optionally substituted C1-C6 alkyl or a C1-C6 hydroxyalkyl;
- SR, where R is an optionally substituted C1-C6 alkyl;
- XR(R′);
- an optionally substituted phenyl;
- or an optionally substituted five or six membered heteroaryl, wherein X is selected from O, S, or N and R and R′ are independently an optionally substituted C1-C6 alkyl, or XRR′ form together an optionally substituted four to six membered heterocyclic alkyl.
Dependencies are inferred from the claim text.