Substituted tetrazolo[1,5-a]pyrazines and tetrazolo[1,5-c]pyrimidines as adenosine receptor antagonists
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12065444-B2
Publication Date
2024-08-20
Expiration Date
Abstract
Provided herein are substituted tetrazolo[1,5-a]pyrazines and tetrazolo[1,5-c]pyrimidines useful for the treatment of diseases and disorders associated with the adenosine receptor, such as cancer. Also provided herein are pharmaceutical compositions, methods of inhibiting the activity of an adenosine receptor, and methods of treating disease and disorders using these compounds.
Core Innovation
The disclosure concerns compounds of Formula (I) and pharmaceutically acceptable salts thereof, including substituted tetrazolo[1,5-a]pyrazine and tetrazolo[1,5-c]pyrimidine compounds. The compounds are defined by substituent patterns for R1 and R2 and additional groups defined by RA and R3 substituents, with m fixed at 2. R1 and R2 are selected from allowed alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclyl options, including cases where R1 and R2, or one of them together with the nitrogen atom, form an (acyloxy)C1-C6 alkyl carbamate or an (oxodioxolenyl)methyl carbamate.
Each RA is independently C5-C7 cycloalkyl, 4- to 7-membered heterocyclyl, phenyl, or 5- to 10-membered heteroaryl, and each such ring is optionally and independently substituted with 1, 2, or 3 independently selected R3 substituents. The R3 substituents are limited to defined groups including halogen, CN, —OR4, —NR4R5, —C(=O)R4A, —C(=O)OR4B, —C(=O)NR4R5, —SR4, —S(=O)R4A, —S(=O)2R4A, —NO2, and related functional variants, together with additional alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, and optional —OH substitution options.
The disclosure presents specific tetrazolo[1,5-a]pyrazin and tetrazolo[1,5-c]pyrimidin derivatives as example structures, including substituted aromatic and heteroaromatic motifs with fluoro, chloro, cyano, methoxy, and methyl groups. The compounds are described in the context of adenosine receptor inhibition, including adenosine receptor antagonists for A1, A2a, and A2b, and in the context of cancer treatment and immune disease/immune-related disorders.
Claims Coverage
The consolidated claim coverage includes one independent compound claim for Formula (I) and one independent pharmaceutical composition claim, with the compound claim containing multiple inventive features centered on a substituted tetrazolo heterocycle scaffold, defined R1/R2 alternatives, a substituted RA/R3 framework, constrained R4/R4A/R4B/R5/R6 variables, and m fixed at 2.
Formula (I) substituted tetrazolo compounds
A compound of Formula (I) or a pharmaceutically acceptable salt thereof, including substituted tetrazolo[1,5-a]pyrazine or tetrazolo[1,5-c]pyrimidine compounds with defined R1 and R2 options and an alternative in which R1 and R2, or one of them together with the nitrogen atom, form an (acyloxy)C1-C6 alkyl carbamate or an (oxodioxolenyl)methyl carbamate, with m fixed at 2.
Defined RA and R3 substitution framework
Each RA is independently C5-C7 cycloalkyl, 4- to 7-membered heterocyclyl, phenyl, or 5- to 10-membered heteroaryl, optionally and independently substituted with 1, 2, or 3 independently selected R3 substituents, where R3 is selected from the enumerated halogen, CN, —OR4, —NR4R5, —C(=O)R4A, —C(=O)OR4B, —C(=O)NR4R5, —SR4, —S(=O)R4A, —S(=O)2R4A, —NO2, and related specified substituent types.
Constrained R4, R4A, R4B, R5, and R6 variables
R4, R4A, R4B, R5, and R6 are each independently selected from the stated classes in Formula (I), and m is fixed at 2.
Pharmaceutical composition with excipient
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the compound of Formula (I), or a pharmaceutically acceptable salt of that compound.
The claim coverage is centered on Formula (I) substituted tetrazolo compounds with defined R1/R2 alternatives, a substituted RA/R3 ring system, constrained R4/R4A/R4B/R5/R6 variables, and m = 2, together with a pharmaceutical composition claim including a pharmaceutically acceptable excipient.
Stated Advantages
Adenosine receptor inhibition is described in the context of cancer treatment and immune disease/immune-related disorders.
Documented Applications
Adenosine receptor antagonists for the adenosine receptors A1, A2a, and A2b.
Methods of inhibiting adenosine receptor activity.
Adenosine receptor inhibition, including treatment of cancer and immune disease/immune-related disorders.
Biological evaluation using adenosine A2a and A2b receptor whole-cell cyclic AMP assays.
Example compound preparation, purification, and characterization, including LCMS and 1H NMR data, are provided.
Interested in licensing this patent?