Back to results
US 2020/0216468 A1Published application
Heterocycle amines and uses thereof
AssigneeLigand Pharmaceuticals Incorporated
InventorsKoc-Kan Ho, David Diller, Jeffrey J. Letourneau, Brian F. McGuinness, Andrew G. Cole, David Rosen, Cornelis A. van Oeveren, Jason C. Pickens, Lin Zhi, Yixing Shen, Bijan Pedram
Life of this patent
Estimating the term…
Abstract
Compounds and methods in the fields of chemistry and medicine are disclosed. Some of the disclosed embodiments include compounds, compositions and methods of using heterocycle amines. Some of the disclosed embodiments include heterocycle amines useful to treat inflammatory disorders.
Claims20
A method of treating a disorder selected from the group consisting of an inflammatory disorder, a skin disorder, a respiratory disorder, diabetes, obesity, allergic disease, cancer, and sepsis, the method comprising administering to a subject in need thereof an effective amount of a compound of Formula (I):
- or a salt thereof, wherein:
- is a single or double bond;
- W is selected from CH, CH—CH, O, S, NR6, and CO;
- Y is N or CR9;
- Z is N or C, and Z is N if W is CH and Y is CR9;
- R4 is selected from hydrogen, halogen, OR6, CN, NR7R8, CH2OR6, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted non-aromatic ring, an optionally substituted carbocycle, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 alkenyl, an optionally substituted C1-C6 alkynyl, CO2R6, SO3R6, SO2R6 and SO2NR7R8;
- R5 is selected from hydrogen, halogen, OR6, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 alkenyl, and an optionally substituted C1-C6 alkynyl;
- or R4 and R5 are linked to form an optionally substituted non-aromatic ring;
- each R6 is independently selected from an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted non-aromatic ring, each optionally fused with a substituted aryl or a substituted heteroaryl, hydrogen, an optionally substituted C1-C10 alkyl, and an optionally substituted C1-C10 haloalkyl,
- each R7 and R8 is independently selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted non-aromatic ring, each optionally fused with a substituted aryl or a substituted heteroaryl, hydrogen, an optionally substituted C1-C10 alkyl, an optionally substituted C1-C10 haloalkyl, an optionally substituted C1-C10 alkenyl, and an optionally substituted C1-C10 alkynyl, or R7 and R8 are linked to form an optionally substituted non-aromatic ring;
- R9 is selected from hydrogen, halogen, OR6, CN, NR7R8, CH2OR6, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted non-aromatic ring, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 alkenyl, an optionally substituted C1-C6 alkynyl, CO2R6, SO3R6, and SO2NR7R8;
- A is an optionally substituted aryl or an optionally substituted heteroaryl group;
- and
- each optionally substituted group is either unsubstituted or substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, haloalkyl, heterohaloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic ring, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, ═O, ═S, amino, and protected derivatives of amino groups.
11 more elements
A method for preparing a compound having a structure of Formula (IV):
- or a salt thereof,
- wherein:
- X is N;
- R1 is selected from hydrogen, halogen, OR6, CN, NR7R8, CH2OR6, CH2NR7R8, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 alkenyl, an optionally substituted C1-C6 alkynyl, CO2R6, CONR7R8, SO3R6, and SO2NR7R8;
- R2 and R3 are hydrogen;
- R4 is selected from hydrogen, halogen, OR6, CN, NR7R8, CH2OR6, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted non-aromatic ring, an optionally substituted carbocycle, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 alkenyl, an optionally substituted C1-C6 alkynyl, CO2R6, SO3R6, SO2R6 and SO2NR7R8;
- R5 is hydrogen;
- each R6 is independently selected from an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted non-aromatic ring, each optionally fused with a substituted aryl or a substituted heteroaryl, hydrogen, an optionally substituted C1-C10 alkyl, an optionally substituted C1-C10 haloalkyl;
- and
- each R7 and R8 is independently selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted non-aromatic ring, each optionally fused with a substituted aryl or a substituted heteroaryl, hydrogen, an optionally substituted C1-C10 alkyl, an optionally substituted C1-C10 haloalkyl, an optionally substituted C1-C10 alkenyl, an optionally substituted C1-C10 alkynyl, or R7 and R8 are linked to form an optionally substituted non-aromatic ring;
- the method comprising:
- coupling a 2-halopyridine with an aminoimidazopyridine in the presence of a base and a catalyst, wherein the 2-halopyridine has the structure:
- and
- the aminoimidazopyridine has the structure:
11 more elements
A method for preparing a compound having the structure:
- or a salt thereof,
- wherein:
- R1 is selected from hydrogen, halogen, OR6, CN, NR7R8, CH2OR6, CH2NR7R8, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 alkenyl, an optionally substituted C1-C6 alkynyl, CO2R6, CONR7R8, SO3R6, and SO2NR7R8;
- and
- R4 is selected from hydrogen, halogen, OR6, CN, NR7R8, CH2OR6, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted non-aromatic ring, an optionally substituted carbocycle, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 alkenyl, an optionally substituted C1-C6 alkynyl, CO2R6, SO3R6, SO2R6 and SO2NR7R8;
- each R6 is independently selected from an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted non-aromatic ring, each optionally fused with a substituted aryl or a substituted heteroaryl, hydrogen, an optionally substituted C1-C10 alkyl, an optionally substituted C1-C10 haloalkyl;
- and
- each R7 and R8 is independently selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted non-aromatic ring, each optionally fused with a substituted aryl or a substituted heteroaryl, hydrogen, an optionally substituted C1-C10 alkyl, an optionally substituted C1-C10 haloalkyl, an optionally substituted C1-C10 alkenyl, an optionally substituted C1-C10 alkynyl, or R7 and R8 are linked to form an optionally substituted non-aromatic ring;
- the method comprising:
- (1) coupling a bromo-benzothiazole with R4—B(OH)2 in the presence of a catalyst and a base, wherein the bromo-benzothiazole has the structure:
- wherein R is R1;
- or
- (2) oxidatively cyclizing a thiourea, wherein the thiourea has the structure:
10 more elements
Dependencies are inferred from the claim text.