US 12,331,034 B2
Substituted pyrrolidine amides V
Florian Jakob, Aachen (DE); Jo Alen, Averbode (BE); Sebastian Krueger, Aachen (DE); Philipp Barbie, Berlin (DE); and Daniela Friebe, Duesseldorf (DE)
Assigned to Gruenenthal GmbH, Aachen (DE)
Filed by GRUENENTHAL GMBH, Aachen (DE)
Filed on Dec. 17, 2021, as Appl. No. 17/554,729.
Application 17/554,729 is a continuation of application No. PCT/EP2020/067063, filed on Jun. 19, 2020.
Claims priority of application No. 19181198 (EP), filed on Jun. 19, 2019.
Prior Publication US 2022/0106294 A1, Apr. 7, 2022
Int. Cl. C07D 401/14 (2006.01); C07D 401/04 (2006.01); C07D 403/04 (2006.01); C07D 403/14 (2006.01); C07D 405/04 (2006.01); C07D 405/14 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 401/04 (2013.01); C07D 403/04 (2013.01); C07D 403/14 (2013.01); C07D 405/04 (2013.01); C07D 405/14 (2013.01)] 12 Claims
 
1. A compound according to general formula (I),

OG Complex Work Unit Chemistry
wherein
R1 represents —C1-10-alkyl; —C3-10-cycloalkyl; —C1-6-alkylene-C3-10-cycloalkyl; 3 to 7 membered heterocycloalkyl; —C1-6-alkylene-(3 to 7 membered heterocycloalkyl); aryl; —C1-6-alkylene-aryl; 5 or 6-membered heteroaryl; or —C1-6-alkylene-(5 or 6-membered heteroaryl);
represents H; —C1-10-alkyl; or —C3-10-cycloalkyl;
or R1 and R1′ together with the carbon atom to which they are bound form a C3-10-cycloalkyl; or 3 to 7 membered heterocycloalkyl;
R2 represents aryl; 5 or 6-membered heteroaryl; —C(═O)—C1-10-alkyl; —C(═O)—O—C1-10-alkyl; —C(═O)—C3-10-cycloalkyl; —C(═O)—C1-6-alkylene-C3-10-cycloalkyl; —C(═O)—O—C3-10-cycloalkyl; —C(═O)-(3 to 7 membered heterocycloalkyl); —C(═O)—C1-6-alkylene-(3 to 7 membered heterocycloalkyl); —C(═O)—O-(3 to 7 membered heterocycloalkyl); —C(═O)-aryl; —C(═O)—C1-6-alkylene-aryl; —C(═O)—O-aryl; —C(═O)-(5 or 6-membered heteroaryl); —C(═O)—C1-6-alkylene-(5 or 6-membered heteroaryl); —C(═O)—O-(5 or 6-membered heteroaryl); —S(═O)1-2—C1-10-alkyl; —S(═O)1-2—C3-10-cycloalkyl; —S(—O)1-2—C1-6-alkylene-C3-10-cycloalkyl; —S(═O)1-2-(3 to 7 membered heterocycloalkyl); —S(═O)1-2—C1-6-alkylene-(3 to 7 membered heterocycloalkyl); —S(═O)1-2-aryl; —S(═O)1-2—C1-6-alkylene-aryl; —S(═O)1-2-(5 or 6-membered heteroaryl); or —S(═O)1-2—C1-6-alkylene-(5 or 6-membered heteroaryl);
R2′ represents H;
R3 and R3′ independently from one another represent H; F; Cl; —C1-10-alkyl; —C3-6-cycloalkyl; —C1-6-alkylene-C3-6-cycloalkyl; 3 to 7 membered heterocycloalkyl; —C1-6-alkylene-(3 to 7 membered heterocycloalkyl); —C1-6-alkylene-aryl; or —C1-6-alkylene-(5 or 6-membered heteroaryl);
or R3 and R3′ together with the carbon atom to which they are bound form a C3-10-cycloalkyl; or 3 to 7 membered heterocycloalkyl;
R4 and R4′ independently from one another represent H; F; Cl; —C1-10-alkyl; —C3-6-cycloalkyl; —C1-6-alkylene-C3-6-cycloalkyl; 3 to 7 membered heterocycloalkyl; —C1-6-alkylene-(3 to 7 membered heterocycloalkyl); —C1-6-alkylene-aryl; or —C1-6-alkylene-(5 or 6-membered heteroaryl);
L represents bond or —C1-6-alkylene-;
A represents indolyl; indazolyl; benzisoxazolyl; benzisothiazolyl; benzotriazolyl; imidazopyridinyl; or benzoimidazolyl; in each case unsubstituted or mono- or disubstituted with R5;
R5 represents H; F; Cl; —C1-10-alkyl; —C1-10-alkenyl; —C1-10-alkynyl; —C3-6-cycloalkyl; —C1-6-alkylene-C3-6-cycloalkyl; 3 to 7 membered heterocycloalkyl; —C1-6-alkylene-(3 to 7 membered heterocycloalkyl); aryl; —C1-6-alkylene-aryl; 5 or 6-membered heteroaryl; —C1-6-alkylene-(5 or 6-membered heteroaryl); —C(═O)—C1-10-alkyl; —C(═O)—C3-10-cycloalkyl; —C(═O)-(3 to 7 membered heterocycloalkyl); —O—C1-10-alkyl; —O—C3-6-cycloalkyl; —O-(3 to 7 membered heterocycloalkyl); —O-aryl; —O-(5 or 6-membered heteroaryl); —S(═O)1-2—C1-10-alkyl; —S(═O)1-2—C3-10-cycloalkyl; —S(═O)1-2-(3 to 7 membered heterocycloalkyl); —S(═O)1-2-aryl; or —S(═O)1-2-(5 or 6-membered heteroaryl);
wherein —C1-10-alkyl, —C1-4-alkyl and —C1-6-alkylene- in each case independently from one another is linear or branched, saturated or unsaturated;
wherein —C1-10-alkyl, —C1-4-alkyl, —C1-6-alkylene-, —C3-10-cycloalkyl and 3 to 7 membered heterocycloalkyl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from —F; —Cl; —Br; —I; —CN; —C1-6-alkyl; —CF3; —CF2H; —CFH2; —CF2Cl; —CFCl2; —C(═O)—C1-6-alkyl; —C(═O)—OH; —C(═O)—O—C1-6-alkyl; —C(═O)—NH2; —C(═O)—NH(C1-6-alkyl); —C(═O)—N(C1-6-alkyl)2; —OH; ═O; —OCF3; —OCF2H; —OCFH2; —OCF2Cl; —OCFCl2; —OC1-6-alkyl; —O—C(═O)—C1-6-alkyl; —O—C(═O)—O—C1-6-alkyl; —O—(CO)—NH(C1-6-alkyl); —O—C(═O)—N(C1-6-alkyl)2; —O—S(═O)2—NH2; —O—S(═O)2—NH(C1-6-alkyl); —O—S(═O)2—N(C1-6-allcyl)2; —NH2; —NH(C1-6-alkyl); —N(C1-6-alkyl)2; —NH—C(═O)—C1-6-alkyl; —NH—C(═O)—O—C1-6-alkyl; —NH—C(═O)—NH2; —NH—C(═O)—NH(C1-6-alkyl); —NH—C(═O)—N(C1-6-alkyl)2; —N(C1-6-alkyl)-C(═O)—C1-6-alkyl; —N(C1-6-alkyl)-C(═O)—O—C1-6-alkyl; —N(C1-6-alkyl)-C(═O)—NH2; —N(C1-6-alkyl)-C(═O)—NH(C1-6-alkyl); —N(C1-6-alkyl)-C(═O)—N(C1-6-alkyl)2; —NH—S(═O)2OH; NH—S(═O)2—C1-6-alkyl; —NH—S(═O)2—O—C1-6-alkyl; —NH—S(═O)2—NH2; —NH—S(═O)2—NH(C1- 6-alkyl); —NH—S(═O)2N(C1-6-alkyl)2; —N(C1-6-alkyl)-S(═O)2—OH; —N(C1-6-alkyl)-S(═O)2—C1-6-alkyl; —N(C1-6-alkyl)-S(═O)2—O—C1-6-alkyl; —N(C1-6-alkyl)-S(═O)2—NH2; —N(C1-6-alkyl)-S(═O)2—NH(C1-6-alkyl); —(C1-6-alkyl)-S(═O)2—N(C1-6-alkyl)2; —SCF3; —SCF2H; —SCFH2; —S—C1-6-alkyl; —S(═O)—C1-6-alkyl; —S(═O)2—C1-6-alkyl; —S(═O)2—OH; —S(═O)2—O—C1-6-alkyl; —S(═O)2—NH2; —S(═O)2—NH(C1-6-alkyl); —S(═O)2—N(C1-6-alkyl)2; —C3-6-cycloalkyl; 3 to 6-membered heterocycloalkyl; phenyl; 5 or 6-membered heteroaryl; —O—C3-6-cycloalkyl; —O-(3 to 6-membered heterocycloalkyl); —O-phenyl; —O-(5 or 6-membered heteroaryl); —C(═O)—C3-6-cycloalkyl; —C(═O)-(3 to 6-membered heterocycloalkyl); —C(═O)-phenyl; —C(═O)-(5 or 6-membered heteroaryl); —S(═O)2—(C3-6-cycloalkyl); —S(═O)2-(3 to 6-membered heterocycloalkyl); —S(═O)2-phenyl or —S(═O)2-(5 or 6-membered heteroaryl);
wherein aryl and 5 or 6-membered heteroaryl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from —F; —Cl; —Br; —I; —CN; —C1-6-alkyl; —CF3; —CF2H; —CFH2; —CF2Cl; —CFCl2; —C1-4-alkylene-CF3; —C1-4-alkylene-CF2H; —C1-4-alkylene-CFH2; —C(═O)—C1-6-alkyl; —C(═O)—OH; —C(═O)—OC1-6-alkyl; —C(═O)—NH(OH); —C(═O)—NH2; —C(═O)—NH(C1-6-alkyl); —C(═O)—N(C1-6-alkyl)2; —OH; ═O; —OCF3; —OCF2H; —OCFH2; —OCF2Cl; —OCFCl2; —OC1-6-alkyl; —O—C3-6-cycloalkyl; —O-(3 to 6-membered heterocycloalkyl); —O-aryl; —O-(5 or 6-membered heteroaryl); —NH2; —NH(C1-6-alkyl); —N(C1-6-alkyl)2; —NH—C(═O)—C1-6-alkyl; —N(C1-6-alkyl)-C(═O)—C1-6-alkyl; —NH—C(═O)—NH2; —NH—C(═O)—NH(C1-6-alkyl); —NH—C(═O)—N(C1-6-alkyl)2; —N(C1-6-alkyl)-C(═O)—NH(C1-6-alkyl); —N(C1-6-alkyl)-C(═O)—N(C1-6-alkyl)2; —NH—S(═O)2—C1-6-alkyl; —SCF3; —S—C1-6-alkyl; —S(═O)—C1-6-alkyl; —S(═O)2—C1-6-alkyl; —S(═O)2—NH2; —S(═O)2—NH(C1-6-alkyl); —S(═O)2—N(C3-6-alkyl)2; —C3-6-cycloalkyl; —C1-4-alkylene-C3-6-cycloalkyl; —C1-4-alkylene-(3 to 6-membered heterocycloalkyl); or phenyl;
in the form of the free compound or a physiologically acceptable salt thereof.