US 12,404,270 B2
Quinazoline derivatives as LPA receptor 2 inhibitors
Gabriele Amari, Parma (IT); Elisabetta Armani, Parma (IT); Mafalda Pagano, Parma (IT); Luca Raveglia, Parma (IT); Marta Giuliani, Parma (IT); and Claudia Beato, Parma (IT)
Assigned to Chiesi Farmaceutici S.p.A., Parma (IT)
Appl. No. 17/784,557
Filed by CHIESI FARMACEUTICI S.P.A., Parma (IT)
PCT Filed Dec. 10, 2020, PCT No. PCT/EP2020/085460
§ 371(c)(1), (2) Date Jun. 10, 2022,
PCT Pub. No. WO2021/116260, PCT Pub. Date Jun. 17, 2021.
Claims priority of application No. 19215719 (EP), filed on Dec. 12, 2019.
Prior Publication US 2023/0063121 A1, Mar. 2, 2023
Int. Cl. C07D 417/12 (2006.01); C07D 239/94 (2006.01); C07D 409/12 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01)
CPC C07D 417/12 (2013.01) [C07D 239/94 (2013.01); C07D 409/12 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01)] 16 Claims
 
1. A compound of formula (I)

OG Complex Work Unit Chemistry
wherein
R is selected from the group consisting of H, (C1-C4)alkyl, halo, (C1-C4)haloalkyl, —NO2, —C(O)OR1, —OR1, —O(C1-C4)haloalkyl, —NRARB, —OC(O)NRARB, —C(O)RC, —C(O)NRARB, and —(C1-C4)alkylene-NRARB;
R1 is H or (C1-C4)alkyl;
R2 is selected from the group consisting of H, (C1-C4)alkyl, (C1-C4)haloalkyl, —(C1-C4)alkylene-OR1 and (C3-C8)cycloalkyl;
R3 is selected from the group consisting of H and (C1-C4)alkyl;
A is selected from the group consisting of 5-6 membered heteroaryl and aryl wherein each of said heteroaryl and aryl is optionally substituted by one or more groups selected from (C1-C4)alkyl, —C(O)R1, —C(O)OR1, —C(O)R1, (C1-C4)haloalkyl, halo, —NRAC(O)R1, —NRAC(O)OR1, —NRAC(O)—(C1-C4)alkylene-OR1, —NRAC(O)RC, —NRAC(O) NRARB, —N(C1-C4)alkylene-NRARB, aryl and heteroaryl optionally substituted by one or more (C1-C4)alkyl and (C1-C4)haloalkyl, or
when A is aryl it is optionally fused to a second saturated or unsaturated ring optionally containing one or more heteroatoms selected from N, O and S to form a bicyclic ring system optionally substituted by one or more groups selected from —C(O)R1, (C1-C4)alkyl and oxo;
RC is selected from the group consisting of from heteroaryl, aryl, (C3-C8)cycloalkyl and (C4-C8)heterocycloalkyl wherein said heteroaryl, aryl, heterocycloalkyl and cycloalkyl is optionally substituted by one or more (C1-C4)alkyl and —C(O)OR1;
RA and RB are at each occurrence independently selected from the group consisting of H, (C1-C4)alkyl, (C3-C8)cycloalkyl, (C1-C6)haloalkyl and halo, or
RA and RB may form together with the nitrogen atom to which they are attached a 4-6 membered saturated heterocyclic ring system optionally containing a further heteroatom selected from N, S and O, wherein said heterocyclic ring system is optionally substituted by one or more groups selected from (C1-C4)alkyl, (C1-C4)haloalkyl and halo, with the proviso that when R2 is H, R is not H.