US 12,466,820 B2
Amino quinazoline derivatives as P2X3 inhibitors
Paolo Bruno, Parma (IT); Matteo Biagetti, Parma (IT); Claudio Fiorelli, Parma (IT); Daniela Pizzirani, Parma (IT); Daniele Pala, Parma (IT); Paolo Ronchi, Parma (IT); Charles Baker-Glenn, Parma (IT); Hervè Van De Poël, Parma (IT); Kim Louise Hirst, Parma (IT); and Sara Guariento, Parma (IT)
Assigned to CHIESI FARMACEUTICI S.P.A., Parma (IT)
Appl. No. 17/615,017
Filed by CHIESI FARMACEUTICI S.p.A., Parma (IT)
PCT Filed May 28, 2020, PCT No. PCT/EP2020/064914
§ 371(c)(1), (2) Date Nov. 29, 2021,
PCT Pub. No. WO2020/239952, PCT Pub. Date Dec. 3, 2020.
Claims priority of application No. 19177604 (EP), filed on May 31, 2019; and application No. 19201168 (EP), filed on Oct. 2, 2019.
Prior Publication US 2022/0227749 A1, Jul. 21, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 417/12 (2006.01); C07D 239/94 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/12 (2006.01); C07D 403/14 (2006.01); C07D 405/14 (2006.01); C07D 409/12 (2006.01); C07D 409/14 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 487/04 (2006.01); C07F 5/02 (2006.01)
CPC C07D 417/12 (2013.01) [C07D 239/94 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/12 (2013.01); C07D 403/14 (2013.01); C07D 405/14 (2013.01); C07D 409/12 (2013.01); C07D 409/14 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 487/04 (2013.01); C07F 5/02 (2013.01)] 9 Claims
 
1. A compound of formula (I)

OG Complex Work Unit Chemistry
wherein
Z is selected from the group consisting of (C3-C8)heterocycloalkyl, (RARB)N, heteroaryl, aryl, wherein any of such alkyl, heteroaryl, heterocycloalkyl and aryl may be optionally substituted by one or more groups selected from (C1-C3)alkyl-, halo, CN, (RARB)NC(O)-, (C1-C6)haloalkyl-, RAO—, (RARB)N(C1-C6)alkylene-, (C3-C7)cycloalkyl-, RCSO2-, (RARB)N-;
R1 is H or (C1-C4)alkyl;
R2 is selected from the group consisting of heteroaryl (C1-C4)alkyl-, (C3-C8)heterocycloalkyl-(C1-C6)alkyl-, heteroaryl-(C1-C6)hydroxyalkyl, (C3-C8)heterocycloalkyl, (C3-C8)cycloalkyl-(C1-C6)alkyl-, aryl-(C1-C4)alkyl-, (RARB)N(C1-C6)alkylene-, (RARB)N(O)C(C1-C4)alkylene-, RAO(C1-C4)alkylene-, wherein any of such alkyl, alkylene, aryl, heteroaryl and heterocycloalkyl may be optionally substituted by one or more groups selected from (C1-C3)alkyl, RAO(C1-C4)alkylene-, (C1-C6)haloalkyl, halo, oxo, RAO-, (C3-C8)heterocycloalkyl-(C1-C6)alkyl-, heteroaryl, (RARB)N—, —NHC(O)RC, —C(O)N(RARB), —SO2N(RARB), —O(C1-C4)alkylene-N(RARB), aryl optionally substituted by halo, —ORC, aryl-(C1-C4)alkyl-, —C(O)RA,
RA and RB are at each occurrence independently H or selected from the group consisting of (C1-C4)alkyl-, (C3-C8)cycloalkyl-, (C1-C6)haloalkyl, or
RA and RB may form together with the nitrogen atom to which they are attached 5- or 6-membered saturated heterocyclic monocyclic ring system optionally further consisting of a heteroatom which is nitrogen or oxygen, which may be optionally substituted by one or more groups selected from (C1-C4)alkyl and oxo;
RC is at each occurrence H or selected from the group consisting of (C1-C6)alkyl, (RARB)N—, aryl-(C1-C4)alkyl-;
Y is selected from the group consisting of —ORD, RCSO2, NHSO2RC, heteroaryl, (C3-C8)heterocycloalkyl, wherein any of such heteroaryl and heterocycloalkyl may be optionally substituted by one or more groups selected from (C1-C3)alkyl, and —C(O)N(RARB);
RD is at each occurrence selected from the group consisting of H, (C1-C6)alkyl, (C3-C8)heterocycloalkyl-(C1-C6)alkyl-, RCOC(O)(C1-C4)alkylene-, (RARB)N(C1-C6)alkylene-, (C3-C8)heterocycloalkyl, (C3-C8)cycloalkyl-(C1-C6)alkyl, RCO(C1-C4)alkylene-, (RARB)N(O)C(C1-C4)alkylene, wherein any of such heterocycloalkyl may be optionally substituted by one or more groups selected from (C1-C3)alkyl-;
J is H or selected from the group consisting of (C1-C6)alkyl, (RARB)N—, (C1-C6)haloalkyl, —ORC and halo.