US 12,312,330 B2
1-((S)-1-(3-chloro-5-fluoro-2-((4-(1h-pyrazol-1-yl)-2-methylquinolin-8-yloxy)methyl)phenyl)ethyl)-imidazolidine-2,4-dione derivatives and related compounds as bradykinin (BK) B2 receptor antagonist for treating skin diseases
Christoph Gibson, Berlin (DE); Joern Saupe, Potsdam (DE); Horst-Dieter Ambrosi, Berlin (DE); and Lars Ole Haustedt, Falkensee (DE)
Assigned to Pharvaris GmbH, Zug (CH)
Appl. No. 17/530,967
Filed by Pharvaris GmbH, Zug (CH)
PCT Filed May 25, 2020, PCT No. PCT/EP2020/064375
§ 371(c)(1), (2) Date Nov. 19, 2021,
PCT Pub. No. WO2020/234479, PCT Pub. Date Nov. 26, 2020.
Claims priority of application No. 19176207 (EP), filed on May 23, 2019.
Prior Publication US 2022/0135542 A1, May 5, 2022
Int. Cl. C07D 401/14 (2006.01); A61K 31/4709 (2006.01); A61K 31/496 (2006.01)
CPC C07D 401/14 (2013.01) [A61K 31/4709 (2013.01); A61K 31/496 (2013.01)] 12 Claims
 
1. A compound of the general formula (I):

OG Complex Work Unit Chemistry
or a salt thereof, wherein
A represents a group:

OG Complex Work Unit Chemistry
A1 is N, or CH;
A2 is N, or C—RA2;
A3 is N, or C—RA3;
A4 is NH, O, or S;
A5 is N—RA5;
RA1 represents a hydrogen atom or a methyl group;
RA2 and RA3 each, independently of one another, represents a hydrogen atom, halogen atom, OH, CN, NH2; (C1-C3) alkyl, which may be substituted by one or more, identical or different, group(s) selected from a halogen atom, OH, ═O, and NH2; (C1-C3) alkoxy, which may be substituted by one or more, identical or different, group(s) selected from a halogen atom, OH, ═O, and NH2; (C2-C5) alkoxyalkyl, which may be substituted by one or more, identical or different, group(s) selected from a halogen atom, OH, ═O, and NH2; C(O)NRA6RA7; or NRA6RA7;
RA5, RA6 and RA7 each, independently of one another, represents a hydrogen atom or a (C1-C3) alkyl group, which may be substituted by one or more, identical or different, group(s) selected from a halogen atom, OH, ═O, and NH2;
R1 represents a (C1-C3) alkyl or (C2-C5) alkoxyalkyl group, which alkyl group or alkoxyalkyl group may be substituted by one or more, identical or different, group(s) selected from a deuterium atom, halogen atom, OH, ═O, and NH2;
R2 represents a hydrogen atom or a deuterium atom;
B represents a 5- or 6-membered nitrogen-containing heterocycloalkyl group having at least one oxo substituent and n substituents R, wherein
n denotes the number 0, 1, 2, 3, 4 or 5; and each R, at each occasion independently, represents a halogen atom, OH, NRC1RC2, ═O, G, OG, or a (C3-C5) cycloalkyl group;
RC1 and RC2 each, independently of one another, represents a hydrogen atom or a (C1-C3) alkyl group;
G represents a (C1-C6) alkyl group, in which 1 to 5 H atoms may, at each occasion independently, be replaced by a halogen atom, ═O, ORG1, or NRG2RG3, and/or in which one CH2 group, or two non-adjacent CH2 groups, may be replaced by O, C(O), OC(O), C(O)O, C(O)NH, NHC(O), NH, S, SO, and/or SO2;
RG1, RG2, and RG3 each, independently of one another, represents a hydrogen atom, (C1-C3) alkyl, (C1-C3) haloalkyl, (C1-C3) hydroxyalkyl, (C1-C3) heteroalkyl, or (C3-C5) cycloalkyl group.