US 12,391,681 B2
(R)-3-(3-chloro-5-fluoro-2-((4-(1h-pyrazol-1-yl)-2-methylquinolin-8-yloxy)methyl)phenyl)morpholine 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. 17/612,951
Filed by Pharvaris GmbH, Zug (CH)
PCT Filed May 25, 2020, PCT No. PCT/EP2020/064379
§ 371(c)(1), (2) Date Nov. 19, 2021,
PCT Pub. No. WO2020/234480, PCT Pub. Date Nov. 26, 2020.
Claims priority of application No. 19176229 (EP), filed on May 23, 2019.
Prior Publication US 2022/0289730 A1, Sep. 15, 2022
Int. Cl. A61K 45/06 (2006.01); C07D 413/14 (2006.01)
CPC C07D 413/14 (2013.01) [A61K 45/06 (2013.01)] 14 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;
R′ represents a hydrogen atom or a deuterium atom;
B is:

OG Complex Work Unit Chemistry
 G is —C(O)—R1;
R1 represents —CR11R12R13, or a 5-membered heterocyclic ring which may optionally be substituted with one or two RB2;
R11 and R12 each, independently of one another, represents a hydrogen atom or a methyl group;
R13 represents a hydrogen atom, OH or OR2;
R2 represents a (C1-C3) alkyl, (C1-C3) haloalkyl, (C1-C3) hydroxyalkyl, or (C1-C3) heteroalkyl group;
RB2 represents a (C1-C3) alkyl, (C1-C3) haloalkyl, (C1-C3) hydroxyalkyl, or (C1-C3) heteroalkyl group;
R is G;
n is 1.