US 12,465,603 B2
Phthalazinone based modulators for the treatment of disease
Nadia Mamoona Ahmad, Essex (GB); Christopher Charles Rennie, Essex (GB); William Rameshchandra Krishna Esmieu, Saffron Walden (GB); Mark Chambers, Saffron Walden (GB); Toby Jonathan Blench, Essex (GB); Susan Mary Cramp, Essex (GB); Toby Matthew Grover Mullins, Essex (GB); Terry Aaron Panchal, Essex (GB); and Joseph Leo Mckenna, Essex (GB)
Assigned to SOLEY THERAPEUTICS, INC., South San Francisco, CA (US)
Filed by Soley Therapeutics, Inc., South San Francisco, CA (US)
Filed on Jul. 11, 2024, as Appl. No. 18/770,015.
Application 18/770,015 is a continuation of application No. PCT/US2023/080304, filed on Nov. 17, 2023.
Claims priority of provisional application 63/426,670, filed on Nov. 18, 2022.
Prior Publication US 2024/0374589 A1, Nov. 14, 2024
Int. Cl. C07D 237/32 (2006.01); A61K 31/502 (2006.01); A61K 31/5025 (2006.01); A61K 31/506 (2006.01); C07D 401/06 (2006.01); C07D 401/12 (2006.01); C07D 403/12 (2006.01); C07D 405/04 (2006.01); C07D 413/12 (2006.01); C07D 471/04 (2006.01)
CPC A61K 31/5025 (2013.01) [A61K 31/502 (2013.01); A61K 31/506 (2013.01); C07D 237/32 (2013.01); C07D 401/06 (2013.01); C07D 401/12 (2013.01); C07D 403/12 (2013.01); C07D 405/04 (2013.01); C07D 413/12 (2013.01); C07D 471/04 (2013.01)] 10 Claims
 
1. A compound represented by the structure of Formula (II):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof wherein:
X1 is N;
R4 is independently selected at each occurrence from (a), (b), and (c):
(a) halogen, —OR20, —SR20, —N(R20)2, —C(O)R20, —C(O)OR20, —OC(O)R20, —OC(O)N(R20)2, —C(O)N(R20)2, —N(R20)C(O)R20, —N(R20)C(O)OR20, —N(R20)C(O)N(R20)2, —N(R20)S(O)2(R20), —S(O)R20, —S(O)2R20, —S(O)2N(R20)2, —NO2, and —CN;
(b) C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR20, —SR20, —N(R20)2, —C(O)R20, —C(O)OR20, —OC(O)R20, —OC(O)N(R20)2, —C(O)N(R20)2, —N(R20)C(O)R20, —N(R20)C(O)OR20, —N(R20)C(O)N(R20)2, —N(R20)S(O)2(R20), —S(O)R20, —S(O)2R20, —S(O)2N(R20)2, —NO2, ═S, ═O, and —CN; and
(c) C3-10 carbocycle and 3- to 10-membered heterocycle, any of which is optionally substituted with one or more substituents independently selected from halogen, —OR20, —SR20, —N(R20)2, —C(O)R20, —C(O)OR20, —OC(O)R20, —OC(O)N(R20)2, —C(O)N(R20)2, —N(R20)C(O)R20, —N(R20)C(O)OR20, —N(R20)C(O)N(R20)2, —N(R20)S(O)2(R20), —S(O)R20, —S(O)2R20, —S(O)2N(R20)2, —NO2, ═S, ═O, and —CN;
R5 is C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, —OR21, —SR21, —N(R21)2, —C(O)R21, —C(O)OR21, —OC(O)R21, —OC(O)N(R21)2, —C(O)N(R21)2, —N(R21)C(O)R21, —N(R21)C(O)OR21, —N(R21)C(O)N(R21)2, —N(R21)S(O)2(R21), —S(O)R21, —S(O)2R21, —S(O)2N(R21)2, —NO2, ═S, ═O, and —CN;
R6 is independently selected at each occurrence from:
C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR22, —SR22, —N(R22)2, —C(O)R22,—C(O)OR22, —OC(O)R22, —OC(O)N(R22)2, —C(O)N(R22)2, —N(R22)C(O)R22, —N(R22)C(O)OR22, —N(R22)C(O)N(R22)2, —N(R22)S(O)2(R22), —S(O)R22, —S(O)2R22, —S(O)2N(R22)2, —NO2, ═S, ═O, and —CN;
Ring B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle;
R7 is independently selected at each occurrence from:
halogen, —OR23, —SR23, —N(R23)2, —C(O)R23, —OC(O)R23, —OC(O)N(R23)2, —C(O)N(R23)2, —N(R23)C(O)R23, —N(R23)C(O)OR23, —N(R23)C(O)N(R23)2, —N(R23)S(O)2(R23), —S(O)R23, —S(O)2R23, —S(O)2N(R23)2, —NO2, and —CN; and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR23, —SR23, —N(R23)2, —C(O)R23, —C(O)OR23, —OC(O)R23, —OC(O)N(R23)2, —C(O)N(R23)2, —N(R23)C(O)R23, —N(R23)C(O)OR23, —N(R23)C(O)N(R23)2, —N(R23)S(O)2(R23), —S(O)R23, —S(O)2R23, —S(O)2N(R23)2, —NO2, ═S, ═O, and —CN;
R20, R21, R22, and R23, are each independently selected at each occurrence from (d), (e), and (f):
(d) hydrogen;
(e) C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —O—C1-6 alkyl, —O—C1-6 haloalkyl, —NH2, —NO2, ═O, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituents independently selected from: halogen, —OH, —O—C1-6 alkyl, —O—C1-6 haloalkyl, —NH2, —NO2, ═O, and —CN; and
(f) C3-10 carbocycle and 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, —OH, —O—C1-6 alkyl, —O—C1-6 haloalkyl, —NH2, —NO2, ═O, and —CN;
x is selected from 0, 1, 2, 3, and 4;
y is selected from 0, 1, 2, 3, and 4; and
z is selected from 0, 1, 2, 3, 4 and 5; wherein
at least one of x or y is selected from 1, 2, 3, and 4.