US 12,479,837 B2
Reversible DPP1 inhibitors and uses thereof
Adam J. Plaunt, Bridgewater, NJ (US); Adrien Cerdan, Strasbourg (FR); Paola Ciapetti, Strasbourg (FR); and Bastien Goegan, Strasbourg (FR)
Assigned to Insmed Incorporated, Bridgewater, NJ (US)
Filed by Insmed Incorporated, Bridgewater, NJ (US)
Filed on Mar. 24, 2025, as Appl. No. 19/088,795.
Application 19/088,795 is a continuation of application No. PCT/US2024/010555, filed on Jan. 5, 2024.
Claims priority of provisional application 63/485,243, filed on Feb. 15, 2023.
Claims priority of provisional application 63/437,557, filed on Jan. 6, 2023.
Prior Publication US 2025/0223284 A1, Jul. 10, 2025
Int. Cl. C07D 413/12 (2006.01); C07D 267/22 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 491/107 (2006.01); C07D 498/10 (2006.01)
CPC C07D 413/12 (2013.01) [C07D 267/22 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 491/107 (2013.01); C07D 498/10 (2013.01)] 41 Claims
 
1. A compound of formula (I)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or deuterated form thereof,
wherein:
R0 is

OG Complex Work Unit Chemistry
X1 and X2 are independently O, S, NH, N(C1-6 alkyl), or CR12R13, wherein at least one of X1 and X2 are not CR12R13;
L is aryl, heterocyclyl, heteroaryl, or

OG Complex Work Unit Chemistry
wherein L is independently substituted by 0-4 R10 and wherein ring B is a carbocycle, or a heterocycle;
R1 is

OG Complex Work Unit Chemistry
R2 is H, F, Cl, Br, OSO2C1-6 alkyl, or C1-6 alkyl;
R3 is H, F, Cl, Br, CN, C1-6haloalkyl, SO2C1-6 alkyl, CONH2, or SO2NR4R5, wherein R4 and R5 together with the nitrogen atom to which they are attached form a heterocyclyl;
X is O, S, CHF, or CF2;
Y is O, S, or CH2;
Q is CH or N;
R6 is C1-6 alkyl optionally substituted by 1, 2 or 3 F, or optionally substituted by OH, OC1-6 alkyl, N(C1-6 alkyl)2, N(C1-6 alkyl)(C1-6alkylene-O—C1-6 alkyl), cycloalkyl, or heterocyclyl;
R7 is H, F, Cl, Br, or C1-6 alkyl;
each R8 and R12 are independently H, OH, halogen, NH2, COOH, C1-6 alkyl, C1-6 alkyl-OH, C2-6alkenyl, C1-6alkoxy, O-cycloalkyl, cycloalkyl, C1-6alkylene-carbocyclyl, C1-6alkylene-heteroaryl, halogenated C1-6 alkyl, halogenated C1-6alkoxy, heteroaryl, or carbocyclyl;
each R13 is independently H, F, Cl, Br, I, or C1-C6 alkyl;
each R10 is independently oxo, halogen, C1-6 alkyl, C1-6alkoxy, S-C1-6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, cyano, hydroxy, NH2, —NH—C1-6 alkyl, N(C1-6 alkyl)2, COOH, COC1-6 alkyl, COOC1-6 alkyl, CON1-6 alkyl, CON(C1-6 alkyl)2, NHCOC1-6 alkyl, or heterocycle; wherein each alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, and heterocycle are independently optionally substituted with 1-3 substituents selected from halogen, cyano, hydroxy, NH2, and COOH;
W, X4, and Y2 are each independently CH or N, provided that a maximum of one of W, X4, and Y2 can be N;
D-E is N(H)—C(O), N(C1-6 alkyl)-C(O), CH2CH2, C(O)—O, or CH2—O;
R11 is H, C1-6 alkyl, alkylene-O-alkyl, or heterocyclyl; and
i and j are each independently 1, 2 or 3, provided that the sum of i+j is 2, 3, or 4.