US 12,145,942 B2
Spiropyrrolidine derived antiviral agents
Hui Cao, Belmont, MA (US); Jiajun Zhang, Cambridge, MA (US); Xuechao Xing, Wilmington, MA (US); Matthew C. Rhodes, Boston, MA (US); Xuri Gao, Newtonville, MA (US); Wei Li, Lexington, MA (US); and Yat Sun Or, Waltham, MA (US)
Assigned to Enanta Pharmaceuticals, Inc., Watertown, MA (US)
Filed by ENANTA PHARMACEUTICALS, INC., Watertown, MA (US)
Filed on Apr. 4, 2023, as Appl. No. 18/130,641.
Claims priority of provisional application 63/327,486, filed on Apr. 5, 2022.
Prior Publication US 2023/0331734 A1, Oct. 19, 2023
Int. Cl. C07D 487/10 (2006.01)
CPC C07D 487/10 (2013.01) 13 Claims
 
1. A compound represented by Formula (I), or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein:
R1, R2, R3, R5, R21, R22, and R23 are each independently selected from:
1) Hydrogen;
2) Optionally substituted —C1-C8 alkyl;
3) Optionally substituted —C2-C8 alkenyl;
4) Optionally substituted —C2-C8 alkynyl;
5) Optionally substituted —C3-C8 cycloalkyl;
6) Optionally substituted 3to 8-membered heterocycloalkyl;
7) Optionally substituted aryl;
8) Optionally substituted arylalkyl;
9) Optionally substituted heteroaryl; and
10) Optionally substituted heteroarylalkyl;
alternatively, R1 and R2 are taken together with the carbon atom to which they are attached to form an optionally substituted 3- to 8-membered carbocyclic ring or an optionally substituted 3- to 8-membered heterocyclic ring;
alternatively, R3 and R5 are taken together with the carbon atom to which they are attached to form an optionally substituted 3- to 8-membered carbocyclic ring or an optionally substituted 3- to 8-membered heterocyclic ring;
alternatively, Rand R3 are taken together with the atoms to which they are attached to form an optionally substituted 3- to 8-membered carbocyclic or heterocyclic ring;
alternatively, R21 and R3 are taken together with the intervening atoms to form an optionally substituted 4- to 8-membered carbocyclic or heterocyclic ring;
alternatively, R22 is absent and R21 and R3 are taken together with the intervening atoms to form an optionally substituted 4- to 8-membered partially unsaturated carbocyclic ring or optionally substituted 4- to 8-membered partially unsaturated heterocyclic ring;
alternatively, R5 is absent and R21 and R3 are taken together with the intervening atoms to form an optionally substituted 4- to 8-membered partially unsaturated carbocyclic ring or optionally substituted 4- to 8-membered partially unsaturated heterocyclic ring;
alternatively, R21 and R22 are taken together with the carbon atom to which they are attached to form an optionally substituted 3- to 8-membered carbocyclic ring or an optionally substituted 3- to 8-membered heterocyclic ring;
R24 is selected from:
1) —C(O)R25;
2) —C(O)OR25;
3) —C(O)NR13R14;
4) —S(O)2R25;
5) Hydrogen;
6) Optionally substituted —C1-C8 alkyl;
7) Optionally substituted —C2-C8 alkenyl;
8) Optionally substituted —C2-C8 alkynyl;
9) Optionally substituted —C3-C12 cycloalkyl;
10) Optionally substituted 3- to 12-membered heterocycloalkyl;
11) Optionally substituted aryl;
12) Optionally substituted arylalkyl;
13) Optionally substituted heteroaryl;
14) Optionally substituted heteroarylalkyl;
15) —(CO)(CO)NR13R14;
16) —(CO)(CO)R25;
17) —S(O)2NR13R14;
18) —C(S)R25; and
19) —C(S)NR13R14;
alternatively, R23 and R24 are taken together with the nitrogen atom to which they are attached to form an optionally substituted 3- to 12-membered heterocyclic ring, or an optionally substituted 5- to 12-membered heteroaryl ring;
alternatively, R21 and R24 are taken together with the intervening atoms to form an optionally substituted 4- to 8-membered heterocyclic ring;
R25 is selected from:
1) Optionally substituted —C1-C8 alkyl;
2) Optionally substituted —C2-C8 alkenyl;
3) Optionally substituted —C2-C8 alkynyl;
4) Optionally substituted —C3-C12 cycloalkyl;
5) Optionally substituted 3- to 12-membered heterocycloalkyl;
6) Optionally substituted aryl;
7) Optionally substituted arylalkyl;
8) Optionally substituted heteroaryl; and
9) Optionally substituted heteroarylalkyl;
R4 is hydrogen, optionally substituted —C1-C4 alkyl, optionally substituted —C2-C4 alkenyl, optionally substituted —C3-C6 cycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, halogen, —CN, —OH, or a prodrug moiety;
B is an optionally substituted aryl or optionally substituted heteroaryl;
X is selected from:
1) —CN;
2) —C(O)R15;
3) —CH(OH)SO3R16;
4) —C(O)NR13R14;
5) —C(O)C(O)NR13R14;
6) —CH═CH—C(O)OR25,
7) —CH═CH—C(O)NR13R14,
8) —CH—CH—S(O)2NR13R14,
9) —B(OR13)2;
10) —C═CR13;
11) —C═C—C(O)OR25;
12) —C═C—C(O)NR13R14;
13) —C═C—S(O)2NR13R14;
14) —(CR13R14)w—CN; and
15) —(CR13R14)w—(C═O)—R25;
w is 1, 2, 3, 4, or 5;
R13 and R14 are each independently selected from:
1) Hydrogen;
2) Optionally substituted —C1-C8 alkyl;
3) Optionally substituted —C2-C8 alkenyl;
4) Optionally substituted —C2-C8 alkynyl;
5) Optionally substituted —C3-C12 cycloalkyl;
6) Optionally substituted 3- to 12-membered heterocycloalkyl;
7) Optionally substituted aryl;
8) Optionally substituted arylalkyl;
9) Optionally substituted heteroaryl; and
10) Optionally substituted heteroarylalkyl;
Alternatively, R13 and R14 are taken together with the nitrogen atom to which they are attached to form an optionally substituted 3- to 8-membered heterocyclic ring;
R15 is hydrogen, hydroxy, optionally substituted —C1-C8 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl; and
R16 is hydrogen or Na+.