Submission Details
Molecule(s):
Cc1ccncc1C(NC(=O)CC1CC1)C(=O)NCc1cccc(C#N)c1
CCNC(=O)NC(C(=O)Nc1cccc(C#N)c1)c1cnccc1C
Cc1ccncc1C(NC(=O)NC1CC1)C(=O)Nc1cccc(C#N)c1
Cc1ccncc1C(NS(C)(=O)=O)C(=O)Nc1cccc(C#N)c1
Cc1ccncc1C(NS(=O)(=O)CC1CC1)C(=O)Nc1cccc(C#N)c1
Cc1ccncc1C(NC(=O)NCCCN(C)C)C(=O)Nc1cccc(C#N)c1
Cc1ccncc1C(NC(=O)NCCCC(=N)N)C(=O)Nc1cccc(C#N)c1
Cc1ccncc1C(NC(=O)NCCNC(=N)N)C(=O)Nc1cccc(C#N)c1
Cc1ccncc1C(NC(=O)NCCCC(C)(C)O)C(=O)Nc1cccc(C#N)c1
Cc1ccncc1C(NC(=O)CCCCN(C)C)C(=O)Nc1cccc(C#N)c1
Cc1ccncc1C(NC(=O)CCCCC(=N)N)C(=O)Nc1cccc(C#N)c1
Cc1ccncc1C(NC(=O)CCCCC(C)(C)O)C(=O)Nc1cccc(C#N)c1
Cc1ccncc1C(NC(=O)CC1CC1)C(=O)Nc1cccc(C#N)c1
Cc1ccncc1C(NC(=O)CCCNC(=N)N)C(=O)Nc1cccc(C#N)c1
Design Rationale:
Attempt to build upon x2572 by engaging Gly143 and Cys145 like in x0397. Additional amine/amidine/guanidine/alcohol pendant is intended to fit in pocket filled by terminal nitrogen of x2193, x0991 or x0387 respectively. Overall, I think that both Gly143/Cys145 and Glu166/Met165 could be engaged by some nice heterocycle possibly extending to reach other pockets. (by eye)
Other Notes:
Could not select x2572 or x2193 as fragments Amides can be prepared by Ugi reaction, alternatively all of these compounds (and possibly more) can be prepared using single intermediate Cc1ccncc1C(N)C(=O)Nc(ccc2)cc2C#N