Submission Details

JOO-PER-d7ab4f65
Molecule(s):
CC(=O)NCCC1C=Nc2c(CN3CCN(C(=O)CCl)CC3)cc(F)cc21

JOO-PER-d7ab4f65-1

CC(=O)NCCC1C=Nc2c(CN3CCN(C(=O)CCl)CC3)cc(F)cc21

piperazine-chloroacetamide Ordered Check Availability on Manifold View
Design Rationale:

Overlay of fragment 0830 with 0104. Nr. 0830 presents the chloroacetamide - piperazine scaffold that is seen in many fragments and which binds covalently to Cys 145. Nr. 0104 has a flexible chain that addresses a backpocket with some nice interactions a.o to Glu 166 and Gln 189, and replaces some crystal waters seen in the complex with 0830. If this works, flexibility in the 0104 can maybe be reduced for better affinity. Also the warhead that binds to Cys 145 needs to be replaced with a more drug-like one.

Inspired By:
Discussion:

Contributor: Joost Uitdehaag, personal title - Wed, 25 Mar 2020 13:46:15 +0000