Submission Details

Molecule(s):
O=C(NCCN1CCN(C(=O)CCl)CC1)c1ccccc1

STE-KUL-2e0d2e88-1

O=C(NCCN1CCN(C(=O)CCl)CC1)c1ccccc1

piperazine-chloroacetamide Assayed Check Availability on Manifold View
O=C(NCCN1CCN(C(=O)CCl)CC1)c1cccc2ccccc12

STE-KUL-2e0d2e88-2

O=C(NCCN1CCN(C(=O)CCl)CC1)c1cccc2ccccc12

piperazine-chloroacetamide Assayed Check Availability on Manifold View
O=C(NCCN1CCN(C(=O)CCl)CC1)c1cccnc1

STE-KUL-2e0d2e88-3

O=C(NCCN1CCN(C(=O)CCl)CC1)c1cccnc1

piperazine-chloroacetamide Ordered Check Availability on Manifold View
O=C(CCl)N1CCCC(n2cc(-c3ccccc3)nn2)C1

STE-KUL-2e0d2e88-4

O=C(CCl)N1CCCC(n2cc(-c3ccccc3)nn2)C1

O=C(CCl)N1CCCC(n2cc(-c3ccc(Cl)cc3)nn2)C1

STE-KUL-2e0d2e88-5

O=C(CCl)N1CCCC(n2cc(-c3ccc(Cl)cc3)nn2)C1

O=C(CCl)N1CCCC(n2cc(COCc3ccccc3)nn2)C1

STE-KUL-2e0d2e88-6

O=C(CCl)N1CCCC(n2cc(COCc3ccccc3)nn2)C1

O=C(CCl)N1CCN(Cc2cn(Cc3ccccc3)nn2)CC1

STE-KUL-2e0d2e88-7

O=C(CCl)N1CCN(Cc2cn(Cc3ccccc3)nn2)CC1

piperazine-chloroacetamide Check Availability on Manifold View

Design Rationale:

We covalently docked all covalent fragments that were crystallized and focused on those that gave a reasonable overlap of the docked structure with the crystallized one. Most of these were piperazines with a CH2-aryl substituent. We suspect this CH2 gives the necessary flexibility to reach the S2 pocket. In the current design, we focused on ease of synthesis while adding more substituents to reach the S2 specificity pocket. Structures are currently being covalently docked to evaluate this.

Inspired By:
Discussion: