Submission Details

PET-UNK-7374c256
Molecule(s):
CN(C)c1ccc(N(Cc2ccsc2)C(=O)Cn2cnc3ccccc32)cc1

PET-UNK-7374c256-1
Duplicate of:
ALP-POS-8ed8d9ec-7

CN(C)c1ccc(N(Cc2ccsc2)C(=O)Cn2cnc3ccccc32)cc1

Duplicate 3-aminopyridine-like Check Availability on Manifold View
CN(C)c1ccc(N(Cc2ccn[nH]2)C(=O)Cn2nnc3ccccc32)cc1

PET-UNK-7374c256-2

CN(C)c1ccc(N(Cc2ccn[nH]2)C(=O)Cn2nnc3ccccc32)cc1

3-aminopyridine-like Assayed Check Availability on Manifold View
Design Rationale:

Atomic modifications to ALP-POS-d2866bdf-1 connection table that are intended to enhance affinity.

Other Notes:

Design 1: Replacement of benzotriazole N2 with CH would be expected to lead to an increase in the hydrogen bond (HB) basicity of N3 (which accepts HB from H163 sidechain) while reducing energetic penalty associated with desolvation of N2 (which does not accept HB from protein). For benzotriazole, I would anticipate that N2 will be a significantly weaker HB acceptor than N3. Design 2: Replace thiophene with pyrazole so as to donate HB to backbone carbonyl oxygen of E166 (interactions with this HB acceptor can be observed in a number of protein structures although some movement of the heterocyclic ring will be necessary).

Discussion:

Contributor: Peter Kenny - Wed, 26 Aug 2020 13:57:29 +0000