Submission: PET-UNK-fe31e24a

PET-UNK-fe31e24a

Molecule(s):

PET-UNK-fe31e24a-1

COc1ccc2cncc(NC(=O)[C@@H]3CNC(=O)c4ccc(Cl)cc43)c2c1

3-aminopyridine-like Check Availability on Manifold View

PET-UNK-fe31e24a-2

CN(C)c1ccc2cncc(NC(=O)[C@@H]3CNC(=O)c4ccc(Cl)cc43)c2c1

3-aminopyridine-like Check Availability on Manifold View

PET-UNK-fe31e24a-3

COc1ccc2cncc(NC(=O)[C@]3(OC)CNC(=O)c4ccc(Cl)cc43)c2c1

3-aminopyridine-like Check Availability on Manifold View

PET-UNK-fe31e24a-4

CO[C@@]1(C(=O)Nc2cncc3ccc(N(C)C)cc23)CNC(=O)c2ccc(Cl)cc21

3-aminopyridine-like Check Availability on Manifold View

PET-UNK-fe31e24a-5

COc1ccc2cncc(NC(=O)[C@@H]3CN(C)C(=O)c4ccc(Cl)cc43)c2c1

3-aminopyridine-like Check Availability on Manifold View

PET-UNK-fe31e24a-6

CN1C[C@@H](C(=O)Nc2cncc3ccc(N(C)C)cc23)c2cc(Cl)ccc2C1=O

3-aminopyridine-like Check Availability on Manifold View

PET-UNK-fe31e24a-7

COc1ccc2cncc(NC(=O)[C@]3(OC)CN(C)C(=O)c4ccc(Cl)cc43)c2c1

3-aminopyridine-like Check Availability on Manifold View

PET-UNK-fe31e24a-8

CO[C@@]1(C(=O)Nc2cncc3ccc(N(C)C)cc23)CN(C)C(=O)c2ccc(Cl)cc21

3-aminopyridine-like Check Availability on Manifold View

Design Rationale:

The 8 designs in this submission combine 2 electron-releasing substituents (dimethylamino; methoxy) at C6 of the P1 isoquinoline with 4 P2 lactam variations (NH/N-methyl; with/without methoxy conformational lock) to see if any of these modifications lead to improved potency, antiviral activity or ADME relative to parent compound MIC-UNK-91acba05-1.

Other Notes:

Protein-ligand complexes (P0157 A chain) were energy-minimized using Szybki (MMFF94S). The PDB file associated with this submission contains the following: [1] P0157 A chain protein structure [2] P0157 A chain crystallographic ligand (PET-UNK-29afea89-2) [3-10] Design 1-8