Submission Details
Molecule(s):
O=C(CN1CC(C(=O)Nc2cncc3ccc(F)cc23)c2ccccc2C1=O)NC1COC1
O=C(CN1CC(C(=O)Nc2cncc3ccc(Cl)cc23)c2ccccc2C1=O)NC1COC1
CNC(=O)C(C)(C)N1CC(C(=O)Nc2cncc3cc(S(C)(=O)=O)ccc23)c2ccccc2C1=O
CNC(=O)C1(N2CC(C(=O)Nc3cncc4cc(S(C)(=O)=O)ccc34)c3ccccc3C2=O)CC1
Design Rationale:
Combine tetrahydroisoquinolone glycine amide potency with metabolism reducing substitution s on NH and isoquinoline keeping logP in bounds to avoid permeability issues. Note gem di methyl and cyclopropyl amides would be expected to show different pofenies due to significantly different conformational preference.