Submission Details
Molecule(s):
[2H]C([2H])([2H])O[C@@]1(C(=O)Nc2cncc3ccccc23)CCOc2ccc(Cl)cc21
[2H]C([2H])([2H])O[C@@]1(C(=O)Nc2cncc3ccc(F)cc23)CCOc2ccc(Cl)cc21
[2H]C([2H])([2H])O[C@@]1(C(=O)Nc2cncc3cc(F)ccc23)CCOc2ccc(Cl)cc21
[2H]C([2H])([2H])O[C@@]1(C(=O)Nc2cncc3ccccc23)CN(S(C)(=O)=O)Cc2ccc(Cl)cc21
[2H]C([2H])([2H])O[C@@]1(C(=O)Nc2cncc3ccc(F)cc23)CN(S(C)(=O)=O)Cc2ccc(Cl)cc21
[2H]C([2H])([2H])O[C@@]1(C(=O)Nc2cncc3cc(F)ccc23)CN(S(C)(=O)=O)Cc2ccc(Cl)cc21
Design Rationale:
Analogs of previously submitted designs in which methoxy is trideuterated (this would be expected to increase metabolic stability if the methoxy is a site of metabolism on account of the primary kinetic isotope effect). Fluoro substitution would be expected to confer metabolic stability with minimal loss of potency.
Other Notes:
A pdb file is not provided since isotopically normal analogs have been submitted previously for all designs.