Carbamates physicochemical properties

Acidic compounds with N—H bonds such as amides, carbamates, and hydan-toins, may be transformed to /V-rnannich bases to form oral prodrugs [2], These prodrugs are generally made by reacting an amide, carbamate, or hydantoin with formaldehyde and a primary or secondary aliphatic or aromatic amine (Fig. 4). The (V-mannich prodrugs tend to have better physicochemical properties than the parent compounds. The derivatives may have increased water solubility, dissolution rate, and/or lipophilicity. 

Calculations of solvation and bitiditig free energy differences between (3S)-tetrahydro-3-fuiyl-Y-((lS,2R0-3-(4-amino-Y-isotbutylbenzenesulfonainido)-l-benzyl-2-hydroxypropyl) carbamate - a potent low molecular weight and orally bioactive inhibitor of tire HlV-1 protease - and its analogues were carried out witii free energy perturbation, SM2/AM1 and SM3/PM3 methods. Results showed how physicochemical properties like aqueous solubilities and bioavailabilities of friese HTV-l protease inhibitors were improved while maintaining their inhibitory potency [92]. 

---