Veber

According to a molecular orbital calculation of Veber and Lwowski, isoindole should be favored over its tautomer, isoindolenine, by about 8 kcal/mole. However, the calculated electronic distribution is markedly different in the two oases, particularly at position 1, and it is to be expected that the nature and pattern of substituents will play an important role in determining the position of tautomeric equilibrium between these two species. 

Submitted by John D. Milkowski, Daniel F. Veber, and Ralph Hirschmann ... 

Veber DF, Johnson SR, Cheng H-Y, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 2002 45 2615-23. 

Veber, D.F., Johnson, S.R., Cheng, H.Y., Smith, B.R., Ward, K.W., Kopple, K.D. (2002) Molecular Properties that Influence the Oral BioavaUability of Drug Candidates. Journal of Medicinal Chemistry, 45, 2671-2623. 

Veber, D., Johnson, S., Cheng, H., Smith, B., Ward, K., Kopple, K. D. Molecular properties that infiuence the oral bioavailability of drug candidates. /. Med. Chem. 2002, 45, 2615-2623. 

In addition to the in vitro assays described above, physical properties should be calculated for all new compounds designed for synthesis. It is necessary to keep in mind the target values for leads, such as MW < 450, clogP < 4.0, and PSA < 80. It has been demonstrated that properties such as MW and clogP increase during optimization [26], so that a lead needs to have lower values for these properties than a drug candidate. Additional factors that make up the rule-of-five [27] as well as the number of rotatable bonds as described by Veber [28] can also be tracked. While... 

---