Fig. 4 The selleck chemicals llc scheme of synthesis of the investigated compounds Estimation of drug-likeness The descriptors used for estimation of drug-likeness are collected in Table 1. Drug-likness was assessed using Lipinski’s
rule as well as the placement of the investigated compounds in the chemical space determined by the databases of the pharmacologically active compounds (CMC, Comprehensive Medicinal Chemistry Database, containing about 7,000 compounds and MDDR, MACCS-II Drug Data Report, containing about 100,000 compounds) according to the methodology of PREADMET service. Regarding Lipinski’s rule, all the compounds possess the molar mass below 500, the number of hydrogen bond donors below 5, the number of hydrogen bond acceptors below 10, and the lipohilicity below 5. Table 1 Parameters for drug-likeness estimation Comp. Molar mass Lipophilicity AlogP98 HBD HBA Number of atoms Molar refractivity Rings
Rigid bonds Rotatable ACP-196 manufacturer bonds 3a 319.36 2.766 1 5 41 92.58 4 41 3 3b 353.80 3.431 1 5 41 97.18 4 41 3 3c 353.80 3.431 1 5 41 97.18 4 41 3 3d 353.80 3.431 1 5 41 97.18 4 41 3 3e 388.24 4.095 1 5 41 101.78 4 41 3 3f 388.24 4.095 1 5 41 101.78 4 41 3 3g 333.38 3.252 1 5 44 97.00 4 44 3 3h 333.38 3.252 1 5 44 97.00 4 44 3 3i 347.41 3.739 1 5 47 101.43 4 47 3 3j find more 349.38 2.750 1 6 45 98.39 4 45 4 3k 349.38 2.750 1 6 45 98.39 4 44 4 3l 333.38 2.773 1 5 44 97.19 4 43 4 3m 353.80 3.431 1 5 41 97.18 4 40 3 3n 388.24 4.095 1 5 41 101.78 4 41 3 3o 388.24 4.095 1 5 41 101.78 4 41 3 3p 388.24 4.095 1 5 41 101.78 4 41 3 3q 422.69 4.759 1 5 41 106.38 4 41 3 3r 422.69 4.759 1 5 41 106.38 4 41 3 3s 367.83 3.917 1 5 44 101.60 4 44 3 3t 367.83 about 3.917 1
5 44 101.60 4 44 3 3u 381.86 4.403 1 5 47 106.03 4 47 3 3v 383.83 3.414 1 6 45 102.99 4 44 4 3w 383.83 3.414 1 6 45 102.99 4 44 4 3x 367.83 3.438 1 5 44 101.79 4 43 4 HBD a number of hydrogen bond donors, HBA a number of hydrogen bond acceptors Concerning subsequent criteria of drug-likeness, most compounds collected in the CMC database has lipophilicity from -0.4 to 5.6, molar refractivity in the range of 40–130, molar mass from 160 to 480, and the number of atoms from 20 to 70. All the investigated compounds fulfill this criterion. In respect to the compounds in MDDR database, the drug-like substances have the number of rings equal or greater than 3, the number of rigid bonds equal or greater than 18, and the number of rotatable bonds equal or greater than 6.