Table 1.
Working molecules (IUPAC name and molecular weight MW are indicated ) and their corresponding SMILES topology, i.e. the longest SMILES molecular chain (LoSMoC) as upper entry and the Branching SMILES (BraS) as down entry, for each pyrimidine structure considered, along the common activity A = log10(1/EC50) employed from half maximal effective concentration (EC50, μM) antiviral activity of 1,3-disubstituted uracils against human immunodeficiency virus (HIV-1) [69], with AIDS code indicated [84], respectively. The solubility parameter of lipophilicity (LogP), and the chemical reactivity parameters such as electronegativity (χ) and chemical hardness (η), chemical power (π) and electrophilicity (ω) are considered within the semiempirical (AM1) framework (Polak-Ribiere conjugate gradient algorithm and geometry optimization till the root mean square RMS gradient was equal to or less than 0.01 kcal/Åmol) as provided by the Hyperchem 7.01 computational environment [140], while the chemical reactivity values were computed in terms of HOMO and LUMO from equations (14) and (15)—see text and Table 2, (7) and (10), respectively. SMILES legend is: 
principal SMILES chain; 
secondary SMILES branch; 
tertiary SMILES branch; 
quaternary SMILES branch; = double bond; # triple bond; /,\ directional bonds; ( ) branch; C, N, F, S, I — atoms present in the molecule; c, n — atoms place in an aromatic ring; C1/2/3, N1/2, c1/2/3, n2 — connectivity points.
| No. | Structure 2D | SMILES configurations | A | LogP | χ (eV) | η (eV) | π | ω (eV) | |
|---|---|---|---|---|---|---|---|---|---|
| IUPAC name MW AIDS code |
LoSMoC | Code LoSMoC | ... LoSMoC ... | ||||||
| BraS | Code BraS | ... BraS ... | |||||||
| 1 |
[3-(2-Methyl-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 255.28 AIDS352092 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2ccc(C)c(C)c2 | 3.716698 | 0.91 | 23.107212 | 1.5817419 | 7.304356 | 168.78330 |
|
O=C1N(Cc(c(C)cc2)cc2)C(N(/C=C1\)CC#N)=O | 0.44 | 13.240955 | 2.8324015 | 2.3374078 | 30.949511 | |||
| 2 |
[3-(3-Methyl-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 255.28 AIDS352093 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2cccc(C)c2 | 5.173925 | 0.47 | 22.812517 | 1.5937610 | 7.156819 | 163.26505 |
|
O=C1N(Cc(cc(C)c2)cc2)C(N(/C=C1\)CC#N)=O | 0.44 | 13.043803 | 2.8273990 | 2.3066788 | 30.087865 | |||
| 3 |
[3-(4-Methyl-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 255.28 AIDS352094 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2ccc(C)cc2 | 4.023191 | 0.47 | 22.852718 | 1.5799314 | 7.232187 | 165.27512 |
|
O=C1N(Cc(ccc2C)cc2)C(N(/C=C1\)CC#N)=O | 0.88 | 13.149213 | 2.8323062 | 2.3212908 | 30.523148 | |||
| 4 |
[3-(2,4-Dimethyl-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 269.30 AIDS352888 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2ccc(C)cc2C | 3.943095 | 1.06 | 22.695343 | 1.4889604 | 7.621204 | 172.96584 |
|
O=C1N(Cc2c(cc(cc2)C)C)C(N(/C=C1\)CC#N)=O | 1.03 | 13.061603 | 2.7061581 | 2.4133112 | 31.521715 | |||
| 5 |
[3-(2,5-Dimethyl-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 269.30 AIDS352889 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2cc(C)ccc2C | 4.610833 | 1.06 | 22.961910 | 1.5967679 | 7.190121 | 165.09891 |
|
O=C1N(Cc(cc(C)c2)c(c2)C)C(N(/C=C1\)CC#N)=O | 0.6 | 13.344068 | 2.8843065 | 2.3132194 | 30.867758 | |||
| 6 |
[3-(2,6-Dimethyl-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 269.30 AIDS352890 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2c(C)cccc2C | 3.707743 | 1.06 | 22.914792 | 1.5375402 | 7.45177 | 170.75577 |
|
O=C1N(Cc(c(C)cc2)c(C)c2)C(N(/C=C1\)CC#N)=O | 0.6 | 13.174123 | 2.7474378 | 2.3975289 | 31.585343 | |||
| 7 |
[3-(3,5-Dimethyl-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 269.30 AIDS352095 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2cc(C)cc(C)c2 | 6.229147 | 0.63 | 22.322613 | 1.3441469 | 8.303636 | 185.35884 |
|
O=C1N(Cc(cc(C)c2)cc2C)C(N(/C=C1\)CC#N)=O | 1.03 | 12.688503 | 2.5160717 | 2.5214906 | 31.993942 | |||
| 8 |
[3-(3,4-Dimethyl-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 269.30 AIDS352891 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2ccc(C)c(C)c2 | 5.425968 | 0.63 | 22.513298 | 1.4966364 | 7.521298 | 169.32923 |
|
O=C1N(Cc(cc(c2C)C)cc2)C(N(/C=C1\)CC#N)=O | 1.03 | 12.964034 | 2.7262701 | 2.3776137 | 30.823468 | |||
| 9 |
[3-(2,4,6-trimethyl-benzyl)- 2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 283.33 AIDS352892 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2c(C)cc(C)cc2C | 3.716698 | 1.22 | 22.436637 | 1.3498377 | 8.310865 | 186.46785 |
|
O=C1N(Cc2c(cc(cc2C)C)C)C(N(/C=C1\)CC#N)=O | 1.62 | 12.848802 | 2.5836971 | 2.4865149 | 31.948740 | |||
| 10 |
[3-(3-cyanophenyl)methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 266.26 AIDS352893 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2cccc(c2)C#N | 5.128427 | 0.04 | 22.981901 | 1.5807784 | 7.269172 | 167.05939 |
|
O=C1N(Cc(cc(C#N)c2)cc2)C(N(/C=C1\)CC#N)=O | 0.01 | 12.984607 | 2.7188679 | 2.3878703 | 31.00556 | |||
| 11 |
[3-(3,5-Dimethoxy-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 301.30 AIDS352897 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2cc(OC)cc(c2)OC | 5.248720 | -1.67 | 21.820275 | 1.0563595 | 10.32805 | 225.36097 |
|
O=C1N(Cc(cc2OC)cc(OC)c2)C(N(/C=C1\)CC#N)=O | -0.72 | 12.366078 | 2.2360288 | 2.7651875 | 34.194524 | |||
| 12 |
[3-(3,4,5-trimethoxy-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 331.33 AIDS352898 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2cc(OC)c(OC)c(c2)OC | 3.423658 | -2.66 | 21.365171 | 1.0625102 | 10.0541 | 214.80760 |
|
O=C1N(Cc2cc(c(OC)c(OC)c2)OC)C(N(/C=C1\)CC#N)=O | -2.26 | 12.143075 | 2.4593788 | 2.4687280 | 29.977950 | |||
| 13 |
|
|
N#CCN1/C=C\C(=O)N(C1=O)Cc3c2ccccc2ccc3 | 5.268411 | 1.16 | 25.868615 | 1.4726275 | 8.78315 | 227.20792 |
| (3-Naphthalen-1-ylmethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-acetonitrile 291.31
AIDS352899 |
|
O=C1N(Cc(c(cc3)c(cc3)c2)cc2)C(N(/C=C1\)CC#N)=O | 0.25 | 14.682316 | 2.7628433 | 2.6571026 | 39.012422 | ||
| 14 |
(3-Naphthalen-2-ylmethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-acetonitrile 291.31 AIDS352900 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc3cc2ccccc2cc3 | 4.435333 | 1.16 | 25.888824 | 1.3140309 | 9.850919 | 255.02871 |
|
O=C1N(Cc(cc(ccc3)c2c3)cc2)C(N(/C=C1\)CC#N)=O | 0.69 | 14.829177 | 2.6159392 | 2.8343888 | 42.031656 | |||
| 15 |
(3-Biphenyl-4-ylmethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-acetonitrile 317.35 AIDS352901 |
|
N#CCN1/C=C\C(=O)N(C1=O)Cc2ccc(cc2)c3ccccc3 | 4.236572 | 1.25 | 27.000458 | 1.2990428 | 10.39244 | 280.60074 |
|
O=C1N(Cc(c2)ccc(c(cc3)ccc3)c2)C(N(/C=C1\)CC#N)=O | 0.79 | 15.020930 | 2.3806514 | 3.1547941 | 47.387942 | |||
| 16 |
1-Benzyl-3-phenyl-1H-pyrimidine-2,4-dione 278.31 AIDS352902 |
|
c1ccccc1CN2/C=C\C(=O)N(C2=O)c3ccccc3 | 3.665546 | 1.55 | 28.617336 | 1.4763650 | 9.691822 | 277.35413 |
|
O=C1N(c(cc2)ccc2)C(N(/C=C1\)Cc(ccc3)cc3)=O | 0.54 | 16.311764 | 2.7002385 | 3.0204302 | 49.268547 | |||
| 17 |
1,3-Dibenzyl-1H-pyrimidine-2,4-dione 292.34 AIDS352903 |
|
c1ccccc1CN2/C=C\C(=O)N(C2=O)Cc3ccccc3 | 4.954677 | 1.53 | 27.627131 | 1.4262804 | 9.685028 | 267.56953 |
|
O=C1N(Cc(ccc2)cc2)C(N(/C=C1\)Cc(ccc3)cc3)=O | 1.06 | 15.538736 | 2.6492805 | 2.9326332 | 45.569415 | |||
| 18 |
1-Benzyl-3-(3,5-dimethyl-benzyl)-1H-pyrimidine-2,4-dione 320.39 AIDS352096 |
|
c1ccccc1CN2/C=C\C(=O)N(C2=O)Cc3cc(C)cc(C)c3 | 6.630784 | 1.84 | 25.860489 | 0.7302591 | 17.70638 | 457.89563 |
|
O=C1N(Cc(cc(C)c2)cc2C)C(N(/C=C1\)Cc(ccc3)cc3)=O | 1.81 | 14.540931 | 1.5875011 | 4.5798175 | 66.594813 | |||
| 19 |
1-Benzyl-3-(4,6-dimethyl-pyridin-2-ylmethyl)-1H-pyrimidine-2,4-dione 321.38 AIDS352904 |
|
c1ccccc1CN2/C=C\C(=O)N(C2=O)Cc3nc(C)cc(C)c3 | 5.136082 | 0.41 | 26.114347 | 0.8253111 | 15.82091 | 413.15277 |
|
O=C1N(Cc(cc(C)c2)nc2C)C(N(/C=C1\)Cc(ccc3)cc3)=O | 0.15 | 14.748792 | 1.7122755 | 4.3067812 | 63.519822 | |||
| 20 |
1-Benzyl-3-(3,5-dimethyl-benzyl)-5-methyl-1H-pyrimidine-2,4-dione334.42 AIDS352905 |
|
c1ccccc1CN2/C=C\(C)C(=O)N(C2=O)Cc3cc(C)cc(C)c3 | 5.841637 | 2.12 | 25.007275 | 1.0403700 | 12.01845 | 300.54873 |
|
O=C1N(Cc(cc(C)c2)cc2C)C(N(/C=C1\C)Cc(ccc3)cc3)=O | 2.39 | 14.063834 | 2.1272754 | 3.3055978 | 46.489379 | |||
| 21 |
1-Benzyl-3-(3,5-dimethyl-benzyl)-5-iodo-1H-pyrimidine-2,4-dione 446.29 AIDS352906 |
|
c1ccccc1CN2/C=C\(I)C(=O)N(C2=O)Cc3cc(C)cc(C)c3 | 4.379863 | 2.48 | 25.393186 | 0.8931783 | 14.21507 | 360.96592 |
|
O=C1N(Cc(cc(C)c2)cc2C)C(N(/C=C1\I)Cc(ccc3)cc3)=O | 2.53 | 13.656576 | 1.4894424 | 4.5844594 | 62.608023 | |||
| 22 |
1-(2,6-Difluoro-benzyl)-3-phenyl-1H-pyrimidine-2,4-dione 314.29 AIDS352907 |
|
Fc1cccc(F)c1CN2/C=C\C(=O)N(C2=O)c3ccccc3 | 3.690369 | 1.08 | 28.610234 | 1.4786792 | 9.674253 | 276.78264 |
|
O=C1N(c(cc2)ccc2)C(N(/C=C1\)Cc(c(F)cc3)c(F)c3)=O | −0.66 | 16.175016 | 2.7665356 | 2.9233342 | 47.284980 | |||
| 23 |
1-(2,6-Difluoro-benzyl)-3-(3,5-dimethyl-benzyl)-1H-pyrimidine-2,4-dione 356.37 AIDS352908 |
|
Fc1cccc(F)c1CN2/C=C\C(=O)N(C2=O)Cc3cc(C)cc(C)c3 | 6.939302 | 1.37 | 25.844444 | 0.7517152 | 17.19032 | 444.27415 |
|
O=C1N(Cc(cc(C)c2)cc2C)C(N(/C=C1\)Cc(c(F)cc3)c(F)c3)=O | 0.6 | 14.486247 | 1.5713578 | 4.6094680 | 66.773895 | |||
| 24 |
1-(2,6-Difluoro-benzyl)-3-(4,6-dimethyl-pyridin-2-ylmethyl)-1H-pyrimidine-2,4-dione357.36 AIDS352909 |
|
Fc1cccc(F)c1CN2/C=C\C(=O)N(C2=O)Cc3nc(C)cc(C)c3 | 5.193820 | −0.06 | 26.085800 | 0.8406863 | 15.51458 | 404.71036 |
|
O=C1N(Cc(cc(C)c2)nc2C)C(N(/C=C1\)Cc(c(F)cc3)c(F)c3)=O | −1.05 | 14.690744 | 1.6779412 | 4.3776098 | 64.310348 | |||
| 25 |
1-(2,6-Difluoro-benzyl)-3-(2,6-dimethyl-pyridin-4-ylmethyl)-1H-pyrimidine-2,4-dione 357.36 AIDS352910 |
|
Fc1cccc(F)c1CN2/C=C\C(=O)N(C2=O)Cc3cc(C)nc(C)c3 | 3.886056 | 0.57 | 26.493803 | 0.9063530 | 14.61561 | 387.22308 |
|
O=C1N(Cc(cc(C)n2)cc2C)C(N(/C=C1\)Cc(c(F)cc3)c(F)c3)=O | 0.77 | 14.950333 | 1.7825743 | 4.1934669 | 62.693730 | |||
| 26 |
1,3-Bis-(2,6-difluoro-benzyl)-1H-pyrimidine-2,4-dione 364.30 AIDS352911 |
|
Fc1cccc(F)c1CN2/C=C\C(=O)N(C2=O)Cc3c(F)cccc3F | 4.379863 | 0.59 | 27.958833 | 1.5546911 | 8.991764 | 251.39924 |
|
O=C1N(Cc(c(F)cc2)c(F)c2)C(N(/C=C1\)Cc(c(F)cc3)c(F)c3)=O | −1.34 | 15.611849 | 2.8690618 | 2.7207236 | 42.475527 | |||
| 27 |
3-(3,5-Dimethyl-benzyl)-1-phenethyl-1H-pyrimidine-2,4-dione334.42 AIDS352912 |
|
c1ccccc1CCN2/C=C\C(=O)N(C2=O)Cc3cc(C)cc(C)c3 | 5.206209 | 2.09 | 25.447501 | 0.8335692 | 15.26418 | 388.43520 |
|
O=C1N(Cc(cc(C)c2)cc2C)C(N(/C=C1\)CCc(cccc3)c3)=O | 2.06 | 14.410323 | 1.8477646 | 3.8993936 | 56.191522 | |||
| 28 |
3-(3,5-Dimethyl-benzyl)-1-prop-2-ynyl-1H-pyrimidine-2,4-dione 268.32 AIDS352913 |
|
C#CCN1/C=C\C(=O)N(C1=O)Cc2cc(C)cc(C)c2 | 5.966576 | 0.77 | 21.628890 | 1.4603086 | 7.405589 | 160.17466 |
|
O=C1N(Cc(cc(C)c2)cc2C)C(N(/C=C1\)CC#C)=O | 1.18 | 12.392809 | 2.5046350 | 2.4739751 | 30.659502 | |||
| 29 |
1,3-Bis-(3,5-dimethyl-benzyl)-1H-pyrimidine-2,4-dione348.44 AIDS352914 |
|
c1c(C)cc(C)cc1CN2/C=C\C(=O)N(C2=O)Cc3cc(C)cc(C)c3 | 6.283996 | 2.14 | 25.233546 | 0.8800182 | 14.33694 | 361.77196 |
|
O=C1N(Cc(cc(C)c2)cc2C)C(N(/C=C1\)Cc(cc(cc3C)C)c3)=O | 2.55 | 14.566107 | 1.9376961 | 3.7586149 | 54.748388 | |||
| 30 |
[3-(3,5-Dimethyl-benzyl)-2-oxo-4-thioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetonitrile 285.36 AIDS352915 |
|
N#CCN1/C=C\C(=S)N(C1=O)Cc2cc(C)cc(C)c2 | 7.309803 | 1.28 | 21.897722 | 1.6182386 | 6.765913 | 148.15807 |
|
S=C1N(Cc(cc(C)c2)cc2C)C(N(/C=C1\)CC#N)=O | 1.68 | 12.764862 | 3.0237637 | 2.1107572 | 26.943525 | |||
| 31 |
1-Benzyl-3-(3,5-dimethyl-benzyl)-4-thioxo-3,4-dihydro-1H-pyrimidin-2-one 336.45 AIDS352916 |
|
c1ccccc1CN2/C=C\C(=S)N(C2=O)Cc3cc(C)cc(C)c3 | 7.292429 | 2.49 | 25.217792 | 1.1471616 | 10.99139 | 277.17849 |
|
S=C1N(Cc(cc(C)c2)cc2C)C(N(/C=C1\)Cc(ccc3)cc3)=O | 2.45 | 14.289267 | 2.4197012 | 2.9526925 | 42.191813 | |||
| 32 |
1-(2,6-Difluoro-benzyl)-3-(3,5-dimethyl-benzyl)-4-thioxo-3,4-dihydro-1H-pyrimidin-2-one 372.43 AIDS352917 |
|
Fc1cccc(F)c1CN2/C=C\C(=S)N(C2=O)Cc3cc(C)cc(C)c3 | 7.229147 | 2.02 | 25.321304 | 1.0761564 | 11.76469 | 297.89740 |
|
S=C1N(Cc(cc(C)c2)cc2C)C(N(/C=C1\)Cc(c(F)cc3)c(F)c3)=O | 1.25 | 14.434969 | 2.3806265 | 3.0317586 | 43.763344 | |||