Trazodone, a well-known antidepressant medication used across the world, functions as a 5-hydroxytryptamine (5-HT2) and 1-adrenergic receptor antagonist and a serotonin reuptake inhibitor

Trazodone, a well-known antidepressant medication used across the world, functions as a 5-hydroxytryptamine (5-HT2) and 1-adrenergic receptor antagonist and a serotonin reuptake inhibitor. d (doublet), t (triplet), m (multiplet). The three-dimensional buildings from the ligands had been completely optimized at CAM-B3LYP/6-31G*19 level using the polarizable continuum model (PCM) (solvent = drinking water) using Gaussian 09 software program (Gaussian, Inc., Wallingford, CT, USA). The correct ionization state governments at pH = 7.4 1.0 were assigned using MarvinSketch 18.29 (ChemAxon European countries, Budapest, Hungary). The AutoDock Equipment was utilized to assign the connection orders, suitable amino acidity ionization states, also to look for steric clashes. The receptor grid was generated by centering the grid container using a size of 12 ? on D76 aspect chain. Automated versatile docking was performed using AutoDock Vina 1.5.6 [26]. The statistics had been ready using PYMOL. The homology types of the chosen serotonin receptors, 5-HT1A and 5-HT2A namely, had been built over the D3 template (Proteins Data Loan provider (PDB) identifier (Identification): 3PBL), utilizing a procedure defined [27] previously. 3.2. General Process of the Planning of 2-Hydrazinopyridine ((8): 1H NMR (400 MHz, CDCl3) 7.78 (ddd, = 5.5, 3.3, 2.2 Hz, 1H, ArH), 7.15C7.07 (m, 2H, ArH), 6.51 (ddd, = 7.2, 4.4, 3.0 Hz, 1H, ArH), 4.02 (t, = 7.1 Hz, 2H, CHNCO), 3.42 (dd, = 8.0, 5.6 Hz, 2H, CHBr), 1.89 (ddd, = 10.3, 7.3, 3.4 Hz, 4H, CHAliph), 1.55C1.48 (m, 2H, CHAliph), 1.46C1.39 (m, 2H, CHAliph). 13C NMR (101 MHz, CDCl3) 148.57 (Ar), 141.47 (Ar), 129.75 (Ar), 123.77 (Ar), 115.38 (Ar), 110.48 (Ar), 45.77 (CAliph), 33.69 (CAliph), 32.56 (CAliph), 28.62 (CAliph), 27.71 (CAliph), 25.75 (CAliph). HPLC 91% (tR = 7.31), Rf = 0,96, produce = 79%, essential oil. 3.10. General Process of the Planning Trazodone Derivatives First of all, 529 mg (2.5 mmol) of 2-(3-chloropropyl)-1,2,4-triazolo[4,3-a]pyridin-3-(2(10a): 1H NMR (300 MHz, CDCl3) 7.76 (d, = 7.1 Hz, 1H, ArH), 7.17 (ddd, = 17.0, 8.8, 3.0 Hz, 4H, 1H, ArH), 7.02 (d, = 8.0 Hz, 1H, 1H, ArH), 6.54 (t, = 6.5 Hz, 1H, 1H, ArH), 4.18 (t, = 6.1 Hz, 2H, CHNCO), 3.67 (dd, = 22.9, 11.2 Hz, 4H, CHpip), 3.37 (d, = 13.5 Hz, 2H, CHpip), 3.17 (s, 2H, CHpip), 3.06 (d, = 11.5 Hz, 2H, CHaliph), 2.60 (s, 2H, CHaliph).13C NMR (75 MHz, CDCl3) 149.07 (Ar), Nevirapine (Viramune) 148.89 (Ar), 142.14 (Ar), 134.44 (Ar), 130.61 (Ar), 128.09 (Ar), 127.82 (Ar), 126.45 (Ar), 123.92 (Ar), 119.52 (Ar), 115.58 (Ar), 111.10 (Ar), 55.54 (Ctriaz), 52.66 (Cpip, Cpip), 48.15 (Cpip, Cpip), 43.45 (Cpip), 23.55 (Caliph). Fourier-transform (Foot)-IR 3000 (CCH Ar, Str), 2954, 2850 (C-HAliph, Str), 1704 (C=O, Str), 1650 (C=N, Str), 1500, 1450 (C=C, Str), 1350 (CCN, Str), 750 (CCCl, Str). HPLC 97% (= 406,19, Rf = 0.87, yield = 25%, melting stage (mp) = 225C230 C. (10b): 1H NMR (300 MHz, CDCl3) 7.76 (d, = 6.9 Hz, 1H, ArH), 7.26 (s, 2H, ArH), 7.12 (d, = 10.0 Nevirapine (Viramune) Hz, 4H, ArH), 6.54 (s, 1H, ArH), 4.18 (s, 2H, CHNCO), 4.03C3.91 (m, 2H, CHpip), 3.62 (s, 2H, CHpip), 3.58C3.49 (m, 2H, CHpip), 3.46C3.30 (m, 2H, CHpip), 3.26C3.16 (m, 2H, CHaliph), 2.66C2.53 (m, 2H, CHaliph). 13C NMR (75 MHz, dimethyl sulfoxide (DMSO)) Nevirapine (Viramune) 155.88 (Ar), 152.63 (Ar), 147.58 (Ar), 140.62 (Ar), 137.71(Ar) 130.04 (Ar), 122.79 (Ar), 119.02 (Ar), 115.72 (Ar), 115.45 (Ar), 114.47 (Ar), 110.31 (Ar), 52.42 (Ctriaz), 50.35 (Cpip, Cpip), 46.41 (Cpip, Cpip), 42.01 (Cpip), 22.38 (Caliph). FT-IR 3000 (CCH Ar, Str), 2946, 2852 (CCHAliph, Str), 1711 (C=O, Str), 1639 (C=N, Str), 1574, 1451 (C=C, Str), 1355 (CCN, Str), 1108 (CCF, Str). HPLC 99% (= 356.21; Rf = 0.70, produce = 30%, mp = 146C150 C. (10c): 1H NMR (300 MHz, CDCl3) 7.76 (d, = WASF1 7.1 Hz, 1H, ArH), 7.26C7.07 (m, 4H, ArH), 7.02 (dd, = 7.8, 1.7 Hz, 1H, ArH), 6.57C6.50 (m, 1H, ArH), 4.18 (t, = 6.1 Hz, 2H, CHNCO), 3.67 (dd, = 22.2, 11.3 Hz, 4H, CHpip), 3.37 (d, = 12.9 Hz, 2H, CHpip), 3.25C3.15 (m, 2H, CHpip), 3.06 (d, = 11.3 Hz, 2H, CHaliph), 2.59 (t, = 14.4 Hz, 2H, CHaliph). 13C NMR (75 MHz, Nevirapine (Viramune) CDCl3) 148.85 (Ar), 148.67 (Ar), 141.93 (Ar), 130.41 (Ar), 127.89 (Ar, Ar) 126.23 (Ar), 119.32 (Ar), 115.37 (Ar), 110.90 (Ar), 55.32(Ctriaz), 52.46 (Cpip, Cpip), 47.94 (Cpip, Cpip), 43.24 (Cpip), 23.34 (Caliph). FT-IR 2990 (C-H Ar, Str), 2946, 2850 (CCHAliph, Str), 1706 (C=O, Str), 1636 (C=N, Str), 1601, 1459 (C=C, Str), 1355 (CCN, Str). HPLC 99% (= 340.46; Rf = 0.68, yield = 34%, mp Nevirapine (Viramune) = 235C240 C. (10d): 1H NMR (300 MHz, CDCl3) 7.76 (d, = 7.1 Hz, 1H, ArH), 7.18C6.95 (m, 4H, ArH), 6.89 (dd, = 17.3 7.4 Hz, 2H, ArH), 6.54 (t, = 6.5 Hz,.