## 3 Experimental
### Chemistry
#### 3.1.1 Synthesis of Tetra-Substituted Pyridine Derivatives (**4a-f** and **6a-f**)  
General procedure: A mixture of ethyl 3-acetyl-1,5-diphenyl-1\(H\)-pyrazole-4-carboxylate (**1**) (0.334 g, 1 mmol), the appropriate aldehyde **2a-f** (1 mmol) and malononitrile (**3**), or ethyl acetoacetate (**5**) (1 mmol) in glacial acetic acid (20 mL) containing ammonium acetate (0.616 g, 8 mmol) was refluxed for 6-8 h (monitored by TLC). After complete reaction, the mixture was cooled and the precipitated products were filtered, washed with water, dried, and crystallized from ethanol to give the pyridine derivatives **4a-f** and **6a-f**, respectively. Compounds **4a-f** and **6a-f** together with their physical and spectral data are listed below:  
_Ethyl 3-(6-amino-5-cyano-4-phenylpyridin-2-yl)-1,5-diphenyl-1\(H\)-pyrazole-4-carboxylate_ (**4a**). Brown solid, (70% yield), mp 169-171 \({}^{\circ}\)C; IR (KBr) \(\
u_{\rm max}\) 3364, 3208 (NH\({}_{2}\)), 2218 (CN), 1715 (C=O) cm\({}^{-1}\); \({}^{1}\)H NMR (DMSO-\(d_{6}\)) \(\delta\) 1.02 (t, J = 7.2 Hz, 3H, CH\({}_{3}\)), 4.13 (q, J = 7.2 Hz, 2H, CH\({}_{2}\)), 6.93 (s, br, 2H, NH\({}_{2}\)), 7.18-7.90 (m, 15H, Ar-H), 8.11 (s, 1H, Pyridine-H5); MS \(m/z\) (%) 485 (M\({}^{+}\), 14), 322 (47), 252 (29), 167 (38), 77 (52), 43 (100). Anal. Calcd. for C\({}_{30}\)H\({}_{23}\)N\({}_{5}\)O\({}_{2}\) (485.55): C, 74.21; H, 4.77; N, 14.42. Found: C, 74.05; H, 4.52; N, 14.26%. _Ethyl 3-(6-amino-5-cyano-4-(\(p\)-tolyl)pyridin-2-yl)-1,5-diphenyl-1\(H\)-pyrazole-4-carboxylate_ (**4b**). Brown solid, (72% yield), mp 180-182 \({}^{\circ}\)C; IR (KBr) \(\
u_{\rm max}\) 3379, 3211 (NH\({}_{2}\)), 2210 (CN), 1712 (C=O) cm\({}^{-1}\); \({}^{1}\)H NMR (DMSO-\(d_{6}\)) \(\delta\) 1.01 (t, J = 7.2 Hz, 3H, CH\({}_{3}\)), 2.36 (s, 3H, CH\({}_{3}\)), 4.12 (q, J = 7.2 Hz, CH\({}_{2}\)), 6.92 (s, br, 2H, NH\({}_{2}\)), 7.14-7.94 (m, 14H, Ar-H), 8.15 (s, 1H, Pyridine-H5); MS \(m/z\) (%) 499 (M\({}^{+}\), 15), 468 (32), 364 (39), 209 (42), 104 (38), 78 (72), 43 (100). Anal. Calcd. for C\({}_{31}\)H\({}_{25}\)N\({}_{5}\)O\({}_{2}\) (499.57): C, 74.53; H, 5.04; N, 14.02. Found: C, 74.37; H, 5.00; N, 13.85%. _Ethyl 3-(6-amino-5-cyano-4-(4-methoxyphenyl))-1,5-diphenyl-1\(H\)-pyrazole-4-carboxylate_ (**4c**). Pale green solid, (68% yield), mp 154-156 \({}^{\circ}\)C; IR (KBr) \(\
u_{\rm max}\) 3367, 3219 (NH\({}_{2}\)), 2210 (CN), 1714 (C=O) cm\({}^{-1}\); \({}^{1}\)H NMR (DMSO-\(d_{6}\)) \(\delta\) 1.02 (t, J = 7.2 Hz, 3H, CH\({}_{3}\)), 3.78 (s, 3H, OCH\({}_{3}\)), 4.15 (q, J = 7.2 Hz, 2H, CH\({}_{2}\)), 6.93 (s, br, 2H, NH\({}_{2}\)), 7.18-7.80 (m, 14H, Ar-H), 8.12 (s, 1H, Pyridine-H5); MS \(m/z\) (%) 515 (M\({}^{+}\), 9), 452 (42), 316 (100), 234 (51), 182 (37), 118 (50), 76 (66). Anal. Calcd. for C\({}_{31}\)H\({}_{25}\)N\({}_{5}\)O\({}_{3}\) (515.57): C, 72.22; H, 4.89; N, 13.58. Found: C, 72.01; H, 4.77; N, 13.30%. _Ethyl 3-(6-amino-5-cyano-4-(4-(dimethylamino)phenyl)pyridin-2-yl)-1,5-diphenyl-1\(H\)-pyrazole-4-carboxylate_ (**4d**). Dark yellow solid, (73% yield), mp 150-152 \({}^{\circ}\)C; IR (KBr) \(\
u_{\rm max}\) 3431, 3212 (NH\({}_{2}\)), 2210 (CN), 1709 (C=O) cm\({}^{-1}\); \({}^{1}\)H NMR (DMSO-\(d_{6}\)) \(\delta\) 1.01 (t, J = 7.2 Hz, 3H, CH\({}_{3}\)), 2.97 (s, 6H, 2 CH\({}_{3}\)), 4.11 (q, J = 7.2 Hz, CH\({}_{2}\)), 6.82 (s, br, 2H, NH\({}_{2}\)), 7.14-7.82 (m, 14H, Ar-H), 8.10 (s, 1H, Pyridine-H5); MS \(m/z\) (%) 528 (M\({}^{+}\), 14), 416 (80), 212 (100), 170 (27), 105 (48), 76 (63). Anal. Calcd. for C\({}_{32}\)H\({}_{28}\)N\({}_{6}\)O\({}_{2}\) (528.62): C, 72.71; H, 5.34; N, 15.90. Found: C, 72.59; H, 5.30; N, 15.73%. _Ethyl 3-(6-amino-4-(4-chlorophenyl)-phenyl)-1,5-diphenyl-1\(H\)-pyrazole-4-carboxylate_ (**4c**).