Download (6Mb) - Etheses - Saurashtra University

More documents

Recommendations

Info

Chapter 6 Synthesis of benzodiazepines Diazepine derivatives constitute an important class of heterocyclic compounds which possess a wide range of therapeutic and pharmacological properties. Derivatives of benzodiazepines are widely used as anticonvulsant, antianxiety, analgesic, sedative, anti-depressive, and hypnotic agents 6-7 as well as antiinflammatory agents. 8 In the last decade, the area of biological interest of 1,5- benzodiazepines has been extended to several diseases such as cancer, viral infection and cardiovascular disorders. 9-10 In addition,1,5-benzodiazepines are key intermediates for the synthesis of various fused ring systems such astriazolo-, oxadiazolo-, oxazino- or furanobenzodiazepines. 11-14 Besides, benzodiazepine derivatives are also of commercial importance as dyes for acrylic fibers in photography. 15 Owing to their versatile applications various methods for the synthesis of benzodiazepines have been reported in the literature. These include condensation reactions of o-phenylenediamines with α,β-unsaturated carbonylcompounds, 16 with ketones in the presence of BF 3·Et 2 O, NaBH 4 , polyphosphoric acid or SiO 2 , MgO/POCl 3 , Yb(OTf) 3 , Al 2 O 3 /P 2 O 5 or AcOH under microwave conditions, Amberlyst-15 in the ionic liquid 1-butyl-3-methylimidazoliumbromide ([bmim]Br), CeCl 3·7H 2 O/NaI supported on silica gel,InBr 3 , Sc(OTf) 3 , sulfated zirconia, InCl 3 , CAN, ZnCl 2 under thermal conditions, AgNO 3 . 17-32 Among all types of benzodiazepines (1,2-,1,3-, 1,4-, 1,5-, 2,3-, & 2,4- ) only 1,4- and 1,5-benodiazepines have found wide applications in medicines, during one of the most important classes of the therapeutic agents with wide spread biological activities 33 including hypnotics, sedatives, anxiolytics and antianxiety etc, effect range from their well-documented anticonvulsive or tranquilizing properties, through pesticidal 34 or antitumor 35 action and to their more recently described peptidomimetic activity. 36 Recently, structural modification has been done in diazepine ring system to enhance biological activity. Diazepine ring system modified at N and 3-position has been studied extensively. They have been tested clinically as an antitrypanosomal activity, 37 antiplasmodial falcipain-2 inhibitors, 38 antileukemic agents, 39 and endothelin Receptor Antagonists. 40 V. I. Pavlovsky et al. 41 has reported that 3- arylideneand 3-hetarylidene 1,4-diazepinederivatives afford good affinity toward CNS benzodiazepine receptors. Department of Chemistry, Saurashtra University, Rajkot-360005 202
Chapter 6 Synthesis of benzodiazepines 6.2 Biological activities associated with diazepine derivatives Buckle et al. 42 has prepared 1H-benzo-1,5-diazepine-2,4-(3H,5H)-diones (Figure-2) from 4,2-R 2 (NH 2 )C 6 H 3 NH 2 (R 2 = H, Cl, F, COOH) by refluxing with malonic acid in 4N HCl for half an hour followed by nitration with fuming HNO 3 which is antiallergic substance useful in the treatment of rhinitis, hay fever and certain type of asthma. Figure-2 K. S. Andronati et al. 43 has prepared 3-Amino-1,2-dihydro-3h-1,4- benzodiazepin-2-one derivatives (Figure-3) via interaction with 3-chloro benzodiazepines, diethylamine, 1,6-diaminohexane, or p-nitroaniline, which is exhibit a pronounced anticonvulsant activity and produce significant anorexigenic effect. H N O Br N R 2 R 1 R 1 =H,Cl R 2 =N(C 2 H 5 ) 2 , NH(CH 2 ) 6 NH 2 Figure-3 More recent analogues of the Benzodiazepines have attracted interest as anti HIV compounds, such as the clinically used nevirapine and as anticancer compounds, such as the pyrrolo fused antitumor antibiotic DC-18 (Figure-4), analogues of which are in clinical development as anticancer agents. 44 Figure-4 Department of Chemistry, Saurashtra University, Rajkot-360005 203
Page 1 and 2:
Saurashtra University Re - Accredit
Page 3 and 4:
Statement under O.Ph.D.7 of Saurash
Page 5 and 6:
Wxw|vtàxw àÉ `ç YtÅ|Äç
Page 7 and 8:
I am thankful to FIST/DST and SAP/U
Page 9 and 10:
Chapter 4 Synthesis and Characteriz
Page 11 and 12:
Chapter - 1 Palladium Catalyzed Syn
Page 13 and 14:
Chapter 1 Synthesis of functionaliz
Page 15 and 16:
Page 17 and 18:
Page 19 and 20:
Page 21 and 22:
Page 23 and 24:
Page 25 and 26:
Page 27 and 28:
Page 29 and 30:
Page 31 and 32:
Page 33 and 34:
Page 35 and 36:
Page 37 and 38:
Page 39 and 40:
Page 41 and 42:
Page 43 and 44:
Page 45 and 46:
Page 47 and 48:
Page 49 and 50:
Page 51 and 52:
Page 53 and 54:
Page 55 and 56:
Chapter - 2 Synthesis and Biologica
Page 57 and 58:
Chapter 2 Synthesis of substituted
Page 59 and 60:
Page 61 and 62:
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
Page 69 and 70:
Page 71 and 72:
Page 73 and 74:
Page 75 and 76:
Page 77 and 78:
Page 79 and 80:
Page 81 and 82:
Page 83 and 84:
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
Page 91 and 92:
Page 93 and 94:
Page 95 and 96:
Chapter 3 Synthesis of trisubstitut
Page 97 and 98:
Page 99 and 100:
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Page 119 and 120:
Page 121 and 122:
Page 123 and 124:
Page 125 and 126:
Page 127 and 128:
Page 129 and 130:
Page 131 and 132:
Page 133 and 134:
Page 135 and 136:
Chapter 4 Synthesis of highly subst
Page 137 and 138:
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
Page 159 and 160:
Page 161 and 162:
Page 163 and 164:
Page 165 and 166:
Page 167 and 168: Chapter 4 Synthesis of highly subst
Page 173 and 174: Chapter-5 Synthesis of highly subst
Page 217: Chapter 6 Synthesis of benzodiazepi
Page 221 and 222: Chapter 6 Synthesis of benzodiazepi
Page 251 and 252: pyrazole derivative were faster and
Page 253: Conferences participated 1. “15 t
show all

Download (6Mb) - Etheses - Saurashtra University

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?