MEDICINAL CHEMISTRY

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Lidocaine is effective as an antiarrhythmic only when given parenterally, and the intravenous route is the most common. Antiarrhythmic activity is not observed after oral administration because of the rapid and efficient first-pass metabolism by the liver. Phenytoin (155) is most useful in treating ventricular arrhythmias associated with digitalis toxicity or acute myocardial infarction. CNS side effects are the most common problems encountered with phenytoin and include vertigo, loss of mental acuity. H 3C CH 3 OCH 2CHNH 2 CH 3 Mexiletine (156) Synthesis of Mexiletine: (158) CH 3 CH 3 OH ClCH 2COCH 3 (159) CH 3 CH 3 H 3C Mexiletine CH 3 NHCOCHNH 2 CH 3 Tocainide (157) O NH2OH OCH 2-C-CH 3 HCl (160) CH 3 CH 3 CH 3 CH 3 NOH OCH 2-C-CH 3 H 2/Ra-Ni NH 2 OCH 2-CH-CH 3 (156) Mexiletine Hydrochloride: (±) 1 -Methyl-2-(2, 6-xylyloxy) ethylamine hydrochloride (156) is most useful in suppressing symptomatic ventricular arrhythmias. It is very similar to lidocaine in its action. It differs from lidocaine in its suitability for oral administration, high systemic availability (90%) after ingestion and is metabolized by hepatic route. It is administered with food and antacid. The major adverse effects of mexiletine are neurologic and include tremors, ataxia and confusion. It is metabolized by N-methylation and p-hydroxylation to inactive metabolites Synthesis of Tocainide: (161) CH 3 CH 3 NH 2 Br-COCH(Br)-CH 3 (162) CH 3 CH 3 Br NHCOCH-CH 3 NH 3 NH 2 NHCOCH-CH 3 H3C CH3 Tocainide (157)
Tocainide Hydrochloride (±)-2-Amino-N-(2,6-dimethyl-phenyl) propionamide hydrochloride (157) is another lidocaine congener, similar to mexiletine its electiophysiologic properties and antiarrhythmic action; A low incidence of bone marrow depression has caused this drug to be used less frequently than mexiletine. Class IC Antiarrhythmic Drugs F 3CCH 2O CONHCH 2 OCH 2CF 3 HN CONH CH 2CH 2 H 3C H 3C H 3C N CHNHCH2CH2CH2 CONH2 OCH3 Flecainide (163) Encainide (164) Indecainide (165) Synthesis of Flecainide (163): HO COOH (166) OH CF 3SO 2OCH 2CF 3 K 2CO 3 Flecainide (163) H 2 PtO 2 OCH 2CF 3 OCH2CF3 (167) CO 2CH 2CF 3 OCH 2CF 3 OCH 2CF 3 N CONHCH 2 (168) N CH 2NH 2 Flecainide Acetate: (±)-N-(2-piperidinylmethyl)-2, 5bis(2,2,2-trifluoroethoxy) benzamide (163) represents the first fluorine containing newer group of antiarrhythmic drugs. It is indicated for use in patients with life-threatening arrhythmias such as sustained ventricular tachycardia. It is able at precipitate cardiac arrest. Other side effects include headache, dizziness and nausea. The major metabolites, meta-O-dealkyl flecainide and meta-O-dealkyl flecainide lactam are inactive. The most potent compounds were having two trifluoroethoxy groups, one of which was ortho to the carboxamide function. The parasubstituted derivatives were less active. Replacement of trifluoro-ethoxy group with 5-CH3, 5-Cl, 5-F resulted in loss of activity. A two-carbon link between amide and amine nitrogen atoms appears to be optimal. Branching at the positions adjacent to the basic nitro-en is responsible for prolonged elimination half-life due to reduced N-dealkylation.
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CONTENTS Antianginal Drugs Anticoag
Page 3 and 4: c) Dihydropyridine derivative: e.g.
Page 5 and 6: 2 (d) 4. H 3C H 3C HO CH-CH 2-O-CH
Page 7 and 8: pentaerythritol, and is supplied di
Page 9 and 10: of' streptokinase, urokinase and ti
Page 11 and 12: Low-molecular-weight Heparins, B.P.
Page 13 and 14: OH COOCH 3 AC 2O Methyl salicylate
Page 15 and 16: Warfarin and other coumarin derivat
Page 17 and 18: Structure-activity Relationship All
Page 19 and 20: Mean Arterial Blood Pressure (MABP)
Page 21 and 22: Table-1 ---------------------------
Page 23 and 24: Ramipril Altace ( Hoechst-Marion) 2
Page 25 and 26: Official drugs: Prazosin Hydrochlor
Page 27 and 28: treatment of hypertension, the dosa
Page 29 and 30: NH ClCH 2CN NCH 2CN Perhydroazocine
Page 31 and 32: B (2). Angiotensin Receptor Antagon
Page 33 and 34: CH3COOC2H5 Diazoxide (90) Cl NH 2 S
Page 35 and 36: Structure-activity Relationships of
Page 37 and 38: N N R Acidic group (102) Acidic gro
Page 39 and 40: Structure-activity Relationships of
Page 41 and 42: HO HO HO HO H 3C CH 3 H Digitoxigen
Page 43 and 44: efractory periods. These are mainly
Page 45 and 46: Structure - Activity Relationship:
Page 47 and 48: Hydralazine is a direct relaxant of
Page 49 and 50: K4[Fe(CN) 6].3H2O + 6HNO3 H2[(NO)Fe
Page 51 and 52: conduction velocity, and decrease s
Page 53: Synthesis of Moricizine: (153) H N
Page 57 and 58: influx through β-receptor blockade
Page 59 and 60: Cl Cl CH2CH=CH2 N N N H Alinidine (
Page 61 and 62: (iii) Intermediate density lipoprot
Page 63 and 64: Structure-activity Relationship Mev
Page 65 and 66: to the bile acids. Thus due to ente
Page 67 and 68: moderate reduction in cholesterol l
Page 69 and 70: (iii) Other types: (a) Insulin rece
Page 71 and 72: non-crystalline insulin as far as o
Page 73 and 74: for better drug in this series. Sub
Page 75 and 76: Key to general structure X SO 2 NH
Page 77 and 78: Official Drugs: Insulin, B.P. It is
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MEDICINAL CHEMISTRY

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