MEDICINAL CHEMISTRY

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atherosclerosis. The antioxidant effects of agents of this group inhibit the oxidantion of LDL, thereby, preventing its uptake by macrophages. This may help pi-event development of atherosclerosis. Probucol [4,4'-(Isopropylidendithio)-bis[2,6-ditertiarybutyl phenol] (193) is the most potent cholesterol lowering agent of a series of alkylidenedithiobisphenols. It is an antioxidant that partitions into lipophilic media Such as LDL particles, where it can prevent or terminate the oxidative process. Probucol has been shown to lower LDL cholesterol levels apparently through stimulation of non-receptor mediated clearance pathways. Synthesis HO HO C(CH 3) 3 H 3C CH 3 C(CH 3) 3 (H 3C) 3C S S C(CH 3) 3 C(CH 3) 3 H 3C CH 3 + + Probucol (193) C(CH 3) 3 (H3C) 3C SH O HS C(CH3) 3 (194) (195) OH OH Probucol (193) (v) Miscellaneous Agents: (a) Nicotinic acid (206): Used in the treatment of hyperlipoproteinemia. It brings about hypolipidemic action by decreasing lipolysis and by promoting hepatic storage of lipids. It also enhances the activity of lipoprotein lipase resulting into low circulating VLDL level. Since VLDL acts as the precursor for most of the circulating LDL, the low VLDL level results into low level of circulating LDL. Nicotinamide, however, lacks hypolipidemic activity. In many cases, nicotinic acid is coadministered along with bile acid binding resin to get better results. In body, nicotinic acid (196) undergoes extensive metabolism resulting into formation of various metabolites, such as nicotinamide, nicotine uric acid, methyl nicotinamide, N- methyl 2-pyridone-3-carboxamide and Nmethyl-2 pyridone-5-carboxamide. These metabolites are mainly excreted in the urine along with some unchanged nicotinic acid. N COOH (206) (b)β – Sitotsterol (197) : It is a plant sterol. Due to the structural similarity with cholesterol, this agent impedes the absorption of dietary cholesterol and produces a
moderate reduction in cholesterol level. Its low efficacy and high cost decrease its popularity as lipid lowering agent. HO CH 3 H 3C CH 3 β−Sitosterol (197) (c) Acipimox: Acipimox is a synthetic derivative of nicotinic acid and like nicotinic acid; it acts by inhibiting adipose tissue lipolysis (hydrolysis of lipid esters). It appears to produce less flushing and GI-intolerance than nicotinic acid. It is about 20 times more active than nicotinic acid. (d) Neomycin: It is an amino glycoside antibiotic. It exerts hypolipidemic activity only in oral administration while if given parenterally, neomycin does not reduce the plasma level of LDL. The poor absorption upon oral administration of neomycin indicates that its site of action is in GIT. The adverse effects like, ototoxicity, nephrotoxicity seen during parenteral administration of neomycin, are not reported to occur with oral use of the drug. (e) Metformin: Chemically it is N, N-dimethyl biguanidine. It has no effect on cholesterol biosynthesis but it affects the lipoprotein composition. It produces about 50% reduction in the serum triglyceride level. It is also a hypoglycemic agent and lowers blood glucose level. (f) Dextrothyroxine: There exist an inversely proportional relationship between plasma levels of cholesterol and thyroxine (198). It increases the hepatic catabolism of LDL and thus lowers the plasma concentration of LDL particles. I I HO O I D-Thyroxine (198) I CH 3 CH 3 NH 2 CH COOH (g) Other agents having hypolipidemic activity include sucrose polymers, eicosapentaenoic acid, propranolol and pindolol. Similarly estrogens also interfere in the fat metabolism resulting into a decrease in plasma LDL concentration and an increase in plasma HDL concentration. These metabolic effects of estrogens are partly opposed by progestin.
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CONTENTS Antianginal Drugs Anticoag
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c) Dihydropyridine derivative: e.g.
Page 5 and 6:
2 (d) 4. H 3C H 3C HO CH-CH 2-O-CH
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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 and 54: Synthesis of Moricizine: (153) H N
Page 55 and 56: Tocainide Hydrochloride (±)-2-Amin
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: to the bile acids. Thus due to ente
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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