MEDICINAL CHEMISTRY

Official drugs:
Prazosin Hydrochloride, B.P. 2-[4{2-Furoyl)-piperazin-1-yl]-6,7-dimethoxyquinazolin-
4-ylamine hydrochloride. It is a white or almost white powder and is very
slightly soluble in water.
Prazosin is well absorbed from the gastrointestinal tract; the bioavailability is about 70%.
On oral administration the peak concentrations in plasma are reached within 1 to 3
hours. Prazosin is extensively metabolized in the liver.
Prazosin hydrochloride is used in the treatment of all grades of hypertension usually as
a second step agent in conjunction with a diuretic or other antihypertensive agent. The
dose of the drug is 500 µg given 2 to 4 times daily.
Preparation: Prazosin Tablets, B.P. Proprietary Names: HYPOVASE; MINIPRESS;
PRAZOPRESS
A (2). β - Adrenoceptor antagonists: Propranolol (53) is an aryloxypropranolamine
and non-selective β-adrenergic antagonist. In aqueous solution propranolol decomposes
with oxidation of the isopropylamino side chain, leading to discoloration of the solution.
Solutions are most stable at pH 3 decomposes rapidly when alkaline. It is highly
lipophilic and completely absorbed from the gastrointestinal tract. It is extensively
metabolized in liver. The major metabolite is 4-hydroxypropranolol (54) which possesses
some β-adrenergic blocking activity.
CH3 O CH2-CH-CH2-NH-CH CH
OH
3
Propranolol (53)
Hepatic Metabolism
CH3 O CH2-CH-CH2-NH-CH CH
OH
3
OH
4 - Hydroxypropranolol (54)
The (-) - enantiomers of propranolol and other β - blockers are the active forms of the
drugs.
OH
OCH 2CHCH 2NHCH
CH 2CONH 2
Synthesis of Propranolol:
OH
CH 3
CH 3
Atenolol (55)
+ ClCH 2CH CH 2
α-Naphthol (57) Epichlorohydrin (58)
O
NaOH
Intermediate
OH
OCH 2CHCH 2NHCH
CH 2CH 2COCH 3
O
OCH 2CH CH 2
CH 3
CH 3
Metoprolol (56)
H 2NCH(CH 3) 2
Propranolol (53)