* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download lec.11-426
Discovery and development of beta-blockers wikipedia , lookup
Discovery and development of cyclooxygenase 2 inhibitors wikipedia , lookup
CCR5 receptor antagonist wikipedia , lookup
Discovery and development of integrase inhibitors wikipedia , lookup
Discovery and development of neuraminidase inhibitors wikipedia , lookup
Discovery and development of angiotensin receptor blockers wikipedia , lookup
Discovery and development of tubulin inhibitors wikipedia , lookup
Discovery and development of non-nucleoside reverse-transcriptase inhibitors wikipedia , lookup
Development of analogs of thalidomide wikipedia , lookup
Discovery and development of antiandrogens wikipedia , lookup
Discovery and development of direct Xa inhibitors wikipedia , lookup
Discovery and development of proton pump inhibitors wikipedia , lookup
Drug discovery wikipedia , lookup
Discovery and development of cephalosporins wikipedia , lookup
NK1 receptor antagonist wikipedia , lookup
Cannabinoid receptor antagonist wikipedia , lookup
Nicotinic agonist wikipedia , lookup
Discovery and development of ACE inhibitors wikipedia , lookup
Metabolism • S-oxidation to give sulfoxide derivative …..inactive. • Terminal N demethylation …….is still active • C7 hydroxylation ……… inactive compound • Terminal N-oxidation ………..N-oxide derivative is inactive General Methods of Analysis: • An accurately weighed sample is dissolved in acetone or glacial acetic acid. Mercuric acetate solution is added and the solution titrated with 0.1 N perchloric acid with methyl orange as indicator. • Spectrophotometrically. • HPLC. Thioxanthene Derivatives Synthesis Fluorobutyrophenones Haloperidol • It is useful in the management of psychotic reactions, and hyperactivity. • It is a drug of choice for Tourett’s syndrome. • It is metabolized by oxidative N-dealkylation. • The oxidation products………………….. Droperidol • It may be used as an adjunct to anaesthesia or as an antiemetic. • It is frequently used in combination with narcotic analgesic, fentanyl citrate. Structure Activity Relationship 1. All potent compounds have 4-fluorophenylgroup, except anisoperidone which has a methoxy group in the para position f phenyl ring. 2. Reduction of the carbonyl group to –CHOH, as well as replacement by oxygen or sulfur decrease neuroleptic potency, whereas replacement of the ketone by a sulfone result in a loss of activity. X=C=O = CHOH = O, N, S or SO2 3. As a rule, lengthening, shortening, or branching of the propylene chain of 4aminobutyrophenones decrease neuroleptic potency. 4. Considerable variation is possible in the tertiary amino group with retention of neuroleptic activity. The basic nitrogen could be a part of a six membered ring, (piperidine, 1,2,3,6-tetrahydropyridyl, or piperazinyl). Replacement of the sixmembered basic heterocycle by larger or smaller or uncyclized amines diminishes neuroleptic potency. 5. Neuroleptic potency is generally associated with 4,4-disubstituted piperidines. Substitution of 2 or 3 positions of piperidines markedly decreases potency. The decrease in basicity of piperidine nitrogen by amide formation or quaternization abolishes activity. 6. High neuroleptic potency among derivatives of 4-piperazinylbutyrophenone requires an aromatic substituent in 4-position of the piperazine ring. e.g. Azabuperone