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Today & Tomorrow’s way of Treatment

Today & Tomorrow’s way of Treatment. An object is “chiral” if and only if it is not super imposable on its mirror image. Chirality changes the 3 dimensional interaction of similar looking objects with its receptors or immediate environment. Enantiomer:

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Today & Tomorrow’s way of Treatment

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  1. Today & Tomorrow’s way of Treatment

  2. An object is “chiral” if and only if it is not super imposable on its mirror image. Chirality changes the 3 dimensional interaction of similar looking objects with its receptors or immediate environment. Enantiomer: Single isomer not super-imposable on its mirror image. What is Chirality ?

  3. Molecules interact stereo specifically

  4. Only one isomer is active, the other is “inactive”: Levocetirizine (active), Levofloxacin (active) S-amlodipine (active CCB) One isomer is active, the other is more potent Esomeprazole (more potent) S-pantoprazole (more potent) Beneficial effects reside in one enantiomer, the other enantiomer having antagonistic activity: Levo-salbutamol (bronchodilator without pro-inflammatory properties) Beneficial effects reside in one enantiomer, the other enantiomer having completely separate beneficial activity: Dextropropoxyphene (analgesic); levopropoxyphene (anti-tussive) Beneficial effects reside in one enantiomer, the other enantiomer having adverse activity: Esketamine (no hallucination/agitation), Levobupivacaine (no cardiotoxicity) S-metoprolol (beta-1 blocker); R-metoprolol (beta-2 blocker) Enantiomers Differ

  5. 50% impurity is not acceptable “Too often, and even without it being noticed, data in the scientific literature on mixture of stereoisomers, racemates, are presented as if only one compound were involved. The neglect of stereochemical aspects of drug action …. degrades many pharmacokinetic studies to expensive “highly sophisticated pseudoscientific nonsense.” “The development of “hybrid” drugs, presented as a step forward in medicinal chemistry, tends to be step backward in therapy.” EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1984, 26, 663-8

  6. US - FDA’s Policy Statement The guidelines strongly encourage the development of single isomers and discourage stereoisomeric (e.g., racemic) mixtures. Approval could not be granted for a drug containing more than one isomer unless the pharmacokinetic and pharmacodynamic properties of each could be described and, more importantly, justified (Chirality 1992;338-40; http://www.fda.gov/cder/guidance/stereo.htm).

  7. Beta adrenergic Antagonists: S(-)Metoprolol, S(-)Atenolol Calcium Channel Antagonists: S(-)Amlodipine, Diltiazem Antiarrhythmic Drugs: Quinidine ACE Inhibitor: Captopril, Enalapril, Ramipril , Lisinopril, Benazepril, Fosinopril , Perindopril Statins: Atorvastatin ,Simvastatin, Pravastatin, Lovastatin, Rosuvastatin Anti-platelet: Clopidogrel Centrally acting antihypertensive: Methyldopa Chirally Pure CVS products

  8. Recent Chiral Switches

  9. There is no place for racemates that cannot justify the existence of the “isomeric ballast” 50% impurity is not acceptable Chiral purification can help to improve the pharmacokinetics and phramcodynamics of racemates. Conclusions

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