Name: Jannatul sumaiyaId: 1631431049SympatholyticsSympatholytics known as adrenergic blockin agents. Sympatholytics have the opposite effect of adrenergic agent.Sympatholytics classification depend on the adrenergic receptor typesAlpha receptorBeta receptorBeta receptor or blockers have 3 part:Competitive agonistPropranololAcetabutolpropranolol1-isopropylamino-3-(1-naphthyloxy)-2-propranololPropranolol is the non selective beta adrenergic antagonist. Hypertension,caqrdiac arrhythmia, myocardial infection indicated by the propranolol. Its control the tachycardia.Synthesis of propranolol. Propranolol interaction with the target O site involved in H bonding to receptor.Benzene groups variable with heteromatic ringsOH essential h bonding interaction2- propanol are branching and extension both beneficial.
Fits hydrophobic receptor.Structure activity relationship Basic structure of propranololІ-blockers’ binding site to the receptor is the same as for endogenous catecholamines, such as noradrenaline and adrenaline. This binding is based on hydrogen bonds between the І-blocker and the recept Propranolol are blocks the or, its not based on covalent bonds,The development of І adrenergic antagonists was the discovery that an oxymethylene bridge (”OCH2”,) compect into the arylethanolamine structure of pronethalol for production of propranolol.
Figure 8: Structural activity relationship for І-blockers.X is part of the propranolol, its linked with aromatic ring or ”OCH2” group .X is( ”CH2CH2”),( ”CH=CH”),( ”SCH2” or ”NCH2”), maximum time there is no activity, some time show little activity.The R1 group can only be a secondary annulment and branched is the appeasement choiceAlkyl (”CH3) annulment on the ±, І or і carbon lower beta blockade, its bind especially ± carbonY is the benzene ring. Benzene , naphthalene, heterocycle and condensed ring. On the ring can be methyl, methoxy and nitro 2,4 or 2,3,6 substitute simultaneously, best activety.Propranolol is the aromatic substitution . we know aromatic substitution is: ortho > meta > para . Its give the non-selective І-blockers. Large ortho-groups usually increase some activity but large para-substituents decrease activity. In Y or benzene ring 2 and 6 carbon inactive the compound, but when substation on 3,5 carbon its makes some activity. the highest cardioactuvety following: para > meta > ortho. All the І-blockade is in one isomer, (S)-aryloxypropylamine and (R)-ethanolamineToday, most of the І-blockers used clinically are aryloxypropanolamines. If the length of the side chain is increased introduced an oxymethylene bridge. Mechanism of action Propranolol are blocks the І1 and І2 receptor in heart and kidney. Then decreases renin secretion and decreases force of contraction and heart rate and cardiac output . after decreases renin secretion effects of renin angiontensin system at the last stage its decreases blood pressure. Development of propranololDue to some adverse effect of propranolol, second generation beta blockers are developed.Propranolol acts against both І1 and І2 adrenoceptorsІ2 adrenoceptor antagonist constricts airways, thus can not be used on asthma patient.This why more selective beta1 blockers are desigened for second generation drug such as practolol. First generation of drug modifying second generation drug Propranolol practolol Side effectsDiarrhea wheezing or symptoms of bronchitis Some time feeling weakIncreasing Hair lossDecreased the heart rateStarting breathing problems or bronchospasmsShow the allergic reactions, such as itching, rashes and hives, or swelling in the face or tonguesudden weight gainchanging blood sugarcirculation problem show the cold hands and feetContraindicationHeart rate become slow Sinus syndrome occur sickAtrioventricular blockLow blood pressureCocaine toxicityThe role of medicinal chemistry in drug discovery .Drug discovery is most important framework for pharmaceutical industry. It is estimated that the average cost to research each successful drug is between $800m to $1bn. Drug discovery ha pass through many changes in before today but all changes object has remained same to express good medicine for all disease . medicinal chemistry is the main part of drug discovery. The traditional method accept by medicinal chemists modifying bio-active molecules from natural products. Natural products are source of active ingredients in most of existing drugs. But now days drug discovery method is change by the modern technology such as combinatorial chemistry, microwave assisted organic synthesis (MAOS) and high-throughput (HTS) biological screening. The medicinal chemistry and biology achieve lead molecule which use to new drug discovery. For example anihypersensitive drug are first discover initially then day by day our pharmacist research on it and discover there classification for treatment of different cause of hypertension . so we can say medicinal chemistry remains the most invaluable science and play most important role in the existing drug discovery. Current and future prospect Modern chemistry of drug discovery foundation were made in 18th and 19th centuries . Development of new molecular drugs from the herbal plants to spurious chemistry is the improvement. About 10-14 years are needed to develop a new molecule with an average cost of more than $800 million. Then pharmaceutical industry invest this highest percentage of revenues but market not response proportionately Conclusion Existing drug Is drug which are modifying generation to generation. For existing drug our medical science are improving. For medicinal chemistry we can research on drug and discover existing drug. The most common cause of ulcer is the infection caused by Helicobacter pylori and long term use of NSAIDS. To prevent ulcer there are drugs like proton inhibitors such as Omeprazole and antibiotics like Amoxicilline.In the first time of hypertensive drug as -SH group which give the side effect like rash and taste disturbances at higher doses, then modifying this drug in second generation ACE inhibitor enalaprilat used a “COOH group to bind Zn except fosinopril. The free “CCOH group cause poor absorption. So its show again side effect then they are synthesized the prodrug esters which help fine absorbed then its made the active drug. Lisinopril and captopril are active compound so do not required conversion.Existing drugs which are safe and pharmacokinetics effects in human are confirmed and clinically approve for use are examined compherehensively that results in development of new medicines . the strategy is based on many existing drugs which mechanism of action is still unknown and based on their side effects to develop more safer drugs.