#MedicinalChemistry #SAR #furosemide #EthacrynicAcid #LoopDiuretics
Hello everyone assalamu alaikum welcome to the new lecture on medicinal chemistry this is me faraz gurban rajvar and in this video lecture i am going to discuss with you about the structure activity relationship of the loop diuretic sa are of loop diuretic as far as loop diuretic are concerned on the basis of their chemical structure they are classified in the
Two main categories one class has the five sulforamide two amino benzoic acid derivative the examples are furosemide azosimite means furosemide or azosemite can be considered as the derivative of 5 sulforamide 2 amino benzoic acid the next class is the 5 sulforamide 3 amino benzoic acid derivative the example of loop diuretic that comes under this class are the
Pyritenide and the bumatinide they have the five sulforamide iii aminobenzoic acid substitution in their chemical structure so this is the chemical structure of the furosemide and now let’s check out the substitution of the different functional group like at the first position the carbonyl functional group are the carboxylic functional group is essential for
The optimal loop diuretic activity means this must be left unsubstituted because we have already observed that these loop diuretic are mainly the carboxylic acid derivative the next is the substitution of the different activating group in the position number four so the position number four of the loop priority can be substituted with the halogen like chlorine
Alkoxy aniline benzyl or benzoyl functional group the substitution of the fourth position with any of these group will enhances their diuretic activity like in this example of furosemide we have the chlorine that is the halogen present at the fourth number position and this is essential for the activity the next point is the presence of the sulphur mild functional
Group the sulforamide functional group is essential for the loop diuretic activity we have already discussed that the basic structural component of the loop diuretic are the five sulforamide benzoic acid clear so in this case you may also observe that in the furosemide we have this surface group at the five position so i am again repeating the numbering this is
The number one two three four five so this five position sulphur my functional group is also essential for the loop diuretic action of the loop diuretics the two series of the five sulforamide benzoic acid are differ only in the nature of the functional group that is in the second and third position so they are mainly a differentiating on the basis of the amino
Group like in some cases we have the amino group present at the second and in the third so this is basically representing what the major classes of the loop diuretic that are the five sulforamide two amino benzoic acid derivative and five sulfomyel three amino benzoic acid derivative the presence of heterocyclic ring like for fury or phenyl are thionyl methyl at
The second amino functional group in case of five sulforamide two amino benzoic acid will gives the maximum diuretic activity so this is telling what this is telling that in case of the five sulforamide two amino benzoic acid derivative of the loop diuretic if we are going to substitute the second position with the for fuel ironing or phenyl or thion ivory like
In case of furosemide we have this fur fury lamin methylamine ring so this will enhances our this will causes the maximum diuretic action of the particular diuretic so this is over here the example of the furosemide that has the fur fury methylamine ring at the second number position now let’s check out the alkyl substitution if we are going to substitute the
Alkyl side chain okay like at the position number third amino group in case of the five sulforamide three amino benzoic acid then it will result in the diuretic that will have the high diuretic activity the example is the bumitinite this is the chemical structure of the metanite then this you may observe that we have the if five sulforamide three amino benzoic
Acid like numbering will start from here one two three means we have the amino group at the third position and beside this this amino group at the third position is being further substituted with the alkyl that is the butyl side chain so this will result in the bumitinide structure sar of bumatinide so the this is again the chemical structure of bumatinide given
Here you may observe that this is formed by the five sulforamide three amino benzoic acid derivative and with the third position a minor is being further substituted with the butyl side chain now let’s observe the other structural changes we can made in the structure of umitinite the bumitinide differ from the furosemide in that it has the phenoxy functional
Group that is also an electron with triangle present at the fourth position in case of furosemide we have the chlorine our halogen functional group at the fourth position so if someone asks you what is the difference between the furosemide and bumatini are in their chemical structure so you have to mention this fourth position difference that is the presence of
Chloro or the presence of the phenoxy functional group so this bumitonite has the shorter duration of action but it’s 50 times more potent than the furosemide or other loop diuretic and we can say that this difference can be due to the presence of this phenoxy functional group and the presence of the three position amino group if we are going to substitute with
The fin this phenoxy functional group at position number four with any type of other like phenylalamine or other type of aromatic side chain then it will result in in the favorable compound mean the resultant derivative will also have the good diuretic activity essay of ether chronic acid eta chronic acid we know that it is the phenoxy acidic acid derivative
This is the phenoxy acetic acid derivative its chemical structure contain the aromatic ring this one is the benzene aromatic ring and on the one side of the ring we have the methyl butyrill ketone this region is the methyl albutory ketone and on the other side we have the anoxyacetic acid and for the maximum optimal loop diuretic effect of the ether chronic acid
The one position in the aromatic ring ortho to the unsaturated ketone must be substituted with the halogen or any type of the methyl so this will enhance the diuretic effect of the ethacarenic acid that is the loop diuretic effect further die substitution in the second and third position with the halogen that are the electron withdrawing group will increases
The diuretic effect means if these position that have the already the chlorine atom they have enhanced the diuretic or the loop diuretic effect of the ethactronic acid the reduction of double bond will decrease the but don’t abolish the activity if we are going to reduce this double bond that is the present in this side chain it will cause the reduction in the
Activity the unsaturated ketone that is this region of the ether chronic acid must be para to the position with respect to the oxy acetic acid so you may observe that this is present directly in para position to the oxy acetic acid region of the ethactrinic acid if we are going to substitute it to the earth our meta position then it will result in the decrease of
The diuretic activity so this was all about the medicinal chemistry of the loop diuretic
Transcribed from video
SAR of Loop Diuretics || Furosemide Bumetanide Ethacrynic Acid || Diuretics || Medicinal Chemistry By Faraz Qurban Rajper
