Medicinal Chemistry Lecture 4 PDF

Medicinal Chemistry I [PC508] Lecture 4  II]-Cephalosporins SAR of cephalosporins : Substitution at C7 wz methoxy gp give a class known as cephamycins that are more...

Medicinal Chemistry I [PC508] Lecture 4  II]-Cephalosporins SAR of cephalosporins : Substitution at C7 wz methoxy gp give a class known as cephamycins that are more resistant to B-lactamases. Double boiund at C3 HH H is must for activitty R N S O N O CH3 O Must for activity COOH O Must for activity Must for activity : Effect of acidity on acetyloxy group containing cephalosporins H H H H H H R N S R N S Hydrolysis O N O CH3 O N OH O O COOH O COOH H H H Lactonization R N S O N O O O 1st generation orally used Cephalosporins: H2N H H H NH S O N O CH3 COOH 1st generation orally used Cephalosporins: H2N H H H NH S O N O CH3 COOH 1st generation orally used Cephalosporins: H2N H H H NH S O N HO O CH3 COOH Cephalothin(thiophene ring) H H NH S O N O CH3 S O O COOH Cephaloridine H H NH S + S O N N O COO  2nd generation Cephalosporins Cephamycins Oximinocephalosprins Cefuroxime III]-Carbapenams  Thienamycien OH H H NH2 CH3 S N O COOH Imipenem : Etapenem Non B-lactam Antibiotics  I]-Tetracyclins Mode of action: Act through inhibiting Protein synthesis by binding to30S ribosomal subunit SAR Effect of acidity  CH3 OH N(CH3)2 H 7 6 5 4 OH 8 3 D CH B A 9 NH2 2 10 11 12 1 OH OH O OH O O Doxycyclin: Tetracyclin of choice in uremic patients. Acid stable due to no OH at C6.  N(CH3)2 R3 N(CH3)2 H 7 6 5 4 OH 8 3 D CH B A 9 NH2 2 10 11 12 1 OH OH O OH O O Minocycline: Most lipophilic tetracycline. It has cidal effect. Acid stable due to no OH at C6. Higher potency due to Subs at C7  II]-Aminoglycosides ▪ MOA: Inhibit protein synthesis through binding with 30S ribosomal subunits. ▪ Highly polar so used IV in systemic infections and orally only in GIT infections. ▪ Have synergistic effect with B-lactam antibiotics. ▪ There are chemical incompatibility with B-lactam antibiotics so should not be used in one compartment.  Kanamycin: NH 2 HO O HO H NH 2 Kanamycin B Ac OH NH 2 HO Ad HO O HO O NH 2 H Phos HO H H2N Kanamycin C HO - NH 2 6 -glucosamnine O HO O 2-Deoxystreptamine HO O OH HO NH 2 // 3 -glucosamine  Amikacin:  Gentamicin:  III]-Macrolides ▪ They formed from large lacton ring its size [14-16] atom attached to two sugars one of them is amino sugar. ▪ MOA: Narrow spectrum , affects mainly +ve bacteria in upper and lower respiratory tract infections through Inhibiting protein synthesis by binding with 50S ribosomal subunits.  Erthromycine Clarithromycine Azithromycine  IV]-Chloramphenicol OH H Cl O2N C C NHCOCH Cl H CH2OH D-(-)-Threo-2-dichloroacetamido-1-p-nitro-phenyl-propan- 1,3-diol  IV]-Chloramphenicol OH H Cl O2N C C NHCOCH Cl H CH2OH D-(-)-Threo-2-dichloroacetamido-1-p-nitro-phenyl-propan- 1,3-diol ▪ MOA: Inhibit protein synthesis through binding with 50S ribosomal subunits. ▪ Drug of choice in the ttt of typhoid and partyphoid. ▪ Its toxic side effects is due to its toxic metabolites. ▪ Has 4 isomers but only the D-Threo- isomer is the active one. ▪ Its main side effects is bone marrow depression and aplastic anemia in adults and gray baby syndrome in neonates. SAR: Thank you