Drug Classes According To Pharmacophore Flashcards
mechanisms of antibacterial agents
- inhibiting cell metabolism
- inhibiting cell wall synthesis
- interacting with plasma membrane
- disrupting protein synthesis
- inhibition of nucleic acid transport and replication
drug class that inhibits cell metabolism
sulfanilamide
sulfanilamide SAR (structure, activity relation)
- para amino group essential
- aromatic and sulfonamide essential
- aromatic ring must have para substitutions
- sulfonamide nitrogen must be primary or secondary
fanisdar
combination of sulfadoxine and pyrimethamine
fanisdar MOA
- blocks synthesis of tetrahydrofolate
- which is an enzyme cofactor that provides one carbon units for synthesis of pyrimidine nucleic acid bases
fanisdar conditions to treat
- malaria
- uti’s
- gut infections
drug class that inhibits cell wall synthesis
penicillins
penicillin SAR
- beta-lactam essential
- free COOH essential
- bicyclic system important
- acylamino side chain essential
- sulfur usual but not essential
- cis stereochemistry important with respect to acylamino side chain (bold wedge)
drug class that interacts with plasma membrane
ion-conducting antibiotics
examples of ion-conducting antibiotics
vancomycin, gramicidin A and polymyxin B
SAR of ion-conducting antibiotics
- they are massive structures
- active for G- bacteria
drug class that disrupts protein synthesis
- aminoglycosides
- tetracyclines
- macrolides
drug class that inhibits nucleic acid transportation and replication
- quinolones
- fluoroquinolones
- work by stabilising complex formed between DNA and topoisomerases
SAR of quinolones
- bicyclic ring
- pyridine
- piperazinyl ring at position 7 beneficial
- cyclopropyl substituent at position 1 increased broad spectrum activity
- replacement of nitrogen at position 8 reduced adverse reactions
drugs that inhibit transcription phase (antiviral agents)
- Efavirenz
- Didanosine
drug that inhibits post transcription phase (antiviral agents)
idinavir
idinavir
- relatively larger molecule
- no weird representations
- not as massive as vancomycin
drugs that are ion channel disruptors (antiviral agent)
- adamantanes
- look like a little hat
- contain NH3+ Cl-
inhibitors of neuraminidase (antiviral agent)
- zanamivir
- tamiflu
- both transition state inhibitors
antidiabetic agents
- insulinotropic agents
- insulin-sensitising agents
insulinotropic agents
- sulfonylureas
- act by closing membrane bound ATP sensitive potassium channels
SAR of sulfonylureas
- Sulfur atom double bonded to two oxygens
insulin-sensitising agents
- biguanides
- thiazolidinediones
SAR of biguanides
- has a double bonded NH side chain
common features in thiazolidinedione agonists
- pentagon structure with NH and S and two double bonded oxygens
- PPARy agonists
- treat diabetes by lowering serum glucose without increasing insulin secretion
PPARy
- nuclear receptor
- regulates fatty acid storage and glucose metabolism
alpha-glucosidase inhibitors
- numerous benzene rings attached to each other with lots of phenol groups
- delays digestion of dietary carbohydrate in the form of starch and sucrose into monosaccharides
- delaying absorption lowers blood glucose
classes of antineoplastics (anti-tumor)
- alkylating agents
- antimetabolites (acting on enzymes
- inhibitors of signaling pathways
- antimitotics
- topoisomerase II inhibitors
central nervous system agents
opioids
SAR of opioids
- 3 benzene rings
- alkene or 6-hydroy groups not essential
- phenol group is important
- tertiary amine is important
point to consider with opioids
analgesic activity not only related to presence of important function groups, but to their relative position with respect to each other
psychoactive drugs (hypnotics)
- benzodiazepines
- enhance effect of GABA at GABAa receptor, resulting in sedative, hypnotic, anxilytic, anticonvulsant and muscle relaxant properties
SAR of benzodiazepines
- benzene ring and 7-member diazepine ring
- activity decreased with substitutions on nitrogen larger than methyl
- activity decreased by substituents at benzene ring positions other that C7
- activity increased by electron withdrawing groups on C7
another psychoactive drug (hypnotics)
- barbiturates
SAR of barbiturates
- benzene ring with nitrogen substitutions in meta-substitution
- double bonded oxygens in ortho position
- hypnotic activity increases with lipid solubility until number of C atoms at both C-5 substituents is between 6 and 10
- unsaturated alkyl, alkenyl and alkynyl derivatives more hypnotic than saturated analogues
- polar substituents at position 5 decreases lipid solubility and potency
- replacement of oxygen at C-2 by sulfur results in faster onset but shorter duration of activity
drugs of alzheimers
- neostigmine
- donepezil
- rivastigmine
- galantamine
SAR of alzheimer’s drugs
- benzene ring attached to ester group
- ester attached to Me2N
SAR of drugs for parkinson’s disease
- based on L-DOPA, the precursor to dopamine, NA and A
- single benzene ring with two phenol groups at the meta and para positions
- R in dopamine = Me2NH2
- R in NA = CH(OH)CH2NH2
- R in A = CH(OH)CH2NHCH3
respiratory agents
- based on ephedrine
- salbutamol and salmeterol
SAR of respiratory agents
- N-alkyl substitution increases potency for beta-adrenergic receptor
- phenol group important
- alpha-methyl substitution increases potency for alpha-adrenergic receptor
- salbutamol has a hydroxymethylene group on meta position
- salmeterol is simply a longer molecule
why does salmeterol have a long duration of action compared to salbutamol?
because it is more lipophilic, so it can cross the BBB more easily
