Block 5 (Test 1) Flashcards
what is a bioisostere?
a substituent or functional group with similar chemical/physical properties and which produces broadly similar biological properties
List examples of classical monovalent bioisosteres
CH3 OH NH2 S
list examples of classical divalent bioisosteres
R-O-R, R-NH-R, R-CH2-R
List examples of classical trivalent bioisosteres
R-N=R, R-CH=R
List examples of classical tetravalent bioisosteres
R=C=R, R=N=R, R=P=R
what are non-classical bioisosteres?
they do not have the same number of atoms and do not fit steric or electronic rules of classical isosteres, but they have similar biological activity
boronic acid is a bioisostere of _______. what is the result of using this bioisostere?
carboxylic acid boronic acid forms a covalent bond instead of a hydrogen bond (how COOH works), thus making it a suicide inhibitor
what is a prodrug?
an inactive compound that is converted (either chemically or enzymatically) to the active form (once in the body)
what are the two main considerations when making a prodrug?
effective conversion to active drug in the blood stream the prodrug “shield” group is not toxic when released
describe the function of ester prodrugs
carboxylic acids are excellent HBA and HBD, but they ionize too easily which can be a problem in crossing membranes a prodrug is used to protect the acid function by making it an ester. the less polar ester can cross the membrane and be hydrolyzed to the acid by an esterase enzyme
how do prodrugs aid in circumventing metabolism?
they are often designed to be slowly converted into the active metabolite in order to prolong plasma levels
give an example of how prodrugs mask toxicity
ex. salicylic acid is known to cause GI bleeding due to its phenolic group. by making it a prodrug (masking the phenol), the active drug is only exposed by esterases once it enters the bloodstream
what is the most common activation pathway of a prodrug?
hydrolysis with esterase
the major objectives of prodrugs are
improved bioavailability improved aqueous solubility improved passive intestinal absorption
NMR stands for
nuclear magnetic resonance
___________ provides a direct link between the genetic alterations and a disease phenotype. _______ identified this way are more likely to be the cause rather than a consequence.
phenotypic screening genes
phenotypic screening is a whole organism (or cell) approach that speeds up ______________.
physicochemical property optimization
iPSC stands for
induced pluripotent stem cells
_____ can be differentiated into neurons (or other cell types) that harbor the same genetic mutation as the patient
iPSCs
describe theranostics
the combination of diagnostics and therapeutics using the same molecular scaffold
what is chemical biology (chemical genetics)
using a chemical to probe to learn about biological functions (usually a signaling pathway)
_______ enables identification of the biomolecular targets of efficacious agents with unknown mechanisms of action
Reverse Pharmacology
______ is a technique that is used with chemical biology approach to understand which proteins are impacted by the process
proteomics
organic elements include
H, C, O, N
essential macronutrients include
Na, K, Mg, Ca, P, S, Cl, Si, Fe
the most important class of inorganic chemical therapeutics by far is
cisplantin (platinum) acts by forming a covalent “complex” with guanine that leads to cytotoxicity and apoptosis
the three approved platinum based treatments for cancer include
carboplatin, oxaliplatin, and cisplatin
why are metals good for structural scaffolds?
they have greater valency and can accommodate more bonds
what useful property does boron possess?
it can exist as both tri and tetra valent it is also non-toxic
_________ was the first non-platinum based chemotherapeutic approved since the approval of platinum
velcade
imaging agents are designed to
provide more information about internal organs or processes
a vast majority of imaging agents have a _______ that acts as a delivery vehicle to deliver the _______ to the site of action you want to image
organic scaffold inorganic element
fluorodeoxyglucose is used in association with
PET scans
________ looks at physiologic parameters of the body (glucose metabolism, protein composition, etc.)
PET scans
SPECT is used for
visualizing vasculature
What is the difference between target validation via gene knockout and via the RNAi method?
Gene knockout inhibits protein expression fully and RNAi results in partial inhibition of protein expression.
Define medicinal chemistry.
The science that deals with the discovery/design of new therapeutic agents and their development into useful medications
