Med Chem Test 2: quick review

what is in between your IND and NDA

clinical trials

a description of molecular features that are necessary for molecular recognition of a ligand by the target protein

pharmacophore

the five rules

low molecular weight

good solubility: low log P

fewer than 10 hydrogen bond acceptors

fewer than 5 hydrogen bond donors

2 ways to start from natural substances in drug design

natural substrate , natural product

drugs that came from natural substances

penicillin, taxane

2 ways to start from existing molecules in drug design

start from another companies compound

drug repurposing

a compound resulting from the exchange of an atom or a group of atoms in a molecule with another atom that is chemically or physically similar enough to retain the molecule'a biological properties

bioisotere

drug from existing molecules

enzalutamide

2 ways to start from rational design in drug design

ligand based

structure-based drug design

drug from rational design (ligand)

albuterol

drug from rational design (SBDD)

gleevec

what drug is designed against BCR-AbI

gleevec (imatinib)

a new strategy for targeting protein-protein interactions

fragement-based drug design

goal of HIt to LEAd

Validate hits from screening

should know target now

enhance potency/selectivity

goal of Lead optimization

refine leads into a preclinical candidate

improve PK and PD in animals

FdUMP is a suicide inhibitor of

thymidylate synthase

What enzyme converts 5-Fu to 5-fluorodeoxyuridine (FdUrd)

thymidine phosophorylase

does thymidaine kinase activate or deactivate FdUrd

activate

thymidine kinase

converts FdUrd to FdUMP by adding a phosphate to the 5' position on ribose

what is the inactivator of 5-FU

DPYP

DPYD converts 5-FU to

an inactive metabolite

reduces double bond

what inactivates thiopurine therapeutics

thiopurine transmethyltransferase (TPMT)

how does NUDT15 inactive thiopurines

converts triphosphate into monophosphate

what compounds can be reabsorbed back into the bloodstream

lipophilic

What is the structure of CYP450

heme and cysteine residues (SH)

what enzyme is required for sulfur oxidation/reduction

flavin monooxygenases

sulfoxide

prodrug that gets reduced

sulfide

active drug that is oxidized to sulfone

ester and amide hydrolysis is phase 1 or 2

1

RNO2 to RNH2 is

phase 1

glucuronidation

phase 2

enzyme donates glucuronic acid

sulfation

phase 2

what two enzymes are important in enterohepatic circulation

beta-glucuronidases and sulfatases

what amino acid participates in amino acid conjugation with aspirin

glycine

what can detoxify NAPQI

glutathione

gluathione reacts with

electron seeking carbons

the study of how an individual's genetic inheritance affects the body's response to drugs

pharmacogenomics

the study of the variation in a targeted gene

pharmacogenetics

MR

unmetabolized/metabolized

we don't want high

when fluoxetine is metabolized what is produced

norfluoxetine (toxic)

what drug requires metabolizing

codeine to morphine (activation)

CYP2D6 is needed for the _______ of nortriptyline

deactivation

what is the prodrug created from the metabolism of tamoxifen

endoxifen