Organic synthesis in drug development Flashcards
linear, convergent and parallel sythesis
singular reactions designed to make one compound in each reaction vessel
linear, convergent and parallel synthesis are useful for __
targeted libraries (lead optimization)
combinatorial chemistry:
collection of techniques that allow for the simultaneous generation of large numbers of chemical compounds at the same time using a variety of starting materials
combinatorial chemistry tests
a mixture of compounds (high throughput screening)
diversity-oriented synthesis
designed to produce as many diverse compounds as possible from a single scaffold
protecting group:
inert group intended to mask the reactivity of a particular functional group to prevent it from interfering with the desired reaction
_____ used to make small sets of targeted analogues
linear, convergent, parallel synthesis
linear, convergent and parallel synthesis are usually performed in the __ phase
solution
linear synthesis:
sequential reactions in which product of first reaction is used in the next reaction in a linear fashion
convergent synthesis:
approach designed to improve overall yield of final compound by synthesizing fragments before coupling them together in final reaction
parallel synthesis:
performing organic reactions (often the same reaction) side by side to generate diverse compounds for SAR
in parallel synthesis, modifications of lead to generate diversity should
be made at last possible step
in organic synthesis for SAR, a lead scaffold is used to generate __ optimized analogues
less than 100
With organic synthesis for SAR, less than ___ reactions is OK, less than ____ is ideal
10/5
combinatorial chemistry:
a particular set of building blocks or precursors are used to prepare all possible derivatives of a given compound class
combinatorial chemistry synthesizes compounds ______ and can test ___
in a single vessel/ as a mixture
combinatorial chemistry: if you have an active mixture:
identify active component
combinatorial chemistry: if you have an inactive mixture:
store for next high througput screening
In solid-phase organic synthesis, the starting compound is ______ bound to ______ and sequential reactions are performed to produce ______
covalently/ insoluble resin bead/ a library of diverse compounds
the ___ and __ used in solid-phase organic synthesis are soluble
linker/ reagents
reactions can be driven to completion with excess reagents that can be easily removed through washing steps: advantage of _____
solid phase organic synthesis
Are purification steps necessary at intermediate stages of solid-phase organic synthesis?
No
Can individual beads be separated at the end of solid-phase organic synthesis to give individual products?
Yes
Can solid-phase organic synthesis be automated?
Yes
for SPOS, ______ and ______ must be inert to reaction conditions
resin bead/ linker
the linker in SPOS must be ____ through a _____ such as _______
easily cleaved/ direct mechanism/ (acid/base)
ideally, in SPOS, _____ should be cleaved through the same mechanism as ____
protecting groups/ linkers
