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From YouTube: Open Source Antibiotics Science Update Oct 2 2020
Description
Weekly open project meeting for Open Source Antibiotics Series 2.
Full Project: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles
Relevant GitHub Issue: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles/issues/30
On the call: Professor Matthew Todd, Dr Dana Klug, Dr Edwin Tse (all University College London), Dr Ben Perry (DNDi), Anthony Sama.
A
Okay,
welcome
everybody
to
open
source
antibiotics
series
2
meeting
on
friday
october
2nd.
So
thanks
for
everyone
for
coming
along
here
is
issue
on
github
that
talks
about
all
things
that
are
going
on
in
this
series
at
the
moment
with
the
various
action
items.
So
I
think
the
main
thing
I'll
just
be
updated
on
chemistry
and
some
compound
design
things,
but
just
as
an
update,
we
got
this
update
from
lead
grades
at
unc
about
the
mechanism
action.
A
So
the
compounds
that
we
sent
over
one
active
and
one
inactive
we
previously
talked
about
the
need
to
make
sure
the
compounds
were
active
and
inactive
in
their
essay,
because
I
think
they're
using
compounds
that
have
been
in
the
freezer
for
a
while
or
fridge
for
a
while.
So
they
had
them
tested
in
a
kind
of
mercer
assay,
that's
being
run
over
there
and
they
were
fine.
So
the
active
was
active
and
the
inactive
was
inactive
kind
of
the
the
active
was
10
micromolar,
which
I
think
is
not
actually
that
far
off
hours.
A
When
you
do
the
calculation,
it's
a
different
unit
to
two
hours,
which
is
a
you
know,
micrograms
per
ml
or
whatever
it
was,
but
I
think
it's
an
active
compound.
So
I
think
it's
fine
and
it's
a
good
control
for
the
for
the
for
the
mechanism
action
study,
so
those
experiments
are
starting
now
and
I
reckon
we'll
have
data
at
the
end
of
october,
which
is
really
good,
so
they're
underway,
which
is
fantastic
for
the
in
vitro
stuff
that
we
talked
about
last
time.
A
We
still
have
this
thing,
which
one
of
us
is
going
to
have
to
solve
about
the
compatibility
of
the
units
which
I
haven't
looked
at
just
to
make
sure
that
we're
talking
about
the
same
things.
But
this
second
point
was
the
crucial
thing
from
last.
Well,
a
crucial
thing
from
last
time
was
that
the
compounds
that
we
were
interested
in
for
the
metabolic
id
studies
and
more
investigation
of
clearance,
we
had
thought
we
were
going
to
use
the
the
main
active
which
had
the
benzothiapene
in
it.
A
But
it
turns
out
that
that
compound
is
declared
ridiculously
fast
and
actually
isn't
that
interesting
and
we
should
go
for
a
compound
which
has
you
know
you
know
fast,
but
not
too
fast
clearance,
which
is
more
typical.
I
think
of
the
series
which
lacks
the
sulfur,
and
so
I
think
we've
become
much
much
in
this
benzofuran
compound,
which
I
think
was
number
compound
with
the
hg1
at
the
end.
A
A
Do
the
suzuki
great
okay,
fantastic
yeah?
I
think
it's
it's
going
to
be
a
good
one
to
go
for.
I
reckon
just
because
it's
more
representative,
you
know
and
it'll
have
metabolites
in
a
more
typical
all
right
good
for
the
screening.
We've
lined
up
a
bunch
of
another
assay
screen
for
potency
for
october.
A
So
that's
that's
progressing
and
we're
nearly
done
by
functionalization
we're
we
that
was
held
up
because
because
of
the
results
from
last
week,
because
I
think
we
need
to
send
compound
821
so
that
that
paperwork
will
go
in
today
and
and
we'll
finalize
that
and
I'm
I've
pinged
this
week,
gsk
just
to
check
that
I
can.
I
can
paste
a
bunch
of
stuff
about
some
history
of
this
series,
I'm
still
waiting
to
hear
back,
but
I'm
I'm
pursuing
that
still.
A
A
A
B
Okay,
so
I'm
still
trying
to
make
the
borinate
of
the
imidazole,
so
I
did
go
back
and
do
some
close
lit
examinations.
There's
a
lot
of
tin
couplings
at
this
four
position,
which
is
how
people
are
getting
heterocycles
on
there,
which
I
kind
of
wanted
to
avoid.
But
I
did
find
an
example
where
they
did
the
borrelation
in
dmf
instead
of
dioxane.
So
I
tried
that-
and
these
reactions
two
are
a
little
bit
hard
to
monitor
because
they
don't
they
don't
ionize
very
well
and
they're,
not
all
that
uv
active.
B
B
Then,
in
parallel
to
that,
I
was
also
looking
at
with
the
title
group
on,
because
there
are
several
examples
of
that.
This
reaction
I
put
in
the
microwave
it
does
look
like
it
went
a
little
bit
better
than
conventional
heating.
So
I
think
I'm
going
to
try
the
same
thing
with
the
crude
material
here,
because
it
was
similar,
it
does
look
like
the
certain
material
has
been
consumed
and,
and
it
could
have
some
product
then
this
at
the
bottom.
A
B
B
D
B
And
then
the
borrelation
so
looking
up
going
forward
if
these
turn
out
that
they
don't
haven't
worked,
I
did
find
this
isopropyl
magnesium
chloride,
prep
of
the
boronic
acid.
So
I
we
have
the
trimethyl
borane,
but
not
the
grignard.
So
I
ordered
that
so
that
we
can
try
and
then,
if
none
of
that
works,
I
can
try
this
sort
of
pathway
b,
which
just
go
puts
in
the
two
periodical
in
sort
of
this
one
pot
procedure,
but
that
we
have
to
order
both
of
the
starting
materials.
C
So
I
tried
to
do
this
acel
bermination
this
week,
but
I
kind
of
gave
up
on
it
because
it's
just
really
messy
just
yeah,
not
very
nice,
to
work
with,
but
there's
another
prep
which
uses
this
pyridinium
bromide,
which
is
a
lot
easier
to
handle
and
I
think,
based
on
the
pattern,
the
reactions
also
a
lot
easier.
So
I'm
I've
ordered
that
so
I'll.
Try
that
when
that
comes
in
and
then
that'll
make
yeah,
I
guess
with
this
core
on
that
one.
C
B
C
And
then
for
these
cores,
so
I've
made
all
of
these,
so
I
just
need
to
do
suzukis.
As
I
said
before,
so
I
made
the
boronate
the
benzofuran
there's
a
bit
of
the
bt,
pin
2
left
in
it,
but
it's
more
trouble
to
try
and
purify
it.
I
think,
because
it
just
cool
loots
and
then
yeah.
So
these
are
the
four
target
compounds
from
that
do
we
do
you
think
we
still
need
to
make
the
benzodiazepine
versions
of
these
since.
E
E
C
A
C
F
F
F
C
D
F
B
F
A
So
I
mean
I
think
what
we're
doing
at
the
moment
is
planning
for.
You
know
another
screen
in
about
a
week's
time
or
so
and
seeing
if
we
can
build
the
potency
out,
because
that
will
inform
what
we
then
send
for
next
in
vitro
pk
and
we're
awaiting
the
moa
stuff.
So
I
guess
they
we're
we're
sort
of
taking
care
of
everything.
I
think.
A
F
I'm
going
to
need
to
see
the
structures
again.
Sorry,
I
was
just
wondering
if
you
I'm
wondering
if
you
thought,
if
you
thought,
or
looked
up
in
the
literature,
whether
it's
possible
to
form
the
two
three
arrow
substituted
targets.
So
let's
look
okay,
compound
one,
one,
four,
four
one,
for
example
right
the
one
at
the
bottom.
A
B
B
F
Is
it
known
to
make
those
compounds?
You
know
using
a
three
plus
two
now
you've
got
the
regiochemistry
problem
right,
which
is
you're,
probably
going
to
end
up
with
a
mixture
of
the
pyridal
and
the
benzothiapine
at
the
at
the
two
positions
and
then
how
using
nmr,
how
you
mean
you
have
to
you're
gonna,
have
to
use
energy
to
be
able
to
distinguish
between
the
two
and
hope
that
it
works.
F
Mean
it's
I'm
just
throwing
out
there
as
an
idea,
because,
but
the
the
kinds
of
coupling
you're
doing
here
the
suzuki
couplings
from
that
three
brominated
position
does
work
right,
so
yeah,
I'm
just
putting
them
back,
I'm
just
saying,
if
you're
having
trouble
with
making
some
of
these
targets.
That
might
be
the
way
to
do
it
and
also
the
other
thing.
It
was
a
question.
It
wasn't
clear
to
me
why
you're
trying
to
make
one
four
five
and
one
three
five,
two
like
the
copper
in
the
top
right.
B
B
F
Yeah
I
mean
I
would
do
that
yeah,
it's
an
interesting
approach,
but
you're
cutting
off
quite
a
large
part
of
your
molecule
and
risk
is
that
you
know
it
means
no.
We
don't
have
these
things,
but
you,
I
would
have
you
thought
about
bulletproofing
the
ring
instead
and
putting
like
incorporating
an
oxygen
in
or
substituting
the
ring
in
such
a
way
that
you
know
you
basically
making
a
little
bit
more
polar.
That
would
be
one
way
and
then
from
our
ex.
E
E
E
A
The
the
compound
donations
are
playing
a
lot
on
the
144
structure.
Right,
that's
the
majority,
so
we're
going
to
get
a
lot
from
that.
I
think
in
a
sense
of
clues
as
to
what
might
be
tolerated,
which
is
going
to
help.
I
think
you
know,
and
some
of
the
judgments
we
made
early
on
about
the
sar
were
a
little
bit
skewed,
because
we
assume
that
a
lot
of
these
things
were
active
and
actually,
maybe
so
sorry
to
see
a
lot
of
these
things
were
inactive
when
actually
they
may
have
been
active.
A
A
B
I
think
we
can
say
a
lot
about
the
sort
of
benz
of
benzothiaphine
benzifioran,
the
basically
with
the
blue,
everything
that's
blue
on
github
that
we
can
say
a
lot
about
because
we
can
compare
back
to
you
know
8
22,
but
the
other,
the
core
and
then
the
periodical
stuff.
That
is
a
little
bit
more
of
a
question
mark.