►
From YouTube: Open Source Antibiotics Science Update Sept 25 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/29
On the call: Professor Matthew Todd, Dr Dana Klug, Dr Edwin Tse (all University College London), Dr Chris Swain (Cambridge MedChem Consulting).
A
A
So
thanks
dana
for
posting,
the
the
agenda
and
stuff
and
a
bunch
of
things
which
I'll
tweak
in
the
in
the
minutes
and
actions
which
lots
of
these
things
haven't
really
progressed
this
week.
The
other
lots
of
the
little
things
haven't
progressed
this
week,
but
the
compound
and
nations
thing
is
going
really
well.
Ben
posted
an
issue
about
all
the
structures
and
they're
coming
in
we've
had
quite
a
lot
of
correspondence
about
that
this
week.
A
I
think
and
lots
of
stuff
coming
in,
which
is
great
and
those
can
be
tested
where
we
are
and
we'll
talk
about
chemistry
in
a
minute.
But
I
guess
the
main
thing
is
to
talk
about
the
the
new
screening
data
metabolic
screening
clearance
study
from
monash.
If
you
want
to
talk
about
that,
so
thanks
for
posting
this
very
much
so
we
we
have
money
in
this
project
for
nine
evaluations
and
we
sent
over
five
compounds
the
original
data
we
had
for
the
project
is
shown
here
where
we
had
mostly
mouse
data.
A
B
I
think
yeah
I
was
trying
to
figure
that
out.
I
think
they
might
have
done
it
at
unc.
A
Okay,
all
right,
so
we
I
mean
these
are
the
original
data
which,
which
was
one
of
the
reasons
for
this
project
in
the
first
place,
was
that
the
clearance
was
very
high.
A
So
these
these
clinton
numbers
are
really
high,
but
it
was
all
mouse
and
only
one
rat
number
where
the
number
the
data
looks
slightly
better,
but
not
a
lot
better
and
it
was
for
these
three
compounds,
so
we
then
send
after
much
discussion,
we
sent
these
five
compounds,
including
the
original
eight
six,
eight,
and
so
the
the
the
danish
got.
The
original
mass
numbers
here-
and
this
one
wrapped
number
here
is-
is
up
there
for
ease
of
comparison
and
the
new
data,
all
the
human
and
most
of
the
rat
here.
B
So
one
thing
I
noticed
is
that
the
the
clint
data
is
different
units
between
unc
and
monash.
B
A
C
B
A
B
B
A
I
don't
know.
That's
okay,
we'll
clarify
that's
important,
so
that
makes
the
comparison
a
little
bit
strange,
but
because
the
the
rat
data
for
eight
six,
eight
there,
if
I
can
maybe
make
that
a
little
bit
bigger,
is,
is
roughly
equivalent
order
of
magnitude
equivalent,
which
is
helpful.
Obviously,
so
I
don't
know
again.
We
support
this
with
the
with
the
endless
malaria
data
that
the
mouse.
B
A
Always
looks
terrible
and
then
the
right
day's
a
bit
better
and
the
human
looks
actually
all
right.
I
don't
know
chris,
you
probably
know
much
more
about
this
night,
but
is
that?
Is
that
a
typical
trend?
Yes,
unfortunately,.
A
Yeah
so
because
we.
A
Yeah,
so
we
pick
where
for
that
reason,
because
you
know,
because
we
have
to
pick
one
or
the
other,
and
I
don't
know
I
mean
I
don't
know
what
we're
looking
for
in
terms
of
you
know
a
desirable
number
here.
I
guess
sorry.
The
thing
I
hadn't
correlated
on
to
was
the
the
correspondence
of
potency
here
dana.
So
the
one
with
the
problematic
data
is
the
one
that's
being
cleared
fastest.
B
A
A
A
B
I
mean
so
the
thiophene
does
seem
to
be
problematic
and
then
so.
The
reason
we
included
814
was
because
we
thought
the
methylene.
The
parent
might
also
be
metabolized,
but
that's
actually
slightly
worse
than
the
sb
compound.
So.
C
B
C
A
Which
is
which
is
interesting
because
you
know
the
original
idea
was
that
this
would
be.
This
was
a
problem
yeah.
B
A
B
A
We're
gonna
have
a
discussion
with
both
monash
and
with
haifa,
about
trying
to
figure
out
what's
being
transformed
here.
I
guess
I
I'm
interested
not
in
thiophene
so
much,
but
in
interested
in
one
of
the
other
compounds
to
see
what
what
the
transformation
is,
whether
it's
the
pyridine,
for
example.
It's.
A
So
yeah,
if
you,
if
you
could
just
tweak
this
table
slightly
and
put
in
potencies,
just
to
remind
us,
there's
an
extra
column
that
would
be
helpful
because
obviously
it
would
be
nice
to
pick
one
of
these,
which
is
more
potent
than
another.
A
We
may
have
that
question
answered
for
us
with
some
of
the
donated
compounds.
It
may
present
a
compound
that
is
structurally
similar
lacking
the
thiophene,
which
has
some
potency.
A
So
you
know
before
deciding
absolutely
what's
going
on.
We
might
want
to
do
that,
but
my
original
plan
had
been
to
to
do
the
met
id
on
the
thigh
fiend,
but
I
think
that's
kind
of
a
good
waste
of
time,
all
right,
good,
but
that's
very,
very
useful
stuff,
okay
and
yeah.
So
the
the
monash
team
did
say
it
did
send
something
to
me
about
options
we
might
have
about
doing
met
id.
A
I
just
need
to
digest
that
and
then
carry
on
with
this
conversation
with
with
haifa,
okay
good
and
we
got
the
full
report
from
them.
So
we
we
posted
that,
and
so
we
have
everything
we
need
if
we
need
to
publish
the
stuff,
which
is
good.
All
right
great,
thank
you
for
that.
Did
you
want
to
do
a
little
nano
update
on
history.
D
B
So
I
am
in
the
process
of
making
basically
the
sort
of
crossover
between
the
sb
or
sorry
osa,
8,
14
and
822.
I
think
so.
That's
the
aromatic
core
with
the
thigh
beam
on
it,
so
I
just
basically
have
to
do
the
suzuki
and
then
that's
done
and
I've
done
a
little
bit
more
on
trying
to
make
these.
A
B
The
unsubstituted
imidazoles,
which
so
some
of
this
is
just
there
for
context
from
last
week,
so
the
the
rose
highlighted
in
yellow
are
the
new
ones,
so
you
can
tosulate
it
and
that
actually
works
nicely.
Then
I
tried
to
do
the
borrelation
on
the
tosylated
and
the
unsubstituted
material,
so
the
unsubstituted
imidazole
I
just
got
starting
material,
backed
by
tlc.
B
The
tauzel
I
basically
worked.
Did
a
work
up
ran
a
column
isolated.
I
got
starting
material
back
and
then
this
acetylated
compound,
which
I
think
is
coming
from
the
potassium
acetate
and
I
did
not
see
any
desired
b
pin
product.
C
If
you
have
that
toesile
group
on
your
imidazole,
how
stable
is
that?
Because
the
midazole
is
quite
a
good
leaving
group.
B
If
it
seems
well,
I
don't
know
I
mean
on
the
bench:
it's
fine.
Obviously,
then
the
yeah
not
sure.
A
Okay,
problematic
yeah.
What's
the
so
just
remind
me
of
the
the
literature
precedence
for
compounds
like
four.
B
So
you
can
get
them
I've
seen
with
a
trial
group.
I've
also
seen
the
unsubstituted,
and
those
are
the
two
sort
of
most
common
that
come
up
when
you're
in
scifinder.
B
I
did
find
an
alternate
route
which
is
sort
of
similar
to
the
one
pot
that
ben
mentioned,
which
is
the
way
that
they
made
those
dndi
compounds.
So
you
have
the
the
aldehyde
at
the
two
position
of
the
pyridyl
and
then
you
have
the
isocyanate
and
then
basically
react
it
with
potassium
cyanide
and
ammonia.
So
not
the
most
pleasant
of
reaction
conditions,
but
story
materials
are
available
and
not
expensive.
A
B
A
I
don't
know
I
mean
it
depends
on
the
you
know.
It
always
depends
on
the
on
the
level
of
certainty.
You've
got
about
the
about
the
lit
here
about
whether
it's
reasonable
to
expect
these
things
working
and
if
you
start
getting
into
the
area
of
kind
of
model
reactions
trying
to
figure
out
what's
going
wrong,
it
can
consume
lots
of
time.
B
A
You
know
if
you
instead
did
a
sort
of
pyrrole
rather
than
imidazole
kind
of
thing,
and
you
sort
of
remove
that
problematic
group
and
stuff
like
that.
Then
you
get
the
certainty
of
knowing
maybe
why
it's
not
working,
but
then
days
have
gone
by
right.
It
doesn't
help
you
with
the
final
thing
I
mean:
do
you
think
that
you've
you've
exhausted
a
bunch
of
reasonable
reaction
conditions
here
or
are
there
more
things?
You
could,
in
theory,
have
a
go.
B
I
mean
it
could
theoretically
try
to
tweak
this
solvent.
Maybe
there
are
some
reports,
I
don't
know
I
just
I.
I
can
I'll
just
do
sort
of
maybe
more
of
a
deeper
dive,
let's
search
because
I've
just
been
sort
of
looking,
you
know,
are
there
examples
of
of
this
reaction
working?
Do
they
have
reasonable
yields,
et
cetera,
so
I
can
go
circle.
B
D
B
D
My
stuff,
this
week
I've
been
making
a
bunch
of
the
cores,
so
the
three
and
four
pyridine,
so
I've
made
those
a
bit
better
yield
than
what
alvaro
got
just
from
extracting
a
bit
more
and
then
brominations.
I
just
put
on
earlier
so
they've
been
worked
up
and
they
should
be
good
to
go
for
suzuki
with
the
benz
of
thiavine
next
week
also
made
some
of
this
core
with
the
extra
nitrogen
and
the
five
six.
D
So
that's
26.
I
think
I
might
just
re-purify
that
just
to
make
sure,
because
there's
one
or
two
extra
peaks
in
the
nmr,
but
then
that's
just
for
emanation
and
suzuki,
and
then
these
two
sulfone
and
sulfoxide
products,
so
this
suzuki
went
pretty
well
66.
D
I
it's
pretty
clean,
but
I
might
just
do
a
reverse
phase,
just
to
get
it
extra
nice
and
then
the
spore
relation
went
really
well
and
then
the
suzuki
I'll
put
on
after
this
meeting
and
then
yeah
so
next
week.
There's
I
mean
that
was
most
of
the
stuff
that
I
had
from
last
week.
D
A
Right:
okay,
that's
good!
I
mean
the
yeah,
the
the
top
line,
the
brominations.
I
always
say
this,
but
there's
nothing
else
that
can
brominate
there.
As
I
mean
it's
got
to
go
there,
doesn't
it
if
something's
happened.
I
hate
to
say
that,
because
I'm
going
to
jinx
it,
but
I
mean
it's
the
one
place.
D
A
B
A
Pretty
impressive,
putting
more
nitrogens
on
there,
we've
got
a
you
know
that
nation
has
it
right,
yeah,
just
just
that
that's
more
tricky,
but
you
know
hope
for
the
best.
I
guess
yeah
I
mean
like
the
top
right
compounds.
Are
those
nice
isomers
so
yeah?
If
we
we'll
get
a
nice
answer
there
about
whether
we
need
that
two,
two
periodon
and
yeah,
I
mean
it's
good,
that
the
suzuki's
are
going
with
the
with
the
soul
phone
and
hopefully
the
sulfoxide.
That's
great
yeah.
D
I
think
because
we
got
a
new
bottle
of
the
tetricus
palladium
and
I
think
that's
helping,
because
the
stuff
we
used
to
use
was
pretty
orange
canary.
A
But
yes,
I've
done
that
reaction.
Okay,
looks
good
great!
All
right!
That's
that's
interesting!
So
I
think
I
mean
yeah,
obviously
we'll
we.
We
can
keep
these
ready
to
go
for
the
next
bit
of
evaluation.
When
some
of
the
compounds
come
in,
I
think
paul
said
he
was
going
to
do
another
evaluation
against
mercer
on,
like
the
eighth
or
ninth
or
something.
C
For
the,
where
are
you
pederador
replacements?
What
are
you
going
to
put
in
this
sort
of
top
left.
D
I
was
just
thinking
at
first
the
bends
of
hyphen,
but
there
should
be
enough
to
do
at
least
two
or
three
different
ones.
I
guess.
D
Yeah
I.
D
A
Okay,
wait
I'll
I'll
do
this
chair.
I
think
I've
got
it.
A
Where
are
we
so
wait?
What
am
I
looking
at
here?
C
C
A
C
A
A
Okay,
great,
that
was
everything
I
think.
Let
me
just
quickly
check.
I
didn't
feel
the
need
to
take
up
your
time
with
anything
here,
because
I
think
it's
all
in
play
everything
else.
Yeah.
A
No,
it's
all
good,
I
think
it's,
I
think
it's
simple.
I
think
everything
else
we
can
do
offline
without
the
meeting,
so
I'm
happy
just
to
tweak
it
now,
after
after
we
log
off
all
right.
Well
good,
I
think
that's,
that's
really
great.
Okay
chemistry
is
rattling
along
and
that's
a
good
suggestion.
Thanks
chris
very
nice,
yeah
yeah.
B
So
just
one
thing
so
lori
sent
me
also
the
admin
data
that
they
have
on
the
dndi
compounds
that
she
shipped
us.
So
it's
solubility
clearance,
plasma,
protein,
binding
and
log
d.
B
So
those
are
the
oh
gosh
imidazole
pyridines.
I
think.
B
B
Yeah,
so
I
can
just
upload
that
also
oh.