►
From YouTube: Open Source Antibiotics Science Update Sept 10th 2021
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/89
On the call: Professor Matthew Todd, Dr Dana Klug, Dr Edwin Tse (UCL), Dr Daniel Gedder (University of Sao Paulo), Dr Quillon Simpson (NEU), Anthony Sama (Citizen Scientist), Dr Chris Swain (Cambridge Medchem Consulting)
A
Okay,
hi
everybody
thanks
for
coming
along
it's
friday,
10th
of
september
and
and
this
is
open
source
antibiotics
series
2
and
I
will
now
share
the
right
screen.
Just
bear
with
me
a
second
okay.
So
here
we
go,
we
we've
had
a
summer
break,
so
I
think
there's
been
some
activity,
but
some
people
have
taken
holidays
so
and
I
guess
we
should
just
sort
of
try
and
work
through
the
most
important
things,
and
the
first
thing
I
was
going
to
mention
is
really
just
about.
You
know.
A
The
next
compounds
that
we're
going
to
evaluate,
because
there
were
there
were
some
that
needed
retesting
and
there
are
some
new
ones
that
have
come
in
and
maybe
quality
and
daniel
can
talk
about
compounds
that
we,
we
think,
need
to
be
tested
the
next
round,
and
things
like
that.
Ed
has
already
posted
very
helpfully
the
current
set
of
molecules
that
will
be
evaluated
by
paul
stapleton
in
this
building
next
tuesday.
A
A
He
can
retest
them
when
he's
back
from
holidays,
which
is
now
and
so
he's
going
to
have
a
look
at
those
compounds
again,
along
with
the
positive
control-
and
he
said,
he's
also
very
kindly
said,
he's
very
happy
to
test
new
compounds
that
come
in
and
so
those
bottom
three
there
in
with
the
orange
new
compounds
will
be
able
to
go
in
there
too.
Ed
dana.
What's
the
origin
of
those
as
the
newly
synthesized
compounds
right.
A
Okay,
that's
fantastic
okay,
so
we
have
until
tuesday.
So
I
think
those
are
going
to
be
those
unless
any
other
compounds
are
coming
in,
but
that's
fine
because
we
need
the
data
right.
So
I.
C
A
A
Yeah,
okay,
so
that's
good,
so
there'll
be
some
crucial
data
there
that
we
need
to
know
before
we
can
plan
too
much
more.
But
I,
while
we're
talking
about
this,
we
can
think
about
which,
if
any
other
companies
are
incoming-
or
you
know
partly
done
and
inevitably
will
arrive
for
subsequent
rounds
of
of
potency,
so
I'm
quillin
daniel
did
you
want
to
talk
about
any
compounds
that
we
have
not
raised
here,
which
may
be
incoming.
B
Yeah
yeah,
I
can
share
my
screen
and
then
I
can
talk
a
little
bit
about
the
the
seats
that
I've
been
working.
B
Let's
start,
can
you
see
my
screen?
It's
coming,
I
think
yeah
there
you
go
good
I'll
start
the
presentation
just
one
second.
B
There
it
is
yeah,
as
I
told
I
told
you
before,
I'm
a
postdoc
here
at
the
university
of
sao
paulo
work
with
flavor
since
2017.
B
And
I've
been
working
with
heterocycle
synthesis,
immediate
pyridine.
I
have
been
working
a
lot
since
my
phd
when
I
was
in
the
health
lab
in
university
at
the
university
of
washington.
During
my
phd
I
work
with
some
imidazole
pyridine
urease.
I
will
talk
about
it
a
bit
late,
just
to
just
to
show
you
some
scaffolds
that
I
have
working
so,
but
so
far
I
start
to
synthesis.
I
start
with
this
synthesis
properly,
because
life
told
me
that
the
position
of
the
nitrogen,
the
purity
in
nitrogen
it's
important.
B
The
first
step
is
just
the
reaction
with
the
proper
bromo
acetophenone
and
the
the
amino
pyridine
no
problem
to
synthesize
and
purify,
and
then
the
second
step
is
a
meniscus
reaction
to
get
diminished
base,
and
the
last
step
is
the
step
that
I
was
struggling
to
work.
First,
I
was
trying
to
optimize
using
the
period
the
the
the
compound
having
the
proper
nitrogen
e
ortho
position,
but
I
was
having
some
problems
to
purify
and
get
the
final
compounds,
because
I
had
already
synthesized
this
intermediate
had
a
cf3.
B
I
thought.
Maybe
I
should
optimize
the
reaction,
the
last
step,
the
losing
this
scaffold.
Then
I
go
for
the
proper
scaffold
that
you
we
are.
We
are
interested
to
to
get
so
I
try
first
without
any
reflux,
but
I
could
get
the
compound
in
using
carbonate
sesame
carbonate,
100
degrees
in
dmf.
I
couldn't
get
any
no
sorry.
I
tried
out
temperature.
Then
I
tried
to
heat
up
200
degrees.
B
I
got
many
spots,
my
tlc,
then
I
decided
to
add
just
sesame
carbonate,
100
degrees
and
they
start
material
in
order
to
deprotonate
the
base,
and
then
I
added
iodophutane
overnight
and
I
could
get
the
compound.
So
after
purification
I
get
more
or
less
five
different
spots.
I
analyze
all
the
spots.
I
always
have
some
nmr
signals
that
show
me.
I
have
the
compounds,
but
I
also
have
too
many
key
signals.
I
was
discussed
with
flavio.
I
guess
sorry,
sorry,
I'm
a
bit
confused
in
this
in
this
in
this
compound.
B
I
get
the
final
compound,
no
problem,
I
optimize
and
then
I
have
the
reaction
reflux
in
one
hour,
then
I
add
the
iodine
and
then
I
get
the
compounds.
No
no
problem
to
purify
and
I
get
the
final
compounds.
Everything
was
fine,
but
when
I
go
for
the
next,
the
next
reaction
using
the
same
conditions
adding
iodine
after
one
hour
refluxing.
B
I
get
five
spots
and
I
prefer
all
the
compounds,
but
I
still
have
too
many
signals
in
the
aliphatic
region,
which
means
maybe
I'm
having
side
reactions,
maybe
with
the
nitrogen
in
the
pyridine
or
maybe
in
other
aromatic
positions,
because
sometimes
I
don't
have
all
the
signals
of
the
aromatic
region.
B
But
I
have
it's
missing
one
hydrogen
and
then
I
have
more
alien
fatty
signals,
which
means
the
io.
The
gluten
is
reacting
with
other
positions
of
this
immediate
protein
having
the
nitrogen
disposition.
This
is
why
I
don't
have
yet
this
final
compound,
but
I
had
this
one
with
the
cf3
and
without
the
nitrogen.
B
B
I
order
the
other
chemical
I,
although
the
other
iodo
allied,
but
here
in
brazil,
have
problems
through
other
chemicals.
Sometimes
they
take
like
one
month
two
months
three
months,
so
I
don't
have
this
this
iodo
yet
and
then
do
you
have
do
you?
Do
you
have.
E
B
Yeah
yeah.
That
would
be
great
because
I
was
too
much
reactive.
Maybe
yes
I
had.
I
think
I
have
your
promo
promo
button.
I
can
try
today
or
maybe
tomorrow
this
reaction,
because
so
I
discussed
with
with
I
discussed
with
flav,
maybe
and
other
research.
You
know
researchers
in
our
lead
and
they
told
me
to
try
to
to
profile
using
biotech,
but
the
problem
is
not
the
purification.
B
B
So
I
have
this
five
intermediates
and
this
last
one
I
still
have
to
work,
but
I
have
this
one
with
the
fluorine
another
one
with
the
cf3
and
then
they
start
materials
I
could
send
for
you
or
we
could
wait
more
until
I
get
more
more
compounds
the
set.
The
set
of
compounds
that
I
was
working
during
my
postdoc
and
also
then-
and
I
still
have
the
compounds-
are
these
these
three
scaffolds.
The
first
scaffolds
are
made
of
creatine
primitive
urease
having
subiciotwins
in
r1
and
r3
positions.
B
Then
I
have
these
scaffolds
that
I
work
with
many
many
bases.
I
have
many
substitutes
in
r2
position
and
then
I
also
have
four
pyridines,
which
are
related
to
to
the
other
scaffolds,
more
or
less.
I
have
24
analogs.
We
test
all
these
194
analogues
against
t
crews,
t
bruce
ci.
Most
of
them
are
active.
It
has
some
potency
against
parasites,
and
here
I
have
like
30
variant
variants
having
urea
basically
or
a
mind.
Also,
but
urea
is
better
than
my
mind
in
case
of
parasites.
B
Here
I
have
amino
acute
groups
in
this
position
that
one
I
have
a
romantic
alifatki
and
in
the
ring
I
have
into
the
ring.
I
have
nitrogen
or
oxygen.
We
published
this
paper.
This
worked
the
first
one
when
I
was
in
guelph
lab
in
seattle,
and
last
year
worked
with
flav
and
also
professor
function.
Germany,
we
published
another
paper
having
this
related
series
of
compounds.
B
I
I
just
would
like
to
show
for
you
that
I
I
have
that
those
compounds
and
if
you
are
interested
into
testing
I
can
send
also
forecasting.
Thank
you.
This.
A
B
The
first
the
first
compounds
in
from
this
paper
new
class
of
extrapolations-
they
are
patent.
They
are
patent
for
tbrci
and
t
crews.
The
second
paper
we
didn't
patent.
So
it's
another,
it's
more!
It's
more
this
this
set
of
compound
having
substituents
in
r2
position
and
also
for
pyridines.
We
tested
them
against
t
cruz
and
t
bruce
ci.
But
if
you
like
to
test,
I
can
I
have
the
compounds
I
can
talk
to
together.
B
B
When
I
have
urea
in
r1
position
the
most
active
compounds,
I
have
the
the
rear
group
in
this
position,
but
this
scaffold,
the
second
one
took
one
to
a
pyridine.
They
are
more
related
with
the
antibiotic
antibiotic
project.
A
A
A
Yeah
but
okay,
okay,
yeah.
B
The
pattern
most
the
pattern
covers
the
first
scaffolds,
the
first
scaffolds
having
urea,
because
all
the
activity
are
related
to
have
a
real
disposition.
For
example,
when
I
change
the
rear
from
r1
region
to
v
region
compound
lost
totally
the
activity,
so
the
scaffold
that
we
patent
says
that
I
have
to
have
rear
in
this
position.
B
A
My
sense
is
that
I
mean
that's
fantastic
and
it's
a
very
kind
offer.
My
sense
is
that
the
we
want
to
avoid
switch.
We
want
to
avoid.
What's
it
called
mechanism
of
action
switch,
so
we
want
to
avoid
moving
to
a
different
mechanism
action.
It
seems
to
me
that
the
ones
that
will
be
of
most
interest
to
us
in
terms
of
the
bottom
structures
on
each
slide
there
were
where
the
r3
is
periodic
right,
because
then
we
know
that
that's
essential
for
activity.
In
our
case.
E
A
compound
using
that
fiero
purity
nucleus,
where
you
have
v
as
a
carbon
atom,
and
then
you
have
basically
furo
furopyrazine
and
then
put
our
normal
substituents.
That
would
be
quite
interesting,
but
that
that
would
probably
be
pretty
difficult
to
make.
B
In
ar3
position,
most
of
the
substituents
are
aromatic
some
of
the
compounds.
I
have
fluorine
in
two
three
position:
three
four
or
four
position:
fluorine
chlorine
bromine
some
compound.
I
have
bromine
israel,
but.
A
B
Right
and
here
in
r2,
I
have
built-in
amino
acid
groups
like
like
piparizins
I
have
here.
I
have
aromatic
as
well
yeah
those
kind
of
things,
but
the
nitrogen
in
that
specific
position
that
I
know
that
is
important
for
the
mechanism,
the
mode
of
reaction.
I
don't
have
any
compound
with
nitrogen.
In
that
position
I
have
from
my
phd,
maybe
foreign
but
yeah,
it's
it's
it's
over
the
compound,
which
I
synthesized
just
few
brands
milligrams
for
testing
and
were
not
achieved.
We
didn't
keep
you
going
with
furan
or
isox
isoxazole.
A
Okay
and
okay,
because
I
mean
I
guess
we
just
have
to
be
careful-
we're
not
screening
too
widely
here,
you
know
we're
still
interested,
obviously,
but
not
necessarily
for
this
project.
If
we're
going
to,
if
we're
going
to
change
that
too
much
yes,
I
mean:
do
you?
Do
you
happen
to
have
a
you
know
a
sheet
where
the
the
full
structures
are
shown
anywhere,
so
you
can
share
those
with
us
without
having
to
do
too
much
work.
B
Yeah,
yes,
I
have
the
cdd,
I
maybe
I
can
access
I'm
going
to
stop
to
to
share
my
screen
just
for
one
second,
and
then
I
can
open
the
cdd,
and
I
can't
show
you
the
the
scaffolds.
A
E
A
Yeah,
so
just
on
the
moa
stuff,
lee
was
wanting
a
sound,
a
source
of
mrsa
lysate.
He
doesn't
have
that
source
anymore.
So
he's
done
some
initial
experiments
with
that,
but
no
longer
has
mrsa
lysa.
He
was
asking
us
for
a
source
of
it.
Can
we.
E
A
So
we
can
access
amarylysate
in
our
building.
The
person
who
does
that
which
is
paul
again
recommends
strongly
against
trying
to
ship
that
overseas,
just
because
it
doesn't
survive
yeah.
So
in
the
meantime
I
mean
we.
It
would
be
very
nice
to
be
able
to
try
to
identify
a
source
of
that
in
the
us.
I
don't
know
how
we
do
that
and
in
the
meantime,
yeah
I
think
lee
could
productively.
A
A
A
So
I
think
within
the
us,
maybe
you
know,
yeah
close
to
lee
would
be
good,
so
I,
if
if
we
could
try
to
do
some
reach
outs,
to
see
if
you
know
someone's
willing.
D
Well,
if
you
post
it
on
the
twitter
again,
I've
got
some
contacts
there
I'll
point
them
towards
the
tweets.
If
you
like,
okay,.
A
A
Yeah
right
I
mean
I'm
not
sure
what
the
issue
is,
because
it's
not
financial,
because
you
know
we.
This
is
a
grant
supported
project,
so
we
can
pay
someone
to
do
it
so.
A
E
All
right
so
flying
back
to
the
the
human
to
the
hector
hewa
tests.
Do
we
know
if
we
has
enough
compounds
to
actually,
you
know
run
it
on
human
cells.
He.
A
E
A
B
Yeah
those
ones
are
not
patterned.
Those
one
is
the
one
that
I
published
last
year:
okay,
so
the
this
compounds
I
synthesize
here
in
flat,
flavour's
lab.
There
are
other
compounds
that
are
related
to
those
that
I
have
here.
Fluoride,
in
this
position,
for
example,
that
I
synthesized
in
germany
is
not
a
problem
also
to
send
for
you,
because
it's
not
included
in
the
patent.
B
B
Yeah
yeah
yeah,
I
agree.
Those
one
are
related
to
the
pattern
from
up
up
to
here
are
not
related
to
the
pattern
they
are.
They
are
new
compounds
planted
here
with
flavor,
and
I
mean
some
of
the
shorter.
A
B
Can
I
can
organize
the
data
that
I
have
those
compounds
that
are
related
to
the
discomfort
and
sent
to
you
or
are
post
there,
and
then
you
can
take
a
look
and
let
me
know
if
you
would
like
to
test
two
five
ten
compounds
of
this
set.
I
can't
I
can
send
to
you
without
problem.
B
B
D
B
When
I
try
without
heating,
I
couldn't
get
the
product.
So
when
I'm
heating,
I
guess
side
reactions
are
occurring,
so
maybe
the
nitrogen
of
the
pyridine
is
also
because
it's
refluxing
and
and
overnight
reaction,
maybe
the
nitrogen
of
the
ring
is
attacked
in
the
iodine,
because
I
have
some
compounds
that
doesn't
move
in
from
the
base.
B
B
Yes,
yes,
and
also
some
nmrs,
that
I
have
it's
missing
one
aromatic
hydrogen
and
I
have
more
aliphatic
signals,
and
I
have
a
limitation
here
right
now
that
I
cannot
perform
mass
mass
spec,
because
then
I
could
check
how
it
what
what
is
the
mass
of
the
compound
and
then
take
a
look
to
analyze
which
compound
is,
but
they
are
super
polar.
They
don't
move
from
the
the
the
in
the
silic.
So
I
need
to
use,
for
example,.
E
You're
getting
quaternarization
you're
getting
quite
salt,
maybe.
G
Yeah,
so
something
I
just
want
to
quickly
add
in
here
when
we
do
the
inoculations,
depending
on
the
stoichiometry
of
the
iodide
or
halide,
that
you're
using
and
you
get
a
mix
of
alkylation
at
the
core
nitrogen
you
get
alkylation
of
the
periodic
nitrogen
and
you
get
an
alkylation
of
the
desired
nitrogen
that
you're
after,
if
you
go
heavy-handed
you'll
also
get
quaternarization
of
that
nitrogen.
B
A
Is
there
a
chance
of
alkylating
your
amine
first
and
then
doing
your
manage
yeah.
B
I
I'm
thinking
to
do
that
also
try
to
do
the
oculation
first
and
then
try
to
work
in
diminished
conditions
to
get
the
compound.
Maybe
it's
a
bit
easier,
flavor
thought
about
this
road
and
me
as
well,
because
I
had
the
compounds
red,
so
I
just
need
to
make
one
reaction
calculation,
but
the
calculations
takes
too
much
time
and
we
are
have.
I
have
another
problem,
many
problems
with.
B
We
can
work
in
the
lab
just
six
hours
per
day,
which
is
of
six
hours.
For
me,
it's
nothing
I
was.
I
was
commonly
staying
the
lab
the
whole
day.
Then
I
had
six
hours
and
many
projects,
and
so
I
need
to
split
my
time.
This
is
the
problem
I
hope
soon
we
can
start
working
a
full
day.
B
Maybe
I
can
accelerate
my
synthesis,
but
we
are
in
these
conditions,
like
the
beginning
of
the
year
so
and
last
year,
nine
months
without
going
in
the
lab,
so
it's
kind
of
complicated
situation
here.
A
Yeah
we
sympathize
very
much
yeah,
so
I
mean,
but
based
on
that,
though
I
mean
we
would
love
to
test
that
one
compound
with
the
cf3
that
you've
managed
to
get
there
with
the
alkylated
group
on
it.
I
mean
right
that
that
is
that's
useful
right
in
terms
of
our
sar,
I'm
pretty
sure
yeah.
C
A
B
I
can
prepare
a
list
of
compounds
with
the
previous
one
that
I
have
and
those
new
one
and
then
you
we
pick
up.
We
pick
up
together,
which
compound
would
you
like
to
ship
and
I
can
lose
fedex
and
fedex
here
in
brazil?
It's
pretty
fast.
I
I
think
two
three
days
would
be
there,
so
they
can
send
the
first
set
of
compounds
and
then
we
can
have
idea
about
the
sar.
A
B
Okay,
I
will
try
to
organize
the
set
of
the
compounds
today
afternoon
and
then
maybe
monday.
I
can
ship
the
compounds.
That'll.
D
B
Yes,
yes,
I
I
thought
that
as
well
or
maybe
trying
to
stand
off
managed
reaction.
Try
another
reactions
in
the
isoxazole
portion.
I
saw
one
reaction
a
couple
of
days
ago
that
I
could
easily
manage.
I
I
think,
would
be
easier.
The
the
the
first
thing
that
I'm
gonna
do
today
stretch
with
bromine.
B
G
B
B
A
A
G
G
Laurie,
isn't
quite
100
sure
on
yet
we'll
have
a
better
idea.
By
next
week.
I
spoke
to
dana
offline
about
some
compounds
to
synthesize
of
interest,
namely
it
was
compounds
where
we
do
a
nitrogen
scan
around
the
core
itself.
So
we.
G
Compounds
on
hand,
so
we
can
just
get
the
undergraduates
to
purify
those
and
there's
a
few
other
compounds
that
have
been
on
our
to-do
list
that
we've
now
sort
of
refined
and
now
they're
handing
on
to
these
undergraduates
when
they
come.
Okay,.
G
Yeah,
when
larry
gets
back
this
afternoon,
I'll
be
able
to
sit
down
with
her
and
we'll
put
a
list
together
right.
G
A
Thanks
great
great
okay,
so
that
all
sounds
very
promising.
So
I
mean
those
are
the
main
things,
as
I
mentioned
when
I
was
just,
we
were
just
talking
about
the
moa
stuff.
A
So
yes,
as
I
mentioned,
we're
pushing
lee
to
see
if
he
can
do
some
human
cells,
while
we're
figuring
out
what
to
do
the
mercer
and
then
yeah
we'll
send
out
another
tweet
for
you
chris
to
to
send
around
and
if
other
people
can
retweet
or
do
a
bit
of
searching
about
an
american
site
that
might
have
some
mrsa
lysate
available.
A
Okay,
so
I
think
we
dealt
with
all
the
synthetic
chemistry
stuff.
We
have
not
much
more
to
do
with
the
at
me
stuff.
As
I
understand
it,
dana
alex
is,
you
know,
finishing
off
her
table
of
talks
data,
but
is,
I
think,
he's
away
at
the
moment.
C
Yeah
she's
on
leave,
I
think
she's
just
on
holiday.
She
said
she's
back
at
the
end
of
the
month,
so
I'll
reconnect
with
her
then
I'll,
try
and
see.
If
there's
enough.
A
Right
right,
okay,
great
right
and
then
I,
I
guess
again,
another
thing
which
I
I
wasn't
sure
to
what
extent
we
were
supposed
to
be
doing.
Anything
here
was
on
the
the
I
don't
know.
That's
the
same
thing
like
that.
We
were
talking
about
yeah,
yeah,
okay,
fine,
so.
A
Oh
yeah,
okay,
okay,
fantastic
great!
So
that's
that's
happening,
okay,
great
whoops,
sorry,
I'm
my
connection's
being
slow,
okay
and
then
I
think
that
was
I
mean.
I
think
those
are
the
main
things
right.
We
don't,
I
think,
that's
everything!
That's
that
we're
currently
waiting
on.
As
far
as
I
can
tell
have
I
if
I
missed
anything
major.
A
So
I
think
that
the
retest
and
the
test
of
the
new
compounds
will
be
in
before
next
week
friday.
So
I
think,
provided
we
get
those
data,
let's
have
a
look
at
them
and
if
we
don't
get
any
chance
before
then
then
we
can
have
a
think
also
about
daniel's
compound
as
well
next
week.
So
hopefully
we'll
have
potsy
data
and
a
decision
to
make
about
compounds
that
we
might
want
to
use
all
good.