pro tide
TRANSCRIPT
-
7/27/2019 Pro Tide
1/17
-
7/27/2019 Pro Tide
2/17
-
7/27/2019 Pro Tide
3/17
This works fits wellinto the WAG
Priority of Health
and biosciences
Avian flu H5N1
Antiviral Drugs?DNA
-
7/27/2019 Pro Tide
4/17
N
N
NH
N
N
HO
H2N
acyclovirZoviraxherpesGSK
ganciclovirCymeveneCMVRoche BVDU
BrivudinVZVMenarini
HN
N
O
N
N
O
HO
H2N
HN
N
Me
O
O
O
HO
d4TStavudine
HIVBMS
abacavirZiagenHIVGSK
HN
N
O
N
N
O
HO
H2N
OH
N
NO
NH2
O
S
HO
3TC
lamivudineHepBGSK
HN
N
OH
C
O
O
O
HO
C
H Br
H
Some Antiviral Nucleosides
Of 37 approved antivirals in UK,
18 (48%) are nucleoside-related.
BNF, 58, 2009
-
7/27/2019 Pro Tide
5/17
Thymidine
O
OH
HO
N
NH
O
O
-
7/27/2019 Pro Tide
6/17
O
N3
HO
N
NH
O
O
AZT
-
7/27/2019 Pro Tide
7/17
deoxyguanosine
O
OH
HO
NH
NN
N
O
NH2
-
7/27/2019 Pro Tide
8/17
O
HO
NH
NN
N
O
NH2
acyclovir
-
7/27/2019 Pro Tide
9/17
HN
N
Me
O
O
OHO
O
OH
HN
N
P
Me
O
O
OO
O
P
O
O
OH
P
O
OH
HO
HO
OH
HN
N
P
Me
O
O
OO
O
-
7/27/2019 Pro Tide
10/17
XLets try masking
the charges?
The pre-formed phosphate(nucleotide) is of limited
use as its charge preventscell entry.
-
7/27/2019 Pro Tide
11/17
X
A blockednucleotide or
ProTide
-
7/27/2019 Pro Tide
12/17
-
7/27/2019 Pro Tide
13/17
Hepatitis C virus. HCV
170M infections worldwide: 3%of the Worlds population.3-4M in USA. Many fromtransfusions.
Current therapy poor.
Ribavirin
N
O
OHOH
HO
N
N
NH2
O
PEG-INF
-
7/27/2019 Pro Tide
14/17
HCV replicon with 14d
treatment with Inx189
Cardiff-Inhibitex HCV candidate Inx189
Working with Inhibitex GA we havedeveloped INX189, a ProTide of 2-C-MeG, with nanomolar potency, and nowin clinical trials for HCV.
-
7/27/2019 Pro Tide
15/17
-
7/27/2019 Pro Tide
16/17
Working with NucanaBioMed we are applying
ProTides to cancernucleosides, such asGemcitabine.
Chris B WoodChairman
Hugh S GriffithCEO
N
NH2
ON
OF
OH
HO
F
-
7/27/2019 Pro Tide
17/17
Further information:[email protected]
mailto:[email protected]:[email protected]