Discovery of biaryl inhibitors of H+/K+ ATPase

Article abstract of DOI:10.1016/j.bmcl.2009.12.040

We report the identification of a novel biaryl template for H⁺/K⁺ ATPase inhibition. Evaluation of critical SAR features within the biaryl imidazole framework and the use of pharmacophore modelling against known imidazopyridine and azaindole templates suggested that the geometry of the molecule is key to achieving activity. Herein we present our work optimising the potency of the molecule through modifications and substitutions to each of the ring systems. In particular sub-micromolar potency is achieved with (4b) presumably through a proposed intramolecular hydrogen bond that ensures the required imidazole basic centre is appropriately located.

Full text of DOI:10.1016/j.bmcl.2009.12.040

Bioorganic & Medicinal Chemistry Letters 20 (2010) 1049–1054
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Discovery of biaryl inhibitors of H+/K+ ATPase
a
a
a
a
Neil Garton a, , Nick Bailey , Mark Bamford , Emmanuel Demont , Irene Farre-Gutierrez ,
*
Gail Hutley a, Gianpaolo Bravi b, Paula Pickering a
a GlaxoSmithKline, Medicinal Chemistry, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
b GlaxoSmithKline, Computational Chemistry, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
a r t i c l e i n f o
a b s t r a c t
We report the identification of a novel biaryl template for H+/K+ ATPase inhibition. Evaluation of critical
SAR features within the biaryl imidazole framework and the use of pharmacophore modelling against
known imidazopyridine and azaindole templates suggested that the geometry of the molecule is key
to achieving activity. Herein we present our work optimising the potency of the molecule through mod-
ifications and substitutions to each of the ring systems. In particular sub-micromolar potency is achieved
with (4b) presumably through a proposed intramolecular hydrogen bond that ensures the required imid-
azole basic centre is appropriately located.
Article history:
Received 23 October 2009
Revised 7 December 2009
Accepted 9 December 2009
Available online 21 December 2009
Keywords:
Biaryl imidazole
Potassium competitive acid blockers
APA
Ó 2009 Elsevier Ltd. All rights reserved.
Acid secretion
Acid pump antagonists
Potassium competitive acid blockers
Reversible imidazopyridine H+/K+ ATPase inhibitors (acid pump
antagonists, APAs) such as AR-HO47108 (1a) (H+/K+ ATPase pIC50
7.0) have become a focus of attention as a means of achieving rapid
and potentially long-lasting inhibition of gastric acid secretion. Un-
like the irreversible proton pump inhibitors (PPIs) that are the cur-
rent gold standard for treatment of GERD (GastroEsophageal Reflux
Disease) they do not require acid activation and would be expected
to be significantly more stable than PPIs under physiological condi-
tions. Thus, their pharmacokinetic half life can be significantly
longer allowing active drug species to be present whatever the
activation state of the target parietal cells. Thus full acid suppres-
sion from first dose, together with long duration of action is ex-
pected to be a key feature of reversible inhibitors.1–4
The geometry of the pendant phenyl ring perpendicular to the
central core ring system is a key factor in potency against H+/K+
ATPase, as is the presence of small lipophilic substituents at the
imidazopyridine C2 and C3 positions5–7(Fig. 1). Also it has been
shown that the protonated form of the molecule binds to the
pump. In addition it has been suggested that mildly basic mole-
cules can accumulate within the parietal cell8, giving higher local
concentrations and hence an increased functional potency. As an
extension of our work exploring basic 6,5 bicyclic ring systems as
acid pump antagonists9,10 we identified an alternative template
containing the critical SAR features necessary for activity in other
templates.11,12 The biarylimidazole template (2c) was designed to
include these features and lack the benzylamine substituent of
the imidazopyridine series, a substituent which we postulated
may be susceptible to metabolism. In Figure 1, (2c) shows an excel-
lent superimposition with the potent imidazopyridine compound
(1b) (H+/K+ ATPase pIC50 7.1) as an alternative to the benzyl-
amino-2,3-dimethylimidazopyridine template, recently reported
to be associated with signals of toxicity in clinical studies.13,14
Variation of substituents on Ar1 of (2) (Table 1) demonstrated a
modest increase in potency with one or two ortho substituents
(2a–d). This reflects the increased orthogonality of the biaryl sys-
tem as a result of increased steric interaction between the substit-
uents and the core ring protons. The dimethyl analogue (2c) shows
approximately the same potency as both its monomethyl (2b) and
diethyl (2d) analogues suggesting scope for further exploration ex-
ists. The methyl thiophene ring system (2e) was less potent than
its phenyl analogue.
Insertion of a one or two atom linker between the two phenyl
rings (2f–j) had a detrimental effect on potency. This was also
the case with the ortho (2k) and para (2l) directly linked biaryl
species.
Next we evaluated imidazole substitution patterns and alterna-
tive heterocycles in order to investigate how the planarity of the
molecule and the location of the basic centre (the imidazole nitro-
gen atom) affected the potency (Table 2).
Removal of, or increasing the size of the R2 and R3 methyl
groups (3a–b) or replacement with benzimidazole (3c) gave lower
potency compounds, suggesting that there is a steric constraint at
* Corresponding author at present address: Gunnels Wood Road, Stevenage,
Herts, SG1 2NY, UK.
E-mail address: Neil.S.Garton@gsk.com (N. Garton).
0960-894X/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2009.12.040

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N. Garton et al. / Bioorg. Med. Chem. Lett. 20 (2010) 1049–1054
O
Me
Me
Me
H
H
H2N
N
Me
N
N
Me
N
Me
N
N
HN
Me
R
Me
Me
X
Ar1
(1a, R=Et)
(1b, R=Me)
(2)
(2c)
Figure 1. Overlay of imidazopyridine (1b) with biaryl imidazole (2c).
(N1) substituent and the core ring protons.15 The addition of
methyl substituents R2 and R3 result in reduced potency (3e), pos-
sibly due to the ring twist causing the R2 and R3 methyl groups to
adopt a more unfavourable orientation. Larger R1 substituents such
as the n-propyl moiety also give lower potency (3f) again suggest-
ing steric constraints.
Isomeric imidazoles (3g) and (3h) also proved to be inadequate
replacements for imidazole (2c). Similarly, replacement of the
imidazole ring with either pyridine (3i) or piperazine (3i) ring sys-
tems or with alkyl amines (3j) gave compounds with reduced
potency.
Table 1
Ex
X
Ar1
H+/K+ ATPase pIC50
2a
2b
2c
2d
2e
2f
2g
2h
2i
—
—
—
—
—
NH
Ph
4.7
5.1
5.2
5.1
4.8
4.9
4.4
4.3
4.3
4.0
4.2
4.4
2-Me-Ph
2,6-diMe-Ph
2,6-diEt-Ph
3-Me-thiophen-4-yl
2,6-diMe-Ph
Ph
(trans)-CH@CH
CH2CH2
NHCH2
CONH
Ortho
Ph
2,6-diMe-Ph
Ph
Ph
2j
2k
2l
Having shown that a loss of co-planarity between the 4,5-
dimethylimidazole and core ring was detrimental to activity we
turned our attention to the core phenyl ring, exploring additional
substituents and alternative ring systems (Table 3).
Para
2,6-diMe-Ph
pIC50 values are reported as mean of >2 experiments.
Thus we introduced the 2- and 6-methoxy substituents (4a,b)
in order to lock the system by means of an intramolecular hydro-
gen bond between the hydrogen atom of the imidazole moiety
and the oxygen atom of the methoxy group. This provided a poten-
tially better mimic of the imidazopyridine by fixing the basic imid-
these positions (comparable to SAR in the imidazopyridine series).
Methyl R1 substitution with unsubstituted imidazole is tolerated
(3d) with a twist being induced by the steric clash between the
Table 2
R2
R1
Me
N
N
N
Me
R3
N
Y
N
H
X
NH2
Me
Me
Me
Me
Me
Me
Me
Me
(3k)
(3i)
(3j)
(3)
Ex
X
Y
R1
R2
R3
H+/K+ ATPase pIC50
2c
3a
3b
3c
3d
3e
3f
3g
3h
3i
N
N
N
N
N
N
N
CH
CH
C
C
C
C
C
C
C
N
N
H
H
H
H
Me
Me
n-Pr
—
Me
H
Et
Ph
H
Me
H
Me
H
Et
5.2
4.5
4.8
4.4
5.2
4.6
4.3
4.8
4.4
4.5
4.4
4.3
H
Me
H
Me
—
Me
H
Me
3j
3k
pIC50 values are reported as mean of >2 experiments.

N. Garton et al. / Bioorg. Med. Chem. Lett. 20 (2010) 1049–1054
1051
Table 3
Me
Me
Me
Me
H
H
1
H
Me
N
N
N
O
O
OMe
N
H
Me
6
Me
Me
Me
N
5
4
N
N
N
N
R
Me
Ar
2
N
3
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
(4)
(4l)
(4m)
(4p)
(5)
Ex
R
H+/K+ ATPase pIC50
Ex
R
H+/K+ ATPase pIC50
Ex
Ar
Ph
H+/K+ ATPase pIC50
4a
4b
4c
4d
4e
4f
2-OMe
6-OMe
4-OMe
4-Me
5,6-DiMeO
6-OH
<4.0
6.1
4.9
4.9
4.6
5.7
5.6
5.3
4i
4j
6-OCHF2
6-OCH2CO2Me
6-OCH2CONH2
—
5.0
5.9
5.7
5.5
5.4
4.8
<4.0
4.9
2c
5a
5b
5c
5d
5.2
4.9
4.1
<4.0
4.5
2,5-Furanyl
2,5-Thienyl
2,4-Furanyl
2,4-Thienyl
4k
4l
4m
4n
4o
4p
—
6-OMe-pyrid-5-yl*
4g
4h
6-OEt
6-OBn
Pyrid-4-yl
—
pIC50 values are reported as mean of >2 experiments.
*
No ortho methyl substituents on phenyl ring.
azole nitrogen atom to a single tautomer. Whilst the 2-methoxy
compound (4a) showed a complete loss of activity, the addition
of the 6-methoxy substituent gave a compound (4b) with sub-
micromolar activity. The methoxy regioisomer (4c) was also lower
in potency than the unsubstituted compound (2c). Other substitu-
ents such as methyl and dimethoxy (4d–e) also reduced potency
suggesting substitution at the 4- and 5- positions is disfavoured.
We hypothesised that a key factor governing potency was the
position of the basic imidazole N-1. Assuming intramolecular
hydrogen bonding locks the imidazole tautomer in place the basic
nitrogen atom in the 6-methoxy compound (4b) superimposes
well with the basic centre in the more potent imidazopyridine ser-
ies which may account for the increase in potency. However the
basic centre in the 2-methoxy analogue (4a) is likely to be located
over the imidazopyridine ring fused nitrogen atom (Fig. 1) which
would appear to be disfavoured. Exploration of other oxygen con-
taining groups that could maintain this putative hydrogen bond
(4f–k) showed that other substituents are tolerated. The presence
of a carboxylate functionality (4k–l) beta to the oxygen is also tol-
erated and could provide a handle for further optimisation.
potent with its unsubstituted phenyl equivalent (2a). Alkylation
of the imidazole at N-1 (4p) unsurprisingly resulted in a significant
loss of potency possibly through the loss of co-planarity and hydro-
gen bonding between the imidazole and core ring systems that is
predicted by modelling16 and the steric clash outlined previously.
Five-membered ring systems (5a–d) proved poor replacements
for the central phenyl ring, which is reflected by the poorer over-
lays with the imidazopyridine template (Fig. 2).
In conclusion we have been able to develop the biarylimidazole
framework to yield a compound with submicromolar activity
against the gastric H+/K+ ATPase (4b) which removes one of the
potentially problematic structural features in the imidazopyridine
series (i.e. the benzylamine functionality). Key components of the
activity have been shown to be the geometry of each of the pen-
dant rings relative to the core in order to fit within a tight binding
pocket, which was influenced by a putative hydrogen bond accept-
ing methoxy substituent. The methoxy group also appears to have
a vector appropriate to allow access to the area of the pharmaco-
phore occupied by the amide substituent in the imidazopyridines
(1a–b). This could provide a handle to introduce appropriate
functionalities to modify the pharmacokinetic properties of the
molecule. The template therefore affords an interesting starting
point for further optimisation which will be reported in due course.
The appropriate dihydrobenzofuran (4l), benzofuran (4m) and
pyridine (4o) core ring systems gave less potent compounds than
the phenyl core (4b). However the methoxypyridine (4n) is equi-
Me
H
Me
H
N
N
Me
i)
Me
N
N
RB(OH)2
or
RNH2
X
Br
Ar1
Scheme 1. Reagents and conditions: (i) boronic acid (2 equiv), Pd(dppf)Cl2
(0.1 equiv), 2 M Na2CO3 (3 equiv), DMF, microwave ( W), 100 °C, 3 h or amine
(2 equiv), CuI (0.2 equiv), Cs2CO3 (2 equiv), DMF, W, 220 °C, 10 h.
l
Figure 2. Overlays of imidazopyridine (1b) with biaryl imidazoles (5a) and (5c).
l

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N. Garton et al. / Bioorg. Med. Chem. Lett. 20 (2010) 1049–1054
N
CHO
Br
N
CHO
i)
Me
Me
Me
Me
+
NH
Me
NH
Me
NH2
Scheme 2. Reagents and conditions: (i) ArBr, aldehyde (3 equiv) Pd2(dba)3 (0.1 equiv), BINAP (0.1 equiv), NaOtBu (1.4 equiv), toluene, 100 °C, 16 h.
Me
using the conditions of Wolkenberg et al. This intermediate was
then coupled with appropriate anilines to yield the amide linked
analogues (2j) (Scheme 3).
H
Me
H
N
N
Me
i)
Me
N
Biarylimidazoles (3a–e,h) were synthesised via Suzuki reac-
tion of 3-bromophenylboronic acid with the appropriate bro-
moimidazole followed by a second Suzuki coupling to form
the biaryl bond as described in Scheme 1. Biarylimidazole
(3g) was prepared in the same manner though the bromoimid-
azole was generated from the equivalent dibromoimidazole fol-
lowing literature precedent.19 n-Propyl analogue (3f) was
synthesised by alkylation of the unsubstituted imidazole
(Scheme 4).
N
O
NH
Ar
CO2H
Scheme 3. Reagents and conditions: (i) biarylcarboxylate, ArNH2 (1.1 equiv), HOBT
(2 equiv), triethylamine (3 equiv), resin bound DCC (1.1 equiv), NMP, 20 °C, 16 h.
The pyridine analogue (3i) was synthesised via an anhydrous
Suzuki reaction between 2-bromo-4-pyridinamine and 2-(20,60-
dimethyl-3-biphenylyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(Scheme 5). The latter was generated by Suzuki reaction between
(2,6-dimethylphenyl)boronic acid and 1-bromo-3-iodobenzene
and a subsequent palladium mediated halogen-metal exchange
with pinacoldiborane.
The piperazine compound (3j) was obtained by Buchwald cou-
pling between 30-bromo-2,6-dimethylbiphenyl (described in syn-
thesis of 3i above) and 1-methylpiperazine
Synthesis of substituted aromatic ring systems Ar1 (2)17 was
readily achieved via coupling of appropriate phenyl (2a–e, k–l)
or vinyl boronic acids (2g) or amines (2i) with 2-(3-bromophe-
nyl)-4,5-dimethyl-1H-imidazole, which was in turn synthesised
from 3-bromobenzaldehyde using the conditions of Wolkenberg
et al.18 (Scheme 1). Ethyl linked compound (2h) was synthesised
by reduction of (2g) using 10% Pd/C and hydrogen in ethanol.
Nitrogen linked compound (2f) was synthesised from interme-
diate generated from a palladium mediated coupling of 3-amino-
benzaldehyde and 2-bromo-1,3-dimethylbenzene followed by
imidazole ring formation as outlined above (Scheme 2).
The alkyl amine (3k) was synthesised via a reductive amination
between 20,60-dimethyl-3-biphenylcarbaldehyde which was in turn
synthesised by a Suzuki reaction between 3-bromobenzaldehyde
and (2,6-dimethylphenyl)boronic acid followed by a reductive
Biaryl carboxylic acid was generated from the methyl ester by
refluxing in 5 M HCl for 16 h. In turn the ester was synthesised
N
N
CHO
i)
iii)
N
H
N
R
ii)
I
Ar
Ar
Scheme 4. Reagents and conditions: (i) NH4OH (10 equiv), glyoxal (10 equiv), ethanol, 20 °C, 16 h; (ii) ArB(OH)2 (1.2 equiv), Na2CO3 (4 equiv), Pd(PPh3)4 (0.1 equiv), 1:1
dioxan/water, 100 °C, 48 h; (iii) R–I (2 equiv), NaH (2 equiv), THF, 20 °C, 16 h.
Br
NH2
N
O
O
O
O
i)
Me
B
B
N
Br
NH2
N
I
Br
ii)
N
+
or
Me
Me
B(OH)2
Me
Me
Me
Me
Me
Me
N
Me
HN
Scheme 5. Reagents and conditions: (1) pinacoldiborane (1.1 equiv), Pd(dppf)Cl2 (0.06 equiv), dppf (0.06 equiv), KOAc (3 equiv), dioxan, 80 °C, 90 h; (2) 2-bromo-4-
aminopyridine (1.5 equiv), Pd(PPh3)4 (0.1 equiv), Cs2CO3 (2 equiv), 99:1 toluene/ethanol, lW, 100 °C, 90 min or Amine (2 equiv) Pd(OAc)2 (0.05 equiv), BINAP (0.15 equiv),
Cs2CO3 (1.5 equiv), dioxan, 100 °C, 16 h.

N. Garton et al. / Bioorg. Med. Chem. Lett. 20 (2010) 1049–1054
1053
O
H
O
Me
H
N
H
Br
Me NH2
+
NaBH(OAc)3
Me
Me
Me
Me
B(OH)2
Me
Me
Scheme 6. Reagents and conditions: methylamine (2 equiv), NaBH(OAc)3 (2 equiv), AcOH (cat), DCM, 20 °C, 16 h.
CO2Me
O
CO2R
O
CO2R
O
B(OH)2
Me
CO2R
O
O
Me
N
N
N
H
i)
N
H
N
H
N
H
ii)
Br
Br
Me
Me
Me
Me
R=H, NH2
R=Me, NH2
R=H, NH2
Scheme 7. Reagents and conditions: (i) oxalyl chloride (1.1 equiv), DCM, 20 °C, 2 h; (ii) methanol or 2 M methanolic ammonia.
OH
Cl
Cl
O
NH2
N
N
OR
N
CHO
i)
ii)
iii)
N
N
H
N
N
H
N
Ph
Ph
Ph
Ph
Ph
Scheme 8. Reagents and conditions: (i) PCl5 (1 equiv), diethyl ether, 20 °C, 5 h; (ii) POCl3 (8 equiv), DMF (12 equiv), 90 °C, 6 h; (iii) NaOR (10 equiv), methanol, 65 °C, 24 h.
amination with methylamine using sodium triacetoxyboro-
hydride as the reducing agent (Scheme 6).
Compounds (4a–e, g–i, l–m, o, 5a–d) were synthesised using
the same methodology outlined in Scheme 1. The phenolic ana-
logue (4f) was generated from the benzyl derivative (4h) using
the hydrogenation conditions for (2h) above.
The carboxylate compounds (4j–k) were made from the start-
ing methyl ester following conditions outlined in Scheme 1. The
ester was transformed into a mixture of carboxylic acid and
amide during imidazole formation and the desired compounds
were obtained after treatment with oxalyl chloride and quench-
ing in methanol or methanolic ammonia as appropriate (Scheme
7).
Alkoxypyridine compound (4n) was synthesised by building up
the core pyridine ring, imidazole formation as described in the lit-
erature and subsequent alkoxide displacement of a chloropyridine
(Scheme 8).
References and notes
1. Sachs, G.; Shin, J. M.; Vagin, O.; Lambrecht, N.; Yakubov, I.; Munson, K. J. Clin.
Gastroenterol. 2007, 41, S226.
2. Scarpignato, C.; Pelosini, I.; Di Mario, F. Dig. Dis. 2006, 24, 11.
3. Parsons, M. E.; Keeling, D. J. Expert Opin. Investig. Drugs 2005, 14, 411.
4. Andersson, K.; Carlsson, E. Pharmacol. Ther. 2005, 108, 294.
5. Kaminski, J. J.; Bristol, J. A.; Puchalski, C.; Solomon, D. M.; Rizvi, R. K.; Conn, D. J.;
Elliott, A. J.; Lovey, R. G.; Guzik, H.; Chiu, P. J. S.; Long, J. F.; McPhail, A. T. J. Med.
Chem. 1989, 32, 1686.
6. Kaminski, J. J.; Wallmark, B.; Briving, C.; Andersson, B. M. J. Med. Chem. 1991, 34,
533.
7. Kaminski, J. J.; Bristol, J. A.; Puchalski, C.; Lovey, R. G.; Elliott, A. J.; Guzik, H.;
Solomon, D. M.; Conn, D. J.; Domalski, M. S.; Wong, S. C.; Gold, E. H.; Long, J. F.;
Chiu, P. J. S.; Steinberg, M.; McPhail, A. T. J. Med. Chem. 1985, 28, 876.
8. Andersson, K.; Carlsson, E. Pharmacol. Ther. 2005, 108, 294.
9. Bailey, N.; Bamford, M. J.; Demont, E.; Elliott, R.; Garton, N.; Farre-Gutierrez, I.;
Hayhow, T.; Hutley, G.; Naylor, A.; Panchal, T. A. Bioorg. Med. Chem. Lett. 2009,
19, 3602.
10. Bailey, N.; Bamford, M. J.; Brissy, D.; Brookfield, J.; Demont, E.; Elliott, R.;
Garton, N.; Farre-Gutierrez, I.; Hayhow, T.; Hutley, G.; Naylor, A.; Panchal, T. A.;
Seow, H. X.; Spalding, D.; Takle Bioorg. Med. Chem. Lett. 2009, 19, 6813.
11. Bristol, J. A.; Lovey, R. G. Imidazo[1,2-b]pyridazines. U.S. (1984), 12 pp. US
4464372.
12. Amin, K.; Dahlstrom, M.; Nordberg, P.; Starke, I. Preparation of heterocyclic
compounds for inhibition of gastric acid secretion. PCT Int. Appl. (1999), 34 pp.
WO 9928322.
13. Berg, A. L.; Bottcher, G.; Andersson, K.; Carlsson, E.; Lindstrom, A. K.; Huby, R.;
Hakansson,H.;Skanberg-Wilhelmsson,I.;Hellmold,H.Toxicol.Pathol.2008,36, 727.
14. Andersson, K. Society for Medicines Research Symposium, September 21, 2006,
London, U.K.
(N1)-Alkylated methoxy derivative (4p) was synthesised using
conditions outlined in Scheme 4.
Acknowledgements
The authors acknowledge the assistance of GlaxoSmithKline
colleagues from the departments of Gene Expression and Protein
Biochemistry for the pig gastric membranes and Assay Develop-
ment & Compound Profiling for assay of the compounds.20
15. A search of the Cambridge crystallography database with the following query
retrieved a total of 43 hits where the twist between the two rings is more
pronounced with R = Me than R = H.

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N. Garton et al. / Bioorg. Med. Chem. Lett. 20 (2010) 1049–1054
8
A
8
6
4
2
0
R=H
8
6
4
2
0
R=Me
H
A
N
H
6
9
A
N
R
A
A
3
3
2
2
2
R=H,Me
A=Any aromatic
1
1
1
1
1
1
1
1
-70 -60 -50 -40 -30 -20 -10
0
10 20 30 40 50 60
-70 -60 -50 -40 -30 -20 -10
0
10 20 30 40 50 60
16. Structures were optimised with MMFF94x force field and superimposed by
maximising volume overlap (rigid-body fit) within MOE (CCG).
17. All novel compounds gave satisfactory 1H NMR and LC/MS data in full
agreement with their proposed structures.
18. Wolkenberg, S. E.; Wisnoski, D. D.; Leister, W. H.; Wang, Y.; Zhao, Z.; Lindsley,
C. W. Org. Lett. 2004, 6, 1453.
19. Breslow, R.; Hunt, J. T.; Smiley, R.; Tarnowski, T. J. Am. Chem. Soc. 1983, 105,
5337.
20. Bamford, Mark James; Elliott, Richard Leonard; Giblin, Gerard Martin Paul;
Naylor, Antoinette; Panchal, Terence Aaron; Takle, Andrew Kenneth;
Witherington, Jason. Preparation of imidazopyridines as acid pump
antagonists. PCT Int. Appl. (2007), 40pp. WO 2007003386.