Access to Imidazo[1,2-a]pyridines via Annulation of α-Keto Vinyl Azides and 2-Aminopyridines

Article abstract of DOI:10.1021/acs.orglett.5b02124

A novel strategy for the synthesis of imidazo[1,2-a]pyridines via efficient catalyst/metal-free annulations of α-keto vinyl azides and 2-aminopyridines is described. Several imidazo[1,2-a]pyridines were synthesized from readily available vinyl azides and

Full text of DOI:10.1021/acs.orglett.5b02124

Letter
pubs.acs.org/OrgLett
Access to Imidazo[1,2‑a]pyridines via Annulation of α‑Keto Vinyl
Azides and 2‑Aminopyridines
Praveen Reddy Adiyala,† Geeta Sai Mani,† Jagadeesh Babu Nanubolu,‡ Kunta Chandra Shekar,†
and Ram Awatar Maurya*,†
†Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500007, India
‡Centre for X-ray Crystallography, CSIR-IICT, Hyderabad-500007, India
S
* Supporting Information
ABSTRACT: A novel strategy for the synthesis of imidazo-
[1,2-a]pyridines via efficient catalyst/metal-free annulations of
α-keto vinyl azides and 2-aminopyridines is described. Several
imidazo[1,2-a]pyridines were synthesized from readily avail-
able vinyl azides and 2-aminopyridines and obtained in highly
pure form by simply evaporating the reaction solvent. This
remarkably high yielding and atom economical protocol allows
the formation of three new C−N bonds through cascade
reactions and rearrangements.
eveloping efficient synthetic routes for biologically
important heterocycles is a continuous enterprise in
herein we report a novel synthetic strategy for imidazo[1,2-
a]pyridines that fulfills the aforementioned criteria. Most of the
organic syntheses require three basic operations (extraction,
filtration, and evaporation) in their workup. However, the
methodology described herein requires evaporation as the only
purification step for getting final products. In addition, the
initial condensation product [N-(imidazo[1,2-a]pyridin-3-yl)-1-
arylmethanimine] of our synthetic strategy has a reactive imine
functionality which can be utilized to yield various other
derivatives of imidazo[1,2-a]pyridine in a one-pot operation.
Presented in this letter are the results of unprecedented
annulations of vinyl azides I and 2-aminopyridines II (Scheme
1). Vinyl azides I can be obtained easily by a Knoevenagel type
D
organic chemistry. Imidazo[1,2-a]pyridine lies among the most
noteworthy pharmaceutically valuable heterocyclic motifs
exhibiting a plethora of biological activities such as anticancer,1
antimycobacterial,2 antileishmanial,3 anticonvulsant,4 antiviral,5
and others.6 Many of the clinically used drugs for the treatment
of insomnia (zolpidem),7 anxiety (alpidem, necopidem and
saripidem),7,8 acute heart failure (olprinone),9 peptic ulcer
(zolimidine),10 HIV infection (GSK812397),11 and bacterial
infections (rifaximin)12 contain imidazo[1,2-a]pyridine as a key
unit in their pharmacophores. Furthermore, imidazo[1,2-
a]pyridine bearing molecules have been utilized as abnormal
N-heterocyclic carbene ligands,13 and as excited state intra-
molecular proton transfer (ESIPT) agents in optoelectronics.14
Owing to their importance and utility, considerable attention
has been paid to construct imidazo[1,2-a]pyridine deriva-
tives.15,16 Among them, the three-component coupling of 2-
aminopyridines, aldehydes, and isocyanides (Groebke reaction)
is the most promising though the distressing odor of
isocyanides and use of Bronsted or Lewis acid catalysts are
the major concerns associated with it. Therefore, in recent
years, synthetic approaches for imidazo[1,2-a]pyridines based
on multicomponent reactions and tandem sequences are being
keenly investigated.16,17 The reported methods have their own
drawbacks, including the necessity of expensive transition metal
catalysts and special reagents, limited structural diversity of the
product, harsh reaction conditions, and tedious workup/
purification procedures. A synthetic route for imidazo[1,2-
a]pyridines that uses simple and readily available starting
materials and mild reaction conditions, gives high yields of
products without formation of byproducts, and does not
require any catalyst/additives and tedious workup/purification
procedures may be considered an ideal synthesis. In this aspect,
Scheme 1. Proposed Annulations of Vinyl Azides I with 2-
Aminopyridines II To Yield Imidazo[1,2-a]pyridine Scaffold
III
reaction of α-azido ketones with aldehydes.18 We envisioned
that the condensation of vinyl azides I with 2-aminopyridines II
would lead to the formation of an imine which should undergo
annulation to yield imidazo[1,2-a]pyridine III.
At the onset, we started investigating the feasibility of the
annulation of vinyl azide 1a with 2-aminopyridine 2a.
Received: July 23, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02124
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Annulations of 1a and 2a did not proceed in toluene at ambient
temperature; however, heating the reaction mixture to a higher
temperature guided the formation of 3a in good yields (Table
1, entries 1−3). The structure of 3a was assigned by analyzing
as toluene, EtOH, CH3CN, CHCl3, THF, 1,2-DCE, and 1,4-
dioxane were screened (Table 1). The reaction proceeded
smoothly in most of the solvents, and it gave a quantitative
yield of imidazo[1,2-a]pyridine in THF (Table 1, entry 7).
Encouraged by the successful efficient annulations of vinyl
azide 1a with 2-aminopyridine 2a, we started exploring the
scope of the reaction. A number of vinyl azides derived from
aromatic aldehydes bearing halogen, electron-withdrawing, and
electron-donating functional groups yielded a quantitative
amount of the desired imidazo[1,2-a]pyridine derivatives
(Table 2).
Table 1. Annulations of Vinyl Azide 1a and 2-Aminopyridine
a
2a To Yield Imidazo[1,2-a]pyridine 3a
Vinyl azides derived from heteroaromatic aldehydes
quantitatively yielded imidazo[1,2-a]pyridine derivatives
(Table 2, entry 9). The reaction was not successful with vinyl
azides derived from the condensation of ketones (cyclo-
hexanone) or aliphatic aldehydes (n-butanal) with α-azido
ketones. These ketones and aldehydes contain α-hydrogen
atoms which probably lead to the formation of reactive imine/
enamines that further reacted with themselves or other
substrates present in the reaction system to give a complex
mixture. Furthermore, vinyl azides derived from aromatic α-
azido ketones bearing halogen and electron withdrawing/
releasing functional groups gave quantitative yields of the
products. Vinyl azides derived from aliphatic α-azido ketones
could not be prepared using our standard protocol; therefore,
they could not be attempted for our study. The reaction was
successful with 2-aminopyridines containing several functional
groups such as halogen and esters (Table 2, entries 21−22).
The reaction was also successful with 1-aminoisoquinoline 2b
b
entry
solvent
toluene
T (°C)
time (h)
yield,
%
1
2
3
4
5
6
7
8
9
30
70
48
12
12
12
6
0
toluene
toluene
EtOH
78
70
110
80
81
CH3CN
CHCl3
85
91
70
6
97
c
THF
70
6
>99
87
1,2-DCE
1,4-dioxane
80
12
12
100
65
a
Reaction conditions: vinyl azide 1a (0.5 mmol), 2-aminopyridine 2a
b
c
(0.5 mmol), solvent (5 mL), stir. Isolated yields. The crude reaction
product obtained after evaporating the solvent was very pure under 1H
NMR analysis.
its MS/HRMS, IR, and H and 13C NMR spectra. In order to
find the best solvent for the annulations, several solvents such
1
a
Table 2. Scope of the Annulations of Vinyl Azide 1 and 2-Aminopyridine 2 To Yield Imidazo[1,2-a]pyridine 3
b
entry
R
R1
R2
product
purity, %
1
4-Cl-C6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
4-Cl
3a
3b
3c
3d
3e
3f
98.3
87.4
98.7
98.5
98.3
98.1
98.7
99.8
98.4
2
4-Br-C6H4
3
2-naphthyl
4
4-NO2-C6H4
3-NO2-C6H4
4-CN-C6H4
5
6
7
3-C6H5O-C6H4
3,5-(OCH3)2-C6H3
2-furyl
3g
3h
3i
8
9
4-F-C6H4
c
10
11
12
13
14
15
16
17
18
19
20
21
22
3,5-(OCH3)2-C6H3
4-Br-C6H4
4-Cl-C6H4
3j
99.3 (99.5)
99.9
4-Cl-C6H4
3k
3l
4-CH3-C6H4
4-NO2-C6H4
3,4,5-(OCH3)3-C6H2
C6H5
4-Cl-C6H4
98.9
4-Cl-C6H4
3m
3n
3o
3p
3q
3r
3s
3t
99.2
4-Cl-C6H4
98.0
4-Cl-C6H4
99.3
4-Cl-C6H4
3-CH3O-C6H4
3-CH3O-C6H4
4-CH3O-C6H4
4-CH3O-C6H4
4-CN-C6H4
4-Cl-C6H4
98.4
4-NO2-C6H4
4-NO2-C6H4
4-Cl-C6H4
99.5
98.2
98.6
3,5-(OCH3)2-C6H3
3,5-(OCH3)2-C6H3
3,5-(OCH3)2-C6H3
95.0
3u
3v
93.9
4-Cl-C6H4
4-COOMe
99.6
a
b
Reaction conditions: vinyl azide 1 (0.5 mmol), 2-aminopyridine 2 (0.5 mmol), dry THF (5 mL), reflux. Determined by HPLC analysis of the
c
crude product which was obtained in quantitative yields after evaporating the reaction solvent. Values in the parentheses represent purity of a
sample which was obtained quantitatively in a gram scale (10 mmol scale) reaction.
B
DOI: 10.1021/acs.orglett.5b02124
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
and yielded imidazo[2,1-a]isoquinoline 3w in quantitative yield
(Scheme 2). Unambiguous proof for the structure of
Scheme 4. Mechanistic Rationalization for the Annulations
of Vinyl Azides and 2-Aminopyridines To Yield Imidazo[1,2-
a]pyridine Derivatives
Scheme 2. Annulation of Vinyl Azide 1b and 1-
Aminoisoquinoline 2b To Yield Imidazo[2,1-a]isoquinoline
3w
imidazo[1,2-a]pyridine was obtained by single crystal X-ray
analysis of the compound 3d (the details of the X-ray analysis
can be found in the Supporting Information).
Under heating the imine 5 generated from the condensation of
vinyl azide 1 and 2-aminopyridine 2 loses nitrogen to yield a
2H-azirine intermediate 6. Formation of the imidazo[1,2-
a]pyridine 3 from the intermediate 6 can be explained in two
ways (Scheme 4, path A and B). Path A: The 2H-azirine is
opened up by the lone pair of the nitrogen forming a C−N
triple bond, and the C−C bond of the 2H-azirine is cleaved.
This leads to the formation of a zwitterion 7 which is attacked
by the lone pair of pyridine yielding a different zwitterion 3′
which is actually a resonance form of the product. Path B: The
lone pair of the pyridine attacks the 2H-azirine intramolecularly
to yield a zwitterion intermediate 8 which rearranges to final
product 3.
An alternative mechanism based on generation of a 2H-
azirine from 1 at the very first step and its subsequent
annulation with 2 seems also possible. However, a significant
amount of byproducts can be expected if the reaction followed
this pathway, since thermal conversion of vinyl azides bearing
an α-keto carbonyl group (vinyl azides of type 1) to 2H-azirines
is a poor yielding process due to competing nitrile and indole
forming reactions.19,20 We did not observe the formation of
noticeable byproducts in our annulations study even when a
control reaction was performed in an NMR tube (for details of
the control experiment, see Supporting Information). This
evidence indicates that the nitrogen of pyridine is the key which
drives the annulation forward right after the formation of imine
5 probably through 2H-azirine type intermediates.
It is noteworthy that the imidazo[1,2-a]pyridines 3a−w were
obtained simply by removing THF from the reaction mixture
under a reduced pressure and were very pure. HPLC analysis of
the crude mass obtained after evaporating the reaction solvent
(THF) was carried out which showed high purity (87.4−
99.9%) of the imidazo[1,2-a]pyridines 3a−w (Table 2). It is
also notable that, in contrast to earlier reports, our method-
ology gives quantitative yields of the products and allows
unsymmetrical substitution (R and R1) in the imidazo[1,2-
a]pyridine unit. Next, in order to demonstrate the synthetic
competence of our strategy, a gram scale reaction (10 mmol
scale) was performed (Table 2, entry 10). The quantitative
yield (purity: 99.5%) of the imidazo[1,2-a]pyridine in the gram
scale synthesis showed that the strategy has the potential for
industrial scale up production.
Since imidazo[1,2-a]pyridine 3 was obtained in pure form
simply by evaporating the reaction solvent, the reactive imine
group of 3 could be utilized to yield numerous derivatives in a
one-pot operation. In order to demonstrate it, after the
formation of 3 was complete, the solvent (THF) was removed
under reduced pressure and the reaction mixtures were directly
treated with NaBH4/MeOH to give amines 4 (Scheme 3). It is
Scheme 3. One-Pot Synthesis of Groebke Imidazo[1,2-
a]pyridines
In conclusion, we have developed a novel and efficient
methodology for the synthesis of diverse and functionalized
imidazo[1,2-a]pyridines through an unprecedented annulation
of readily available vinyl azides and 2-aminopyridines. To the
best of our knowledge, it is the first report of any heterocycle
synthesis which gives quantitative yields of products and
requires evaporation of the solvent as the only purification step.
This operationally simple strategy allows the formation of three
new C−N bonds, with the release of H2O and N2 as the sole
byproduct, through a condensation, cyclization, and ring
opening reaction cascade, in a process that is highly atom
economical, convenient, and scalable to fulfill the demands of
academia and industry. A series of 23 different imidazo[1,2-
a]pyridine derivatives were synthesized in high yields by
reacting vinyl azides and 2-aminopyridines. In addition, this
catalyst/metal-free synthetic route allows the formation of N-
(imidazo[1,2-a]pyridin-3-yl)-1-arylmethanimines that contain a
reactive imine functionality which can be utilized in multiple
ways to generate numerous imidazo[1,2-a]pyridines in a one-
pot protocol.
worth noting that highly pure (98.3−99.0%) amines 4 were
obtained after removing methanol and extracting the crude
product by EtOAc/water in excellent yields (>98%). Since
imidazo[1,2-a]pyridines 4 can be synthesized by Groebke
reaction, prior to synthesizing them one can compare both
strategies based on their pros and cons. In general, our
methodology is superior to other reported syntheses in terms of
reaction simplicity, purity, workup/purifications, yields, and
more importantly offering reactive imines 3 for further
derivatization.
Annulations of vinyl azides 1 with 2-aminopyridines 2 can be
explained by a plausible mechanism depicted in Scheme 4.
C
DOI: 10.1021/acs.orglett.5b02124
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
C. K. F.; da Silva, L. L.; Romeiro, N. C.; Miranda, A. L. P.; Barreiro, E.
J.; Fraga, C. A. M. Bioorg. Med. Chem. 2009, 17, 74.
(7) Langer, S. Z.; Arbilla, S.; Benavides, J.; Scatton, B. Adv. Biochem.
ASSOCIATED CONTENT
■
S
* Supporting Information
Psychopharmacol. 1990, 46, 61.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.5b02124.
(8) Boerner, R. J.; M?ller, H. J. Psychopharmakother 1997, 4, 145.
(9) Mizushige, K.; Ueda, T.; Yukiiri, K.; Suzuki, H. Cardiovasc. Drug
Rev. 2002, 20, 163.
(10) Almirante, L.; Polo, L.; Mugnaini, A.; Provinciali, E.; Rugarli, P.;
Biancotti, A.; Gamba, A.; Murmann, W. J. Med. Chem. 1965, 8, 305.
(11) Gudmundsson, K.; Boggs, S. D. PCT Int. Appl. WO
2006026703, 2006.
Full experimental details, characterization data for all
1
products, copies of H and 13C spectra, X-ray analysis,
and HPLC chromatograms (PDF)
(12) Koo, H. L.; Dupont, H. L. Curr. Opin. Gastroenterol. 2010, 26,
17.
AUTHOR INFORMATION
■
(13) (a) John, A.; Shaikh, M. M.; Ghosh, P. Dalton Trans. 2009,
10581. (b) Song, G.; Zhang, Y.; Li, X. Organometallics 2008, 27, 1936.
(14) (a) Douhal, A.; Amat-Guerri, F.; Acuna, A. U. J. Phys. Chem.
1995, 99, 76. (b) Douhal, A.; Amat-Guerri, F.; Acuna, A. U. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1514. (c) Douhal, A. Ber. Bunsen-Ges.
1998, 102, 448.
Corresponding Author
*E-mail: ramaurya@iict.res.in.
Notes
The authors declare no competing financial interest.
(15) (a) Groebke, K.; Weber, L.; Mehlin, F. Synlett 1998, 1998, 661.
(b) Bienayme, H.; Bouzid, K. Angew. Chem., Int. Ed. 1998, 37, 2234.
(c) Blackburn, C.; Guan, B.; Fleming, P.; Shiosaki, K.; Tsai, S.
Tetrahedron Lett. 1998, 39, 3635. (d) Sharma, S.; Maurya, R. A.; Min,
K.-I.; Jeong, G.-Y.; Kim, D.-P. Angew. Chem., Int. Ed. 2013, 52, 7564.
(16) For recent reviews on the synthesis of imidazo[1,2-a]pyridines,
see: (a) Pericherla, K.; Kaswan, P.; Pandey, K.; Kumar, A. Synthesis
2015, 47, 887. (b) Bagdi, A. K.; Santra, S.; Monir, K.; Hajra, A. Chem.
Commun. 2015, 51, 1555. (c) Liu, Z.-Q. Curr. Org. Synth. 2015, 12, 20.
(17) For selected recent publications on the synthesis of imidazo[1,2-
a]pyridines, see: (a) Lee, S. K.; Park, J. K. J. Org. Chem. 2015, 80,
3723. (b) Manna, S.; Narayan, R.; Golz, C.; Strohmann, C.;
Antonchick, A. P. Chem. Commun. 2015, 51, 6119. (c) Cao, H.; Liu,
X.; Liao, J.; Huang, J.; Qiu, H.; Chen, Q.; Chen, Y. J. Org. Chem. 2014,
79, 11209. (d) Donthiri, R. R.; Pappula, V.; Reddy, N. N. K.; Bairagi,
D.; Adimurthy, S. J. Org. Chem. 2014, 79, 11277. (e) Cao, H.; Liu, X.;
Zhao, L.; Cen, J.; Lin, J.; Zhu, Q.; Fu, M. Org. Lett. 2014, 16, 146.
(f) Huang, H.; Ji, X.; Tang, X.; Zhang, M.; Li, X.; Jiang, H. Org. Lett.
2013, 15, 6254. (g) Mohan, D. C.; Rao, S. N.; Adimurthy, S. J. Org.
Chem. 2013, 78, 1266. (h) He, C.; Hao, J.; Xu, H.; Mo, Y.; Liu, H.;
Han, J.; Lei, A. Chem. Commun. 2012, 48, 11073. (i) Nair, D. K.;
Mobin, S. M.; Namboothiri, I. N. N. Org. Lett. 2012, 14, 4580. (j) Ma,
L.; Wang, X.; Yu, W.; Han, B. Chem. Commun. 2011, 47, 11333.
(k) Guchhait, S. K.; Chaudhary, V. Org. Biomol. Chem. 2014, 12, 6694.
(l) Rahmati, A.; Moazzam, A.; Khalesi, Z. Tetrahedron Lett. 2014, 55,
3840. (m) Kamal, A.; Reddy, C. N.; Satyaveni, M. S.; Chandrasekhar,
D.; Nanubolu, J. B.; Singarapu, K. K.; Maurya, R. A. Chem. Commun.
2015, 51, 10475.
ACKNOWLEDGMENTS
■
R.A.M. is thankful to the Department of Science & Technology,
India for financial support (GAP 0378 and GAP 0470).
Financial support in part from 12th Five Year Plan Project
“Affordable Cancer Therapeutics (ACT-CSC-0301)” is also
acknowledged. P.R.A. acknowledges CSIR New Delhi, and
G.S.M. acknowledges NIPER Hyderabad for financial support.
REFERENCES
■
(1) (a) McKeown, M. R.; Shaw, D. L.; Fu, H.; Liu, S.; Xu, X.;
Marineau, J. J.; Huang, Y.; Zhang, X.; Buckley, D. L.; Kadam, A.;
Zhang, Z.; Blacklow, S. C.; Qi, J.; Zhang, W.; Bradner, J. E. J. Med.
Chem. 2014, 57, 9019. (b) Arama, D. P.; Soualmia, F.; Lisowski, V.;
Longevial, J.-F.; Bosc, E.; Maillard, L. T.; Martinez, J.; Masurier, N.; El
Amri, C. Eur. J. Med. Chem. 2015, 93, 202. (c) Kim, Y. B.; Kang, C. W.;
Ranatunga, S.; Yang, H.; Sebti, S. M.; Del Valle, J. R. D. Bioorg. Med.
Chem. Lett. 2014, 24, 4650.
(2) (a) Moraski, G. C.; Oliver, A. G.; Markley, L. D.; Cho, S.;
Franzblau, S. G.; Miller, M. J. Bioorg. Med. Chem. Lett. 2014, 24, 3493.
(b) Kang, S.; Kim, R. Y.; Seo, M. J.; Lee, S.; Kim, Y. M.; Seo, M.; Seo,
J. J.; Ko, Y.; Choi, I.; Jang, J.; Nam, J.; Park, S.; Kang, H.; Kim, H. J.;
Kim, J.; Ahn, S.; Pethe, K.; Nam, K.; No, Z.; Kim, J. J. Med. Chem.
2014, 57, 5293. (c) Shukla, N. M.; Salunke, D. B.; Yoo, E.; Mutz, C.
A.; Balakrishna, R.; David, S. A. Bioorg. Med. Chem. 2012, 20, 5850.
(3) (a) Castera-Ducros, C.; Paloque, L.; Verhaeghe, P.; Casanova,
M.; Cantelli, C.; Hutter, S.; Tanguy, F.; Laget, M.; Remusat, V.;
Cohen, A.; Crozet, M. D.; Rathelot, P.; Azas, N.; Vanelle, P. Bioorg.
(18) (a) Knittel, D.; Hemetsberger, H.; Weidmann, H. Monatsh.
Chem. 1970, 101, 157. (b) Hemetsberger, H.; Knittel, D.; Weidmann,
H. Monatsh. Chem. 1969, 100, 1599.
(19) Hassner, A.; Wiegand, N. H.; Gottlieb, H. E. J. Org. Chem. 1986,
51, 3176.
́
Med. Chem. 2013, 21, 7155. (b) Hernandez, P.; Rojas, R.; Gilman, R.
H.; Sauvain, M.; Lima, L. M.; Barreiro, E. J.; Gonzalez, M.; Cerecetto,
H. Eur. J. Med. Chem. 2013, 59, 64.
(4) (a) Ulloora, S.; Shabaraya, R.; Adhikari, A. V. Bioorg. Med. Chem.
Lett. 2013, 23, 3368. (b) Ulloora, S.; Shabaraya, R.; Aamir, S.;
Adhikari, A. V. Bioorg. Med. Chem. Lett. 2013, 23, 1502.
(20) Singh, P. N. D.; Carter, C. L.; Gudmundsdottir, A. D.
Tetrahedron Lett. 2003, 44, 6763.
(5) (a) Enguehard-Gueiffier, C.; Musiu, S.; Henry, N.; Veron, J. B.;
Mavel, S.; Neyts, J.; Leyssen, P.; Paeshuyse, J.; Gueiffier, A. Eur. J. Med.
Chem. 2013, 64, 448. (b) Bode, M. L.; Gravestock, D.; Moleele, S. S.;
van der Westhuyzen, C. W.; Pelly, S. C.; Steenkamp, P. A.; Hoppe, H.
C.; Khan, T.; Nkabinde, L. A. Bioorg. Med. Chem. 2011, 19, 4227.
(6) (a) Vitse, O.; Laurent, F.; Pocock, T. M.; Benezech, V.; Zanik, L.;
Elliott, K. R. F.; Subra, G.; Portet, K.; Bompart, J.; Chapat, J.-P.; Small,
R. C.; Michel, A.; Bonnet, P.-A. Bioorg. Med. Chem. 1999, 7, 1059.
(b) Scribner, A.; Dennis, R.; Lee, S.; Ouvry, G.; Perrey, D.; Fisher, M.;
Wyvratt, M.; Leavitt, P.; Liberator, P.; Gurnett, A.; Brown, C.;
Mathew, J.; Thompson, D.; Schmatz, D.; Biftu, T. Eur. J. Med. Chem.
2008, 43, 1123. (c) Buckley, G. M.; Fosbeary, R.; Fraser, J. L.; Gowers,
L.; Higueruelo, A. P.; James, L. A.; Jenkins, K.; Mack, S. R.; Morgan,
T.; Parry, D. M.; Pitt, W. R.; Rausch, O.; Richard, M. D.; Sabin, V.
Bioorg. Med. Chem. Lett. 2008, 18, 3656. (d) Lacerda, R. B.; de Lima,
D
DOI: 10.1021/acs.orglett.5b02124
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