Erratum: Design, synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing methyl ferulate (Bioorg. Med. Chem. Lett. (2013) 23 (2089-2092))

Full text of DOI:10.1016/j.bmcl.2013.07.065

Bioorganic & Medicinal Chemistry Letters 23 (2013) 5453–5455
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Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Corrigendum
Corrigendum to ‘‘Design, synthesis and antithrombotic evaluation
of novel dabigatran prodrugs containing methyl ferulate’’
[Bioorg. Med. Chem. Lett. 23 (2013) 2089–2092]
Xiao-Zhi Yang a, Xiao-Juan Diao a, Wen-Hui Yang b, Feng Li c, Guang-Wei He c, Guo-Qing Gong b,
Yun-Gen Xu a,
⇑
a Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China
b Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China
c Hefei Yi Gong Pharmaceutical Co., Ltd, Hefei 230088, China
The authors regret that the structures of methyl ferulate and X-2 appeared incorrectly. The corrected figures, tables and Supplementary
material appear here.
Supplementary data
Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.bmcl.2013.07.065.
O
N
CH3
O
CH3
N
N
NH
NH2
N
CH3
O
N
Dabigatran etexilate
O
O
OCH3
OH
OCH3
OH
H3COOC
HOOC
Ferulic acid
Methyl ferulate
O
CH3
O
CH3
N
N
NH
N
OCH3
NH2
N
O
N
O
O
H3COOC
X-2
Figure 1. Structures of dabigatran etexilate, ferulic acid, methyl ferulate and X-2.
DOI of original article: http://dx.doi.org/10.1016/j.bmcl.2013.01.126
⇑
Corresponding author. Tel./fax: +86 25 83271244.
E-mail addresses: xu_yungen@hotmail.com, xyg@cpu.edu.c (Y.-G. Xu).
0960-894X/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bmcl.2013.07.065

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X.-Z. Yang et al. / Bioorg. Med. Chem. Lett. 23 (2013) 5453–5455
X-2
O
CH3
O
CH3
N
N
N
HN
OCH3
NH2
N
O
N
O
O
H3CO
in vivo
hydrolysis
O
Ferulic acid
Dabigatran
OCH3
CH3
N
NH
OH
N
HN
NH2
N
N
HOOC
HOOC
O
Ca2+
-
-
-
Thrombin
Platelet
ADP
-
Venous Thrombosis
Figure 3. Proposed metabolic route of compound X-2.
CH3
N
CH3
N
O
N
NH
O
O
N
N
a
HN
HN
O R1~7
N
N
NH2
NH2
. 2HCl
N
N
O
CH3
O
CH3
O
O
a1~a7
1
b
O
CH3
N
CH3
N
N
HN
O R1~7
O
NH2
N
c
O
N
N
O
N
N
N
HN
O R1~7
NH2
N
OCH3
O
OH
O
O
COOCH3
b1~b7
X-1~X-7
R1: tert-butyl, R2: n-hexyl, R3: ethyl, R4: benzyl,
R5: n-pentyl, R6: isopropyl, R7:methyl
Scheme 1. Reagents, conditions and range of yields: (a) R1–R7 chloroformate, K2CO3, THF/H2O, yields: 57–74%; (b) NaOH, EtOH/H2O, yields: 70–92%; (c) methyl ferulate,
EDCI, DMAP, DMF, yields: 54–69%.

X.-Z. Yang et al. / Bioorg. Med. Chem. Lett. 23 (2013) 5453–5455
5455
Table 1
Structures of target compounds X-1–X-7 and their activities for inhibiting thrombin-induced rabbit platelet aggregation after the
incubation with rabbit liver microsomes
R
O
O
CH3
N
N
N
NH
OCH3
NH2
N
O
N
O
O
H3COOC
a
Compd
R
/
IC50 (lM)
Dabigatran etexilate
0.337 0.021
0.607 0.039
0.290 0.060
0.453 0.014
0.687 0.045
0.206 0.039
0.784 0.012
0.841 0.024
X-1
X-2
X-3
X-4
X-5
X-6
X-7
tert-Butyl
n-Hexyl
Ethyl
Benzyl
n-Pentyl
Isopropyl
Methyl
a
Drug concentration to achieve half-maximal inhibition of rabbit platelet aggregation induced by thrombin. Data were
expressed as mean SD from six independent experiments.