Journal of Medicinal Chemistry
Brief Article
mg/mL for each setup. Crystallization condition for the 20·C139A Ns
H-NOX complex was 1.9 M sodium malonate, pH 7.0. Crystals were
cryoprotected in 3.0 M sodium malonate, pH 7.0, prior to dunking the
crystals in liquid nitrogen for storage and data collection. For data
collection, see SI.
(10) Mitrovic, V. H., A. F.; Meyer, M.; Gheorghiade, M. Role of
guanylate cyclase modulators in decompensated heart failure. Heart
Failure Rev. 2009, 14, 309−319.
(11) Martin, F.; Baskaran, P.; Ma, X.; Dunten, P. W.; Schaefer, M.;
Stasch, J.-P.; Beuve, A.; van den Akker, F. Structure of cinaciguat (BAY
58-2667) bound to Nostoc H-NOX domain reveals insights into heme-
mimetic activation of the soluble guanylyl cyclase. J. Biol. Chem. 2010,
285, 22651−22657.
ASSOCIATED CONTENT
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S
* Supporting Information
(12) Schmidt, P. M.; Schramm, M.; Schroder, H.; Wunder, F.; Stasch,
̈
Synthesis details, 1H NMR and 13C NMR of synthesized
compounds, and pharmacological and molecular biological
methods. This material is available free of charge via the Internet
J.-P. Identification of residues crucially involved in the binding of the
heme moiety of soluble guanylate cyclase. J. Biol. Chem. 2004, 279,
3025−3032.
(13) Heck, R. F.; Nolley, J. P. Palladium-catalyzed vinylic hydrogen
substitution reactions with aryl, benzyl, and styryl halides. J. Org. Chem.
1972, 37, 2320−2322.
Accession Codes
The structure is deposited in the Protein Data Bank with the
PDB ID 4JQH.
(14) Moeller, D.; Tian, J. Electrochemically assisted Heck reactions.
Org. Lett. 2005, 7, 5381−5383.
(15) Schiemenz, G. P.; Finzenhagen, M. Aromatische phosphane mit
substituenten zweiter ordnung, XVI. Phenyloge PO-aktivierte olefinier-
ung: synthese 4′-donator-substituierter 4-(diphenylphosphinyl)-
stilbene. Liebigs Ann. Chem. 1981, 1981, 1476−1484.
(16) Taylor, E. C.; Harrington, P. M.; Shih, C. A facile route to “open
chain” analogs of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF).
Heterocycles 1989, 28, 1169−1178.
(17) Tidwell, T. T.; Dalton, A. I. Mechanisms of induced
decomposition. I. Reactivity of di-tert-butylperoxy homoterephthalate.
J. Org. Chem. 1972, 37, 1504−1510.
(18) CollingtonE. W. H., P.WallisC. J.BradshawJ.Prostanoid com-
pounds and their preparation and pharmaceutical formulations. Eur. Pat.
Appl. 32432, 1981.
(19) Lin, J.; Gerstenberger, B. S.; Stessman, N. Y. T.; Konopelski, J. P.
Diazonamide support studies: stereoselective formation of the C10
chiral center in both the CDEFG and AEFG fragments. Org. Lett. 2008,
10, 3969−3972.
(20) Lv, P.-C.; Xiao, Z.-P.; Fang, R.-Q.; Li, H.-Q.; Zhu, H.-L.; Liu, C.-
H. Synthesis, characterization and structure−activity relationship
analysis of novel depsides as potential antibacterials. Eur. J. Med.
Chem. 2009, 44, 1779−1787.
AUTHOR INFORMATION
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Corresponding Authors
Author Contributions
⊥M.v.W.R., V.K., F.v.d.A., A.G., and A.P. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work has been supported by NIH grant R01 HL075329 (to
F.v.d.A.), EU FP7 REGPOT CT-2011-285950, “SEE-DRUG”,
the Thorax Foundation (Athens, Greece), and by the COST
Action BM1005 (European Network on Gasotransmitters,
ENOG). We thank Dr. Leontari Iliana for performing the
UPLC analysis.
(21) Goodyer, C. L. M.; Chinje, E. C.; Jaffar, M.; Stratford, I. J.;
Threadgill, M. D. Synthesis of N-benzyl- and N-phenyl-2-amino-4,5-
dihydrothiazoles and thioureas and evaluation as modulators of the
isoforms of nitric oxide synthase. Bioorg. Med. Chem. 2003, 11, 4189−
4206.
ABBREVIATIONS USED
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sGC, soluble guanylyl cyclase; H-NOX, heme−nitric oxide/
oxygen binding
(22) Zhang, X.; Zhou, Z.; Yang, H.; Chen, J.; Feng, Y.; Du, L.; Leng, Y.;
Shen, J. 4-(Phenylsulfonamidomethyl)benzamides as potent and
selective inhibitors of the 11β-hydroxysteroid dehydrogenase type 1
with efficacy in diabetic ob/ob mice. Bioorg. Med. Chem. Lett. 2009, 19,
4455−4458.
(23) Alonso-Alija, C. H., M.; ; Flubacher, D.; Naab, P.; Pernerstorfer, J.;
Stasch, J.-P.; Wunder, F.; Dembowsky, K.; Perzborn, E.; Stahl, E.
Synthesis of novel phenylacetic acid derivatives with halogenated benzyl
subunit and evaluation as aldose reductase inhibitor. DE19943635A1,
2001.
(24) Kumar, V.; Martin, F.; Hahn, M. G.; Schaefer, M.; Stamler, J. S.;
Stasch, J. P.; van den Akker, F. Insights into BAY 60-2770 activation and
S-nitrosylation-dependent desensitization of soluble guanylyl cyclase via
crystal structures of homologous Nostoc H-NOX domain complexes.
Biochemistry 2013, 52, 3601−3608.
(25) Winger, J. A.; Marletta, M. A. Expression and characterization of
the catalytic domains of soluble guanylate cyclase: interaction with the
heme domain. Biochemistry 2005, 44, 4083−4090.
REFERENCES
■
(1) Lucas, K. A.; Pitari, G. M.; Kazerounian, S.; Ruiz-Stewart, I.; Park,
J.; Schulz, S.; Chepenik, K. P.; Waldman, S. A. Guanylyl cyclases and
signaling by cyclic GMP. Pharmacol. Rev. 2000, 52, 375−414.
(2) Hobbs, A. J. Soluble guanylate cyclase: the forgotten sibling. Trends
Pharmacol. Sci. 1997, 18, 484−491.
(3) Friebe, A.; Koesling, D. Regulation of nitric oxide-sensitive guanylyl
cyclase. Circ. Res. 2003, 93, 96−105.
(4) Harrison, D. G.; JN., B. The nitrovasodilators. New ideas about old
drugs. Circulation 1993, 87, 1461−1467.
(5) Munzel, T.; Daiber, A.; T., G. Nitrate therapy: new aspects
̈
concerning molecular action and tolerance. Circulation 2011, 123,
2132−2144.
(6) Evgenov, O. V.; Pacher, P.; Schmidt, P. M.; Hasko, G.; Schmidt, H.
H. H. W.; Stasch, J.-P. NO-independent stimulators and activators of
soluble guanylate cyclase: discovery and therapeutic potential. Nature
Rev. Drug Discovery 2006, 5, 755−768.
(7) Stasch, J. P.; Pacher, P.; OV., E. Soluble guanylate cyclase as an
emerging therapeutic target in cardiopulmonary disease. Circulation
2011, 123, 2263−2273.
(8) Stasch, J. P.; AJ., H. NO-independent, haem-dependent soluble
guanylate cyclase stimulators. Handb. Exp. Pharmacol. 2009, 191, 277−
308.
(9) Schmidt, H. H.; Schmidt, P. M.; JP., S. NO- and haem-independent
soluble guanylate cyclase activators. Handb. Exp. Pharmacol. 2009, 191,
309−339.
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