Journal of Medicinal Chemistry
Brief Article
was stirred for 1 h at 25 °C, and an ice cooled solution of HCl 1N and
chloroform were added. The organic layer was separated, washed with
brine, dried, and concentrated in vacuum. Purification by column
chromatography on silica gel (DCM−EtOAc) provided title compounds
(yields, physical, and spectral data are reported in Table S4, SI).
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ASSOCIATED CONTENT
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S
* Supporting Information
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imaging of neuroinflammation: a comprehensive review of [11C]PK11195
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A. M.; Salerno, S.; Bellandi, M.; Novellino, E.; Greco, G.; Cosimelli, B.;
Da Pozzo, E.; Costa, B.; Simola, N.; Morelli, M.; Martini, C.
Anxiolytic-like effects of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides
by modulation of translocator protein promoting neurosteroid
biosynthesis. J. Med. Chem. 2008, 51, 5798−5806.
(11) Cosimelli, B.; Simorini, F.; Taliani, S.; La Motta, C.; Da Settimo,
F.; Severi, E.; Greco, G.; Novellino, E.; Costa, B.; Da Pozzo, E.;
Bendinelli, S.; Martini, C. Tertiary amides with a five-membered
heteroaromatic ring as new probes for the translocator protein. Eur. J.
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(12) Dubroeucq, M. C.; Renault, C.; Le Fur, G. Derivatives of arene
and hetero-arene carboxamides and their use as medicaments. US
1983/482082, US19830482082, 19830405, Feb 12, 1985.
General chemistry directions, general procedure for the
synthesis of 4-phenylquinazoline-2-carboxylic acids 77−82,
yields, physical, and spectral data of compounds 1−70, and
77−82, computational chemistry, calculated physicochemical
and pharmacokinetic properties of compound 14 and PK11195,
biological methods, BzR binding data of compounds 1−58,
increase in pregnenolone production of selected quinazoline
derivatives, effect on proliferation/viability of U87MG glioma
cells of compounds 9 and 14. This material is available free of
AUTHOR INFORMATION
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Corresponding Author
*Phone: (+39)0502219547. Fax: (+39)0502219605. E-mail:
(13) Campiani, G.; Nacci, V.; Fiorini, I.; De Filippis, M. P.; Garofalo,
A.; Ciani, S. M.; Greco, G.; Novellino, E.; Williams, D. C.; Zisterer,
D. M.; Woods, M. J.; Mihai, C.; Manzoni, C.; Mennini, T. Synthesis,
biological activity, and SARs of pyrrolobenzoxazepine derivatives, a
new class of specific “peripheral-type” benzodiazepine receptor ligands.
J. Med. Chem. 1996, 39, 3435−3450.
Author Contributions
All authors have given approval to the final version of the
manuscript.
Funding
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of anilines. J. Am. Chem. Soc. 1978, 100, 4842−4845.
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L.; Salvetti, A.; Scatena, F.; Ceruti, S.; Abbracchio, M. P.; Gremigni, V.;
Martini, C. Peripheral benzodiazepine receptor ligands: mitochondrial
transmembrane potential depolarization and apoptosis induction in rat C6
glioma cells. Biochem. Pharmacol. 2004, 68, 125−134.
(16) Ruan, S.; Okcu, M. F.; Pong, R. C.; Andreeff, M.; Levin, V.;
Hsieh, J. T.; Zhang, W. Attenuation of WAF1/Cip1 expression by an
antisense adenovirus expression vector sensitizes glioblastoma cells to
apoptosis induced by chemotherapeutic agents 1,3-bis(2-chloroethyl)-
1-nitrosourea and cisplatin. Clin. Cancer Res. 1999, 5, 197−202.
(17) Cappelli, A.; Anzini, M.; Vomero, S.; De Benedetti, P. G.;
Menziani, M. C.; Giorgi, G.; Manzoni, C. Mapping the peripheral benzo-
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(18) Shah, F.; Hume, S. P.; Pike, V. W.; Ashworth, S.; McDermott, J.
Synthesis of the enantiomers of [N-methyl-11C]PK11195 and
comparison of their behaviours as radioligands for PK binding sites
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This study was financially supported by grants from Istituto
Toscano Tumori (grant 2007), MIUR (PRIN 2009, Futuro in
Ricerca 2010), Universita di Salerno and Universita di Trieste.
̀ ̀
Notes
The authors declare no competing financial interest.
ABBREVIATIONS USED
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BBB, blood−brain barrier; BzR, central benzodiazepine receptor;
CNS, central nervous system; PBR, peripheral benzodiazepine
receptor; PET, positron emission tomography; SARs, structure−
activity relationships; TSPO, 18 kDa translocator protein
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