Bioorganic & Medicinal Chemistry Volume 21, Issue 9, 2013

Contents

REVIEW

A comprehensive review on synthesis and designing aspects of coumarin derivatives as monoamine oxidaseinhibitors for depression and Alzheimer’s disease

pp 2434–2450

Pravin O. Patil*, Sanjay B. Bari, Sandip D. Firke, Prashant K. Deshmukh,Shailesh T. Donda, Dilip A. Patil

ARTICLES

Synthesis and biological evaluation of novel azole derivatives as selective potent inhibitors of brassinosteroidbiosynthesis

pp 2451–2461

Kazuhiro Yamada, Osamu Yajima, Yuko Yoshizawa, Keimei Oh*

Structure–activity relationship studies revealed that 2RS, 4RS-1-[4-(2-allyloxyphenoxymethyl)-2-(4-chlorophenyl)-[1,3]dioxolan-2-ylmethyl]-1H-[1,2,4]triazole (G2) is a selective inhibitor of BR biosynthesis, with an IC50 value of approximately 46 ± 2 nM.

Design, synthesis and evaluation of tacrine–flurbiprofen–nitrate trihybrids as novel anti-Alzheimer’s disease agents pp 2462–2470

Yao Chen, Jianfei Sun, Zhangjian Huang, Hong Liao*, Sixun Peng, Jochen Lehmann*, Yihua Zhang*

N

HN NH

m

O

FO ONO2

n

3a, m=6, n=2

Ki for AChE = 16.1 nMKi for BuChE = 1.7 nM

Eight tacrine–flurbiprofen–nitrate trihybrids were synthesized and biologically evaluated and most of them exhibited good performance. Particularly,compound 3a showed higher in vitro activity (Ki for AChE = 16.1 nM; Ki for BuChE = 1.7 nM) and lower hepatotoxicity than tacrine.

Bioorganic & Medicinal Chemistry 21 (2013) 2427–2433

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Bioorganic & Medicinal Chemistry

journal homepage: www.elsevier .com/locate /bmc

Synthesis and cytotoxic activity of metallic complexes of lawsone pp 2471–2477

Sandra Oramas-Royo, Concepción Torrejón, Irene Cuadrado, Rita Hernández-Molina, Sonsoles Hortelano*,Ana Estévez-Braun*, Beatriz de las Heras*

O

O

OMO

O

O

H2O

OH2 2 M=Zn3 M=Co4 M=Cu5 M=Ni6 M=Mn

Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatmentof diabetic macular edema: Part 2

pp 2478–2494

Takayuki Inoue*, Masataka Morita, Takashi Tojo, Akira Nagashima, Ayako Moritomo, Keisuke Imai, Hiroshi Miyake

1

2

35c 35a

HCl

HN

NH 2NH

O

NH

S

N O

OS

HN

NH2NH

O

NH N

S

N

O

NH

O

OS

NF

HN

NH2NH

N

O

NH

S

OS

O

The thiazole derivative 35c is a potent and selective VAP-1 inhibitor.

Novel hybrids of natural isochroman-4-one bearing N-substituted isopropanolamine as potential antihypertensivecandidates

pp 2495–2502

Renren Bai, Xiaojing Huang, Xue Yang, Wen Hong, Yiqun Tang, Hequan Yao, Jieyun Jiang, Jie Liu*, Mingqin Shen,Xiaoming Wu*, Jinyi Xu*

Synthesis of (S)-FTY720 vinylphosphonate analogues and evaluation of their potential as sphingosine kinase 1 inhibitorsand activators

pp 2503–2510

Zheng Liu, Neil MacRitchie, Susan Pyne, Nigel J. Pyne, Robert Bittman*

C8H17

PNH2

OH

O

OHOH CO2H

F

N3

(S)-FTY720 vinylphosphonate (SK1 allosteric inhibitor)

SK1 activator at low concentrationsbut SK1 inhibitor above 50 μM

SK1 weak inhibitor

neither inhibitor nor activator

(S)-FTY720 vinyl-phosphonate analogueswere synthesized:OH to F; NH2 to N3;P(O)(OH)2 to CO2H

2428 Contents / Bioorg. Med. Chem. 21 (2013) 2427–2433

Covalent inhibition of SUMO and ubiquitin-specific cysteine proteases by an in situ thiol–alkyne addition pp 2511–2517

Stefanie Sommer, Nadine D. Weikart, Uwe Linne, Henning D. Mootz*

CD4 mimics as HIV entry inhibitors: Lead optimization studies of the aromatic substituents pp 2518–2526

Tetsuo Narumi, Hiroshi Arai, Kazuhisa Yoshimura, Shigeyoshi Harada, Yuki Hirota, Nami Ohashi, Chie Hashimoto,Wataru Nomura, Shuzo Matsushita, Hirokazu Tamamura*

Design, synthesis and biological activities of Nilotinib derivates as antitumor agents pp 2527–2534

Xiaoyan Pan, Fang Wang, Yanmin Zhang, Hongping Gao, Zhigang Hu, Sicen Wang, Jie Zhang*

A series of pyrimidin-2-ylamino-benzamide derivatives was designed and synthesized as potent Bcr–Abl inhibitors.

Macrophage specific delivery of TNF-a siRNA complexed with b-1,3-glucan inhibits LPS-induced cytokine production in amurine acute hepatitis model

pp 2535–2542

Shinichi Mochizuki, Hiromi Morishita, Kazuo Sakurai*

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

TNF-

α(n

g/m

l)

*SPG dA-siRNA

dA G G

dA

Complex

siRNA

Contents / Bioorg. Med. Chem. 21 (2013) 2427–2433 2429

Design and synthesis of novel chromenone derivatives as interleukin-5 inhibitors pp 2543–2550

Eeda Venkateswararao, Vinay K. Sharma, Ki-Cheul Lee, Eunmiri Roh, Youngsoo Kim, Sang-Hun Jung*

O

OO OH

OHO

OO O

OH

8

O O

OHOH

3 9

IC50 = 12.6 μM(99% inhibition at 50 μM)

IC50 = 15.0 μM(80% inhibition at 30 μM)

IC50 = 4.0 μM(94% inhibition at 30 μM)

Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan–CD44v6 pathway and inducingcytotoxicity in colon cancer cells

pp 2551–2559

Suniti Misra, Shibnath Ghatak, Neha Patil, Prasad Dandawate, Vinita Ambike, Shreelekha Adsule, Deepak Unni,K. Venkateswara Swamy, Subhash Padhye*

N

HHN

BQ

N

O

O

QNH Doockkingg inn COOXX-2 pprooteinn DDoccking in 55-LLOXX prroteein

The structural analogs of 2,6 di-tert-butyl-p-benzoquinone (BQ) appendedwith hydrazide side chain were found to inhibit COX-2 and 5-LOX atmicromolar concentrations. Molecular docking of the compounds into COX-2 and 5-LOX protein cavities indicated strong binding interactionssupporting the observed cytotoxicities. It has been observed for the firsttime, that three of our COX/5-LOX dual inhibitors inhibit proliferation uponhydrazide substitution preventing the activity of pro-angiogenic factors inHCA-7, HT-29, Apc10.1 cells as well as prohibit the hyaluronan synthase-2(Has2) enzyme over-expressed in colon cancer cells, through inhibition ofthe hyaluronan/CD44v6 cell survival pathway.

Systematic screening of the cellular uptake of designed alpha-helix peptides pp 2560–2567

Kenji Usui*, Takuya Kikuchi, Masayasu Mie, Eiry Kobatake, Hisakazu Mihara*

Discovery of aryl-biphenyl-2-ylmethylpiperazines as novel scaffolds for 5-HT7 ligands and role of the aromaticsubstituents in binding to the target receptor

pp 2568–2576

Youngjae Kim, Jeeyeon Kim, Jinsung Tae, Bryan L. Roth, Hyewhon Rhim, Gyochang Keum, Ghilsoo Nam*, Hyunah Choo*

R1

NN

R2

1-24 R1 = 2-OMe, R2 = 2-OMe, 5-HT7 K i = 43 nM1-26 R1 = 4-OMe, R2 = 2-OMe, 5-HT7 K i = 46 nM

Aryl-biphenyl-2-ylmethylpiperazines 1 as 5-HT7 ligands were designed and synthesized, and their biological results were reported.

2430 Contents / Bioorg. Med. Chem. 21 (2013) 2427–2433

Identification of RC-33 as a potent and selective r1 receptor agonist potentiating NGF-induced neurite outgrowth inPC12 cells. Part 2: g-Scale synthesis, physicochemical characterization and in vitro metabolic stability

pp 2577–2586

Daniela Rossi, Annamaria Marra, Pietro Picconi, Massimo Serra, Laura Catenacci, Milena Sorrenti, Erik Laurini,Maurizio Fermeglia, Sabrina Pricl*, Stefania Brambilla, Nicoletta Almirante, Marco Peviani, Daniela Curti, Simona Collina*

Design, synthesis and anti-tuberculosis activity of 1-adamantyl-3-heteroaryl ureas with improved in vitropharmacokinetic properties

pp 2587–2599

E. Jeffrey North, Michael S. Scherman, David F. Bruhn, Jerrod S. Scarborough, Marcus M. Maddox, Victoria Jones,Anna Grzegorzewicz, Lei Yang, Tamara Hess, Christophe Morisseau, Mary Jackson, Michael R. McNeil, Richard E. Lee*

HN

HN

O R

SO

O NHAr N

O

N ON

R

S

N R

O

NNR

NNR

R1Mycobacteriumtuberculosis

Selectivity for anti-TB activityover human sEH activity

Pharmacokinetic properties

Maintain target inhibition

Pyridinylpyrimidines selectively inhibit human methionine aminopeptidase-1 pp 2600–2617

Pengtao Zhang, Xinye Yang, Feiran Zhang, Sandra B. Gabelli, Renxiao Wang, Yihua Zhang, Shridhar Bhat, Xiaochun Chen,Manuel Furlani, L. Mario Amzel, Jun O. Liu*, Dawei Ma*

NH

HN

Cl

N

Cl

IC50 for HsMetAP1 (0.15 µM): 0.86 µMIC50 for HsMetAP2 (0.10 µM): 9.0 µM

IC50 for HsMetAP1 (0.15 µM): 0.20 µMIC50 for HsMetAP2 (0.10 µM): >100 µM

A hit (2)

After SAR (26d)Purple: HsMetAP1 in complex with 2Cyan: HsMetAP1 in complex with 26d

26d2

HEPESHN

NN

NN

Cl

N

Structure activity relationship of phenolic diterpenes from Salvia officinalis as activators of the nuclear factor E2-relatedfactor 2 pathway

pp 2618–2622

Justin T. Fischedick, Miranda Standiford, Delinda A. Johnson, Jeffrey A. Johnson*

Contents / Bioorg. Med. Chem. 21 (2013) 2427–2433 2431

Development of cyclic peptomer inhibitors targeting the polo-box domain of polo-like kinase 1 pp 2623–2634

Ravichandran N. Murugan, Jung-Eun Park, Dan Lim, Mija Ahn, Chaejoon Cheong, Taeho Kwon, Ky-Youb Nam, Sun Ho Choi,Bo Yeon Kim, Do-Young Yoon, Michael B. Yaffe, Dae-Yeul Yu, Kyung S. Lee*, Jeong Kyu Bang*

Radiosynthesis and first evaluation in mice of [18F]NS14490 for molecular imaging of a7 nicotinic acetylcholinereceptors

pp 2635–2642

Sven Rötering*, Matthias Scheunemann, Steffen Fischer, Achim Hiller, Dan Peters, Winnie Deuther-Conrad, Peter Brust

Synthesis and structure–activity relationships of carboxylic acid derivatives of pyridoxal as P2X receptor antagonists pp 2643–2650

Kwan-Young Jung, Joong-Heui Cho, Jung Sun Lee, Hyo Jun Kim, Yong-Chul Kim*

Discovery of subtype selective muscarinic receptor antagonists as alternatives to atropine using in silico pharmacophoremodeling and virtual screening methods

pp 2651–2662

Apurba K. Bhattacharjee*, James W. Pomponio, Sarah A. Evans, Dmitry Pervitsky, Richard K. Gordon*

H3CO

ON

Adopting in silico pharmacophore modeling, 28 new antimuscarinic compounds were discovered, 9 showing specificity for M1 and low specificity for M3 receptors. The pKi valuesrange from 4.5 to 8.5 nM compared to 8.7 nM for atropine. Key pharmacophore features for subtype selectivity of the most potent molecule were two H-bond acceptors on theoxygen atoms, one ring aromaticity, and aliphatic hydrophobicity of the diethyl moiety.

2432 Contents / Bioorg. Med. Chem. 21 (2013) 2427–2433

Novel indoline-2,3-dione derivatives as inhibitors of aminopeptidase N (APN) pp 2663–2670

Kang Jin, Xiaopan Zhang, Chunhua Ma, Yingying Xu, Yumei Yuan, Wenfang Xu*

N

OO

Cl

O

O

HN OH12a

Aminopeptidase N (APN/CD13), as a zinc-containing ectoenzyme, plays a critical role in the process of tumor angiogenesis,invasion and metastasis. Through the docking-based virtual screening of chemical databases and the further activity assay, wediscovered that compound 10c exhibits potent and selective inhibitory ability towards APN. In addition, a series of indoline-2,3-dione derivates have been designed and synthesized as APN inhibitors. The results of preliminary activity evaluation showed thatcompound 12a (IC50 = 0.074 ± 0.0026 lM) exhibited the best inhibitory activity against APN, which could be used for furtheranticancer agent research.

OTHER CONTENTS

Corrigendum p 2671

Bioorganic & Medicinal Chemistry Reviews and Perspectives pp I–III

*Corresponding authorSupplementary data available via SciVerse ScienceDirect

COVER

Terminal alkynes are considered to be bioinert and are widely used for click chemistry reactions in proteome research. Now they were found tocovalently react with the catalytic thiol moiety of a cysteine protease to form a vinyl sulfide thereby inhibiting the enzyme. [Sommer, S.;Weikart, N.D.; Linne, U.; Mootz, H.D. Bioorg. Med. Chem. 2013, 21, 2511–2517.]

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Indexed/Abstracted in: Beilstein, Biochemistry & Biophysics Citation Index, CANCERLIT, Chemical Abstracts, ChemistryCitation Index, Current Awareness in Biological Sciences/BIOBASE, Current Contents: Life Sciences, EMBASE/ExcerptaMedica, MEDLINE, PASCAL, Research Alert, Science Citation Index, SciSearch, TOXFILE. Also covered in the abstract and citationdatabase SciVerse Scopus�. Full text available on SciVerse ScienceDirect�

ISSN 0968-0896

Contents / Bioorg. Med. Chem. 21 (2013) 2427–2433 2433