Bioorganic & Medicinal Chemistry Letters Volume 22, Issue 20, 2012

Contents

ARTICLES

Substituted thiazoles VII. Synthesis and antitumor activity of certain 2-(substituted amino)-4-phenyl-1,3-thiazoleanalogs

pp 6318–6323

Ghada S. Hassan, Shahenda M. El-Messery, Fatmah A. M. Al-Omary, Hussein I. El-Subbagh*

The first activation study of a bacterial carbonic anhydrase (CA). The thermostable a-CA fromSulfurihydrogenibium yellowstonense YO3AOP1 is highly activated by amino acids and amines

pp 6324–6327

Daniela Vullo, Viviana De Luca, Andrea Scozzafava, Vincenzo Carginale, Mosè Rossi, Claudiu T. Supuran*,Clemente Capasso*

NH2

O

OH

L-Phe, KA = 8 nMD-Phe, KA = 5.13 μM

Trypsin resistance of a decapeptide KISS1R agonist containing an Nx-methylarginine substitution pp 6328–6332

Taiji Asami*, Naoki Nishizawa, Yoshihiro Ishibashi, Kimiko Nishibori, Yasuko Horikoshi, Hirokazu Matsumoto,Tetsuya Ohtaki, Chieko Kitada

Bioorganic & Medicinal Chemistry Letters 22 (2012) 6307–6317

Contents lists available at SciVerse ScienceDirect

Bioorganic & Medicinal Chemistry Letters

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

Discovery of potent inhibitors of receptor protein tyrosine phosphatase sigma through thestructure-based virtual screening

pp 6333–6337

Hwangseo Park*, Pham Ngoc Chien, Seong Eon Ryu*

N N

SN

N

N

N

N

NH

N

HN

O

O

HOOC

IC50 = 0.1 μM IC50 = 0.2 μM

We have identified novel inhibitors of receptor protein tyrosine phosphatase sigma based on the structure-based virtual screening and in vitro enzyme assay.

Discovery of novel dihydroimidazothiazole derivatives as p53–MDM2 protein–protein interactioninhibitors: Synthesis, biological evaluation and structure–activity relationships

pp 6338–6342

Masaki Miyazaki*, Haruko Kawato, Hiroyuki Naito, Masahiro Ikeda, Masaya Miyazaki, Mayumi Kitagawa, Takahiko Seki,Setsuko Fukutake, Masashi Aonuma, Tsunehiko Soga

cis

(+/-)-9c (+/-)-190.14μMp53-MDM2 inhibitory activity: IC50 = 0.26 μM

cisN

Cl

Cl

NS

O

NHNN

Cl

Cl

NS

O

NHN O

Synthesis of b-ionone derived chalcones as potent antimicrobial agents pp 6343–6346

Vishal Sharma, Gurpreet Singh, Harpreet Kaur, Ajit K. Saxena, Mohan Paul S. Ishar*

O

CH3

O

EtOH

H2ONaOH,Ar-CHO

Ar+

1 2 3

Cytotoxicity and DNA binding property of phenanthrene imidazole with polyglycol side chains pp 6347–6351

Shuxiang Wang, Hongdong Li, Chao Chen, Jinchao Zhang*, Shenghui Li, Xinying Qin, Xiaoliu Li*, Kerang Wang

NHN

OO

OHn

N

OO

OHn

I

3a n = 03b n = 13c n = 2

2a n = 02b n = 12c n = 2

2a IC50= 4.65±0.16 μM (Bel-7402) 3c IC50= 7.01±0.47 μM (BGC-823)

N

6308 Contents / Bioorg. Med. Chem. Lett. 22 (2012) 6307–6317

Synthesis and biological evaluation of a novel 99mTc cyclopentadienyl tricarbonyl complex([(Cp-R)99mTc(CO)3]) for sigma-2 receptor tumor imaging

pp 6352–6357

Xin Chen, Meng-Chao Cui, Winnie Deuther-Conrad, Ying-Feng Tu, Teng Ma, Ying Xie, Bing Jia, Yan Li, Fang Xie, Xia Wang,Jörg Steinbach, Peter Brust, Bo-Li Liu, Hong-Mei Jia*

A rhodamine-deoxylactam based sensor for chromo-fluorogenic detection of nerve agent simulant pp 6358–6361

Zhisheng Wu, Xuanjun Wu, Yuhui Yang, Ting-bin Wen, Shoufa Han*

O

N OH

N NCl

OOEt

OEtO

N

N N

fluorescent and colorednonfluorescent

P

N-(rhodamine B)-deoxylactam-5-amino-1-pentanol (dRB-APOH) was designed and prepared as the chromogenic and fluorogenic chemodosimerter fordetection of a nerve agent simulant via analyte triggered tandem phosphorylation and opening of the intramolecualr deoxylactam.

Antioxidant properties of Mannich bases pp 6362–6367

Dong Ho Park, Jayachandran Venkatesan, Se-Kwon Kim, Venkatachalm Ramkumar, Paramasivam Parthiban*

Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: Synthesis and SAR study as tyrosine kinasec-Met inhibitors

pp 6368–6372

Kui Wu, Jing Ai, Qiufeng Liu, TianTian Chen, Ailing Zhao, Xia Peng, Yuanxiang Wang, Yinchun Ji, Qizheng Yao*, Yechun Xu*,Meiyu Geng*, Ao Zhang*

NF3C

NHN

N

NO2

Earlier lead (zgwatinib)N

NNH

F3C

NX

R'

NN

NNR

N

N NF3C

NN

NH

Y X

I, quinoxaline series II, pyrido[2,3-d]pyrimidine series

R

Y

Contents / Bioorg. Med. Chem. Lett. 22 (2012) 6307–6317 6309

Synthesis and pharmacological evaluation of a novel series of 3-aryl-2-(2-substituted-4-methylthiazole-5-yl)thiazolidin-4-one as possible anti-inflammatory and antimicrobial agents

pp 6373–6376

Shivaji H. Shelke, Pravin C. Mhaske, Mukesh Nandave, Sachin Narkhade, Namdeo M. Walhekar, Vivek D. Bobade*

N S

H3C

Ar

HO

+

NH2

R1

CH3COOH

Toluene, reflux N S

H3C

Ar

HN

R1

SHCH2COOH

Toluenereflux, 64-76 %

N S

H3C

Ar

N

R1

SO

H

3a-c r-a5r-a4 6a-r

Zizimauritic acids A–C, three novel nortriterpenes from Ziziphus mauritiana pp 6377–6380

Chang-Jiu Ji, Guang-Zhi Zeng, Jing Han, Wen-Jun He, Yu-Mei Zhang, Ning-Hua Tan*

1 R = α-OCH32 R = β-OCH33a R = α-OH3b R = β-OH

O

O

H

H

H

OHO

R

Preparation and optimization of new 4-(morpholin-4-yl)-(6-oxo-1,6-dihydropyrimidin-2-yl)amidederivatives as PI3Kb inhibitors

pp 6381–6384

Victor Certal, Frank Halley*, Angela Virone-Oddos, Fabienne Thompson,Bruno Filoche-Rommé, Youssef El-Ahmad, Jean-Christophe Carry,Cécile Delorme, Andreas Karlsson, Pierre-Yves Abecassis,Loic Vincent, Hélène Bonnevaux, Jean-Paul Nicolas, Renaud Morales,Nadine Michot, Isabelle Vade, Audrey Louboutin, Sébastien Perron,Gilles Doerflinger, Bernadette Tric, Sylvie Monget, Christoph Lengauer, Laurent Schio

Synthesis and biological evaluation of novel piperazine derivatives of flavone as potentanti-inflammatory and antimicrobial agent

pp 6385–6390

Girish D. Hatnapure, Ashish P. Keche, Atish H. Rodge, Satish S. Birajdar,Rajesh H. Tale*, Vandana M. Kamble* O

OOH

HO

O

OO

O N

OCH3

Chrysin Wogonin

N

S

NN

H2N

O

OOH

HO

NR

11

Hybride structure

A series of novel 6-methoxy-2-(piperazin-1-yl)-4H-chromen-4-one and 5,7-dimethoxy-2-(piperazin-1-ylmethyl)-4H-chromen-4-one derivatives of biological interest have been designed and synthesized. All thenew compounds were evaluated for anti-inflammatory activity (TNF-a and IL-6 inhibitory activity) andantimicrobial (antifungal and antibacterial) activities against some selected pathogenic bacteria and fungi.

6310 Contents / Bioorg. Med. Chem. Lett. 22 (2012) 6307–6317

Serum stability of selected decapeptide agonists of KISS1R using pseudopeptides pp 6391–6396

Taiji Asami*, Naoki Nishizawa, Yoshihiro Ishibashi, Kimiko Nishibori, Masaharu Nakayama, Yasuko Horikoshi,Shin-ichi Matsumoto, Masashi Yamaguchi, Hirokazu Matsumoto, Naoki Tarui, Tetsuya Ohtaki, Chieko Kitada

HN

NH

HN

NH

HN

NH

HN

NH

O

NH2

O

OOO

OOO

NH

NHHN

H3CCH3

NH

O

H2NO

H H H H H

H HHOH

NH

H2NO

H2N

O

OH

H

H2N

HN

NH

O

O

NH

NHHN

H3CCH3

H

H

HN

NH

HN

NH

OO

OO

NH

O

H2NO

H H H

H HOH

NH

H2NO

OH

O

H2N

H

OH

NH2

O

H

H2NX

O

OH

X: CH2 (Gly)NH (azaGly)

HN

NH

HN

NH

HN

NH

NH

HN

NH

O

NH2

O

OOO

OOO

NH

NHHN

H3CCH3

NH

O

H2NO

H H H H H

H HHOH

NH

H2NO

H2N

O

OH

H

Compound 1

Cleavage product in serum at 37OC

Compound 5

Induced production of mycotoxins in an endophytic fungus from the medicinal plant Daturastramonium L.

pp 6397–6400

Jieyin Sun, Takayoshi Awakawa, Hiroshi Noguchi, Ikuro Abe*

Inhibition of NaV1.6 sodium channel currents by a novel series of 1,4-disubstituted-triazole derivativesobtained via copper-catalyzed click chemistry

pp 6401–6404

Mirko Rivara*, Manoj K. Patel, Laura Amori, Valentina Zuliani

R + R1 N3 NN

NR1

R

Compound instability in dimethyl sulphoxide, case studies with 5-aminopyrimidines and theimplications for compound storage and screening

pp 6405–6409

Eliška Procházková, Petr Jansa, Anna Brezinová, Lucie Cechová, Helena Mertlíková-Kaiserová, Antonín Holy,Martin Dracínsky*

HN

N

O

H2N NH2

NH2N

N

O

H2N NH2

N

NH

N

O NH2

NH2

HN

N N

N

N

N

O

H2N

NH2

NH2

DMSO

Contents / Bioorg. Med. Chem. Lett. 22 (2012) 6307–6317 6311

Substrate-like water soluble lipase inhibitors from Filipendula kamtschatica pp 6410–6412

Eisuke Kato, Michitsugu Yama, Ryo Nakagomi, Toshiro Shibata, Keizo Hosokawa, Jun Kawabata*

Novel AI-2 quorum sensing inhibitors in Vibrio harveyi identified through structure-based virtualscreening

pp 6413–6417

Peng Zhu, Hanjing Peng, Nanting Ni, Binghe Wang*, Minyong Li*

0.5 millioncompounds

ChemScoreOEChemscorePLPScreenScoreChemGauss3CGOShapeGauss

42 molecules42 compounds

SOO

O O

5

N+O

-O

O O

Cl

Cl OH

12

NN

SNH

N NSO

19

NO

N

SCl

23

SOO

S

27

NN

NNN

H2N31

OO

NH

F

33

Biological ActivityScreening

Imidazo–benzothiazoles a potent microRNA modulator involved in cell proliferation pp 6418–6424

Sreerangam N. C. V. L. Pushpavalli, M. Janaki Ramaiah, A. Lavanya, A. Raksha Ganesh, Ravindra M. Kumbhare,Kaustav Bhadra, Utpal Bhadra*, Manika Pal-Bhadra*

Synthesis of highly water-soluble fibrate derivatives via BGLation pp 6425–6428

Hisao Nemoto*, Masaki Kamiya, Aki Nakamoto, Tsuyoshi Matsushita, Kosuke Matsumura, Hatsuhiko Hattori,Tomoyuki Kawamura, Chiaki Taoka, Shinji Abe, Keisuke Ishizawa, Licht Miyamoto, Koichiro Tsuchiya

O

O

O

OOH

OH

OH

OHO

O

OH

O

OCl

O=Oral

administrationOH

O

Several thousandtimes more water-soluble

Concentration in blood was

5 times higher

Fenofibrate

O

OO

O

An anti-hyperlipemia drugvery poorly water-soluble

6312 Contents / Bioorg. Med. Chem. Lett. 22 (2012) 6307–6317

Synthesis and evaluation of novel 1,3,4-oxadiazole derivatives of marine bromopyrrole alkaloids asantimicrobial agent

pp 6429–6432

Rajesh A. Rane*, Shweta D. Gutte, Niteshkumar U. Sahu

NH

Br

Br NN

O R

A B

R = aryl or heteroaryl or SH or S-aryl/alkyl

A series of 20 novel hybrids of marine bromopyrrole alkaloids containing 1,3,4-oxadiazole scaffold were designed and synthesized. Synthesized molecules wereevaluated for their antibacterial, antifungal and antitubercular activities. Few compounds showed promising antibacterial, antifungal and antitubercular activity.

Pyrrolo[2,3-b]quinoxalines as inhibitors of firefly luciferase: Their Cu-mediated synthesis and evaluationas false positives in a reporter gene assay

pp 6433–6441

Ali Nakhi, Md. Shafiqur Rahman, Ravada Kishore, Chandana Lakshmi T. Meda, Girdhar Singh Deora, Kishore V. L. Parsa,Manojit Pal*

XX-ray

P

y

Cu

2d/C

R'

R'

u(O

,3-DichloroquinoxalineC-Cu

OAc

u cat.a

)2

N

N

N

N

N

N

N

NH2

C

2SO

R

Cl

NH

O2M

R

R

e

Rluciferase

Synthesis, characterization and biological evaluation of some novel 2,4-thiazolidinediones as potentialcytotoxic, antimicrobial and antihyperglycemic agents

pp 6442–6450

Vasudeva Rao Avupati*, Rajendra Prasad Yejella, Annapurna Akula, Girija Sankar Guntuku, Bhagya Raju Doddi,Venkata Rao Vutla, Suvarna Ratna Anagani, Lakshmana Santhi Adimulam, Aruna Kumar Vyricharla

Transformation of 8-prenylnaringenin by Absidia coerulea and Beauveria bassiana pp 6451–6453

Agnieszka Bartmanska*, Tomasz Tronina, Ewa Huszcza

O

O

OH

OH

HO

O O

O

OH

OH

O

OH

O

HO OH

O O

O

OH

OH

O3S

O

OH

HO

HO OH

O O

O

OH

OH

1

3 4

-

2

A. coerulea

B. bassiana

mediumbuffer

medium

buffer

Contents / Bioorg. Med. Chem. Lett. 22 (2012) 6307–6317 6313

Discovery of 1H-pyrrolo[2,3-c]pyridine-7-carboxamides as novel, allosteric mGluR5 antagonists pp 6454–6459

Manuel Koller*, David A. Carcache, David Orain, Peter Ertl, Dirk Behnke, Sandrine Desrayaud, Grit Laue, Ivo Vranesic

N

NH

O

HN

N

Allosteric mGluR5 antagonistCellular Ca-assay: IC50 = 13 nM

4

1-(sulfonyl)-5-(arylsulfonyl)indoline as activators of the tumor cell specific M2 isoform of pyruvatekinase

pp 6460–6468

Avihai Yacovan*, Rachel Ozeri, Tzofit Kehat, Sima Mirilashvili, Daniel Sherman, Alex Aizikovich, Alina Shitrit,Efrat Ben-Zeev, Nili Schutz, Osnat Bohana-Kashtan, Alexander Konson, Vered Behar, Oren M. Becker

S

O

O

NS

OO

O

O

(19) AC50 = 45 nM

Azetidinyl oxadiazoles as potent mGluR5 positive allosteric modulators pp 6469–6474

Mathivanan Packiarajan*, Christine G. Mazza Ferreira, Sang-Phyo Hong, Andrew D. White, Gamini Chandrasena, Xiaosui Pu,Robbin M. Brodbeck, Albert J. Robichaud

N N

N O O

Cl

F

N

N O

Cl

7a: IC50 4000 nM (60%)6: EC50 10.7 nM (55%)

NO

F

N

N O

Cl

17c: EC50 72 nM (140%)

N

H

O

PAMNAM

N

N O

Cl

13n: EC50 180 nM (75%)

NO

PAMPAMF

F

A new class of pyrimidine nucleosides: inhibitors of hepatitis B and C viruses pp 6475–6480

Neeraj Shakya, Satish Vedi, Chao Liang, Babita Agrawal, D. Lorne Tyrrell, Rakesh Kumar*

HOO

O

R1

O

HN

N

X

R

HOO

O

O

HN

N

O

CH3

HOO

O

O

HN

N

O

CH3

H3COO

O

O

N

N

NH2

6314 Contents / Bioorg. Med. Chem. Lett. 22 (2012) 6307–6317

Optimization of an ether series of mGlu5 positive allosteric modulators: Molecular determinants ofMPEP-site interaction crossover

pp 6481–6485

Jason T. Manka, Paige N. Vinson, Karen J. Gregory, Ya Zhou, Richard Williams, Kiran Gogi, Emily Days, Satya Jadhav,Elizabeth J. Herman, Hilde Lavreysen, Claire Mackie, José M. Bartolomé, Gregor J. Macdonald, Thomas Steckler,J. Scott Daniels, C. David Weaver, Colleen M. Niswender, Carrie K. Jones, P. Jeffrey Conn, Craig W. Lindsley,Shaun R. Stauffer*

O

NH

O

F

F

VU0357121

iterativeparallel

synthesis

non-MPEP mGlu5 PAM[3H]methoxyPEPyKi > 100 μM

mGlu5 EC50 = 33 nMFold-Shift~2.6x XO

N

OR'

RAr/R

Allylic thiocyanates as a new class of antitubercular agents pp 6486–6489

Gustavo P. Silveira, Misael Ferreira, Luciano Fernandes, Garrett C. Moraski, Sanghyun Cho, Changhwa Hwang,Scott G. Franzblau, Marcus M. Sá*

G = N3, SCN, SC(CNH)NH2, SC(CNC6H5)NH2, SC(CNCOCH3)NHCOCH3

X = H, Br, Cl, F, CH3, NO2, etc.

G

SCNSCN

X

2-Br4-Cl

Mtb H37RvMIC (μμM)

0.250.25

VEROIC50 (μM)

3216

NR MtbMIC (μM)

4.08.0

O

O

GX

G = N3, SCN, SC(CNH)NH2, SC(CNC6H5)NH2, SC(CNCOCH3)NHCOCH3

X = H, Br, Cl, F, CH3, NO2, etc.

SCNSCN

2-Br4-Cl

μ

0.250.25

μ

3216

μ

4.08.0

O

O

Chiral separation, configurational identification and antihypertensive evaluation of (±)-7,8-dihydroxy-3-methyl-isochromanone-4

pp 6490–6493

Renren Bai, Jie Liu, Yao Zhu, Xue Yang, Chen Yang, Lingyi Kong, Xiaobing Wang, Hengyuan Zhang, Hequan Yao,Mingqin Shen, Xiaoming Wu*, Jinyi Xu*

HOOH

O

O

*

XJP

HOOH

O

O

S -(+)-XJP

HOOH

O

O

R-(-)-XJP

chiral separation

Synthesis of quinoline derivatives for fluorescent imaging certain bacteria pp 6494–6497

Ramu Dhanapal, Paramasivan T. Perumal*, Munusamy Damodiran, Chandrasekaran Ramprasath,Narayanasamy Mathivanan

NH2

R1

Ar CHON O

NH

N

Ar

O

R1

N

N

Ar

O

R1+

R1 = H, CN, OMe, Cl, Br, n-Butyl

DDQ

HN

Ar

O HN

Ar

O

O

+

Ar = Phenanthrene

Contents / Bioorg. Med. Chem. Lett. 22 (2012) 6307–6317 6315

Design, synthesis and pharmacological evaluation of novel tacrine–caffeic acid hybrids as multi-targetedcompounds against Alzheimer’s disease

pp 6498–6502

Xiaojuan Chao, Xixin He, Yilin Yang, Xie Zhou, Minghua Jin, Shu Liu, Zhiyi Cheng, Peiqing Liu, Yuting Wang, Jianchen Yu,Yi Tan, Yingjuan Huang, Jian Qin, Simona Rapposelli, Rongbiao Pi*

Identification of a potent and metabolically stable series of fluorinated diphenylpyridylethanamine-based cholesteryl ester transfer protein inhibitors

pp 6503–6508

Michael M. Miller*, Yalei Liu, Ji Jiang, James A. Johnson, Muthoni Kamau, David S. Nirschl, Yufeng Wang,Lalgudi Harikrishnan, David S. Taylor, Alice Ye A. Chen, Xiaohong Yin, Ramakrishna Seethala, Tara L. Peterson,Tatyana Zvyaga, Jun Zhang, Christine S. Huang, Ruth R. Wexler, Michael A. Poss, R. Michael Lawrence, Leonard P. Adam,Mark E. Salvati

HN

N

F

Cl

F3C

O

HN H

NN

F

Cl

O

O

HN

FF

F F

FF

HHN

N

F

Cl

O

O

HN

FF

F F

improvepotency

CF3

(S) > (R)antipode

modulatepotency & MTS

(R) acyclic;improved

MTS

Camptothecins in tumor homing via an RGD sequence mimetic pp 6509–6512

Domenico Alloatti, Giuseppe Giannini*, Loredana Vesci, Massimo Castorina, Claudio Pisano, Elena Badaloni, Walter Cabri

N

NN

O O

OHNH

OO

O

N

N

OO

N N

O

O

OOH

HN

N

H

(ST7456CL1)

αvβ3 = 1.30 nM; αvβ5= 1.00 nM

PC3 (IC50, 72h): 3.4 μMA2780 (IC50, 72h): 0.033 μM

Compound 8HCl

Studies on the antimicrobial properties of N-acylated ciprofloxacins pp 6513–6520

Ryan Cormier, Whittney N. Burda, Lacey Harrington, Jordan Edlinger, Karthik M. Kodigepalli, John Thomas,Rebecca Kapolka, Glen Roma, Burt E. Anderson, Edward Turos*, Lindsey N. Shaw*

O

N

F

NN

O

OH

R

O

6316 Contents / Bioorg. Med. Chem. Lett. 22 (2012) 6307–6317

An enthalpic basis of additivity in biphenyl hydroxamic acid ligands for stromelysin-1 pp 6521–6524

Erin M. Wilfong, Yu Du, Eric J. Toone*

Erratum p 6525

Available online at www.sciencedirect.com

Indexed/Abstracted in: Beilstein, Biochemistry & Biophysics Citation Index, CANCERLIT, Chemical Abstracts, ChemistryCitation Index, Current Awareness in Biological Sciences/BIOBASE, Current Contents: Life Sciences, EMBASE/Excerpta Medica,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 0960-894X

Corrigendum p 6526

*Corresponding authorSupplementary data available via SciVerse ScienceDirect

COVER

Molecular recognition of protein targets by organic molecules is influenced by three-dimensional shape complementarity. As illustrated in thecover photograph, increasingly complex binding pockets may be better approached with small molecules possessing structural complexity inthe chemical core and diversity in appending groups. Products of diversity-oriented synthesis (DOS) possess these attributes, and may befurther biased toward specific protein families by appending reactive functional groups. Recently, Schreiber and colleagues reported thedevelopment of potent, selective inhibitors of histone deacetylase isoforms by biasing DOS macrocycles using metal-binding chemical features(Bioorg Med Chem Lett. 2011 May 1;21(9):2601-5). This strategy may be applicable to many other targets of interest in ligand discovery.Photograph by Richard Oakley and James Bradner (Dana-Farber Cancer Institute, Boston, MA).

Contents / Bioorg. Med. Chem. Lett. 22 (2012) 6307–6317 6317