Bioorganic & Medicinal Chemistry Letters Volume 22, Issue 18, 2012 Contents BMCL DIGEST Ras inhibition via direct Ras binding—is there a path forward? pp 5766–5776 Weiru Wang, Guowei Fang, Joachim Rudolph* REGULAR ARTICLES Synthesis and antifungal activity of 1-thia-4b-aza-cyclopenta[b]fluorene-4,10-diones pp 5777–5779 Chung-Kyu Ryu*, Aram Kim, Hyun Ah Im, Ji Young Kim O O N + Cl R 2 R 1 S Cl - O O N R 1 R 2 S O R 3 O O O O R 1 ,R 2 ,R 3 = H, X, Alkyl,.. 1-Thia-4b-aza-cyclopenta[b]fluorene-4,10-diones were synthesized and tested for in vitro antifungal activity against pathogenic strains of fungi. Many of these tested compounds exhibited potent antifungal activity. A highly sensitive fluorescent viscosity sensor pp 5780–5783 Rahimi M. Yusop*, Asier Unciti-Broceta, Mark Bradley Bioorganic & Medicinal Chemistry Letters 22 (2012) 5753–5765 Contents lists available at SciVerse ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl
Ras inhibition via direct Ras binding—is there a path forward? pp 5766–5776
Weiru Wang, Guowei Fang, Joachim Rudolph*
REGULAR ARTICLES
Synthesis and antifungal activity of 1-thia-4b-aza-cyclopenta[b]fluorene-4,10-diones pp 5777–5779
Chung-Kyu Ryu*, Aram Kim, Hyun Ah Im, Ji Young Kim
O
O
N+
Cl
R2
R1
S
Cl-
O
O
N
R1
R2
S
OR3
O
O
O
O
R1, R2, R3 = H, X, Alkyl,..
1-Thia-4b-aza-cyclopenta[b]fluorene-4,10-diones were synthesized and tested for in vitro antifungal activity against pathogenic strains of fungi. Many of these tested compoundsexhibited potent antifungal activity.
A highly sensitive fluorescent viscosity sensor pp 5780–5783
Rahimi M. Yusop*, Asier Unciti-Broceta, Mark Bradley
From a series of 12 synthesized diversely substituted 4-oxycoumarin derivatives the most potent bioactive molecule as anti-proliferative on breast adenocarcinoma cells (MCF-7), human promyelocytic leukemia cells (HL-60), human histiocyticlymphoma cells (U937) and mouse neuroblastoms cells (Neuro2a) was the 4-hydroxy-5,7-dimethoxycoumarin (compound1). It showed similar potency in all cancer cell lines tested, with IC50 = 0.2–2 lM, higher than tamoxifen (IC50 = 8–14 lM)and coumarin (IC50 = >50 lM) used as positive controls. Intriguingly its structural isomer, compound 2, in which only onemethoxy group is changed from 5 to 8 position, is not active in MCF-7 cells, while it is weakly active in HL-60, U937 andNeuro2a cells.
Exploration of the structure–activity relationship of the diaryl anilide class of ligands for translocatorprotein—potential novel positron emitting tomography imaging agents
pp 5795–5800
Harry Wadsworth, Paul A. Jones, Wai-Fung Chau, Clare Durrant, Véronique Morisson-Iveson, Joanna Passmore,Dennis O’Shea, Duncan Wynn, Imtiaz Khan, Andrew Black, Michelle Avory, William Trigg*
O
N
O
O
F18N
O
O
O
F18
OO
N
O
O
O
F18
14 27 30
Inhibition of a-class cytosolic human carbonic anhydrases I, II, IX and XII, and b-class fungal enzymes bycarboxylic acids and their derivatives: New isoform-I selective nanomolar inhibitors
pp 5801–5806
Mario Sechi*, Alessio Innocenti, Nicolino Pala, Dominga Rogolino, Mauro Carcelli, Andrea Scozzafava, Claudiu T. Supuran*
5754 Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765
Synthesis of phosphoantigens: Scalable accesses to enantiomers of BrHPP and studies on N-HDMAPPsynthesis
pp 5807–5810
Delphine Brégeon, Laurent Ferron, Antony Chrétien, Frédéric Guillen, Viacheslav Zgonnik, Marion Rivaud,Marie-Rose Mazières, Gérard Coquerel, Christian Belmant*, Jean-Christophe Plaquevent*
HOOCCOOH
OH
OH
Chiral poolsynthesis
Asymmetricsynthesis
Citramalic acid
BrO
PO
P
OH
O-
O- O-
O O1, BrHPP5
Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C) pp 5811–5813
Ulrike Leurs, Rasmus P. Clausen, Jesper L. Kristensen, Brian Lohse*
NHN
OHO
OO
O
KDM4C (JMJD2C) inhibitor
Ki = 51µM
Synthesis and biological evaluation of optically active conjugated c- and d-lactone derivatives pp 5814–5818
Melis S�ardan, Serdar Sezer, Aslıhan Günel, Mahinur Akkaya, Cihangir Tanyeli*
R
O
O
R' R
O
O
R'
+_( )
(S)O
O
R
R'O
O
R
R'
O
O
R
R'
+_( )
(S) (R)
O
O
R
R'
n
n= 0 or 1
Heteroaryl part
Me or H
A new antifungal and cytotoxic C-methylated flavone glycoside from Picea neoveitchii pp 5819–5822
Wei-Quan Chen, Zhi-Jun Song, Han-Hong Xu*
O
RR
HO
OH
OCH3
O
2
3
456
7
8
9
10
1'6'
2'
3'
4'
5'
O
OH
HOHO
OH
R=
A new C-methylated flavone glycoside, 5,7-dihydroxy-3-methoxy-6-C-methylflavone 8,40-di-O-b-DD-glucopyranoside (1), together with seven knowncompounds (2–9) were isolated from the twigs and leaves of Picea neoveitchii Mast. The cytotoxicities of the isolated compounds on Spodoptera lituraFabricius cell were evaluated by MTT assay and their antifungal activities were evaluated by disc diffusion method. Three of these compounds wereisolated from the Pinaceae family for the first time.
Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765 5755
Identification of 8-amino-2,5,7-trihydroxynaphthalene-1,4-dione, a novel intermediate in thebiosynthesis of Streptomyces meroterpenoids
A series of polyhydric, amino alcohol and tricyclic derivatives weresynthesized by D-ring modification of isosteviol. Cytotoxic activitiesevaluation showed 15-a-aminomethyl-16-b-hydroxyl isosteviol ethyl esteras the most potent inhibitory activities to EC9706 with IC50 value of4.01 lM.
Phosphodiesterase inhibitors. Part 4: Design, synthesis and structure-activity relationships of dualPDE3/4-inhibitory fused bicyclic heteroaromatic-4,4-dimethylpyrazolones
pp 5833–5838
Koji Ochiai, Satoshi Takita, Akihiko Kojima, Tomohiko Eiraku, Naoki Ando, Kazuhiko Iwase, Tetsuya Kishi, Akira Ohinata,Yuichi Yageta, Tokutaro Yasue, David R. Adams, Yasushi Kohno*
NN
CF3
N
NH
O
OMe
KCA-1490 (-)-form
*N
NH
O
NN
OMe
CF3
PDE3A IC50 (μM): 0.36
PDE4B IC50 (μM): 0.042
achiral replacementfor top ring
PDE3A IC50 (μM): 4.13
PDE4B IC50 (μM): 0.11
optimization ofheteroaromatics
N
NH
O
N
S
OMe
CF3
PDE3A IC50 (μM): 0.54
PDE4B IC50 (μM): 0.063
N
NH
O
N
N
OMe
CF3
PDE3A IC50 (μM): 0.14
PDE4B IC50 (μM): 0.15
achiral KCA-1490 analogs
Synthesis, biological evaluation, and docking studies of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines as potent anti-inflammatory and antioxidant agents
pp 5839–5844
Babasaheb P. Bandgar*, Laxman K. Adsul, Hemant V. Chavan,Shivkumar S. Jalde, Sadanand N. Shringare, Rafique Shaikh, Rohan J. Meshram,Rajesh N. Gacche, Vijay Masand
A series of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines has been synthe-sized, and evaluated for their in vitro and in vivo anti-inflammatory activity, and also for theirantioxidant activity.
5756 Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765
Synthesis and biological evaluation of novel N-acyl substituted quinolin-2(1H)-one derivatives aspotential antimicrobial agents
N-Acyl substituted quinolin-2(1H)-one derivatives were synthesized and some of them displayed comparable or even better antibacterial and antifungal efficacy compared toreference drugs Streptomycin and Fluconazole.
Design, synthesis and molecular docking studies of sinomenine derivatives pp 5849–5852
Thirty-eight sinomenine derivatives have been synthesized and evaluated for their inhibition activities against NF-jBactivation induced by LPS. Compound 2v was found to be the most potent compound.
Facile synthesis of a dimeric dipyrrole–polyamide and synergetic DNA-cleaving activity of its Cu(II)complex
A symmetrical dipyrrole–polyamide dimer was synthesized and its Cu(II) complex exhibited potent DNA-cleaving activity.
Discovery of liver selective non-steroidal glucocorticoid receptor antagonist as novel antidiabetic agents pp 5857–5862
Kiran Shah, Dipam Patel, Pradip Jadav, Mubeen Sheikh, Kalapatapu V.V.M. Sairam, Amit Joharapurkar, Mukul R. Jain,Rajesh Bahekar*
Series of benzyl-phenoxybenzyl amino-phenyl acid derivatives are reported as non-steroidal GR antagonist. The lead compound8g exhibited significant oral antidiabetic and antihyperlipidemic effects (in vivo), along with liver selectivity.
Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765 5757
A novel aminopeptidase N inhibitor developed by virtual screening approach pp 5863–5869
Jinhong Feng, Kang Jin, Huawei Zhu, Xiaopan Zhang, Lei Zhang, Jianhua Liu, Wenfang Xu*
Discovery of 6-substituted 4-anilinoquinazolines with dioxygenated rings as novel EGFR tyrosine kinaseinhibitors
It had been reported that some dioxygenated rings fusing with the quinazoline scaffold could lead to newEGFR inhibitors. Based on this, several kinds of oxygenated alkane quinazoline derivatives weresynthetized and evaluated as EGFR inhibitors. Their antiproliferative activities were tested against fourcancer cell lines: A431, MCF-7, A549, and B16-F10. Most derivatives could counteract EGF-induced EGFRphosphorylation, and their potency was comparable to the reference compound Erlotinib. The size of thefused dioxygenated ring was crucial for the biological activity and the heptatomic ring derivative 19showed potent in vitro inhibitory activity in the enzymatic assay as well as in the cellular assay.
Novel triazines as potent and selective phosphodiesterase 10A inhibitors pp 5876–5884
Michael S. Malamas*, Hans Stange, Rudolf Schindler, Hans-Joachim Lankau, Christian Grunwald,Barbara Langen, Ute Egerland, Thorsten Hage, Yike Ni, James Erdei, Kristi Yi Fan, Kevin Parris,Karen L. Marquis, Steve Grauer, Julie Brennan, Rachel Navarra, Radka Graf, Boyd L. Harrison,Albert Robichaud, Thomas Kronbach, Menelas N. Pangalos, Nicholas J. Brandon, Norbert Hoefgen
Novel triazines are potent, selective and orally active Phosphodiestarase 10A inhibitors.
Phenolic compounds as antiangiogenic CMG2 inhibitors from costa rican endophytic fungi1 pp 5885–5888
Shugeng Cao, Lorna Cryan, Kaiane A. Habeshian, Catalina Murillo, Giselle Tamayo-Castillo, Michael S. Rogers, Jon Clardy*
5758 Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765
Biologically active ester derivatives as potent inhibitors of the soluble epoxide hydrolase pp 5889–5892
In-Hae Kim, Kosuke Nishi, Takeo Kasagami, Christophe Morisseau, Jun-Yan Liu, Hsing-Ju Tsai, Bruce D. Hammock*
NH
O
NH
Linker
Primarypharmacophore
Secondarypharmacophore
Linker = n-butyl, cyclohexyl
R = OO
O
O
R1
R
R1 =CN
H
Novel oxysterols activate the Hedgehog pathway and induce osteogenesis pp 5893–5897
Frank Stappenbeck*, Wei Xiao, Matt Epperson, Mariko Riley, Aaron Priest, Danwen Huang, KhanhLinh Nguyen,Michael E. Jung, R. Scott Thies, Francine Farouz
HO
Me
Me
H
H
H
H
HO
HOH
R1R1
R2 R2
4: R1= H, R2= H, R3= isopropyl
18: R1= D, R2= D, R3= isopropyl
21: R1= H, R2= H, R3= n-propyl
30: R1= D, R2= D, R3= n-propyl
R3
Structure–activity relationship studies of oxysterol 4 have identified analogues such as 18, 21 and 30. These analogues are characterized byhigher potency in a osteoblast differentiation assay and/or by increased metabolic stability in human liver microsomes. Oxysterols 4, 18and 21 were evaluated in vivo in a rat spinal fusion model.
Synthesis and DNA binding properties of 1-(3-aminopropyl)-imidazole-containing triamide f-Im*PyIm: Anovel diamino polyamide designed to target 50-ACGCGT-30
pp 5898–5902
Vijay Satam, Balaji Babu, Alexander Porte, Mia Savagian, Megan Lee, Thomas Smeltzer, Yang Liu, Joseph Ramos, W. DavidWilson, Shicai Lin, Kostantinos Kiakos, John A. Hartley, Moses Lee*
N
N
HN
O N
CH3
HN
O
N
N
CH3
HN
O
HN
NO
H
CH3
CH3
H2N
5' - A C G C G T - 3'
3' - T G C G C A - 5'
f
f (+
+)
NH3+
+H3N
f-Im*PyIm (5)
Discovery of tetrahydropyridopyrimidine phosphodiesterase 10A inhibitors for the treatment ofschizophrenia
pp 5903–5908
Izzat T. Raheem*, Michael J. Breslin, Christine Fandozzi, Joy Fuerst, Nicole Hill, Sarah Huszar, Monika Kandebo, SomangH. Kim, Bennett Ma, Georgia McGaughey, John J. Renger, John D. Schreier, Sujata Sharma, Sean Smith, Jason Uslaner,Youwei Yan, Paul J. Coleman, Christopher D. Cox
N
N
N N
N O
NH
CH3
N
THPP-2 (HTS)PDE 10 Ki = 94 nM
N
R3
N
NR1
R2
THPP-1PDE 10 Ki = 1.0 nM
cGMP: (+) at 10 mpk PO
LMA: (+) at 3 mpk PO
favorable AE profile
N
N
N N
O O
Cl
NN
H3CO
Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765 5759
Structure-based design of 7-azaindole-pyrrolidine amides as inhibitors of 11b-hydroxysteroiddehydrogenase type I
pp 5909–5914
Eric Valeur, Serge Christmann-Franck*, Franck Lepifre, Denis Carniato, Daniel Cravo, Christine Charon, Sophie Bozec,Djordje Musil, Per Hillertz, Liliane Doare, Fabien Schmidlin, Marc Lecomte, Melanie Schultz, Didier Roche
Structure-based optimisation of 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1)-directed high-throughput screening hit led to 7-azaindole-derivativesdisplaying single digit nanomolar IC50, selective against 11b-HSD2 and exhibit-ing good inhibition of 11b-HSD1 (IC50 < 1 lM) in 3T3L1 adipocytes.
Antiplasmodial activities of 4-aminoquinoline–statine compounds pp 5915–5918
Nadia Vaiana, Melissa Marzahn, Silvia Parapini, Peng Liu, Mario Dell’Agli, Andrea Pancotti, Enrico Sangiovanni,Nicoletta Basilico, Enrica Bosisio, Ben M. Dunn, Donatella Taramelli, Sergio Romeo*
Synthesis and structure-activity relationship of 4-(1,3-benzothiazol-2-yl)-thiophene-2-sulfonamides ascyclin-dependent kinase 5 (cdk5)/p25 inhibitors
pp 5919–5923
Jonas Malmström*, Jenny Viklund, Can Slivo, Ana Costa, Mickaël Maudet,Catrin Sandelin, Gösta Hiller, Lise-Lotte Olsson, Anna Aagaard, Stefan Geschwindner,Yafeng Xue, Mervi Vasänge
N S
S
SO
ON
R2
R4
R3
R1
b-DD-20-a-F-20-b-C-Methyl-6-O-substituted 30,50-cyclic phosphate nucleotide prodrugs as inhibitors ofhepatitis C virus replication: A structure–activity relationship study
pp 5924–5929
Jinfa Du*, Donghui Bao, Byoung-Kwon Chun, Ying Jiang, P. Ganapati Reddy, Hai-Ren Zhang, Bruce S. Ross, Shalini Bansal,Haiying Bao, Christine Espiritu, Angela M. Lam, Eisuke Murakami, Congrong Niu, Holly M. Micolochick Steuer, PhillipA. Furman, Michael J. Otto, Michael J. Sofia*
OO N
N
N
N
NH2
OR
O F
PO
R'
O
11
5760 Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765
Sequences in the HSP90 promoter form G-quadruplex structures with selectivity for disubstitutedphenyl bis-oxazole derivatives
pp 5930–5935
Stephan A. Ohnmacht, Marialuisa Micco, Vanessa Petrucci, Alan K. Todd, Anthony P. Reszka, Mekala Gunaratnam,Marta A. Carvalho, Mire Zloh, Stephen Neidle*
Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as anovel, potent and selective Kv7.1 (KCNQ1) potassium channel activator
pp 5936–5941
Margrith E. Mattmann, Haibo Yu, Zhihong Lin, Kaiping Xu, Xiaofang Huang, Shunyou Long, Meng Wu, Owen B. McManus,Darren W. Engers, Uyen M. Le, Min Li*, Craig W. Lindsley, Corey R. Hopkins*
N
HN N
S
O
O
S
ML277VU0458298KCNQ1 EC50 = 260 nM
O
O
Discovery and optimization of a novel series of GPR142 agonists for the treatment of type 2 diabetesmellitus
pp 5942–5947
Mike Lizarzaburu*, Simon Turcotte, Xiaohui Du, Jason Duquette, Angela Fu, Jonathan Houze, Leping Li, Jinqian Liu,Michiko Murakoshi, Kozo Oda, Ryo Okuyama, Futoshi Nara, Jeff Reagan, Ming Yu, Julio C. Medina
HN
N
O
NH
O
NH2 NH
HN
O HN S
NO
N
h-GPR142 EC50 = 4.8 uM h-GPR142 EC50 = 0.067 uM
N-Benzoyl anthranilic acid derivatives as selective inhibitors of aldo–keto reductase AKR1C3 pp 5948–5951
Maša Sinreih, Izidor Sosic, Nataša Beranic, Samo Turk, Adegoke O. Adeniji, Trevor M. Penning, Tea Lanišnik Rizner,Stanislav Gobec*
Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765 5761
Synthesis and characterization of pH-sensitive conjugate of isoniazid – methoxypoly(ethylene glycol)-b-poly(LL-lysine)
pp 5952–5955
Aleš Imramovsky*, Ludmila Grusová, Ludvík Beneš, Vladimír Pejchal, Miloš Sedlák
H3CO
OHN
NH
O ~4~112
HN N
HN
O
N
N
HN
O
NBiocompatible carrier
Poly(ethylene glycol) Isoniazid
Released drug
L-Lysine
Slow release linker
Methylene bridge
Poly(amino acid) chain
mPEG-b-PLL-INH slow-acting polymeric conjugate
NH
O
NH
O
O
Hydrophobic part
An expeditious regioselective synthesis of novel bioactive indole-substituted chromene derivatives viaone-pot three-component reaction
Synthesis and evaluation of substituted hexahydronaphthalenes as novel inhibitors of the Mcl-1/BimBH3interaction
pp 5961–5965
Young B. Kim, Maria E. Balasis, Kenichiro Doi, Norbert Berndt, Courtney DuBoulay, Chih-Chi Andrew Hu, Wayne Guida,Hong-Gang Wang, Saïd M. Sebti, Juan R. Del Valle*
H
OO
NH
O
NH
O
O
19
Cl
Mcl-1/BimBH3 IC50 = 8.3 μM
Discovery and optimization of a series of liver X receptor antagonists pp 5966–5970
XianYun Jiao*, David J. Kopecky, Ben Fisher, Derek E. Piper, Marc Labelle, Sharon McKendry, Martin Harrison, Stuart Jones,Juan Jaen, Andrew K. Shiau, Patrick Escaron, Jean Danao, Anne Chai, Peter Coward, Frank Kayser
SN
OH
O O CF3
F3C
2 (T0901317)
dual LXRα/β agonists
CF3
SN
CF3
O O
HO
S
O
O
54dual LXRα/β antagonists
5762 Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765
Synthesis, antimycobacterial and antibacterial activity of ciprofloxacin derivatives containing aN-substituted benzyl moiety
We report herein a series of novel ciprofloxacin (CPFX) derivatives. Results reveal that compound 4f has good in vitro activity against all of the tested Gram-positive strainsincluding MRSA and MRSE (MICs: 0.06–32 lg/mL) which is two to eight-fold more potent than or comparable to the parent drug CPFX (MICs: 0.25–128 lg/mL), Gram-negativebacteria P. aeruginosa (MICs: 0.5–4 lg/mL) and mycobacterium tuberculosis H37Rv ATCC 27294 (MIC: 1 lg/mL).
Triazolbenzo[d]thiazoles: Efficient synthesis and biological evaluation as neuroprotective agents pp 5976–5978
Belem Avila, Aaron Roth, Heather Streets, Donard S. Dwyer, Mark J. Kurth*
Synthesis and biological activity of pyridopyridazin-6-one p38a MAP kinase inhibitors. Part 2 pp 5979–5983
Robert M. Tynebor*, Meng-Hsin Chen, Swaminathan R. Natarajan, Edward A. O’Neill, James E. Thompson,Catherine E. Fitzgerald, Stephen J. O’Keefe, James B. Doherty
NN O
O
F
F
R
A novel series of G-quadruplex ligands with selectivity for HIF-expressing osteosarcoma and renal cancercell lines
pp 5984–5988
Caterina M. Lombardo, Sarah J. Welsh, Sandra J. Strauss, Aaron G. Dale, Alan K. Todd, Rupesh Nanjunda, W. David Wilson,Stephen Neidle*
N
N N N N
N
HN NH
O
N
O
N
Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765 5763
Novel monobactams utilizing a siderophore uptake mechanism for the treatment of gram-negativeinfections
pp 5989–5994
Mark J. Mitton-Fry, Joel T. Arcari, Matthew F. Brown*, Jeffrey M. Casavant, Steven M. Finegan,Mark E. Flanagan, Hongying Gao, David M. George, Brian S. Gerstenberger, Seungil Han,Joel R. Hardink, Thomas M. Harris, Thuy Hoang, Michael D. Huband, Rebecca Irvine,Manjinder S. Lall, M. Megan Lemmon, Chao Li, Jian Lin, Sandra P. McCurdy, John P. Mueller,Lisa Mullins, Mark Niosi, Mark C. Noe, David Pattavina, Joseph Penzien, Mark S. Plummer,Hud Risley, Brandon P. Schuff, Veerabahu Shanmugasundaram, Jeremy T. Starr, Jianmin Sun,Jennifer Winton, Jennifer A. Young
S
HN
O
NO
OH
O
NH2N
Me
Me
NO SO3H
X
O
L N
O
OH
R
Modulation of cofilin phosphorylation by inhibition of the Lim family kinases pp 5995–5998
Liqi He*, Steven P. Seitz, George L. Trainor, David Tortolani, Wayne Vaccaro, Michael Poss, Christine M. Tarby, JohnS. Tokarski, Becky Penhallow, Chen-Yi Hung, Ricardo Attar, Tai-An Lin
The design, synthesis, and SAR for a series of aminothiazole pyrimidines as potent LIMK inhibitors are described. Compound 31 effectively inhibited cofilin phosphorylation incells in a dose dependent manner.
Synthesis and evaluation of 4-(substituted styryl/alkenyl)-3,5-bis(4-hydroxyphenyl)-isoxazoles asligands for the estrogen receptor
pp 5999–6003
Terra Haddad, Rachel Gershman, Robert Dilis, David Labaree, Richard B. Hochberg, Robert N. Hanson*
ON
OH
HO
I
ON
OH
HO
R R = Substituted aryl
Substituted alkyl
13 examples
Design, synthesis, stereochemistry and antioxidant properties of various 7-alkylated 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones
pp 6004–6009
Dong Ho Park, Jayachandran Venkatesan, Se-Kwon Kim, Paramasivam Parthiban*
Ha
Ha
N
O
Ha
RHe
HH
HaHa
5
6
1
7
8
He
24
3
9
H R1R1
MethylEthyltert -Pentyl
OH OCH3
OC2H5
5764 Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765
Synthesis and evaluation of novel 2-pyridone derivatives as inhibitors of phosphodiesterase3 (PDE3): Atarget for heart failure and platelet aggregation
Design, solvent free synthesis, and antimicrobial evaluation of 1,4 dihydropyridines pp 6016–6023
Y.L.N. Murthy, Abdul Rajack*, M. Taraka Ramji, J. Jeson babu, Ch. Praveen, K. Aruna Lakshmi
*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).
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
Contents / Bioorg. Med. Chem. Lett. 22 (2012) 5753–5765 5765
![FLAMING CLIFFS 2 - [FLAMING CLIFFS 2] 1 TABLE OF CONTENTS | GRAPHICAL USER INTERFACE TABLE OF CONTENTS MAIN MENU .....4 ...](https://static.documents.pub/doc/80x56/5af425d67f8b9ae9488ba3f5/flaming-cliffs-2-flaming-cliffs-2-1-table-of-contents-graphical-user-interface.jpg)
