Synthesis and SAR studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off-target kinase selectivity.

abstract：:Human telomeric DNA is transcribed into telomeric RNA in cells. Telomeric RNA performs the fundamental biological functions such as regulation and protection of chromosome ends. This digest highlights the human telomere RNA G-quadruplex structures, telomere RNA functions, G-quadruplex-binding small molecules, and futu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu Y

更新日期：2018-08-15 00:00:00

abstract：:On-resin macrocyclization via an SNAr reaction is employed in the synthesis of tocinoic acid analogs. Specifically, an N-terminal nitrofluorobenzene is attacked by a nucleophilic C-terminal sidechain. The remaining nitro group can be reduced and acylated. NMR is used to compare the conformation of the new macrocyclic ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fotsch C,Kumaravel G,Sharma SK,Wu AD,Gounarides JS,Nirmala NR,Petter RC

更新日期：1999-08-02 00:00:00

abstract：:Synthesis of a symmetrically branched diglycerol (BGL002, involving one iminodiacetic residue) as a G2 dendron, and the tetradecaglycerol (BGL014, involving one iminodiacetic residue) as a G4 dendron, is described. Several members of the BGL family of G2-G4 dendrons were assembled, with G2 bearing four hydroxyl groups...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nemoto H,Ishihara A,Araki T,Katagiri A,Kamiya M,Matsushita T,Hattori H,Mimura Y,Tomoda Y,Yamasaki M

更新日期：2011-08-15 00:00:00

abstract：:Hypoxia is a characteristic feature of solid tumors. Herein, we have developed novel hypoxia-sensitive probes (IM-ACs) for Raman spectroscopic analysis, consisting of nitroimidazole as a hypoxia-targeting unit and acetylene group as the signal-emitting unit. Among IM-ACs synthesized in this study, IM-AC possessing a d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kurihara R,Ikemura Y,Tanabe K

更新日期：2016-10-15 00:00:00

abstract：:Hydrogen sulfide (H2S) has been investigated for its potential in therapy. Recently, we reported novel H2S donor molecules based on a thiophosphorus core, which slowly release H2S and have improved anti-proliferative activity in cancer cell lines compared to the most widely studied H2S donor GYY4137 (1). Herein, we ha...

journal_title：Bioorganic & medicinal chemistry letters

authors： Feng W,Novera W,Peh K,Neo D,Ramanujulu PM,Moore PK,Deng LW,Dymock BW

更新日期：2017-02-15 00:00:00

abstract：:Many types of cancer, including glioma, melanoma, NSCLC, among others, are resistant to apoptosis induction and poorly responsive to current therapies with propaptotic agents. We describe a series of 2,3-disubstituted indoles, which display cytostatic rather than cytotoxic effects in cancer cells, and serve as a new c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Magedov IV,Lefranc F,Frolova LV,Banuls LM,Peretti AS,Rogelj S,Mathieu V,Kiss R,Kornienko A

更新日期：2013-06-01 00:00:00

abstract：:Selectivity of enzymatic and chemical methods for transesterifications of cytarabine with divinyl dicarboxylates was described. Catalysis by lipase acrylic resin from Candida antarctica (CAL-B) in acetone facilitated the single step synthesis of polymerizable 5'-O-acyl cytarabine derivatives in high yields, while the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang N,Chen ZC,Lu DS,Lin XF

更新日期：2005-09-15 00:00:00

abstract：:The strategy and SAR studies that led to the discovery of a novel potent and orally available 5-lipoxygenase (5-LO) inhibitor 3-(4-fluorophenyl)-6-({4-[(1S)-1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-1-benzothiophene-2-carboxamide ((S)-2l or MK-5286) were described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li L,Berthelette C,Chateauneuf A,Ouellet M,Sturino CF,Wang Z

更新日期：2010-12-15 00:00:00

abstract：:Novel arylethynyltriazole acyclonucleosides were synthesized and assessed for their anticancer activity on drug-resistant pancreatic cancer MiaPaCa-2 cells. One lead compound was found to have much more potent apoptosis-related antiproliferative effects than gemcitabine, the current first-line treatment for pancreatic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Xia Y,Fan Y,Rocchi P,Qu F,Iovanna JL,Peng L

更新日期：2010-10-15 00:00:00

abstract：:Death associated protein kinase (DAPK) is a calcium and calmodulin regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for acute brain injury, the first small molecule DAPK inhibitor was synthesized and tested in vivo. A single ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Velentza AV,Wainwright MS,Zasadzki M,Mirzoeva S,Schumacher AM,Haiech J,Focia PJ,Egli M,Watterson DM

更新日期：2003-10-20 00:00:00

abstract：:A new class of O-arylmandelic acid PPAR agonists show excellent anti-hyperglycemic efficacy in a db/db mouse model of DM2. These PPARalpha-weighted agonists do not show the typical PPARgamma associated side effects of BAT proliferation and cardiac hypertrophy in a rat tolerability assay. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Adams AD,Hu Z,von Langen D,Dadiz A,Elbrecht A,MacNaul KL,Berger JP,Zhou G,Doebber TW,Meurer R,Forrest MJ,Moller DE,Jones AB

更新日期：2003-10-06 00:00:00

abstract：:In a previous study, we found that the 3,4-dihydroquinazoline derivative, 4-(Benzylcarbamoylmethyl)-2-(biphenyl-4-ylamino)-3-(5-tert-butyloxycarbamoyl-1-pentyl)-3,4-dihydroquinazoline (KYS05047), was a selective T-type Ca(2+) channel blocker with anti-proliferative effects against various cancer cells. However, the me...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rim HK,Lee HW,Choi IS,Park JY,Choi HW,Choi JH,Cho YW,Lee JY,Lee KT

更新日期：2012-12-01 00:00:00

abstract：:The present report describes our efforts to convert an existing LXR agonist into an LXR antagonist using a structure-based approach. A series of benzenesulfonamides was synthesized based on structural modification of a known LXR agonist and was determined to be potent dual liver X receptor (LXR α/β) ligands. Herein we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jiao X,Kopecky DJ,Fisher B,Piper DE,Labelle M,McKendry S,Harrison M,Jones S,Jaen J,Shiau AK,Escaron P,Danao J,Chai A,Coward P,Kayser F

更新日期：2012-09-15 00:00:00

abstract：:A series of pyrimidine derivatives as acid pump antagonists (APAs) was synthesized and the inhibitory activities against H(+)/K(+) ATPase isolated from hog gastric mucosa were determined. After elaborating on substituents at C2 and C4 position of the pyrimidine scaffold, we have observed that the compound 7h is a pote...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yoon YA,Park CS,Cha MH,Choi H,Sim JY,Kim JG

更新日期：2010-10-01 00:00:00

abstract：:A series of 2-phenylbenzofuran derivatives with a diphenylmethylcarbamoyl group at the 5 or 6 position of the benzofuran ring were synthesized and evaluated for rat and human testosterone 5 alpha-reductase inhibitory activities in vitro. They had inhibitory activities against both enzymes and the 6-carbamoyl derivativ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishibashi K,Nakajima K,Sugioka Y,Sugiyama M,Hamada T,Horikoshi H,Nishi T

更新日期：1998-03-17 00:00:00

abstract：:The synthesis of N-(O,O-diisopropylphosphoryl)-benzyltetrahydroisoquinoline (3) has been achieved in a 'one pot' procedure from imine (2) and diisopropyl-phosphorochloridate (1) generated in situ (POCl3 + iPrOH). Compound 3 is the first benzyltetrahydroisoquinoline derivative found to be a potent inhibitor of mitochon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Andreu I,Cabedo N,Tormo JR,Bermejo A,Mello R,Cortes D

更新日期：2000-07-03 00:00:00

abstract：:The dopamine D(3) receptor subtype has been targeted as a potential neurochemical modulator of the behavioral actions of psychomotor stimulants, such as cocaine. Previous synthetic studies provided structural requirements for high affinity binding to D(3) receptors which included a 2,3-dichloro-phenylpiperazine linked...

journal_title：Bioorganic & medicinal chemistry letters

authors： Newman AH,Cao J,Bennett CJ,Robarge MJ,Freeman RA,Luedtke RR

更新日期：2003-07-07 00:00:00

abstract：:The discovery of the CNS-penetrant and selective alpha(2C) adrenergic receptor antagonist N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, 13 is described. Structure-activity studies demonstrate the structural requirements for binding affinity, functional activity, a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patel SD,Habeski WM,Min H,Zhang J,Roof R,Snyder B,Bora G,Campbell B,Li C,Hidayetoglu D,Johnson DS,Chaudhry A,Charlton ME,Kablaoui NM

更新日期：2008-10-15 00:00:00

abstract：:Total syntheses of prenylated pyrrolidinoindoline alkaloids, (-)-mollenines A [(-)-1'] and B (2'), were accomplished via three- and four-step sequences including a bioinspired indole prenylation reaction followed by dioxomorpholine ring formation. Then, the stereochemistry of mollenines A and B was reassigned to 3S,6S...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shiomi S,Wada K,Umeda Y,Kato H,Tsukamoto S,Ishikawa H

更新日期：2018-09-01 00:00:00

abstract：:A series of 14-deoxy-11,12-didehydroandrographolide analogues were synthesized from naturally occurring andrographolide and their cytotoxicity evaluated against nine cancer cell lines including cholangiocarcinoma. Analogues 5a and 5b exhibited the most potent cytotoxicity with ED50s of 3.37 and 3.08 μM on KKU-M213 cel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sombut S,Bunthawong R,Sirion U,Kasemsuk T,Piyachaturawat P,Suksen K,Suksamrarn A,Saeeng R

更新日期：2017-12-01 00:00:00

abstract：:The synthesis of novel C6-aryl substituted derivatives of 3-(dimethylamino)chroman is described. The novel derivatives display 5-HT(7) receptor affinities that varies from nM to muM, indicating that this small set of derivatives constitute a novel and interesting starting point for further structure-serotonin 5-HT(7) ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Holmberg P,Tedenborg L,Rosqvist S,Johansson AM

更新日期：2005-02-01 00:00:00

abstract：:Highly potent and novel derivatives of doxorubicin were linked to monoclonal antibodies (mAbs) for site-specific drug delivery. Drug linker 5 consisted of a dipeptide linker attached directly to the daunosamine nitrogen of the n-butyldiacetate doxorubicin derivative 2a. Upon hydrolysis of the peptide linker and acetat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jeffrey SC,Nguyen MT,Andreyka JB,Meyer DL,Doronina SO,Senter PD

更新日期：2006-01-15 00:00:00

abstract：:A non-methionine FT inhibitor lead structure (1) was designed through computer modeling of the peptidomimetic FT inhibitor ABT839. Optimization of this lead resulted in compounds 2e and 2g, with FT IC(50) values of 1.3 and 1.8 nM, GGT IC(50) of 1400 nM, and EC(50) (Ras processing) values of 13 and 11 nM, respectively....

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang GT,Wang X,Wang W,Hasvold LA,Sullivan G,Hutchins CW,O'Conner S,Gentiles R,Sowin T,Cohen J,Gu WZ,Zhang H,Rosenberg SH,Sham HL

更新日期：2005-01-03 00:00:00

abstract：:We have developed clickable active site-directed photoaffinity probes for γ-secretase which incorporate a photoreactive benzophenone group and an alkyne handle for subsequent click chemistry mediated conjugation with azide-linked reporter tags for visualization (e.g., TAMRA-azide) or enrichment (e.g., biotin-azide) of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Crump CJ,am Ende CW,Ballard TE,Pozdnyakov N,Pettersson M,Chau DM,Bales KR,Li YM,Johnson DS

更新日期：2012-04-15 00:00:00

abstract：:Novel 5-HT(7) receptor antagonists containing the benzocycloheptanone core were identified from high throughput screening. Molecular modelling and SAR studies have converted these intractable hits into a more potent, selective and tractable series, exemplified by compound (25), SB-691673. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Forbes IT,Cooper DG,Dodds EK,Douglas SE,Gribble AD,Ife RJ,Lightfoot AP,Meeson M,Campbell LP,Coleman T,Riley GJ,Thomas DR

更新日期：2003-03-24 00:00:00

abstract：:Regioselective synthesis, biological evaluation and 3D-molecular modeling for a series of novel diastereomeric 2-thioxo-5H-dispiro[imidazolidine-4,3-pyrrolidine-2,3-indole]-2,5(1H)-diones are described. The studied compounds have been tentatively identified as potent small molecule MDM2/p53 PPI inhibitors and can ther...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ivanenkov YA,Vasilevski SV,Beloglazkina EK,Kukushkin ME,Machulkin AE,Veselov MS,Chufarova NV,Chernyaginab ES,Vanzcool AS,Zyk NV,Skvortsov DA,Khutornenko AA,Rusanov AL,Tonevitsky AG,Dontsova OA,Majouga AG

更新日期：2015-01-15 00:00:00

abstract：:Two nemadectin congeners 1 and 2 were isolated from the fermentation broth of a mutant strain (Y-3) of Streptomyces microflavus neau3. Their structures were determined on the basis of extensive spectroscopic analysis and comparison with data from the literature. Compound 2 possessed a 5-membered ring lactone that is u...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang LY,Wang JD,Zhang J,Xue CY,Zhang H,Wang XJ,Xiang WS

更新日期：2013-10-15 00:00:00

abstract：:A series of thiazole bearing thiazolidin-4-one was discovered via high-throughput screening as non-competitive inhibitors of ADAMTS-5. Compound 31 appeared to give the best ADAMTS-5 inhibition and good selectivity over other metalloproteases. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Atobe M,Maekawara N,Ishiguro N,Sogame S,Suenaga Y,Kawanishi M,Suzuki H,Jinno N,Tanaka E,Miyoshi S

更新日期：2013-04-01 00:00:00

abstract：:To explore the hydrophobic groove subsite within the CB1 cannabinoid receptor we have designed and synthesized a group of tail-substituted anandamide analogs. Our design involves the introduction of aryl or heterocyclic ring as terminal substituents that are connected to the last cis-arachidonyl double bond through al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yao F,Li C,Vadivel SK,Bowman AL,Makriyannis A

更新日期：2008-11-15 00:00:00

abstract：:Several p-terphenyl compounds have been isolated from the edible Chinese mushroom Thelephora vialis. Vialinin A, a p-terphenyl compound, strongly inhibits tumor necrosis factor-α production and release. Vialinin A inhibits the enzymatic activity of ubiquitin-specific peptidase 5, one of the target molecules in RBL-2H3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yoshioka Y,Namiki D,Makiuchi M,Sugaya K,Onose J,Ashida H,Abe N

更新日期：2016-09-01 00:00:00