Novel dual inhibitors of calpain and lipid peroxidation.

abstract：:We have developed two novel series of tetrasubstituted pyrazoles, embodying 1,3-diaryl-4,5-dialkyl or 3,5-diaryl-1,4-dialkyl substitution patterns. The scope of a regioselective method, developed by us earlier, was expanded to allow the synthesis of the first series of these tetrasubstituted pyrazoles directly from al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishiguchi GA,Rodriguez AL,Katzenellenbogen JA

更新日期：2002-03-25 00:00:00

abstract：:We previously showed that fluorination of the carborane-containing selective estrogen receptor modulator (SERM) BE360 altered the agonist/antagonist activity balance and the estrogen receptor (ER) α/β subtype selectivity. Here, we designed and synthesized a series of fluorinated carboranyl phenols as candidate ERβ-sel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohta K,Ogawa T,Kaise A,Endo Y

更新日期：2013-12-15 00:00:00

abstract：:Human 5-lipoxygenase (5-LOX) is responsible for the formation of leukotriene (LT)A4, a pivotal intermediate in the biosynthesis of the leukotrienes, a family of proinflammatory lipid mediators. 5-LOX has thus gained attention as a potential drug target. However, details of the kinetic mechanism of 5-LOX are still obsc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mittal M,Kumar RB,Balagunaseelan N,Hamberg M,Jegerschöld C,Rådmark O,Haeggström JZ,Rinaldo-Matthis A

更新日期：2016-08-01 00:00:00

abstract：:Indolopropellane 2 was reported to show almost no binding affinity to the δ opioid receptor (DOR) in spite of the fact that 2 has both the propellane fundamental skeleton (message part) with binding ability to the opioid receptors and a possible DOR address structure (indole moiety). We developed the working hypothesi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nagase H,Nakajima R,Yamamoto N,Hirayama S,Iwai T,Nemoto T,Gouda H,Hirono S,Fujii H

更新日期：2014-07-01 00:00:00

abstract：:The derivatization of resin-bound aminobenzimidazole toward the parallel solid-phase synthesis of aminobenzimidazole tethered pharmacologically important heterocycles such as quinazoline-2,4-diones, thioxoquinazolin-4-ones, benzodiazepine-2,3,5-triones, isoxazoles and isoxazolines is reported. All the compounds were t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dadiboyena S,Arfaoui A,Amri H,Piedrafita FJ,Nefzi A

更新日期：2015-02-01 00:00:00

abstract：:Some ergostane triterpenoids from Taiwanofungus camphoratus have been shown to exhibit anti-inflammatory activity in vitro. However, the effect of ergostane triterpenoids on the immune response remains unknown. In this study, we elucidated that ergostane triterpenoids significantly decreased the cytokines and chemokin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lin MK,Lee MS,Chang WT,Chen HY,Chen JF,Li YR,Lin CC,Wu TS

更新日期：2015-10-15 00:00:00

abstract：:A novel series of 3,5,6-trisubstituted pyrazolo[4,3-d]pyrimidin-7-one derivatives, especially 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-ones were synthesized and evaluated for their in vitro anticancer activities against various human cancer cell lines. The inhibitory activities for several kinases have also been ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Devegowda VN,Kim JH,Han KC,Yang EG,Choo H,Pae AN,Nam G,Choi KI

更新日期：2010-03-01 00:00:00

abstract：:3-O-tert-Butyldimethylsilyl-17 alpha-(6-mesyloxyhexynyl)estradiol was converted to the azide in 60-70% yield with NaN3/DMPU, then reduced to the corresponding amine (> 95% yield). Acylation with the N-hydroxysuccinimide esters of biotin, 5-carboxyfluorescein and 10-(3-sulfopropyl)-N-tosyl-N-(3- carboxypropyl)acridiniu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Adamczyk M,Chen YY,Moore JA,Mattingly PG

更新日期：1998-06-02 00:00:00

abstract：:The concept of sequential cytotoxicity, which states that successive chemical attacks on cellular constituents can be more deleterious to neoplasms than normal cells, was evaluated using a series of 3,5-bis(benzylidene)-1-diethylphosphono-4-oxopiperidines 1 and related phosphonic acids 2, which were screened against a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Das S,Das U,Sakagami H,Hashimoto K,Kawase M,Gorecki DK,Dimmock JR

更新日期：2010-11-15 00:00:00

abstract：:A series of dehydroabietic acid (DHAA, 2) derivatives was synthesized and evaluated as BK channel openers in an assay system of CHO-K1 cells expressing hBKalpha channels. Systematic modifications of the peripheral functionality of ring C of DHAA showed that the introduction of a nitro or (thio)urea group in ring C gre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cui YM,Yasutomi E,Otani Y,Yoshinaga T,Ido K,Sawada K,Ohwada T

更新日期：2008-10-01 00:00:00

abstract：:Exogenous short-chain nucleic acids undergo rapid import into the nucleus. Fluorescence-labeled dT1-13 DNA microinjected into the cytoplasm domain of a HeLa cell was rapidly imported into the nucleus domain within 1min. This is much more rapid than what has been observed for intracellular diffusion of small molecules....

journal_title：Bioorganic & medicinal chemistry letters

authors： Kitagawa M,Okamoto A

更新日期：2016-10-01 00:00:00

abstract：:Three series of rhodanine derivatives bearing a quinoline moiety (6a-h, 7a-g, and 8a-e) have been synthesized, characterized, and evaluated as antibacterial agents. The majority of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-re...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guo M,Zheng CJ,Song MX,Wu Y,Sun LP,Li YJ,Liu Y,Piao HR

更新日期：2013-08-01 00:00:00

abstract：:A novel series of CXCR4 antagonists were identified based on the substantial redesign of AMD070. These compounds possessed potent anti-HIV-1 activity and showed excellent pharmacokinetics in rat and dog. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Skerlj R,Bridger G,McEachern E,Harwig C,Smith C,Kaller A,Veale D,Yee H,Skupinska K,Wauthy R,Wang L,Baird I,Zhu Y,Burrage K,Yang W,Sartori M,Huskens D,De Clercq E,Schols D

更新日期：2011-03-01 00:00:00

abstract：:Herein we report the preparation of a combinatorial library of compounds with potent CCR5 binding affinity. The library design was aided by SAR generated in a traditional medicinal chemistry effort. Compounds with novel combinations of subunits were discovered that have high binding affinity for the CCR5 receptor. A p...

journal_title：Bioorganic & medicinal chemistry letters

authors： Willoughby CA,Berk SC,Rosauer KG,Degrado S,Chapman KT,Gould SL,Springer MS,Malkowitz L,Schleif WA,Hazuda D,Miller M,Kessler J,Danzeisen R,Holmes K,Lineberger J,Carella A,Carver G,Emini EA

更新日期：2001-12-17 00:00:00

abstract：:The human epidermal growth factor receptor (EGFR) family is known to be involved in cell signaling pathways. The extracellular domain of EGFR consists of four domains, of which domain II and domain IV are known to be involved in the dimerization process. Overexpression of these receptors is known to play a significant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Naik H,Gauthier T,Singh S,Jois S

更新日期：2018-12-01 00:00:00

abstract：:A series of novel (1S)-(-)-verbenone derivatives was synthesized bearing a 4-styryl scaffold. The synthesized compounds were tested for their anti-oxidant, anti-excitotoxic, and anti-ischemic activities. These derivatives significantly reduced oxygen-glucose deprivation-induced neuronal injury and N-methyl-D-aspartic ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ju C,Song S,Hwang S,Kim C,Kim M,Gu J,Oh YK,Lee K,Kwon J,Lee K,Kim WK,Choi Y

更新日期：2013-10-01 00:00:00

abstract：:Three novel metabolites of the angiotensin-II (A-II) receptor antagonist tasosartan have been identified in humans, and the syntheses and pharmacologic profiling of these metabolites are reported. Each metabolite bound the human A-II receptor with IC(50)s between 20 and 45nM. The in vivo effects of these compounds in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Elokdah HM,Friedrichs GS,Chai SY,Harrison BL,Primeau J,Chlenov M,Crandall DL

更新日期：2002-08-05 00:00:00

abstract：:A series of m-carborane derivatives was prepared based upon the structures of antiestrogenic drugs and their activities were evaluated by estrogen receptor alpha (ERalpha) binding assay and transactivation assay using human breast cancer cell line, MCF-7 cells. The m-carborane bisphenol 5 exhibited about a thousand ti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ogawa T,Ohta K,Yoshimi T,Yamazaki H,Suzuki T,Ohta S,Endo Y

更新日期：2006-08-01 00:00:00

abstract：:Thermal transformation of the (+)-catechin (1) with heating processing afforded a new oxidation product, gambiriin D (2), along with catechin [6'-8]-catechin (3), and (+)-epicatechin (4). The structure of a new catechin dimer with C-C linkage was determined on the basis of spectroscopic data interpretation. The catech...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim T,Choi HJ,Eom SH,Lee J,Kim TH

更新日期：2014-03-15 00:00:00

abstract：:A total of 106 nitric oxide-releasing derivatives of oleanolic acid were synthesized and their effects on the inhibition of anti-Fas-mediated HepG2 cell apoptosis were evaluated in vitro. Several compounds inhibited anti-Fas-mediated HepG2 cell apoptosis in a dose-dependent manner. Within this series of compounds, 8b ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen L,Zhang Y,Kong X,Peng S,Tian J

更新日期：2007-06-01 00:00:00

abstract：:Small molecule mu agonists based on the 4-phenyl piperidine scaffold were designed and synthesized to further investigate the therapeutic potential of loperamide analogs. The resulting compounds show excellent agonistic activity towards the human mu receptor with interesting SAR trends within the series. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen Z,Davies E,Miller WS,Shan S,Valenzano KJ,Kyle DJ

更新日期：2004-11-01 00:00:00

abstract：:The C17-THP derivative of 7alpha-(11-azidoundecanyl)-estradiol (4) was synthesized and coupled to an aminomethyl resin via a photolabile o-nitrobenzyl linker. Reduction of the azide by the Staudinger reaction to its corresponding amine followed by acylation using four activated NFmoc protected amino acids gave a first...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tremblay MR,Simard J,Poirier D

更新日期：1999-10-04 00:00:00

abstract：:A series of N-acyl-N-hydroxy-beta-Phe were designed, synthesized, and shown to have potent inhibitory activity for carboxypeptidase A (CPA). They are the first examples of CPA inhibitors having a hydroxamate functionality. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim DH,Jin Y

更新日期：1999-03-08 00:00:00

abstract：:We report the synthesis and biological activity of a series of 2-cyano-4-fluoro-1-thiovalylpyrrolidine inhibitors of DPP-IV. Within this series, compound 19 provided a potent, selective, and orally active DPP-IV inhibitor which demonstrated a very long duration of action in both rat and dog. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Haffner CD,McDougald DL,Reister SM,Thompson BD,Conlee C,Fang J,Bass J,Lenhard JM,Croom D,Secosky-Chang MB,Tomaszek T,McConn D,Wells-Knecht K,Johnson PR

更新日期：2005-12-01 00:00:00

abstract：:A novel analog of nucleic acids bearing an optically active serine ester backbone, serine-based nucleobase-linked polyester (SNE), was synthesized. Monomers containing a thymine base were synthesized from L- and D-serines. Furthermore, reaction conditions were thoroughly examined for the ester bond formation by using ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Murata A,Wada T

更新日期：2006-06-01 00:00:00

abstract：:Selective monofluorination of the alpha-glycosidase inhibitor and antidiabetic agent Miglitol at position C2 creates an competitive inhibitor of five times higher activity than the parent compound. Its screening against a panel of human cell lines showed a low cytotoxicity therefore making this compound an interesting...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prell E,Csuk R

更新日期：2009-10-01 00:00:00

abstract：:Chalcones form a class of compounds that belong to the flavonoid family and are widely distributed in plants. Their simple structure and the ease of preparation make chalcones attractive scaffolds for the synthesis of a large number of derivatives enabling the evaluation of the effects of different functional groups o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Passalacqua TG,Dutra LA,de Almeida L,Velásquez AM,Torres FA,Yamasaki PR,dos Santos MB,Regasini LO,Michels PA,Bolzani Vda S,Graminha MA

更新日期：2015-08-15 00:00:00

abstract：:Positive allosteric modulation of metabotropic glutamate receptor 5 (mGluR5) is regarded as a potential novel treatment for schizophrenic patients. Herein we report the synthesis and SAR of 4-aryl piperazine and piperidine amides as potent mGluR5 positive allosteric modulators (PAMs). Several analogs have excellent ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiong H,Brugel TA,Balestra M,Brown DG,Brush KA,Hightower C,Hinkley L,Hoesch V,Kang J,Koether GM,McCauley JP Jr,McLaren FM,Panko LM,Simpson TR,Smith RW,Woods JM,Brockel B,Chhajlani V,Gadient RA,Spear N,Sygowski LA

更新日期：2010-12-15 00:00:00

abstract：:The histone methylation on lysine residues is one of the most studied post-translational modifications, and its aberrant states have been associated with many human diseases. In 2012, Kruidenier et al. reported GSK-J1 as a selective Jumonji H3K27 demethylase (JMJD3 and UTX) inhibitor. However, there is limited informa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hu J,Wang X,Chen L,Huang M,Tang W,Zuo J,Liu YC,Shi Z,Liu R,Shen J,Xiong B

更新日期：2016-02-01 00:00:00

abstract：:5-Carboxamido-1,3,2-dioxaphosphorinanes have been identified as potent inhibitors of microsomal triglyceride-transfer protein. The 1,3,2-dioxaphosphorine functionality acted as a neutral and stable replacement for piperidine and piperidine N-oxide. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sulsky R,Robl JA,Biller SA,Harrity TW,Wetterau J,Connolly F,Jolibois K,Kunselman L

更新日期：2004-10-18 00:00:00