Synthesis and biological evaluation of two novel DAT-binding technetium complexes containing a piperidine based analogue of cocaine.

abstract：:Substitution at the alpha center of the known human arginase inhibitor 2-amino-6-boronohexanoic acid (ABH) is acceptable in the active site pockets of both human arginase I and arginase II. In particular, substituents with a tertiary amine linked via a two carbon chain show improved inhibitory potency for both enzyme ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Golebiowski A,Paul Beckett R,Van Zandt M,Ji MK,Whitehouse D,Ryder TR,Jagdmann E,Andreoli M,Mazur A,Padmanilayam M,Cousido-Siah A,Mitschler A,Ruiz FX,Podjarny A,Schroeter H

更新日期：2013-04-01 00:00:00

abstract：:Clausenamide, isolated from aqueous extract of dry leaves of Clausena lansium, a Chinese folk medicine, was found to have potent activity in enhancing LTP and show nootropic activity in animal tests. In order to discovery more potent stereoisomers and to analyze the relationship of structure-activity, the synthesis of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Feng Z,Li X,Zheng G,Huang L

更新日期：2009-04-15 00:00:00

abstract：:The inhibition of ribonuclease Bi by 3'-N-hydroxyurea-3'-deoxythymidine 5'-phosphate is enhanced by 30-fold in the presence of Zn(2+). Thus, an N-hydroxyurea nucleotide can recruit Zn(2+) to inhibit the enzymatic activity of a ribonuclease. This result engenders a general strategy for the inhibition of non-metalloenzy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Higgin JJ,Yakovlev GI,Mitkevich VA,Makarov AA,Raines RT

更新日期：2003-02-10 00:00:00

abstract：:A novel series of diphenylpyridylethanamine-based inhibitors of cholesteryl ester transfer protein is described. Optimization of the urea moiety, particularly by incorporation of fluorine, is explored to balance in vitro metabolic stability with CETP potency in the whole plasma assay. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miller MM,Liu Y,Jiang J,Johnson JA,Kamau M,Nirschl DS,Wang Y,Harikrishnan L,Taylor DS,Chen AY,Yin X,Seethala R,Peterson TL,Zvyaga T,Zhang J,Huang CS,Wexler RR,Poss MA,Lawrence RM,Adam LP,Salvati ME

更新日期：2012-10-15 00:00:00

abstract：:The affinity of a series of 2', 3'- and 5-modified thymidine analogues for Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) was evaluated. The affinities of several non-phosphorylated analogues are in the same order of magnitude as those of their phosphorylated congeners. In view of drug delivery pro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vanheusden V,Van Rompaey P,Munier-Lehmann H,Pochet S,Herdewijn P,Van Calenbergh S

更新日期：2003-09-15 00:00:00

abstract：:Identification of a number of highly potent M2 receptor antagonists with >100-fold selectivity against the M1 and M3 receptor subtypes is described. In the rat microdialysis assay, this series of compounds showed pronounced enhancement of brain acetylcholine release after oral administration. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Y,Chackalamannil S,Hu Z,Clader JW,Greenlee W,Billard W,Binch H,Crosby G,Ruperto V,Duffy RA,McQuade R,Lachowicz JE

更新日期：2000-10-16 00:00:00

abstract：:A series of quinazolinone derived Schiff base derivatives 7-28 were synthesized and characterized as novel antioxidants and anti-inflammatory agents. The in vitro antioxidant activities of these compounds were evaluated and compared with commercial antioxidants ascorbic acid (AA), gallic acid (GA), butylatedhydroxytol...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rakesh KP,Manukumar HM,Gowda DC

更新日期：2015-03-01 00:00:00

abstract：:A new cytotoxic oxysterol, 16beta-hydroxy-5alpha-cholestane-3,6-dione was isolated from the red alga Jania rubens. Its structure was established by spectroscopic method. The ID50 value was 0.5 microg/mL. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ktari L,Blond A,Guyot M

更新日期：2000-11-20 00:00:00

abstract：:A novel series of non-nucleoside small molecules containing a tricyclic dihydropyridinone structural motif was identified as potent HCV NS5B polymerase inhibitors. Driven by structure-based design and building on our previous efforts in related series of molecules, we undertook extensive SAR studies, in which we ident...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ruebsam F,Murphy DE,Tran CV,Li LS,Zhao J,Dragovich PS,McGuire HM,Xiang AX,Sun Z,Ayida BK,Blazel JK,Kim SH,Zhou Y,Han Q,Kissinger CR,Webber SE,Showalter RE,Shah AM,Tsan M,Patel RA,Thompson PA,Lebrun LA,Hou HJ,

更新日期：2009-11-15 00:00:00

abstract：:Using a genetic selection we identified mutants of the M. janaschii tyrosyl-tRNA synthetase that selectively charge an amber suppressor tRNA with para-propargyloxyphenylalanine in Escherichia coli. These evolved tRNA-synthetase pairs were used to site-specifically incorporate an alkynyl group into a protein, which was...

journal_title：Bioorganic & medicinal chemistry letters

authors： Deiters A,Schultz PG

更新日期：2005-03-01 00:00:00

abstract：:Fourty-two thiazolyl-pyrazoline derivatives were synthesized to screen for their EGFR kinase inhibitory activity. Compound 4-(4-chlorophenyl)-2-(3-(3,4-dimethylphenyl)-5-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazole (11) displayed the most potent EGFR TK inhibitory activity with IC(50) of 0.06 μM, which was comparable ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lv PC,Li DD,Li QS,Lu X,Xiao ZP,Zhu HL

更新日期：2011-09-15 00:00:00

abstract：:Two types of P1-P3-linked macrocyclic renin inhibitors containing the hydroxyethylene isostere (HE) scaffold just outside the macrocyclic ring have been synthesized. An aromatic or aliphatic substituent (P3sp) was introduced in the macrocyclic ring aiming at the S3 subpocket (S3sp) in order to optimize the potency. A ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sund C,Belda O,Wiktelius D,Sahlberg C,Vrang L,Sedig S,Hamelink E,Henderson I,Agback T,Jansson K,Borkakoti N,Derbyshire D,Eneroth A,Samuelsson B

更新日期：2011-01-01 00:00:00

abstract：:Herein we describe the discovery of a novel series of ATP competitive B-Raf inhibitors via structure based drug design (SBDD). These pyridopyrimidin-7-one based inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 17, a potent, selective ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ren L,Ahrendt KA,Grina J,Laird ER,Buckmelter AJ,Hansen JD,Newhouse B,Moreno D,Wenglowsky S,Dinkel V,Gloor SL,Hastings G,Rana S,Rasor K,Risom T,Sturgis HL,Voegtli WC,Mathieu S

更新日期：2012-05-15 00:00:00

abstract：:Starting from thienobenzopyran HTS hit 1, co-crystallization, molecular modeling and metabolic analysis were used to design potent and metabolically stable inhibitors of PI3-kinase. Compound 15 demonstrated PI3K pathway suppression in a mouse MCF7 xenograft model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Staben ST,Siu M,Goldsmith R,Olivero AG,Do S,Burdick DJ,Heffron TP,Dotson J,Sutherlin DP,Zhu BY,Tsui V,Le H,Lee L,Lesnick J,Lewis C,Murray JM,Nonomiya J,Pang J,Prior WW,Salphati L,Rouge L,Sampath D,Sideris S,

更新日期：2011-07-01 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：:A novel series of hepatitis C virus (HCV) NS3/4A protease inhibitors bearing a P2-P4 macrocycle and a P1-P1' alpha-ketoamide serine trap is reported. The NS3 protease, which is essential for viral replication, is considered one of the most attractive targets for developing novel anti-HCV therapies. The optimization of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Avolio S,Robertson K,Hernando JI,DiMuzio J,Summa V

更新日期：2009-04-15 00:00:00

abstract：:From our modulator library an interesting inhibitor of breast cancer resistance protein (BCRP) was identified. Due to its high inhibitory potency, this compound may serve as a promising novel lead for the design of new and potent modulators. This adds a new structural class to the few known highly active BCRP inhibito...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pick A,Müller H,Wiese M

更新日期：2010-01-01 00:00:00

abstract：:The synthesis and SAR of a series of 6-(4-(substituted)phenyl)-2-aminopyridines as inhibitors of nitric oxide synthase are described. Compound 3a from this series shows potent and selective inhibition of the human nNOS isoform, with pharmacokinetics sufficient to provide in vivo inhibition of nNOS activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lowe JA 3rd,Qian W,Volkmann RA,Heck S,Nowakowski J,Nelson R,Nolan C,Liston D,Ward K,Zorn S,Johnson C,Vanase M,Faraci WS,Verdries KA,Baxter J,Doran S,Sanders M,Ashton M,Whittle P,Stefaniak M

更新日期：1999-09-06 00:00:00

abstract：:Protein tyrosine phosphatase 1B (PTP1B) has been proposed to be an ideal target for treatment of type II diabetes and obesity. However, no druggable PTP1B inhibitor has been established and there is still an urgent demand for the development of structurally novel PTPIB inhibitor. Herein, we reported core-structurally ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dong S,Lei Y,Jia S,Gao L,Li J,Zhu T,Liu S,Hu W

更新日期：2017-02-15 00:00:00

abstract：:Casein kinase 2 catalytic subunit (CK2α) is classified into two subtypes CK2α1 and CK2α2. CK2α1 is a drug discovery target, whereas CK2α2 is an off-target of CK2α1 inhibitors. High amino acid sequence homology between these subtypes hampers efforts to produce ATP competitive inhibitors that are highly selective to CK2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tsuyuguchi M,Nakaniwa T,Hirasawa A,Nakanishi I,Kinoshita T

更新日期：2020-01-15 00:00:00

abstract：:Methylation of the carbon atom C of compound 1, a potent and not selective muscarinic antagonist, was carried out. The resulting diastereomers were separated and the corresponding racemate further resolved to give four enantiomers, which were tested both as hydrogen oxalate and methiodide salts. The pharmacological re...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gulini U,Angeli P,Marucci G,Buccioni M,Giardinà D,Antolini L,Franchini S,Sorbi C,Brasili L

更新日期：2001-01-22 00:00:00

abstract：:A novel neurokinin-1 receptor antagonist, (+/-)-(1R( *),3S( *),4S( *),5S( *))-4-[(N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-3-phenyl-2-aza-7-oxabicyclo[3.3.0]octane (1), was synthesized stereoselectively using Padwa's intramolecular 1,3-dipolar cycloaddition methodology as the key step. Compound (+/-)-1 showed high...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shishido Y,Ito F,Morita H,Ikunaka M

更新日期：2007-12-15 00:00:00

abstract：:(-)-Renieramycin G and fifteen C-22 analogs were prepared employing l-tyrosine as the chiral starting material. These analogs, along with (-)-renieramycin G itself, were evaluated in vitro for cytotoxicity against HCT-8, BEL-7402, A2780, MCF-7, A549, BGC-823, Ketr3, KB, Hela cells. The IC(50) values of most of these a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu W,Dong W,Liao X,Yan Z,Guan B,Wang N,Liu Z

更新日期：2011-03-01 00:00:00

abstract：:The bacterial protein tyrosine phosphatase YopH is an essential virulence determinant in Yersinia pestis and a potential antibacterial drug target. Here we report our studies of screening for small molecule inhibitors of YopH using both high throughput and in silico approaches. The identified inhibitors represent a di...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hu X,Vujanac M,Southall N,Stebbins CE

更新日期：2013-02-15 00:00:00

abstract：:New RXR-selective modulators possessing a 6-fluoro trienoic acid moiety (6Z olefin) or a fluorinated/heterocyclic-substituted benzene core ring, were synthesized in an expedient and selective way. A subset of these compounds was evaluated for their metabolic properties (exposure in IRC male mice) and show a dramatic i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Michellys PY,Boehm MF,Chen JH,Grese TA,Karanewsky DS,Leibowitz MD,Liu S,Mais DA,Mapes CM,Reifel-Miller A,Ogilvie KM,Rungta D,Thompson AW,Tyhonas JS,Yumibe N,Ardecky RJ

更新日期：2003-11-17 00:00:00

abstract：:Current therapy for blood vessel thrombosis has the risk of leading to gastrointestinal bleeding and thrombocytopenia. We previously reported that a new derivative of diosgenin, compound 5, had significant anti-inflammatory activity superior to that of aspirin, prolonged bleeding time, and inhibited platelet aggregati...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng H,Wei Z,Xin G,Ji C,Wen L,Xia Q,Niu H,Huang W

更新日期：2016-07-15 00:00:00

abstract：:A series of novel 1,3-benzodiazapine based D1 antagonists was designed according to the understanding of pharmacophore models derived from SCH 23390 (1b), a potent and selective D1 antagonist. The new design features an achiral cyclic-amidine that maintains desired basicity. Solid phase synthesis was developed for SAR...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhu Z,Sun ZY,Ye Y,McKittrick B,Greenlee W,Czarniecki M,Fawzi A,Zhang H,Lachowicz JE

更新日期：2009-09-01 00:00:00

abstract：:Four novel porphyrins containing nitric oxide (NO) donors were synthesized, and the structures of all the products were characterized by IR, UV-vis, (1)H NMR, and elementary analysis. Interestingly, these new compounds not only were able to release NO, but also showed cancer cell-oriented accumulation. Higher accumula...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu W,Liu C,Gong C,Lin W,Guo C

更新日期：2009-03-15 00:00:00

abstract：:Accumulation of Aβ in the brains of Alzheimer disease (AD) patients reflects an imbalance between Aβ production and clearance from their brains. Alternative cleavage of amyloid precursor protein (APP) by processing proteases generates soluble APP fragments including the neurotoxic amyloid Aβ40 and Aβ42 peptides that a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Matveev SV,Kwiatkowski S,Sviripa VM,Fazio RC,Watt DS,LeVine H 3rd

更新日期：2014-12-01 00:00:00

abstract：:Prostate specific membrane antigen (PSMA) is recognized as an attractive molecular target for the development of radiopharmaceuticals to image and potentially treat metastatic prostate cancer. A series of novel (99m)Tc/Re-tricarbonyl radiolabeled PSMA inhibitors were therefore synthesized by the attachment of glutamat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lu G,Maresca KP,Hillier SM,Zimmerman CN,Eckelman WC,Joyal JL,Babich JW

更新日期：2013-03-01 00:00:00