Synthesis and antiproliferative activity of unnatural enantiomers of 7-epi-goniofufurone and crassalactone C.

abstract：:A series of yohimbine dimers was prepared and evaluated at the human alpha2a- and alpha2b-adrenergic receptors (ARs) expressed in Chinese hamster ovary (CHO) cells. All dimers display higher binding selectivities for alpha2a versus alpha2b subtype than yohimbine, and four compounds (3d, 3e, 3g and 3i) represent the mo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng W,Lei L,Lalchandani S,Sun G,Feller DR,Miller DD

更新日期：2000-04-03 00:00:00

abstract：:We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fuchi N,Iura Y,Kaneko H,Nitta A,Suyama K,Ueda H,Yamaguchi S,Nishimura K,Fujii S,Sekiya Y,Yamada M,Takahashi T

更新日期：2012-07-01 00:00:00

abstract：:Novel 8-aryl and 8-aroyl substituted derivatives of 3-(dipropylamino)chroman are described. The compounds have been prepared by a palladium catalyzed reaction of iodoarenes and a stannylated derivative of [eta6-3-(dipropylamino)chroman]Cr(CO)3. Several of the compounds have high affinity for 5-HT1A receptors whereas t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Caldirola P,Chowdhury R,Unelius L,Mohell N,Hacksell U,Johansson AM

更新日期：1999-06-07 00:00:00

abstract：:The structures of the uracil and thiouracils were examined using NMR spectroscopy and crystal structure data when available. The relationships between the extent of polarization and the C5-C6 bond length as well as the H5-H6 coupling constants were probed. It was found that the bond length and coupling constants corre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang S,Gronert S,Wu W

更新日期：2011-11-01 00:00:00

abstract：:A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin CH,Krishnaiah M,Sreenu D,Subrahmanyam VB,Rao KS,Mohan AV,Park CY,Son JY,Sheen YY,Kim DK

更新日期：2011-10-15 00:00:00

abstract：:In an effort to develop antagonists for kappa-mu opioid receptor heterodimers, a series of bivalent ligands 3-6 containing kappa- and mu-antagonist pharmacophores were designed and synthesized. Evaluation of the series in HEK-293 cells revealed 4 (KMN-21) to selectively antagonize the activation of kappa-mu heterodime...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang S,Yekkirala A,Tang Y,Portoghese PS

更新日期：2009-12-15 00:00:00

abstract：:A novel class of 4-aryl-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1- ones have been discovered and developed as potent and selective GlyT1 inhibitors. The molecules are devoid of activity at the GlyT2 isoform and display excellent selectivities against the mu-opioid receptor as well as the Nociceptin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alberati D,Hainzl D,Jolidon S,Krafft EA,Kurt A,Maier A,Pinard E,Thomas AW,Zimmerli D

更新日期：2006-08-15 00:00:00

abstract：:Two new antiinflammatory macrolides, lobophorins A and B (1 and 2), have been isolated from fermentation broths of a marine bacterium isolated from the surface the Caribbean brown alga Lobophora variegata (Dictyotales). The new compounds, distantly related to antibiotics of the kijanimicin class, are potent inhibitors...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jiang ZD,Jensen PR,Fenical W

更新日期：1999-07-19 00:00:00

abstract：:Structure-activity relationship studies directed toward improving the metabolic stability of compound 1 resulted in the identification of 3-[5-(3,5-difluorophenyl)-3-({[(1S,3R)-3-fluorocyclopentyl]amino}methyl)-4-methyl-1H-pyrazol-1-yl]propanenitrile 39 (MK-1925) as a selective, orally available and brain-penetrable o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kobayashi K,Tsujita T,Ito H,Ozaki S,Tani T,Ishii Y,Okuda S,Tadano K,Fukuroda T,Ohta H,Okamoto O

更新日期：2009-08-15 00:00:00

abstract：:Glutathione reductase (GR), is responsible for the existence of GSH molecule, a crucial antioxidant against oxidative stress reagents. The antimalarial activities of some redox active compounds are attributed to their inhibition of antioxidant flavoenzyme glutathione reductase, and inhibitors are therefore expected to...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sentürk M,Talaz O,Ekinci D,Cavdar H,Küfrevioğlu OI

更新日期：2009-07-01 00:00:00

abstract：:RO4396686 is a small molecule KDR, FGFR, and PDGFR inhibitor with good pharmacokinetic properties in rodents. In a mouse corneal neovascularization assay, this compound inhibited VEGF-induced angiogenesis. Tested in a H460a xenograft tumor model this agent effected significant tumor growth inhibition at doses as low a...

journal_title：Bioorganic & medicinal chemistry letters

authors： McDermott LA,Higgins B,Simcox M,Luk KC,Nevins T,Kolinsky K,Smith M,Yang H,Li JK,Chen Y,Ke J,Mallalieu N,Egan T,Kolis S,Railkar A,Gerber L,Liu JJ,Konzelmann F,Zhang Z,Flynn T,Morales O,Chen Y

更新日期：2006-04-01 00:00:00

abstract：:NCSi-gb is a neocarzinostatin chromophore (NCS-chrom) metabolite which binds strongly to certain two-base DNA bulges. Compared with previously reported NCSi-gb analogues, a new analogue with a different aminoglycoside position was synthesized, and it showed strong fluorescence and improved binding and sequence selecti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiao Z,Kappen LS,Goldberg IH

更新日期：2006-06-01 00:00:00

abstract：:In the screening search for Hepatitis B virus inhibitory agents from medicinal plants, the ethanol extract of Piper longum Linn. was found to possess superior anti-HBV activity in vitro. Bioassay-guided fractionation coupled with repeated purification resulted in the isolation of four new compounds, involving two new ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jiang ZY,Liu WF,Zhang XM,Luo J,Ma YB,Chen JJ

更新日期：2013-04-01 00:00:00

abstract：:The structure-based design, synthesis, and anticancer activity of novel inhibitors of protein kinase CK2 are described. Using pyrazolo[1,5-a][1,3,5]triazine as the core scaffold, a structure-guided series of modifications provided pM inhibitors with microM-level cytotoxic activity in cell-based assays with prostate an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nie Z,Perretta C,Erickson P,Margosiak S,Almassy R,Lu J,Averill A,Yager KM,Chu S

更新日期：2007-08-01 00:00:00

abstract：:Many membrane-associated proteins are involved in various signaling pathways, including the phosphoinositide 3-kinase (PI3K) pathway, which has key roles in diverse cellular processes. Disruption of the activities of these proteins is involved in the development of disease in humans, making these proteins promising ta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kang Y,Kim BG,Kim S,Lee Y,Yoon Y

更新日期：2017-02-01 00:00:00

abstract：:A protocol applicable for the synthesis of an oseltamivir positron emission tomography (PET) tracer was developed. Acetylation of amine 3 with CH(3)COCl, followed by deprotection and aqueous workup, produced oseltamivir 4 from 3 within 10 min. The obtained 4 was sufficiently pure for PET studies. This method can be ex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morita M,Sone T,Yamatsugu K,Sohtome Y,Matsunaga S,Kanai M,Watanabe Y,Shibasaki M

更新日期：2008-01-15 00:00:00

abstract：:A series of derivatives of the new ring system pyrrolo[2,3-h]quinoline-2-one was synthesized and evaluated as photoreagents toward cultured human tumor cells. Remarkable phototoxycity resulted for some derivatives, especially those bearing the phenyl group at the 7-position. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barraja P,Diana P,Lauria A,Montalbano A,Almerico AM,Dattolo G,Cirrincione G,Viola G,Dall'Acqua F

更新日期：2003-08-18 00:00:00

abstract：:6-Nitroquipazine has been known as one of the most potent and selective inhibitors of serotonin transporter in vitro and in vivo. Nine derivatives of 6-nitroquipazine were synthesized and tested for their potential abilities to displace [3H]citalopram binding to the rat cortical membranes. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee BS,Chu S,Lee BC,Chi DY,Choe YS,Jeong KJ,Jin C

更新日期：2000-07-17 00:00:00

abstract：:A number of new amine scaffolds with good inhibitory activity in the ADP-induced platelet aggregation assay have been found to be potent antagonists of the P2Y1 receptor. SAR optimization led to the identification of isoindoline 3c and piperidine 4a which showed good in vitro binding and functional activities, as well...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ruel R,L'Heureux A,Thibeault C,Lapointe P,Martel A,Qiao JX,Hua J,Price LA,Wu Q,Chang M,Zheng J,Huang CS,Wexler RR,Rehfuss R,Lam PY

更新日期：2013-12-15 00:00:00

abstract：:Synthesis of the potent antiplasmodial 4-aminoquinoline, phenylequine (PQ), is reported for the first time. PQ and the two analogues show increased efficacy in moving from the chloroquine sensitive D10 to the chloroquine resistant K1 strain in vitro. The in vivo efficacy of PQ, and salts thereof, have been determined ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Blackie MA,Yardley V,Chibale K

更新日期：2010-02-01 00:00:00

abstract：:Post-translational modulation of eIF4E through phosphorylation by Mnks is highly integral to the pathogenesis of different cancers. Therefore, inhibition of Mnks offers a strategy for cancer treatment. Herein, a series of 2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione derivatives is presented as Mnk in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Abdelaziz AM,Basnet SKC,Islam S,Li M,Tadesse S,Albrecht H,Gerber C,Yu M,Wang S

更新日期：2019-09-15 00:00:00

abstract：:Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hu CH,Wang TC,Qiao JX,Haque L,Chen AYA,Taylor DS,Ying X,Onorato JM,Galella M,Shen H,Huang CS,Toussaint N,Li YX,Abell L,Adam LP,Gordon D,Wexler RR,Finlay HJ

更新日期：2018-12-15 00:00:00

abstract：:Lead Generation represents a critical drug discovery phase where chemical starting points and their respective mechanism of action, quality, and potential liabilities are largely predefined. Recent advances such as DNA-encoded libraries or fragment-, chemical biology-, and virtual screening-based approaches are today ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Holenz J,Stoy P

更新日期：2019-02-15 00:00:00

abstract：:We identified a novel class of triazolothienopyrimidine (TTPM) compounds as potent HIV-1 replication inhibitors during a high-throughput screening campaign that evaluated more than 200,000 compounds using a cell-based full replication assay. Herein, we report the optimization of the antiviral activity in a cell-based ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim J,Kwon J,Lee D,Jo S,Park DS,Choi J,Park E,Hwang JY,Ko Y,Choi I,Ju MK,Ahn J,Kim J,Han SJ,Kim TH,Cechetto J,Nam J,Ahn S,Sommer P,Liuzzi M,No Z,Lee J

更新日期：2013-01-01 00:00:00

abstract：:A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Antoszczak M,Maj E,Stefańska J,Wietrzyk J,Janczak J,Brzezinski B,Huczyński A

更新日期：2014-04-01 00:00:00

abstract：:Chaetocin (1), a structurally complex epidithiodiketopiperazine (ETP) alkaloid produced by Chaetomium minutum, is a potent inhibitor of protein lysine methyltransferase G9a, which plays important roles in many biological processes. Here we present our synthetic investigations to identify a simple prototype G9a inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujishiro S,Dodo K,Iwasa E,Teng Y,Sohtome Y,Hamashima Y,Ito A,Yoshida M,Sodeoka M

更新日期：2013-02-01 00:00:00

abstract：:Several unnatural derivatives of narciclasine were prepared in which the C-7 carbon was replaced with nitrogen. The 7-aza derivative and its N-oxide were prepared by the coupling of iodopicolinic acid with a conduramine unit derived chemoenzymatically from bromobenzene. Intramolecular Heck reaction was used to constru...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vshyvenko S,Reisenauer MR,Rogelj S,Hudlicky T

更新日期：2014-09-01 00:00:00

abstract：:The structure-activity relationship (SAR) of the vinyl pyridine region of himbacine derived thrombin receptor (PAR-1) antagonists is described. A 2-vinylpyridyl ring substituted with an aryl or a heteroaryl group at the 5-position showed the best overall PAR-1 affinity and pharmacokinetic properties. One of the newly ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xia Y,Chackalamannil S,Clasby M,Doller D,Eagen K,Greenlee WJ,Tsai H,Agans-Fantuzzi J,Ahn HS,Boykow GC,Hsieh Y,Lunn CA,Chintala M

更新日期：2007-08-15 00:00:00

abstract：:Novel bendazac analogues and their salts have been designed and prepared. The resulting compounds (13c-d, 15c, 17c) showed very good aqueous solubility (>100 mg/mL). An in vitro assay showed that most of the resulting compounds had potent protective activity against the oxidative damage. Particularly, compound 13d was...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shen H,Gou S,Shen J,Zhu Y,Zhang Y,Chen X

更新日期：2010-04-01 00:00:00

abstract：:Four novel mononuclear complexes, [Cd(L)2·2H2O] (1), [Ni(L)2·2H2O] (2) [Cu(L)2·H2O] (3), and [Zn(L)2·2H2O] (4) (CCDC numbers: 1444630-1444633 for complexes 1-4) (HL=4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid) were synthesized, and have been characterized by IR spectroscopy, elemental analysis, and X-ray crysta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang DD,Chen YN,Wu YS,Wang R,Chen ZJ,Qin J,Qian SS,Zhu HL

更新日期：2016-07-15 00:00:00