Lithospermic acid derivatives from Lithospermum erythrorhizon increased expression of serine palmitoyltransferase in human HaCaT cells.

abstract：:A novel curcumin mimic library (14a-14h and 15a-15h) possessing variously substituted benzimidazole groups was synthesized through the aldol reaction of (E)-4-(4-hydroxy-3-methoxyphenyl)but-3-en-2-one (7) or (E)-4-(3-hydroxy-4-methoxyphenyl)but-3-en-2-one (13) with diversely substituted benzimidazolyl-2-carbaldehyde (...

journal_title：Bioorganic & medicinal chemistry letters

authors： Woo HB,Eom YW,Park KS,Ham J,Ahn CM,Lee S

更新日期：2012-01-15 00:00:00

abstract：:The synthesis of a series of novel 4-substituted 2,3,6,7-tetrahydrobenzo [1,2-b;4,5-b']difuran-1H-imidazolium salts is presented. The biological properties of the compounds were evaluated in vitro against a panel of human tumor cell lines. Results suggest that the 5,6-dimethyl-benzimidazole or 2-methyl-benzimidazole r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang CB,Liu Y,Liu ZF,Duan SZ,Li MY,Chen W,Li Y,Zhang HB,Yang XD

更新日期：2017-04-15 00:00:00

abstract：:Structural modifications to the peptide deformylase inhibitor BB-3497 are described. In this paper, we describe the initial SAR around this lead for modifications to both the P2' and P3' side chains. Enzyme inhibition and antibacterial activity data revealed that a variety of substituents are tolerated at the P2' and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Davies SJ,Ayscough AP,Beckett RP,Clements JM,Doel S,Pratt LM,Spavold ZM,Thomas SW,Whittaker M

更新日期：2003-08-18 00:00:00

abstract：:In the present study we report the synthesis of halogen-substituted phenanthrene β-diketo acids as new HIV-1 integrase inhibitors. The target phenanthrenes were obtained using both standard thermal- and microwave-assisted synthesis. 4-(6-Chlorophenanthren-2-yl)-2,4-dioxobutanoic acid (18) was the most active compound ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharma H,Sanchez TW,Neamati N,Detorio M,Schinazi RF,Cheng X,Buolamwini JK

更新日期：2013-11-15 00:00:00

abstract：:IkappaB kinase beta (IKK-beta) is a serine-threonine protein kinase critically involved in the activation of the transcription factor Nuclear Factor kappa B (NF-kappaB) in response to various inflammatory stimuli. We have identified a small molecule inhibitor of IKK-beta. Optimization of the lead compound resulted in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Murata T,Shimada M,Sakakibara S,Yoshino T,Kadono H,Masuda T,Shimazaki M,Shintani T,Fuchikami K,Sakai K,Inbe H,Takeshita K,Niki T,Umeda M,Bacon KB,Ziegelbauer KB,Lowinger TB

更新日期：2003-03-10 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：:Novel, low brain penetrant, orally bioavailable CB1 receptor agonists were designed starting from a mature lead series of potent brain penetrant CB1 receptor agonists. Increasing the calculated polar surface area was found to be a good strategy for reducing brain penetration whilst retaining drug-like properties. This...

journal_title：Bioorganic & medicinal chemistry letters

authors： Adam JM,Clark JK,Davies K,Everett K,Fields R,Francis S,Jeremiah F,Kiyoi T,Maidment M,Morrison A,Ratcliffe P,Prosser A,Schulz J,Wishart G,Baker J,Boyce S,Campbell R,Cottney JE,Deehan M,Martin I

更新日期：2012-04-15 00:00:00

abstract：:Mammalian target of rapamycin (mTOR) is a promising target for the development of anticancer medicines. Here, we report the first example for a successful application of the structure-based virtual screening to identify new mTOR inhibitors. Using the scoring function improved by implementing the ligand solvation effec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park H,Choe H,Hong S

更新日期：2014-02-01 00:00:00

abstract：:Chimeric oligonucleotides comprised of alternating residues of 2'-deoxy-2'-fluoro-D-arabinonucleic acid (2'F-ANA) and DNA were synthesized and evaluated for an important antisense property-the ability to elicit ribonuclease H (RNase H) degradation of complementary RNA. Experiments used both human RNase HII and Escheri...

journal_title：Bioorganic & medicinal chemistry letters

authors： Min KL,Viazovkina E,Galarneau A,Parniak MA,Damha MJ

更新日期：2002-09-16 00:00:00

abstract：:A series of alpha-alkyl-alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Becker DP,DeCrescenzo G,Freskos J,Getman DP,Hockerman SL,Li M,Mehta P,Munie GE,Swearingen C

更新日期：2001-10-22 00:00:00

abstract：:MDM2 and MDMX are oncoproteins that negatively regulate the activity and stability of the tumor suppressor protein p53. The inhibitors of protein-protein interactions (PPIs) of MDM2-p53 and MDMX-p53 represent potential anticancer agents. In this study, a novel approach for identifying MDM2-p53 and MDMX-p53 PPI inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Noguchi T,Oishi S,Honda K,Kondoh Y,Saito T,Kubo T,Kaneda M,Ohno H,Osada H,Fujii N

更新日期：2013-07-01 00:00:00

abstract：:A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different hydroxyprolinamide P2 ligands were designed and synthesized. Variation of substitutions at the P2 significantly affected the enzyme inhibitory potency of the inhibitors. Compounds 2a and 2d showed excellent enzyme inhibitory activi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao BL,Zhang CM,Yin YZ,Tang LQ,Liu ZP

更新日期：2011-06-15 00:00:00

abstract：:Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell line...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alaoui S,Dufies M,Driowya M,Demange L,Bougrin K,Robert G,Auberger P,Pagès G,Benhida R

更新日期：2017-05-01 00:00:00

abstract：:The SAR studies to optimise both potency and rate of clearance in the rat for a series of pyrimidine and pyridine based VLA-4 antagonists are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Porter JR,Archibald SC,Brown JA,Childs K,Critchley D,Head JC,Hutchinson B,Parton TA,Robinson MK,Shock A,Warrellow GJ,Zomaya A

更新日期：2002-06-17 00:00:00

abstract：:In order to define the structural requirements of phenylthiourea (PTU), a series of thiourea and thiosemicarbazone analogs were prepared and evaluated as inhibitors of melanogenesis in melanoma B16 cells. The most potent analog was 2-(4-tert-butylbenzylidene)hydrazinecarbothioamide (1u) with an IC(50) value of 2.7 mic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thanigaimalai P,Hoang TA,Lee KC,Bang SC,Sharma VK,Yun CY,Roh E,Hwang BY,Kim Y,Jung SH

更新日期：2010-05-01 00:00:00

abstract：:A scaffold hopping strategy was successfully applied in discovering 2-aminooxazole amides as potent DGAT1 inhibitors for the treatment of dyslipidemia. Further optimization in potency and PK properties resulted in a lead series with oral in vivo efficacy in a mouse postprandial triglyceridemia (PPTG) assay. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim HM,Smith MD,Kim JH,Caplen MA,Chan TY,McKittrick BA,Cook JA,van Heek M,Lachowicz J

更新日期：2013-12-01 00:00:00

abstract：:Four new lanostane triterpenes, butyl lucidenate P (1), butyl lucidenate D(2) (2), butyl lucidenate E(2) (3) and butyl lucidenate Q (4) along with 11 known compounds (5-15) were isolated from the fruiting bodies of Ganoderma lucidum. Their chemical structures were established mainly by 1D and 2D NMR techniques and mas...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tung NT,Cuong TD,Hung TM,Lee JH,Woo MH,Choi JS,Kim J,Ryu SH,Min BS

更新日期：2013-03-01 00:00:00

abstract：:We designed and synthesized an estrogen receptor (ER) down-regulator (5), which is a derivative of tamoxifen with a long alkyl side chain. Compound 5 effectively reduced ER protein levels in MCF-7 cells and had an antagonistic effect. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shoda T,Okuhira K,Kato M,Demizu Y,Inoue H,Naito M,Kurihara M

更新日期：2014-01-01 00:00:00

abstract：:Dysregulation of cell signalling processes caused by an enhanced activity of protein kinases mainly contributes to cancer progression. Protein kinase inhibitors have been established as promising drugs that inhibit such overactive protein kinases in cancer cells. The formation of metastases, which makes a therapy diff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mahmoud KA,Krug M,Wersig T,Slynko I,Schächtele C,Totzke F,Sippl W,Hilgeroth A

更新日期：2014-04-15 00:00:00

abstract：:VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has proved to be a promising target for the development of therapeutics for the treatment of a variety of human cancers. Here, we report the first example of a successful application of the structure-based virtual screening to identify novel BRAF inhibitors...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park H,Choi H,Hong S,Hong S

更新日期：2011-10-01 00:00:00

abstract：:Cannabinoid CB(1) receptor antagonists reduce body weight in rodents and humans, but their clinical utility as anti-obesity agents is limited by centrally mediated side effects. Here, we describe the first mixed CB(1) antagonist/CB(2) agonist, URB447 ([4-amino-1-(4-chlorobenzyl)-2-methyl-5-phenyl-1H-pyrrol-3-yl](pheny...

journal_title：Bioorganic & medicinal chemistry letters

authors： LoVerme J,Duranti A,Tontini A,Spadoni G,Mor M,Rivara S,Stella N,Xu C,Tarzia G,Piomelli D

更新日期：2009-02-01 00:00:00

abstract：:The synthesis and evaluation of antiplasmodial activity of benzothiazole, benzimidazole, benzoxazole and pyridine analogues of amodiaquine is hereby reported. Benzothiazole and benzoxazole analogues with a protonatable tertiary nitrogen atom possessed excellent activity against the W2 and K1 chloroquine resistant stra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ongarora DS,Gut J,Rosenthal PJ,Masimirembwa CM,Chibale K

更新日期：2012-08-01 00:00:00

abstract：:In an effort to better understand the conformational preferences that inform the biological activity of naltrexone and related naltrexol derivatives, a new synthesis of the restricted analog 3-OBn-6β,14-epoxymorphinan 4 is described. 4 was synthesized starting from naltrexone in 50% overall yield, proceeding through t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Martin DJ,FitzMorris PE,Li B,Ayestas M,Sally EJ,Dersch CM,Rothman RB,Deveau AM

更新日期：2012-11-15 00:00:00

abstract：:Described here is the asymmetric synthesis of iminosugar 2b, a Lipid II analog, designed to mimic the transition state of transglycosylation catalyzed by the bacterial transglycosylase. The high density of functional groups, together with a rich stereochemistry, represents an extraordinary challenge for chemical synth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang X,Krasnova L,Wu KB,Wu WS,Cheng TJ,Wong CH

更新日期：2018-09-01 00:00:00

abstract：:A novel series of 4-arylphthalazin-1(2H)-one linked to arylpiperidines were synthesized and evaluated as MCH-R1 antagonists. The results of an extensive SAR study probing the effects of substituents on the 4-arylphthalazin-1(2H)-one C-4 aryl group led to the identification of the 4-(3,4-difluorophenyl) derivative as a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lim CJ,Kim SH,Lee BH,Oh KS,Yi KY

更新日期：2012-01-01 00:00:00

abstract：:A new series of 3,6-diaryl-1H-pyrazolo[3,4-b]pyridine compounds have been discovered as potent anaplastic lymphoma kinase (ALK) inhibitors. The 4-hydroxyphenyl in the 6-position of 1H-pyrazolo[3,4-b]pyridine were crucial and a fluorine atom substitution could give promising inhibitory activity. The IC50 of compound 9v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen C,Pan P,Deng Z,Wang D,Wu Q,Xu L,Hou T,Cui S

更新日期：2019-04-01 00:00:00

abstract：:A new class of NO-donor phenol derivatives is described. The products were obtained by joining appropriate phenols with either nitrooxy or 3-phenylsulfonylfuroxan-4-yloxy moieties. All the compounds proved to inhibit the ferrous salt/ascorbate induced lipidic peroxidation of membrane lipids of rat hepatocytes. They we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cena C,Boschi D,Tron GC,Chegaev K,Lazzarato L,Di Stilo A,Aragno M,Fruttero R,Gasco A

更新日期：2004-12-20 00:00:00

abstract：:Alzheimer's disease is characterized by the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. We previously developed [(18)F]fluoropropylcurcumin ([(18)F]FP-curcumin), which demonstrated excellent binding affinity (K(i)=0.07 nM) for Aβ(1-40) aggregates and good pharmacokinetics in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee I,Yang J,Lee JH,Choe YS

更新日期：2011-10-01 00:00:00

abstract：:Two (99m)Tc/Re complexes based on flavone and aurone were tested as potential probes for imaging β-amyloid plaques using single photon emission computed tomography. Both (99m)Tc-labeled derivatives showed higher affinity for Aβ(1-42) aggregates than did (99m)Tc-BAT. In sections of brain tissue from an animal model of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ono M,Ikeoka R,Watanabe H,Kimura H,Fuchigami T,Haratake M,Saji H,Nakayama M

更新日期：2010-10-01 00:00:00

abstract：:The discovery of a series of novel, potent, and selective blockers of the cyclic nucleotide-modulated channel HCN1 is disclosed. Here we report an SAR study around a series of selective blockers of the HCN1 channel. Utilization of a high-throughput VIPR assay led to the identification of a novel series of 2,2-disubsti...

journal_title：Bioorganic & medicinal chemistry letters

authors： McClure KJ,Maher M,Wu N,Chaplan SR,Eckert WA 3rd,Lee DH,Wickenden AD,Hermann M,Allison B,Hawryluk N,Breitenbucher JG,Grice CA

更新日期：2011-09-15 00:00:00