Furans with basic side chains: synthesis and biological evaluation of a novel series of antagonists with selectivity for the estrogen receptor alpha.

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：:Virtual screening, a fast, computational approach to identify drug leads [Perola, E.; Xu, K.; Kollmeyer, T. M.; Kaufmann, S. H.; Prendergast, F. G. J. Med. Chem.2000, 43, 401; Miller, M. A. Nat. Rev. Drug Disc.2002, 1 220], is limited by a known challenge in crystallographically determining flexible regions of protein...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dooley AJ,Shindo N,Taggart B,Park JG,Pang YP

更新日期：2006-02-15 00:00:00

abstract：:N-Phthaloyl 3-amino-3-arylpropionic acid analogs of thalidomide that are potent inhibitors of tumor necrosis factor-alpha are reported. These compounds were found to be potent inhibitors of phosphodiesterase 4. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Muller GW,Shire MG,Wong LM,Corral LG,Patterson RT,Chen Y,Stirling DI

更新日期：1998-10-06 00:00:00

abstract：:Three new pseudo-symmetrical tamoxifen derivatives, RID-B (15), C (16), and D (17), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of the pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 15 strongly inhibits the viability of HL-6...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shiina I,Sano Y,Nakata K,Kikuchi T,Sasaki A,Ikekita M,Hasome Y

更新日期：2007-05-01 00:00:00

abstract：:Herein we describe the SAR of 1,5-biaryl pyrrole derivatives, with substituents in the 6-position of the benzoic acid moiety, as EP(1) receptor antagonists. Substitution at this position was well tolerated and led to the identification of several analogues with high affinity for the EP(1) receptor that displayed good ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hall A,Brown SH,Chessell IP,Chowdhury A,Clayton NM,Coleman T,Giblin GM,Hammond B,Healy MP,Johnson MR,Metcalf A,Michel AD,Naylor A,Novelli R,Spalding DJ,Sweeting J,Winyard L

更新日期：2007-02-15 00:00:00

abstract：:The present work reports on the preparation of glass surfaces coated with NPPOC-protected aminooxy groups and their use for the patterning of oligonucleotides on glass slides and in capillary tubes. The method involves the use of surfaces coated with amino groups using (gamma-aminopropyl)triethoxy silane and subsequen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dendane N,Hoang A,Defrancq E,Vinet F,Dumy P

更新日期：2008-04-15 00:00:00

abstract：:p38alpha Mitogen Activated Protein Kinase (MAP kinase) is an intracellular soluble serine threonine kinase. p38alpha kinase is activated in response to cellular stresses, growth factors and cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). The central role of p38alpha activation in se...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mavunkel BJ,Chakravarty S,Perumattam JJ,Luedtke GR,Liang X,Lim D,Xu YJ,Laney M,Liu DY,Schreiner GF,Lewicki JA,Dugar S

更新日期：2003-09-15 00:00:00

abstract：:Bis-(aryl)thioureas were found to be potent and selective inhibitors of cytomegalovirus (CMV) in cultured HFF cells. Of these, the thiazole analogue 38 was investigated as a potential development candidate. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bloom JD,DiGrandi MJ,Dushin RG,Curran KJ,Ross AA,Norton EB,Terefenko E,Jones TR,Feld B,Lang SA

更新日期：2003-09-01 00:00:00

abstract：:A high throughput screen allowed the identification of N-hydroxyimide inhibitors of ERCC1-XPF endonuclease activity with micromolar potency, but they showed undesirable selectivity profiles against FEN-1. A scaffold hop to a hydroxypyrimidinone template gave compounds with similar potency but allowed selectivity to be...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chapman TM,Wallace C,Gillen KJ,Bakrania P,Khurana P,Coombs PJ,Fox S,Bureau EA,Brownlees J,Melton DW,Saxty B

更新日期：2015-10-01 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：:Three new polyhydroxytriterpenoid derivatives, 23-O-neochebuloylarjungenin 28-O-β-d-glycopyranosyl ester (1), 23-O-4'-epi-neochebuloylarjungenin (2), and 23-O-galloylpinfaenoic acid 28-O-β-d-glucopyranosyl ester (17) were isolated from the fruits of Terminalia chebula Retz. along with fourteen known ones. Their struct...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee DY,Yang H,Kim HW,Sung SH

更新日期：2017-01-01 00:00:00

abstract：:A novel series of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R) is reported. Members of this series have been identified, which exhibit sub-micromolar binding affinity for the MC4-R, functional potency <100nM, and good oral exposure in rat. Antagonists of the MC4-R are potentially u...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marsilje TH,Roses JB,Calderwood EF,Stroud SG,Forsyth NE,Blackburn C,Yowe DL,Miao W,Drabic SV,Bohane MD,Daniels JS,Li P,Wu L,Patane MA,Claiborne CF

更新日期：2004-07-16 00:00:00

abstract：:The epithelial-mesenchymal transition (EMT) is an important cellular process during which polarized epithelial cells become motile mesenchymal cells, which promote cancer metastasis. Ginger, the rhizome of Zingiber officinale, is extensively used in cooking worldwide and also as a traditional medicinal herb with antio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim YJ,Jeon Y,Kim T,Lim WC,Ham J,Park YN,Kim TJ,Ko H

更新日期：2017-02-15 00:00:00

abstract：:Two series of triamino pyrimidines and a series of triamino pyridines have been synthesized and their structure-activity relationships evaluated for activity at the H(4) receptor in competitive binding and functional assays. Small structural changes in these three hetereoaromatic cores influenced the functional activi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Meduna SP,Savall BM,Cai H,Edwards JP,Thurmond RL,McGovern PM

更新日期：2011-05-15 00:00:00

abstract：:The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh K,Tanui R,Gameiro A,Eisenberg G,Colas C,Schlessinger A,Grewer C

更新日期：2017-02-01 00:00:00

abstract：:Novel derivatives of the D-glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol bearing lipophilic aliphatic or aromatic amides attached to C-1 have been found to inhibit beta-glucosidase from Agrobacterium sp. in the nanomolar range. One of them, a coumarin derivative, ranks amongst the most active compounds in the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wrodnigg TM,Withers SG,Stütz AE

更新日期：2001-04-23 00:00:00

abstract：:Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patterson JT,Isaacson J,Kerwin L,Atassi G,Duggal R,Bresson D,Zhu T,Zhou H,Fu Y,Kaufmann GF

更新日期：2017-12-15 00:00:00

abstract：:Apoptotic cell death is the cause of the loss of insulin-producing β-cells in all forms of diabetes mellitus. The identification of small molecules capable of protecting cytokine-induced apoptosis could form the basis of useful therapeutic interventions. Here in, we present the discovery and synthesis of new benzimida...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zawawi NK,Rajput SA,Taha M,Ahmat N,Ismail NH,Abdullah N,Khan KM,Choudhary MI

更新日期：2015-10-15 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：:Stable nitroxides are potential antioxidant drugs. In this study, we have linked nitroxide to natural amino acids with the aim to improve therapeutic activity. The radical scavenging activities of two nitronyl nitroxide-amino acid conjugates (NNR and NNK) were evaluated in PC 12 cell survival assays. The NO scavenging...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bi W,Cai J,Xue P,Zhang Y,Liu S,Gao X,Li M,Wang Z,Baudy-Floc'h M,Green SA,Bi L

更新日期：2008-03-15 00:00:00

abstract：:A total of 24 pirfenidone derivatives were designed, synthesized and evaluated for their inhibitory activity against the human lung fibroblast cell line MRC-5. These compounds showed the remarkable proliferation inhibition against MRC-5 compared to pirfenidone as the positive control. The possible mechanism of this ki...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ma Z,Pan Y,Huang W,Yang Y,Wang Z,Li Q,Zhao Y,Zhang X,Shen Z

更新日期：2014-01-01 00:00:00

abstract：:A series of fluconazole analogues 5-20 incorporating azaindole and indole moieties were prepared using oxirane intermediates synthesized under microwave irradiation. All of the compounds were evaluated in vitro against two clinically important fungi, Candida albicans and Aspergillus fumigatus. Four derivatives 6, 13, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lebouvier N,Pagniez F,Duflos M,Le Pape P,Na YM,Le Baut G,Le Borgne M

更新日期：2007-07-01 00:00:00

abstract：:Metabolites of the potent DP antagonist, MK-0524, were generated using in vitro systems including hepatic microsomes and hepatocytes. Four metabolites (two hydroxylated diastereomers, a ketone and an acyl glucuronide) were characterized by LC-MS/MS and 1H NMR. Larger quantities of these metabolites were prepared by ei...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nicoll-Griffith DA,Seto C,Aubin Y,Lévesque JF,Chauret N,Day S,Silva JM,Trimble LA,Truchon JF,Berthelette C,Lachance N,Wang Z,Sturino C,Braun M,Zamboni R,Young RN

更新日期：2007-01-15 00:00:00

abstract：:Retinoid X Receptor (RXR) specific ligands are currently being investigated for the treatment of metabolic diseases such as type II diabetes. We report the synthesis of conformationally locked retinoids, which are potent RXR selective ligands, and the attempted synthesis of 9-cyclopropyl locked analogs of RA and 9-cis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vuligonda V,Garst ME,Chandraratna RA

更新日期：1999-02-22 00:00:00

abstract：:Two new photoactive compounds (1 and 2) derived from the 9-amidoacridine chromophore have been synthesized and fully characterized. Their abilities to produce singlet oxygen upon irradiation have been compared. The synthesized compounds show very different self-aggregating properties since only 1 present a strong tend...

journal_title：Bioorganic & medicinal chemistry letters

authors： Felip-León C,Martínez-Arroyo O,Díaz-Oltra S,Miravet JF,Apostolova N,Galindo F

更新日期：2018-03-01 00:00:00

abstract：:A series of new triazole fused imidazo[2,1-b]thiazole hybrids (9a-u) were designed, synthesized and evaluated as antimicrobial agents. Compounds 9c, 9d, 9e, 9j and 9l showed promising broad spectrum antimicrobial activity. Further, compound 9c exhibited significant anti-biofilm activity with single and mixed biofilm d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shareef MA,Sirisha K,Sayeed IB,Khan I,Ganapathi T,Akbar S,Ganesh Kumar C,Kamal A,Nagendra Babu B

更新日期：2019-10-01 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 SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a butynyloxy P1' group was explored. In particular, compound 5k has excellent in vitro potency against TACE enzyme and in cells, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Levin JI,Chen JM,Laakso LM,Du M,Du X,Venkatesan AM,Sandanayaka V,Zask A,Xu J,Xu W,Zhang Y,Skotnicki JS

更新日期：2005-10-01 00:00:00

abstract：:The 2,4,6-trimethylpyridinium derivative of histamine is an effective activator of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). However, unlike other CA activators, which bind at the entrance of the active site cavity, an X-ray crystal structure of hCA II in complex with the 1-[2-(1H-imidazol-4-yl)-ethyl]-2,4,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dave K,Ilies MA,Scozzafava A,Temperini C,Vullo D,Supuran CT

更新日期：2011-05-01 00:00:00

abstract：:The design, synthesis, and enzyme kinetics evaluation of a transition-state inhibitor of glyoxalase-I is described. The union of the hydroxamic acid zinc-chelator with a urea isostere for the glu-cys amide bond led to a glutathione analog which retained inhibitory potency toward glyoxalase-I while possessing resistanc...

journal_title：Bioorganic & medicinal chemistry letters

authors： More SS,Vince R

更新日期：2006-12-01 00:00:00