Structure-activity relationship of a series of cyclohexylpiperidines bearing an amide side chain as antagonists of the human melanocortin-4 receptor.

abstract：:Esculentoside A (EsA) has been reported to possess anti-inflammatory activity and selective inhibitory activity towards cyclooxygenase-2. A series of derivatives of EsA were synthesized by converting the C-28 carboxylic acid group into amides. The haemolytic activity and inhibitory activity towards cyclooxygenase-2 we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wu F,Yi Y,Sun P,Zhang D

更新日期：2007-12-01 00:00:00

abstract：:Oxomollugin (2) is a degradation product of mollugin (1) and a potent inhibitor of NO-production including nuclear factor kappa B signals. In our endeavor to develop a potent anti-inflammatory compound, we synthesized several aza-derivatives of oxomollugin (2) and evaluated their NO-production inhibitory activity. Aza...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishino H,Nakajima Y,Kakubari Y,Asami N,Deguchi J,Nugroho AE,Hirasawa Y,Kaneda T,Kawasaki Y,Goda Y,Morita H

更新日期：2016-01-15 00:00:00

abstract：:Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of the S1P signaling pathway has attracted significant attention because alteration of S1P levels is linked to several disease states including cancer, fibrosis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Congdon MD,Childress ES,Patwardhan NN,Gumkowski J,Morris EA,Kharel Y,Lynch KR,Santos WL

更新日期：2015-11-01 00:00:00

abstract：:A series of substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles has been prepared as Src kinase inhibitors. Optimal activity is observed with compounds that have basic amines attached via the para position of the 7-phenyl ring, and a hydrogen atom at the C-6 position. The best compounds are low nanomolar inhibitor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Berger D,Dutia M,Powell D,Wissner A,DeMorin F,Raifeld Y,Weber J,Boschelli F

更新日期：2002-10-21 00:00:00

abstract：:Two regioisomeric isoxazoline monoacetates 1 and 2 were synthesized from the corresponding diacetate 3 via PPL or PLE catalyzed hydrolysis. With both the enzymes, the initial regioselectivity (approximately 3-4:1) was offset by an intramolecular acyl transfer. In addition to a non-enzymatic catalysis for the acyl tran...

journal_title：Bioorganic & medicinal chemistry letters

authors： Basak A,Bisai S

更新日期：2005-05-16 00:00:00

abstract：:Tetrapeptides derived from glycine and beta-alanine were hooked at the C-3beta position of the modified cholic acid to realize novel linear tetrapeptide-linked cholic acid derivatives. All the synthesized compounds were tested against a wide variety of microorganisms (gram-negative bacteria, gram-positive bacteria and...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bavikar SN,Salunke DB,Hazra BG,Pore VS,Dodd RH,Thierry J,Shirazi F,Deshpande MV,Kadreppa S,Chattopadhyay S

更新日期：2008-10-15 00:00:00

abstract：:4-Aryl-5-pyrimidyl based cytokine synthesis inhibitors that contain a novel monocyclic, pyrazolone heterocyclic core are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-alpha production. One of the compounds (6e) was found to be efficacious in the rat iodoacetate (RIA) in vivo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Golebiowski A,Townes JA,Laufersweiler MJ,Brugel TA,Clark MP,Clark CM,Djung JF,Laughlin SK,Sabat MP,Bookland RG,VanRens JC,De B,Hsieh LC,Janusz MJ,Walter RL,Webster ME,Mekel MJ

更新日期：2005-05-02 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

abstract：:A series of novel, potent and selective pyrido[1,2-a]pyrazine dopamine D4 receptor antagonists are reported including CP-293,019 (D4 Ki = 3.4 nM, D2 Ki > 3,310 nM), which also inhibits apomorphine-induced hyperlocomotion in rats after oral dosing. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sanner MA,Chappie TA,Dunaiskis AR,Fliri AF,Desai KA,Zorn SH,Jackson ER,Johnson CG,Morrone JM,Seymour PA,Majchrzak MJ,Faraci WS,Collins JL,Duignan DB,Prete Di CC,Lee JS,Trozzi A

更新日期：1998-04-07 00:00:00

abstract：:Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new drugs acting at the dopamine receptors (DR) as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous stud...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moreno L,Cabedo N,Ivorra MD,Sanz MJ,Castel AL,Carmen Álvarez M,Cortes D

更新日期：2013-09-01 00:00:00

abstract：:A novel series of malonamide derivatives was synthesized. These amides were shown to be potent and selective kappa opioid receptor agonists. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu GH,Gu M,Cassel JA,Belanger S,Graczyk TM,DeHaven RN,Conway-James N,Koblish M,Little PJ,DeHaven-Hudkins DL,Dolle RE

更新日期：2007-04-01 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：:The docking approach for the screening of designed small molecule ligands, led to the identification of a critical arginine residue in peptide deformylase for spiro cyclopropyl PDF inhibitor's extra hydrophobic binding, providing us a useful tool for searching more efficient PDF inhibitors to fight for horrifying anti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lv F,Chen C,Tang Y,Wei J,Zhu T,Hu W

更新日期：2016-08-01 00:00:00

abstract：:A library of conjugates of chromones and 2,4-thiazolidinedione has been synthesized by Knoevenagel condensation followed by reduction using hydrogen gas and Pd/C as a catalyst. Compounds 5c and 5e were most effective in lowering the blood glucose level comparable to standard drug pioglitazone. Compound 5e exhibited po...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nazreen S,Alam MS,Hamid H,Yar MS,Dhulap A,Alam P,Pasha MA,Bano S,Alam MM,Haider S,Kharbanda C,Ali Y,Pillai KK

更新日期：2014-07-15 00:00:00

abstract：:In order to exploit cyclophilin as a potential target for neurological drug design, we demonstrate in this presentation that several nonimmunosuppressant analogues of cyclosporin A, modified at the various positions in the 'effector' domain, are equipotent nerve growth agents compared to cyclosporin A. Our results sug...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wei L,Steiner JP,Hamilton GS,Wu YQ

更新日期：2004-09-06 00:00:00

abstract：:We report the discovery of a novel azetidine scaffold for colony stimulating factor-1 receptor (CSF-1R) Type II inhibitors by using a structure-based drug design (SBDD) based on a docking model. The work leads to the representative compound 4a with high CSF-1R inhibitory activity (IC50 = 9.1 nM). The obtained crystal ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ikegashira K,Ikenogami T,Yamasaki T,Hase Y,Yamaguchi T,Inagaki K,Doi S,Adachi T,Koga Y,Hashimoto H

更新日期：2019-01-01 00:00:00

abstract：:5'-Dipeptidyl derivatives of 5-fluorodeoxyuridine (FdU) (1a-d) were synthesized. These compounds are biologically inactive but can be activated by peptide deformylase, which removes the N-terminal formyl group of the dipeptide, to release the active drug FdU via an intramolecular cyclization reaction. Because the defo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wei Y,Pei D

更新日期：2000-05-15 00:00:00

abstract：:To elucidate the inhibitory action of acetogenins, the most potent inhibitors of mitochondrial complex I, we synthesized an acetogenin analogue which possesses a ubiquinone ring (i.e., the physiological substrate of complex I) in place of the alpha,beta-unsaturated gamma-lactone ring of natural acetogenins, and named ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yabunaka H,Abe M,Kenmochi A,Hamada T,Nishioka T,Miyoshi H

更新日期：2003-07-21 00:00:00

abstract：:A novel series of imidazo[1,5-a]pyrazines was synthesized and evaluated as corticotropin releasing hormone (CRH) receptor ligands. SAR studies focused primarily on dialkylamino side chain optimization. SAR of the aryl and small alkyl substituents was also explored. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hartz RA,Gilligan PJ,Nanda KK,Tebben AJ,Fitzgerald LW,Miller K

更新日期：2002-02-11 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：: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

abstract：:3-(N-Alkyl)aminopropylphosphonic acids are potent agonists of four of the five known sphingosine-1-phosphate (S1P) receptor subtypes. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hale JJ,Doherty G,Toth L,Li Z,Mills SG,Hajdu R,Ann Keohane C,Rosenbach M,Milligan J,Shei GJ,Chrebet G,Bergstrom J,Card D,Rosen H,Mandala S

更新日期：2004-07-05 00:00:00

abstract：:Novel polyhalo 2,4-diaminoquinazolines 3a-3d were prepared by reacting polyhaloisophthalonitriles with guanidine carbonate under solvent-free conditions and in the absence of a catalyst with good yields (74-95%). A series of highly functionalized 2,4-diaminoquinazolines 4-5 were then synthesized based on 3a-3c. The an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yan SJ,Zheng H,Huang C,Yan YY,Lin J

更新日期：2010-08-01 00:00:00

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：:A series of novel coumarin-benzimidazole hybrids, 3-(1H-benzo[d]imidazol-2-yl)-7-(substituted amino)-2H-chromen-2-one derivatives of biological interest were synthesized. Six out of the newly synthesized compounds were screened for in vitro antitumor activity against preliminary 60 tumor cell lines panel assay. A sign...

journal_title：Bioorganic & medicinal chemistry letters

authors： Paul K,Bindal S,Luxami V

更新日期：2013-06-15 00:00:00

abstract：:A series of compounds based on a 4-phenyl-2-phenylaminopyridine scaffold that are potent and selective inhibitors of Traf2- and Nck-interacting kinase (TNIK) activity are described. These compounds were used as tools to test the importance of TNIK kinase activity in signaling and proliferation in Wnt-activated colorec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ho KK,Parnell KM,Yuan Y,Xu Y,Kultgen SG,Hamblin S,Hendrickson TF,Luo B,Foulks JM,McCullar MV,Kanner SB

更新日期：2013-01-15 00:00:00

abstract：:The discovery and optimisation of novel, potent and selective small molecule inhibitors of the α-isoform of type III phosphatidylinositol-4-kinase (PI4Kα) are described. Lead compounds show cellular activity consistent with their PI4Kα potency inhibiting the accumulation of IP1 after PDGF stimulation and reducing cell...

journal_title：Bioorganic & medicinal chemistry letters

authors： Raubo P,Andrews DM,McKelvie JC,Robb GR,Smith JM,Swarbrick ME,Waring MJ

更新日期：2015-08-15 00:00:00

abstract：:The structure-based approaches were implemented to design and rationally select the molecules for synthesis and anti-HCV activity evaluation. The systematic structure-activity relationships of previously discovered molecules (types I, II, III) were analyzed to design new molecules (type IV) by bioisosteric replacement...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thiyagarajan A,Salim MT,Balaraju T,Bal C,Baba M,Sharon A

更新日期：2012-12-15 00:00:00

abstract：:STAT3 is a promising molecular target for the design of new anticancer drugs. In this paper, we report the design and synthesis of a conformationally constrained macrocyclic peptidomimetic 2 via click chemistry. Compound 2 was determined to bind to STAT3 with a K(i) value of 7.3 microM in a competitive fluorescence-po...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen J,Nikolovska-Coleska Z,Yang CY,Gomez C,Gao W,Krajewski K,Jiang S,Roller P,Wang S

更新日期：2007-07-15 00:00:00

abstract：:Optically active phenylpropanoic acid derivatives [(S)-5, and (R)-5] were prepared, and their affinities for peroxisome proliferator-activated receptor (PPAR)alpha and PPAR gamma were evaluated. Binding assay and cell-based reporter assay indicated that the activity of these compounds is enantio-dependent, and resides...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miyachi H,Nomura M,Tanase T,Suzuki M,Murakami K,Awano K

更新日期：2002-02-11 00:00:00