Structure-activity relationship of cyclic peptide penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2) at the human melanocortin-1 and -4 receptors: His(6) substitution.

abstract：:A series of inhibitors of the soluble epoxide hydrolase (sEH) containing two urea groups has been developed. Inhibition potency of the described compounds ranges from 2.0 μM to 0.4 nM. 1,6-(Hexamethylene)bis[(adamant-1-yl)urea] (3b) was found to be a potent slow tight binding inhibitor (IC50=0.5 nM) with a strong bind...

journal_title：Bioorganic & medicinal chemistry letters

authors： Burmistrov V,Morisseau C,Lee KS,Shihadih DS,Harris TR,Butov GM,Hammock BD

更新日期：2014-05-01 00:00:00

abstract：:Bcl homologs prominently contribute to apoptotic resistance in cancer cells and serve as molecular targets in treatment of various cancers. Herein, we report the synthesis of biphenyl-adamantane derivatives by a ligand free palladium on carbon based Suzuki reaction using diisopropylamine as a base for the coupling of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Anusha S,Mohan CD,Ananda H,Baburajeev CP,Rangappa S,Mathai J,Fuchs JE,Li F,Shanmugam MK,Bender A,Sethi G,Basappa,Rangappa KS

更新日期：2016-02-01 00:00:00

abstract：:A series of 2-phenoxy-indan-1-one derivatives have been designed, synthesized, and tested as acetylcholinesterase inhibitors. The most potent compound exhibited high AChE inhibitory activity (IC50 = 50 nM), and the molecular docking study indicated that it was nicely accommodated by AChE. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sheng R,Lin X,Li J,Jiang Y,Shang Z,Hu Y

更新日期：2005-09-01 00:00:00

abstract：:Spatiotemporal control of protein fluorescence is a powerful tool in tracking protein movements within cells. Here we report an approach to using genetically encoded photo-caged amino acids to control labeling protein tetracysteine tags with biarsenical fluorescein dyes (FlAsH). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wilkins BJ,Yang X,Cropp TA

更新日期：2009-08-01 00:00:00

abstract：:A new class of kappa-opioid receptor agonists is described. The design of these agents was based upon energy minimization and structural overlay studies of the generic azepin-2-one structure 3 with the crystal structure of arylacetamide kappa agonist 1, ICI 199441. The most active compound identified was ligand 4a (K(...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tuthill PA,Seida PR,Barker W,Cassel JA,Belanger S,DeHaven RN,Koblish M,Gottshall SL,Little PJ,DeHaven-Hudkins DL,Dolle RE

更新日期：2004-11-15 00:00:00

abstract：:Breast cancer is the most common malignancy among females, and cancer invasion and metastasis are the leading causes of cancer death in breast cancer patients. Pterostilbene, a naturally occurring dimethylether analogue of resveratrol, has been demonstrated to possess anti-cancer effects. However, inhibitory effects o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ko HS,Kim JS,Cho SM,Lee HJ,Ahn KS,Kim SH,Lee EO

更新日期：2014-02-15 00:00:00

abstract：:3-Phenyl-3.4-dihydro-1-isoquinolinamine is a weak inhibitor of iNOS and nNOS. Structural variation of 5a results in inhibitors with a range of potency and selectivity for the NOS enzymes, including a potent and very selective iNOS inhibitor 5j. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Beaton H,Hamley P,Nicholls DJ,Tinker AC,Wallace AV

更新日期：2001-04-23 00:00:00

abstract：:Invasive fungal infections have become an important healthcare issue due in large part to high mortality rates under standard of care (SOC) therapies creating an urgent need for new and effective anti-fungal agents. We have developed a series of non-peptide, structurally-constrained analogs of host defence proteins th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baugh SDP,Chaly A,Weaver DG,Pelletier JC,Thanna S,Freeman KB,Reitz AB,Scott RW

更新日期：2020-12-13 00:00:00

abstract：:Protein kinase C (PKC) is a family of enzymes, which play important roles in intracellular signal transduction. To examine the distance between the two ligand binding sites (C1A and C1B) of PKC, we designed and synthesized two series of isobenzofuranone dimers. Peak binding activities were observed for the C3-acyl cha...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baba Y,Mayumi S,Hirai G,Kawasaki H,Ogoshi Y,Yanagisawa T,Hashimoto Y,Sodeoka M

更新日期：2004-06-07 00:00:00

abstract：:Novel 5-HT(7) receptor antagonists containing the benzocycloheptanone core were identified from high throughput screening. Molecular modelling and SAR studies have converted these intractable hits into a more potent, selective and tractable series, exemplified by compound (25), SB-691673. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Forbes IT,Cooper DG,Dodds EK,Douglas SE,Gribble AD,Ife RJ,Lightfoot AP,Meeson M,Campbell LP,Coleman T,Riley GJ,Thomas DR

更新日期：2003-03-24 00:00:00

abstract：:To explore the hydrophobic groove subsite within the CB1 cannabinoid receptor we have designed and synthesized a group of tail-substituted anandamide analogs. Our design involves the introduction of aryl or heterocyclic ring as terminal substituents that are connected to the last cis-arachidonyl double bond through al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yao F,Li C,Vadivel SK,Bowman AL,Makriyannis A

更新日期：2008-11-15 00:00:00

abstract：:Two analogues possessing steric hindered substituents on C-15 of arenastatin A (1), a potent cytotoxic spongean depsipeptide, were synthesized and shown to enhance stability in mouse serum. Notably, 15-tert-butylanalogue (6) with higher cytotoxicity exhibited in vivo anti-tumor activity through iv administration diffe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Murakami N,Tamura S,Koyama K,Sugimoto M,Maekawa R,Kobayashi M

更新日期：2004-05-17 00:00:00

abstract：:Tricyclic sulfones were designed as gamma-secretase inhibitors and found to have excellent potency. Extensive SAR shows that a large number of sulfonamides at position 7 of the tricycle are very well tolerated. Compounds such as 15a and 15c showed remarkable in vivo potency. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sasikumar TK,Qiang L,Burnett DA,Cole D,Xu R,Li H,Greenlee WJ,Clader J,Zhang L,Hyde L

更新日期：2010-06-15 00:00:00

abstract：:Enzastaurin (LY317615) is a potent and selective protein kinase C (PKC) inhibitor with an IC(50) value of ∼6 nM. [(11)C]Enzastaurin (3-(1-[(11)C]methyl-1H-indol-3-yl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-1H-indol-3-yl]-1H-pyrrole-2,5-dione), a new potential PET agent for imaging of PKC, was first designed and sy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Xu L,Gao M,Miller KD,Sledge GW,Zheng QH

更新日期：2011-03-15 00:00:00

abstract：:Various bis(2-hydroxy-3-chloropropyl)alkylamines were synthesized by coupling primary amine with epichlorohydrin and utilized as a monomer to react with ethylenediamine (EDA), N,N'-dimethylethylenediamine (DMEDA), or tetramethylethylenediamine (TMEDA) to generate a series of lipopolyhydroxylalkyleneamines. The number-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Q,Zhang G,Marhefka J,Kameneva MV,Liu D

更新日期：2006-05-01 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：:Brønsted acid-induced fragmentation of a triazoline is used as a tool to identify Brønsted base additives capable of playing the role of a proton shuttle. Relative to water, dimethyl formamide accelerates proton transfer substantially under these conditions. A series of alcohols and ethers were also used to demonstrat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donahue MG,Hong KB,Johnston JN

更新日期：2009-09-01 00:00:00

abstract：:In this paper, we present the results of a ligand- and structure-based virtual screen targeting LRRK2, a kinase that has been implicated in Parkinson's disease. For the ligand-based virtual screen, the structures of 12 competitor compounds were used as queries for a variety of 2D and 3D searches. The structure-based v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gancia E,De Groot M,Burton B,Clark DE

更新日期：2017-06-01 00:00:00

abstract：:A new class of benzimidazole-5-sulfonamides has been identified as nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists. Initial structure-activity relationships are presented resulting in compounds 19 and 28 with submicromolar dual functional activity on human and rat receptors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hashimoto K,Tatsuta M,Kataoka M,Yasoshima K,Shogase Y,Shimazaki M,Yura T,Li Y,Yamamoto N,Gupta JB,Urbahns K

更新日期：2005-02-01 00:00:00

abstract：:Prototypical thrombin inhibitors were synthesized based on a trisubstituted phenol as a core motif. A naphthylsulfonamide analogue showed excellent antithrombin activity. An X-ray co-crystal structure showed the expected interactions. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanessian S,Therrien E,van Otterlo WA,Bayrakdarian M,Nilsson I,Fjellström O,Xue Y

更新日期：2006-02-15 00:00:00

abstract：:By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 μM; MIC = 0.48 μM) than the positive controls AHA (IC50 = 17.2 μM) and Metronidazole (MIC = 31.3 ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang YS,Su MM,Zhang XP,Liu QX,He ZX,Xu C,Zhu HL

更新日期：2018-10-15 00:00:00

abstract：:We have developed two novel series of tetrasubstituted pyrazoles, embodying 1,3-diaryl-4,5-dialkyl or 3,5-diaryl-1,4-dialkyl substitution patterns. The scope of a regioselective method, developed by us earlier, was expanded to allow the synthesis of the first series of these tetrasubstituted pyrazoles directly from al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishiguchi GA,Rodriguez AL,Katzenellenbogen JA

更新日期：2002-03-25 00:00:00

abstract：:New inverse agonists of the ghrelin receptor (ghrelinR) were obtained through high-throughput screening and subsequent structural modification of 2-aminoalkyl nicotinamide derivatives. The key structural feature to improve in vitro activity was the introduction of a diazabicyclo ring at the 5-position of the pyridine ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takahashi B,Funami H,Iwaki T,Maruoka H,Nagahira A,Koyama M,Kamiide Y,Matsuo T,Muto T,Annoura H

更新日期：2015-07-01 00:00:00

abstract：:Myelin associated glycoprotein (Siglec-4) is a myelin adhesion receptor, that is, well established for its role as an inhibitor of axonal outgrowth in nerve injury, mediated by binding to sialic acid containing ligands on the axonal membrane. Because disruption of myelin-ligand interactions promotes axon outgrowth, we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zeng Y,Rademacher C,Nycholat CM,Futakawa S,Lemme K,Ernst B,Paulson JC

更新日期：2011-09-01 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：:A labeled variant of MSH(4), a tetrapeptide that binds to the human melanocortin 4 receptor (hMC4R) with low microM affinity, was prepared by solid-phase synthesis methods, purified, and characterized. The labeled ligand, Eu-DTPA-PEGO-His-dPhe-Arg-Trp-NH(2), exhibited a K(d) for hMC4R of 9.1+/-1.4 microM, approximatel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu L,Vagner J,Alleti R,Rao V,Jagadish B,Morse DL,Hruby VJ,Gillies RJ,Mash EA

更新日期：2010-04-15 00:00:00

abstract：:A novel series of benzothiophene derivatives was discovered as phosphodiesterase 10A (PDE10A) inhibitors. Structure-activity relationship studies on high-throughput screening hit compound 1 led to the identification of 7-acetyl-3-methyl-N-(quinolin-2-yl)-1-benzothiophene-2-carboxamide (16), with potent inhibitory acti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kawamoto Y,Tomino M,Hiramatsu K,Oyama Y,Hayashi Y

更新日期：2019-06-01 00:00:00

abstract：:A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gapil Tiamas S,Daressy F,Abou Samra A,Bignon J,Steinmetz V,Litaudon M,Fourneau C,Hoong Leong K,Ariffin A,Awang K,Desrat S,Roussi F

更新日期：2020-04-01 00:00:00

abstract：:In this paper, we describe the synthesis of N-(6-cyano-1,3-dimethyl-2,4-dioxo-5-substituted-1,3-dihydropyridino[2,3-d] pyrimidin-7-yl)imides 1. We will show the synthesis of 1 using both conventional heating and microwave techniques. In addition, the imide was attached to polystyrene and this immobilized imide was equ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nicewonger RB,Ditto L,Kerr D,Varady L

更新日期：2002-07-22 00:00:00

abstract：:A series of pyrimidine derivatives as acid pump antagonists (APAs) was synthesized and the inhibitory activities against H(+)/K(+) ATPase isolated from hog gastric mucosa were determined. After elaborating on substituents at C2 and C4 position of the pyrimidine scaffold, we have observed that the compound 7h is a pote...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yoon YA,Park CS,Cha MH,Choi H,Sim JY,Kim JG

更新日期：2010-10-01 00:00:00