3-Hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carboxylates--a new class of HIV-1 integrase inhibitors.

abstract：:Accumulation of beta-amyloid (Abeta), produced by the proteolytic cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase, is widely believed to be associated with Alzheimer's disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identificati...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cole DC,Stock JR,Kreft AF,Antane M,Aschmies SH,Atchison KP,Casebier DS,Comery TA,Diamantidis G,Ellingboe JW,Harrison BL,Hu Y,Jin M,Kubrak DM,Lu P,Mann CW,Martone RL,Moore WJ,Oganesian A,Riddell DR,Sonnenberg-Reine

更新日期：2009-02-01 00:00:00

abstract：:Ligand efficient fragments binding to PDK1 were identified by an NMR fragment-based screening approach. Computational modeling of the fragments bound to the active site led to the design and synthesis of a series of novel 6,7-disubstituted thienopyrimidin-4-one compounds, with low micromolar inhibitory activity agains...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee AC,Ramanujulu PM,Poulsen A,Williams M,Blanchard S,Ma DM,Bonday Z,Goh KL,Goh KC,Goh MK,Wood J,Dymock BW

更新日期：2012-06-15 00:00:00

abstract：:To identify small molecule inhibitors of TNF-α, bioassay- and LC-MS-guided chemical investigation on EtOAc extract of Pseudomonas aeruginosa ABS-36 culture broth (EEPA) was performed, which yielded four proline-based cyclic dipeptides, cyclo(Gly-l-Pro) (1), cyclo(l-Pro-l-Phe) (2), cyclo(trans-4-hydroxy-l-Pro-l-Phe) (3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Khan R,Basha A,Goverdhanam R,Rao PC,Tanemura Y,Fujimoto Y,Begum AS

更新日期：2015-12-15 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：:A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dai L,Zang C,Tian S,Liu W,Tan S,Cai Z,Ni T,An M,Li R,Gao Y,Zhang D,Jiang Y

更新日期：2015-01-01 00:00:00

abstract：:The synthesis of 22 2-aryl-1H-indoles, including 12 new compounds, has been achieved via Pd- or Rh-mediated methodologies, or selective electrophilic substitution. All three methods were based on elaborations from simple indole precursors. SAR studies on these indoles and 2-phenyl-1H-indole in Staphylococcus aureus as...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ambrus JI,Kelso MJ,Bremner JB,Ball AR,Casadei G,Lewis K

更新日期：2008-08-01 00:00:00

abstract：:The identification of a novel series of PKCθ inhibitors and subsequent optimization using docking based on a crystal structure of PKCθ is described. SAR was rapidly generated around an amino pyridine-ketone hit; (6-aminopyridin-2-yl)(2-aminopyridin-3-yl)methanone 2 leading to compound 21 which significantly inhibits p...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jimenez JM,Davis C,Boyall D,Fraysse D,Knegtel R,Settimo L,Young S,Bolton C,Chiu P,Curnock A,Rasmussen R,Tanner A,Ager I

更新日期：2012-07-15 00:00:00

abstract：:A series of 43, 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues (D01-D43) were analysed using Petra, Osiris, Molinspiration and ALOGPS (POMA) to identify pharmacophore, toxicity prediction, lipophilicity and bioactivity. All the compounds were evaluated for anti-HIV activity. 3-(4-Chloroph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ahsan MJ,Govindasamy J,Khalilullah H,Mohan G,Stables JP

更新日期：2012-12-01 00:00:00

abstract：:We demonstrated an intriguing method to discriminate adenine by incident appearance of an intense new emission via exciplex formation in hybridization of target DNA with newly designed fluorescent 8-arylethynylated deoxyguanosine derivatives. We described the synthesis of such highly electron donating fluorescent guan...

journal_title：Bioorganic & medicinal chemistry letters

authors： Saito Y,Kugenuma K,Tanaka M,Suzuki A,Saito I

更新日期：2012-06-01 00:00:00

abstract：:Based on our earlier reported neuropeptide FF receptors antagonist (RF9), we carried out an extensive structural exploration of the N-terminus part of the amidated dipeptide Arg-Phe-NH(2) in order to establish a structure-activity relationships (SAR) study towards both NPFF receptor subtypes. This SAR led to the disco...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gealageas R,Schneider S,Humbert JP,Bertin I,Schmitt M,Laboureyras E,Dugave C,Mollereau C,Simonnet G,Bourguignon JJ,Simonin F,Bihel F

更新日期：2012-12-15 00:00:00

abstract：:Double-stranded RNA has become a ubiquitous tool for inhibition of gene expression in the laboratory. If similar success could be achieved in vivo, duplex RNA might provide a new class of therapeutics capable of treating a broad spectrum of disease. Chemists and biologists developing duplex RNA as a drug have made pro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watts JK,Corey DR

更新日期：2010-06-01 00:00:00

abstract：:The inhibition of the newly discovered cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozyme XIII of murine origin (mCA XIII) has been investigated with a series of anions, such as the physiological ones (bicarbonate, chloride), or the metal complexing anions (cyanate, cyanide, azide, hydrogen sulfide, etc), nitrate, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Innocenti A,Lehtonen JM,Parkkila S,Scozzafava A,Supuran CT

更新日期：2004-11-01 00:00:00

abstract：:Synthetic array technology was utilized to rapidly synthesize and analyze a diverse set of reductive alkylation analogues of daptomycin. Analysis of the array suggested the use of polar functionality such as sulfonamides or amide or polar spaces such as piperazine would beneficially affect activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Siedlecki J,Hill J,Parr I,Yu X,Morytko M,Zhang Y,Silverman J,Controneo N,Laganas V,Li T,Li J,Keith D,Shimer G,Finn J

更新日期：2003-12-01 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：:Herein, we report the design and synthesis of the novel 12-membered non-antibiotic macrolide (8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), which was found to be a potent anti-inflammatory and/or immunomodulatory agent, capable of promoting monocyte to macrophage differentiation. This molecule ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sugawara A,Sueki A,Hirose T,Nagai K,Gouda H,Hirono S,Shima H,Akagawa KS,Omura S,Sunazuka T

更新日期：2011-06-01 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：:Matrix metalloproteinase-13 (MMP-13) has been implicated as the protease responsible for collagen degradation in cartilage during osteoarthritis (OA). Compounds that inhibit the metalloproteinase at the Zn binding site typically lack specificity among MMP family members. Analogs of the low-micromolar lead MMP-13 inhib...

journal_title：Bioorganic & medicinal chemistry letters

authors： Roth J,Minond D,Darout E,Liu Q,Lauer J,Hodder P,Fields GB,Roush WR

更新日期：2011-12-01 00:00:00

abstract：:High throughput screening of the corporate compound collection led to the discovery of a novel series of substituted aminoalkoxybenzyl pyrrolidines as human urotensin-II receptor antagonists. The synthesis, initial structure-activity relationships, and optimization of the initial hit that led to the identification of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin J,Dhanak D,Knight SD,Widdowson K,Aiyar N,Naselsky D,Sarau HM,Foley JJ,Schmidt DB,Bennett CD,Wang B,Warren GL,Moore ML,Keenan RM,Rivero RA,Douglas SA

更新日期：2005-07-01 00:00:00

abstract：:Beta-hemoglobinopathies such as sickle cell disease represent a major global unmet medical need. De-repression of fetal hemoglobin in erythrocytes is a clinically validated approach for the management of sickle cell disease, but the only FDA-approved medicine for this purpose has limitations to its use. We conducted a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Benowitz AB,Eberl HC,Erickson-Miller CL,Gilmartin AG,Gore ER,Montoute MN,Wu Z

更新日期：2018-12-15 00:00:00

abstract：:A series of 6/7-mono and disubstituted quinolone-3-carboxamide derivatives (1-12) were synthesized and their in vitro methemoglobin producing capacity have been delineated. The compounds 5, 6, 9 and 10 showed minimum methemoglobin toxicity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Srivastava S,Srivastava SK,Shukla A,Chauhan PM,Puri SK,Bhaduri AP,Pandey VC

更新日期：1999-01-04 00:00:00

abstract：:Serine racemase, the enzyme responsible for d-serine synthesis in the central nervous system, has been identified as a potential therapeutic target to treat N-methyl-d-aspartate receptors-related pathologies. The search for specific inhibitors of the enzyme has revealed that serine racemase is a difficult target, with...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dellafiora L,Marchetti M,Spyrakis F,Orlandi V,Campanini B,Cruciani G,Cozzini P,Mozzarelli A

更新日期：2015-10-01 00:00:00

abstract：:A novel series of triazole tethered coumarin-benzotriazole hybrids based on donepezil skeleton has been designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Among the synthesized compounds 13b showed most potent acetylcholinesterase (AChE) inhibition (IC50 = 0.059 μΜ) with ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh A,Sharma S,Arora S,Attri S,Kaur P,Kaur Gulati H,Bhagat K,Kumar N,Singh H,Vir Singh J,Mohinder Singh Bedi P

更新日期：2020-10-15 00:00:00

abstract：:In the course of studies on novel retinoids, we have designed and synthesized a series of quinoline derivatives. One of them, 4-[5-[8-(1-methylethyl)-4-phenyl-2-quinolinyl]-1H-2-pyrrolyl]benzoic acid (12f) shows potent RARalpha-selective antagonistic activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kikuchi K,Tagami K,Hibi S,Yoshimura H,Tokuhara N,Tai K,Hida T,Yamauchi T,Nagai M

更新日期：2001-05-07 00:00:00

abstract：:A flexible, direct, high yielding synthesis of 2-alkylsulfanyl estrogens from estrone has been developed. 2-Methylsulfanyl estradiol (2-MeSE2) 7 displays a similar anti-proliferative activity to the established 2-methoxyestradiol (2-MeOE2) 1, whilst its 3-O-sulfamate derivative (2-MeSE2MATE) 9 exhibits greatly enhance...

journal_title：Bioorganic & medicinal chemistry letters

authors： Leese MP,Newman SP,Purohit A,Reed MJ,Potter BV

更新日期：2004-06-21 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：:We report the identification of a novel biaryl template for H(+)/K(+) ATPase inhibition. Evaluation of critical SAR features within the biaryl imidazole framework and the use of pharmacophore modelling against known imidazopyridine and azaindole templates suggested that the geometry of the molecule is key to achieving...

journal_title：Bioorganic & medicinal chemistry letters

authors： Garton N,Bailey N,Bamford M,Demont E,Farre-Gutierrez I,Hutley G,Bravi G,Pickering P

更新日期：2010-02-01 00:00:00

abstract：:Vancomycin resistance is currently a major healthcare problem. The development of a catalytic monoclonal antibody (mAb) that hydrolyzes the D-Ala-D-Lac depsipeptide provides a potentially novel antibiotic strategy. A phosphonate hapten design was used to program antibody catalysis. The characteristics of the hapten we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Isomura S,Ashley JA,Wirsching P,Janda KD

更新日期：2002-03-25 00:00:00

abstract：:A series of acetylenic chalcones were evaluated for antimalarial and antitubercular activity. The antimalarial data for this series suggests that growth inhibition of the W2 strain of Plasmodium falciparum can be imparted by the introduction of a methoxy group ortho to the acetylenic group. Most compounds were more ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hans RH,Guantai EM,Lategan C,Smith PJ,Wan B,Franzblau SG,Gut J,Rosenthal PJ,Chibale K

更新日期：2010-02-01 00:00:00

abstract：:A series of novel pyrimido and other fused quinoline derivatives like 4-methyl pyrimido [5,4-c]quinoline-2,5(1H,6H)-dione (4a), 4-methyl-2-thioxo-1,2-dihydropyrimido [5,4-c]quinoline-5(6H)-one (4b), 2-amino-4-methyl-1,2-dihydropyrimido [5,4-c]quinolin-5(6H)-one (4c), 3-methylisoxazolo [4,5-c]quinolin-4(5H)-one (4d), 3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sankaran M,Kumarasamy C,Chokkalingam U,Mohan PS

更新日期：2010-12-01 00:00:00

abstract：:The synthesis and anti-angiogenic activities of linomide and its analogues are reported. Three of the analogues are 3.3-69 times more potent than linomide at inhibiting blood vessel formation in the CAM angiogenesis assay. These compounds possessed considerable anti-proliferative activity against isolated HUVEC cells ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi J,Xiao Z,Ihnat MA,Kamat C,Pandit B,Hu Z,Li PK

更新日期：2003-03-24 00:00:00