Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility.

abstract：:A three-dimensional pharmacophore model has been generated for HIV-1 integrase (HIV-1 IN) from known inhibitors. A dataset consisting of 26 inhibitors was selected on the basis of the information content of the structures and activity data as required by the catalyst/HypoGen program. Our model was able to predict the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mustata GI,Brigo A,Briggs JM

更新日期：2004-03-22 00:00:00

abstract：:A series of pyrrolo[2,3-d]pyrimidines was synthesized and evaluated as inhibitors of Lck. Lck accommodates a diverse set of substituents at N-7. Altering the substituent at N-7 provided compound 13, an orally available lck inhibitor which inhibited TCR mediated IL-2 production after oral dosing. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Calderwood DJ,Johnston DN,Munschauer R,Rafferty P

更新日期：2002-06-17 00:00:00

abstract：:There is a great urgency in developing a new generation of antibiotics and antimicrobial agents since the bacterial resistance to antibiotics have increased dramatically. A series of overlapped peptide fragments of Ixosin-B, an antimicrobial peptide with amino acid sequence of QLKVDLWGTRSGIQPEQHSSGKSDVRRWRSRY, was des...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wu YS,Liao ZJ,Wang KS,Lung FD

更新日期：2013-05-15 00:00:00

abstract：:A series of N-substituted 3-(4-piperidinyl)-1,3-benzoxazolinones and oxindoles are reported which were found to be potent and selective muscarinic M1 agonists. By control of the physicochemical characteristics of the series, particularly the lipophilicity, compounds with good metabolic stability and excellent brain pe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Johnson DJ,Forbes IT,Watson SP,Garzya V,Stevenson GI,Walker GR,Mudhar HS,Flynn ST,Wyman PA,Smith PW,Murkitt GS,Lucas AJ,Mookherjee CR,Watson JM,Gartlon JE,Bradford AM,Brown F

更新日期：2010-09-15 00:00:00

abstract：:The synthesis of two separable isomeric testosterone dimers is reported. The dimers are made from testosterone in a 5 step sequence and with 36% overall yield. The key dimerization step was performed using Hoveyda-Grubb's metathesis catalysts on 7alpha-allyltestosterone with 75% yield. The synthesis led to separable i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bastien D,Leblanc V,Asselin E,Bérubé G

更新日期：2010-04-01 00:00:00

abstract：:PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studie...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nankervis JL,Feil SC,Hancock NC,Zheng Z,Ng HL,Morton CJ,Holien JK,Ho PW,Frazzetto MM,Jennings IG,Manallack DT,Martin TJ,Thompson PE,Parker MW

更新日期：2011-12-01 00:00:00

abstract：:A series of 4'-hydroxyphenyl-aryl-carbaldehyde oximes (5b) was prepared and found to have high affinity (4nM) and modest selectivity (39-fold) for estrogen receptor-beta (ERbeta). Substitution of one of the core rings of the scaffold based around these novel ligands further expanded our knowledge in the quest toward a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mewshaw RE,Bowen SM,Harris HA,Xu ZB,Manas ES,Cohn ST

更新日期：2007-02-15 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：:A novel series of diphenylpyridylethanamine-based inhibitors of cholesteryl ester transfer protein is described. Optimization of the urea moiety, particularly by incorporation of fluorine, is explored to balance in vitro metabolic stability with CETP potency in the whole plasma assay. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miller MM,Liu Y,Jiang J,Johnson JA,Kamau M,Nirschl DS,Wang Y,Harikrishnan L,Taylor DS,Chen AY,Yin X,Seethala R,Peterson TL,Zvyaga T,Zhang J,Huang CS,Wexler RR,Poss MA,Lawrence RM,Adam LP,Salvati ME

更新日期：2012-10-15 00:00:00

abstract：:This Letter describes the synthesis of two regioisomers of a new class of vesamicol analogs as possible ligands for imaging the vesicular acetylcholine transporter in future PET studies. The two pyrrolovesamicols (±)-6a and (±)-6b were synthesized by nucleophilic ring opening reaction of a tetrahydroindole epoxide pre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wenzel B,Li Y,Kraus W,Sorger D,Sabri O,Brust P,Steinbach J

更新日期：2012-03-15 00:00:00

abstract：:In this report, the design and synthesis of a series of pyrimidine based adenosine A(2A) antagonists are described. The strategy and outcome of expanding SAR exploration to attenuate hERG and improve selectivity over A(1) are discussed. Compound 33 exhibited excellent potency, selectivity over A(1), and reduced hERG l...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moorjani M,Zhang X,Chen Y,Lin E,Rueter JK,Gross RS,Lanier MC,Tellew JE,Williams JP,Lechner SM,Malany S,Santos M,Ekhlassi P,Castro-Palomino JC,Crespo MI,Prat M,Gual S,Díaz JL,Saunders J,Slee DH

更新日期：2008-02-15 00:00:00

abstract：:Factor Xa, a critical serine protease in the blood coagulation cascade, has become a target for inhibition as a strategy for the invention of novel anti-thrombotic agents. Here we describe the development of phenylglycine containing benzamidine carboxamides as novel, potent and selective inhibitors of factor Xa. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jones SD,Liebeschuetz JW,Morgan PJ,Murray CW,Rimmer AD,Roscoe JM,Waszkowycz B,Welsh PM,Wylie WA,Young SC,Martin H,Mahler J,Brady L,Wilkinson K

更新日期：2001-03-12 00:00:00

abstract：:Synthetic and biological evaluation of novel diphenyloxazole derivatives containing a pyrrolidine ring, as a prostacyclin mimetic without the PG skeleton, are described. Asymmetric reduction of a ketone using a chiral Ru complex and reductive amination by NaBH(4) produces four isomers of the tetrahydronaphthalene ring...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hattori K,Okitsu O,Tabuchi S,Taniguchi K,Nishio M,Koyama S,Seki J,Sakane K

更新日期：2005-07-01 00:00:00

abstract：:The enantioselective activation of nitroalkanes was attempted on the basis of the complexation between chiral guanidinium and nitronate through two hydrogen bonds. The proposed enantioselective activation was applied to the diastereo- and enantioselective Henry (nitroaldol) reaction of nitroalkanes with aldehydes usin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ube H,Terada M

更新日期：2009-07-15 00:00:00

abstract：:We have developed a novel series of heteroaromatic BACE-1 inhibitors. These inhibitors interact with the enzyme in a unique fashion that allows for potent binding in a non-traditional paradigm. In addition to the elucidation of their binding profile, we have discovered a pH dependent effect on the binding affinity as ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stachel SJ,Coburn CA,Rush D,Jones KL,Zhu H,Rajapakse H,Graham SL,Simon A,Katharine Holloway M,Allison TJ,Munshi SK,Espeseth AS,Zuck P,Colussi D,Wolfe A,Pietrak BL,Lai MT,Vacca JP

更新日期：2009-06-01 00:00:00

abstract：:A series of novel methyl 5-substituted 1H-benzo[d]imidazol-2-ylcarbamates were designed, synthesized, and their acrosin inhibitory activities evaluated in vitro. The results of acrosin inhibitory activity showed that all title compounds were more potent than the control TLCK. Compound 4w displayed the most potent acro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu X,Chen Q,Zhu J,Fan Y,Ding L,Zhao J,Han G,Tian W,Qi J,Zhou Y,Lv J

更新日期：2012-05-15 00:00:00

abstract：:A series of conformationally restricted bis-azaaromatic quaternary ammonium salts (3 and 4) have been designed and synthesized in order to investigate the possible binding conformations of N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB; 2), a compound which potently inhibits neuronal nicotinic acetylcholin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng G,Zhang Z,Pivavarchyk M,Deaciuc AG,Dwoskin LP,Crooks PA

更新日期：2007-12-15 00:00:00

abstract：:In continuation of our efforts to find new antimicrobial compounds, series of fatty N-acyldiamines were prepared from fatty methyl esters and 1,2-ethylenediamine, 1,3-propanediamine or 1,4-butanediamine. The synthesized compounds were screened for their antibacterial activity against Gram-positive bacteria (Staphyloco...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ferreira BDS,de Almeida AM,Nascimento TC,de Castro PP,Silva VL,Diniz CG,Le Hyaric M

更新日期：2014-10-01 00:00:00

abstract：:Biphenylacetic acid (5) was identified through a library screen as an inhibitor of the prostaglandin D(2) receptor DP2 (CRTH2). Optimization for potency and pharmacokinetic properties led to a series of selective CRTH2 antagonists. Compounds demonstrated potency in a human DP2 binding assay and a human whole blood eos...

journal_title：Bioorganic & medicinal chemistry letters

authors： Scott JM,Baccei C,Bain G,Broadhead A,Evans JF,Fagan P,Hutchinson JH,King C,Lorrain DS,Lee C,Prasit P,Prodanovich P,Santini A,Stearns BA

更新日期：2011-11-01 00:00:00

abstract：:Rhus verniciflua Stokes has been used as a traditional herbal medicine in Asia. In this study, the effect of R. verniciflua extract on human aromatase (cytochrome P450 19, CYP19) activity was investigated to elucidate the mechanism for the effect of R. verniciflua extract on androgen hormone levels. Androstenedione wa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park MH,Kim IS,Kim SA,Na CS,Hong CY,Dong MS,Yoo HH

更新日期：2014-04-01 00:00:00

abstract：:Bioassay-guided fractionation of a MeOH extract of the rhizomes of Astilbe koreana (Saxifragaceae), using an in vitro protein tyrosine phosphatase 1B (PTP1B) inhibitory assay, resulted in the isolation of a new triterpene, 3alpha,24-dihydroxyolean-12-en-27-oic acid (4), along with four triterpenes, 3-oxoolean-12-en-27...

journal_title：Bioorganic & medicinal chemistry letters

authors： Na M,Cui L,Min BS,Bae K,Yoo JK,Kim BY,Oh WK,Ahn JS

更新日期：2006-06-15 00:00:00

abstract：:A new class of PARP-1 inhibitors, namely substituted fused uracil derivatives were synthesised. Starting from a derivative with an IC(50)=2microM the chemical optimisation program led to compounds with more than a 100-fold increase in potency (IC(50)<20nM). Additionally, physicochemical and pharmacokinetic properties ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Steinhagen H,Gerisch M,Mittendorf J,Schlemmer KH,Albrecht B

更新日期：2002-11-04 00:00:00

abstract：:Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase is being pursued with computational guidance. Extension of azine-containing inhibitors into the entrance channel between Lys103 and Glu138 has led to the discovery of potent and structurally novel derivatives including dimeric inhibitors in an NNRTI-li...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ekkati AR,Bollini M,Domaoal RA,Spasov KA,Anderson KS,Jorgensen WL

更新日期：2012-02-15 00:00:00

abstract：:A series of 4beta-arylamino-4'-O-demethylepipodophyllotoxins and 4beta-arylaminoepipodophyllotoxins have been synthesized with significant stereoselectivity and improved yields by employing the methanesulphonic acid/sodium iodide reagent system. Compounds NPF. W-68 and other DNA topoisomerase II inhibitors are prepare...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kamal A,Laxman N,Ramesh G

更新日期：2000-09-18 00:00:00

abstract：:The Hedgehog (Hh-) signalling pathway is a key developmental pathway and there is a growing body of evidence showing that this pathway is aberrantly reactivated in a number of human tumors. Novel agents capable of inhibiting this pathway are sought, and an entirely novel series of smoothened (Smo) antagonists capable ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ontoria JM,Bufi LL,Torrisi C,Bresciani A,Giomini C,Rowley M,Serafini S,Bin H,Hao W,Steinkühler C,Jones P

更新日期：2011-09-15 00:00:00

abstract：:Ligand-based virtual screening led to the discovery of a new class of potent inverse agonists of the human cannabinoid receptor 1, hCB(1), which are selective versus hCB(2). These CB(1) ligands present intriguing departures from a classical CB(1) antagonist pharmacophore. Elements of SAR are discussed in this context....

journal_title：Bioorganic & medicinal chemistry letters

authors： Foloppe N,Allen NH,Bentley CH,Brooks TD,Kennett G,Knight AR,Leonardi S,Misra A,Monck NJ,Sellwood DM

更新日期：2008-02-01 00:00:00

abstract：:Fluorination is a well-known strategy for improving the bioavailability of bioactive molecules in the lead optimization phase of drug discovery projects. In an attempt to improve the antitumor activity of camptothecins (CPTs), novel 10-fluoro-CPT derivatives were designed, synthesized and evaluated for cytotoxicity ag...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang CJ,Song ZL,Goto M,Hsu PL,Zhang XS,Yang QR,Liu YQ,Wang MJ,Morris-Natschke SL,Shang XF,Lee KH

更新日期：2017-10-15 00:00:00

abstract：:By performing RNA-targeted structure-activity relationship studies, we discovered a novel peptidomimetic containing squaryldiamide as a potential bioisostere replacement for guanidine that binds transactivation responsive RNA with high affinity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee CW,Cao H,Ichiyama K,Rana TM

更新日期：2005-10-01 00:00:00

abstract：:A series of mechanism-based heteroaryl urea fatty acid amide hydrolase (FAAH) inhibitors with fused bicyclic diamine cores is described. In contrast to compounds built around a piperazine core, most of the fused bicyclic diamine bearing analogs prepared exhibited greater potency against rFAAH than the human enzyme. Se...

journal_title：Bioorganic & medicinal chemistry letters

authors： Keith JM,Jones W,Pierce JM,Seierstad M,Palmer JA,Webb M,Karbarz M,Scott BP,Wilson SJ,Luo L,Wennerholm M,Chang L,Rizzolio M,Rynberg R,Chaplan S,Guy Breitenbucher J

更新日期：2020-10-15 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