Design and synthesis of pyridone inhibitors of non-nucleoside reverse transcriptase.

abstract：:Two new kelsoane-type sesquiterpenes, namely kelsoenethiol (1) and dikelsoenyl ether (2), were obtained from the Formosan soft coral Nephthea erecta. Their structures were elucidated through extensive spectroscopic analyses, ESI orbitrap mass and quantum chemical calculations (QCC). The cytotoxicity against A-459 (hum...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheng SY,Shih NL,Hou KY,Ger MJ,Yang CN,Wang SK,Duh CY

更新日期：2014-01-15 00:00:00

abstract：:A series of novel ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives were designed and synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds exhibited acrosin inhibitory activities. Among them, three compounds (5l, 5n, and 5v) were more potent than that of the co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qi J,Zhu J,Liu X,Ding L,Zheng C,Han G,Lv J,Zhou Y

更新日期：2011-10-01 00:00:00

abstract：:The 1,3-dipolar cycloaddition of azomethine ylides derived from acenaphthenequinone and alpha-amino acids viz. sarcosine, phenylglycine, 1,3-thiazolane-4-carboxylic acid and proline to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones afforded novel spiro-heterocycles chemo-, regio- and stereoselectively in quant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ranjith Kumar R,Perumal S,Manju SC,Bhatt P,Yogeeswari P,Sriram D

更新日期：2009-07-01 00:00:00

abstract：:The discovery and optimization of a novel class of quinolone small-molecules that inhibit NS5B polymerase, a key enzyme of the HCV viral life-cycle, is described. Our research led to the replacement of a hydrolytically labile ester functionality with bio-isosteric heterocycles. An X-ray crystal structure of a key anal...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar DV,Rai R,Brameld KA,Riggs J,Somoza JR,Rajagopalan R,Janc JW,Xia YM,Ton TL,Hu H,Lehoux I,Ho JD,Young WB,Hart B,Green MJ

更新日期：2012-01-01 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：:In continuation of our program aimed at the discovery and development of compounds with superior anti-human immunodeficiency virus type 1 (HIV-1) activity, 21N-arylsulfonyl-3-acetylindole analogs (2a-u) were synthesized and preliminarily evaluated as HIV-1 inhibitors in vitro. Among of all the analogs, several compoun...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ran JQ,Huang N,Xu H,Yang LM,Lv M,Zheng YT

更新日期：2010-06-15 00:00:00

abstract：:Chemical modifications are essential to improve metabolic stability and pharmacokinetic properties of siRNA to enable their systemic delivery. We investigated the effect of combing the phosphorothioate (PS) modification with metabolically stable phosphate analog (E)-5'-vinylphosphonate and GalNAc cluster conjugation o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prakash TP,Kinberger GA,Murray HM,Chappell A,Riney S,Graham MJ,Lima WF,Swayze EE,Seth PP

更新日期：2016-06-15 00:00:00

abstract：:The discovery and optimization of a new class of non-peptidyl, pyridazinone derived melanocortin subtype-4 receptor agonists is disclosed. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ujjainwalla F,Warner D,Walsh TF,Wyvratt MJ,Zhou C,Yang L,Kalyani RN,MacNeil T,Van der Ploeg LH,Rosenblum CI,Tang R,Vongs A,Weinberg DH,Goulet MT

更新日期：2003-12-15 00:00:00

abstract：:The formation of blood clots in blood vessels causes severe ischemic diseases such as cerebral infarction and myocardial infarction. While searching for microbial products that increase fibrinolytic activity using an in vitro fibrin degradation assay, we found malformin A1, a disulfide form of cyclo(-d-Cys-d-Cys-l-Val...

journal_title：Bioorganic & medicinal chemistry letters

authors： Koizumi Y,Nagai K,Hasumi K,Kuba K,Sugiyama T

更新日期：2016-11-01 00:00:00

abstract：:The synthesis of three series of quinol fatty alcohols (QFAs) and their biological activities on the promotion of axonal growth are described. Interestingly, the 15-(2,5-dimethoxyphenyl)pentadecan-1-ol, the QFA bearing 15 carbon atoms on the side chain (n=15), shows the most potent promotion of axonal growth in the pr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanbali M,Vela-Ruiz M,Bagnard D,Luu B

更新日期：2006-05-15 00:00:00

abstract：:2-(Anilino)imidazolines were identified as novel human 5-HT(1D) receptor ligands, but offered no particular advantage over previously reported 2-(benzyl)imidazolines. Pharmacokinetic and functional data were obtained for selected 2-(benzyl)imidazoline derivatives. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prisinzano T,Dukat M,Law H,Slassi A,MacLean N,DeLannoy I,Glennon RA

更新日期：2004-09-20 00:00:00

abstract：:It is suggested that the ratio of dopamine D(2) to 5-hydroxytryptamine 5-HT(1A) activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sukalovic V,Ignjatovic D,Tovilovic G,Andric D,Shakib K,Kostic-Rajacic S,Soskic V

更新日期：2012-06-15 00:00:00

abstract：:The present study describes the optimization of a series of novel benzoxazole-piperidine (piperazine) derivatives combining high dopamine D2 and serotonin 5-HT1A, 5-HT2A receptor affinities. Of these derivatives, the pharmacological features of compound 29 exhibited high affinities for the DA D2, 5-HT1A and 5-HT2A rec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang L,Zhang W,Zhang X,Yin L,Chen B,Song J

更新日期：2015-11-15 00:00:00

abstract：:GTP cyclohydrolase (GCYH-I) is an enzyme in the folate biosynthesis pathway that has not been previously exploited as an antibiotic target, although several pathogens including N. gonorrhoeae use a form of the enzyme GCYH-IB that is structurally distinct from the human homologue GCYH-IA. A comparison of the crystal st...

journal_title：Bioorganic & medicinal chemistry letters

authors： Samaan GN,Paranagama N,Haque A,Hecht DA,Swairjo MA,Purse BW

更新日期：2020-01-15 00:00:00

abstract：:The structure-activity relationships of new Aurora A/B kinase inhibitors derived from the previously identified kinase inhibitor 12 are described. Introduction of acetic acid amides onto the pyrazole of compound 12 was postulated to influence Aurora A/B selectivity and improve the profile against off-target kinases. T...

journal_title：Bioorganic & medicinal chemistry letters

authors： Voss ME,Rainka MP,Fleming M,Peterson LH,Belanger DB,Siddiqui MA,Hruza A,Voigt J,Gray K,Basso AD

更新日期：2012-05-15 00:00:00

abstract：:The first enantioselective biocatalytic synthesis of (S)-monastrol has been developed via an unexpected and unusual enzymatic pathway as suitable route. Whereas attempts for a direct hydrolysis of racemic monastrol were not successful, formation of racemic O-butanoyl monastrol and subsequent enantioselective hydrolysi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Blasco MA,Thumann S,Wittmann J,Giannis A,Gröger H

更新日期：2010-08-01 00:00:00

abstract：:Several derivatives of hadacidin have been developed and evaluated for activity against adenylosuccinate synthetase. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tibrewal N,Elliott GI

更新日期：2011-01-01 00:00:00

abstract：:High-throughput screening of the GSK compound collection against the P2Y(1) receptor identified a novel series of tetrahydro-4-quinolinamine antagonists. Optimal substitution around the piperidine group was pivotal for ensuring activity. An exemplar analog from this series was shown to inhibit platelet aggregation. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morales-Ramos AI,Mecom JS,Kiesow TJ,Graybill TL,Brown GD,Aiyar NV,Davenport EA,Kallal LA,Knapp-Reed BA,Li P,Londregan AT,Morrow DM,Senadhi S,Thalji RK,Zhao S,Burns-Kurtis CL,Marino JP Jr

更新日期：2008-12-01 00:00:00

abstract：:A novel series of 7-amino 4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-quinolines was synthesized and their TbetaR-1 inhibitory, p38 MAPK inhibitory, and TbetaR-1-dependent cellular activity were evaluated. Compound 5a was found to be a highly potent in the enzyme assay and TbetaR-1-dependent cellular ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li HY,Wang Y,Yan L,Campbell RM,Anderson BD,Wagner JR,Yingling JM

更新日期：2004-07-05 00:00:00

abstract：:The effect of 2'-O-(N-methylcarbamoyl)ethyl (MCE) modification on splice-switching oligonucleotides (SSO) was systematically evaluated. The incorporation of five MCE nucleotides at the 5'-termini of SSOs effectively improved the splice switching effect. In addition, the incorporation of 2'-O-(N-methylcarbamoylethyl)-5...

journal_title：Bioorganic & medicinal chemistry letters

authors： Masaki Y,Yamamoto K,Inde T,Yoshida K,Maruyama A,Nagata T,Tanihata J,Takeda S,Sekine M,Seio K

更新日期：2019-01-15 00:00:00

abstract：:To investigate why 3-substituted benzamide derivatives show dual inhibition of Abl and Lyn protein tyrosine kinases, we determined their inhibitory activities against Abl and Lyn, carried out molecular modeling, and conducted a structure-activity relationship study with the aid of a newly determined X-ray structure of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Horio T,Hamasaki T,Inoue T,Wakayama T,Itou S,Naito H,Asaki T,Hayase H,Niwa T

更新日期：2007-05-15 00:00:00

abstract：:A novel β-tryptase inhibitor with a basic benzylamine P1 group, a piperidine-amide linker, and a substituted indole P4 group was discovered. A substitution at 4-indole position was introduced to constrain the conformational flexibility of the inhibitor to the bioactive conformation exhibited by X-ray structures so tha...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liang G,Choi-Sledeski YM,Poli G,Chen X,Shum P,Minnich A,Wang Q,Tsay J,Sides K,Cairns J,Stoklosa G,Nieduzak T,Zhao Z,Wang J,Vaz RJ

更新日期：2010-11-15 00:00:00

abstract：:A high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li D,Gao N,Zhu N,Lin Y,Li Y,Chen M,You X,Lu Y,Wan K,Jiang JD,Jiang W,Si S

更新日期：2015-11-15 00:00:00

abstract：:Fibronectin contains the active sequence Arg-Gly-Asp (RGD), along with its synergic site Pro-His-Ser-Arg-Asn (PHSRN). However, the PHSRN peptide does not show synergic activity when it is mixed with the RGD peptide, indicating that a spatial array between RGD and PHSRN in fibronectin may be necessary for synergic acti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hojo K,Susuki Y,Maeda M,Okazaki I,Nomizu M,Kamada H,Yamamoto Y,Nakagawa S,Mayumi T,Kawasaki K

更新日期：2001-06-04 00:00:00

abstract：:Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a deficiency in pancreatic beta-cells. Since their discovery, three subtypes of peroxisome proliferator activated receptors have been identified, namely PPARalpha, PPARgamma and P...

journal_title：Bioorganic & medicinal chemistry letters

authors： Parmenon C,Guillard J,Caignard DH,Hennuyer N,Staels B,Audinot-Bouchez V,Boutin JA,Dacquet C,Ktorza A,Viaud-Massuard MC

更新日期：2009-05-15 00:00:00

abstract：:We report the discovery of a novel series of ATP-competitive Janus kinase 3 (JAK3) inhibitors based on the 5H-pyrrolo[2,3-b]pyrazine scaffold. The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family. Computational and crystal...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jaime-Figueroa S,De Vicente J,Hermann J,Jahangir A,Jin S,Kuglstatter A,Lynch SM,Menke J,Niu L,Patel V,Shao A,Soth M,Vu MD,Yee C

更新日期：2013-05-01 00:00:00

abstract：:Six diam(m)ineplatinum(II) complexes with 2,2-bis(hydroxymethyl)malonate as the leaving group were synthesized and characterized by elemental analysis, FAB-MS, FT-IR, (1)H and (13)C NMR along with a single crystal X-ray diffraction for a representative compound. All the complexes were evaluated for the cytotoxicity ag...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xing Y,Lou L,Chen X,Ye Q,Xu Y,Xie C,Jiang J,Liu W

更新日期：2012-03-15 00:00:00

abstract：:Backbone-modified DNA analogs were synthesized in good yields by the boranophosphotriester method on a solid support. The oligodeoxyribonucleoside boranophosphates, protected with 2-(azidomethyl)benzoyl groups for nucleobases, were converted into DNA and its backbone-modified analogs via the corresponding H-phosphonat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kawanaka T,Shimizu M,Shintani N,Wada T

更新日期：2008-07-01 00:00:00

abstract：:Pd(II), Cu(II) and Zn(II) complexes (1-3) based on 4'-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-2,2':6',2″-terpyridine were synthesized and characterized by UV, IR, NMR, EPR, HRMS, elemental analyses, and molar conductivity measurements. The cytotoxicity of these complexes against HL-60, BGC-823, KB, Bel-7402, A549, Hela, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu W,Wang Y,Liu S,Yang X,Wang S,Li S,Zhou G,Qin X,Zhou C,Zhang J

更新日期：2013-09-15 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