Substituted piperazines as nootropic agents: 2- or 3-phenyl derivatives structurally related to the cognition-enhancer DM235.

abstract：:4-(Substituted-benzylidine)-2-substituted-5,6-dihydrobenzo[h]quinazoline (5a-p) and 4-(substituted-benzylidine)-2-substituted-3, 4, 5, 6-tetrahydrobenzo[h]quinazoline (6a-p) have been synthesized from 2-(substituted-benzylidine)tetralone-1(3a-d) and several substituted guanidine sulfates(4a-d).These compounds were tes...

journal_title：Bioorganic & medicinal chemistry letters

authors： Agarwal KC,Sharma V,Shakya N,Gupta S

更新日期：2009-09-15 00:00:00

abstract：:The structure-activity relationships of 5,6-positions of aminopyridine carboxamide-based c-Jun N-terminal Kinase (JNK) inhibitors were explored to expand interaction with the kinase specificity and ribose-binding pockets. The syntheses of analogues and the impact of structural modification on in vitro potency and cell...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu G,Zhao H,Liu B,Xin Z,Liu M,Kosogof C,Szczepankiewicz BG,Wang S,Clampit JE,Gum RJ,Haasch DL,Trevillyan JM,Sham HL

更新日期：2006-11-15 00:00:00

abstract：:A highly practicable synthesis of both enantiomers of 3-hydroxypipecolic acid derivatives 1, 2, 3, 4 is described. Screening of these molecules for glycosidase inhibition has been examined. Compound 3 was shown to be a potent inhibitor of beta-N-acetylglucosaminidase as well as Escherichia coli beta-glucuronidase. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohara C,Takahashi R,Miyagawa T,Yoshimura Y,Kato A,Adachi I,Takahata H

更新日期：2008-03-15 00:00:00

abstract：:Multiple-targeted ligands can have certain advantages for the management of hypertension which has multiple controls. Molecules with dual bioactivities are available in literature for treating metabolic disorders like diabetes, hypertension and hypercholesterolemia. After scrutinizing the SAR of prazosin-type α1-block...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yadav MR,Naik PP,Gandhi HP,Chauhan BS,Giridhar R

更新日期：2013-07-01 00:00:00

abstract：:We previously identified the methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its obligate transcriptional coactivators and prevent thyroid hormone signaling. As part of our lead optimization work we demonstrated that sulfonylnitrophenylthiazoles (SNPTs), which repla...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hwang JY,Attia RR,Carrillo AK,Connelly MC,Guy RK

更新日期：2013-03-15 00:00:00

abstract：:Chalcone type compound 1a ((E)-6'-benzylidene-4a'-methyl-4',4a',7',8'-tetrahydro-3'H-spiro[[1,3]dithiolane-2,2'-naphthalen]-5'(6'H)-one) was discovered as an potent inhibitor in melanogenesis. To define its structure-activity relationship, a series of analogs 1b-n, dithiolane truncated 2a-b and ring A removed 3a-e wer...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thanigaimalai P,Lee KC,Sharma VK,Rao EV,Roh E,Kim Y,Jung SH

更新日期：2011-04-01 00:00:00

abstract：:A series of competitive, reversible cathepsin S (CatS) inhibitors was investigated. An earlier disclosure detailed the discovery of the 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety as an effective replacement for the 4-arylpiperazin-1-yl group found in our screening hit. Continued investigation into replacement...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grice CA,Tays K,Khatuya H,Gustin DJ,Butler CR,Wei J,Sehon CA,Sun S,Gu Y,Jiang W,Thurmond RL,Karlsson L,Edwards JP

更新日期：2006-04-15 00:00:00

abstract：:A series of 3-aryl-2-propenoates including cinnamates, (E)-methyl/ethyl 3-[2-(1,4-dimethoxy-5,8-dione)naphthalenyl]-2-propenoates (8ba, 8bb) and (E)-methyl/ethyl 3-[2-(1,4-dihydroxy-9,10-dione)anthracenyl]-2-propenoates (9aa,9ab) was synthesized and evaluated for antitumor cytotoxicity. It was found that the ortho- or...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nam NH,You YJ,Kim Y,Hong DH,Kim HM,Ahn BZ

更新日期：2001-05-07 00:00:00

abstract：:Homology modeling of candida lanosterol C-14 demethylase, synthesis and in vitro antifungal activities of cyclohexyl analogs of restricticin are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tsukuda T,Shiratori Y,Watanabe M,Ontsuka H,Hattori K,Shirai M,Shimma N

更新日期：1998-07-21 00:00:00

abstract：:Optimization of clearance of adenosine inhibitors of bacterial NAD(+)-dependent DNA ligase is discussed. To reduce Cytochrome P-450-mediated metabolic clearance, many strategies were explored; however, most modifications resulted in compounds with reduced antibacterial activity and/or unchanged total clearance. The al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stokes SS,Gowravaram M,Huynh H,Lu M,Mullen GB,Chen B,Albert R,O'Shea TJ,Rooney MT,Hu H,Newman JV,Mills SD

更新日期：2012-01-01 00:00:00

abstract：:To improve the DNA hydrolytic activity of the zinc finger nuclease, we have created a new artificial zinc finger nuclease (ZWH4) by connecting two distinct zinc finger domains possessing different types of Zn(II) binding sites (Cys(2)His(2)- and His(4)-types). The overall fold of ZWH4 is similar to that of the wild-ty...

journal_title：Bioorganic & medicinal chemistry letters

authors： Negi S,Umeda Y,Masuyama S,Kano K,Sugiura Y

更新日期：2009-05-15 00:00:00

abstract：:The structure-based design, synthesis, and anticancer activity of novel inhibitors of protein kinase CK2 are described. Using pyrazolo[1,5-a][1,3,5]triazine as the core scaffold, a structure-guided series of modifications provided pM inhibitors with microM-level cytotoxic activity in cell-based assays with prostate an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nie Z,Perretta C,Erickson P,Margosiak S,Almassy R,Lu J,Averill A,Yager KM,Chu S

更新日期：2007-08-01 00:00:00

abstract：:The glycoprotein IIb/IIIa receptor is the final common pathway of platelet aggregation, regardless of the agonist, and thus represents an ideal therapeutic target for blocking thrombus formation. RUC-2 is a novel glycoprotein IIb/IIIa inhibitor of adenosine-5'-diphosphate (ADP)-induced platelet aggregation, importantl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Y,Zhao Y,Sun R,Kong W,Wang B,Yang G,Li Y

更新日期：2015-03-15 00:00:00

abstract：:The synthesis and structure-activity relationships of zygosporamide, a known potent and selective cytotoxic natural product against SF-268 and RXF 393 cell lines, are described. The potencies of the synthetic zygosporamide are similar to those reported for the natural product toward all cancer cell lines examined with...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Y,Zhang F,Zhang Y,Liu JO,Ma D

更新日期：2008-08-01 00:00:00

abstract：:Incorporation of a 4-hydroxy-N-acetylprolinol nucleotide analogue at the 3'-terminus of DNA or 2-5A-DNA sequences resulted in a significantly enhanced 3'-exonuclease resistance while the affinity for complementary RNA was only slightly decreased. Furthermore, the binding to and activation of human RNase L by thus modi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Verheijen JC,van Roon AM,Meeuwenoord NJ,Stuivenberg HR,Bayly SF,Chen L,van der Marel GA,Torrence PF,van Boom JH

更新日期：2000-04-17 00:00:00

abstract：:The diacylglycerol acyltransferase enzyme, DGAT1, presents itself as a potential target for obesity as this enzyme is dedicated to the final committed step in triglyceride biosynthesis. Biphenyl ureas, exemplified by compound 4, have been reported to be potent hDGAT1 inhibitors. We have synthesized and evaluated 2-pyr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Motiwala H,Kandre S,Birar V,Kadam KS,Rodge A,Jadhav RD,Mahesh Kumar Reddy M,Brahma MK,Deshmukh NJ,Dixit A,Doshi L,Gupte A,Gangopadhyay AK,Vishwakarma RA,Srinivasan S,Sharma M,Nemmani KV,Sharma R

更新日期：2011-10-01 00:00:00

abstract：:A new near-infrared fluorescent compound containing two cyclic RGD motifs, cypate-[c(RGDfK)](2) (1), was synthesized based on a carbocyanine fluorophore bearing two carboxylic acid groups (cypate) for integrin α(v)β(3)-targeting. Compared with its monovalent counterpart cypate-c(RGDfK) (2), 1 exhibited remarkable impr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ye Y,Akers W,Xu B,Bloch S,Odonkor C,Achilefu S

更新日期：2012-09-01 00:00:00

abstract：:A new class of selective nonsteroidal glucocorticoid receptor modulators typified by N-[3-[benzyl-(4-chloro-2-fluoro-benzyl)-amino]-2-methyl-phenyl]-methanesulfonamide 19 has been discovered. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Link JT,Sorensen BK,Patel J,Emery M,Grynfarb M,Goos-Nilsson A

更新日期：2004-05-03 00:00:00

abstract：:Inhibition of BCR-ABL tyrosine kinase activity has shown to be essential for the treatment of chronic myelogenous leukemia (CML). However, drug resistance has quickly arisen in recent clinical trials for STI571 (Gleevec), which is the first approved drug of CML by inhibiting ABL tyrosine kinase. It is desirable to dev...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peng H,Huang N,Qi J,Xie P,Xu C,Wang J,Yang C

更新日期：2003-11-03 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 series of substituted sulfonamide bioisosteres of 8-hydroxyquinoline were evaluated for their antibacterial activity against the common mastitis causative pathogens Streptococcus uberis, Staphylococcus aureus and Escherichia coli, both in the presence and absence of supplementary zinc. Compounds 9a-e, 10a-c, 11a-e, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： McGowan JE,Harper AD,Davison EK,Jeong JY,Mros S,Harbison-Price N,Van Zuylen EM,Knottenbelt MK,Heikal A,Ferguson SA,McConnell MA,Cook GM,Krittaphol W,Walker GF,Brimble MA,Rennison D

更新日期：2020-06-01 00:00:00

abstract：:The proprotein convertases PCSK8 and PCSK4 are, respectively, the 8th and 4th members of Ca(+2)-dependent serine endoprotease of Proprotein Convertase Subtilisin Kexin (PCSK) super family structurally related to the bacterial subtilisin and yeast kexin. The membrane bound PCSK8 (also called SKI-1 or S1P) is implicated...

journal_title：Bioorganic & medicinal chemistry letters

authors： Basak A,Goswami M,Rajkumar A,Mitra T,Majumdar S,O'Reilly P,Bdour HM,Trudeau VL,Basak A

更新日期：2015-01-01 00:00:00

abstract：:A series of novel small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH), based upon a 3-cyanoindole core, were explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dhar TG,Shen Z,Gu HH,Chen P,Norris D,Watterson SH,Ballentine SK,Fleener CA,Rouleau KA,Barrish JC,Townsend R,Hollenbaugh DL,Iwanowicz EJ

更新日期：2003-10-20 00:00:00

abstract：:We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fuchi N,Iura Y,Kaneko H,Nitta A,Suyama K,Ueda H,Yamaguchi S,Nishimura K,Fujii S,Sekiya Y,Yamada M,Takahashi T

更新日期：2012-07-01 00:00:00

abstract：:Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was con...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song JL,Zhang J,Liu CL,Liu C,Zhu KK,Yang FF,Liu XG,Figueiró Longo JP,Alexandre Muehlmann L,Azevedo RB,Zhang YY,Guo YW,Jiang CS,Zhang H

更新日期：2017-10-15 00:00:00

abstract：:A novel series of quinolizidine salicylamides was synthesized as specific inhibitors of the H1 subtype of influenza A viruses. These inhibitors inhibit the pH-induced fusion process, thereby blocking viral entry into host cells. Compound 16 was the most active inhibitor in this series with an EC50 of 0.25 microg/mL in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu KL,Ruediger E,Luo G,Cianci C,Danetz S,Tiley L,Trehan AK,Monkovic I,Pearce B,Martel A,Krystal M,Meanwell NA

更新日期：1999-08-02 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：:A novel class of 2,3-diaminopyridine bradykinin B1 receptor antagonists is disclosed. Structure-activity relationship studies (SARs) that led to compounds with significantly improved potency and pharmacokinetic properties relative to the lead compound are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Feng DM,Wai JM,Kuduk SD,Ng C,Murphy KL,Ransom RW,Reiss D,Chang RS,Harrell CM,MacNeil T,Tang C,Prueksaritanont T,Freidinger RM,Pettibone DJ,Bock MG

更新日期：2005-05-02 00:00:00

abstract：:Potent and selective antagonists of the adenosine A2A receptor often contain a nitrogen-rich fused-ring heterocyclic core. Replacement of the core with an isomeric ring system has previously been shown to improve target affinity, selectivity, and in vivo activity. This paper describes the preparation, by a novel route...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dowling JE,Vessels JT,Haque S,Chang HX,van Vloten K,Kumaravel G,Engber T,Jin X,Phadke D,Wang J,Ayyub E,Petter RC

更新日期：2005-11-01 00:00:00

abstract：:Naphthalimide-derived azoles as a new type of antimicrobial agents were synthesized and evaluated for their efficiency in vitro against eight bacteria and two fungi by two fold serial dilution technique. Most title compounds exhibited good antimicrobial potency with low MIC values ranging from 1 to 16μg/mL. Notably, s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang YY,Zhou CH

更新日期：2011-07-15 00:00:00