Synthesis and biological evaluation of novel tacrine derivatives and tacrine-coumarin hybrids as cholinesterase inhibitors.

abstract：:Despite the availability of large amounts of data for HIV-protease inhibitors and their effectiveness with wild type and resistant enzyme, there is limited knowledge about how this and other information can be systematically applied to the development of new antiviral compounds. To identify in vitro parameters that co...

journal_title：Journal of medicinal chemistry

authors： Shuman CF,Vrang L,Danielson UH

更新日期：2004-11-18 00:00:00

abstract：:Four nucleoside analogues ( 1- 4) containing a common heterocyclic base, 4(7)-amino-6(5) H-imidazo[4,5- d]pyridazin-7(4)one, were screened against calf-intestine adenosine deaminase. Compounds 1 and 3 with K(i) values of 10-12 microM are more than four times as potent inhibitors of ADA compared with 2 and 4, with K(i)...

journal_title：Journal of medicinal chemistry

authors： Ujjinamatada RK,Phatak P,Burger AM,Hosmane RS

更新日期：2008-02-14 00:00:00

abstract：:Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys(16)PAL) and GIP(Lys(37)PAL) were resistant to dipeptidyl peptidase ...

journal_title：Journal of medicinal chemistry

authors： Irwin N,O'Harte FP,Gault VA,Green BD,Greer B,Harriott P,Bailey CJ,Flatt PR

更新日期：2006-02-09 00:00:00

abstract：:The endocannabinoid system consists of two cannabinoid receptors (CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes involved in the metabolism of the endocannabinoids, including fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL). In the present study, virtual screening of MGL inhibitor...

journal_title：Journal of medicinal chemistry

authors： Saario SM,Poso A,Juvonen RO,Järvinen T,Salo-Ahen OM

更新日期：2006-07-27 00:00:00

abstract：:To provide practical means for rapidly scanning the extensive experimental combinatorial chemistry libraries now available for high-throughput screening (HTS), it is essential to establish computational virtual ligand screening (VLS) techniques to rapidly identify out of a large library all active compounds against a ...

journal_title：Journal of medicinal chemistry

authors： Floriano WB,Vaidehi N,Zamanakos G,Goddard WA 3rd

更新日期：2004-01-01 00:00:00

abstract：:Human melanocortin receptors (hMCRs) have been challenging targets to develop ligands that are explicitly selective for each of their subtypes. To modulate the conformational preferences of the melanocortin ligands and improve the biofunctional agonist/antagonist activities and selectivities, we have applied a backbon...

journal_title：Journal of medicinal chemistry

authors： Cai M,Marelli UK,Bao J,Beck JG,Opperer F,Rechenmacher F,McLeod KR,Zingsheim MR,Doedens L,Kessler H,Hruby VJ

更新日期：2015-08-27 00:00:00

abstract：:Membrane-bound aminopeptidase P (AP-P) participates in the degradation of bradykinin in several vascular beds. We have developed an inhibitor of AP-P called apstatin (1) (N-[(2S, 3R)-3-amino-2-hydroxy-4-phenyl-butanoyl]-L-prolyl-L-prolyl-L-al aninam ide); IC50,human = 2.9 microM. In the rat, apstatin can potentiate th...

journal_title：Journal of medicinal chemistry

authors： Maggiora LL,Orawski AT,Simmons WH

更新日期：1999-07-01 00:00:00

abstract：:We report here the design, preparation, and systematic evaluation of a novel cycloalkane[d]isoxazole pharmacophoric fragment-containing androgen receptor (AR) modulators. Cycloalkane[d]isoxazoles form new core structures that interact with the hydrophobic region of the AR ligand-binding domain. To systematize and rati...

journal_title：Journal of medicinal chemistry

authors： Poutiainen PK,Oravilahti T,Peräkylä M,Palvimo JJ,Ihalainen JA,Laatikainen R,Pulkkinen JT

更新日期：2012-07-26 00:00:00

abstract：:Thirty-five analogues of Phe-Leu-Glu-Glu-Leu, the pentapeptide sequence 5-9 of bovine prothrombin precursor, were synthesized and assayed as potential substrates or inhibitors of rat liver vitamin K dependent carboxylase. Carboxylation of substrate was determined by measuring the incorporation of carbon-24 labeled bic...

journal_title：Journal of medicinal chemistry

authors： Rich DH,Lehrman SR,Kawai M,Goodman HL,Suttie JW

更新日期：1981-06-01 00:00:00

abstract：:The synthesis of a series of 1-amino-substituted pyrido[4,3-b]carbazole derivatives, based on the substitution of corresponding 1-chloroellipticines, is reported. The cytotoxic properties on tumor cells grown in vitro, the in vivo acute toxicity of the most potent in vitro cytotoxic compounds, and the antitumor proper...

journal_title：Journal of medicinal chemistry

authors： Ducrocq C,Wendling F,Tourbez-Perrin M,Rivalle C,Tambourin P,Pochon F,Bisagni E,Chermann JC

更新日期：1980-11-01 00:00:00

abstract：:In an intensive study of South American medicinal plants, herein we report the isolation, structure elucidation and biological activity of fourteen new and five known dihydro-beta-agarofuran sesquiterpenes from the leaves of Zinowiewia costaricensis (1-19). Their structures were determined by means of (1)H and (13)C N...

journal_title：Journal of medicinal chemistry

authors： Muñoz-Martínez F,Mendoza CR,Bazzocchi IL,Castanys S,Jiménez IA,Gamarro F

更新日期：2005-06-30 00:00:00

abstract：:A series of 2'- and 3'-fluorinated 2',3'-dideoxynucleosides and 3'-azido-2',3'-dideoxynucleosides were synthesized and evaluated for their inhibitory activity against human immunodeficiency virus-1 (HIV-1) replication in MT-4 cells. Neither conversion of 3'-fluoro- or 3'-azido-2',3'-dideoxyadenosine to the correspondi...

journal_title：Journal of medicinal chemistry

authors： Van Aerschot A,Herdewijn P,Balzarini J,Pauwels R,De Clercq E

更新日期：1989-08-01 00:00:00

abstract：:Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alph...

journal_title：Journal of medicinal chemistry

authors： Nagarathnam D,Miao SW,Lagu B,Chiu G,Fang J,Murali Dhar TG,Zhang J,Tyagarajan S,Marzabadi MR,Zhang F,Wong WC,Sun W,Tian D,Wetzel JM,Forray C,Chang RS,Broten TP,Ransom RW,Schorn TW,Chen TB,O'Malley S,Kling P,Sch

更新日期：1999-11-18 00:00:00

abstract：:The cardiotonic 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3- pyridazinyl)-2H-indol-2-one (1, LY195115) is a potent, competitive inhibitor (Ki = 80 nM) of sarcoplasmic reticulum derived phosphodiesterase (SR-PDE). Moreover, the compound is a potent positive inotrope both in vitro and in vivo. To assist furth...

journal_title：Journal of medicinal chemistry

authors： Robertson DW,Jones ND,Krushinski JH,Pollock GD,Swartzendruber JK,Hayes JS

更新日期：1987-04-01 00:00:00

abstract：:In an effort to develop selective inhibitors of vesicular acetylcholine storage, we have synthesized a series of semirigid vesamicol receptor ligands based on the structure of 2-(4-phenylpiperidino)-cyclohexanol (vesamicol, AH5183, 1). In these compounds, the planes of the phenyl and piperidyl moieties of the parent l...

journal_title：Journal of medicinal chemistry

authors： Efange SM,Khare AB,Foulon C,Akella SK,Parsons SM

更新日期：1994-08-05 00:00:00

abstract：:The syntheses of 2-amino-N-(2-benzoyl)-4-chlorophenyl)acetamides are reported. The pharmacological properties of these compounds were compared with data obtained from the corresponding cyclized products [5-(2,6-dichlorophenyl)-1,4-benzodiazepin-2-ones]. Evidence is presented which suggests that the central nervous sys...

journal_title：Journal of medicinal chemistry

authors： Fryer RI,Leimgruber W,Trybulski EJ

更新日期：1982-09-01 00:00:00

abstract：:Bivalent molecules containing two beta-turn mimics with side chains that correspond to hot-spots on the neurotrophin NT-3 were prepared. Binding assays showed the mimetics to be selective TrkC ligands, and biological assays showed one mimetic to be an antagonist of the TrkC receptor. ...

journal_title：Journal of medicinal chemistry

authors： Liu J,Brahimi F,Saragovi HU,Burgess K

更新日期：2010-07-08 00:00:00

abstract：:In search of water-soluble artemisinin derivatives that are more stable than sodium artesunate, over 30 derivatives containing an amino group (compounds 3-5) were synthesized and tested in mice. All products tested (except 5a and 5b) are the beta isomers. These basic compounds combined with organic acids (oxalic acid,...

journal_title：Journal of medicinal chemistry

authors： Li Y,Zhu YM,Jiang HJ,Pan JP,Wu GS,Wu JM,Shi YL,Yang JD,Wu BA

更新日期：2000-04-20 00:00:00

abstract：:The synthesis, biological evaluation, and structure-activity relationships of a series of N-phenyl heteroaryl-fused isothiazolones are described. These isothiazolones have been shown to exhibit potent, dose-dependent inhibition of IL-1 beta-induced breakdown of proteoglycan in a cartilage organ culture assay. This eff...

journal_title：Journal of medicinal chemistry

authors： Wright SW,Petraitis JJ,Abelman MM,Batt DG,Bostrom LL,Corbett RL,Decicco CP,Di Meo SV,Freimark B,Giannaras JV

更新日期：1994-09-16 00:00:00

abstract：:In order to develop selective radioactive ligands for the study of presynaptic monoamine uptake sites, iodinated derivatives of tomoxetine were synthesized and evaluated in radioligand binding assays. Iodotomoxetine derivatives showed high affinity for serotonin (5-HT) uptake sites using a rat cortical membrane prepar...

journal_title：Journal of medicinal chemistry

authors： Chumpradit S,Kung MP,Panyachotipun C,Prapansiri V,Foulon C,Brooks BP,Szabo SA,Tejani-Butt S,Frazer A,Kung HF

更新日期：1992-11-13 00:00:00

abstract：:A new class of 2,3-diaziridinyl-1,4-naphthoquinone sulfonates (27 compounds) has been synthesized and evaluated as potential antineoplastic agents. The most active compounds, benzenesulfonate 4, p-toluenesulfonate 5, p-methoxybenzenesulfonate 7,8-quinolinesulfonate 17, and 2-thiophenesulfonate 20, in the aromatic sulf...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Xu SP,Zhu LY,Cosby LA,Sartorelli AC

更新日期：1989-07-01 00:00:00

abstract：:A new group of potent inhibitors of glutamine synthetase was designed and synthesized. The X-ray structure of bacterial glutamine synthetase complexed with phosphinothricin was used for computer-aided structure-based design of the inhibitors, in which the methyl group of phosphinothricin was chosen as the modification...

journal_title：Journal of medicinal chemistry

authors： Berlicki Ł,Obojska A,Forlani G,Kafarski P

更新日期：2005-10-06 00:00:00

abstract：:Target identification is a high-priority, albeit challenging, aspect of drug discovery. Diazirine-based photoaffinity probes (PAPs) can facilitate the process by covalently capturing transient molecular interactions. This can help identify target proteins and map the ligand's interactome. Diazirine probes have even be...

journal_title：Journal of medicinal chemistry

authors： Hill JR,Robertson AAB

更新日期：2018-08-23 00:00:00

abstract：:Three series of 4-anilino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic esters were synthesized as part of a program to study potential anti-Leishmania drugs. These compounds were obtained by a condensation reaction of 4-chloro-1H-pyrazolo[3,4-b]pyridine with several aniline derivatives. Some of them were also obtained by a...

journal_title：Journal of medicinal chemistry

authors： de Mello H,Echevarria A,Bernardino AM,Canto-Cavalheiro M,Leon LL

更新日期：2004-10-21 00:00:00

abstract：:Retinoic acid receptor-related orphan receptor γt (RORγt) is a nuclear receptor associated with the pathogenesis of autoimmune diseases. Allosteric inhibition of RORγt is conceptually new, unique for this specific nuclear receptor, and offers advantages over traditional orthosteric inhibition. Here, we report a highly...

journal_title：Journal of medicinal chemistry

authors： Meijer FA,Doveston RG,de Vries RMJM,Vos GM,Vos AAA,Leysen S,Scheepstra M,Ottmann C,Milroy LG,Brunsveld L

更新日期：2020-01-09 00:00:00

abstract：:The novel lead bis(1H-2-indolyl)methanone inhibits autophosphorylation of platelet-derived growth factor (PDGF) receptor tyrosine kinase in intact cells. Various substituents in the 5- or 6-position of one indole ring increase or preserve potency, whereas most modifications of the ring structures and of the methanone ...

journal_title：Journal of medicinal chemistry

authors： Mahboobi S,Teller S,Pongratz H,Hufsky H,Sellmer A,Botzki A,Uecker A,Beckers T,Baasner S,Schächtele C,Uberall F,Kassack MU,Dove S,Böhmer FD

更新日期：2002-02-28 00:00:00

abstract：:New fluorinated 2-aryl-benzothiazoles, -benzoxazoles, and -chromen-4-ones have been synthesized and their activity against MCF-7 and MDA 468 breast cancer cell lines compared with the potent antitumor benzothiazole 5. Analogues such as 9a, b and 12a, d yielded submicromolar GI50 values in both cell lines; however, non...

journal_title：Journal of medicinal chemistry

authors： Aiello S,Wells G,Stone EL,Kadri H,Bazzi R,Bell DR,Stevens MF,Matthews CS,Bradshaw TD,Westwell AD

更新日期：2008-08-28 00:00:00

abstract：:There is currently no ideal radiotracer for imaging of protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18-labeled amino acid-based radiotracers predominantly visualize amino acid transporter processes, and in many cases they are not incorporated into nascent proteins at all. Other...

journal_title：Journal of medicinal chemistry

authors： Betts HM,Milicevic Sephton S,Tong C,Awais RO,Hill PJ,Perkins AC,Aigbirhio FI

更新日期：2016-10-27 00:00:00

abstract：:A new series of compounds were designed as structural analogues of the alpha(1)-AR ligand RN5 (4), characterized by a tricyclic 5H-pyrimido[5,4-b]indole-(1H,3H)2,4-dione system connected through an alkyl chain to a phenylpiperazine (PP) moiety. These compounds were synthesized and tested in binding assays on human alp...

journal_title：Journal of medicinal chemistry

authors： Romeo G,Materia L,Manetti F,Cagnotto A,Mennini T,Nicoletti F,Botta M,Russo F,Minneman KP

更新日期：2003-07-03 00:00:00

abstract：:Selective inhibition of the isoforms of nitric oxide synthase (NOS) in pathologically elevated synthesis of nitric oxide has great therapeutic potential. We previously reported nitroarginine-containing dipeptide amides and some peptidomimetic analogues as potent and selective inhibitors of neuronal NOS (nNOS). Here we...

journal_title：Journal of medicinal chemistry

authors： Gómez-Vidal JA,Martásek P,Roman LJ,Silverman RB

更新日期：2004-01-29 00:00:00