6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: a new potent and selective triple reuptake inhibitor.

abstract：:Certain L1210-active bis(guanylhydrazones) have structural and biological properties in common with the DNA minor groove binding, antileukemic, bisquaternary ammonium heterocycles. Monitoring of the DNA binding of the bis(guanylhydrazones), by fluorimetric quantitation of drug displacement of DNA-bound ethidium, shows...

journal_title：Journal of medicinal chemistry

authors： Denny WA,Cain BF

更新日期：1979-10-01 00:00:00

abstract：:The 3,4-dichloro-N-(1-(dimethylamino)cyclohexyl)methyl benzamide scaffold was studied as a template for 18F-positron emission tomography (18F-PET) radiotracer development emphasizing sensitivity to changes in opioid receptor (OR) occupancy over high affinity. Agonist potency, binding affinity, and relevant pharmacolog...

journal_title：Journal of medicinal chemistry

authors： Ott J,Spilhaug MM,Maschauer S,Rafique W,Jakobsson JE,Hartvig K,Hübner H,Gmeiner P,Prante O,Riss PJ

更新日期：2020-09-10 00:00:00

abstract：:(-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first thymidine kinase-activated nucleoside that is significantly active against all of the clinically significant NRTI-resistant HIV-1 mutants, including AZT (D67N/K70R/T215Y/K219Q), Tenofovir (K65R), and Lamivudine (M184V). To understand the molec...

journal_title：Journal of medicinal chemistry

authors： Chu CK,Yadav V,Chong YH,Schinazi RF

更新日期：2005-06-16 00:00:00

abstract：:The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses are attractive targets for the development of antiviral drugs. We report the synthesis and evaluation of a new, proline-based compound class that displays allosteric inhibition of both proteases. The structural features relevant for protease binding and...

journal_title：Journal of medicinal chemistry

authors： Millies B,von Hammerstein F,Gellert A,Hammerschmidt S,Barthels F,Göppel U,Immerheiser M,Elgner F,Jung N,Basic M,Kersten C,Kiefer W,Bodem J,Hildt E,Windbergs M,Hellmich UA,Schirmeister T

更新日期：2019-12-26 00:00:00

abstract：:Cytochrome P450 aromatase catalyzes the conversion of androgen substrates into estrogens. Aromatase inhibitors (AIs) have been used as first-line drugs in the treatment of estrogen-dependent breast cancer in postmenopausal women. However, the search for new, more potent, and selective AIs still remains necessary to av...

journal_title：Journal of medicinal chemistry

authors： Caporuscio F,Rastelli G,Imbriano C,Del Rio A

更新日期：2011-06-23 00:00:00

abstract：:A series of substituted 3-aryl- and hydroxy-3-aryloctahydropyrido[2,1-c][1,4]oxazines has been synthesized for purposes of investigating potentially useful CNS pharmacological actions of this novel heterocyclic system. The preferred conformation of the bicyclic system of the parent compounds, 1 and 2, has been shown t...

journal_title：Journal of medicinal chemistry

authors： Rankin GO,Riley TN,Murphy JC

更新日期：1978-05-01 00:00:00

abstract：:A series of both aliphatic and aromatic amides and aromatic amidines derived from 2-amino-1,10-phenanthroline (3) according to the Topliss scheme were synthesized and subsequently tested for antimycoplasmal potency. Although the compounds themselves showed no activity, in the presence of a nontoxic copper concentratio...

journal_title：Journal of medicinal chemistry

authors： de Zwart MA,Bastiaans HM,van der Goot H,Timmerman H

更新日期：1991-03-01 00:00:00

abstract：:Neurofibrillary tangles (NFTs) made up of aggregated tau protein have been identified as the pathologic hallmark of several neurodegenerative diseases including Alzheimer's disease. In vivo detection of NFTs using PET imaging represents a unique opportunity to develop a pharmacodynamic tool to accelerate the discovery...

journal_title：Journal of medicinal chemistry

authors： Walji AM,Hostetler ED,Selnick H,Zeng Z,Miller P,Bennacef I,Salinas C,Connolly B,Gantert L,Holahan M,O'Malley S,Purcell M,Riffel K,Li J,Balsells J,OBrien JA,Melquist S,Soriano A,Zhang X,Ogawa A,Xu S,Joshi E,Del

更新日期：2016-05-26 00:00:00

abstract：:A pharmacophore for the phosphono amino acid antagonists of the NMDA receptor has been developed using computer-based molecular modeling techniques. An important feature of this model is that a single binding site is proposed for the phosphonic acid moiety. All competitive antagonists we have examined incorporating am...

journal_title：Journal of medicinal chemistry

authors： Whitten JP,Harrison BL,Weintraub HJ,McDonald IA

更新日期：1992-05-01 00:00:00

abstract：:2-Hydroxy-5-(3,4-dichlorophenyl)-6,7-bis(hydroxymethyl)-2,3-dihydro-1H- pyrrolizine bis(2-propylcarbamate) (11) was prepared in a multistep synthesis. The 2-hydroxy group was used to prepare ester prodrugs 14 and 15, and the antineoplastic activities of 11, 14, and 15a were compared to 1 (the 2-deoxy analogue of 11) i...

journal_title：Journal of medicinal chemistry

authors： Anderson WK,Chang CP,McPherson HL Jr

更新日期：1983-09-01 00:00:00

abstract：:A series of 4(6)- and 5-phenyl-substituted 2-amino- and 2-[(alkoxycarbonyl)amino]-1,4,5,6-tetrahydropyrimidines were prepared and evaluated for central nervous system (CNS) effects in animal models. Several 5-phenyl-substituted compounds possessed potent antidepressant activity and all compounds in this series were de...

journal_title：Journal of medicinal chemistry

authors： Weinhardt K,Wallach MB,Marx M

更新日期：1985-06-01 00:00:00

abstract：:Quantitative structure-activity relationships (QSAR) have been established for the inhibition of dihydrofolate reductase and thymidylate synthetase by 2,4-diaminoquinazoline-glutamic acid analogues. For dihydrofolate reductase from both human acute lymphocytic leukemia cells and murine L1210R cells, QSAR's obtained wi...

journal_title：Journal of medicinal chemistry

authors： Chen BK,Horváth C,Bertino JR

更新日期：1979-05-01 00:00:00

abstract：:To better understand the difficulties surrounding the identification of novel antibacterial compounds from corporate screening collections, physical properties of ∼3200 antibacterial project compounds with whole cell activity against Gram-negative or Gram-positive pathogens were profiled and compared to actives found ...

journal_title：Journal of medicinal chemistry

authors： Brown DG,May-Dracka TL,Gagnon MM,Tommasi R

更新日期：2014-12-11 00:00:00

abstract：:The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4'-phenyl-6,7:2',3'-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent deltaopioid receptor (DOR) antagonists while ...

journal_title：Journal of medicinal chemistry

authors： Srivastava SK,Shefali S,Miller CN,Aceto MD,Traynor JR,Lewis JW,Husbands SM

更新日期：2004-12-16 00:00:00

abstract：:The mixed topoisomerase I/II inhibitor N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) is currently in clinical trial as an anticancer drug. A series of acridine-substituted analogues were prepared, using a new synthetic route to substituted acridine-4-carboxylic acids (conversion of substituted diphenylamine ...

journal_title：Journal of medicinal chemistry

authors： Spicer JA,Gamage SA,Atwell GJ,Finlay GJ,Baguley BC,Denny WA

更新日期：1997-06-06 00:00:00

abstract：:The synthesis and biological evaluation of the two known phenolic metabolites of paclitaxel are described. The C3'-phenolic metabolite 2 of paclitaxel was prepared from 7-(triethylsilyl)-baccatin III (8) and enantioenriched N-benzoyl-2-azetidinone 7. The C2-phenolic metabolite 3 was synthesized from paclitaxel (1a) vi...

journal_title：Journal of medicinal chemistry

authors： Park H,Hepperle M,Boge TC,Himes RH,Georg GI

更新日期：1996-07-05 00:00:00

abstract：:We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray...

journal_title：Journal of medicinal chemistry

authors： Savechenkov PY,Zhang X,Chiara DC,Stewart DS,Ge R,Zhou X,Raines DE,Cohen JB,Forman SA,Miller KW,Bruzik KS

更新日期：2012-07-26 00:00:00

abstract：:The synthesis, characterization, inhibitory activity against topoisomerase I, and biological evaluation of a series of oligopeptide-substituted bisindolylmaleimides 7-12 are described. Compounds 7-9, which contain a basic C-terminus function such as (dimethylamino)propyl and bind to DNA with C(50) values of 200, 160, ...

journal_title：Journal of medicinal chemistry

authors： Xie G,Gupta R,Atchison K,Lown JW

更新日期：1996-03-01 00:00:00

abstract：:The N-2 atoms of phosphorus 2,2-dimethylhydrazides, contrary to a previous report, can be methylated by iodomethane. Treatment of the resulting dihydrazinium iodides with aqueous sodium hydroxide results in mono- instead of didehydroiodination, apparently due to resonance stabilization of the inner salt form. The phos...

journal_title：Journal of medicinal chemistry

authors： Cates LA,Li VS,Saddawi BH,Alkadhi KA

更新日期：1985-05-01 00:00:00

abstract：:Human immunodeficiency virus (HIV) infection is now pandemic. Targeting HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a defin...

journal_title：Journal of medicinal chemistry

authors： Namasivayam V,Vanangamudi M,Kramer VG,Kurup S,Zhan P,Liu X,Kongsted J,Byrareddy SN

更新日期：2019-05-23 00:00:00

abstract：:Compounds acting via the neurotensin receptor type 2 (NTS2) are known to be active in animal models of acute and chronic pain. To identify novel NTS2 selective analgesics, we searched for NTS2 selective nonpeptide compounds using a FLIPR assay and identified the title compound (NTRC-824, 5) that, to our knowledge, is ...

journal_title：Journal of medicinal chemistry

authors： Thomas JB,Giddings AM,Wiethe RW,Olepu S,Warner KR,Sarret P,Gendron L,Longpre JM,Zhang Y,Runyon SP,Gilmour BP

更新日期：2014-09-11 00:00:00

abstract：:By applying a novel cell- and caspase-based HTS assay, 2-amino-3-cyano-7-(dimethylamino)-4-(3-methoxy-4,5-methylenedioxyphenyl)-4H-chromene (1a) has been identified as a potent apoptosis inducer. Compound 1a was found to induce nuclear fragmentation and PARP cleavage, as well as to arrest cells at the G(2)/M stage and...

journal_title：Journal of medicinal chemistry

authors： Kemnitzer W,Drewe J,Jiang S,Zhang H,Wang Y,Zhao J,Jia S,Herich J,Labreque D,Storer R,Meerovitch K,Bouffard D,Rej R,Denis R,Blais C,Lamothe S,Attardo G,Gourdeau H,Tseng B,Kasibhatla S,Cai SX

更新日期：2004-12-02 00:00:00

abstract：:In a search for structurally new alpha(1)-adrenoreceptor (alpha(1)-AR) antagonists, prazosin (1)-related compounds 2-11 were synthesized and their affinity profiles were assessed by functional experiments in isolated rat vas deferens (alpha(1A)), spleen (alpha(1B)), and aorta (alpha(1D)) and by binding assays in CHO c...

journal_title：Journal of medicinal chemistry

authors： Rosini M,Antonello A,Cavalli A,Bolognesi ML,Minarini A,Marucci G,Poggesi E,Leonardi A,Melchiorre C

更新日期：2003-11-06 00:00:00

abstract：:Inhibition of the cell cycle kinase, cyclin-dependent kinase-4 (Cdk4), is expected to provide an effective method for the treatment of proliferative diseases such as cancer. The pyrido[2,3-d]pyrimidin-7-one template has been identified previously as a privileged structure for the inhibition of ATP-dependent kinases, a...

journal_title：Journal of medicinal chemistry

authors： VanderWel SN,Harvey PJ,McNamara DJ,Repine JT,Keller PR,Quin J 3rd,Booth RJ,Elliott WL,Dobrusin EM,Fry DW,Toogood PL

更新日期：2005-04-07 00:00:00

abstract：:This work reports on the synthesis, characterization, and in vitro cytotoxic activity of some new platinum(II), palladium(II), and gold(III) derivatives of methylsarcosinedithiocarbamate and its S-methyl ester, to study their behavior as potential antitumor agents. The biological activity of these compounds, as determ...

journal_title：Journal of medicinal chemistry

authors： Giovagnini L,Ronconi L,Aldinucci D,Lorenzon D,Sitran S,Fregona D

更新日期：2005-03-10 00:00:00

abstract：:N5-Acetyl-N5-hydroxy-L-ornithyl-N5-acetyl-N5-hydroxy-L-ornithyl-N5-acety l- N5-hydroxy-L-ornithine, the functionally instrumental component of the albomycins and ferrichromes, has been incorporated as a "carrier" substructure into both carbacephalosporin and oxamazin type beta-lactam antibiotics. The previously synthe...

journal_title：Journal of medicinal chemistry

authors： Dolence EK,Minnick AA,Lin CE,Miller MJ,Payne SM

更新日期：1991-03-01 00:00:00

abstract：:Ruthenium polypyridyl complexes show great promise as new photodynamic therapy (PDT) agents. However, a lack of detailed understanding of their mode of action in cells poses a challenge to their development. We have designed a new Ru(II) PDT candidate that efficiently enters cells by incorporation of the lipophilic ar...

journal_title：Journal of medicinal chemistry

authors： Cloonan SM,Elmes RB,Erby M,Bright SA,Poynton FE,Nolan DE,Quinn SJ,Gunnlaugsson T,Williams DC

更新日期：2015-06-11 00:00:00

abstract：:The accessible surface, described by Lee and Richards (the L&R surface: J. Mol. Biol. 1971, 55, 379), has remarkably useful properties for displaying ligand-protein interactions. The surface is placed one van der Waals radius plus one probe radius away from the protein atoms. The ligands are displayed in skeletal form...

journal_title：Journal of medicinal chemistry

authors： Bohacek RS,McMartin C

更新日期：1992-05-15 00:00:00

abstract：:G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and major targets for drug development. Herein, we sought to identify the regions of the human angiotensin II (AngII) type 1 (hAT(1)) receptor binding cleft that interact with all positions of the AngII using photoaffinity labeling. W...

journal_title：Journal of medicinal chemistry

authors： Fillion D,Lemieux G,Basambombo LL,Lavigne P,Guillemette G,Leduc R,Escher E

更新日期：2010-03-11 00:00:00

abstract：:In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic...

journal_title：Journal of medicinal chemistry

authors： Talamas FX,Abbot SC,Anand S,Brameld KA,Carter DS,Chen J,Davis D,de Vicente J,Fung AD,Gong L,Harris SF,Inbar P,Labadie SS,Lee EK,Lemoine R,Le Pogam S,Leveque V,Li J,McIntosh J,Nájera I,Park J,Railkar A,Rajyagur

更新日期：2014-03-13 00:00:00