Synthesis of steroidal nitrosoureas with antitumor activity.

abstract：:n-Octyl, n-dodecyl, and n-hexadecyl alpha- and gamma-esters of methotrexate (MTX) were compared with the previously described alpha- and gamma-n-butyl esters and with MTX as inhibitors of dihydrofolate reductase (DHFR) and human leukemic lymphoblasts (CEM cells) in culture. The overall order of activity in both test s...

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Forsch RA,Yu CS,Lazarus H,Beardsley GP

更新日期：1984-05-01 00:00:00

abstract：:We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship...

journal_title：Journal of medicinal chemistry

authors： Ghosh AK,Takayama J,Aubin Y,Ratia K,Chaudhuri R,Baez Y,Sleeman K,Coughlin M,Nichols DB,Mulhearn DC,Prabhakar BS,Baker SC,Johnson ME,Mesecar AD

更新日期：2009-08-27 00:00:00

abstract：:4-[4-(N-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives such as KN1022 are potent inhibitors of the phosphorylation of platelet derived growth factor receptor (PDGFR). Structure activity relationships in the (thio)urea moiety, the phenyl ring itself, the linker between these two moieti...

journal_title：Journal of medicinal chemistry

authors： Matsuno K,Nakajima T,Ichimura M,Giese NA,Yu JC,Lokker NA,Ushiki J,Ide S,Oda S,Nomoto Y

更新日期：2002-09-26 00:00:00

abstract：:Glycosylated β-endorphin analogues of various amphipathicity were studied in vitro and in vivo in mice. Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. All were pan-agonists, binding to μ-, δ-,...

journal_title：Journal of medicinal chemistry

authors： Li Y,St Louis L,Knapp BI,Muthu D,Anglin B,Giuvelis D,Bidlack JM,Bilsky EJ,Polt R

更新日期：2014-03-27 00:00:00

abstract：:A series of homo- and heterodimeric ligands containing kappa agonist and mu agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors. The functional activities of these compounds were measured...

journal_title：Journal of medicinal chemistry

authors： Peng X,Knapp BI,Bidlack JM,Neumeyer JL

更新日期：2006-01-12 00:00:00

abstract：:1,4-Oxazines are presented, which show good in vitro inhibition in enzymatic and cellular BACE1 assays. We describe lead optimization focused on reducing the amidine pKa while optimizing interactions in the BACE1 active site. Our strategy permitted modulation of properties such as permeation and especially P-glycoprot...

journal_title：Journal of medicinal chemistry

authors： Rombouts FJ,Tresadern G,Delgado O,Martínez-Lamenca C,Van Gool M,García-Molina A,Alonso de Diego SA,Oehlrich D,Prokopcova H,Alonso JM,Austin N,Borghys H,Van Brandt S,Surkyn M,De Cleyn M,Vos A,Alexander R,Macdonald G,Mo

更新日期：2015-10-22 00:00:00

abstract：:A close analogue of the antileukemic agent 5,8-dideaza-N10 propargylfolic acid (2) was synthesized by replacing the propargyl moiety of 2 with a cyanomethyl group. This compound, N10-(cyanomethyl)-5,8-dideazafolic acid (3), was evaluated for its antifolate and antitumor activities in several biological test systems. A...

journal_title：Journal of medicinal chemistry

authors： Nair MG,Salter DC,Kisliuk RL,Gaumont Y,North G,Sirotnak FM

更新日期：1983-04-01 00:00:00

abstract：:We disclose the first selective, nonpeptidic, small-molecule somatostatin receptor subtype 5 (SST5R) antagonists that were identified by a chemogenomics approach based on the analysis of the homology of amino acids defining the putative consensus drug binding site of SST5R. With this strategy, opioid, histamine, dopam...

journal_title：Journal of medicinal chemistry

authors： Martin RE,Green LG,Guba W,Kratochwil N,Christ A

更新日期：2007-12-13 00:00:00

abstract：:The (E)- and (Z)-m-(trifluoromethyl)-alpha, beta-dimethylcinnamamides and some of their N-alkyl derivatives were prepared and pharmacologically tested as anticonvulsant agents in order to verify if a ring substituent, like the m-CF3 group, different from a halogen but possessing the same electronic effect could lead t...

journal_title：Journal of medicinal chemistry

authors： Balsamo A,Crotti P,Lapucci A,Macchia B,Macchia F,Cuttica A,Passerini N

更新日期：1981-05-01 00:00:00

abstract：:Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been developed using comparative molecular field analysis (CoMFA) on a large data set (118 compounds) of diverse cyclic urea derivatives as protease inhibitors against the human immunodeficiency virus type 1 (HIV-1). X-ray crystal str...

journal_title：Journal of medicinal chemistry

authors： Debnath AK

更新日期：1999-01-28 00:00:00

abstract：:The dedifferentiation agent "reversine" [2-(4-morpholinoanilino)-N(6)-cyclohexyladenine 2] was found to be a moderately potent antagonist for the human A(3) adenosine receptor (AR) with a K(i) value of 0.66 microM. This result prompted an exploration of the structure-activity relationship of related derivatives, synth...

journal_title：Journal of medicinal chemistry

authors： Perreira M,Jiang JK,Klutz AM,Gao ZG,Shainberg A,Lu C,Thomas CJ,Jacobson KA

更新日期：2005-07-28 00:00:00

abstract：:We report on the design, synthesis, and evaluation of a series of furanyl-salicyl-nitroxide derivatives as effective chemical probes for second-site screening against phosphotyrosine phosphatases (PTPs) using NMR-based techniques. The compounds have been tested against a panel of PTPs to assess their ability to inhibi...

journal_title：Journal of medicinal chemistry

authors： Vazquez J,Tautz L,Ryan JJ,Vuori K,Mustelin T,Pellecchia M

更新日期：2007-05-03 00:00:00

abstract：:A series of neutral, lipophilic 99mTc mixed-ligand complexes of the general formula 99mTcOL1L2, where L1H2 is an N-substituted bis-(2-mercaptoethyl)amine, [X-CH2CH2N(CH2CH2SH)2], [SNS], and L2H is a monodentate thiol (RSH), [S], has been synthesized and evaluated in rodents for potential use in brain blood flow imagin...

journal_title：Journal of medicinal chemistry

authors： Pirmettis IC,Papadopoulos MS,Chiotellis E

更新日期：1997-08-01 00:00:00

abstract：:A number of cytostatic compounds (2-4, 7, and 8), which can be described as "diaryl", inhibit tubulin polymerization, cause cells to accumulate in mitotic arrest, and competitively inhibit the binding of colchicine to tubulin. They differ, however, in the separation of the two aryl moieties. To attempt to understand t...

journal_title：Journal of medicinal chemistry

authors： Getahun Z,Jurd L,Chu PS,Lin CM,Hamel E

更新日期：1992-03-20 00:00:00

abstract：:Improvement in the therapeutic index of doxorubicin, a cytotoxic molecule, has been sought through its chemical conjugation to short (15-23 amino acid) peptide sequences called Vectocell peptides. Vectocell peptides are highly charged drug delivery peptides and display a number of characteristics that make them attrac...

journal_title：Journal of medicinal chemistry

authors： Meyer-Losic F,Quinonero J,Dubois V,Alluis B,Dechambre M,Michel M,Cailler F,Fernandez AM,Trouet A,Kearsey J

更新日期：2006-11-16 00:00:00

abstract：:2,6,8-Trichloro-7-methylpurine (3) was converted to 2-chloro-8,9-dihydro-7-methyl-8-thioxopurin-6(1H)-one (5) by utilizing the difference in reactivity of the 2-, 6-, and 8-positions in the trichloropurine ring system to nucleophilic displacement. Compound 5 was subsequently glycosylated with 1-O-acetyl-2,3,5-tri-O-be...

journal_title：Journal of medicinal chemistry

authors： Henry EM,Kini GD,Larson SB,Robins RK,Alaghamandan HA,Smee DF

更新日期：1990-08-01 00:00:00

abstract：:This paper reports the synthesis of 4-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (2) and 2-(3,4-dihydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)propylamine (3). The biological activity of these agents relative to that of trimetoquinol (1) in guinea pig atria and guinea pig trachea is reported. Th...

journal_title：Journal of medicinal chemistry

authors： Kador PF,Venkatraman R,Feller DR,Miller DD

更新日期：1977-07-01 00:00:00

abstract：:The syntheses of three new cyclosporin A (CsA) analogues that contain novel MeBmt derivatives in the 1-position are described. The MeBmt analogue that contains an additional methyl group on C4, (2S,3R,6E)-4,4-dimethyl-3-hydroxy-2-(N-methylamino)-6-octenoic acid (MeBm2t), was synthesized in four steps beginning with th...

journal_title：Journal of medicinal chemistry

authors： Aebi JD,Deyo DT,Sun CQ,Guillaume D,Dunlap B,Rich DH

更新日期：1990-03-01 00:00:00

abstract：:The free fatty acid receptor GPR40 is predominantly expressed in pancreatic β-cells and enhances insulin secretion in a glucose dependent manner. Therefore, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia for the treatment of type 2 diabetes mellitus (T2DM). Chemically a...

journal_title：Journal of medicinal chemistry

authors： Li H,Huang Q,Chen C,Xu B,Wang HY,Long YQ

更新日期：2017-04-13 00:00:00

abstract：:The insertion of single 1,4-disubstituted 1,2,3-triazoles as metabolically stable bioisosteres of trans-amide bonds (triazole scan) was recently applied to the 177Lu-labeled tumor-targeting analog of minigastrin, [Nle15]MG11. The reported novel mono-triazolo-peptidomimetics of [Nle15]MG11 showed either improved resist...

journal_title：Journal of medicinal chemistry

authors： Grob NM,Schmid S,Schibli R,Behe M,Mindt TL

更新日期：2020-05-14 00:00:00

abstract：:Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2...

journal_title：Journal of medicinal chemistry

authors： Villhauer EB,Brinkman JA,Naderi GB,Burkey BF,Dunning BE,Prasad K,Mangold BL,Russell ME,Hughes TE

更新日期：2003-06-19 00:00:00

abstract：:As part of an ongoing effort to discover novel small-molecule antifolates combining the enzyme-binding species selectivity of trimethoprim (TMP) with the potency of piritrexim (PTX), 10 previously unreported 2,4-diamino-5-(2'-methoxy-5'-substituted)benzylpyrimidines (2-11) containing a carboxyl group at the distal end...

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Forsch RA,Queener SF

更新日期：2003-04-24 00:00:00

abstract：:A new computational method for the in situ generation of small molecules within the binding site of a protein is described. The method has been evaluated using two well-studied systems, dihydrofolate reductase and thymidylate synthase. The method has also been used to guide improvements to inhibitors of HIV-1 protease...

journal_title：Journal of medicinal chemistry

authors： Gehlhaar DK,Moerder KE,Zichi D,Sherman CJ,Ogden RC,Freer ST

更新日期：1995-02-03 00:00:00

abstract：:The discovery of an exceptionally potent series of thrombin receptor (PAR-1) antagonists based on the natural product himbacine is described. Optimization of this series has led to the discovery of 4 (SCH 530348), a potent, oral antiplatelet agent that is currently undergoing Phase-III clinical trials for acute corona...

journal_title：Journal of medicinal chemistry

authors： Chackalamannil S,Wang Y,Greenlee WJ,Hu Z,Xia Y,Ahn HS,Boykow G,Hsieh Y,Palamanda J,Agans-Fantuzzi J,Kurowski S,Graziano M,Chintala M

更新日期：2008-06-12 00:00:00

abstract：:Compound 1 (1-benzyl-3-methyl-4-[4-(4-fluorophenyl)-4-oxobutyl]piperazine), a synthetic intermediate identified as a potential atypical antipsychotic, was selected as the starting point for pharmacological improvement. From 1, sequential structural variations were conducted in order to improve its potency and oral bio...

journal_title：Journal of medicinal chemistry

authors： Bolós J,Gubert S,Anglada L,Planas JM,Burgarolas C,Castelló JM,Sacristán A,Ortiz JA

更新日期：1996-07-19 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：:The diester 2a obtained from 1,1'-ferrocenedicarboxylic acid and the highly and indiscriminately cytotoxic fungal metabolite illudin M (1) displayed antiproliferative activity at submicromolar IC(50) (72 h) values against a panel of eight cancer cell lines. Compound 2a was about 40 times less toxic than 1 to nonmalign...

journal_title：Journal of medicinal chemistry

authors： Schobert R,Seibt S,Mahal K,Ahmad A,Biersack B,Effenberger-Neidnicht K,Padhye S,Sarkar FH,Mueller T

更新日期：2011-09-22 00:00:00

abstract：:Twenty-six episilon-rhodomycinone glycosides have been synthesized. These include the episilon-rhodomycinone glycosides of 2-deoxy-L-fucose, 2-deoxy-L-rhamnose, and 2-deoxy-D-ribose as well as their 2-hydroxyl derivatives. NMR spectroscopy showed that all the glycosides prepared had the saccharide residues linked to p...

journal_title：Journal of medicinal chemistry

authors： Khadem HS,Swartz DL,Cermak RC

更新日期：1977-07-01 00:00:00

abstract：:Several heterocyclic analogues of the potent 1-[[4-(aminoalkoxy)phenyl]sulfonyl]indolizines were synthesized and evaluated for their antagonistic calcium activities in comparison with the 1-sulfonylindolizine SR 33557 and the usual calcium antagonist references verapamil, cis-(+)-diltiazem, and nifedipine. The bicycli...

journal_title：Journal of medicinal chemistry

authors： Gubin J,de Vogelaer H,Inion H,Houben C,Lucchetti J,Mahaux J,Rosseels G,Peiren M,Clinet M,Polster P

更新日期：1993-05-14 00:00:00

abstract：:4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with...

journal_title：Journal of medicinal chemistry

authors： Rosen T,Seeger TF,McLean S,Nagel AA,Ives JL,Guarino KJ,Bryce D,Furman J,Roth RW,Chalabi PM

更新日期：1990-11-01 00:00:00