The identification of perillyl alcohol glycosides with improved antiproliferative activity.

abstract：:Evidence indicating that modifications at the 5- and 10-positions of classical folic acid antimetabolites lead to compounds with favorable differential membrane transport in tumor vs. normal proliferative tissue prompted an investigation of 5-alkyl-5-deaza analogues. 2-Amino-4-methyl-3,5-pyridinedicarbonitrile, prepar...

journal_title：Journal of medicinal chemistry

authors： Piper JR,McCaleb GS,Montgomery JA,Kisliuk RL,Gaumont Y,Sirotnak FM

更新日期：1986-06-01 00:00:00

abstract：:FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophospho...

journal_title：Journal of medicinal chemistry

authors： Mahboobi S,Uecker A,Sellmer A,Cénac C,Höcher H,Pongratz H,Eichhorn E,Hufsky H,Trümpler A,Sicker M,Heidel F,Fischer T,Stocking C,Elz S,Böhmer FD,Dove S

更新日期：2006-06-01 00:00:00

abstract：:The JAK-STAT3 pathway regulates genes that are important in cell proliferation and thus is a promising target for cancer therapy. A high-throughput screening (HTS) campaign using an Apo-ONE Homogenous Caspase 3/7 assay in U266 cells identified 4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 4 as a po...

journal_title：Journal of medicinal chemistry

authors： Xu J,Cole DC,Chang CP,Ayyad R,Asselin M,Hao W,Gibbons J,Jelinsky SA,Saraf KA,Park K

更新日期：2008-07-24 00:00:00

abstract：:2-Fluoro-, 4-fluoro-, and 6-fluorophenylephrine (6-FPE) were synthesized from the corresponding fluorinated 3-hydroxybenzaldehydes. New routes to 2-fluoro- and 6-fluoro-3-hydroxybenzaldehydes were developed based on regioselective lithiation of 2- and 4-[(dimethyl-tert-butylsilyl)oxy]fluorobenzene ortho to fluorine. A...

journal_title：Journal of medicinal chemistry

authors： Kirk KL,Olubajo O,Buchhold K,Lewandowski GA,Gusovsky F,McCulloh D,Daly JW,Creveling CR

更新日期：1986-10-01 00:00:00

abstract：:A novel class of 2-(4-heterocyclylphenyl)-1,4-dihydropyridines (2-38) possessing antagonist activity against platelet activating factor (PAF) was prepared by the Hantzsch synthesis from a variety of ethyl 4'-heterocyclic-substituted benzoylacetates, aryl or heteroaryl aldehydes, and substituted 3-aminocrotonamides or ...

journal_title：Journal of medicinal chemistry

authors： Cooper K,Fray MJ,Parry MJ,Richardson K,Steele J

更新日期：1992-08-21 00:00:00

abstract：:Angiogenesis is vital for solid tumor growth, and its prevention is a proven strategy for the treatment of disease states such as cancer. The vascular endothelial growth factor (VEGF) pathway provides several opportunities by which small molecules can act as inhibitors of endothelial proliferation and migration. Criti...

journal_title：Journal of medicinal chemistry

authors： La DS,Belzile J,Bready JV,Coxon A,DeMelfi T,Doerr N,Estrada J,Flynn JC,Flynn SR,Graceffa RF,Harriman SP,Larrow JF,Long AM,Martin MW,Morrison MJ,Patel VF,Roveto PM,Wang L,Weiss MM,Whittington DA,Teffera Y,Zhao Z

更新日期：2008-03-27 00:00:00

abstract：:Mercaptopurine (6-MP), thioguanine (6-TG), and azathioprine (AZA) are purine antimetabolites introduced as anticancer or immunosuppressive drugs decades ago. Methylated AZA, called MAZA, is among the investigational drugs. The present study compares MAZA to the widely recognized drugs AZA, 6-MP, and 6-TG with respect ...

journal_title：Journal of medicinal chemistry

authors： Hoffmann M,Chrzanowska M,Hermann T,Rychlewski J

更新日期：2005-06-30 00:00:00

abstract：:A series of 1-R-5-alkoxy-3H-1,4-benzodiazepin-2(1H)-ones was prepared and evaluated for central nervous system depressant activity. Several of these compounds, in particular, 7-chloro-5-ethoxy-1-methyl-3H-1,4-benzodiazepin-2(1H)-one (2), gave a profile and activity level similar to diazepam when measured in mice. ...

journal_title：Journal of medicinal chemistry

authors： Gogerty JH,Griot RG,Habeck D,Iorio LC,Houlihan WJ

更新日期：1977-07-01 00:00:00

abstract：:Our laboratory recently reported the development of novel prodrug chemistry for the intracellular delivery of phosphotyrosine mimetics. This chemistry has now been adapted for the synthesis of a prodrug that delivers the nonhydrolyzable difluoromethylphosphonate moiety intracellularly. Activation of the prodrug genera...

journal_title：Journal of medicinal chemistry

authors： Boutselis IG,Yu X,Zhang ZY,Borch RF

更新日期：2007-02-22 00:00:00

abstract：:The coupling of two different pharmacophores, each endowed with different biological properties, afforded the hybrid compound lipocrine (7), whose biological profile was markedly improved relative to those of prototypes tacrine and lipoic acid. Lipocrine is the first compound that inhibits the catalytic activity of AC...

journal_title：Journal of medicinal chemistry

authors： Rosini M,Andrisano V,Bartolini M,Bolognesi ML,Hrelia P,Minarini A,Tarozzi A,Melchiorre C

更新日期：2005-01-27 00:00:00

abstract：:Cancer cell targeting peptides have emerged as a highly efficient approach for selective delivery of chemotherapeutics and diagnostics to different cancer cells. However, the use of α-peptides in pharmaceutical applications is hindered by their enzymatic degradation and low bioavailability. Starting with a 10-mer α-pe...

journal_title：Journal of medicinal chemistry

authors： Soudy R,Gill A,Sprules T,Lavasanifar A,Kaur K

更新日期：2011-11-10 00:00:00

abstract：:A family of analogues of des-AA(1,2,5)-[DTrp(8)/D2Nal(8)]-SRIF that contain a 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 was identified that has high affinity and selectivity for human somatostatin receptor subtype 1 (sst1). The binding affinities of des-AA(1,2,5)-[DTrp(8),IAmp(9)]-SRIF (c[H-Cys-Lys...

journal_title：Journal of medicinal chemistry

authors： Rivier JE,Hoeger C,Erchegyi J,Gulyas J,DeBoard R,Craig AG,Koerber SC,Wenger S,Waser B,Schaer JC,Reubi JC

更新日期：2001-06-21 00:00:00

abstract：:omega-Acryloyl anionic surfactants, whose polar heads are derived from amino acids, have been telomerized to prepare polyanions of a predetermined molecular weight. The main goal of this study was to verify whether the antiviral activity is influenced by the degree of polymerization of the polyanions. The oligomeric p...

journal_title：Journal of medicinal chemistry

authors： Leydet A,Barragan V,Boyer B,Montéro JL,Roque JP,Witvrouw M,Este J,Snoeck R,Andrei G,De Clercq E

更新日期：1997-01-31 00:00:00

abstract：:Androgens are well-known to stimulate prostate cancer (PC) growth. Thus, blockade of androgen production in testes and adrenals by CYP17 inhibition is a promising strategy for the treatment of PC. Moreover, many PC patients suffer from glucocorticoid overproduction, and importantly mutated androgen receptors can be st...

journal_title：Journal of medicinal chemistry

authors： Hu Q,Jagusch C,Hille UE,Haupenthal J,Hartmann RW

更新日期：2010-08-12 00:00:00

abstract：:We have reported the preparation and anticancer evaluation of certain 4-anilinofuro[2,3-b]quinolines. However, drawbacks such as lack of selective cytotoxicity, poor oral bioavailability, and poor water solubility exhibited by these compounds prompted us to search for newer derivatives. Among them, (E)-1-(4-(furo[2,3-...

journal_title：Journal of medicinal chemistry

authors： Chen YW,Chen YL,Tseng CH,Liang CC,Yang CN,Yao YC,Lu PJ,Tzeng CC

更新日期：2011-07-14 00:00:00

abstract：:Several potentially irreversible ligands (i.e., wash-resistant binding inhibitors) for the cocaine receptor site on the dopamine transporter, derived from (-)-cocaine or 3 beta-phenyltropan-2 beta-carboxylic acid methyl ester (WIN 35,065-2), were prepared and shown to produce wash-resistant inhibition of [3H]-3 beta-(...

journal_title：Journal of medicinal chemistry

authors： Carroll FI,Gao Y,Abraham P,Lewin AH,Lew R,Patel A,Boja JW,Kuhar MJ

更新日期：1992-05-15 00:00:00

abstract：:The five dopamine receptor subtypes (D1-5) are activated by the endogenous catecholamine dopamine. Sustained research has sought to identify selective ligands for receptor subtypes. In particular, activation of the D1 receptor has attracted attention due to its promising role in neurological diseases. Initial attempts...

journal_title：Journal of medicinal chemistry

authors： Hall A,Provins L,Valade A

更新日期：2019-01-10 00:00:00

abstract：:Dimethylallylguanidine, also known as galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing p...

journal_title：Journal of medicinal chemistry

authors： Coxon GD,Furman BL,Harvey AL,McTavish J,Mooney MH,Arastoo M,Kennedy AR,Tettey JM,Waigh RD

更新日期：2009-06-11 00:00:00

abstract：:A series of 2,6- and 2,4-dihydroxyphenyl alkyl ketones has been investigated as inhibitors of hepatic microsomal aniline hydroxylase and aminopyrine demethylase activities. Structural alterations in both series did little to enhance the inhibitory activity of the parent compounds 2,6-dihydroxyacetophenone (3) and 2,4-...

journal_title：Journal of medicinal chemistry

authors： Bobik A,Holder GM,Ryan AJ

更新日期：1977-09-01 00:00:00

abstract：:The crystal and molecular structure of metyrapone, a powerful inhibitor of certain cytochromes P-450, is described. Cytochrome P-450 enzymes are involved in metabolic processes, including those activating insecticides, drugs, and carcinogens. Metyrapone inhibits both the adrenal cytochrome P-450 catalyzing 11-beta-hyd...

journal_title：Journal of medicinal chemistry

authors： Rossi M

更新日期：1983-09-01 00:00:00

abstract：:In the framework of the design and development of TGR5 agonists, we reported that the introduction of a C(23)(S)-methyl group in the side chain of bile acids such as chenodeoxycholic acid (CDCA) and 6-ethylchenodeoxycholic acid (6-ECDCA, INT-747) affords selectivity for TGR5. Herein we report further lead optimization...

journal_title：Journal of medicinal chemistry

authors： Pellicciari R,Gioiello A,Macchiarulo A,Thomas C,Rosatelli E,Natalini B,Sardella R,Pruzanski M,Roda A,Pastorini E,Schoonjans K,Auwerx J

更新日期：2009-12-24 00:00:00

abstract：:Fragment-based drug design exploits initial screening of low molecular weight compounds and their concomitant affinity improvement. The multitude of possible chemical modifications highlights the necessity to obtain structural information about the binding mode of a fragment. Herein we describe a novel NMR methodology...

journal_title：Journal of medicinal chemistry

authors： Geist L,Mayer M,Cockcroft XL,Wolkerstorfer B,Kessler D,Engelhardt H,McConnell DB,Konrat R

更新日期：2017-11-09 00:00:00

abstract：:Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute the peptide pharmacophore i...

journal_title：Journal of medicinal chemistry

authors： Van der Poorten O,Knuhtsen A,Sejer Pedersen D,Ballet S,Tourwé D

更新日期：2016-12-22 00:00:00

abstract：:In the present study, L-prolyl-L-leucyl-glycinamide (1) peptidomimetics 3a-3d and 4a-4d were synthesized utilizing alpha, alpha-disubstituted amino acids. These analogues were designed to explore the conformational effects of constraints at the phi3 and psi3 torsion angles. Constrained conformations were verified by t...

journal_title：Journal of medicinal chemistry

authors： Evans MC,Pradhan A,Venkatraman S,Ojala WH,Gleason WB,Mishra RK,Johnson RL

更新日期：1999-04-22 00:00:00

abstract：:Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-targeted kinase inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tum...

journal_title：Journal of medicinal chemistry

authors： Daydé-Cazals B,Fauvel B,Singer M,Feneyrolles C,Bestgen B,Gassiot F,Spenlinhauer A,Warnault P,Van Hijfte N,Borjini N,Chevé G,Yasri A

更新日期：2016-04-28 00:00:00

abstract：:To determine if the conjugation of a small receptor ligand to a peptidic carrier to potentially facilitate transport across the blood-brain barrier (BBB) by "molecular Trojan horse" transcytosis is feasible, we synthesized several transport peptide-fallypride fusion molecules as model systems and determined their bind...

journal_title：Journal of medicinal chemistry

authors： Wängler C,Chowdhury S,Höfner G,Djurova P,Purisima EO,Bartenstein P,Wängler B,Fricker G,Wanner KT,Schirrmacher R

更新日期：2014-05-22 00:00:00

abstract：:The influence of structure on DT-diaphorase substrate activity, topoisomerase II inhibition activity, and DNA reductive alkylation was studied for the 6-aziridinylpyrrolo[1,2-alpha]benzimidazolequinones (PBIs) and the 6-acetamidopyrrolo[1,2-alpha]benzimidazolequinones (APBIs). The PBIs are reductively activated by DT-...

journal_title：Journal of medicinal chemistry

authors： Skibo EB,Gordon S,Bess L,Boruah R,Heileman MJ

更新日期：1997-04-25 00:00:00

abstract：:This is a review of the macrolide and ketolide field focusing on differentiating the pharmacodynamics and especially the toxicology of the macrolides and ketolides. We emphasize the diversity in pharmacodynamics and toxicity of the macrolides and ketolides, resulting from even small structural changes, which makes it ...

journal_title：Journal of medicinal chemistry

authors： Fernandes P,Pereira D,Watkins PB,Bertrand D

更新日期：2020-06-25 00:00:00

abstract：:The importance of steric factors in quantitative structure-activity relationships involving steroid hormones is discussed. a variety of steric parameters, such as parachlor, molecular volume, van der Waals volume, and including difference and squared steric terms, is explored in an attempt to find preferred forms for...

journal_title：Journal of medicinal chemistry

authors： Coburn RA,Solo AJ

更新日期：1976-06-01 00:00:00

abstract：:We have previously identified phenylguanidine and phenyl-2-aminoimidazoline compounds as high affinity ligands with conflicting functional activity at the α2-adrenoceptor, a G-protein-coupled receptor with relevance in several neuropsychiatric conditions. In this paper we describe the design, synthesis, and pharmacolo...

journal_title：Journal of medicinal chemistry

authors： Kelly B,McMullan M,Muguruza C,Ortega JE,Meana JJ,Callado LF,Rozas I

更新日期：2015-01-22 00:00:00