Doxazosin-related alpha1-adrenoceptor antagonists with prostate antitumor activity.

abstract：:Seven pyranoses and three furanoses with a nitrogen in the ring were prepared by chemical synthesis, microbial conversion, and isolation from plants to investigate the contribution of epimerization, deoxygenation, and conformation to the potency of inhibition and specificity of mammalian glycosidases. The seven pyrano...

journal_title：Journal of medicinal chemistry

authors： Asano N,Oseki K,Kizu H,Matsui K

更新日期：1994-10-28 00:00:00

abstract：:Various 3'-deoxythymidine analogues with an heterocyclic five-membered ring in the 3'-erythro position have been synthesized. The pyrrol-1-yl (3) and the 1,2,4-triazol-4-yl (5) compounds were synthesized from 1-(3-amino-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine. The pyrazol-1-yl (16a), imidazol-1-yl (16b), and...

journal_title：Journal of medicinal chemistry

authors： Wigerinck P,Van Aerschot A,Janssen G,Claes P,Balzarini J,De Clercq E,Herdewijn P

更新日期：1990-02-01 00:00:00

abstract：:4-Deoxy-alpha-GalCer analogues are considered weaker agonists than KRN7000 for the stimulation of human iNKT cells, but this remains strongly debated. In this work, we described a strategy toward 4-deoxy-alpha-GalCers with, as a key step, a metathesis reaction allowing sphingosine modifications from a single ethylenic...

journal_title：Journal of medicinal chemistry

authors： Lacône V,Hunault J,Pipelier M,Blot V,Lecourt T,Rocher J,Turcot-Dubois AL,Marionneau S,Douillard JY,Clément M,Le Pendu J,Bonneville M,Micouin L,Dubreuil D

更新日期：2009-08-13 00:00:00

abstract：:New analogues of human cholecystokinin in which the Tyr(SO3H) has been replaced by Phe(p-CH2SO3Na), methionines by norleucines, and tryptophan by 2-naphthylalanine([Phe(p-CH2- SO3Na)27,Nle28,31,Nal30]-CCK26-33 and [Phe(p-CH2SO3Na)27,Nle7,28,31,Nal30]-CCK-33) were synthesized by Fmoc solid phase methodology on two diff...

journal_title：Journal of medicinal chemistry

authors： Miranda MT,Liddle RA,Rivier JE

更新日期：1993-06-11 00:00:00

abstract：:The design and preparation of ortho-substituted benzofused macrocyclic lactams are described. The benzofused macrocyclic lactams were designed as neutral endopeptidase 24.11 (NEP) inhibitors. Docking studies were carried out in a model of thermolysin (TLN) using the MACROMODEL and QXP modeling programs to select suita...

journal_title：Journal of medicinal chemistry

authors： Ksander GM,de Jesus R,Yuan A,Ghai RD,Trapani A,McMartin C,Bohacek R

更新日期：1997-02-14 00:00:00

abstract：:2-Acetamido-5-O-acetyl-6-O-acyl-2-deoxy-3-O-[(R)-2-propionyl-L-alanyl-D- isoglutamine]-D-glucofuranoses, designed as prodrug forms of the corresponding immunoadjuvant-active 6-O-acyl derivatives of N-acetylmuramyl dipeptide (MDP), were synthesized from benzyl 2-acetamido-2-deoxy-5, 6-O-isopropylidene-beta-D-glucofuran...

journal_title：Journal of medicinal chemistry

authors： Durette PL,Dorn CP Jr,Friedman A,Schlabach A

更新日期：1982-09-01 00:00:00

abstract：:A series of 59 alpha-aryl-alpha-thioether-alkyl, -alkanenitrile, and -alkanecarboxylic acid methyl ester tetrahydroisoquinoline and isoindoline derivatives (15a-48) were synthesized and evaluated as multidrug resistance (MDR) reversal agents. The compounds were tested on S1-B1-20 human colon carcinoma cells selected f...

journal_title：Journal of medicinal chemistry

authors： Berger D,Citarella R,Dutia M,Greenberger L,Hallett W,Paul R,Powell D

更新日期：1999-06-17 00:00:00

abstract：:The alcohol-abuse deterrent disulfiram (DSF) is shown to have a highly selective toxicity against melanoma in culture, inducing a largely apoptotic response, with much lower toxicity against several other cell lines. Melanoma cell lines derived from different stages (radial, vertical, and metastatic phase) were all se...

journal_title：Journal of medicinal chemistry

authors： Cen D,Brayton D,Shahandeh B,Meyskens FL Jr,Farmer PJ

更新日期：2004-12-30 00:00:00

abstract：:A metabolism-based approach toward the optimization of a series of N-arylsulfonamide-based γ-secretase inhibitors is reported. The lead cyclohexyl analogue 6 suffered from extensive oxidation on the cycloalkyl motif by cytochrome P450 3A4, translating into poor human liver microsomal stability. Knowledge of the metabo...

journal_title：Journal of medicinal chemistry

authors： Stepan AF,Karki K,McDonald WS,Dorff PH,Dutra JK,Dirico KJ,Won A,Subramanyam C,Efremov IV,O'Donnell CJ,Nolan CE,Becker SL,Pustilnik LR,Sneed B,Sun H,Lu Y,Robshaw AE,Riddell D,O'Sullivan TJ,Sibley E,Capetta S,Atch

更新日期：2011-11-24 00:00:00

abstract：:A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2-(alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7-12 and the related 6-(2,6-difluorobenzyl) counterparts 13-15 in HIV-1 infected cells and in the HIV-1 reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs showed up to picomola...

journal_title：Journal of medicinal chemistry

authors： Rotili D,Tarantino D,Nawrozkij MB,Babushkin AS,Botta G,Marrocco B,Cirilli R,Menta S,Badia R,Crespan E,Ballante F,Ragno R,Esté JA,Maga G,Mai A

更新日期：2014-06-26 00:00:00

abstract：:5-(2,2-Difluorovinyl)uracil (IV) was synthesized from 2,4-dimethoxy-5-bromopyrimidine by sequential formylation, difluoromethylenation, and removal of the 2- and 4-methyl groups. Condensation of the trimethylsilyl derivative of IV with protected D-erythro-pentofuranosyl chloride followed by separation of anomers and d...

journal_title：Journal of medicinal chemistry

authors： Bobek M,Kavai I,De Clercq E

更新日期：1987-08-01 00:00:00

abstract：:A series of new amine cyanoborane derivatives were synthesized and exhibited antifungal activity. A long alkyl chain attached to the nitrogen of the amine cyanoboranes and carboxyboranes enhances antifungal activity. An enhanced activity was also obtained upon the halogenation of the amine cyanoboranes as well as in t...

journal_title：Journal of medicinal chemistry

authors： Takrouri K,Oren G,Polacheck I,Sionov E,Shalom E,Katzhendler J,Srebnik M

更新日期：2006-08-10 00:00:00

abstract：:Emerging studies have shown that mitochondrial DNA (mtDNA) is a potential target for cancer therapy. Herein, six cyclometalated Ir(III) complexes Ir1-Ir6 containing a series of extended planar diimine ligands have been designed and assessed for their efficacy as anticancer agents. Ir1-Ir6 show much higher cytotoxicity...

journal_title：Journal of medicinal chemistry

authors： Cao JJ,Zheng Y,Wu XW,Tan CP,Chen MH,Wu N,Ji LN,Mao ZW

更新日期：2019-04-11 00:00:00

abstract：:Specific interactions between Src homology 2 (SH2) domain-containing proteins and the phosphotyrosine-containing counterparts play significant role in cellular protein tyrosine kinase (PTK) signaling pathways. The SH2 domain inhibitors could potentially serve as drug candidates in treating human diseases. Here we have...

journal_title：Journal of medicinal chemistry

authors： Chu CY,Chang CP,Chou YT,Handoko,Hu YL,Lo LC,Lin JJ

更新日期：2013-04-11 00:00:00

abstract：:Twenty-two structural derivatives of clonidine [2-(2,6-dichlorophenylimino)imidazolidine] have been synthesized and their main physicochemical parameters (log P, deltaRM, pKa) determined. Quantitative correlations between the peripheral alpha-mimetic action (pithed rats) and physicochemical parameters pointed out the ...

journal_title：Journal of medicinal chemistry

authors： Rouot B,Leclerc G,Wermuth CG

更新日期：1976-08-01 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：:Inherently conducting polymers (ICPs) are a specific category of synthetic polymers with distinctive electro-optic properties, which involve conjugated chains with alternating single and double bonds. Polyaniline (PANI), as one of the most well-known ICPs, has outstanding potential applications in biomedicine because ...

journal_title：Journal of medicinal chemistry

authors： Zare EN,Makvandi P,Ashtari B,Rossi F,Motahari A,Perale G

更新日期：2020-01-09 00:00:00

abstract：:Kadsurenone, a specific receptor antagonist of platelet-activating factor (PAF), and its analogues were prepared from derivatives of cinnamyl alcohol and (allyloxy)phenol. Racemic kadsurenone, resolvable by a Chiralpak column at low temperatures, has an IC50 value of 2 X 10(-7) M, which is about 50% of the activity of...

journal_title：Journal of medicinal chemistry

authors： Ponpipom MM,Bugianesi RL,Brooker DR,Yue BZ,Hwang SB,Shen TY

更新日期：1987-01-01 00:00:00

abstract：:A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed s...

journal_title：Journal of medicinal chemistry

authors： Nielsen SF,Thastrup O,Pedersen R,Olsen CE,Christensen SB

更新日期：1995-01-20 00:00:00

abstract：:Dispiro-1,2,4,5-tetraoxanes and 1,2,4-trioxolanes represent attractive classes of synthetic antimalarial peroxides due to their structural simplicity, good stability, and impressive antimalarial activity. We investigated the reactivity of a series of potent amide functionalized tetraoxanes with Fe(II)gluconate, FeSO(4...

journal_title：Journal of medicinal chemistry

authors： Bousejra-El Garah F,Wong MH,Amewu RK,Muangnoicharoen S,Maggs JL,Stigliani JL,Park BK,Chadwick J,Ward SA,O'Neill PM

更新日期：2011-10-13 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：:Analogues of nicotinic acid adenine dinucleotide phosphate (NAADP) with substitution at either the 4- or the 5-position position of the nicotinic acid moiety have been synthesized from NADP enzymatically using Aplysia californica ADP-ribosyl cyclase or mammalian NAD glycohydrolase. Substitution at the 4-position of th...

journal_title：Journal of medicinal chemistry

authors： Jain P,Slama JT,Perez-Haddock LA,Walseth TF

更新日期：2010-11-11 00:00:00

abstract：:It is common practice to calculate large numbers of molecular descriptors, apply variable selection procedures to reduce the numbers, and then construct multiple linear regression (MLR) models with biological activity. The significance of these models is judged using the usual statistical tests. Unfortunately, these t...

journal_title：Journal of medicinal chemistry

authors： Livingstone DJ,Salt DW

更新日期：2005-02-10 00:00:00

abstract：:Based on the X-ray cocrystal structure of the Tang-Ghosh heptapeptide inhibitor 1 (OM00-3), a series of macroheterocyclic analogues were designed and synthesized. Analogues containing dithia, dioxa, oxathia, and carbathia macrocycles were synthesized by methods relying on ring-closing olefin metathesis for the dioxa a...

journal_title：Journal of medicinal chemistry

authors： Hanessian S,Yang G,Rondeau JM,Neumann U,Betschart C,Tintelnot-Blomley M

更新日期：2006-07-27 00:00:00

abstract：:A variety of 2,3-disubstituted 5,7-dimethyl-1,8-naphthyridines was synthesized and tested in saline-loaded rats for their diuretic properties. The 2-amino-3-carbomethoxy and four 2-amino-3-N-alkylcarbamoyl compounds exhibited significant activity as measured by volume output; however, they were generally less potent t...

journal_title：Journal of medicinal chemistry

authors： Hawes EM,Gorecki DK,Gedir RG

更新日期：1977-06-01 00:00:00

abstract：:Several esters of beta-carboline-3-carboxylic acid were synthesized and tested in respect to their affinity for the benzodiazepine receptor in bovine cortex membranes. Out of these derivatives, the methyl, ethyl, and n-propyl ester were clearly the most potent, while the n-butyl, benzyl, and 3-pyridylmethyl ester were...

journal_title：Journal of medicinal chemistry

authors： Lippke KP,Schunack WG,Wenning W,Müller WE

更新日期：1983-04-01 00:00:00

abstract：:The synthesis of various chiral derivatives of (+)-erythro-9-(2-hydroxy-3-nonyl)adenine, (+)-EHNA, from (2S,3R)-3-amino-1,2-O-isopropylidene-1,2-nonanediol by condensation with 5-amino-4,6-dichloropyrimidine is described. The compounds synthesized were C1'- and nor-C1'-(+)-EHNA derivatives. When tested with calf splee...

journal_title：Journal of medicinal chemistry

authors： Harriman GC,Poirot AF,Abushanab E,Midgett RM,Stoeckler JD

更新日期：1992-10-30 00:00:00

abstract：:6-Substituted 6-deoxy-L-galactose (L-fucose) derivatives were synthesized as potential antimetabolites of L-fucose. The cytotoxic effects of these compounds were evaluated on P388 leukemia cells in culture. The L-fucose analogues which showed the most potent growth inhibition were the sulfonyl ester, bromo, and iodo d...

journal_title：Journal of medicinal chemistry

authors： May JA Jr,Sartorelli AC

更新日期：1979-08-01 00:00:00

abstract：:A unique strategy for the enhancement of secondary binding of an inhibitor to an enzyme has been demonstrated in the design of new human immunodeficiency virus (HIV) protease inhibitors. When the planar benzene ring of a 4-hydroxycoumarin lead compound (1a, Ki = 0.800 microM) was replaced with medium-sized (i.e., 7-9)...

journal_title：Journal of medicinal chemistry

authors： Romines KR,Watenpaugh KD,Tomich PK,Howe WJ,Morris JK,Lovasz KD,Mulichak AM,Finzel BC,Lynn JC,Horng MM

更新日期：1995-05-26 00:00:00

abstract：:A series of 1-H-pyrazole-3-carboxamide derivatives have been designed and synthesized that exhibit excellent FLT3 and CDK inhibition and antiproliferative activities. A structure-activity-relationship study illustrates that the incorporation of a pyrimidine-fused heterocycle at position 4 of the pyrazole is critical f...

journal_title：Journal of medicinal chemistry

authors： Wang Y,Zhi Y,Jin Q,Lu S,Lin G,Yuan H,Yang T,Wang Z,Yao C,Ling J,Guo H,Li T,Jin J,Li B,Zhang L,Chen Y,Lu T

更新日期：2018-02-22 00:00:00