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 NMR spectroscopic studies, including homonuclear and heteronuclear correlation experiments. The absolute configurations of the new compounds were determined by CD studies, chemical correlations or biogenetic grounds. All the natural compounds and derivative 20 have been tested on human MDR1-transfected NIH-3T3 cells, to determine their ability to revert the multidrug resistance phenotype due to P-glycoprotein overexpression. Six compounds from this series (1, 8, 11, 12, 13 and 14) showed similar effectiveness to the classical P-glycoprotein modulator verapamil when reversing resistance to daunorubicin, but it is up to sixteen times greater than that of verapamil when reversing resistance to vinblastine. The structure-activity relationships are discussed.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Muñoz-Martínez F,Mendoza CR,Bazzocchi IL,Castanys S,Jiménez IA,Gamarro Fdoi
10.1021/jm058003fkeywords:
subject
Has Abstractpub_date
2005-06-30 00:00:00pages
4266-75issue
13eissn
0022-2623issn
1520-4804journal_volume
48pub_type
杂志文章abstract：:SHP-2, a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene, mediates cell signaling by growth factors and cytokines via the RAS/MAP kinase pathway. Somatic mutations in PTPN11 gene account for approximately 18% of juvenile myelomonocytic leukemia (JMML) patients. Moreover, SHP-2 mutations leading to ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8004306
更新日期：2008-09-11 00:00:00
abstract：:Two new long-acting hydrazone derivatives of 14-hydroxydihydromorphinones have been synthesized, oxymorphazone and naltrexazone. Both derivatives show high affinity for opiate binding sites in vitro, similar to naloxazone, the hydrazone analogue of naloxone. Sodium and manganese shifts imply that naltrexazone, like na...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00180a019
更新日期：1980-06-01 00:00:00
abstract：:We describe a new method, Compass, for predicting the biological activities of molecules based on the activities and three-dimensional structures of other molecules. The method improves on previous techniques by representing only the surface of molecules, by incorporating a nonlinear statistical method, and by automat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00041a010
更新日期：1994-07-22 00:00:00
abstract：:Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles, isoxazol-3- and -5-ones and a pyrazol-3-one, showed...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00004a008
更新日期：1995-02-17 00:00:00
abstract：:In a previous paper, we reported the N-hydroxyformamidine derivative HET0016 as a potent and selective 20-HETE synthase inhibitor. Despite its attraction as a potential therapeutic agent for cerebral diseases, the preparation of an injectable formulation of HET0016 was limited by its poor solubility under neutral cond...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020557k
更新日期：2003-12-04 00:00:00
abstract：:The recently described potent and selective GABAA antagonist SR 95531 (gabazine) is compared to six other GABAA antagonists: (+)-bicuculline, (-)-securinine, (+)-tubocurarine, iso-THAZ, R-5135, and pitrazepine. Starting from ab initio molecular orbital calculations performed on crystal atomic coordinates, attempts wer...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00089a005
更新日期：1992-05-29 00:00:00
abstract：:A series of 1-imidazolyl(alkyl)-substituted quinoline, isoquinoline, naphthalene, benzo[b]furan, and benzo[b]thiophene derivatives was synthesized as dual inhibitors of thromboxane A(2) synthase (P450 TxA(2)) and aromatase (P450 arom). Dual inhibition of these enzymes could be a novel strategy for the treatment of mam...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm991180u
更新日期：2000-05-04 00:00:00
abstract：:To further develop and evaluate a pharmacophore model previously proposed by Cook and co-workers (Drug Des. Discovery 1995, 12, 193-248) for ligands binding to the benzodiazepine site of the GABA(A) receptor, 40 new flavone derivatives have been synthesized and their affinities for the benzodiazepine site have been de...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020839k
更新日期：2002-09-12 00:00:00
abstract：:As part of our studies on the design of agonists of the luteinizing hormone-releasing hormone (LH-RH), we have synthesized the [des-Gly-NH2(10)]-LH-RH N-methylhydrazide (1), the corresponding thiosemicarbazide (2), and the N-formyl- (3) N-acetyl- (4) and N-(trifluoroacetyl)hydrazide (5). Analogue 1 may be regarded as ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00134a021
更新日期：1981-02-01 00:00:00
abstract：:Members of the Wee family of kinases negatively regulate the cell cycle via phosphorylation of CDK1 and are considered potential drug targets. Herein, we investigated the structure-function relationship of human Wee1, Wee2, and Myt1 (PKMYT1). Purified recombinant full-length proteins and kinase domain constructs diffe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00996
更新日期：2017-09-28 00:00:00
abstract：:A series of cyclopropane-based conformationally restricted analogues of histamine, the "folded" cis-analogues, i.e., (1S,2R)-2-(aminomethyl)-1-(1H-imidazol-4-yl)cyclopropane (11), (1S,2S)-2-(2-aminoethyl)-1-(1H-imidazol-4-yl)cyclopropane (13), and their enantiomers ent-11 and ent-13, and the "extended" trans-analogues...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020415q
更新日期：2003-05-08 00:00:00
abstract：:A number of bis(diazeniumdiolates) that we designed to release up to 4 mol of nitric oxide (NO) and that are structural analogues of the NO prodrug and anticancer lead compound O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2- diolate (PABA/NO) were synthesized and studied...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800831y
更新日期：2008-12-25 00:00:00
abstract：:Isoform-selective antagonists of the lysophosphatidic acid (LPA) G-protein coupled receptors (GPCRs) have important potential uses in cell biology and clinical applications. Novel phosphonothioate and fluoromethylene phosphonate analogues of carbacyclic phosphatidic acid (ccPA) were prepared by chemical synthesis. The...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060351+
更新日期：2006-08-24 00:00:00
abstract：:Family 18 chitinases play an essential role in a range of pathogens and pests. Several inhibitors are known, including the potent inhibitors argadin and allosamidin, and the structures of these in complex with chitinases have been elucidated. Recent structural analysis has revealed that CI-4 [cyclo-(L-Arg-D-Pro)] inhi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049940a
更新日期：2004-11-04 00:00:00
abstract：:Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of he...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500531z
更新日期：2014-06-26 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
pub_type： 杂志文章
doi：10.1021/jm200359n
更新日期：2011-09-22 00:00:00
abstract：:The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity. Imidazoles VIII a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00154a017
更新日期：1986-04-01 00:00:00
abstract：:1,2-Dihydro-1-(chloromethyl)-5-hydroxy-8-methyl-3H-furano[3,2-e]in dole (CFI) as a novel replacement of the cyclopropylpyrroloindoline (CPI) alkylation subunit of CC-1065, U-71184, and U-73975 (adozelesin) has been synthesized and incorporated into a series of efficacious antineoplastic agents. A partial solution to a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00028a005
更新日期：1994-01-21 00:00:00
abstract：:The modification of 3'-((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1H-inden-5-yloxy)methyl)biphenyl-4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing the cyclopentyl moiety led to the development of new mGluR2 positive allosteric modulators (PAMs) with optimized potency and s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1012165
更新日期：2011-01-13 00:00:00
abstract：:The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as w...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200464w
更新日期：2011-07-14 00:00:00
abstract：:A series of quinolone and naphthyridine antibacterial agents possessing as the C7-heterocycle bicyclic 2,5-diazabicyclo[n.2.m]alkanes, where n = 2, 3 and m = 1, 2, and a series including 4-aminopiperidine and 3-amino-8-azabicyclo[3.2.1]octanes have been prepared and evaluated in vitro and in vivo for antibacterial act...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00106a029
更新日期：1991-02-01 00:00:00
abstract：:We explore the significance of pi-cation interactions in the binding of ligands to nicotinic acetylcholine receptors. Specifically, the Austin method of semiempirical molecular orbital theory is utilized to estimate the interaction of aromatic amino acid side chains with the cation-containing heterocyclic ring fragmen...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990093z
更新日期：1999-08-12 00:00:00
abstract：:1-beta-D-Arabinofuranosylthymine (aThy; ara-T) is a potent selective anti herpes simplex virus drug. Its anhydro analogue, 2,2'-anhydro-aThy, was shown to be 9-fold less active and at least 3-fold less toxic than aThy. This compound was relatively stable at physiological pH and in strong acid but was rapidly hydrolyze...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00354a025
更新日期：1982-12-01 00:00:00
abstract：:New 2-piperazinylbenzothiazole and 2-piperazinylbenzoxazole derivatives were prepared and tested as 5-HT3 receptor antagonists. Some of the new compounds antagonized the effect of 5-HT at the longitudinal muscle myenteric plexus (LMMP) preparation of the guinea pig ileum, and two benzothiazole derivatives, compounds 2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00035a012
更新日期：1994-04-29 00:00:00
abstract：:Two natural occurring melanotropins, camel betaC2-MSH and bovine beta-MSH, have been synthesized by improved solid-phase procedures. The coupling reaction of tert-butyloxycarbonylamino acids was achieved by using their preformed symmetrical anhydrides. The synthetic hormones were purified by gel filtration on Sephadex...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00225a006
更新日期：1976-03-01 00:00:00
abstract：:A series of novel β-carboline-based N-heterocyclic carbenes was prepared via Mannich reaction between methyl 1-(dimethoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate, formaldehyde, and primary amines. All compounds were evaluated for their antiproliferative activity using human breast cancer and lung cancer cell lines...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00016
更新日期：2015-04-23 00:00:00
abstract：:To eliminate an unwarranted metabolic pathway of the quinoline ring, a set of two compounds, where C-2 position of the antimalarial drug primaquine is blocked by metabolically stable bulky alkyl group are synthesized. Compound 2 [R = C(CH(3))(3)] of the series has produced excellent antimalarial efficacy against P. be...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304562
更新日期：2004-01-15 00:00:00
abstract：:We have designed and evaluated 45 linear analogues of the natural constrained cyclopeptide TMC-95A. These synthetically less demanding molecules are based on the tripeptide sequence Y-N-W of TMC-95A. Structural variations in the amino acid side chains and termini greatly influenced both the efficiency and selectivity ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0701324
更新日期：2007-06-14 00:00:00
abstract：:A new family of chelating agents based on 4-(substituted-carbamoyl)-3-hydroxy-2-pyridinones is reported. These have optional terminal substituents on the nitrogens, and the hydroxypyridonate (HOPO) rings are attached to molecular backbones through amide linkages. A very important feature of the methyl-substituted liga...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00014a013
更新日期：1995-07-07 00:00:00
abstract：:Starting from a hit series from a GNF compound library collection and based on a cell-based proliferation assay of Plasmodium falciparum, a novel imidazolopiperazine scaffold was optimized. SAR for this series of compounds is discussed, focusing on optimization of cellular potency against wild-type and drug resistant ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2003359
更新日期：2011-07-28 00:00:00
