Abstract：
:The objective of this study is the measurement of the rates of hydrolysis of a series of chloroethyl sulfide derivatives, under stimulated physiological conditions. Interferences encountered with the conventional spectrophotometric method prompted the use of a rapid-response, chloride selective electrode. This probe was readily capable of monitoring the hydrolytic rate, which is identical with the rate of chloride ion formation. Since the desired subsecond half-lives were not achieved by any of the compounds, factors influencing the rates were investigated. The results suggest that the rate-controlling cyclization step may be inhibited, due to coordination of undissociated protonic functional groups on the aromatic portions of the structures with the lone-pair electrons on sulfur.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Wright JE,Hayes MJ,Subramanyam V,Soloway AHdoi
10.1021/jm00222a037subject
Has Abstractpub_date
1977-12-01 00:00:00pages
1700-2issue
12eissn
0022-2623issn
1520-4804journal_volume
20pub_type
杂志文章abstract：:Starting with a previously reported linear breast cancer targeting decapeptide WxEAAYQkFL, here we report the synthesis of a novel cyclic peptide analogue cyclic WXEAAYQkFL. The N- to C-terminus amide cyclized peptide with one d-amino acid (k) displayed higher uptake by breast cancer cells, with minimal uptake by the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00163
更新日期：2017-06-22 00:00:00
abstract：:Bromodomains (BD) are readers of lysine acetylation marks present in numerous proteins associated with chromatin. Here we describe a dual inhibitor of the bromodomain and PHD finger (BRPF) family member BRPF2 and the TATA box binding protein-associated factors TAF1 and TAF1L. These proteins are found in large chromati...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00306
更新日期：2017-05-11 00:00:00
abstract：:The G protein-coupled chemokine receptors CXCR1 and CXCR2 play key roles in inflammatory diseases and carcinogenesis. In inflammation, they activate and recruit polymorphonuclear cells (PMNs) through binding of the chemokines CXCL1 (CXCR1) and CXCL8 (CXCR1 and CXCR2). Structure-activity studies that examined the effec...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500827t
更新日期：2014-10-23 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：:Alkylation-elimination of adenine and 2-amino-6-chloropurine with gem-difluorocyclopropane dibromide 10 gave E- and Z-methylene-gem-difluorocyclopropanes 11a, 11b, 12a, and 12b and gem-difluorocyclopropenes 13a and 13b. Debenzylation of intermediates 11a, 11b, 12a, and 12b afforded E- and Z-methylenecyclopropanes 4a, ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010191w
更新日期：2001-11-08 00:00:00
abstract：:The inhibitory effect of 108 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(substituted-phenyl)-s-triazines on murine L5178Y tumor cells, resistant and sensitive to methotrexate (MTX), has been studied. From the pI50 values, quantitative structure-activity relationships have been formulated which show that the lipophilic tri...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00369a019
更新日期：1984-03-01 00:00:00
abstract：:All of the selective COX-2 inhibitors described to date inhibit the isoform by binding tightly but noncovalently at the substrate binding site. Recently, we reported the first account of selective covalent modification of COX-2 by a novel inactivator, 2-acetoxyphenyl hept-2-ynyl sulfide (70) (Science 1998, 280, 1268-1...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980303s
更新日期：1998-11-19 00:00:00
abstract：:Analogues of 9-oxo-9H-xanthene-4-acetic acid (XAA) bearing small, lipophilic 5-substituents are among the most dose-potent compounds yet reported with the capability of causing hemorrhagic necrosis of implanted colon 38 tumors in mice. To further extend structure-activity relationships among this class of compound, a ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00105a034
更新日期：1991-01-01 00:00:00
abstract：:HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepinedione antagonists of the HDM2-p53 interaction. The X-ray crystal struc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049137g
更新日期：2005-02-24 00:00:00
abstract：:The main recognition characteristics of the ATP binding site of p38 mitogen activated protein kinase alpha (p38alpha MAPK) have been explored by a combination of modeling and bioinformatics techniques, making special emphasis in the characteristics of the site that justifies binding specificity with respect to other M...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061073h
更新日期：2007-01-25 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
pub_type： 杂志文章
doi：10.1021/jm960142x
更新日期：1996-07-05 00:00:00
abstract：:In this Perspective, recent advances and challenges in the development of GPR119 agonists as new oral antidiabetic drugs will be discussed. Such agonists are expected to exhibit a low risk to induce hypoglycemia as well as to have a beneficial impact on body weight. Many pharmaceutical companies have been active in th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.5b01198
更新日期：2016-04-28 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
pub_type： 杂志文章
doi：10.1021/jm501635e
更新日期：2015-01-22 00:00:00
abstract：:Five series of pyrrolo[3,2-d]pyrimidines were synthesized and evaluated with respect to potency and selectivity toward multidrug resistance-associated protein 1 (MRP1, ABCC1). This transport protein is a major target to overcome multidrug resistance in cancer patients. We investigated differently substituted pyrrolopy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01644
更新日期：2016-04-14 00:00:00
abstract：:The first stereoselective synthesis of the hexahydroimidazo[1,5b]isoquinoline (HHII) scaffold as a surrogate for the steroidal A-B ring system is described. The structure-activity relationships of the analogs derived from this scaffold show that the basic imidazole moiety is tolerated by the glucocorticoid receptor (G...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901551w
更新日期：2010-02-11 00:00:00
abstract：:A new approach to rapidly score protein-ligand interactions is tested on several protein-ligand systems. Results using this approach - the OWFEG free energy grid - are quite promising and are generally in better agreement with experiment (in some cases much better) than those obtained employing scoring techniques curr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000375v
更新日期：2001-02-15 00:00:00
abstract：:Among a series of benzopyridone-based scaffolds investigated as human transient receptor potential vanilloid 1 (TRPV1) ligands, two isomeric benzopyridone scaffolds demonstrated a consistent and distinctive functional profile in which 2-oxo-1,2-dihydroquinolin-5-yl analogues (e.g., 2) displayed high affinity and poten...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00982
更新日期：2021-01-14 00:00:00
abstract：:The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (1) (R1 = OMe) had previously been identified as the most interesting member of a series of selective beta 3-adrenergic agonists of brown adipose tissue and thermogenesis in the rat. In vivo it acts mainly via the related acid 1 (R1 = OH)....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00088a010
更新日期：1992-05-15 00:00:00
abstract：:We have focused on optimization of the inadequate pharmacokinetic profile of trans-4-substituted cyclohexanecarboxylic acid 5, which is commonly observed in many small molecule very late antigen-4 (VLA-4) antagonists. We modified the lipophilic moiety in 5 and found that reducing the polar surface area of this moiety ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901154c
更新日期：2009-12-24 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
pub_type： 杂志文章
doi：10.1021/jm200750x
更新日期：2011-11-10 00:00:00
abstract：:The in vivo antitumor activity and in vitro metabolic dealkylation have been measured for an homologous series of 3-alkyl-1-(4-carbamoylphenyl)-3-methyltriazenes and have been compared with their partition coefficients. This investigation has shown that the extent of oxidative metabolism in vitro and the antitumor act...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00373a011
更新日期：1984-07-01 00:00:00
abstract：:Agents that target the two highly conserved Zn fingers of the human immunodeficiency virus (HIV) nucleocapsid p7 (NCp7) protein are under development as antivirals. These agents covalently modify Zn-coordinating cysteine thiolates of the fingers, causing Zn ejection, loss of native protein structure and nucleic acid b...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9708543
更新日期：1998-04-23 00:00:00
abstract：:Several new phospholipid-ara-C conjugates have been prepared and tested as prodrugs of the parent ara-C. The new derivative include ara-CMP-L-dipalmitin, ara-CDP-L-distearin, ara-CDP-L dimyristin, ara-CDP-L-diolein, and the radioactively labeled derivative ara-CDP-L-di[1-14C]palmitin. In addition, the unusually stable...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00353a010
更新日期：1982-11-01 00:00:00
abstract：:Angiogenesis is a requirement for the sustained growth and proliferation of solid tumors, and the development of new compounds that induce a sustained inhibition of the proangiogenic signaling generated by tumor hypoxia still remains as an important unmet need. In this work, we describe a new antiangiogenic compound (...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5019252
更新日期：2015-05-14 00:00:00
abstract：:A series of transition-state analogues having heterocyclythio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00089a023
更新日期：1992-05-29 00:00:00
abstract：:The three dimers 3, 4, and 5 of mitomycin C (MC), a natural antibiotic and cancer chemotherapeutic agent, were synthesized in which two MC molecules were linked with -(CH(2))(4)-, -(CH(2))(12)-, and -(CH(2))(3)N(CH(3))(CH(2))(3)- tethers, respectively. The dimeric mitomycins were designed to react as polyfunctional DN...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049863j
更新日期：2004-06-03 00:00:00
abstract：:A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00443
更新日期：2017-08-24 00:00:00
abstract：:Absolute configuration assignments have been made for the diastereomers of DL-beta-fluoroaspartate by X-ray analysis. The cytotoxicity of these isomers against various mammalian cells was examined. DL-threo-beta-Fluoroaspartate shows selective cytotoxicity. Growth of the most sensitive cells is completely inhibited by...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00347a013
更新日期：1982-05-01 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
pub_type： 杂志文章
doi：10.1021/jm00230a014
更新日期：1976-08-01 00:00:00
abstract：:Targeted imaging requires contrast agents that remain in the vasculature for extended periods of time. A new contrast agent is described in which gadolinium is encapsulated within an extremely stable carbon sphere, thus allowing for safe extended residence. Water solubility and small particle size is achieved with nov...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800521j
更新日期：2008-07-10 00:00:00
