Abstract：
:As the number of cases and cancer-related deaths are projected to rise in upcoming years, it is urgent to find ways to prevent or treat cancer. As such, food-derived products have gained attention as potential chemopreventive agents due to their availability, safety, and low cost. Isothiocyanates, the breakdown products of sulfur-containing glucosinolates in cruciferous vegetables, have shown substantial anticarcinogenic and chemopreventive activities for different human cancers. Furthermore, organoselenium compounds are known to exhibit chemopreventive and chemotherapeutic activity; moreover, these compounds are more effective anticancer agents than their sulfur isosteres. Hence, isothiocyanates have been modified to yield isoselenocyanates, which are more cytotoxic toward cancer cells when compared to their corresponding sulfur analogues. Herein, the synthesis and development of isoselenocyanates as novel treatments for cancer and other diseases are reviewed, highlighting the diverse chemistry and computational studies of this class of compounds as well as their pertinent biological applications.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Frieben EE,Amin S,Sharma AKdoi
10.1021/acs.jmedchem.8b01698subject
Has Abstractpub_date
2019-06-13 00:00:00pages
5261-5275issue
11eissn
0022-2623issn
1520-4804journal_volume
62pub_type
杂志文章,评审abstract：:We have recently reported the phosphodiesterase 10A (PDE10A) inhibitor 2-[4-[1-(2-[(18)F]fluoroethyl)-4-pyridin-4-yl-1H-pyrazol-3-yl]-phenoxymethyl]-quinoline ([(18)F]1a) as a promising candidate for in vivo imaging using positron emission tomography (PET). We now describe the synthesis and biological evaluation of a ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200536d
更新日期：2011-08-25 00:00:00
abstract：:A series of 3',5'-diesters of a 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine salt bearing functional substituents on the ester side chains (4--16) have been synthesized. The synthesis of these diesters involved the reaction between cytidine and the corresponding acid anhydride or acid chloride in the presence of b...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00192a007
更新日期：1979-06-01 00:00:00
abstract：:We here report the synthesis of compounds structurally related to the high-affinity dopamine D(3) receptor ligand N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-methoxy-2-benzofurancarboxamide (1). All compounds were specifically designed as potential PET radioligands for brain D(3) receptors visualization, havin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050734s
更新日期：2006-01-12 00:00:00
abstract：:p38 MAP kinase has received considerable interest in the pharmaceutical industry and remains a valid and interesting target for the treatment of inflammation. To discover novel p38 inhibitors, we applied the ligand-based virtual screening technique, FieldScreen, to 1.2 million commercially available compounds. Fifty-e...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801399r
更新日期：2009-07-23 00:00:00
abstract：:Tumor suppressor protein, p53, is an intracellular protein that is critical within the biochemical cascade that leads to cell death via apoptosis. Recent studies identified the tetrahydrobenzothiazole analogue, pifithrin-alpha (2), as a p53 inhibitor that was effective in protecting neuronal cells against a variety of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020044d
更新日期：2002-11-07 00:00:00
abstract：:Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. Genetic knockdown of G9a inhibits cancer cell growth, and the dimethylation of p53 K373 results in the inactivation of p53. Initial SAR exploration of the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100478y
更新日期：2010-08-12 00:00:00
abstract：:Contilisant, a permeable, antioxidant, and neuroprotectant agent, showing high nM affinity at H3R and excellent inhibition of the monoamine oxidases and cholinesterases, is an affine and selective S1R agonist in the nanomolar range, based on the binding affinity and functional experiment, a result confirmed by molecul...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00848
更新日期：2018-08-09 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
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01704
更新日期：2019-04-11 00:00:00
abstract：:A series of D-erythro- and L-threo-ceramide analogues was synthesized and investigated for their ability to reverse the inhibitory effects of fumonisin B(1) (FB(1)) on axonal growth in hippocampal neurons. The analogues contained either a C(7) side chain or a phenyl group substituted for the C(13) residue present in n...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990091e
更新日期：1999-07-15 00:00:00
abstract：:Gamma9delta2T cells represent the most abundant population of human blood gammadeltaT lymphocytes. They produce and promote strong cytotoxic activity against many pathogens that are implicated in several human infectious diseases. Their activation requires their exposure to small phosphorus-containing antigens in the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049861z
更新日期：2004-08-26 00:00:00
abstract：:(-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first thymidine kinase-activated nucleoside that is significantly active against all of the clinically significant NRTI-resistant HIV-1 mutants, including AZT (D67N/K70R/T215Y/K219Q), Tenofovir (K65R), and Lamivudine (M184V). To understand the molec...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050060l
更新日期：2005-06-16 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：:Optimization of a 5-oxopyrrolopyridine series based upon structure-activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4008906
更新日期：2013-09-26 00:00:00
abstract：:Forty-eight heterocyclic amino acid trimers, analogues of distamycin, with a number of features that enhance lipophilicity are described. They contain alkyl or cycloalkyl groups larger than methyl; some are N-terminated by acetamide or methoxybenzamide and are C-terminated by dimethylaminopropyl or aliphatic heterocyl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm031089x
更新日期：2004-04-08 00:00:00
abstract：:The imidazoquinoline (R)-5,6-Dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine [(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and ox...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960360q
更新日期：1997-02-28 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：:Lymphatic filariasis (elephantiasis) is a global public health problem caused by the parasitic nematodes Wuchereria bancrofti and Brugia malayi. We have previously reported anthraquinones from daylily roots with potent activity against pathogenic trematode Schistosoma mansoni. Here we report the synthesis of novel ant...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0492655
更新日期：2005-04-21 00:00:00
abstract：:New phenoxyacetic acid antagonists of CRTH2 are described. Following the discovery of a hit compound by a focused screening, high protein binding was identified as its main weakness. Optimization aimed at reducing serum protein binding led to the identification of several compounds that showed not only excellent affin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200866y
更新日期：2011-10-27 00:00:00
abstract：:Despite the availability of numerous antiepileptic drugs, 20-30% of epileptic patients are pharmacoresistant with seizures not appropriately controlled. Consequently, new strategies to address this unmet medical need are required. T-type calcium channels play a key role in neuronal excitability and burst firing, and s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01356
更新日期：2016-12-08 00:00:00
abstract：:Interleukin-2 inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, plays a major role in T-cell signaling downstream of the T-cell receptor (TCR), and considerable efforts have been directed toward discovery of ITK-selective inhibitors as potential treatments of inflammatory disorders such as...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500550e
更新日期：2014-07-10 00:00:00
abstract：:The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 co...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00150a024
更新日期：1985-12-01 00:00:00
abstract：:A series of 6-benzoxazinylpyridazin-3-ones was prepared and evaluated for inhibition of cardiac phosphodiesterase (PDE) fraction III in vitro and for positive inotropic activity in vivo. 6-[3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl]-2,3,4,5-tetrahydro-5 - methylpyridazin-3-one (bemoradan) was found to be an extremely ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00163a061
更新日期：1990-01-01 00:00:00
abstract：:Tocotrienols exhibit antioxidant and cholesterol-biosynthesis-inhibitory activities and may be of value as antiatherosclerotic agents. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase (HMGR) in a manner mimicking the action of putative non-sterol feedback inhibi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00030a012
更新日期：1994-02-18 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
pub_type： 杂志文章
doi：10.1021/jm901390p
更新日期：2009-12-24 00:00:00
abstract：:In the treatment of cardiovascular diseases, it could be of therapeutic interest to associate the hypotensive effects resulting from the inhibition of angiotensin II formation, ensured by endothelial angiotensin-converting enzyme (ACE), with the diuretic and natriuretic responses due to the protection of the endogenou...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00034a005
更新日期：1994-04-15 00:00:00
abstract：:The compounds N6-allyl-, N6-isopropyl-, N6-propargyl-, and N6-(2-methylallyl)adenosine were prepared by reacting 6-chloropurine riboside with an excess of the corresponding amines in ethanol, in the presence of two acid acceptors resulting in virtually quantitative yields. The compounds showed biological activity in a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00186a031
更新日期：1980-12-01 00:00:00
abstract：:Using a combination of in silico and experimental approaches, we present evidence that the G-quadruplex (G4) motif (an alternative higher-order DNA conformation) has regulatory potential. Genome-wide analyses of 99980 human, chimpanzee, mouse, and rat promoters showed enrichment of sequence with potential to adopt G4 ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800448a
更新日期：2008-09-25 00:00:00
abstract：:The synthesis, characterization, inhibitory activity against topoisomerase I, and biological evaluation of a series of 14 camptothecin derivatives of polypyrrolecarboxamide (lexitropsin) conjugates of two structural classes: (A) camptothecin-NHCO-lexitropsin 44-51 and (B) camptothecin-CONH-lexitropsin 38-43 are descri...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9605804
更新日期：1997-01-17 00:00:00
abstract：:Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways and thus an attractive therapeutic target for diabetes and obesity. Starting with a high micromolar lead compound, structure-based optimization of novel PTP1B inhibitors by extension of the molecule from the enz...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0702478
更新日期：2007-09-20 00:00:00
abstract：:Interleukin-2 inducible T-cell kinase (Itk) plays a role in T-cell functions, and its inhibition potentially represents an attractive intervention point to treat autoimmune and allergic diseases. Herein we describe the discovery of a series of potent and selective novel inhibitors of Itk. These inhibitors were identif...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm101499u
更新日期：2011-04-14 00:00:00
