Abstract：
:A series of thymidylate synthetase inhibitors was synthesized, some of which were potential irreversible inhibitors. 5-Formyl-2'-deoxyuridine (9) and its dithiolane derivative 11 were prepared by condensation of the bis(trimethylsilyl) derivative of 5-formyluracil dimethyl acetal and the protected chloro sugar followed by saponification of the protective groups. 5-Acetyl-2'-deoxyuridine (15) was prepared in the same way from 5-acetyluracil. Treatment of the diester of 5-allyl-2'-deoxyuridine (17 or 22) with m-chloroperbenzoic acid gave the corresponding epoxide. Dimethylamine removed the ester groups and opened the epoxide to give the amino alcohol 24. The diester of 5-chloromethyl-2'-deoxyuridine (27) treated with methanol or sodium azide gave 5-methoxymethyl- (29) and 5-azidomethyl- (31) 2'-deoxyuridines. Compound 27 also was converted to 5-iodoacetamidomethyl-2'-deoxyuridine by treatment with ammonia, chloroacetyl chloride, base saponification, and finally sodium iodide.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Kampf A,Pillar CJ,Woodford WJ,Mertes MPdoi
10.1021/jm00229a010subject
Has Abstractpub_date
1976-07-01 00:00:00pages
909-15issue
7eissn
0022-2623issn
1520-4804journal_volume
19pub_type
杂志文章abstract：:Reformatski condensation of benzyl 2-bromopropionate with 4-carbomethoxybenzaldehyde, followed by dehydration afforded benzyl 2-methyl-p-carbomethoxycinnamate (4a). Hydrogenation over a Pd catalyst gave the hydrocinnamic acid 5a. Conversion to the chloromethyl (6a) and azidomethyl ketone (7a) was followed by hydrogena...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00163a035
更新日期：1990-01-01 00:00:00
abstract：:In an effort to determine the stereochemical requirements for pharmacological activity among the series of nonclassical cannabinoids synthesized at Pfizer, we have studied the conformational properties of the parent bicyclic analog CP-47,497. For this study, we have used a combination of solution NMR and theoretical c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00036a006
更新日期：1994-05-13 00:00:00
abstract：:The ability to develop a chemical into a drug depends on multiple factors. Beyond potency and selectivity, ADME/PK and the toxicological profile of the compound play a significant role in its evaluation as a candidate for development. Those factors are being brought into bear earlier in the discovery process and even ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0004594
更新日期：2001-08-16 00:00:00
abstract：:Modern rational drug design not only deals with the search for ligands binding to interesting and promising validated targets but also aims to identify the function and ligands of yet uncharacterized proteins having impact on different diseases. Additionally, it contributes to the design of inhibitors with distinct se...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00078
更新日期：2016-05-12 00:00:00
abstract：:9-(5-O-α-D-galactopyranosyl)-D-arabinityl-1,3,7-trihydropurine-2,6,8-trione (1) was designed and synthesized as a nonionic inhibitor for the donor binding site of human blood group B galactosyltransferase (GTB). Enzymatic characterization showed 1 to be extremely specific, as the highly homologous human N-acetylgalact...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300642a
更新日期：2013-03-14 00:00:00
abstract：:Glioblastoma multiforme (GBM) is the deadliest form of brain tumor. It is known for its ability to escape the therapeutic options available to date thanks to the presence of a subset of cells endowed with stem-like properties and ability to resist to cytotoxic treatments. As the cytosolic enzyme aldehyde dehydrogenase...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01910
更新日期：2020-05-14 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
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00451
更新日期：2015-06-11 00:00:00
abstract：:In an effort to identify selective ligands for the estrogen receptor subtype ERbeta, a series of aryl benzthiophenes was synthesized. In a radioligand binding assay and reporter gene assays in HeLa and SH-SY5Y cells, compounds were characterized as ERbeta-selective agonists. By targeting ERbeta in the brain, these com...
journal_title：Journal of medicinal chemistry
pub_type： 信件
doi：10.1021/jm015577l
更新日期：2002-03-28 00:00:00
abstract：:In the past few years sirtuins have gained growing attention for their involvement in many biological processes such as cellular metabolism, apoptosis, aging and inflammation. In this contribution, we report the synthesis of a library of thioacetylated pseudopeptides that were screened against human sirtuins 1-3 to re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400438k
更新日期：2013-09-12 00:00:00
abstract：:A small library of boron-cluster- and metallacarborane-cluster-based ligands was designed, prepared, and tested for isoform-selective activation or inhibition of the three nitric oxide synthase isoforms. On the basis of the concept of creating a hydrophobic analogue of a natural substrate, a stable and nontoxic basic ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300805x
更新日期：2012-11-26 00:00:00
abstract：:This paper describes the synthesis and pharmacological evaluation of a number evaluation of a number of substituted 1,3,4-thiadiazoles. The first member of the series, 2-(aminomethyl)-5-(2-biphenylyl)-1,3,4-thiadiazole (7) was found to possess potent anticonvulsant properties in rats and mice and compared favorably wi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00161a025
更新日期：1986-11-01 00:00:00
abstract：:The prevalence of neurotensin receptor (NTR) in several human tumors makes it an attractive target for the delivery of cytotoxic drugs and imaging agents. Native neurotensin (NT) is a tridecapeptide that binds to NTR and induces tumor growth. Unfortunately, NT has a short plasma half-life, which hinders its use for in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030081k
更新日期：2003-07-17 00:00:00
abstract：:The lack of molecules endowed with selective and potent agonistic activity toward the hA2B adenosine receptors has limited the studies on this pharmacological target and consequently the evaluation of its therapeutic potential. We report the design and the synthesis of the first potent (EC50 in the nanomolar range) an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061170a
更新日期：2007-01-25 00:00:00
abstract：:In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) models are important tools in combating late-stage attrition in the drug discovery process. This work shows how ADMET models can be combined to tailor predictions depending on one's needs. We demonstrate how the judicious use of data and c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049254b
更新日期：2005-02-24 00:00:00
abstract：:Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01586
更新日期：2017-04-13 00:00:00
abstract：:The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00171a024
更新日期：1990-09-01 00:00:00
abstract：:Metoclopramide (1) is a gastric motility stimulant and a weak dopamine and 5-HT3 receptor antagonist. Conformational restriction of the (diethylamino)ethyl side chain of 1 in the form of the azabicyclic tropane gave 3, a very potent gastric motility stimulant and 5-HT3 receptor antagonist but devoid of significant dop...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00169a016
更新日期：1990-07-01 00:00:00
abstract：:A one-pot synthesis of ageladine A and analogues is reported. The key Pictet-Spengler reaction between 2-aminohistamine and aryl aldehydes has been successfully utilized for the synthesis of the natural product and 14 analogues. These compounds were screened for their matrix metalloprotease (MMP) and kinase inhibition...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200039m
更新日期：2011-04-14 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
pub_type： 杂志文章
doi：10.1021/jm5004123
更新日期：2014-05-22 00:00:00
abstract：:A number of derivatives of 4-amino-6-hydroxy-2-mercaptopyrimidine ( 5) were synthesized and biologically evaluated as A 3 adenosine receptor (A 3 AR) antagonists. The new compounds were designed as open chain analogues of a triazolopyrimidinone derivative displaying submicromolar affinity for the A 3 AR, which had bee...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701159t
更新日期：2008-03-27 00:00:00
abstract：:We report the esterification of the carboxyl groups of the cyclic peptide toxins nodularin-R and microcystin-LA to produce stable diacetoxymethyl and dipropionyloxymethyl ester derivatives. The derivatives had no activity but were reactivated upon esterase treatment. When injected into cells, the acyloxymethyl moietie...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900502e
更新日期：2009-09-24 00:00:00
abstract：:Antitumor activity in mice was observed for the oxime of the previously reported ethyl [6-amino-4-[(1-methyl-2-phenyl-2-oxoethyl)amino]-5-nitropyridin -2-yl] carbamate (8) and several related compounds. These compounds are precursors of the active ethyl pyrido[3,4-b]pyrazin-7-ylcarbamates (e.g., 4), which are potent a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00098a014
更新日期：1992-10-02 00:00:00
abstract：:The DEDDh family of exonucleases plays essential roles in DNA and RNA metabolism in all kingdoms of life. Several viral and human DEDDh exonucleases can serve as antiviral drug targets due to their critical roles in virus replication. Here using RNase T and CRN-4 as the model systems, we identify potential inhibitors ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00794
更新日期：2016-09-08 00:00:00
abstract：:Several 4-alkyl-1-arylpiperazines that present a tetralin moiety on the terminal part of the side chain were synthesized in order to increase the selectivity on the 5-HT1A versus D-2, alpha 1, sigma, and other 5-HT receptors. Many changes have been effected on previous structures of type 3(1-aryl-4-[3-(1,2-dihydronaph...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00006a013
更新日期：1995-03-17 00:00:00
abstract：:The ability of molecular docking, using the program Glide and an MM-GBSA postdocking scoring protocol, to correctly rank a number of congeneric kinase inhibitors was assessed. The approach was successful for the cases considered and suggests that this may be useful for the design of inhibitors in the lead optimization...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060522a
更新日期：2006-08-10 00:00:00
abstract：:Members of the JAK family of nonreceptor tyrosine kinases play a critical role in the growth and progression of many cancers and in inflammatory diseases. JAK2 has emerged as a leading therapeutic target for oncology, providing a rationale for the development of a selective JAK2 inhibitor. A program to optimize select...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300248q
更新日期：2012-06-14 00:00:00
abstract：:Thalidomide, 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione, has been shown to inhibit angiogenesis, the formation of new blood vessels from existing vasculature. As a result, there is renewed interest in this drug as a potential therapy for solid tumors. Thalidomide forms a number of metabolites and has been ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304820
更新日期：2004-04-22 00:00:00
abstract：:The bradykinin B1 receptor is rapidly induced upon tissue injury and inflammation, stimulating the production of inflammatory mediators resulting in plasma extravasation, leukocyte trafficking, edema, and pain. We have previously reported on sulfonamide and sulfone-based B1 antagonists containing a privileged bicyclic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200808v
更新日期：2011-10-27 00:00:00
abstract：:A series of 42 6-arylpyrrolo[2,1-d][1,5]benzothiazepines, which we have recently described as selective ligands of the mitochondrial benzodiazepine receptor (MBR) (Fiorini I.; et al. J. Med. Chem. 1994, 37, 1427-1438), have been investigated using the comparative molecular field analysis (CoMFA) approach. The resultin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00050a007
更新日期：1994-11-25 00:00:00
abstract：:A series of 26 derivatives of the novel muscarinic antagonist 3-(2-benzofuranyl)quinuclidin-2-ene (1) has been synthesized and evaluated for muscarinic and antimuscarinic properties. The affinity of the compounds was determined by competition experiments in homogenates of cerebral cortex, heart, parotid gland, and uri...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950455c
更新日期：1996-08-16 00:00:00
