Abstract：
:Syntheses of 2-fluoroformycin [7-amino-5-fluoro-3-(beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine] (2b) and 2-aminoformycin [5,7-diamino-3-(beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine] (2c) are described. Cytotoxicity data are given for 2b and 2c alone as well as with added pentostatin. Kinetic parameters for adenosine deaminase are also provided. 2-Fluoroformycin, although a much poorer substrate for adenosine deaminase than formycin A, is not nearly as cytotoxic to cells in culture.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Secrist JA 3rd,Shortnacy AT,Montgomery JAdoi
10.1021/jm00149a033subject
Has Abstractpub_date
1985-11-01 00:00:00pages
1740-2issue
11eissn
0022-2623issn
1520-4804journal_volume
28pub_type
杂志文章abstract：:The protein kinase C (PKC) family of serine/threonine kinases is implicated in a wide variety of cellular processes. The PKC theta (PKCtheta) isoform is involved in TCR signal transduction and T cell activation and regulates T cell mediated diseases, including lung inflammation and airway hyperresponsiveness. Thus inh...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800214a
更新日期：2008-10-09 00:00:00
abstract：:Recent evidence suggests that intraneuronal metabolism of ethanol by catalase/H2O2 and an ethanol-inducible form of cytochrome P450 together generate acetaldehyde and oxygen radicals including the hydroxyl radical (HO.). Within the cytoplasm of serotonergic neurons, these metabolic processes would thus provide acetald...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9504870
更新日期：1996-03-29 00:00:00
abstract：:Selected derivatives of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazole, a new heterocyclic ring system, and their S-oxides have been prepared and evaluated for antiallergic activity in the rat passive cutaneous anaphylaxis screen. Several of the compounds show intravenous potencies similar to or greater than that o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00368a021
更新日期：1984-02-01 00:00:00
abstract：:Macrophage elastase [matrix metalloproteinase (MMP)-12] is the most upregulated MMP in abdominal aortic aneurysm (AAA) and, hence, MMP-12-targeted imaging may predict AAA progression and rupture risk. Here, we report the design, synthesis, and evaluation of three novel hydroxamate-based selective MMP-12 inhibitors (CG...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01514
更新日期：2020-12-10 00:00:00
abstract：:Developing methods to incorporate protein flexibility into structure-based drug design is an important challenge. Our approach uses multiple protein structures (MPS) to create a receptor-based pharmacophore model of the desired target. We have previously demonstrated the success of the method by applying it to human i...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050755m
更新日期：2006-06-15 00:00:00
abstract：:Hydrogen sulfide (H2S) is now recognized as a physiologically important gasotransmitter. Compounds which release H2S slowly are sought after for their potential in therapy. Herein the synthesis of a series of phosphordithioates based on 1 (GYY4137) are described. Their H2S release profiles are characterized using 2,6-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00848
更新日期：2015-08-27 00:00:00
abstract：:Selective inhibition of neuronal nitric oxide synthase (nNOS) has been shown to prevent brain injury and is important for the treatment of various neurodegenerative disorders. This study shows that not only greater inhibitory potency and isozyme selectivity but more druglike properties can be achieved by fragment hopp...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801220a
更新日期：2009-02-12 00:00:00
abstract：:c-Met has emerged as an attractive target for targeted cancer therapy because of its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonylpyrazolo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm502018y
更新日期：2015-03-12 00:00:00
abstract：:Nitrosourea derivatives 9--13 which utilize phensuximide (1) as the carrier were synthesized as potential central nervous system antitumor agents. The N-(2-chloroethyl)-N-nitrosourea 13 was active in the mouse ependymoblastoma brain-tumor system, as well as the intraperitoneal L1210 leukemia system. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00177a024
更新日期：1980-03-01 00:00:00
abstract：:The Mediterranean tunicate Stolonica socialis contains a new class of powerful cytotoxic acetogenins, generically named stolonoxides. In this paper, which also details the isolation and chemical characterization of a minor component (3a) of the tunicate extract, we report the potent inhibitory activity (IC(50) < 1 mic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0011373
更新日期：2001-07-05 00:00:00
abstract：:Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippoca...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5011012
更新日期：2014-11-13 00:00:00
abstract：:Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2001508
更新日期：2011-07-14 00:00:00
abstract：:The programmed cell death or apoptosis plays both physiological and pathological roles in biology. Anomalous activation of apoptosis has been associated with malignancies. The intrinsic mitochondrial pathway of apoptosis activation occurs through a multiprotein complex named the apoptosome. We have discovered molecule...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701195j
更新日期：2008-02-14 00:00:00
abstract：:Protein arginine methyltransferase 1 (PRMT1) is involved in many biological activities, such as gene transcription, signal transduction, and RNA processing. Overexpression of PRMT1 is related to cardiovascular diseases, kidney diseases, and cancers; therefore, selective PRMT1 inhibitors serve as chemical probes to inv...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501452j
更新日期：2015-02-12 00:00:00
abstract：:Whereas the 2-propyl- and 2-butyl-5,6-(methylenedioxy)indene calcium antagonists reversed the spasmogenic action of several agonists including PGF2alpha and acetylcholine at 5 X 10(-5) to 10(-4) M on the rat ileum, the corresponding 5,6-dimethoxy analogues exhibited spasmogenic activity at higher concentration (10(-4)...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00210a028
更新日期：1978-12-01 00:00:00
abstract：:The kinase PIM-1 plays a pivotal role in cytokine signaling and is implicated in the development of a number of tumors. The three-dimensional structure of PIM-1 is characterized by an unique hinge region which lacks a second hydrogen bond donor and makes it particularly important to determine how inhibitors bind to th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0504858
更新日期：2005-12-01 00:00:00
abstract：:Tocotrienols are farnesylated benzopyran natural products that exhibit hypocholesterolemic activity in vitro and in vivo. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase by a process distinct from other known inhibitors of cholesterol biosynthesis. An efficient...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00098a002
更新日期：1992-10-02 00:00:00
abstract：:The availability of peptide and non-peptide Ang II receptor antagonists has permitted the study of Ang II receptor heterogeneity. It is now widely recognized that there are at least two distinct Ang II receptor subtypes. AT1 receptors are selective in their recognition of agents such as losartan, DuP 532, L-158,809, S...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00077a001
更新日期：1993-12-10 00:00:00
abstract：:The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for certain neurological diseases. In particular, the DAT is depleted in Parkinson's disease, and the extent of depletion correlates with the loss of dopamine. Herein we describe the design, synthesis, and biological evaluat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960868t
更新日期：1997-06-06 00:00:00
abstract：:Details of the interaction between HIV-1 reverse transcriptase and non-nucleoside inhibitors (NNRTIs) have been elucidated using a biosensor-based approach. This initial study was performed with HIV-1 reverse transcriptase mutant K103N, the phenethylthioazolylthiourea compound (PETT) MIV-150, and the three NNRTIs lice...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0504048
更新日期：2006-04-20 00:00:00
abstract：:Alkenylidene bisphenols are prepared by condensation of an appropriate phenol with a haloacetaldehyde, followed by base-induced elimination, or by condensation of the corresponding aryl methyl ether, elimination, and deprotection of the phenol with boron tribromide. The resulting compounds may be further elaborated by...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00194a022
更新日期：1979-08-01 00:00:00
abstract：:The formation of intramolecular hydrogen bonds has a very pronounced effect on molecular structure and properties. We study both aspects in detail with the aim of enabling a more rational use of this class of interactions in medicinal chemistry. On the basis of exhaustive searches in crystal structure databases, we de...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100087s
更新日期：2010-03-25 00:00:00
abstract：:The discovery of 8-(5,8-dichloro-1,2,3,4-tetrahydro-naphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one, 1a, as a high-affinity ligand for the human ORL1 (orphanin FQ/nociceptin) receptor led to the synthesis of a series of optimized ligands. These compounds exhibit high affinity for the human ORL1 receptor, e...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm991129q
更新日期：2000-04-06 00:00:00
abstract：:On the basis of docking studies carried out using the recently published cannabinoid receptor models,35 new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives were designed, synthesized, and tested for their affinities toward the cannabinoid CB1 and CB2 receptors. Compound 10, whic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0603466
更新日期：2006-10-05 00:00:00
abstract：:A number of 7-benzoylbenzofuran-5-ylacetic acids and 7-benzoylbenzothiophene-5-ylacetic acids were synthesized. The compounds were generally only 1/2 to 3 times as potent as phenylbutazone in the rat paw edema antiinflammatory assay. However, they show greater activity as analgetic agents. The most active compound is ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00161a030
更新日期：1986-11-01 00:00:00
abstract：:Glycosylation of 2-fluoroadenine with the appropriate protected thioglycoside derivatives, followed by deprotection and anomer separation, produced the alpha- and beta-anomers of 2',5'-dideoxy-2-fluoroadenosine (1), 2',5'-dideoxy-2,5'-difluoroadenosine (2), and 2'-deoxy-2-fluoroadenosine (3). These were examined as P-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0303599
更新日期：2004-02-26 00:00:00
abstract：:The discovery of potent and pan-genotypic HCV NS5A inhibitors faces many challenges including the significant diversity among genotypes, substantial potency shift conferred on some key resistance-associated variants, inconsistent SARs between different genotypes and mutants, and the lacking of models of inhibitor/prot...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01234
更新日期：2016-11-23 00:00:00
abstract：:Serotonin (5-HT) binds with nearly identical affinity at the various central 5-HT binding sites. Few agents bind with selectivity for 5-HT1A sites. The beta-adrenergic antagonist propranolol binds stereoselectively both at 5-HT1A and 5-HT1B sites (with a several-fold selectivity for the latter) and, whereas it is a 5-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00124a021
更新日期：1989-04-01 00:00:00
abstract：:Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such stud...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5007947
更新日期：2014-07-24 00:00:00
abstract：:The dedifferentiation agent "reversine" [2-(4-morpholinoanilino)-N(6)-cyclohexyladenine 2] was found to be a moderately potent antagonist for the human A(3) adenosine receptor (AR) with a K(i) value of 0.66 microM. This result prompted an exploration of the structure-activity relationship of related derivatives, synth...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050221l
更新日期：2005-07-28 00:00:00
