Abstract：
:Reaction of 3'-acetylthymidine with phosphorus oxychloride in trimethyl phosphate yielded the phosphorodichloridate 5, which was subsequently reacted with aziridine, or 2,2-dimethylaziridine to give compounds 6 and 7, respectively. The 2,2-dimethylaziridine derivative 7 was considerably more active than 6 against leukemia L1210 and P-388 in mice but less active than the previously synthesized, simpler phosphinate derivatives 2 and 3. It appears that the thymidine moiety did not enable these compounds to use the nucleoside transport mechanism of the cells and also failed to increase the selectivity of the 2,2-dimethylaziridine analogues by interference with their binding to cholinesterase. Compound 7 strongly inhibited horse serum cholinesterase, while 6 was inactive.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Hsiao LY,Bardos TJdoi
10.1021/jm00139a024subject
Has Abstractpub_date
1981-07-01 00:00:00pages
887-9issue
7eissn
0022-2623issn
1520-4804journal_volume
24pub_type
杂志文章abstract：:Partially hydrogenated derivatives of the new heterocyclic ring systems benz[d]indolo[2,3-g]azecine and bisindolo[3,2-d][2, 3-g]azecine were synthesized starting from lactones and amines via the described synthetic methods. In binding assays with rat striatal receptors, 7-methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indol...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9911478
更新日期：2000-05-18 00:00:00
abstract：:Penicillin-binding proteins represent well-established, validated, and still very promising targets for the design and development of new antibacterial agents. The transglycosylase domain of penicillin-binding proteins is especially important, as it catalyzes polymerization of glycan chains, using the peptidoglycan pr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01482
更新日期：2015-12-24 00:00:00
abstract：:The steroidal sulfonylpyrazole 1 bound to the rat ventral prostate androgen receptor in vitro; it inhibited testosterone propionate induced increases in ventral prostate weight in vivo in the castrated, immature male rat with an ED50 of 15 mg/kg po. Compound 1 lacked androgenic activity in vivo in contrast to the pare...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00170a008
更新日期：1990-08-01 00:00:00
abstract：:Emericedins A, B, and C, new betaines having inhibitory activity of long chain fatty acid oxidation, were isolated from the culture broth of Emericella quadrilineata IFO 5859. Their structures were determined by spectroscopic analyses as (R)-3-(acylamino)-4-(trimethylammonio)butyrate (acyl: A, acetyl; B, propionyl; C,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00391a030
更新日期：1987-08-01 00:00:00
abstract：:The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00424
更新日期：2015-06-25 00:00:00
abstract：:A series of analogues of the potent and selective sigma receptor ligand 1,3-ditolylguanidine (DTG) were synthesized and demonstrated to have high affinity for the sigma receptor as measured by in vitro [3H]DTG displacement studies using guinea pig brain tissue. Three of these 1-aryl-3-(1-adamantyl)guanidines were radi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00110a017
更新日期：1991-06-01 00:00:00
abstract：:Interaction of 2-iodoaniline or 5-fluoro-2-iodoaniline with a range of arylsulfonyl chlorides affords sulfonamides that undergo Sonogashira couplings under thermal or microwave conditions with the alkyne 4-ethynyl-4-hydroxycyclohexa-2,5-dien-1-one followed by cyclization to 4-[1-(arylsulfonyl-1H-indol-2-yl)]-4-hydroxy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061163m
更新日期：2007-04-05 00:00:00
abstract：:The synthesis and CNS activity of a noval class of annelated 1,4-benzodiazepines, the aminomethylene-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepines, are described. An investigation of the structure--activity relationships in the series derived from 8-chloro-2,4-dihydro-2-dimethylaminomethylene-6-phenyl-1H-imidazo[1...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00218a009
更新日期：1977-08-01 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：:The fumagillin family of natural products inhibits angiogenesis through the irreversible inhibition of the type 2 methionine aminopeptidase (MetAP2). Herein is reported a novel fumagillin analogue named fumarranol. It is shown that, like fumagillin, fumarranol selectively inhibits MetAP2 and endothelial cell prolifera...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060559v
更新日期：2006-09-21 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：:A number of analogues of ibotenic acid [(RS)-3-hydroxy-5- isoxazoleglycine ] were synthesized; they were tested as excitants on neurons in the cat spinal cord, by using microelectrophoretic techniques, and as inhibitors of the binding of kainic acid (KA) in vitro, by using synaptic membranes prepared from rat brains. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00371a005
更新日期：1984-05-01 00:00:00
abstract：:Recently we have described the antitumor activities of 2-benzoxazolylhydrazones derived from 2-formyl and 2-acetylpyridines. In search of a more efficacious analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2-acylpyridine and alpha-(N)-acetyldiazine/quinoline groups have been synthesized. T...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060232u
更新日期：2006-10-19 00:00:00
abstract：:1-Methyl-5-(3-azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)uracil (C-AZT), a C-nucleoside isostere of the potent anti-AIDS nucleoside 3'-azido-3'-deoxythymidine (AZT), was synthesized. 1-Methyl-2'-deoxy-5'-O-tritylpseudouridine (2a) was oxidized with CrO3/pyridine/Ac2O complex to 1-methyl-5-(5-O-trityl-beta-D-glyce...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00169a030
更新日期：1990-07-01 00:00:00
abstract：:Select chemokine receptors act as coreceptors for HIV-1 entry into human cells and represent targets for antiviral therapy. In this report we describe a distamycin analogue, 2,2'-[4, 4'-[[aminocarbonyl]amino]bis[N,4'-di[pryrrole-2-carboxamide- 1, 1'-dimethyl]]-6,8-naphthalenedisulfonic acid]hexasodium salt (NSC 651016...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9801253
更新日期：1998-06-18 00:00:00
abstract：:Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity ( 7, 18- 20) ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8000949
更新日期：2008-06-26 00:00:00
abstract：:A 26-residue peptide BimBH3 binds indiscriminately to multiple oncogenic Bcl2 proteins that regulate apoptosis of cancer cells. Specific inhibition of the BimBH3-Bcl2A1 protein-protein interaction was obtained in vitro and in cancer cells by shortening the peptide to 14 residues, inserting two cyclization constraints ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00010
更新日期：2018-04-12 00:00:00
abstract：:Rhenium-cyclized CCMSH analogues are novel melanoma-targeting metallopeptides with high tumor uptake, long tumor retention, and low background in normal tissues, which make these metallopeptides an ideal structural motif for designing novel melanoma-targeting agents. ReCCMSH has been derivatized with a 1,4,7,10-tetraa...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010408m
更新日期：2002-07-04 00:00:00
abstract：:Adenosine induces glioma cell proliferation by means of an antiapoptotic effect, which is blocked by cotreatment with selective A(3) AR antagonists. In this study, a novel series of N(2)-substituted pyrazolo[3,4-d]pyrimidines 2a-u was developed as highly potent and selective A(3) AR antagonists. The most performing co...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901785w
更新日期：2010-05-27 00:00:00
abstract：:A new paradigm for drug research has emerged, namely the deliberate search for molecules able to selectively affect the proliferation, differentiation, and migration of adult stem cells within the tissues in which they exist. Recently, there has been significant interest in medicinal chemistry toward the discovery and...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm500838d
更新日期：2015-04-09 00:00:00
abstract：:The selective inhibition of the lipid signaling enzyme PI3Kγ constitutes an opportunity to mediate immunosuppression and inflammation within the tumor microenvironment but is difficult to achieve due to the high sequence homology across the class I PI3K isoforms. Here, we describe the design of a novel series of poten...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01203
更新日期：2020-10-08 00:00:00
abstract：:Two isoforms of the cyclooxygenase (COX) enzyme have been identified: COX-1, which is expressed constitutively, and COX-2, which is induced in inflammation. Recently, it has been shown that selective COX-2 inhibitors have antiinflammatory activity and lack the GI side effects typically associated with NSAIDs. Initial ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980570y
更新日期：1999-04-08 00:00:00
abstract：:Spatial correspondence between apomorphine, a prototype dopaminergic (DA) drug, and ergoline and some of its (partial) analogues were derived by matching their molecular electrostatic potential (MEP) patterns surrounding the aromatic moieties with respect to the coincident aliphatic N atoms. The MEP patterns were calc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00158a017
更新日期：1986-08-01 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：:Several novel azulene-containing retinoids were prepared and evaluated for their ability to suppress carcinogen-induced neoplastic transformation and to concomitantly up-regulate gap junctional communication in the in vitro mouse fibroblast C3H/10T1/2 cell bioassay. The azulenic retinoids were divided into two groups:...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00073a013
更新日期：1993-10-15 00:00:00
abstract：:We have synthesized a set of bis-pyranobenzoquinones through a direct and highly efficient approach based on a double intramolecular domino Knoevenagel hetero Diels-Alder reaction. These bis-pyranobenzoquinone derivatives are compounds whose skeletons have similarities to those of some anticancerous and leishmanicidal...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800403b
更新日期：2008-11-27 00:00:00
abstract：:NAD+ has a central function in linking cellular metabolism to major cell-signaling and gene-regulation pathways. Defects in NAD+ homeostasis underpin a wide range of diseases, including cancer, metabolic disorders, and aging. Although the beneficial effects of boosting NAD+ on mitochondrial fitness, metabolism, and li...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01254
更新日期：2018-02-08 00:00:00
abstract：:The optimization of a class of indole cPLA 2 alpha inhibitors is described herein. The importance of the substituent at C3 and the substitution pattern of the phenylmethane sulfonamide region are highlighted. Optimization of these regions led to the discovery of 111 (efipladib) and 121 (WAY-196025), which are shown to...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701467e
更新日期：2008-06-26 00:00:00
abstract：:(N)-Methanocarba adenosine 5'-methyluronamides containing known A(3) AR (adenosine receptor)-enhancing modifications, i.e., 2-(arylethynyl)adenine and N(6)-methyl or N(6)-(3-substituted-benzyl), were nanomolar full agonists of human (h) A(3)AR and highly selective (K(i) ∼0.6 nM, N(6)-methyl 2-(halophenylethynyl) analo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300396n
更新日期：2012-05-24 00:00:00
abstract：:Retinoic acid receptor-related orphan receptor γt (RORγt) is a nuclear receptor associated with the pathogenesis of autoimmune diseases. Allosteric inhibition of RORγt is conceptually new, unique for this specific nuclear receptor, and offers advantages over traditional orthosteric inhibition. Here, we report a highly...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01372
更新日期：2020-01-09 00:00:00
