Abstract:
:Selectively substituted hydantoins 1 (15 examples), 4-hydroxy-2-imidazolidinones 2 (13 examples), 2-imidazolones 3 (10 examples), 2-imidazolidinones 4 (four examples), vicinal diamines 5 (two examples), and simple amino acid derivatives 6 (four examples) have been prepared and evaluated in the maximal electroshock seizure (MES), subcutaneous pentylenetetrazole seizure threshold (sc Met), and rotorod (Tox) tests. The medium effective doses (ED50) and the medium toxic dose (TD50) for the most active compounds are reported. In general, the most pronounced activity was observed for hydantoins 1 and protected amino acids 6. Within each series of compounds, enhanced anticonvulsant activity was often noted for compounds containing an aromatic group one carbon removed from a nitrogen atom. Among the most active compounds observed were the amino acid derivative N-acetyl-D,L-alanine benzylamide (6d) and the two 2-imidazolones 4-methyl-1-(phenylmethyl)-1,3-dihydro-2H-imidazol-2-one (3e) and 1-phenyl-1,3-dihydro-2H-imidazol-2-one (3g). Compound 6d proved to be slightly more potent in the MES test than phenacemide.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Cortes S,Liao ZK,Watson D,Kohn Hdoi
10.1021/jm50001a012subject
Has Abstractpub_date
1985-05-01 00:00:00pages
601-6issue
5eissn
0022-2623issn
1520-4804journal_volume
28pub_type
杂志文章abstract::Bis (1-aziridinyl)(hexahydro-1H-azepin-1-yl)phosphine sulfide, an active anticancer agent with low hematopoietic toxicity in animals and man, was recommended several years ago for breast cancer adjuvant chemotherapy as an alternate drug to thiotepa. This hope had led to the syntheses of aziridinylallylaminophosphine o...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00228a014
更新日期:1976-06-01 00:00:00
abstract::The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we disclosed the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind the KAc region and then building into the LPF shelf. Herein, we report the "hybridization" of a v...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.7b01372
更新日期:2017-12-28 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::Bifunctional quinolinonyl DKA derivatives were first described as nonselective inhibitors of 3'-processing (3'-P) and strand transfer (ST) functions of HIV-1 integrase (IN), while 7-aminosubstituted quinolinonyl derivatives were proven IN strand transfer inhibitors (INSTIs) that also displayed activity against ribonuc...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b00159
更新日期:2015-06-11 00:00:00
abstract::A novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A' ') for sequestering radiometals (86Y or 111In) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm070657w
更新日期:2007-09-20 00:00:00
abstract::The new pyrimidine derivatives of 2,3-O, O-dibenzyl-6-deoxy-L-ascorbic acid (8-10) were synthesized by condensation of uracil and its 5-fluoro- and 5-trifluoromethyl-substituted derivatives with 4-(5,6-epoxypropyl)-2, 3-O,O-dibenzyl-L-ascorbic acid (7), while pyrimidine derivatives of 4,5-didehydro-5,6-dideoxy-L-ascor...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0009540
更新日期:2000-12-14 00:00:00
abstract::Four novel steroidal alpha-methylene delta-lactones have been synthesized and shown to be active against human nasopharyngeal carcinoma (KB) cells in culture. The syntheses involved the use of known alpha-methylenation procedures. In addition, the lactone 6 was directly methylenated by reaction with CH2O/KOH or Et2NH/...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00175a019
更新日期:1980-01-01 00:00:00
abstract::Iodonium ion mediated cyclization of unsaturated hydroperoxides 1 afforded the expected yingzhaosu A analogues 2. In some cases, however, the corresponding cyclic ethers 5 were formed competitively with the cyclic peroxides 2, the ratios of these two products being a marked function of the structure of the starting ma...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm020208q
更新日期:2002-10-10 00:00:00
abstract::3,4-Dihydro-2(1H)-quinolones, evolved from 2-carboxy-1,2,3,4,- tetrahydroquinolines and 3-carboxy-4-hydroxy-2(1H)-quinolones, have been synthesized and evaluated in vitro for antagonist activity at the glycine site on the NMDA receptor and for AMPA [(RS)-alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid] antag...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00074a021
更新日期:1993-10-29 00:00:00
abstract::New N-alkylanilinoquinazoline derivatives 5, 12, 20, and 22 have been prepared from 4-chloro-6,7-dimethoxyquinazoline 3, 4-chloro-6,7-methylenedioxyquinazoline 19, and commercially available anilines. Differents classes of compounds substituted by an aryloxygroup (6a-c, 16a,b, and 17a,b), (aminophenyl)ureas (12a,b and...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm1009605
更新日期:2010-11-25 00:00:00
abstract::Glucuronidation and transporter-mediated efflux into bile are important in the elimination of xeno- and endobiotics, including the natural biladienone pigment bilirubin. The mechanisms of these processes and the structural factors that dictate whether cholephilic compounds are excreted directly in bile or require prio...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0609521
更新日期:2007-02-08 00:00:00
abstract::The polyhalogenated benzimidazole nucleosides 2,5, 6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were synthesized in our laboratory and established as potent and selective inhibitors of human cytomegalovirus (HCMV) with a novel mode of action. In an effort to study the behav...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm990290y
更新日期:2000-06-15 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::We report a three-dimensional model of the alpha5beta1 integrin headgroup bound to the most potent and selective ligand (SJ749) known to date. The model was built using the comparative protein modeling method, and it is consistent with experimental data. From this study, we identified two potentially important regions...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm040224i
更新日期:2005-06-30 00:00:00
abstract::We have previously reported a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands to serve as potential nonaddictive opioid analgesics. These ligands have been shown to be active in vivo, do not manifest withdrawal syndromes or reward behavior in conditioned-place preference assays in ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.9b00219
更新日期:2019-04-25 00:00:00
abstract::Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-targeted kinase inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tum...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.6b00087
更新日期:2016-04-28 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::With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm010080x
更新日期:2001-11-22 00:00:00
abstract::Since the discovery of the serotonin 4 receptor (5-HT(4)R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4-piperidinyl)methyl]-1H-indazol...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm300573d
更新日期:2012-11-26 00:00:00
abstract::We have synthesized and evaluated azaquinoxalinediones 3a-c for their activity in inhibiting [3H]AMPA binding from rat whole brain. It was found that the azaquinoxalinedione nucleus functions as a bioisostere for quinoxalinedione in AMPA receptor binding. The detailed structure-activity relationships of 6- and/or 7-su...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm950304+
更新日期:1996-03-15 00:00:00
abstract::We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm300631e
更新日期:2012-07-26 00:00:00
abstract::The diphenylsulfonyl sulfonamide scaffold represented by 1 (WAY-316606) are small molecule inhibitors of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic agents for the treatment of osteoporosis or other bone-related di...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm801144h
更新日期:2009-01-08 00:00:00
abstract::Novel 19-norvitamin D analogues (ADYW1-4, 5a-d) in which an adamantyl diyne side chain is attached directly to the 17-position of the D ring are designed and stereoselectively synthesized. The adamantane ring of these analogues was expected to interfere with helix 12 (H12, activation function 2) of the vitamin D recep...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b00792
更新日期:2015-12-24 00:00:00
abstract::Monophenolic (2-(dipropylamino)indans and related compounds have been synthesized and tested for central dopamine-receptor stimulating activity, using biochemical and behavioral tests in rats and emesis tests in dogs. The active compounds possess similar relative potencies in eliciting the three different dopamine-rec...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00136a012
更新日期:1981-04-01 00:00:00
abstract::A comprehensive herbal medicine information system for cancer (CHMIS-C) has been developed. The current version of the database integrates information on more than 200 anticancer herbal recipes that have been used for the treatment of different types of cancer in clinic, 900 individual ingredients, and 8500 small orga...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm049838d
更新日期:2005-03-10 00:00:00
abstract::The syntheses of 2-amino-N-(2-benzoyl)-4-chlorophenyl)acetamides are reported. The pharmacological properties of these compounds were compared with data obtained from the corresponding cyclized products [5-(2,6-dichlorophenyl)-1,4-benzodiazepin-2-ones]. Evidence is presented which suggests that the central nervous sys...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00351a009
更新日期:1982-09-01 00:00:00
abstract::A study of the structure-activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed, targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12-14) revealed that the optimal position for substitution was the meta-positi...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0611509
更新日期:2007-03-08 00:00:00
abstract::4,5-Diphenyl-2-oxazolenonanoic acid (18b) was synthesized and found to inhibit ADP-induced aggregation of human platelets with an IC50 of 2.5 microM. Acid 18b displaced [3H]iloprost from human platelet membranes in a concentration-dependent fashion, consistent with 18b inhibiting platelet function by acting as a prost...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00097a006
更新日期:1992-09-18 00:00:00
abstract::A new series of compounds were designed as structural analogues of the alpha(1)-AR ligand RN5 (4), characterized by a tricyclic 5H-pyrimido[5,4-b]indole-(1H,3H)2,4-dione system connected through an alkyl chain to a phenylpiperazine (PP) moiety. These compounds were synthesized and tested in binding assays on human alp...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0307741
更新日期:2003-07-03 00:00:00
abstract::Most bromodomain inhibitors mimic the interactions of the natural acetylated lysine (KAc) histone substrate through key interactions with conserved asparagine and tyrosine residues within the binding pocket. Herein we report the optimization of a series of phenyl sulfonamides that exhibit a novel mode of binding to no...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c00021
更新日期:2020-05-28 00:00:00