Abstract：
:Gossypol and 17 derivatives were tested as inhibitors of aldose reductase from human placenta. Gossypol and a number of the derivatives were potent inhibitors. The order of inhibitory activity was interpreted in relation to the Kador-Sharpless pharmacophor model for the aldose reductase inhibitor site. The structural but not the electronic aspects of the model were found to apply to this series of compounds.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Deck LM,Vander Jagt DL,Royer REdoi
10.1021/jm00115a021subject
Has Abstractpub_date
1991-11-01 00:00:00pages
3301-5issue
11eissn
0022-2623issn
1520-4804journal_volume
34pub_type
杂志文章abstract：:A new series of quinazolinone derivatives was synthesized and evaluated as nonimidazole H 3 receptor inverse agonists. 2-Methyl-3-(4-[[3-(1-pyrrolidinyl)propyl]oxy]phenyl)-5-(trifluoromethyl)-4(3 H)-quinazolinone ( 1) was identified as a promising derivative for further evaluation following optimization of key paramet...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8003834
更新日期：2008-08-14 00:00:00
abstract：:17β-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00293
更新日期：2016-07-28 00:00:00
abstract：:Two new peptides, tailored after Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (TRI), namely, Ac-Thr-D-Trp(CHO)-Phe-NMe alpha MeBzl (TRA) and Ac-Thr-D-Trp(CHO)-Oic-NMeBzl (TOI), in which Phe is replaced by (3aS, 7aS)-octahydroindole-2-carboxylic acid, proved more potent and selective NK1 antagonists. The conformational properties of a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960213s
更新日期：1997-02-14 00:00:00
abstract：:Utilizing NNC 26-9100 (11) as a structural lead, a variety of nonpeptide derivatives of somatostatin were synthesized and evaluated for sst2 and sst4 receptor binding affinity. A novel thiourea scaffold was utilized to attach (1) a heteroaromatic nucleus to mimic the Trp8 residue, (2) a nonheteroaromatic nucleus to mi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980118e
更新日期：1998-11-19 00:00:00
abstract：:Ligands for retinoid X receptors (RXRs), "rexinoids", are attracting interest as candidates for therapy of type 2 diabetes and Alzheimer's and Parkinson's diseases. However, current screening methods for rexinoids are slow and require special apparatus or facilities. Here, we created 7-hydroxy-2-oxo-6-(3,5,5,8,8-penta...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00995
更新日期：2019-10-10 00:00:00
abstract：:Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049884d
更新日期：2004-10-07 00:00:00
abstract：:We disclose a novel series of indenopyrazole-based cyclin-dependent kinase (CDK) inhibitors. Kinetic experiments confirmed our initial molecular modeling studies that the compounds are competitive with respect to adenosine 5'-triphosphate (ATP) and bind in the kinase ATP pocket. A unique combination of active pharmaco...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020171+
更新日期：2002-11-21 00:00:00
abstract：:The vinyl ethers of choline and of its alpha- and beta-methyl homologues were prepared to determine their cholinergic effects and to determine whether a separation of the dual physiologic activity (nicotinic and muscarinic) reported for the vinyl ether of choline could be achieved by this modification. A literature me...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00229a015
更新日期：1976-07-01 00:00:00
abstract：:Etoxadrol (2a), one of the eight possible optical isomers of 2-ethyl-2-phenyl-4-(2-piperidyl)-1,3-dioxolane, was synthesized from (S,S)-1-(2-piperidyl)-1,2-ethanediol, which was obtained from cleavage of dexoxadrol (1a, (S,S)-2,2-diphenyl-4-(2-piperidyl)-1,3-dioxolane). The absolute configuration of etoxadrol hydrochl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00120a004
更新日期：1988-12-01 00:00:00
abstract：:Cancer cells generally possess higher levels of reactive oxygen species than normal cells, and this can serve as a possible therapeutic target. In this proof-of-concept study, an antioxidant-inspired drug discovery strategy was evaluated using a hydroxycinnamic acid derivative. The processing of oxidized mixtures of p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01994
更新日期：2019-02-14 00:00:00
abstract：:The synthesis and the biological and pharmacological evaluation of several 14-phenylpropoxy analogues of 14-methoxymetopon are described. Most of the new compounds were nonselective and exhibited binding affinities in the subnanomolar or low nanomolar range at opioid receptors mu, kappa, delta), with 14-phenylpropoxym...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030878b
更新日期：2003-09-11 00:00:00
abstract：:The photo "Wolff" rearrangement of readily available 2-diazoceph-3-em oxides (1) directly affords carbapen-2-ems, allowing a facile entry into a ring system previously accessible only by total synthesis, lengthly semisynthesis or fermentation. The chirality of the cephalosporin is accurately translated into the corres...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00163a048
更新日期：1990-01-01 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 antitumor prodrug temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (E.C. 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401121k
更新日期：2013-09-12 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：:Novel tumor-targeting theranostic conjugates 1 and 2, bearing either a fluorine-labeled prosthetic as a potential (18)F-PET radiotracer (1) or a fluorescence probe (2) for internalization studies in vitro, were designed and synthesized. We confirmed efficient internalization of 2 in biotin-receptor positive (BR+) canc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5019115
更新日期：2015-03-12 00:00:00
abstract：:The four stereoisomers of the muscarinic agonist 7 have been synthesized from enantiomerically pure exo-azanorbornane esters (13a,b). The esters were obtained in optically active form by separation of the carboxamide diastereomers 12a,b, formed from the borane complex of exo-azanorbornane-3-carboxylate 10 and a chiral...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00083a016
更新日期：1992-03-06 00:00:00
abstract：:The synthesis of the first 4-amino-3-carboxy-beta-carboline derivative (35) is described. This synthesis is based on ozonolysis of the 4-vinyl-beta-carboline-3-carboxamide 17 to give the 4-aldehyde 20 and potassium permanganate oxidation of the latter to the 4-carboxylic acid 34 followed by a DPPA-promoted Curtius rea...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00001a024
更新日期：1995-01-06 00:00:00
abstract：:A molecular model of the alpha(IIb)beta(3) integrin has been developed utilizing (i). the crystal structure of alpha(v)beta(3), (ii). homology model of the alpha(IIb) subdomain, and (iii). the docking of alpha(IIb)beta(3)/alpha(v)beta(3) dual and selective inhibitors into the putative binding sites of alpha(IIb)beta(3...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030146j
更新日期：2003-12-04 00:00:00
abstract：:A series of analogues of the fungal peptaibol type metabolite ampullosporin A containing modifications in the C and N terminus as well as alpha-aminoisobutyric acid (Aib) substitutions in different positions of the peptide were synthesized by solid phase synthesis using the 9-fluorenylmethyloxycarbonyl strategy. Depen...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0208018
更新日期：2002-06-20 00:00:00
abstract：:A series of aryl bicyclic analogs of succinimide and glutarimide was prepared and evaluated for CNS depressant activity. The 8a-aryl-3,4,6,7,8,8a-hexahydro-2H-pyrrolo[2,1-beta][1,3]oxazin-6-ones possessed the best overall spectrum of activity relative to the standard agents glutethimide and phenobarbital. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00225a023
更新日期：1976-03-01 00:00:00
abstract：:C5-unsubstituted-C6-aryl-1,4-dihydropyridines were prepared by a CAN-catalyzed multicomponent reaction from chalcones, β-dicarbonyl compounds, and ammonium acetate. These compounds were able to block Ca(2+) entry after a depolarizing stimulus and showed an improved Cav1.3/Cav1.2 selectivity in comparison with nifedipi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500263v
更新日期：2014-05-22 00:00:00
abstract：:A number of 6-sulfenamide, 6-sulfinamide, and 6-sulfonamide derivatives of 2-aminopurine and certain related purine ribonucleosides have been synthesized and evaluated for antileukemic activity in mice. Amination of 6-mercaptopurine ribonucleoside (7a) and 6-thioguanosine (7b) with chloramine solution gave 9-beta-D-ri...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00163a020
更新日期：1990-01-01 00:00:00
abstract：:As FDA-approved chemotherapeutic agents, cisplatin, oxaliplatin, and 5-fluorouracil are widely used in clinic but limited by severe side-effects. To ameliorate their respective defects, a series of "dual-prodrug" by linking oxoplatin and 5-FU were designed and synthesized. The assembled compounds 10-17, named Fuplatin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00128
更新日期：2019-05-09 00:00:00
abstract：:Mycophenolic alcohol (MPAlc), obtained by reduction of the carboxylic group of mycophenolic acid (MPA), was coupled with 2',3'-O-isopropylideneadenosine 5'-methylenebis(phosphonate) (4) in the presence of diisopropylcarbodiimide (DIC) to give P1-(2',3'-O-isopropylideneadenosin-5'-yl)-P2-(mycophenolic alcohol-6'-yl)met...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970705k
更新日期：1998-02-12 00:00:00
abstract：:7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661, 1) is a potent inhibitor of the enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28). In contrast to other inhibitors of PNMT, it is also highly selective toward PNMT in comparison with its affinity toward the alpha 2-adrenoceptor (PNMT Ki = 0....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960235e
更新日期：1997-12-05 00:00:00
abstract：:Using the crystal structure of an inhibitor complexed with the serine protease thrombin (PDB code ) and the functional group definitions contained within the Catalyst software, a representation of the enzyme's active site was produced (structure-based pharmacophore model). A training set of 16 homologous non-peptide i...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm021028j
更新日期：2003-04-10 00:00:00
abstract：:A variety of esters of methyldopa was synthesized with the objective of obtaining derivatives that would be more efficiently absorbed from the gastrointestinal tract than the free amino acid and would undergo conversion to methyldopa readily in the blood or target tissues. Two of the esters, alpha-pivaloyloxyethyl (4u...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00206a006
更新日期：1978-08-01 00:00:00
abstract：:In order to determine the influence of a 6alpha-methyl group activity, the 6alpha-methyl derivative of digitoxigenin 3-acetate 14 was prepared and pharmacologically tested in comparison with digitoxigenen 3-acetate. The synthesis of 6alpha-methyldigitoxigenin 3-acetate (14) was performed starting from 21-hydroxy-4-pre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00246a020
更新日期：1975-12-01 00:00:00
abstract：:Nintedanib (BIBF1120) is a potent, oral, small-molecule tyrosine kinase inhibitor, also known as a triple angiokinase inhibitor, inhibiting three major signaling pathways involved in angiogenesis. Nintedanib targets proangiogenic and pro-fibrotic pathways mediated by the VEGFR family, the fibroblast growth factor rece...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm501562a
更新日期：2015-02-12 00:00:00
