Abstract：
:The N alpha-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of H-Pro-Lys(X)-Pro-Val-NH2 (X: tert-butyloxycarbonyl, formyl, (2-chloroethyl)nitrosocarbamoyl) were synthesized. It was found that the bis-substitution of the urea N3 in these derivatives does not decrease the antitumor activity influenced mainly by the nature of the carrier molecule as a whole.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Süli-Vargha H,Jeney A,Lapis K,Medzihradszky Kdoi
10.1021/jm00386a024subject
Has Abstractpub_date
1987-03-01 00:00:00pages
583-6issue
3eissn
0022-2623issn
1520-4804journal_volume
30pub_type
杂志文章abstract：:In previous studies, we have grouped regions in space occupied by the vitamin D side chain into four: A, G, EA, and EG. We showed that the receptor (VDR) affinity of 1alpha,25-dihydroxyvitamin D3 derivatives increases, in terms of side-chain region, in the order EG, G, A, and EA. We called this the active space group ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970761l
更新日期：1998-04-23 00:00:00
abstract：:Three phosphapeptides designed to mimic two distinct tetrahedral intermediates formed during either the synthesis or hydrolysis of glutathionylspermidine (Gsp) were synthesized and evaluated as inhibitors of the bifunctional enzyme Gsp synthetase/amidase. While the polyamine-containing phosphapeptides were determined ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970414b
更新日期：1997-11-07 00:00:00
abstract：:The mechanism-based risk for hyperkalemia has limited the use of mineralocorticoid receptor antagonists (MRAs) like eplerenone in cardio-renal diseases. Here, we describe the structure and property-driven lead generation and optimization, which resulted in identification of MR modulators ( S)-1 and ( S)-33. Both compo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01523
更新日期：2019-02-14 00:00:00
abstract：:Condensation of cyanothioacetamide (4) with ethyl alpha-(ethoxymethylene)acetoacetate (5b), ethyl 4-ethoxy-2-(ethoxymethylene)-3-oxobutanoate (5c), ethyl 2-(ethoxymethylene)-3-oxo-4-phenylpropanoate (5d) afforded exclusively the corresponding 6-substituted pyridines (6b-d). Cyclization of 4 with 3-carbethoxybutane-2,4...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00401a023
更新日期：1988-06-01 00:00:00
abstract：:Osteoclast-mediated bone matrix resorption has been attributed to cathepsin K, a cysteine protease of the papain family that is abundantly and selectively expressed in osteoclast. Inhibition of cathepsin K could potentially be an effective method to prevent osteoporosis. Structure-activity studies on a series of rever...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030373l
更新日期：2004-01-29 00:00:00
abstract：:To design and synthesize new potent and selective antagonists of the human A(3) adenosine receptor, pharmacophoric hypotheses were generated with the software Catalyst for a comprehensive set of compounds retrieved from previous literature. Three of these pharmacophores were used to drive the optimization of a molecul...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm051112+
更新日期：2006-07-13 00:00:00
abstract：:Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway of tryptophan metabolism, which is involved in immunity, neuronal function, and aging. Its implication in pathologies such as cancer and neurodegenerative diseases has stimulated the development of IDO1 inhibitors. However,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00942
更新日期：2019-10-10 00:00:00
abstract：:The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON, 1) has shown robust anticancer efficacy in preclinical and clinical studies, but its development was halted due to marked systemic toxicities. Herein we demonstrate that DON inhibits glutamine metabolism and provides antitumor efficacy in a murine model of glio...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01069
更新日期：2016-09-22 00:00:00
abstract：:A novel piperidine series of farnesyltransferase (FTase) inhibitors is described. Systematic medicinal chemistry studies starting with the lead compound, discovered from a 5-nitropiperidin-2-one combinatorial library, resulted in a potent series of novel FTase inhibitors. We found that all of four substituents of the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020522k
更新日期：2003-06-05 00:00:00
abstract：:Structure dependent efficacy studies in the field of selective D4 ligands led to the 2-aminomethyl substituted azaindole 2 (FAUC 213) that displayed strong D4 binding, high subtype selectivity, and complete antagonist properties in ligand-induced mitogenesis experiments. According to our schematic molecular model, the...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm015522j
更新日期：2001-08-16 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：:A number of cycloalkyl substituents (from C-3 to C-8) have been introduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guano...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9911231
更新日期：2000-01-27 00:00:00
abstract：:A series of (fluorobenzyl)triazolo[4,5-c]pyridines was synthesized and tested for activity against maximal electroshock-induced seizures in rodents. The most promising compound, 14 (BW 534U87), which is a carbon-nitrogen isoster of a purine anticonvulsant, has a profile in rodents that suggests 14 will be free of emes...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00020a030
更新日期：1995-09-29 00:00:00
abstract：:Protein target-based discovery of novel antibiotics has been largely unsuccessful despite rich genome information. Particularly in need are new antibiotics for tuberculosis, which kills 1.6 million people annually and shows a rapid increase in multiple-drug-resistant cases. By combining fragment-based drug discovery w...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100993z
更新日期：2010-12-09 00:00:00
abstract：:Four new 2-(2-piperidinoethyl)benzocycloalkanone derivatives, 20-23, were prepared and evaluated as potential antipsychotic agents in receptor binding assays for dopamine (DA) and 5-HT2A receptors and in functional and behavioral screens. Their affinities for D2 receptors (Ki's in the nanomolar range: 46.7-70.7) and D...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00042a009
更新日期：1994-08-05 00:00:00
abstract：:Two prototype N-methyl-4-thio-substituted cyclophosphamide (CP) derivatives (5 and 6), prodrugs of 4-hydroxycyclophosphamide (4-HO-CP), were designed to undergo oxidative N-demethylation to release the active alkylating agent. These prodrugs were chemically stable until oxidatively N-demethylated in the presence of he...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00005a012
更新日期：1995-03-03 00:00:00
abstract：:We recently described a novel series of CA(1)A(2)X peptidomimetics as farnesyl transferase inhibitors (FTIs). These compounds possess an N-(4-piperidinyl)benzamide scaffold mimicking A(1)A(2) residue. Extensive exploration of structure--activity relationships revealed that replacement of cysteine by substituted benzyl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030502y
更新日期：2004-12-30 00:00:00
abstract：:A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones were synthesized and evaluated for anticonvulsant activity in DBA/2 mice against sound-induced seizures and in rats against maximal electroshock-induced seizures. Most of the derivatives showed an anticonvulsant effect better than that of valproate, ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00121a019
更新日期：1989-01-01 00:00:00
abstract：:The protein kinase PfCLK3 plays a critical role in the regulation of malarial parasite RNA splicing and is essential for the survival of blood stage Plasmodium falciparum. We recently validated PfCLK3 as a drug target in malaria that offers prophylactic, transmission blocking, and curative potential. Herein, we descri...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00451
更新日期：2020-09-10 00:00:00
abstract：:A series of 9-(hydroxyalkenyl)purines (adenines and 3-deazaadenines), which are analogues of neplanocin A, were synthesized. The analogues were tested as inhibitors of bovine liver and murine L929 cell S-adenosyhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1) and as inhibitors of vaccinia virus replication in murine L929 ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00117a011
更新日期：1988-09-01 00:00:00
abstract：:A series of new nitrogen-carbon-linked (azolylphenyl)oxazolidinone antibacterial agents has been prepared in an effort to expand the spectrum of activity of this class of antibiotics to include Gram-negative organisms. Pyrrole, pyrazole, imidazole, triazole, and tetrazole moieties have been used to replace the morphol...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990373e
更新日期：2000-03-09 00:00:00
abstract：:A pharmacophore model for triple reuptake inhibitors and the new class of 1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes were recently reported. Further investigation in this area led to the identification of a new series of potent and selective triple reuptake inhibitors endowed with good developability characte...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100481d
更新日期：2010-07-08 00:00:00
abstract：:A series of amide, urea, and carbamate analogues of the muscarinic (M1) ganglionic stimulant [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride (McN-A-343; 1) was prepared. The C1-methyl-substituted carbamates 8-11 were resolved into the enantiomers. In order to investigate the ganglionic stimu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00093a011
更新日期：1992-07-24 00:00:00
abstract：:As part of an ongoing effort to discover novel small-molecule antifolates combining the enzyme-binding species selectivity of trimethoprim (TMP) with the potency of piritrexim (PTX), 10 previously unreported 2,4-diamino-5-(2'-methoxy-5'-substituted)benzylpyrimidines (2-11) containing a carboxyl group at the distal end...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020466n
更新日期：2003-04-24 00:00:00
abstract：:In an attempt to determine which conformational parameters are important for the biological activity of ovine corticotropin-releasing factor (oCRF), we have synthesized in significant amounts (50-200 mg) and characterized chemically, structurally (CD), and biologically, oCRF analogues with substitution of each amino a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00072a003
更新日期：1993-10-01 00:00:00
abstract：:The preparation and testing of the two racemic diastereoisomers and the four optically active enantiomers of the title compound in in vitro and in vivo models for determining potential antipsychotic activity are described. Both racemic diastereoisomers and two of the four chiral enantiomers are potent and long-acting ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00182a025
更新日期：1980-08-01 00:00:00
abstract：:Understanding the "limits and boundaries" of the central nervous system (CNS) property space is a critical aspect of modern CNS drug design. Medicinal chemists are often guided by the physicochemical properties of marketed CNS drugs, which are heavily biased toward "traditional" aminergic targets and commonly describe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,收录出版
doi：10.1021/acs.jmedchem.6b01469
更新日期：2017-07-27 00:00:00
abstract：:Since their discovery over 5 decades ago, quinolone antibiotics have found enormous success as broad spectrum agents that exert their activity through dual inhibition of bacterial DNA gyrase and topoisomerase IV. Increasing rates of resistance, driven largely by target-based mutations in the GyrA/ParC quinolone resist...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00347
更新日期：2020-07-23 00:00:00
abstract：:In a continuation of studies directed toward characterizing the hydrophilic pocket within the aromatic ring binding region of the active site of phenylethanolamine N-methyltransferase (PNMT), 5-, 6-, 7-, and 8-hydroxy-1,2,3,4-tetrahydroisoquinoline were prepared and evaluated as substrates and inhibitors of PNMT. In o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00395a006
更新日期：1987-12-01 00:00:00
abstract：:The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses are attractive targets for the development of antiviral drugs. We report the synthesis and evaluation of a new, proline-based compound class that displays allosteric inhibition of both proteases. The structural features relevant for protease binding and...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01697
更新日期：2019-12-26 00:00:00
