Abstract：
:An approach to the development of new anticandidal drugs is described that employs peptides as carriers of toxic agents into cells. 5-Flurorcytosine (5-FC) was chosen as a toxic agent with which to prepare 5-FC-peptide conjugates as models to test the carrier proposal. Model compounds were synthesized and then tested for antiyeast activity against S. Cerevisiae 9763, C. albicans 1-V, C. albicans WD 18-4, and C. Krusei 1-T. The 5-FC derivatives showed antiyeast activity comparable to 5-FC in all strains except C. krusei 1-T, in which case the compounds were less active. The solution stabilities of 5-FC conjugates at 37 degrees C were tested in the same growth medium used for susceptibility testing. The results indicated a range of stabilities where the half-life (t1/2) = 0.3--17.6 h. These results and those obtained in the susceptibility testing suggest extracellular hydrolysis and indicate that the type of linkage used to conjugate 5-FC to peptides will not provide appropriate compounds to evaluate the peptide-carrier concept.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Steinfeld AS,Naider F,Becker JMdoi
10.1021/jm00195a019subject
Has Abstractpub_date
1979-09-01 00:00:00pages
1104-9issue
9eissn
0022-2623issn
1520-4804journal_volume
22pub_type
杂志文章abstract：:A series of novel triazol-3-ones have been synthesized, and their in vitro and in vivo antifungal properties are reported. Compound 68 (itraconazole), which displays a pronounced oral activity against vaginal candidosis in rats and against microsporosis in guinea pigs, has been selected for clinical evaluation. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00373a015
更新日期：1984-07-01 00:00:00
abstract：:We present a comprehensive study of the performance of fast scoring functions for library docking using the program FlexX as the docking engine. Four scoring functions, among them two recently developed knowledge-based potentials, are evaluated on seven target proteins whose binding sites represent a wide range of siz...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0003992
更新日期：2001-03-29 00:00:00
abstract：:A series of 1-(p-nitrophenyl)-2-aminoethanol derivatives and their morpholine analogues have been synthesized and pharmacologically investigated in order to confirm some pharmacological observations made with the N-isopropyl-substituted compounds. In agreement with the previously obtained results, the weak alpha-adren...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00192a023
更新日期：1979-06-01 00:00:00
abstract：:We have designed and synthesized eight compounds 2-9 which incorporate various amino acid residues in positions 17, 18, and 21 of the glucagon molecule: 2, [Lys17]glucagon amide; 3, [Lys18]glucagon amide; 4, [Nle17,Lys18,Glu21]glucagon amide; 5, [Orn17,18, Glu21]glucagon amide; 6, [d-Arg17]glucagon; 7, [d-Arg18]glucag...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980084a
更新日期：1998-07-16 00:00:00
abstract：:Modulation of sphingosine 1-phosphate (S1P) signaling represents a solid opportunity for multiple sclerosis (MS) treatment. In this issue, a team at Novartis reports on the identification of the first direct S1P lyase (S1PL) inhibitors as new MS agents. One of the most potent inhibitors reported in their work was demo...
journal_title：Journal of medicinal chemistry
pub_type： 评论,杂志文章
doi：10.1021/jm500845y
更新日期：2014-06-26 00:00:00
abstract：:Kadsurenone, a specific receptor antagonist of platelet-activating factor (PAF), and its analogues were prepared from derivatives of cinnamyl alcohol and (allyloxy)phenol. Racemic kadsurenone, resolvable by a Chiralpak column at low temperatures, has an IC50 value of 2 X 10(-7) M, which is about 50% of the activity of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00384a023
更新日期：1987-01-01 00:00:00
abstract：:The synthesis, antiarrhythmic activity, and blood hydrolysis properties of a series of mono- and bis(aminomethyl)phenylacetic acid esters related to a previously reported class Ic antiarrhythmic agent (ACC-9358) are described. Of the various oxa-, aza-, thia-, and carbacyclic esters initially prepared in the bis(pyrro...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00069a007
更新日期：1993-08-20 00:00:00
abstract：:The N-2 atoms of phosphorus 2,2-dimethylhydrazides, contrary to a previous report, can be methylated by iodomethane. Treatment of the resulting dihydrazinium iodides with aqueous sodium hydroxide results in mono- instead of didehydroiodination, apparently due to resonance stabilization of the inner salt form. The phos...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm50001a010
更新日期：1985-05-01 00:00:00
abstract：:We report the esterification of the carboxyl groups of the cyclic peptide toxins nodularin-R and microcystin-LA to produce stable diacetoxymethyl and dipropionyloxymethyl ester derivatives. The derivatives had no activity but were reactivated upon esterase treatment. When injected into cells, the acyloxymethyl moietie...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900502e
更新日期：2009-09-24 00:00:00
abstract：:Aromatic side-chain analogues (arocalciferols 6-9) of the steroid hormone 1 alpha,25-dihydroxyvitamin D3 (1) were synthesized and biologically evaluated. The analogues were prepared by coupling the vitamin D A-ring enyne 14 with the appropriate enol triflate of a modified CD steroid fragment of the type 22. The result...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00112a021
更新日期：1991-08-01 00:00:00
abstract：:Androgens are well-known to stimulate prostate cancer (PC) growth. Thus, blockade of androgen production in testes and adrenals by CYP17 inhibition is a promising strategy for the treatment of PC. Moreover, many PC patients suffer from glucocorticoid overproduction, and importantly mutated androgen receptors can be st...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100317b
更新日期：2010-08-12 00:00:00
abstract：:A series of 5-substituted tetrahydroisoquinolines was synthesized via a 10-step linear synthesis to assess whether replacement of noscapine's southern isobenzofuranone with other moieties resulted in retained cytotoxic activity. One such molecule, 18g, bearing a para-methoxybenzyl functionality with N-ethylcarbamoyl s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00986
更新日期：2018-09-27 00:00:00
abstract：:A novel series of nonsteroidal progestins, 5-benzylidene-1, 2-dihydrochromeno[3,4-f]quinolines (2), was discovered, and a preliminary structure-activity relationship study around the 5-benzylidene ring generated several potent human progesterone receptor agonists (compounds 8, 16). These new progestins showed biologic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980366a
更新日期：1998-10-22 00:00:00
abstract：:Development of orally available phosphodiesterase 4 (PDE4) inhibitors as anti-inflammatory drugs has been going on for decades. However, only roflumilast has received FDA approval. One key challenge has been the low therapeutic window observed in the clinic for PDE4 inhibitors, primarily due to PDE4 mediated side effe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm500378a
更新日期：2014-07-24 00:00:00
abstract：:Rebeccamycin analogues containing uncommon sugars and substitutions on the imide nitrogen have been synthesized. Their cytotoxicities were tested in colon cancer and leukemia cells. Their ability to target topoisomerase I was examined using the in vivo complex of the topoisomerase bioassay in Hela cells. Compared with...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0493764
更新日期：2005-04-07 00:00:00
abstract：:There has been significant interest in developing a transient receptor potential A1 (TRPA1) antagonist for the treatment of pain due to a wealth of data implicating its role in pain pathways. Despite this, identification of a potent small molecule tool possessing pharmacokinetic properties allowing for robust in vivo ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00039
更新日期：2016-03-24 00:00:00
abstract：:A facile route to perillyl alcohol (POH) differential glycosylation and the corresponding synthesis of a set of 34 POH glycosides is reported. Subsequent in vitro studies revealed a sugar dependent antiproliferative activity and the inhibition of S6 ribosomal protein phosphorylation as a putative mechanism of represen...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500870u
更新日期：2014-09-11 00:00:00
abstract：:Substrate-selective inhibition or modulation of the activity of γ-secretase, which is responsible for the generation of amyloid-β peptides, might be an effective strategy for prevention and treatment of Alzheimer's disease. We have shown that helical β-peptide foldamers are potent and specific inhibitors of γ-secretas...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301306c
更新日期：2013-02-28 00:00:00
abstract：:The recently discovered nicotinic agonist pyrido[3,4-b]norhomotropane [corrected] (PHT) as well as its N-methyl and 2'-methyl derivatives (syntheses reported herein) were compared with nicotine, nornicotine, and anatoxin a in a series of in vitro and in vivo assays. The results reveal that PHT possesses activity compa...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00398a004
更新日期：1988-03-01 00:00:00
abstract：:The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9910369
更新日期：1999-08-12 00:00:00
abstract：:A variety of derivatives of 2-pyridinecarboxaldehyde 1-oxide benzenesulfonylhydrazone, containing substituents on the benzene or pyridine rings as well as on the nitrogen atom which is bonded directly to the sulfonyl group, have been synthesized. The antineoplastic activity of these compounds has been assessed in mice...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00180a010
更新日期：1980-06-01 00:00:00
abstract：:Histone deacetylase 6 (HDAC6) is an emerging target for the treatment of cancer, neurodegenerative diseases, inflammation, and other diseases. Here, we present the multicomponent synthesis and structure-activity relationship of a series of tetrazole-based HDAC6 inhibitors. We discovered the hit compound NR-160 by inve...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01888
更新日期：2020-09-24 00:00:00
abstract：:The cardiac activity of a series of analogues of the positive inotropic bipyridines amrinone (5-amino-[3,4'-bipyridin]-6(1H)-one) and milrinone (2-methyl-5-cyano-[3,4'-bipyridin]-6(1H)-one) was evaluated in vitro in a rabbit myocardial membrane Mg(2+)-dependent, Ca(2+)-stimulable adenosine triphosphatase (Ca(2+)-ATPas...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00011a018
更新日期：1995-05-26 00:00:00
abstract：:Pulmonary edema is a common ailment of heart failure patients and has remained an unmet medical need due to dose-limiting side effects associated with current treatments. Preclinical studies in rodents have suggested that inhibition of transient receptor potential vanilloid-4 (TRPV4) cation channels may offer an alter...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01344
更新日期：2018-12-27 00:00:00
abstract：:A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-carbamate analogues have been synthesized and evaluated for antibacterial activity. These compounds were found to be potent antibacterial agents against Gram-positive organisms in vitro, many having MIC values below 1 microg/mL for the macrolide-s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970547x
更新日期：1998-05-07 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：:In this article we introduce a molecular docking algorithm called MolDock. MolDock is based on a new heuristic search algorithm that combines differential evolution with a cavity prediction algorithm. The docking scoring function of MolDock is an extension of the piecewise linear potential (PLP) including new hydrogen...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm051197e
更新日期：2006-06-01 00:00:00
abstract：:Recently, we have discovered that the registered pesticide, tolfenpyrad, unexpectedly and potently inhibits the development of the L4 larval stage of the parasitic nematode Haemonchus contortus with an IC50 value of 0.03 μM while displaying good selectivity, with an IC50 of 37.9 μM for cytotoxicity. As a promising mol...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01789
更新日期：2019-01-24 00:00:00
abstract：:This paper describes the chemical synthesis and CCK-B and CCK-A receptor binding affinities of a series of compounds in which the central amide bond of the CCK-B "dipeptoid" ligand tricyclo[3.3.1.1(3,7)]dec-2-yl [R-(R*,S*)]-[2-[[1-(hydroxymethyl)- 2-phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]carb amate (4) ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00086a017
更新日期：1992-04-17 00:00:00
abstract：:The atypical chemokine receptor 3 (ACKR3)/CXC chemokine receptor 7 (CXCR7) recognizes stromal cell-derived factor 1 (SDF-1)/CXCL12 and is involved in a number of physiological and pathological processes. Here, we investigated the SAR of the component amino acids in an ACKR3-selective ligand, FC313 [ cyclo(-d-Tyr-l-Arg...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00336
更新日期：2018-04-26 00:00:00
