Abstract:
:A series of pepstatin analogues having structural variations in the P2', P1', and P2 positions have been synthesized and tested for inhibition of porcine pepsin. The standard peptide for this study was Iva-Sta-Val-Ala-Iaa. Structural variations in the P2' and P1' positions have relatively little effect on Ki; however, small variations in the P2 position have a more dramatic effect on Ki and time-dependent inhibition. A series of pepstatin fragments were also synthesized and tested for inhibition of porcine pepsin.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Rich DH,Salituro FGdoi
10.1021/jm00360a022subject
Has Abstractpub_date
1983-06-01 00:00:00pages
904-10issue
6eissn
0022-2623issn
1520-4804journal_volume
26pub_type
杂志文章abstract::Two isomeric 6-endo- and 6-exo-(3',4'-dihydroxyphenyl) derivatives (1 and 2) of 2-azabicyclo[2.2.2]octane were synthesized as semirigid analogues of dopamine (DA) to help evaluate the preferred conformation of dopamine at the uptake site of the presynaptic nerve terminal and at the DA receptor. Against the uptake of 0...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00345a004
更新日期:1982-03-01 00:00:00
abstract::Three analogs of luteinizing hormone-releasing hormone (LH-RH) of the structure less than Glu-His-Trp-Ser-Tyr-Gly-Gly-Leu-Arg-Pro-Gly-NH2, involving substitutions inpositions 1, 3, and 8 with nonprotein amino acids, have been synthesized by the solid-phase method. They are [pyro-L-alpha-(1-aminoadipic)]-LH-RH, [3-(2-n...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00226a008
更新日期:1976-04-01 00:00:00
abstract::A series of 2,3-diaminopropionanilides was synthesized by acylation of mono- and disubstituted aniline derivatives with 2,3-dibromopropionyl chloride and subsequent amination with the appropriate secondary amines. The target compounds were evaluated in mice for antiarrhythmic efficacy against chloroform-induced tachyc...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00141a008
更新日期:1981-09-01 00:00:00
abstract::As part of a study on the antitumor activities of tropolone derivatives prepared from hinokitiol, which naturally occurs in the plants of Chamaecyparis species, effects of aromatic substituents of alpha,alpha-bis(7-hydroxy-5-isopropyltropon-2-yl)toluenes on the activity were examined. Several of the compounds showed h...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00157a014
更新日期:1986-07-01 00:00:00
abstract::G-protein coupled receptor (GPCR) GPR109a is a molecular target for nicotinic acid and is expressed in adipocytes, spleen, and immune cells. Nicotinic acid has long been used for the treatment of dyslipidemia due to its capacity to positively affect serum lipids to a greater extent than other currently marketed drugs....
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章,随机对照试验
doi:10.1021/jm2010964
更新日期:2012-04-26 00:00:00
abstract::The cytotoxicity of oxysterols was systematically studied in tumor and normal cells. Synthetic strategies to prepare this library included oxidations at ring B and a new method to yield 6β-hemiphthalates directly from Δ(5)-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer cells, LAMA-84 cel...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm1007769
更新日期:2010-11-11 00:00:00
abstract::This report describes the syntheses and structure-activity relationships of 8-(4-methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF(1)) receptor antagonists. CRF(1) receptor antagonists may be potential anxiolytic or antidepressant drugs. This research culminated in the discove...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm9000242
更新日期:2009-05-14 00:00:00
abstract::A unique, dual-function, photoactivatable anticancer prodrug, RuEuL, has been tailored that features a ruthenium(II) complex linked to a cyclen-europium chelate via a π-conjugated bridge. Under irradiation at 488 nm, the dark-inactive prodrug undergoes photodissociation, releasing the DNA-damaging ruthenium species. U...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.7b01162
更新日期:2017-11-09 00:00:00
abstract::We present and thoroughly characterize a large collection of 3,4-dihydropyrimidin-2(1H)-ones as A2BAR antagonists, an emerging strategy in cancer (immuno) therapy. Most compounds selectively bind A2BAR, with a number of potent and selective antagonists further confirmed by functional cyclic adenosine monophosphate exp...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c01431
更新日期:2021-01-14 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::N,N'-Diarylureas were prepared, and the structure-activity relationship relative to the CXCR2 receptor was examined. This led to the identification of a potent and highly selective CXCR2 antagonist, which in addition was shown to be functionally active both in vitro against human neutrophils and in vivo in rabbit mode...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm034248l
更新日期:2004-03-11 00:00:00
abstract::In this work, we describe the synthesis and in vitro evaluation of a novel series of multitarget-directed ligands (MTDL) displaying both nanomolar dual-binding site (DBS) acetylcholinesterase inhibitory effects and partial 5-HT4R agonist activity, among which donecopride was selected for further in vivo evaluations in...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b00115
更新日期:2015-04-09 00:00:00
abstract::4,6,6a,7,8,12b-Hexahydroindolo[4,3-ab]phenanthridines ("benzergolines") was the first structural class of potent and selective dopamine D1 agonists lacking a catechol group. In order to determine the enantioselectivity of the 7-methyl derivative in the adenylate cyclase assay, its 5,5a-dihydro precursor was resolved a...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00060a004
更新日期:1993-04-16 00:00:00
abstract::In order to define the role of the cholestane moiety in the anti-HIV agent cosalane, a series of cosalane analogs was synthesized in which the cholestane ring system was replaced by normal alkenyl and phosphodiester substituents having varied chain lengths and lipophilicities. The compounds containing simple alkenyl s...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm950666h
更新日期:1996-01-19 00:00:00
abstract::Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.6b00600
更新日期:2016-06-23 00:00:00
abstract::Dimeric DNA cross-linking compounds have emerged as important new antitumor agents. We report the synthesis and biochemical evaluation of a select set of dimeric mitomycins in which the two mitomycin units are tethered at either the mitomycin C(7) amino or the aziridine N(1a) positions. Significantly, mitomycin C (1) ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm010090y
更新日期:2001-10-11 00:00:00
abstract::Cationic amphiphiles derived from aminoglycosides (AGs) have been shown to exhibit enhanced antimicrobial activity. Through the attachment of hydrophobic residues such as linear alkyl chains on the AG backbone, interesting antibacterial and antifungal agents with a novel mechanism of action have been developed. Herein...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b01375
更新日期:2015-12-10 00:00:00
abstract::Metoclopramide (1) is a gastric motility stimulant and a weak dopamine and 5-HT3 receptor antagonist. Conformational restriction of the (diethylamino)ethyl side chain of 1 in the form of the azabicyclic tropane gave 3, a very potent gastric motility stimulant and 5-HT3 receptor antagonist but devoid of significant dop...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00169a016
更新日期:1990-07-01 00:00:00
abstract::A series of 3-hydroxy-substituted analogues (3-7) of the mu selective opioid antagonist cyprodime has been synthesized in order to evaluate the role of a hydroxy group at C-3 concerning mu opioid antagonist selectivity. Compounds 3-7 were tested in bioassays (electrical stimulated mouse vas deferens preparation and my...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00016a010
更新日期:1995-08-04 00:00:00
abstract::The first nonpeptidic, noncovalent inhibitors of the cysteine protease cathepsin S (CatS) are described. Electronic database searching using the program DOCK generated a screening set of potential CatS inhibitors from which two lead structures were identified as promising starting points for a drug discovery effort. L...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0496133
更新日期:2004-09-23 00:00:00
abstract::A novel series of diaminoanthraquinones was discovered initially as protein kinase C inhibitors with IC50s in the 50-100 microM range. They exhibited potent tumor cell growth inhibitory activity in vitro without cross resistance to adriamycin. Further evaluation of two of the most active compounds NSC 639365 (3) and N...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00101a001
更新日期:1992-11-13 00:00:00
abstract::New analogues of flavone-8-acetic acid were synthesized, bearing an alkoxy group in position 3 and different substituents on the benzene ring in position 2 of the flavone nucleus. The compounds were tested for direct cytotoxicity against four human tumor cell lines and for indirect antitumor effects by measuring their...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm030771o
更新日期:2003-08-14 00:00:00
abstract::The development of novel non-nucleoside inhibitors (NNRTIs) with activity against variants of HIV reverse transcriptase (RT) is crucial for overcoming treatment failure. The NNRTIs bind in an allosteric pocket in RT ∼10 Å away from the active site. Earlier analogues of the catechol diether compound series have picomol...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm501908a
更新日期:2015-03-26 00:00:00
abstract::In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D2 receptors, albeit somewha...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm9804533
更新日期:1999-03-11 00:00:00
abstract::A three-dimensional structure of the complex of human renin and the scissile site P4 Pro to P1' Val of angiotensinogen was deduced in order to design potent human renin inhibitors rationally. On the basis of this structure, an orally potent human renin inhibitor (1a) was designed from the angiotensinogen transition st...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00172a005
更新日期:1990-10-01 00:00:00
abstract::The intense intrinsic fluorescence emissions from several clinically relevant camptothecin drugs have been exploited in order to study the structural basis of drug binding to human serum albumin. Both HPLC and time-resolved fluorescence spectroscopic methodologies were employed to characterize the associations of camp...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00027a005
更新日期:1994-01-07 00:00:00
abstract::The discovery of inhibitors of bromodomain and extra terminal domain (BET) has achieved great progress, and at least seven inhibitors have progressed into clinical trials for the treatment of cancer or inflammatory diseases. Here, we describe the identification, optimization, and evaluation of benzo[cd]indol-2(1H)-one...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b01511
更新日期:2016-02-25 00:00:00
abstract::Lipophilicity/bioavailibility of Mn(III) N-alkylpyridylporphyrin-based superoxide dismutase (SOD) mimics has a major impact on their in vivo ability to suppress oxidative stress. Meta isomers are less potent SOD mimics than ortho analogues but are 10-fold more lipophilic and more planar. Enhanced lipophilicity contrib...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm900576g
更新日期:2009-12-10 00:00:00
abstract::In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected a...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm401992e
更新日期:2014-04-24 00:00:00
abstract::Synthetic routes were developed to access a variety of novel 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-one analogs which were evaluated as 5-lipoxygenase (5-LO) inhibitors. The parent structure, 1-phenylperhydro-1,2,4-triazin-3-one (4), was found to be a selective inhibitor of 5-LO in broken cell, intact cell, and human...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm960372b
更新日期:1996-09-27 00:00:00