Abstract:
:Renin inhibitors 2-4 with the D-Lys renin inhibitory peptide (RIP) sequence, but containing Leu psi[CH2O]Ala (2), Leu psi[CH2O]Val (3), and Leu psi[CH2O]Leu (4) at the P1-P1' site, were of a comparable potency to RIP. N-Terminal Boc-protected inhibitors containing Pro psi[CH2O]Phe in positions P4-P3 were potent inhibitors of renin, with Boc-Phe-Pro psi[CH2O]Phe-His-Leu psi[CH(OH)CH2]Val-Ile-(2-aminomethyl) pyridine (17) having an IC50 of 1.6 X 10(-9) M.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
TenBrink RE,Pals DT,Harris DW,Johnson GAdoi
10.1021/jm00398a029subject
Has Abstractpub_date
1988-03-01 00:00:00pages
671-7issue
3eissn
0022-2623issn
1520-4804journal_volume
31pub_type
杂志文章abstract::We have recently reported the phosphodiesterase 10A (PDE10A) inhibitor 2-[4-[1-(2-[(18)F]fluoroethyl)-4-pyridin-4-yl-1H-pyrazol-3-yl]-phenoxymethyl]-quinoline ([(18)F]1a) as a promising candidate for in vivo imaging using positron emission tomography (PET). We now describe the synthesis and biological evaluation of a ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm200536d
更新日期:2011-08-25 00:00:00
abstract::Several optically active N-(indol-3-ylglyoxylyl)amino acid derivatives were synthesized and tested for [3H]flunitrazepam displacing activity in bovine brain membranes. IC50 values were measured and revealed that the D form of the amino acid moiety of the compounds was more potent than both the L form and racemic form,...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00132a004
更新日期:1989-12-01 00:00:00
abstract::The tremendous therapeutic potential of voltage-gated sodium channels (Na(v)s) has been the subject of many studies in the past and is of intense interest today. Na(v)1.7 channels in particular have received much attention recently because of strong genetic validation of their involvement in nociception. Here we summa...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1021/jm501981g
更新日期:2015-09-24 00:00:00
abstract::A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinitie...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b01293
更新日期:2016-03-10 00:00:00
abstract::A systematic exploration of bioisosteric replacements for furan and thiophene cores in a series of potent A2BAR antagonists has been carried out using the nitrogen-walk approach. A collection of 42 novel alkyl 4-substituted-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates, which contain 18 differe...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c00564
更新日期:2020-07-23 00:00:00
abstract::(±)-MRJF22 [(±)-2], a novel prodrug of haloperidol metabolite II (sigma-1 receptor antagonist/sigma-2 receptor agonist ligand) obtained by conjugation to valproic acid (histone deacetylase inhibitor) via an ester bond, exhibits antiangiogenic activity, being able to reduce human retinal endothelial cell (HREC) viabili...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.6b01039
更新日期:2016-11-10 00:00:00
abstract::The discovery and structure-activity relationship of first-generation small-molecule malonyl-CoA decarboxylase (MCD; CoA = coenzyme A) inhibitors are reported. We demonstrated that MCD inhibitors increased malonyl-CoA concentration in the isolated working rat hearts. Malonyl-CoA is a potent, endogenous, and allosteric...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm050109n
更新日期:2006-03-09 00:00:00
abstract::New 2-[2'-(dimethylamino)ethyl]-3H-dibenz[de,h]isoquinoline-1,3-diones with substituents at the 6- and 7-positions were prepared. Nucleophilic aromatic displacement was a key reaction in the syntheses. Ten of the new compounds were more potent than the unsubstituted compound, azonafide, in a panel of tumor cells inclu...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm950742g
更新日期:1996-04-12 00:00:00
abstract::Select chemokine receptors act as coreceptors for HIV-1 entry into human cells and represent targets for antiviral therapy. In this report we describe a distamycin analogue, 2,2'-[4, 4'-[[aminocarbonyl]amino]bis[N,4'-di[pryrrole-2-carboxamide- 1, 1'-dimethyl]]-6,8-naphthalenedisulfonic acid]hexasodium salt (NSC 651016...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm9801253
更新日期:1998-06-18 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::The synthesis of 15 compounds related either to the benz[c]acridine or to the benz[a]acridine series is reported. Spectral data, i.e., NMR and EI fragmentation, are given. These compounds were tested for carcinogenic activity in mice of the XVIInc/Z strain by subcutaneous injection. Only three weak carcinogens were de...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00356a038
更新日期:1983-02-01 00:00:00
abstract::With the emergence of oseltamivir-resistant influenza viruses and in view of a highly pathogenic flu pandemic, it is important to develop new anti-influenza agents. Here, the development of neuraminidase (NA) inhibitors that were designed to overcome resistance mechanisms along with unfavorable pharmacokinetic (PK) pr...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm401492x
更新日期:2014-02-13 00:00:00
abstract::Increased usage of daptomycin to treat infections caused by Gram-positive bacterial pathogens has resulted in emergence of resistant mutants. In a search for more effective daptomycin analogues through medicinal chemistry studies, we found that methylation at the nonproteinogenic amino acid kynurenine in daptomycin co...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.9b01957
更新日期:2020-03-26 00:00:00
abstract::A conceptionally new 3D molecular descriptor type and methodology are deduced by simple statistical thermodynamic reasoning, based on the free energy change encountered during a transformation of a conformational ensemble of the ligand to an active conformation. The performance of the descriptor was first tested on 37...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm049157i
更新日期:2005-05-05 00:00:00
abstract::A series of substituted phenyl analogues of 5-[[4-(4,5-dihydro-2-oxazolyl) phenoxy]alkyl]-3-methylisoxazoles has been synthesized and evaluated in vitro against several human rhinovirus (HRV) serotypes. Substituents in the 2-position greatly enhanced activity when compared to the unsubstituted compound. Many of these ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00385a021
更新日期:1987-02-01 00:00:00
abstract::A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0109964
更新日期:2002-01-31 00:00:00
abstract::Ergosterol, the predominant sterol of fungi, is postulated to have many cellular functions which include a bulk membrane role and a regulatory role. Studies with sterol auxotrophs show that, even in the presence of sterols which can fulfill the bulk membrane requirements, a small concentration of ergosterol is absolut...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm9605851
更新日期:1996-12-20 00:00:00
abstract::3-O-tert-Butylmorphine (5) was prepared from 6-O-acetylmorphine (3) via alkylation with N,N-dimethylformamide di-tert-butyl acetal, followed by hydrolytic removal of the 3-(dimethylamino)-2-propenoate group. The same process was used to prepare the tert-butyl ether of levorphanol (6), (-)-3-tert-butoxy-N-methylmorphin...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00352a037
更新日期:1982-10-01 00:00:00
abstract::Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute the peptide pharmacophore i...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1021/acs.jmedchem.6b01029
更新日期:2016-12-22 00:00:00
abstract::A set of 30 substituted 5,5'-diphenyl-2-thioxoimidazolidin-4-one (thiohydantoins) derivatives was synthesized, and their affinity for the human CB(1) cannabinoid receptor has been evaluated. These compounds are derived from the previously described cannabinoid ligands 5,5'-diphenylimidazolidine-2,4-dione (hydantoins)....
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm049263k
更新日期:2005-04-07 00:00:00
abstract::A 2A adenosine receptor antagonists usually have bi- or tricyclic N aromatic systems with varying substitution patterns to achieve desired receptor affinity and selectivity. Using a pharmacophore model designed by overlap of nonxanthine type of previously known A 2A antagonists, we synthesized a new class of compounds...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm701594y
更新日期:2008-08-14 00:00:00
abstract::Glycogen synthase kinase 3beta (GSK-3beta) inhibition is expected to be a promising therapeutic approach for treating Alzheimer's disease. Previously we reported a series of 1,3,4-oxadiazole derivatives as potent and highly selective GSK-3beta inhibitors, however, the representative compounds 1a,b showed poor pharmaco...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm900647e
更新日期:2009-10-22 00:00:00
abstract::Two compounds, analogues of cephalexin with 2- and 4-pyridone groups at C-3, were prepared. Biological evaluation found the compounds to exhibit activity against Gram-positive and Gram-negative organisms in vitro and in vivo. The compounds were only active in vivo on subcutaneous administration. ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00197a026
更新日期:1979-11-01 00:00:00
abstract::This series of reports describe the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. The compounds reported in this paper contain an additional phenyl ring, which has significantly improved the receptor affinity. The effect of...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00166a017
更新日期:1990-04-01 00:00:00
abstract::Targeted imaging requires contrast agents that remain in the vasculature for extended periods of time. A new contrast agent is described in which gadolinium is encapsulated within an extremely stable carbon sphere, thus allowing for safe extended residence. Water solubility and small particle size is achieved with nov...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm800521j
更新日期:2008-07-10 00:00:00
abstract::The preparation of a series of 2-(1H-imidazol-1-ylmethyl)-substituted carboxylic acids of benzo[b]furan, benzo-[b]thiophene, indole, and naphthalene is described. All compounds showed a similar level of activity as TxA2 synthetase inhibitors in vitro, having IC50 values between 1 and 7 X 10(-8) M. In the cases examine...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00159a013
更新日期:1986-09-01 00:00:00
abstract::The preparation of a series of indole N-acyl and N-carbamic esters of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazolin-4-one (1) is reported. These derivatives were synthesized as potential water-soluble precursors of the antiviral thiazolinone 1, for evaluation by intranasal administration against i...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00188a013
更新日期:1979-02-01 00:00:00
abstract::A new class of substituted 1-phenyl-3-piperazinyl-2-propanones with antimuscarinic activity is reported. As part of a structure-activity relationship study of this class, various structural modifications, particularly ones involving substitution of position 1 and the terminal piperazine nitrogen, were investigated. Th...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00057a010
更新日期:1993-03-05 00:00:00
abstract::The synthesis and testing of potential multisubstrate inhibitors of tyrosine-specific protein kinases are described. One of the substrates, ATP, was mimicked by the known kinase inhibitor 5'-[4-(fluorosulfonyl)benzoyl]adenosine, which was covalently linked via the sulfonyl moiety to tyrosine mimics. The resulting mult...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00117a015
更新日期:1988-09-01 00:00:00
abstract::Computational ADME (absorption, distribution, metabolism, and excretion) models may be used early in the drug discovery process in order to flag drug candidates with potentially problematic ADME profiles. We report the development, validation, and application of quantitative structure-property relationship (QSPR) mode...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm020491t
更新日期:2003-07-03 00:00:00