Abstract：
:Analogues of luliberin containing an alpha-azaamino acid in position 6, 9, or 10 (I--XIV) have been synthesized by the solution method of peptide synthesis. Two nonaza analogues, [D-Phe6]- and [D-Ser(But)6,des-Gly-NH2(10),Pro-ethylamide9]luliberin, were also synthesized for comparison. The ovulation-inducing activity of the compounds was evaluated in androgen-sterilized constant-estrus rats. A combination of D-amino acid replacement in position 6 with an azaglycine residue at position 10 resulted in highly active compounds which were superior to the corresponding nonaza analogues. The most active compoungs, [D-Phe6,Azgly10-a1-, [D-Tyr(Me)6,Azgly10]-, and [D-Ser(But)6,Azgly10]luliberin, were about 100 times as potent as luliberin. N-Methylleucine substitution in position 7 in these compounds resulted in decreased activity; [D-Phe6,MeLeu7,Azgly10]- and [D-Tyr(Me)6,MeLeu7,Azgly10]luliberin were only 50 times as active as luliberin. The presence of either an azaproline residue in position 9, an azaphenylalanine or azaglycine residue in positions 6 and 10, or a tert-butyl ether protecting group on the hydroxyl group of the tyrosine residue in position 5 resulted in compounds with significantly reduced biological activity.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Dutta AS,Furr BJ,Giles MB,Valcaccia Bdoi
10.1021/jm00208a004subject
Has Abstractpub_date
1978-10-01 00:00:00pages
1018-24issue
10eissn
0022-2623issn
1520-4804journal_volume
21pub_type
杂志文章abstract：:Three series of H(4) receptor ligands, derived from indoly-2-yl-(4-methyl-piperazin-1-yl)-methanones, have been synthesized and their structure-activity relationships evaluated for activity at the H(4) receptor in competitive binding and functional assays. In all cases, substitution of small lipophilic groups in the 4...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0502081
更新日期：2005-12-29 00:00:00
abstract：:A series of 4- and 5-[2,3-dihydro-6,7-bis[[(N-alkylcarbamoyl)oxy]methyl]-1H-pyrrol izin-5- yl]-2-halopyridinium iodides were synthesized. The rates of hydrolysis of the alpha-halopyridinium salts to the corresponding pyridones, and the reactivities of the carbamate moieties were studied as a function of pH, buffer com...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00168a021
更新日期：1990-06-01 00:00:00
abstract：:Taking advantage of a proposed hydrophobic region on 5-HT2 receptors previously identified by radioligand-binding studies utilizing various phenylisopropylamine derivatives, we prepared and evaluated several N1 - and/or C7-alkyl-substituted derivatives of alpha-methyltryptamine in order to improve its affinity and sel...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00172a016
更新日期：1990-10-01 00:00:00
abstract：:The present study evaluates the utility of the dihydropyridine in equilibrium pyridinium salt redox system for the specific delivery and sustained release of a model 2',3'-dideoxynucleoside to the brain of mice as the initial effort in a search for agents that may prove effective in reversing the complicating neurolog...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00123a020
更新日期：1989-03-01 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：: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：:This paper describes the synthesis and biological evaluation of a new class of peptidomimetic falcipain-2 inhibitors based on a 1,4-benzodiazepine scaffold combined with various alpha,beta-unsaturated electrophilic functions such as vinyl-ketone, -amide, -ester, and -nitrile. The profile of reactivity of this class of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900047j
更新日期：2009-04-09 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
abstract：:We synthesized 5-substituted pyrrolo[2,3-d]pyrimidine antifolates (compounds 5-10) with one-to-six bridge carbons and a benozyl ring in the side chain as antitumor agents. Compound 8 with a 4-carbon bridge was the most active analogue and potently inhibited proliferation of folate receptor (FR) α-expressing Chinese ha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401328u
更新日期：2013-12-27 00:00:00
abstract：:The variation in amino acid sequence within sets of peptides is described by three principal properties, z1, z2, and z3, per varied amino acid position. These principal properties are derived from a principal components analysis of a matrix of 29 physicochemical variables for the 20 coded (in mRNA) amino acids. The sc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00390a003
更新日期：1987-07-01 00:00:00
abstract：:8-Methoxy-1-oxo-2,3-dihydro-1H-cyclopenta]a]naphthalene (4) was converted to the oxalyl derivative (7) by treatment with diethyl oxalate in the presence of sodium ethoxide. Compound 7 in the form of the sodium salt was alkylated with ethyl bromoacetate in DMF to 2-(carbethoxymethyl)-8-methoxy-1-oxo-2,3-dihydro-1H-cycl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00179a008
更新日期：1980-05-01 00:00:00
abstract：:A novel series of 16-substituted-4-azasteroids has been identified as potential tissue-selective androgen receptor modulators. These ligands display potent hAR binding and agonist activity, low virilizing potential, and good pharmacokinetic profiles in dogs. On the basis of its in vitro profile, 21 was evaluated in th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900880r
更新日期：2009-08-13 00:00:00
abstract：:Novel dicationic triazoles 1-60 were synthesized by the Pinner method from the corresponding dinitriles, prepared via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The type and the placement of cationic moieties as well as the nature of aromatic substituents influenced in vitro antiprotozoal activities o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901178d
更新日期：2010-01-14 00:00:00
abstract：:A number of 7-benzoylbenzofuran-5-ylacetic acids and 7-benzoylbenzothiophene-5-ylacetic acids were synthesized. The compounds were generally only 1/2 to 3 times as potent as phenylbutazone in the rat paw edema antiinflammatory assay. However, they show greater activity as analgetic agents. The most active compound is ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00161a030
更新日期：1986-11-01 00:00:00
abstract：:Reports of a high-affinity ligand for E-selectin, sialyl di-Lewis(x) (sLe(x)Le(x), 1), motivated us to incorporate modifications to previously reported biphenyl-based inhibitors that would provide additional interactions with the protein. These compounds were assayed for the ability to inhibit the binding of sialyl Le...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9704917
更新日期：1998-03-26 00:00:00
abstract：:A series of alpha,alpha-diaryl-1-piperidinebutanols was evaluated for antiarrhythmic activity in the coronary ligated dog model. Structure-activity relationship studies indicated that the 2,6-dimethylpiperidine group yielded compounds with the best antiarrhythmic profiles in this series. The length of the methylene ch...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00105a003
更新日期：1991-01-01 00:00:00
abstract：:4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00173a017
更新日期：1990-11-01 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：:A series of novel β-carboline-based N-heterocyclic carbenes was prepared via Mannich reaction between methyl 1-(dimethoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate, formaldehyde, and primary amines. All compounds were evaluated for their antiproliferative activity using human breast cancer and lung cancer cell lines...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00016
更新日期：2015-04-23 00:00:00
abstract：:As a continuation of our efforts to develop innovative ligands for D(3), 5-HT(1A), and 5-HT(2A) receptors with low propensity to block hERG channels, we propose a series bishetero(homo)arylpiperazines 5a-m as novel and potent multifunctional ligands characterized by low occupancy at D(2) and 5-HT(2C) receptors. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100294b
更新日期：2010-06-24 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：:Tuberculosis (TB) accounted for 1.5 million deaths in 2014, and new classes of anti-TB drugs are required. We report a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic mycobacteria. These compounds inhibit intracellular growth of Mycobacterium tubercu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00432
更新日期：2016-06-23 00:00:00
abstract：:The present study describes a novel in vitro platform for physicochemical profiling of compounds, based on their impact on the air/water interfacial tension. Interfacial partitioning coefficient, cross-sectional area, and critical micelle concentration were derived from the Gibbs adsorption isotherms recorded for 76 s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0309001
更新日期：2004-03-25 00:00:00
abstract：:A series of 6,7-dichloro-1,4-dihydro-(1H, 4H)-quinoxaline-2,3-diones (1-17) were prepared in which the 5-position substituent was a heterocyclylmethyl or 1-(heterocyclyl)-1-propyl group. Structure-activity relationships were evaluated where binding affinity for the glycine site of the N-methyl-D-aspartate (NMDA) recep...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm001124p
更新日期：2001-06-07 00:00:00
abstract：:A number of cytostatic compounds (2-4, 7, and 8), which can be described as "diaryl", inhibit tubulin polymerization, cause cells to accumulate in mitotic arrest, and competitively inhibit the binding of colchicine to tubulin. They differ, however, in the separation of the two aryl moieties. To attempt to understand t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00084a011
更新日期：1992-03-20 00:00:00
abstract：:A series of 2-aminotetralins, substituted with a methoxy or a hydroxy group on the 5- or 7-position, and with varying N-alkyl or N-arylalkyl substituents, were prepared and evaluated in binding assays for human dopamine (DA) D2, D3, and D4 receptors. Some members of this series were prepared in former studies, but wer...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960345l
更新日期：1996-10-11 00:00:00
abstract：:The selective inhibition of the lipid signaling enzyme PI3Kγ constitutes an opportunity to mediate immunosuppression and inflammation within the tumor microenvironment but is difficult to achieve due to the high sequence homology across the class I PI3K isoforms. Here, we describe the design of a novel series of poten...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01203
更新日期：2020-10-08 00:00:00
abstract：:Proton magnetic spectra have been recorded for muscarine and two biologically active cyclopentane analogues. In order to observe homonuclear intramolecular nuclear Overhauser effects, the -N+(CH3)3 signal was irradiated and increases in integrated intensities for other key signals in the molecule were observed. The re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00205a028
更新日期：1978-07-01 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：:2,5-Dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4' - yl]methyl]-3H-1,2,4-triazol-3-one, SC-51316, was synthesized as a potent and orally active angiotensin II (AII) receptor antagonist with a long duration of action. To explore the lipophilic pocket in the AII receptor interacting with the substituent ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00067a015
更新日期：1993-07-23 00:00:00
