Abstract：
:A series of pyridinyltetrahydropyridine derivatives was synthesized and evaluated as adrenoceptor and tetrabenazine antagonists. 4-(3-Fluoro-2-pyridinyl)-1,2,5,6-tetrahydropyridine proved to be the most potent and selective alpha 2-adrenoceptor antagonist of the series as measured in vitro by displacement of [3H]clonidine and [3H]prazosin from membrane binding sites of calf cerebral cortex and by antagonism of the effects of clonidine and methoxamine in the rat isolated, field-stimulated vas deferens. In addition, this compound, and the corresponding desfluoro derivative, blocked tetrabenazine-induced ptosis in the mouse.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Saari WS,Halczenko W,Huff JR,Guare JP Jr,Hunt CA,Randall WC,Lotti VJ,Yarbrough GGdoi
10.1021/jm00375a017subject
Has Abstractpub_date
1984-09-01 00:00:00pages
1182-5issue
9eissn
0022-2623issn
1520-4804journal_volume
27pub_type
杂志文章abstract：:Adenosine (ADO) is an endogenous homeostatic inhibitory neuromodulator that reduces cellular excitability at sites of tissue injury and inflammation. Inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO, selectively increases ADO concentrations at sites of tissue trauma and enhances the analgesic ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000314x
更新日期：2001-06-21 00:00:00
abstract：:It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3 beta-phenyltropane-2 beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [3H]-3 beta-(4-fluorophenyl)tro...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00059a010
更新日期：1993-04-02 00:00:00
abstract：:Two-bivalent ligands (P-X-P) containing the beta-naltrexamine pharmacophore (P) and a connecting oligoethylene glycol spanner (X) were synthesized and evaluated for narcotic antagonistic activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD). The bivalent ligand 2 whose spanner contains three ethylene uni...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00349a016
更新日期：1982-07-01 00:00:00
abstract：:1-Methyl-5-(3-azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)uracil (C-AZT), a C-nucleoside isostere of the potent anti-AIDS nucleoside 3'-azido-3'-deoxythymidine (AZT), was synthesized. 1-Methyl-2'-deoxy-5'-O-tritylpseudouridine (2a) was oxidized with CrO3/pyridine/Ac2O complex to 1-methyl-5-(5-O-trityl-beta-D-glyce...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00169a030
更新日期：1990-07-01 00:00:00
abstract：:The synthesis of a new class of multisubstrate adduct inhibitors of polyamine biosynthesis has been investigated. The first target compound, designed to inhibit spermidine synthase, was obtained and proved to be a very potent inhibitor of that enzyme. Two synthetic routes to effect the coupling of the polyamine spermi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00014a023
更新日期：1995-07-07 00:00:00
abstract：:Whereas the 2-propyl- and 2-butyl-5,6-(methylenedioxy)indene calcium antagonists reversed the spasmogenic action of several agonists including PGF2alpha and acetylcholine at 5 X 10(-5) to 10(-4) M on the rat ileum, the corresponding 5,6-dimethoxy analogues exhibited spasmogenic activity at higher concentration (10(-4)...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00210a028
更新日期：1978-12-01 00:00:00
abstract：:Attempts to develop new (aryloxy)acetic acids with a better profile of diuretic and uricosuric activities as well as with fewer side effects have produced a series of compounds in which the ring system has been varied. Diuretic screening of these analogues in rats indicated that the great difference in the activity be...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00113a006
更新日期：1991-09-01 00:00:00
abstract：:A novel series of C(3)-substituted piperdinylindoles were developed as nociceptin opioid receptor (NOP) partial agonists to explore a pharmacological hypothesis that NOP partial agonists would afford a dual pharmacological action of attenuating Parkinson's disease (PD) motor symptoms and development of levodopa-induce...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b02134
更新日期：2020-03-12 00:00:00
abstract：:Following erythrocyte invasion, malaria parasites export a catalogue of remodeling proteins into the infected cell that enable parasite development in the human host. Export is dependent on the activity of the aspartyl protease, plasmepsin V (PMV), which cleaves proteins within the Plasmodium export element (PEXEL; Rx...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500797g
更新日期：2014-09-25 00:00:00
abstract：:The antimicrobial and cytotoxic properties of a series of 9,10-dihydrophenanthrenes structurally related to juncusol (1a), a postulated phytoalexin with confirmed cytotoxic properties, are detailed. Two simple 9,10-dihydrophenanthrenes, 2,7-dihydroxy-3,8-dimethyl-9,10-dihydrophenanthrene (2h, desvinyljuncusol) and 2-h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00148a031
更新日期：1985-10-01 00:00:00
abstract：:Novel lavendamycins including two water soluble derivatives were synthesized via short and efficient methods. Pictet-Spengler condensation of 7-N-acylamino-2-formylquinoline-5,8-diones with tryptophans produced lavendamycin esters or amides 11-17. Lavendamycins 18-21 were obtained, respectively, by further transformat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304414
更新日期：2003-12-18 00:00:00
abstract：:Malaria is still a leading cause of mortality among children in the developing world, and despite the immense progress made in reducing the global burden, further efforts are needed if eradication is to be achieved. In this context, targeting transmission is widely recognized as a necessary intervention toward that go...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00898
更新日期：2020-03-12 00:00:00
abstract：:A series of biphenyl analogues of the new tuberculosis drug PA-824 was prepared, primarily by coupling the known (6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-ol with iodobenzyl halides, followed by Suzuki coupling of these iodides with appropriate arylboronic acids or by assembly of the complete biaryl side...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901207n
更新日期：2010-01-14 00:00:00
abstract：:Protein disulfide isomerase (PDI) is responsible for nascent protein folding in the endoplasmic reticulum (ER) and is critical for glioblastoma survival. To improve the potency of lead PDI inhibitor BAP2 (( E)-3-(3-(4-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzonitrile), we designed and synthesized 67 analogues. We determ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01951
更新日期：2019-04-11 00:00:00
abstract：:The modification of 3'-((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1H-inden-5-yloxy)methyl)biphenyl-4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing the cyclopentyl moiety led to the development of new mGluR2 positive allosteric modulators (PAMs) with optimized potency and s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1012165
更新日期：2011-01-13 00:00:00
abstract：:(+/-)-7-Aminosulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline (7) is one of the most potent and selective inhibitors of phenylethanolamine N-methyltransferase (PNMT) reported to date, but a blood-brain barrier (BBB) model indicates that it cannot penetrate the BBB. To increase the lipophilicity of 7 by addition ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0400653
更新日期：2004-08-26 00:00:00
abstract：:Influenza virus (IFV) causes periodic global influenza pandemics, resulting in substantial socioeconomic loss and burden on medical facilities. Yearly variation in the effectiveness of vaccines, slow responsiveness to vaccination in cases of pandemic IFV, and emerging resistance to available drugs highlight the need t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.6b01227
更新日期：2017-05-11 00:00:00
abstract：:The literature reports on cationic and anionic phthalocyanines (Pcs) for photodynamic therapy suggest systematically significant differences in activity. In this work, ten different zinc(II) Pcs with carboxylate functions or quaternary nitrogens (hydrophilic anionic, hydrophilic cationic, amphiphilic anionic, and amph...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00481
更新日期：2020-07-23 00:00:00
abstract：:Polynuclear Pt(II) complexes are a novel class of promising anticancer agents with potential clinical significance. A series of pyrazine (pz) bridged dinuclear Pt(II) complexes with general formulas {[Pt(L)Cl]2(μ-pz)}(2+) (L, ethylenediamine, en; (±)-1,2-propylenediamine, 1,2-pn; isobutylenediamine, ibn; trans-(±)-1,2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5017686
更新日期：2015-02-12 00:00:00
abstract：:The pro-inflammatory mediator macrophage migration inhibitory factor (MIF) is produced by immune and endocrine cells and inhibits the antiinflammatory activities of glucocorticoids. MIF also catalyzes the tautomerization of the non-naturally occurring D-isomer of dopachrome, phenylpyruvate, and certain catecholamines,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010534q
更新日期：2002-06-06 00:00:00
abstract：:Two novel analogues, N-[2-amino-4-ethyl[(pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid (2) and N-[2-amino-4-ethyl-6-methyl[(pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid (4), were designed and synthesized as potent dual inhibitors of thymidylate synthase (TS) and dihydrofolate reductase (DH...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0203534
更新日期：2003-02-13 00:00:00
abstract：:We report the syntheses of first-generation derivatives of isothiazolopyridones and their in vitro evaluation as antibacterial agents. These compounds, containing a novel heterocyclic nucleus composed of an isothiazolone fused to a quinolizin-4-one (at C-2 and C-3 of the quinolizin-4-one), were prepared using a sequen...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm051066d
更新日期：2006-01-12 00:00:00
abstract：:Anthraquinone derivatives related to the moderately potent, nonselective P2Y(12) receptor antagonist reactive blue 2 (6) have been synthesized and optimized with respect to P2Y(12) receptor affinity. A radioligand binding assay utilizing human blood platelet membranes and the P2Y(12) receptor-selective antagonist radi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9003297
更新日期：2009-06-25 00:00:00
abstract：:A structure-based virtual screening (SBVS) was conducted on a ligand-supported homology model of the human histamine H4 receptor (hH4R). More than 8.7 million 3D structures derived from different vendor databases were investigated by docking to the hH4R binding site using FlexX. A total of 255 selected compounds were ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm7014777
更新日期：2008-06-12 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：:Family 18 chitinases play an essential role in a range of pathogens and pests. Several inhibitors are known, including the potent inhibitors argadin and allosamidin, and the structures of these in complex with chitinases have been elucidated. Recent structural analysis has revealed that CI-4 [cyclo-(L-Arg-D-Pro)] inhi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049940a
更新日期：2004-11-04 00:00:00
abstract：:A series of 3-(1,2-disubstituted-1H-benzimidazol-5-yl)-N-hydroxyacrylamides (1) were designed and synthesized as HDAC inhibitors. Extensive SARs have been established for in vitro potency (HDAC1 enzyme and COLO 205 cellular IC(50)), liver microsomal stability (t(1/2)), cytochrome P450 inhibitory (3A4 IC(50)), and clog...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2003552
更新日期：2011-07-14 00:00:00
abstract：:2,9beta-Dimethyl-2'-hydroxy-6,7-benzomorphan (18) has been synthesized from m-methoxyphenylacetone (6a) or m-methoxyphenylacetonitrile (1) via bromo-alpha-tetralone (10). Isomeric bromo-alpha-tetralone 9, instead of undergoing cyclization to a 6,7-benzomorphan, gave aromatization product 12. The structures and stereoc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00242a005
更新日期：1975-08-01 00:00:00
abstract：:The effect of aromatic nitro compounds on the oxidative metabolism of representative type I (hexobarbital and aminopyrene) and type II (aniline and zoxazolamine) substrates by cytochrome P-450 dependent liver enzymes was studied. Nitro compounds (nitrobenzene, p-nitrobenzoate, 2-nitrofluorene, and 2-nitronaphthalene) ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00223a034
更新日期：1976-01-01 00:00:00
abstract：:The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues of L-chicoric acid, a potent inhibitor of HIV integrase, were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010359d
更新日期：2002-08-15 00:00:00
