Abstract：
:Twenty-two structural derivatives of clonidine [2-(2,6-dichlorophenylimino)imidazolidine] have been synthesized and their main physicochemical parameters (log P, deltaRM, pKa) determined. Quantitative correlations between the peripheral alpha-mimetic action (pithed rats) and physicochemical parameters pointed out the critical role of the steric effect in the ortho positions. On the other hand, attempted quantitative correlations between physicochemical parameters and central hypotensive activity were unsuccessful. These results are discussed in the light of the postulated mechanism of action of clonidine.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Rouot B,Leclerc G,Wermuth CGdoi
10.1021/jm00230a014subject
Has Abstractpub_date
1976-08-01 00:00:00pages
1049-54issue
8eissn
0022-2623issn
1520-4804journal_volume
19pub_type
杂志文章abstract：:A series of new 9-phenanthrene amino alcohols has been prepared in which each compound bears from one to five halogen or halogen-containing moieties. A number of these compounds are extremely active against Plasmodium berghei in the mouse. Some structural requirements for optimal efficacy are considered. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00244a012
更新日期：1975-10-01 00:00:00
abstract：:Analogues of cyclic ADP-ribose (cADPR) incorporating a methylenebisphosphonate linkage in the place of the pyrophosphate have been synthesized from nicotinamide adenine dinucleotide analogues enzymatically using Aplysia californica ADP-ribosyl cyclase. Methylenebisphosphonate cyclic ADP-ribose (cADPR[CH(2)]) and methy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049469l
更新日期：2005-06-16 00:00:00
abstract：:Rotigaptide (3) is an antiarrhythmic peptide that improves cardiac conduction by modifying gap-junction communication. Small molecule gap-junction modifiers with improved physical properties were identified from a Zealand Pharma peptide library using pharmaceutical profiling, established SAR around 3, and a putative p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801558d
更新日期：2009-02-26 00:00:00
abstract：:Previously reported 2-(hydroxymethyl)indoloquinones, prepared as their acetates or carbamates, were less active than 2-methyl analogues in bacterial cultures and they had no activity in mice, despite functionality appropriate for DNA cross-linking. On the basis of the hypothesis that these compounds might have been to...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00128a030
更新日期：1989-08-01 00:00:00
abstract：:Ten analogues of the highly mu-receptor selective cyclic opioid peptide H-Tyr-D-Orn-Phe-Asp-NH2 (1) were synthesized by the solid phase method and were characterized in vitro in mu- and delta-receptor representative binding assays and bioassays. These cyclic analogues are structurally related to the linear opioid pept...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00394a027
更新日期：1987-11-01 00:00:00
abstract：:The interaction between leukocyte function-associated antigen-1 (LFA-1) and intracellular adhesion molecule-1 (ICAM-1) has been implicated in inflammatory and immune diseases. Recently, a novel series of p-arylthio cinnamides has been described as potent antagonists of the LFA-1/ICAM-1 interaction. These compounds wer...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000503f
更新日期：2001-04-12 00:00:00
abstract：:Introduction of a nitrogen atom into the cyclohexane ring of 2-(4-phenylpiperidinyl)cyclohexanol (vesamicol, AH5183) yielded two positional isomers, 5-azavesamicol (5, prezamicol) and 4-azavesamicol (6, trozamicol). As inhibitors of vesicular acetylcholine transport, 5 and 6 were found to be 147 and 85 times less pote...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00060a005
更新日期：1993-04-16 00:00:00
abstract：:The intracellular delivery of nucleic acid molecules is a complex process involving several distinct steps; among these the endosomal escape appeared to be of particular importance for an efficient protein production (or inhibition) into host cells. In the present study, a new series of ionizable vectors, derived from...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01679
更新日期：2016-04-14 00:00:00
abstract：:2,4-Diaminoquinazoline antifolates with a lipophilic side chain at the 5-position, and in one case with a classical (p-aminobenzoyl)-L-glutamate side chain, were synthesized as potentially selective inhibitors of a site-directed mutant of human dihydrofolate reductase (DHFR) containing phenylalanine instead of leucine...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00005a002
更新日期：1995-03-03 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：:FK506-binding proteins (FKBPs) are evolutionarily conserved proteins that display peptidyl-prolyl isomerase activities and act as coreceptors for immunosuppressants. Microbial macrophage-infectivity-potentiator (Mip)-type FKBPs can enhance infectivity. However, developing druglike ligands for FKBPs or Mips has proven ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00137
更新日期：2018-04-26 00:00:00
abstract：:Three types of brassinosteroid analogues with perfluoroalkylated side chains were synthesized by using alkene cross-metathesis of a brassinosteroid derivative bearing a terminal alkene moiety with different (perfluoroalkyl)propenes. The presence of the double bonds in the cross-metathesis products allowed a facile one...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900495f
更新日期：2009-09-24 00:00:00
abstract：:The S-adenosylmethionine (AdoMet) analogue S-(5'-deoxy-5'-adenosyl)-1-aminoxy-4-(methylsulfonio)-2-cycl opentene (AdoMao) was synthesized in two of its four possible diastereomeric forms using a facile chemoenzymatic route. The trans-1R,4R- and trans-1S,4S-diastereomers of AdoMao, as well as the corresponding diastere...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00010a021
更新日期：1995-05-12 00:00:00
abstract：:Analogues of 9-oxo-9H-xanthene-4-acetic acid (XAA) bearing small, lipophilic 5-substituents are among the most dose-potent compounds yet reported with the capability of causing hemorrhagic necrosis of implanted colon 38 tumors in mice. To further extend structure-activity relationships among this class of compound, a ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00105a034
更新日期：1991-01-01 00:00:00
abstract：:Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of he...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500531z
更新日期：2014-06-26 00:00:00
abstract：:Several candidate retinoid antagonists were designed on the basis of the ligand superfamily concept and synthesized. Retinoidal activities of these benzimidazole and benzodiazepine derivatives were examined by assay of differentiation-inducing activity on human promyelocytic leukemia cell line HL-60. The parent benzim...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00036a017
更新日期：1994-05-13 00:00:00
abstract：:Due to its function in the rate limiting initial step of the renin-angiotensin system, renin is a particularly promising target for drugs designed to control hypertension, a growing risk to health worldwide. Despite vast efforts over more than two decades, no orally efficacious renin inhibitor had reached the market. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070316i
更新日期：2007-10-04 00:00:00
abstract：:The enantiomers of two isosteric phosphonate analogs of the ether-linked antitumor agent 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OMe) were synthesized and evaluated for their cytotoxicity against various mouse leukemic cell lines in vitro and in vivo. The key step in the synthesis of the alkyloxy a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00029a016
更新日期：1994-02-04 00:00:00
abstract：:A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones were synthesized and evaluated for anticonvulsant activity in DBA/2 mice against sound-induced seizures and in rats against maximal electroshock-induced seizures. Most of the derivatives showed an anticonvulsant effect better than that of valproate, ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00121a019
更新日期：1989-01-01 00:00:00
abstract：:There is growing interest in using tumor associated antigens presented by class I major histocompatibility complex (MHC-I) proteins as cancer vaccines. As native peptides are poorly stable in biological fluids, researchers have sought to engineer synthetic peptidomimetics with greater biostability. Here, we demonstrat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100683p
更新日期：2010-10-14 00:00:00
abstract：:Analogues of 9-(2-fluorobenzyl)-6-(methylamino)-9H-purine (1) containing isosteric replacements of the imidazole ring atoms were synthesized and tested for anticonvulsant activity. The pyrrolo[2,3-d]-, pyrazolo[3,4-d]-, and triazolo[4,5-d]pyrimidines were less active than 1 against maximal electroshock-induced seizure...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00019a019
更新日期：1995-09-15 00:00:00
abstract：:A total of 53 N-benzoylated phenoxazines and phenothiazines, including their S-oxidized analogues, were synthesized and evaluated for antiproliferative activity, interaction with tubulin, and cell cycle effects. Potent inhibitors of multiple cancer cell lines emerged with the 10-(4-methoxybenzoyl)-10H-phenoxazine-3-ca...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200436t
更新日期：2011-06-23 00:00:00
abstract：:Structure-activity relationship studies of substituted arylsulfoanilides as antiproliferatives, which are mediated by the partial depletion of intracellular Ca(2+) stores, resulted in the identification of compounds with micromolar activity against lung cancer cells in a growth inhibition assay. Incorporating the subs...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0496234
更新日期：2004-10-07 00:00:00
abstract：:Di-tert-butyl (E)-4,4'-stilbenedicarboxylate and tert-butyl 4-vinylbenzoate were copolymerized with maleic anhydride and tert-butyl 4-maleimidobenzoate, individually and respectively. After conversion into polyanions, these four copolymers exhibited activity against four HIV-1 strains: IIIb, BaL, JR-CSF, and 92UG037. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401913w
更新日期：2014-08-14 00:00:00
abstract：:A novel series of optically active 2,6-disubstituted alkylphenols with improved anesthetic profiles compared to widely used propofol were synthesized. The incorporation of the cyclopropyl group not only increased the steric effect but also introduced stereoselective effects over their anesthetic properties. Compounds ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00254
更新日期：2017-05-11 00:00:00
abstract：:The linear interaction energy method with continuum electrostatics (LIECE) is evaluated in depth on five kinases. The two multiplicative coefficients for the van der Waals energy and electrostatic free energy are shown to be transferable among different kinases. Moreover, good enrichment factors are obtained for a lib...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070654j
更新日期：2008-03-13 00:00:00
abstract：:The binding structures of 11 human oxidosqualene cyclase inhibitors designed as cholesterol-lowering agents were determined for the squalene-hopene cyclase from Alicyclobacillus acidocaldarius, which is the only structurally known homologue of the human enzyme. The complexes were produced by cocrystallization, and the...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0211218
更新日期：2003-05-22 00:00:00
abstract：:We previously reported the discovery of 4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1'-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4'-methyl-1,4'-bipiperidine N-oxide 1 (SCH 351125) as an orally bioavailable human CCR5 antagonist for the treatment of HIV-1 infection. Herein, we describe in detail the discovery of 1 from our i...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0200815
更新日期：2002-07-04 00:00:00
abstract：:H(3) receptor antagonists based on a 2-aminoethylbenzofuran skeleton have been discovered, which are potent in vitro at human and rat H(3) receptors, with K(i) values of 0.1-5.8 nM. Analogues were discovered with potent (0.01-1 mg/kg) cognition and attention enhancing properties in animal models. One compound in parti...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040118g
更新日期：2005-01-13 00:00:00
abstract：:The JAK-STAT3 pathway regulates genes that are important in cell proliferation and thus is a promising target for cancer therapy. A high-throughput screening (HTS) campaign using an Apo-ONE Homogenous Caspase 3/7 assay in U266 cells identified 4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 4 as a po...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701271y
更新日期：2008-07-24 00:00:00
