Abstract：
:4-Amino-5-arylpyrimidines were synthesized by a variety of methods and have demonstrated antiinflammatory activity in the carrageenan-induced edema in the rat but displayed little activity against adjuvant-induced arthritis in rats or against uv-induced erythema in guinea pigs.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Lang SA Jr,Cohen Edoi
10.1021/jm00240a021keywords:
subject
Has Abstractpub_date
1975-06-01 00:00:00pages
623-5issue
6eissn
0022-2623issn
1520-4804journal_volume
18pub_type
杂志文章abstract：:Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor. The purpose of the set was to look for a possible relationship in binding affinity or receptor subtype selectivity with aromatic substituent p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00114a005
更新日期：1991-10-01 00:00:00
abstract：:A physiologically based model for gastrointestinal transit and absorption in humans is presented. The model can be used to study the dependency of the fraction dose absorbed (F(abs)) of both neutral and ionizable compounds on the two main physicochemical input parameters (the intestinal permeability coefficient (P(int...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030999b
更新日期：2004-07-29 00:00:00
abstract：:The sphingoid base derived class of lipids (sphingolipids) is a family of interconverting molecules that play key roles in numerous structural and signaling processes. The biosynthetic pathway of the sphingolipids affords many opportunities for therapeutic intervention: targeting the ligands directly, targeting the va...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.6b01575
更新日期：2017-07-13 00:00:00
abstract：:Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701049p
更新日期：2008-01-10 00:00:00
abstract：:Polyamine analogues 7, 10, 18, 27, and 32 containing cyclopropane rings were obtained by chemical synthesis. Their antineoplastic activities were assessed against the cultured human prostate tumor cell lines DU-145, DuPro, and PC-3. Decamines 32 and 27 exhibited variable levels of cytotoxicity against all three cell l...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030175u
更新日期：2003-10-09 00:00:00
abstract：:High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4, 5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent tha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9800090
更新日期：1998-06-18 00:00:00
abstract：:Several N(1)-arylalkylpolyamines containing various aromatic ring systems were synthesized as their respective HCl salts. The N(1)-substituents evaluated ranged in size from N(1)-benzyl, N(1)-naphthalen-1-ylmethyl, N(1)-2-(naphthalen-1-yl)ethyl, N(1)-3-(naphthalen-1-yl)propyl, N(1)-anthracen-9-ylmethyl, N(1)-2-(anthra...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0497040
更新日期：2004-11-18 00:00:00
abstract：:A promising strategy for selecting synthetic targets is similarity-based searching of very large "virtual libraries", which comprise all structures accessible by linking two or three commercially available building blocks with combinatorial syntheses. To assess the general applicability of this strategy, leading struc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000003m
更新日期：2000-05-04 00:00:00
abstract：:Endosomal toll-like receptors (TLRs) 7 and 8 recognize viral single-stranded RNAs, a class of imidazoquinoline compounds, 8-oxo-adenosines, 8-aminobenzodiazepines, pyrimidines, and guanosine analogues. Substantial evidence is present linking chronic inflammation mediated specifically by TLR7 to the progression of auto...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01201
更新日期：2019-11-27 00:00:00
abstract：:A series of novel tacrine derivatives and tacrine-coumarin heterodimers were designed, synthesized, and biologically evaluated for their potential inhibitory effect on both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Of these compounds, tacrine-coumarin heterodimer 7c and tacrine derivative 6b were ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5008648
更新日期：2014-08-28 00:00:00
abstract：:The structure-based design, synthesis, and biological activity of a novel indazole-containing inhibitor series for S-adenosyl homocysteine/methylthioadenosine (SAH/MTA) nucleosidase are described. Use of 5-aminoindazole as the core scaffold provided a structure-guided series of low nanomolar inhibitors with broad-spec...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0302039
更新日期：2003-12-18 00:00:00
abstract：:A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC(50) = 8.98 +/- 0.90 microM) which was used as a lead compo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000145g
更新日期：2001-05-10 00:00:00
abstract：:A series of novel (1,3-dialkyl-5-amino-1H-pyrazol-4-yl)arylmethanones was synthesized. Pharmacological evaluation of these compounds demonstrated central nervous system depressant activity, potential anticonvulsant properties, and a low order of acute toxicity. In addition, selected compounds showed potential antipsyc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00377a003
更新日期：1984-11-01 00:00:00
abstract：:Imidazolium [trans-tetrachloro(1H-imidazole)(S-dimethylsulfoxide)ruthenate(III)] (NAMI-A) and indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) are the most promising ruthenium complexes for anticancer chemotherapy. In this study, the azole ligand of NAMI-A was systematically varied (from imidazole...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061081y
更新日期：2007-05-03 00:00:00
abstract：:The sulfoxides 5-methylsulfinyl-2-furaldehyde semicarbazone (2) and 1-[(5-methylsulfinyl-2-fufurylidene)amino]hydantoin (3) as well as the sulfones 1-[(5-methylsulfonyl-2-furfurylidene)animo]hydantoin (1) and 1-(5-methylsulfonly-2-furyl)-2-(6-amino-3-p-ridazyl)ethylene hydrochloride (4) have been prepared and tested f...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00245a030
更新日期：1975-11-01 00:00:00
abstract：:Replacement of the catecholic hydroxyl groups of the beta-adrenergic receptor agonist 6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline (trimetoquinol) with chloro substituents results in a compound with marked beta-adrenoceptor antagonist properties. This, therefore, parallels the similar transf...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00161a039
更新日期：1986-11-01 00:00:00
abstract：:In drug discovery, it is essential to identify binding sites on protein surfaces that drug-like molecules could exploit to exert a biological effect. Both X-ray crystallography and NMR experiments have demonstrated that organic solvents bind precisely at these locations. We show that this effect is reproduced using mo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801385d
更新日期：2009-04-23 00:00:00
abstract：:(R)-(-)- and (S)-(+)-alpha-methyl-beta-4-(fluorophenyl)-N-methyl-N- propynylethylamine [R)-(-)- and (S)-(+)-4-fluorodeprenyl) were synthesized via the reaction of 4-fluorobenzaldehyde with nitroethane followed by reduction with lithium aluminum hydride to produce racemic 4-fluoroamphetamine, which was resolved by recr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00169a034
更新日期：1990-07-01 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 lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060435i
更新日期：2006-08-10 00:00:00
abstract：:The preparation, determination of isomeric configuration, and antifungal properties of (E)-1-(5-chlorothien-2-yl)-2-(1H-imidazol-1-yl)ethanone 2,6-dichlorophenylhydrazone hydrochloride (1) are described. In vitro, compound 1 has been shown to have activity against Candida albicans comparable with miconazole. When admi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00357a023
更新日期：1983-03-01 00:00:00
abstract：:The need for drugs that lack the obtrusive and limiting side effects of the tricyclic antidepressants has prompted the search for agents with greatly enhanced selectivity for specific mechanisms believed to be essential for antidepressant efficacy. The potential role of derangements of 5-HT pathways in the etiology of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00377a021
更新日期：1984-11-01 00:00:00
abstract：:A six-stage stereoselective synthesis of indanyl-7-(3'-pyridyl)-(3R,6R,7R)-2,5-diketopiperazines oxytocin antagonists from indene is described. SAR studies involving mono- and disubstitution in the 3'-pyridyl ring and variation of the 3-isobutyl group gave potent compounds (pK(i) > 9.0) with good aqueous solubility. E...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm201287w
更新日期：2012-01-26 00:00:00
abstract：:Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing lipophilic electron-donating 1'-anilino substituents are active against both the promastigote and amastigote forms of the parasite Leishmania major. A series of analogues of the known 1'-NHhexyl lead compound were prepared and evaluated agai...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970232h
更新日期：1997-08-01 00:00:00
abstract：:2-Alkylchromen-4-one 6-O-sulfamates, a new class of potent steroid sulfatase (STS) inhibitors, were evaluated for their estrogenic potential. Structure-activity relationships for estrogenic activity were identified; however, no correlation with STS inhibition was found. Estrogenicity is favored by bulky side chains an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030926s
更新日期：2003-11-06 00:00:00
abstract：:(N)-Methanocarba adenosine 5'-methyluronamides containing known A(3) AR (adenosine receptor)-enhancing modifications, i.e., 2-(arylethynyl)adenine and N(6)-methyl or N(6)-(3-substituted-benzyl), were nanomolar full agonists of human (h) A(3)AR and highly selective (K(i) ∼0.6 nM, N(6)-methyl 2-(halophenylethynyl) analo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300396n
更新日期：2012-05-24 00:00:00
abstract：:Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg(-1) dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00134
更新日期：2016-04-28 00:00:00
abstract：:In our ongoing program aimed at the design, synthesis, and biological evaluation of novel gem-difluoromethylenated glycosidase inhibitors, gem-4,4-difluoromethylenated iminosugars (5-9) were synthesized. The biological evaluation of these synthetic iminosugars showed that the gem-difluoromethylenyl group generally red...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060066q
更新日期：2006-05-18 00:00:00
abstract：:Anthelmintic efficacies of a series of 6-substituted methyl imidazo[1,2-alpha]pyridine-2-carbamates were compared to similarly substituted benzimidazole-2-carbamates. With only one exception, methyl 6-benzoylimidazo[1,2-alpha]pyridine-2-carbamate, both classes of compounds exhibited similar activity vs. Nematospiroide...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00144a030
更新日期：1981-12-01 00:00:00
abstract：:The synthesis, biological evaluation, and structure-activity relationships of a series of N-phenyl heteroaryl-fused isothiazolones are described. These isothiazolones have been shown to exhibit potent, dose-dependent inhibition of IL-1 beta-induced breakdown of proteoglycan in a cartilage organ culture assay. This eff...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00045a012
更新日期：1994-09-16 00:00:00
