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 effect is likely due to inhibition of MMP activation and a consequent reduction in MMP activity following IL-1 beta stimulation. Thus these compounds potentially represent simple, non-peptidic disease-modifying agents for the treatment of arthritic diseases. To examine the effects of structure on in vitro activity, three general features of the molecules were varied, substituents on the pendant N-phenyl group, the position of ring fusion to the isothiazolone, and substituents on the fused ring peri to the isothiazolone sulfur.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Wright SW,Petraitis JJ,Abelman MM,Batt DG,Bostrom LL,Corbett RL,Decicco CP,Di Meo SV,Freimark B,Giannaras JVdoi
10.1021/jm00045a012subject
Has Abstract,Author List Incompletepub_date
1994-09-16 00:00:00pages
3071-8issue
19eissn
0022-2623issn
1520-4804journal_volume
37pub_type
杂志文章abstract：:A series of 4(6)-(benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues of which 4(6)-benzyloxy groups were replaced with a (2-, 3-, or 4-fluorobenzyl)oxy or (2-, 3-, or 4-pyridylmethyl)oxy group, was synthesized. The abilities of these compounds to inhibit human O6-alkylguanine-DNA alkylt...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970363i
更新日期：1998-02-12 00:00:00
abstract：:A series of 2-substituted methyl 2,3-dihydroimidazo[1, 2-c]quinazolin-5(6H)-ones (4), 3-substituted methyl 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-ones (5), 3-substituted methyl 2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-ones (15a,b), 3-substituted methyl 2,3-dihydroimidazo[2,1-b]quinazolin-5(1H)-ones (16a,b), 3-su...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970159v
更新日期：1998-08-13 00:00:00
abstract：:New fluorinated 2-aryl-benzothiazoles, -benzoxazoles, and -chromen-4-ones have been synthesized and their activity against MCF-7 and MDA 468 breast cancer cell lines compared with the potent antitumor benzothiazole 5. Analogues such as 9a, b and 12a, d yielded submicromolar GI50 values in both cell lines; however, non...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800418z
更新日期：2008-08-28 00:00:00
abstract：:The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyzes the transfer of ADP-ribose units onto substrate proteins by using nicotinamide adenine dinucleotide (NAD(+)) as a cosubstrate. They have a documented role in chromatin remodelling and DNA repair, and inhibitors of ARTD1 and 2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300746d
更新日期：2012-09-13 00:00:00
abstract：:From the whole plant of Euphorbia peplus L., five new diterpenes based on a jatrophane skeleton (pepluanins A-E, 1-5) were isolated, together with two known analogues (6 and 7), which served to divulge in detail the structure-activity relationships within this class of P-glycoprotein inhibitors. The results revealed t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030951y
更新日期：2004-02-12 00:00:00
abstract：:Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049884d
更新日期：2004-10-07 00:00:00
abstract：:17β-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00293
更新日期：2016-07-28 00:00:00
abstract：:The N-2 atoms of phosphorus 2,2-dimethylhydrazides, contrary to a previous report, can be methylated by iodomethane. Treatment of the resulting dihydrazinium iodides with aqueous sodium hydroxide results in mono- instead of didehydroiodination, apparently due to resonance stabilization of the inner salt form. The phos...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm50001a010
更新日期：1985-05-01 00:00:00
abstract：:The preparation of 6-chloro-5-(cyclopentylmethyl)indan-1-carboxylic acid is described. This acid has good anti-inflammatory and analgesic activities without producing irritation in the gastrointestinal tract up to the highest tested dose. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00369a033
更新日期：1984-03-01 00:00:00
abstract：:Aliphatic amino acids glycine, alanine, valine, and leucine were conjugated to the antitumor drug N2-methyl-9-hydroxyellipticinium (NMHE) through a peroxidase-catalyzed oxidation reaction. NMR studies of the adducts so obtained have indicated (i) that the amino acids were linked to NMHE between the nitrogen of their p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00375a013
更新日期：1984-09-01 00:00:00
abstract：:A series of 1-thia analogues of the pyrrolizine bis(carbamate) 9 (NSC-278214), namely 5-aryl-2,3-dihydropyrrolo-[2,1-b]thiazole-6,7-dimethanol 6,7-bis(isopropylcarbamates) (7a-d), were prepared by multistep syntheses from the proline analogue thiazolidine-2-carboxylic acid. The compounds were tested for growth inhibit...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00402a030
更新日期：1988-07-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049534r
更新日期：2005-03-24 00:00:00
abstract：:From the discovery of competitive hexapeptide inhibitors, potent and selective HCV NS3 protease macrocyclic inhibitors have been identified. Structure-activity relationship studies were performed focusing on optimizing the N-terminal carbamate and the aromatic substituent on the (4R)-hydroxyproline moiety. Inhibitors ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0342414
更新日期：2004-03-25 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0501432
更新日期：2005-05-05 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00358a021
更新日期：1983-04-01 00:00:00
abstract：:Four nucleoside analogues ( 1- 4) containing a common heterocyclic base, 4(7)-amino-6(5) H-imidazo[4,5- d]pyridazin-7(4)one, were screened against calf-intestine adenosine deaminase. Compounds 1 and 3 with K(i) values of 10-12 microM are more than four times as potent inhibitors of ADA compared with 2 and 4, with K(i)...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm700931t
更新日期：2008-02-14 00:00:00
abstract：:A weak, nonselective G protein-coupled receptor 120 (GPR120) agonist 10 was found by screening a series of carboxylic acids derived from the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist 3. Modification based on the homology model of GPR120 led to the first GPR120-selective agonist 12. These res...
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pub_type： 杂志文章
doi：10.1021/jm800970b
更新日期：2008-12-11 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：:The high secretion rate of 18-hydroxydeoxycorticosterone in hypertensives and the steroids implication as a mineralocorticoid has led to the synthesis of potential di-, tetra-, and hexahydro metabolites of it and 18-hydroxy-progesterone. These potential metabolites have been synthesized by reduction of the double bond...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00380a014
更新日期：1985-02-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300642a
更新日期：2013-03-14 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00127a041
更新日期：1989-07-01 00:00:00
abstract：:Synthesis and identification of novel phenylalkyl isoselenocyanates (ISCs), isosteric selenium analogues of naturally occurring phenylalkyl isothiocyanates (ITCs), as effective cytotoxic and antitumor agents are described. The structure-activity relationship comparison of ISCs with ITCs and effect of the increasing al...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800993r
更新日期：2008-12-25 00:00:00
abstract：:The synthesis and biological evaluation of three classes of chain-modified derivatives of (+)-EHNA are described. Among the 5', 6'-unsaturated derivatives, the Z-isomer was the most potent inhibitor of adenosine deaminase (ADA) but 3-fold less active than (+)-EHNA. Several 9-aralkyladenines (ARADs) have been prepared,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0002533
更新日期：2000-11-30 00:00:00
abstract：:New antiproliferative compounds, dimethyl-5H-pyrido[3,2-a]phenoxazin-5-ones (1-6), tetrahydro-5H-benzopyrido[2,3-j]phenoxazin-5-ones (7-9), and 5H-benzopyrido[3,2-a]phenoxazin-5-ones (10-12) were synthesized and evaluated against representative human neoplastic cell lines. Dimethyl derivatives 1-6 were more active aga...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050745l
更新日期：2006-08-24 00:00:00
abstract：:We have previously described the design and development of CI-988, a peptoid analogue of CCK-4 with excellent binding affinity and selectivity for the CCK-B receptor. Due to its anxiolytic profile in animal models of anxiety, this compound was developed as a clinical candidate. However, during its development, it was ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970065l
更新日期：1998-01-01 00:00:00
abstract：:The synthesis and biological activities of four novel bispyridinium cyclophanes as choline kinase (ChoK) inhibitors are presented. Their synthetic methodology has been optimized according to dilution, temperature, and reaction time and provides pure bispyridinium cyclophanes in high yields very easily. One of these cy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030792i
更新日期：2003-08-14 00:00:00
abstract：:A novel series of substituted (pyrroloamino)pyridines was synthesized, and the compounds were evaluated for cholinomimetic-like properties in vitro (inhibition of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine-induced dementia) as potential agents for the treatment of Alzheimer's disease. Co...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950644v
更新日期：1996-01-19 00:00:00
abstract：:A series of (substituted amino)-1,2,4-benzothiadiazine 1-oxides has been synthesized and most members of the series have been shown to have blood pressure lowering effects in normotensive rabbits and in spontaneously hypertensive rats. The most active member of the series was 3-[4-(2-furoyl)-1-piperazinyl]-6,7-dimetho...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00181a003
更新日期：1980-07-01 00:00:00
abstract：:The first stereoselective synthesis of the hexahydroimidazo[1,5b]isoquinoline (HHII) scaffold as a surrogate for the steroidal A-B ring system is described. The structure-activity relationships of the analogs derived from this scaffold show that the basic imidazole moiety is tolerated by the glucocorticoid receptor (G...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901551w
更新日期：2010-02-11 00:00:00
abstract：:sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in breast cancer cells, was taken as a template to prepare new analogs. One of the two basic N-atoms was alternatively replaced by a methine or converted into an a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9007505
更新日期：2009-12-10 00:00:00
