Synthesis and structure–activity relationships of 5-phenylthiophenecarboxylic acid derivatives as antirheumatic agents

Noguchi, Toshiya; Hasegawa, Masahiro; Tomisawa, Kazuyuki; Mitsukuchi, Morihiro

doi:10.1016/j.bmc.2003.08.009

Cited by 17 publications

(13 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(4). This study supports the SAR study obtained from the dataset [5]. The Observed (Obs) and Predicted (Pred) activities of phenylthiopheneacetic acid derivatives, phenylthiophenepropionic acid derivatives and phenylthiophenecarboxylic acid derivatives according to eq.…”

Section: Discussionsupporting

confidence: 67%

“…We tried here to theoretically predict the activities of some molecules which had no reported activity in the dataset [5]. In case of IL-1 inhibitory activity, 7 compounds were found to have no IL-1 inhibitory activity among the total set of fifty one compounds.…”

Section: Prediction Of Il-1 Inhibitory Activity and Aia Suppressive Amentioning

confidence: 99%

“…Anti-rheumatic activities (IC 50 ) of forty-four compounds against IL-1 in mice and % suppression on adjuvantinduced arthritis (%AIA) in rats of forty-six (1-2, 4-13, 15-21, 23-29, 31-39, 41-51) of these compounds in a total dataset of fifty-one 5-Phenylthiophenecarboxylic acid derivatives were collected [5]. The negative logarithm of IL-1 inhibitory activity (pIC 50 ) and logarithm of percentage suppressive edema volume on AIA (Log%AIA) of these compounds were used to develop QSAR models.…”

Section: Datasetmentioning

confidence: 99%

“…Recently, some works are reported on molecular modeling of agents that are effective in arthritis [3,4]. 5-Phenylthiophenecarboxylic acid derivatives [5] were shown to be effective against IL-1 and adjuvant induced arthritis (AIA) and, thus, in arthritis. To find the structural requirements for more active agents to be used in arthritis, chemometric modeling through validated predictive QSAR studies were done on 5-Phenylthiophenecarboxylic acid derivatives [5] as a part of our composite program of rational drug design, discovery and development .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chemometric Modeling of 5-Phenylthiophenecarboxylic Acid Derivatives as Anti-Rheumatic Agents

Adhikari

Jana²,

Halder³

et al. 2012

CAD

View full text Add to dashboard Cite

Arthritis involves joint inflammation, synovial proliferation and damage of cartilage. Interleukin-1 undergoes acute and chronic inflammatory mechanisms of arthritis. Non-steroidal anti-inflammatory drugs can produce symptomatic relief but cannot act through mechanisms of arthritis. Diseases modifying anti-rheumatoid drugs reduce the symptoms of arthritis like decrease in pain and disability score, reduction of swollen joints, articular index and serum concentration of acute phage proteins. Recently, some literature references are obtained on molecular modeling of antirheumatic agents. We have tried chemometric modeling through 2D-QSAR studies on a dataset of fifty-one compounds out of which forty-four 5-Phenylthiophenecarboxylic acid derivatives have IL-1 inhibitory activity and forty-six 5-Phenylthiophenecarboxylic acid derivatives have %AIA suppressive activity. The work was done to find out the structural requirements of these anti-rheumatic agents. 2D QSAR models were generated by 2D and 3D descriptors by using multiple linear regression and partial least square method where IL-1 antagonism was considered as the biological activity parameter. Statistically significant models were developed on the training set developed by k-means cluster analysis. Sterimol parameters, electronic interaction at atom number 9, 2D autocorrelation descriptors, information content descriptor, average connectivity index chi-3, radial distribution function, Balaban 3D index and 3D-MoRSE descriptors were found to play crucial roles to modulate IL-1 inhibitory activity. 2D autocorrelation descriptors like Broto-Moreau autocorrelation of topological structure-lag 3 weighted by atomic van der Waals volumes, Geary autocorrelation-lag 7 associated with weighted atomic Sanderson electronegativities and 3D-MoRSE descriptors like 3D-MoRSE-signal 22 related to atomic van der Waals volumes, 3D-MoRSE-signal 28 related to atomic van der Waals volumes and 3D-MoRSE-signal 9 which was unweighted, were found to play important roles to model %AIA suppressive activity.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Prediction Of Il-1 Inhibitory Activity and Aia Suppressive Amentioning

confidence: 99%

Section: Datasetmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Chemometric Modeling of 5-Phenylthiophenecarboxylic Acid Derivatives as Anti-Rheumatic Agents

Adhikari

Jana²,

Halder³

et al. 2012

CAD

View full text Add to dashboard Cite

show abstract

“…see [8,9]). 5-Aryl-2-thiophenecarbaldehydes have also found widespread use as reagents [10][11][12][13]. They are usually prepared by formylation of arylthiophenes [10] or by palladium-catalyzed arylation of 2-thiophenecarbaldehyde by various reagents [11][12][13][14][15].…”

mentioning

confidence: 99%

Synthesis and reactions of 5-aryl-2-thiophenecarbaldehydes

Обушак

Matiychuk

Lytvyn

2008

Chem Heterocycl Comp

View full text Add to dashboard Cite

The Krapcho Dealkoxycarbonylation Reaction of Esters with α‐Electron‐Withdrawing Substituents

Krapcho

Ciganek

2013

Organic Reactions

View full text Add to dashboard Cite

The Krapcho reaction involves esters with α‐electron‐withdrawing substituents such as malonates, β‐keto esters, and α‐cyano esters, which undergo dealkoxycarbonylation on being heated in polar aprotic solvents (such as DMSO, DMF, or HMPT) in the presence of water, or in polar aprotic solvents with water in the presence of added salts (such as NaCN, NaCl, LiCl, LiI, or MgCl 2 ). This procedure avoids the use of strongly aqueous acidic and alkaline conditions and tolerates many functional and protecting groups. The chapter presents the mechanistic aspects of this procedure, which include reaction parameters such as solvents, salts, other additives, and the use of microwave irradiation. The diastereoselectivity of protonation of the enolate intermediate leading to the dealkoxycarbonylated products is discussed. Trapping of the intermediate enolate by electrophiles other than a proton is illustrated. Potential side reactions and same‐pot subsequent reactions of substrates are discussed along with functional‐group compatibility for halogens and nitrogen, oxygen, sulfur, selenium, and carbon functional groups. Several examples of applications of this methodology for the synthesis of natural products along with experimental conditions and procedures are presented. Closely related methods are discussed in the Comparison with Other Methods section. The tables, which consist of 371 pages, are grouped according to substrate structure. Selective entries for other methods (excluding classical aqueous acidic or basic methods) are included in the tabular survey for comparative purposes.

show abstract

Synthesis and structure–activity relationships of 5-phenylthiophenecarboxylic acid derivatives as antirheumatic agents

Cited by 17 publications

References 10 publications

Chemometric Modeling of 5-Phenylthiophenecarboxylic Acid Derivatives as Anti-Rheumatic Agents

Chemometric Modeling of 5-Phenylthiophenecarboxylic Acid Derivatives as Anti-Rheumatic Agents

Synthesis and reactions of 5-aryl-2-thiophenecarbaldehydes

The Krapcho Dealkoxycarbonylation Reaction of Esters with α‐Electron‐Withdrawing Substituents

Contact Info

Product

Resources

About