Synthesis of new chemical entities from paracetamol and NSAIDs with improved pharmacodynamic profile

Yadav, Mange Ram; Nimekar, Datta M.; Ananthakrishnan, Ashwin N.; Brahmkshatriya, Pathik S.; Shirude, S. T.; Giridhar, Rajani; Balaraman, R

doi:10.1016/j.bmc.2006.08.017

Cited by 22 publications

(9 citation statements)

References 18 publications

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“…Synthesis of prodrugs of NSAIDs is not only an effective way of overcoming the GI toxicity but could also be used for combining other pharmacological properties or incorporating a chemical moiety for an added beneficial effect (like development of NO-NSAIDs [103,104], conjugation with H 2 receptor antagonist [75] or an analgesic agent [87] and incorporating anticholinergic activity for reducing gastric acid secretion [138][139][140][141][142][143].…”

Section: Discussionmentioning

confidence: 99%

“…With the goal of combining high antipyretic activity of paracetamol into commonly used NSAIDs, seven different NSAIDs were chemically combined with p-aminophenol to yield the p-amidophenol derivatives [87]. These were acetylated at the phenolic hydroxyl group to yield corresponding acetate derivatives for evaluating the impact of blocked phenolic hydroxy group on the biological activity of these derivatives.…”

Section: Mutual Prodrugsmentioning

confidence: 99%

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Prodrug Designing of NSAIDs

Halen¹,

Murumkar²,

Giridhar³

et al. 2009

MRMC

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Non-steroidal anti-inflammatory drugs (NSAIDs), commonly used for the treatment of chronic inflammatory diseases suffer from several undesired side effects, the most important being gastrointestinal (GI) irritation and ulceration. The prodrug designing is one of the several strategies used to overcome this drawback. The rationale behind the prodrug concept is to achieve temporary blockade of the free carboxylic group present in the NSAIDs till their systemic absorption. In this paper, a review on the concept of prodrugs designing of NSAIDs to improve their efficacy and reduce the toxicity is being presented.

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Section: Discussionmentioning

confidence: 99%

Section: Mutual Prodrugsmentioning

confidence: 99%

Prodrug Designing of NSAIDs

Halen¹,

Murumkar²,

Giridhar³

et al. 2009

MRMC

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“…Some of the biaryldiacid derivatives have been evaluated as potential anti‐inflammatory agents through the inhibition of 14 kDa human platelet phospholipase A2 (HP‐PLA2) 21. Some of the biphenylic compounds that contain free carboxyl groups cause ulceration 22–23.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Some New S‐Alkylated 1,2,4‐Triazoles, Their Mannich Bases and Their Biological Activities

Alam

Nazreen

Haider

et al. 2011

Archiv der Pharmazie

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A series of 1-(4-methoxyphenyl)-2-[5-{(biphenyl-4-yloxy)methyl}4-(substituted phenyl)-3-mercapto-(4H)-1,2,4-triazol-3-ylthio)] ethanones (6a-6s) and 4-(substituted phenyl)-3-(morpholin/pyrrolidin-4-ylmethylthio)-5-(4-phenylphenoxymethyl)-4H-1,2,4-triazoles (7a-7e) were synthesized in order to obtain new compounds with potent anti-inflammatory and analgesic activity with insignificant ulceration. Among the synthesized compounds, (6c), (6e), (6g) and (6l) from triazole series and (7b) and (7e) from Mannich base series were found to exhibit significant anti-inflammatory activity with 59.69, 59.69, 64.69, 79.84, 54.54, 79.69% and 52.55, 57.50, 72.52, 83.03, 60.06, 84.08% inhibition of paw edema at 3 h and 5 h respectively, in comparison to the standard drug ibuprofen (78.93 and 82.58% at 3 h and 5 h). The active compounds were further tested for their analgesic activity and gastric ulceration study. Compounds 6g, 7b and 7e exhibited significant analgesic activity with reaction time (3.60, 3.22, 3.88 s) respectively at 60 min. without causing any gastric irritation. These compounds were also screened for their in vitro antimicrobial activity, Compounds 6f, 6g, 6h, 6l, 6o, 6p, 7a, 7b and 7c showed significant zone of inhibition against various antimicrobial stains. It is concluded that the compounds 6g, 7b and 7e possess a good spectrum of activities. Compound 7e may be considered potent for development of better anti-inflammatory agent. The antimicrobial activity revealed that most of the compounds showed moderate to significant activity. Compounds containing nitro, chloro, bromo and fluoro group showing better activity. All the compounds from 7a, 7b and 7e were active against gram positive bacteria (S. aureus).

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“…Analgesic activity was carried out using acetic acid induced writhing method [13]. Group I served as a control and received vehicle 1% (v/v) Tween-80 in water at the dose of 10 mL/kg of body weight while group II, III and IV received naproxen (10 m /kg), glyceride prodrugs 6a g…”

Section: Analgesic Activitymentioning

confidence: 99%

Synthesis and Evaluation of Glyceride Prodrugs of Naproxen

Redasani¹,

Bari²

2013

OJMC

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The glyceride ester derivatives 6a and 6b were prepared by reacting 1,2,3-trihydroxy propane 1,3-dipalmitate/stearate with (S)-naproxen as potential prodrugs. The synthesis was achieved successfully with the aid of N,N'-dicyclohexylcarbodiimide. These prodrugs were evaluated for anti inflammatory, analgesic and gastroprotective activity. It was found that prodrugs 6a and 6b showed less irritation to gastric mucosa as indicated by ulcer index. The synthesized glyceride esters were found to possess good pharmacological profile as shown by results of anti inflammatory and analgesic activity. The aqueous studies were performed in order to ensure the release of prodrugs. Both prodrugs were found to stable at acidic pH while underwent hydrolysis at pH 7.4. These findings suggest that the glyceride prodrugs 6a and 6b might be used as potential biolabile derivatives.

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Synthesis of new chemical entities from paracetamol and NSAIDs with improved pharmacodynamic profile

Cited by 22 publications

References 18 publications

Prodrug Designing of NSAIDs

Prodrug Designing of NSAIDs

Synthesis of Some New S‐Alkylated 1,2,4‐Triazoles, Their Mannich Bases and Their Biological Activities

Synthesis and Evaluation of Glyceride Prodrugs of Naproxen

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