Molecular docking design and one-pot expeditious synthesis of novel 2,5-diarylpyrazolo[1,5-a]pyrimidin-7-amines as anti-inflammatory agents

Aggarwal, Ranjana; Singh, G. B.; Kaushik, Pawan; Kaushik, Dhirender; Paliwal, Deepika; Kumar, Ajay

doi:10.1016/j.ejmech.2015.06.011

Cited by 22 publications

(12 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the anti-inflammatory activity of pyrazolo[1,5-a]pyrimidine, 2,5-diarylpyrazolo[1,5-a]pyrimidin-7-amines, new compounds were synthesized. Eleven compounds ( 4 – 14 ; Figure 2 ) showed interesting anti-inflammatory properties compared to indomethacin ( Table 1 ) [ 2 ]. As shown in Table 1 , all compounds except for 7 achieve more than 50% inhibition after 4 h. Furthermore, compound 9 presents only 3.5% less inhibition than indomethacin.…”

Section: Nonsteroidal Anti-inflammatory Drugs (Nsaids)mentioning

confidence: 99%

“…There are five classical signs of inflammation, i.e., pain, redness, swelling, heat, and loss of function. Although the function of an inflammatory process is to eliminate the cause of injury and heal damaged tissue by clearing dead cells, sometimes this response is too aggressive, causing excessive pain and incapacity [ 2 ]. In these cases, an anti-inflammatory drug is needed to ameliorate symptoms and allow the person to continue a normal life.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Organic Small Molecules in Pain Management

Cuesta

Meneses

2021

Molecules

View full text Add to dashboard Cite

In this review, a timeline starting at the willow bark and ending in the latest discoveries of analgesic and anti-inflammatory drugs will be discussed. Furthermore, the chemical features of the different small organic molecules that have been used in pain management will be studied. Then, the mechanism of different types of pain will be assessed, including neuropathic pain, inflammatory pain, and the relationship found between oxidative stress and pain. This will include obtaining insights into the cyclooxygenase action mechanism of nonsteroidal anti-inflammatory drugs (NSAID) such as ibuprofen and etoricoxib and the structural difference between the two cyclooxygenase isoforms leading to a selective inhibition, the action mechanism of pregabalin and its use in chronic neuropathic pain, new theories and studies on the analgesic action mechanism of paracetamol and how changes in its structure can lead to better characteristics of this drug, and cannabinoid action mechanism in managing pain through a cannabinoid receptor mechanism. Finally, an overview of the different approaches science is taking to develop more efficient molecules for pain treatment will be presented.

show abstract

Section: Nonsteroidal Anti-inflammatory Drugs (Nsaids)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Role of Organic Small Molecules in Pain Management

Cuesta

Meneses

2021

Molecules

View full text Add to dashboard Cite

show abstract

“…In literature, 5-aryl-1-(4-substitutedpyridazinyl) pyrazol-3-propanoic acids (A) have been reported to inhibit LTB 4 biosynthesis in human neutrophils with IC 50 values of 12-14 µM [20,21]. Keeping this in view and in continuation of our interest in 5-aminopyrazoles as precursors for the synthesis of heterocyclic rings and as a promising biological active entity [22][23][24][25][26][27][28][29], target molecules have been designed by replacing acidic chain of pyrazole ring with aryl ring, aryl ring at position-5 of pyrazole ring with amino group and widening the scope of substituents such as R group at phenyl ring present at position-3 of pyrazole ring, and substitution of Cl group by pyrrolidine, piperidine and morpholine of pyridazine ring (▶Fig. 2).…”

Section: Aim: Designing Of Target Moleculesmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of 5-amino-3-aryl-1-(6'-chloropyridazin-3'-yl)pyrazoles and their Derivatives as Analgesic Agents

et al. 2020

Self Cite

View full text Add to dashboard Cite

An efficient and environmental benign solvent-free synthesis of 5-amino-3-aryl-1-(6'-chloropyridazin-3'-yl)pyrazoles (4a-e) was accomplished by grinding 3-chloro-6-hydrazinopyridazine (2) and β-ketonitriles (3a-e) in the presence of p-toulenesulfonic acid as a catalyst. Subsequently, 6'-chloro group in 4a-e was replaced with cyclic 2° amine derivatives viz. pyrrolidine 5a, piperidine 5b and morpholine 5c to obtain 6a-e, 7a-e, 8a-e respectively. The newly synthesized compounds were characterized by using IR, NMR (1H and 13C), mass spectral studies, elemental analyses. All the synthesized compounds were studied for their docking interaction with target protein 6COX and screened for their in vivo analgesic mode of action against swiss albino mice (animal model) using acetic-acid induced writhing test. Consequently, docking simulations data justifies the potential of synthesized series as an analgesic and very well correlated with in vivo study. Preliminary results revealed that most of the synthesized compounds exhibited moderate to good analgesic activity as compared to reference/standard drug (s) sodium diclofenac and candidates 4d and 7c protrude out as a promising lead for further investigation.

show abstract

“…In another report Aggarwal et al [ 101 ] synthesized similar 7-aminopyrazolo[1,5- a ]pyrimidine 148 from the reaction of hydrazine hydrate with two different 3-oxo-3-arylpropanenitriles 15 which are successively added one after the other in toluene/ethanol (9:1) at reflux temperature in presence of p -TSA. The reaction carried out in pure ethanol provided a mixture of 5-aminopyrazoles ( Scheme 42 ).…”

Section: Reviewmentioning

confidence: 99%

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

Aggarwal

Kumar

2018

Beilstein J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

The condensation of 5-aminopyrazole with various bielectrophilic moieties results in the formation of pyrazoloazines, an interesting array of fused heterocyclic systems. The development of new synthetic routes towards pyrazoloazines for their biological and medicinal exploration is an attractive area for researchers throughout the world. The present review focuses on various synthetic methods developed in the last decade for the synthesis of differently substituted pyrazoloazines by a broad range of organic reactions by means of 5-aminopyrazole as a precursor. ReviewPyrazole and its derivatives are known to exhibit significant biological and pharmacological activities such as: anticancer [1,2], anti-inflammatory [3,4], antioxidant [5], antibacterial [6][7][8], analgesic [9], antiviral [10,11], antimicrobial [12,13], antifungal [6], antiglycemic [14], antiamoebic [15] and antidepressive [16,17]. Considering the immense biological properties pyrazole is one of the most widely studied nitrogen-containing heterocyclic nuclei. Fused pyrazole derivatives are composed of the pyrazole nucleus attached to other heterocyclic moieties which enable them to exhibit improved pharmacological activities compared to the isolated fragments. These compounds are currently used in several marketed drugs like cartazolate (1), zaleplon (2), sildenafil (3), allopurinol (4), indiplon (5), etazolate (6) etc. (Figure 1). Fused pyrazole derivatives, especially pyrazoloazines have been reported to mimic purine bases, present in DNA and RNA, due to close structural resemblance.In addition to the immense biological potential related to fused pyrazoles, their synthetic potential needs to be reviewed for further improvements and extension of interests. Various efforts have been developed for the synthesis of pyrazole-based fused heterocycles. 5-Aminopyrazoles have been extensively employed as useful synthons in designing and constructing a Beilstein J. Org. Chem. 2018, 14, 203-242. 204 A number of review articles have been published by us and others highlighting the synthetic and biological aspects of 5-aminopyrazoles [26][27][28] as well as on the synthesis of fused pyrazole derivatives [25]. However, a perusal of literature reveals that the importance of 5-aminopyrazoles as synthetic precursors for fused heterocycles has not been reported till now to the best of our knowledge. Recent literature shows resurgence of interest in the chemistry and bioactivity of 5-aminopyrazole derivatives leading to improvements in several already known reactions and syntheses of various fused heterocyclic derivatives with various biological activities. Considering the synthetic importance of 5-aminopyrazoles and synthesis of fused pyrazole derivatives with the need for a more general collection, herein we report an exhaustive overview of the main developments in the last decade in the chemistry of 5-aminopyrazoles for the design and synthesis of fused pyrazoloazines.The typical reactivity of 5-aminopyrazoles 5-Aminopyrazoles are polyfunctional co...

show abstract

Molecular docking design and one-pot expeditious synthesis of novel 2,5-diarylpyrazolo[1,5-a]pyrimidin-7-amines as anti-inflammatory agents

Cited by 22 publications

References 16 publications

The Role of Organic Small Molecules in Pain Management

The Role of Organic Small Molecules in Pain Management

Design, Synthesis and Biological Evaluation of 5-amino-3-aryl-1-(6'-chloropyridazin-3'-yl)pyrazoles and their Derivatives as Analgesic Agents

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

Contact Info

Product

Resources

About