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Monographs of Topical Drugs that Have Caused Contact Allergy/Allergic Contact Dermatitis
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Phenylbutazone is a synthetic pyrazolone derivative and nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, antipyretic, and analgesic activities. Phenylbutazone was formerly used for the treatment of backache, ankylosing spondylitis, rheumatoid arthritis, and reactive arthritis. Because of serious systemic side effects and cutaneous adverse drug reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis, it is probably hardly used anymore, except for therapy-resistant ankylosing spondylitis. It does, however, still have applications in veterinary medicine (1). Topical use was formerly recommended for superficial phlebitis and some inflammatory diseases in the muscles and connective tissues (16).
The Application of Fragment-based Approaches to the Discovery of Drugs for Neglected Tropical Diseases
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Christina Spry, Anthony G. Coyne
Dawidowski et al. (2017) went on to show that in the presence of compound 5, glycosomal enzymes mislocalize to the cytosol and trypanosomal ATP levels are reduced as was predicted if hexokinase and phosphofructokinase mislocalize, and glucose phosphorylation is, as a consequence, unregulated. These data, and the observed correlation between affinity for PEX14 and antitrypanosomal activity for the pyrazolo[4,3-c]pyridine derivatives tested, are consistent with the antitrypansomal activity of the PEX14-PEX5 inhibitors being on target, and hence validate PEX5-PEX14 as a trypanosomal drug target. Following modification of the lead PEX5-PEX14 inhibitor to reduce plasma protein binding, antitrypanosomal activity could be observed also in a murine model of HAT. A reduction in parasitemia, with no adverse effects on the mice, was observed when the compound was administered at 100 mg/kg twice a day for five days. Further optimization of absorption, distribution, metabolism and excretion (ADME) properties is expected to yield a clinical candidate.
Orthopaedic Pharmacology
Published in Manoj Ramachandran, Tom Nunn, Basic Orthopaedic Sciences, 2018
Manoj Ramachandran, Daud Chou, Natasha Rahman
Salicylic acid derivatives: aspirin (rarely used for analgesia).Propionic acid derivatives: ibuprofen, naproxen (first line treatment in inflammatory arthropathies).Acetic acid derivatives: diclofenac (also available for topical application), indomethacin, ketorolac.Selective COX-2 inhibitors: celecoxib (reduced gastrointestinal effects).Oxicams: piroxicam (long half-life, but associated with high incidence of gastrointestinal bleeding in elderly people).Pyrazolones: azapropazone (potent, but high incidence of side-effects).
Synthesis, in silico modelling, and in vitro biological evaluation of substituted pyrazole derivatives as potential anti-skin cancer, anti-tyrosinase, and antioxidant agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Samuel T. Boateng, Tithi Roy, Kara Torrey, Uchechi Owunna, Sergette Banang-Mbeumi, David Basnet, Eleonora Niedda, Alexis D. Alexander, Denzel El Hage, Siriki Atchimnaidu, Bolni Marius Nagalo, Dinesh Aryal, Ann Findley, Navindra P. Seeram, Tatiana Efimova, Mario Sechi, Ronald A. Hill, Hang Ma, Jean Christopher Chamcheu, Siva Murru
Numerous small-molecule compounds incorporating a pyrazole substructure exhibit one or more biological activities among a wide array thereof. Of medicinal relevance, these activities include analgesic, anticancer, antibacterial, antifungal, anti-inflammatory, antiviral, antidiabetic, antitubercular, antidepressant, anticonvulsant, antipyretic, anxiolytic, antimalarial, immunosuppressive, and antioxidant (reviewed in refs.60–67) The large number of structurally diverse compounds elaborated from a pyrazole core includes representatives exhibiting anticancer activities of wide-ranging character and demonstrated or apparent efficacies against cancers appearing in almost every human organ or tissue, including lung, brain, colon, kidney, prostate, pancreas, and blood68,69. Exemplary market-approved pyrazole-based anti-cancer drugs include crizotinib, encorafenib, pyrazofurin, and tartrazine. Various other pyrazole and pyrazolone derivatives have also exhibited antiproliferative activities mediated through their interactions with various cancer related targets, or directly (Figure 1)65,70–75.
Neuronal and non-neuronal TRPA1 as therapeutic targets for pain and headache relief
Published in Temperature, 2023
Luigi F. Iannone, Romina Nassini, Riccardo Patacchini, Pierangelo Geppetti, Francesco De Logu
Some analgesics and herbal medicines/natural products widely used for the acute treatment of headache attacks seem to act via TRPA1. The highly reactive metabolite of acetaminophen N-Acetyl-parabenzoquinone-imine (NAPQI), responsible for hepato- and nephron-toxic effects of the drug, target TRPA1, promoting a mild neurogenic inflammatory response [112]. CYP450 monooxygenase activity may produce NAPQI and parabenzoquinone (p-BQ) in the spinal cord, thus locally activating TRPA1 and causing a prolonged desensitization of voltage-gated calcium and sodium currents in primary sensory neurons. The effect of spinal and systemic administration of acetaminophen was absent in TRPA1 deleted mice, suggesting that NAPQI and p-BQ produce a TRPA1-mediated spinal antinociception in [113]. Pyrazolone derivatives (including dipyrone, antipyrine, aminopyrine, and propyphenazone) have been used for decades for the acute relief of migraine attacks, although the specific mechanism of their antimigraine and analgesic action remains unknown [114]. Dipyrone and propyphenazone have been found to selectively antagonize TRPA1 in vitro and in vivo and to attenuate nociception and allodynia in animal models of neuropathic and inflammatory pain, independently from prostaglandin production and via a TRPA1-mediated mechanism [115].
An updated patent review of p38 MAP kinase inhibitors (2014-2019)
Published in Expert Opinion on Therapeutic Patents, 2020
Vanessa Haller, Philipp Nahidino, Michael Forster, Stefan A. Laufer
As an example for new indications, hVIVO Services Limited developed a 2 H-pyrazolo[3,4-b]pyridine-based compound with slight structural similarity to pyridinyl imidazole inhibitors like SB203580 and a method for treatment and prevention of hypercytokinemia and severe influenza resulting therefrom [75]. In 2018 the Streking AG patented the use of an p38 inhibitor (e.g. pamapimod) in combination with a PPAR agonist (e.g. pioglitazone) to treat ophthalmic diseases, such as age-related macular degeneration (AMD) [76]. a method for the treatment of rosacea using a combination of a p38 and ERK inhibitor was claimed by the Albany Medical College [77]. In 2017 EIP Pharma disclosed a composition of their p38 MAPK inhibitor VX-745 for treating dementia [10]. GlaxoSmithKline (GSK) patented the use of Losmapimod for the treatment of several glomerular diseases in 2015 [78], which is up to now the latest patent in the field of p38 inhibitors from GSK.