ChemInform Abstract: PYRAZOLECARBOXYLIC ACID HYDRAZIDES AS ANTIINFLAMMATORY AGENTS. NEW SELECTIVE LIPOXYGENASE INHIBITORS

Abstract

Die Titelverbindungen des Typs (IV) werden durch Reaktion der Pyrazole (I) bzw. des Dimeren (II) mit Hydrazinen des Typs (III) synthetisiert.

N-Substituted pyrazole-3-carboxamides as inhibitors of human 15-lipoxygenase

“…Carboxamides 5 are then obtained by heating 4 with an excess of the amine neat (e.g., in a microwave reactor) 31 or in the presence of DMAP, or at rt with equimolar amounts of the amine using, for example, DMAP in CH 2 Cl 2 . 28 The sequential dimerization of pyrazole-3-carboxylic acids followed by addition of nucleophiles is well known [32][33][34][35][36][37][38] and has also been used to develop anti-inflammatory 15-LOX-1 inhibitors, albeit using soybean and potato lipoxygenase assays in combination with a rat carrageenan edema model. 34 Acylation of 5 with acid chlorides affords the final product 1.…”

“…28 The sequential dimerization of pyrazole-3-carboxylic acids followed by addition of nucleophiles is well known [32][33][34][35][36][37][38] and has also been used to develop anti-inflammatory 15-LOX-1 inhibitors, albeit using soybean and potato lipoxygenase assays in combination with a rat carrageenan edema model. 34 Acylation of 5 with acid chlorides affords the final product 1. Typically, the reaction is performed by first deprotonating 5 with NaH in THF at rt and then adding the acid chloride, or by heating a mixture of 5 and the acid chloride in CH 2 Cl 2 in the presence of DMAP for 2 d. The latter method is also used for the synthesis of carbamates 6 using chloroformates.…”

Metathesis Reactions of Pyrazolotriazinones Generate Dynamic Combinatorial Libraries

“…The pyrazolotriazine scaffold was particularly attractive in this context since it could be constructed from readily available carbonyl compounds and acylhydrazides. The 6,7-dihydro-5 H -pyrazolo[1,5- d ][1,2,4]triazin-4-one was first reported by Ainsworth in 1955, and this scaffold was subsequently shown to have anti-inflammatory properties …”

“…The cyclocondensation of 3 with hydrazine in basic aqueous media led the pyrazole carboxylic acid 4 , which could be converted into pyrazolecarboxylic hydrazide 5 by acylation of methyl hydrazine using DCC as an activating agent. Ring closure of 5 was achieved with a range of aliphatic aldehydes to give the corresponding pyrazolotriazinone derivatives 6 . However, attempts to synthesize pyrazolotriazinones from aromatic aldehydes or ketones failed.…”