4-(6-Methoxy-2-naphthyl)butan-2-one and related analogs, a novel structural class of antiinflammatory compounds

Abstract

A series of compounds related to 4-(6-methoxy-2-naphthyl)butan-2-one has been prepared and tested for antiinflammatory activity by the cotton pellet granuloma method. Compounds possessing a small lipophilic group such as methoxyl, methyl, or chloro in the 6 position in conjunction with a butan-2-one side chain in the 2 position of the naphthalene ring were most active. The indtroduction of a methyl group along the side chain was invariably deleterious. Good activity was generally retained by forming esters of a butan-2-ol side chain.

Carbon-Carbon Bond Cleavage in Activation of the Prodrug Nabumetone

“…Other potential intermediates in P450-mediated cleavage of the nabumetone side chain, diols 6 and 7, were accessible from the known 5 (Goudie et al, 1978) in three steps. Treatment of 5 with POCl 3 in pyridine gave the corresponding chloride 5a, and subsequent sodium ethoxide-mediated elimination yielded the alkenes 5b, E-5c, and Z-5c as a mixture in a 4:4:1 ratio.…”

“…Finally, the alkene E-11 (Viviano et al, 2011) was synthesized from aldehyde 11a (Schmidt et al, 2005) via an aldol reaction with acetone as described in the literature (Goudie et al, 1978). Interestingly, we had observed 11a as a significant product during attempted oxidation of 2 under a variety of conditions and thus used 2 as a precursor for 11a.…”

“…1, 36.5, 55.3, 80.9, 105.5, 119.0, 127.2, 127.3, 127.5, 128.0, 128.3, 128.8, 129.2, 129.5, 130.0, 131.6, 133.6, 157.7, 166.3, 203.3 1-(6-Methoxynaphthalen-2-yl)butane-2,3-diol (6) and 4-(6-Methoxynaphthalen-2-yl)butane-1,2-diol (7). POCl 3 (1.65 g, 10.95 mmol) was added dropwise to a solution of 5 (Goudie et al, 1978) (250 mg, 1.09 mmol) in pyridine (7.5 ml) at 0°C for over a period of 40 minutes. The resulting solution was allowed to warm to room temperature and stirred overnight.…”

Analgesics and Antipyretics, 2. Nonsteroidal Anti‐inflammatory Drugs

“…Nabumetone [42924-53-8], 4-(6-methoxynaphthalen-2-yl)butan-2-one, C 15 H 16 O 2 , M r 228.29, mp 80 C. Synthesis: Condensation of 6-methoxy-2-naphthaldehyde with acetone in an aqueous solution of NaOH gives 4-(6-methoxy-2-naphthyl)-3-buten-2-one, which is reduced with H 2 over Pd-C in ethyl acetate [48,[146][147][148][149].…”

Synthesis and Antimicrobial Activity of Some Novel Hydrazide, Pyrazole, Triazine, Isoxazole, and Pyrimidine Derivatives

“…The bicyclic naphthalene skeleton constitutes a great number of medical drugs, such as an anti-inflammatory agent and a cardiovascular agent [1,2]. The chemistry of a carbon-nitrogen double bond of hydrazone is becoming the vertebrae of condensation reaction in benzo-fused N-heterocycles [3]; also, it constitutes an essential class of compounds for new drug development [4].…”