23981-48-8Relevant articles and documents
Iridium-Catalyzed α-Methylation of α-Aryl Esters Using Methanol as the C1 Source
Tsukamoto, Yuya,Itoh, Satoshi,Kobayashi, Masaki,Obora, Yasushi
supporting information, p. 3299 - 3303 (2019/05/10)
IrCl(cod)2]/dppe-catalyzed α-methylation of aryl esters using methanol as the C1 source was developed. This methylation process is useful in several fields including organic chemistry, biochemistry, and medicinal chemistry. Readily available methanol as methylation reagent was successfully adapted. The reaction processed high atom economy and efficient. By applying the reaction system, the synthesis method of naproxen was provided.
N-{[2-(PIPERIDIN-1-YL)PHENYL](PHENYL)METHYL}-2-(3-OXO-3,4-DIHYDRO-2H-1,4-BENZOXA ZIN-7-YL)ACETAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ROR-GAMMA MODULATORS FOR TREATING AUTOIMMUNE DISEASES
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Page/Page column 68; 96, (2018/08/20)
The present invention provides e.g. N-{[2-(piperidin-1-yl)phenyl] (phenyl)methyl}-2-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)acetamide derivatives and related compounds as ROR-gamma modulators for treating e.g. autoimmune diseases, autoimmune-related diseases, inflammatory diseases, metabolic diseases, fibrotic diseases or cholestatic diseases, such as e.g. arthitis and asthma.
COMPOSITIONS AND METHODS FOR SUBSTRATE-SELECTIVE INHIBITION OF ENDOCANNABINOID OXYGENATION
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Page/Page column 58; 60, (2014/02/15)
Methods for selectively inhibiting endocannabinoid oxygenation but not arachidonic acid oxygenation. In some embodiments, the methods include contacting a COX-2 polypeptide with an effective amount of a substrate-selective COX-2 inhibitor. Also provided are methods for elevating a local endogenous cannabinoid concentrations; methods of reducing depletion of an endogenous cannabinoid; methods for inducing analgesia; methods of providing anxiolytic therapy; methods for providing anti-depressant therapy; and compositions for performing the disclosed methods.
Substrate-selective inhibition of cyclooxygenase-2: Development and evaluation of achiral profen probes
Windsor, Matthew A.,Hermanson, Daniel J.,Kingsley, Philip J.,Xu, Shu,Crews, Brenda C.,Ho, Winnie,Keenan, Catherine M.,Banerjee, Surajit,Sharkey, Keith A.,Marnett, Lawrence J.
supporting information, p. 759 - 763 (2012/10/29)
Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). We recently reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not arachidonic acid oxygenation. In this work, we synthesized achiral derivatives of five profen scaffolds and evaluated them for substrate-selective inhibition using in vitro and cellular assays. The size of the substituents dictated the inhibitory strength of the analogs, with smaller substituents enabling greater potency but less selectivity. Inhibitors based on the flurbiprofen scaffold possessed the greatest potency and selectivity, with desmethylflurbiprofen (3a) exhibiting an IC50 of 0.11 μM for inhibition of 2-AG oxygenation. The crystal structure of desmethylflurbiprofen complexed to mCOX-2 demonstrated a similar binding mode to other profens. Desmethylflurbiprofen exhibited a half-life in mice comparable to that of ibuprofen. The data presented suggest that achiral profens can act as lead molecules toward in vivo probes of substrate-selective COX-2 inhibition.
NAPTHYLENE INHIBITORS OF CYCLOOXYGENASE
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Page/Page column 37, (2010/11/18)
The present invention relates to new napthylene inhibitors of cyclooxygenase activity, pharmaceutical compositions thereof, and methods of use thereof.
Synthesis and evaluation of some gastrointestinal sparing anti-inflammatory aminoethyl ester derivatives of naphthalene-based NSAIDs
Halen, Parmeshwari K.,Raval, Manisha K.,Chagti, Kewal K.,Giridhar, Rajani,Yadav, Mange R.
, p. 88 - 94 (2008/02/05)
To overcome the local gastric toxicity associated with use of, common non-steroidal anti-inflammatory drugs (NSAIDs), some aminoalcohol esters of NSAIDs bearing structural resemblance to the aminoalcohol ester class of anticholinergics were specially designed and synthesized. Besides blocking the acidic carboxyl group to overcome the local gastric irritation, the anticholinergic activity was incorporated with the expected advantage of reducing the gastric toxicity by decreasing gastric acid secretions and motility. Derivatives of naproxen and 6-methoxy-2-napthylacetic acid (6-MNA) were synthesized. The hydrolysis studies in buffers revealed the majority of the compounds to be sufficiently stable with a high enzymatic susceptibility in 80% human serum. Most of the derivatives exhibited a fairly good anticholinergic action against acetylcholine with a significant reduction in ulcerogenicity while retaining the anti-inflammatory potency of the parent drug. The combination of anti-inflammatory and anticholinergic activities, with a simultaneous reduction of the acidic character, may lead to development of therapeutically better compounds than the parent NSAIDs for long-term oral anti-inflammatory therapy.
Alkyl esters of 6-methoxy-2-naphthylacetic acid as potential prodrugs - Synthesis, physicochemical properties, chemical stability and enzymatic hydrolysis
Wadhwa, Lalit Kumar,Chandiran, Senthilkumar,Sharma, Pritam Dev
, p. 1292 - 1298 (2007/10/03)
Various alkyl esters of 6-methoxy-2-naphthylacetic acid (6-MNA), the active metabolite of nabumetone (1), have been synthesized with the objective of obtaining the prodrugs that would release the active drug only. To assess their prodrug potential, these esters are evaluated for solubility, partition coefficient and capacity factors. The correlation between the partition coefficients, capacity factors and ester chain lengths are established. The hydrolysis of these prodrugs has been studied at various temperatures and pseudo first order rate constants and half lives in aqueous buffer, human plasma and liver homogenate were determined. The hydrolysis of the representative methyl ester has been studied in various buffers of pH range 1.2 to 9. Second order rate constants for specific acid and specific base catalyzed hydrolysis and first order rate constant for spontaneous hydrolysis are determined. The esters show maximum stability between pH 4-5 and are easily cleavable in liver homogenate.
NAPHTHALENE AMIDES HAVING LEUKOTRIENE-ANTAGONISTIC ACTION
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, (2008/06/13)
Naphthalene amides of formula (I) wherein the substituent containing A is bound to the 6- or 7- position of the 2-naphthol system; the substituent containing B is bound to the benzene ring at any free position; R is hydrogen or methyl; R is hydrogen, fluorine, chlorine or -OCH3, which is bound to the naphthalene system at any positions except the 2- and the one occupied by the other substituent; R is hydrogen, fluorine, chlorine or bromine; A- is -CO-NR- or -NR-CO- group, wherein R is hydrogen or methyl; B is a 5-tetrazolyl or -COOR group, wherein R is hydrogen, a (C1-C4)-alkyl or a phenylalkyl group of less than 10 carbon atoms; m is 0 or 1; n and p are integers from 0 to 6, with the proviso that n + p is less or equal to 6; as well as the solvates and pharmaceutically acceptable salts thereof, have leukotriene antagonistic action.
A photophysical and photochemical study of 6-methoxy-2-naphthylacetic acid, the major metabolite of the phototoxic nonsteroidal antiinflammatory drug nabumetone
Bosca,Canudas,Marin,Miranda
, p. 173 - 177 (2007/10/03)
Nabumetone is a phototoxic nonsteroidal antiinflammatory drug used for the treatment of osteoarthritis. However, nabumetone is considered a prodrug with its metabolite 6-methoxy-2-naphthylacetic acid the active form. Photophysical and photochemical studies on this metabolite have been undertaken. It undergoes photodecarboxylation in aerated aqueous and organic solvents. In addition to the accepted photodegradation pathway for related molecules, a new mechanism that implies generation of the naphthalene radical cation from the excited singlet and addition of O2 prior to the decarboxylation process has been demonstrated. Evidence for the involvement of the excited singlet state in this mechanism have been obtained by steady-state and time-resolved fluorescence experiments. The fluorescence quenching by O2 and the shorter singlet lifetime in aerated solvents support this assignment. Laser flash photolysis also supports this mechanism by showing the noninvolvement of the triplet in the formation of the naphthalene radical cation. Finally, the well-known electron acceptor CCl4 acts as an efficient singlet quencher, enhancing the route leading to the radical cation, preventing intersystem crossing to the triplet and thus resulting in a dramatic increase in the yield of 6-methoxy-2-naphthaldehyde, the major oxidative decarboxylation product; this constitutes unambiguous proof in favor of the new mechanistic proposals.
