- Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
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The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.
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Page/Page column 123; 124
(2016/06/28)
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- Synthesis, biological evaluation, and 3D QSAR study of 2-methyl-4-oxo-3-oxetanylcarbamic acid esters as N -acylethanolamine acid amidase (NAAA) inhibitors
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N-(2-Oxo-3-oxetanyl)carbamic acid esters have recently been reported to be noncompetitive inhibitors of the N-acylethanolamine acid amidase (NAAA) potentially useful for the treatment of pain and inflammation. In the present study, we further explored the
- Ponzano, Stefano,Berteotti, Anna,Petracca, Rita,Vitale, Romina,Mengatto, Luisa,Bandiera, Tiziano,Cavalli, Andrea,Piomelli, Daniele,Bertozzi, Fabio,Bottegoni, Giovanni
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supporting information
p. 10101 - 10111
(2015/02/02)
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- DISUBSTITUTED BETA-LACTONES AS INHIBITORS OF N-ACYLETHANOLAMINE ACID AMIDASE (NAAA)
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The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.
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Paragraph 0357
(2013/06/06)
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- Preparation and characterization of poly[2,3-dimethyl-1-(4-thien-3-ylbenzyl)-1H-imidazol-3-ium] bis((trifluoromethyl)sulfonyl)imide
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A new 3-fluorophenylthiophene derivative bearing a cationic imidazolium group in the para position of the phenyl ring was synthesized by a multistep procedure which involves, in a key step, the reaction of 3-[4-(bromomethyl)phenyl]thiophene with 1,2-dimet
- Naudin, Eric,Ho, Hoang Anh,Bonin, Marc-Andre,Breau, Livain,Belanger, Daniel
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p. 4983 - 4987
(2007/10/03)
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- Inhibitors of farnesyl-protein transferase
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The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invent
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- Inhibitors of acyl-coA:cholesterol O-acyltransferase. 2. Identification and structure-activity relationships of a novel series of N-alkyl-N- (heteroaryl-substituted benzyl)-N'-arylureas
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A series of N-alkyl-N-(heteroaryl-substituted benzyl)-N'-arylurea and related derivatives represented by 2 and 3 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Among these novel compounds, the type 3 series was superior. A pyrazol-3-yl group on the N-benzyl group of this trisubstituted urea (i.e. 3, Ar1 = pyrazol-3- yl) was identified as a heteroaromatic ring providing a good profile of biological activity. As a result of optimization of the combination with the N-alkyl group (R) and N-aryl group (At3), compound 3aq (FR186054) was identified as a new, orally efficacious ACAT inhibitor, which exhibited potent in vitro ACAT inhibitory activity (rabbit intestinal microsomes IC50 = 99 nM) and excellent hypocholesterolemic effects in cholesterol-fed rats, irrespective of administration mode (ED50 = 0.046 mg/kg dosed via the diet, ED50 = 0.44 mg/kg administered by gavage in PEG400 vehicle). Moreover, a toxicological study revealed compound 3aq to be nontoxic to the adrenal glands of dogs when tested at a single dose of 10 mg/kg po.
- Tanaka, Akira,Terasawa, Takeshi,Hagihara, Hiroyuki,Sakuma, Yuri,Ishibe, Noriko,Sawada, Masae,Takasugi, Hisashi,Tanaka, Hirokazu
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p. 2390 - 2410
(2007/10/03)
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- Synthesis and &β-adrenoceptor blocking activity of some aryloxy- and benzyloxy-propanolamines
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4-(3-Thienyl)phenoxypropanolamines 9a-n and 4-(3-thienyl)benzyloxypropanolamines 10a-n have been synthesised starting from 3-(p-tolyl)thiophene (1) and 3-(4-methoxyphenyl)thiophene (2).Compound 1 on treatment with N-bromosuccinimide in refluxing CCl4 using dibenzoylperoxide or 2,2'-azobis(2-methylpropionitrile) as a catalyst gives 4-(3-thienyl)benzyl bromide (4) which on refluxing with AcOK/AcOH yields 4-(3-thienyl)benzyl acetate (5).The acetate 5 on hydrolysis furnishes 4-(3-thienyl)benzyl alcohol (6).Further, 3,4-(methoxyphenyl)thiophene (2) on demethylation yields 4-(3-thienyl)phenol (3).The phenol (3) and alcohol 6 on treatment with epichlorohydrin undergo alkylation to give 2,3-epoxy-4-(3-thienyl)phenoxypropane (7) and 2,3-epoxy-4-(3-thienyl)benzyloxypropane (8) respectively which on condensation with various amines in refluxing ethanol furnish 4-(3-thienyl)phenoxypropanolamines (9) and 4-(3-thienyl)benzyloxypropanolamines (10) respectively.Compounds 9 and 10 have been evaluated for their β-adrenergic blocking activity and a few of them shown moderate β-adrenergic blocking activity.
- Marwah, A. K.,Marwah, Padma,Rao, G. Shankar,Trivedi, B. S.,Rao, B. E.,et al.
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p. 197 - 200
(2007/10/02)
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