282728-65-8 Usage
Biological Activity
indomethacin n-octyl amide is a potent and non-selective inhibitor of both cox-1 and cox-2 [1].cyclooxygenase (cox) is the key enzyme required for the conversion of arachidonic acid to prostaglandins. cyclooxygenase enzymes have been involved in diverse physiological situations and disease processes ranging from inflammation to cancer. until now, two cyclooxygenase isoforms have been identified, cox-1 and cox-2. the cox-1 enzyme is produced constitutively (i.e., gastric mucosa) and cox-2 is inducible (i.e., sites of inflammation) [2].indomethacin is a potent but non-selective inhibitor of both cox-1 and cox-2. indomethacin is a substituted indole acetic acid, wherein the carboxylate can be derivitized as an ester or amide. conversion of indomethacin into ester and amide derivatives provides a facile strategy for generating highly selective cox-2 inhibitors. indomethacin n-octyl amide inhibited the activity of ovine cox-1 and human recombinant cox-2 with the ic50 values of 66 μm and 40 nm, respectively. while the ic50 of indomethacin for the inhibition of cox-1 and cox-2 were 0.67 μm and 0.05 μm, respectively [1].
references
[1] kalgutkar a s, marnett a b, crews b c, et al. ester and amide derivatives of the nonsteroidal antiinflammatory drug, indomethacin, as selective cyclooxygenase-2 inhibitors[j]. journal of medicinal chemistry, 2000, 43(15): 2860-2870.[2] dubois r n, abramson s b, crofford l, et al. cyclooxygenase in biology and disease[j]. the faseb journal, 1998, 12(12): 1063-1073.
Check Digit Verification of cas no
The CAS Registry Mumber 282728-65-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,8,2,7,2 and 8 respectively; the second part has 2 digits, 6 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 282728-65:
(8*2)+(7*8)+(6*2)+(5*7)+(4*2)+(3*8)+(2*6)+(1*5)=168
168 % 10 = 8
So 282728-65-8 is a valid CAS Registry Number.
282728-65-8Relevant articles and documents
Ester and amide derivatives of the nonsteroidal antiinflammatory drug, indomethacin, as selective cyclooxygenase-2 inhibitors
Kalgutkar, Amit S.,Marnett, Alan B.,Crews, Brenda C.,Remmel, Rory P.,Marnett, Lawrence J.
, p. 2860 - 2870 (2007/10/03)
Recent studies from our laboratory have shown that derivatization of the carboxylate moiety in substrate analogue inhibitors, such as 5,8,11,14- eicosatetraynoic acid, and in nonsteroidal antiinflammatory drugs (NSAIDs), such as indomethacin and meclofenamic acid, results in the generation of potent and selective cyclooxygenase-2 (COX-2) inhibitors (Kalgutkar et al. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 925-930). This paper summarizes details of the structure-activity studies involved in the transformation of the arylacetic acid NSAID, indomethacin, into a COX-2-selective inhibitor. Many of the structurally diverse indomethacin esters and amides inhibited purified human COX-2 with IC50 values in the low-nanomolar range but did not inhibit ovine COX-1 activity at concentrations as high as 66 μM. Primary and secondary amide analogues of indomethacin were more potent as COX-2 inhibitors than the corresponding tertiary amides. Replacement of the 4- chlorobenzoyl group in indomethacin esters or amides with the 4-bromobenzyl functionality or hydrogen afforded inactive compounds. Likewise, exchanging the 2-methyl group on the indole ring in the ester and amide series with a hydrogen also generated inactive compounds. Inhibition kinetics revealed that indomethacin amides behave as slow, tight-binding inhibitors of COX-2 and that selectivity is a function of the time-dependent step. Conversion of indomethacin into ester and amide derivatives provides a facile strategy for generating highly selective COX-2 inhibitors and eliminating the gastrointestinal side effects of the parent compound.