59512-16-2Relevant articles and documents
Hydration of Aliphatic Nitriles Catalyzed by an Osmium Polyhydride: Evidence for an Alternative Mechanism
Babón, Juan C.,Esteruelas, Miguel A.,López, Ana M.,O?ate, Enrique
, p. 7284 - 7296 (2021/05/29)
The hexahydride OsH6(PiPr3)2 competently catalyzes the hydration of aliphatic nitriles to amides. The main metal species under the catalytic conditions are the trihydride osmium(IV) amidate derivatives OsH3{κ2-N,O-[HNC(O)R]}(PiPr3)2, which have been isolated and fully characterized for R = iPr and tBu. The rate of hydration is proportional to the concentrations of the catalyst precursor, nitrile, and water. When these experimental findings and density functional theory calculations are combined, the mechanism of catalysis has been established. Complexes OsH3{κ2-N,O-[HNC(O)R]}(PiPr3)2 dissociate the carbonyl group of the chelate to afford κ1-N-amidate derivatives, which coordinate the nitrile. The subsequent attack of an external water molecule to both the C(sp) atom of the nitrile and the N atom of the amidate affords the amide and regenerates the κ1-N-amidate catalysts. The attack is concerted and takes place through a cyclic six-membered transition state, which involves Cnitrile···O-H···Namidate interactions. Before the attack, the free carbonyl group of the κ1-N-amidate ligand fixes the water molecule in the vicinity of the C(sp) atom of the nitrile.
NO-NSAIDs. Part 3: Nitric oxide-releasing prodrugs of non-steroidal anti-inflammatory drugs
Borhade, Namdev,Pathan, Asif Rahimkhan,Halder, Somnath,Karwa, Manoj,Dhiman, Mini,Pamidiboina, Venu,Gund, Machhindra,Deshattiwar, Jagannath Janardhan,Mali, Sunil Vasantrao,Deshmukh, Nitin Janardanrao,Senthilkumar, Subrayan Palanisamy,Gaikwad, Parikshit,Tipparam, Santhosh Goud,Mudgal, Jayesh,Dutta, Milan Chandra,Burhan, Aslam Usmangani,Thakre, Gajanan,Sharma, Ankur,Deshpande, Shubhada,Desai, Dattatraya Chandrakant,Dubash, Nauzer Pervez,Jain, Arun Kumar,Sharma, Somesh,Nemmani, Kumar Venkata Subrahmanya,Satyam, Apparao
experimental part, p. 465 - 481 (2012/05/31)
In continuation of our efforts to discover novel nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) as potentially "Safe NSAIDs," we report herein the design, synthesis and evaluation of 21 new NO-NSAIDs of commonly used NSAIDs such as aspirin, diclofenac, naproxen, flurbiprofen, ketoprofen, sulindac, ibuprofen and indomethacin. These prodrugs have NO-releasing disulfide linker attached to a parent NSAID via linkages such as an ester (compounds 9-16), a double ester (compounds 17-24), an imide (compounds 25-30) or an amide (compounds 31-33). Among these NO-NSAIDs, the ester-containing NO-aspirin (9), NO-diclofenac (10), NO-naproxen (11), and the imide-containing NO-aspirin (25), NO-flurbiprofen (27) and NO-ketoprofen (28) have shown promising oral absorption, anti-inflammatory activity and NO-releasing property, and also protected rats from NSAID-induced gastric damage. NO-aspirin compound 25, on further co-evaluation with aspirin at equimolar doses, exhibited comparable dose-dependent pharmacokinetics, inhibition of gastric mucosal prostaglandin E2 (PGE2) synthesis and analgesic properties to those of aspirin, but retained its gastric-sparing properties even after doubling its oral dose. These promising NO-NSAIDs could therefore represent a new class of potentially "Safe NSAIDs" for the treatment of arthritic pain and inflammation.
HETEROAROMATIC RING COMPOUNDS
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, (2008/06/13)
Heteroaromatic ring compounds or pharmaceutically acceptable salts thereof, which have excellent characteristics and have strong curative effects to immuno-imbalance and choronic inflammation. Representative is the compound of the formula:
