1373939-87-7Relevant academic research and scientific papers
Discovery of a Novel Potent and Selective Calcium Release-Activated Calcium Channel Inhibitor: 2,6-Difluoro- N-(2′-methyl-3′-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-[1,1′-biphenyl]-4-yl)benzamide. Structure-Activity Relationship and Preclinical Characterization
Ahirrao, Prajakta,Bakhle, Dhananjay,Bhankhede, Trupti,Bhonde, Mandar,Bokan, Sanjay,Budhe, Sagar,Dadke, Disha,Daler, Jagadeesh,Deshmukh, Gokul,George, Shaji K.,Gholve, Milind,Gundu, Jaysagar,Gupta, Rajesh,Ingawale, Sachin,Irlapatti, Nageswara Rao,Jachak, Santosh,Kalia, Anil,Kamalakannan, Prabakaran,Kamboj, Rajender Kumar,Kanoje, Vijay,Karche, Vijay,Khedkar, Nilesh Raghunath,Kizhakinagath, Praveenkumar Anidil,Kuldharan, Sandip,Kumar, Hemant,Kumar, Swaroop,Mallurwar, Sadanand,Mehta, Maneesh,Modi, Dipak,Naik, Kumar,Narasimham, Lakshmi,Nemade, Harshal Narendra,Nemmani, Kumar V. S.,Nigade, Prashant,Padiya, Kamlesh J.,Palle, Venkata P.,Pandey, Dilip,Pareek, Himani,Patil, Amit,Patil, Vinod,Pawar, Shashikant,Phukan, Samiron,Shah, Chirag,Shaikh, Zubair,Shankar, Rajesh,Sharma, Nidhi,Sharma, Sharad,Shinde, Vikas,Sindkhedkar, Milind,Singh, Minakshi,Sinha, Neelima,Tamane, Kaustubh,Venugopal, Spinvin,Vishwase, Gururaj,Wagh, Akshaya,Yeshodharan, Rajesh
, p. 17004 - 17030 (2021/12/09)
The role of calcium release-activated calcium (CRAC) channels is well characterized and is of particular importance in T-cell function. CRAC channels are involved in the pathogenesis of several autoimmune diseases, making it an attractive therapeutic target for treating inflammatory diseases, like rheumatoid arthritis (RA). A systematic structure-activity relationship study with the goal of optimizing lipophilicity successfully yielded two lead compounds, 36 and 37. Both compounds showed decent potency and selectivity and a remarkable pharmacokinetic profile. Further characterization in in vivo RA models and subsequent histopathological evaluation of tissues led to the identification of 36 as a clinical candidate. Compound 36 displayed an excellent safety profile and had a sufficient safety margin to qualify it for use in human testing. Oral administration of 36 in Phase 1 clinical study in healthy volunteers established favorable safety, tolerability, and good target engagement as measured by levels of IL-2 and TNF-α.
Synthesis of 4-Oxoisoxazoline N-Oxides via Pd-Catalyzed Cyclization of Propargylic Alcohols with tert-Butyl Nitrite
Feng, Kai-Wen,Ban, Yong-Liang,Yuan, Pan-Feng,Lei, Wen-Long,Liu, Qiang,Fang, Ran
, p. 3131 - 3135 (2019/05/10)
A cyclization of propargylic alcohols with tert-butyl nitrite at room temperature in air was achieved using Pd(OAc)2 as catalyst. The first reported 4-oxoisoxazoline N-oxides could be directly accessed from a range of multisubstituted propargylic alcohols in moderate to excellent yields under mild conditions. Density functional theory calculations indicated that the reaction proceeds through a palladium-catalyzed NO2 addition that efficiently generates a ketoxime radical, which eventually produces 4-oxoisoxazoline N-oxide.
OXAZOLE AND ISOXAZOLE CRAC MODULATORS
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Page/Page column 40-41, (2012/05/19)
The present invention relates to compounds of Formula (I) along with processes for their preparation that are useful for treating, preventing and/or managing the diseases, disorders, syndromes or conditions associated with the modulation of CRAC. The invention further relates to methods of treating, preventing managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of CRAC of Formula (I).
