874959-68-9Relevant articles and documents
N-LINKED GLYCOSYLATION INHIBITORS AND METHODS OF USING SAME
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, (2022/03/22)
The present disclosure includes compounds, compositions, and methods for preventing or treating diseases associated with N-linked glycosylation and/or oligosaccharyltransferase function in a subject in need thereof. The methods comprise administering to the subject an effective amount of at least one compound and/or pharmaceutical composition of the disclosure.
INHIBITOR COMPOUNDS
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, (2021/01/29)
The disclosure relates to heterocyclic compounds and methods for their preparation. The disclosure provides compounds that may have beneficial therapeutic activity in the treatment of a disease or condition mediated by excessive or otherwise undesirable Des1 and/or fibrotic activity.
Selective IKur Inhibitors for the Potential Treatment of Atrial Fibrillation: Optimization of the Phenyl Quinazoline Series Leading to Clinical Candidate 5-[5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide
Gunaga, Prashantha,Lloyd, John,Mummadi, Somanadham,Banerjee, Abhisek,Dhondi, Naveen Kumar,Hennan, James,Subray, Veena,Jayaram, Ramya,Rajugowda, Nagendra,Umamaheshwar Reddy, Kommuri,Kumaraguru, Duraimurugan,Mandal, Umasankar,Beldona, Dasthagiri,Adisechen, Ashok Kumar,Yadav, Navnath,Warrier, Jayakumar,Johnson, James A.,Sale, Harinath,Putlur, Siva Prasad,Saxena, Ajay,Chimalakonda, Anjaneya,Mandlekar, Sandhya,Conder, MaryLee,Xing, Dezhi,Gupta, Arun Kumar,Gupta, Anuradha,Rampulla, Richard,Mathur, Arvind,Levesque, Paul,Wexler, Ruth R.,Finlay, Heather J.
, p. 3795 - 3803 (2017/05/19)
We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine 1 as a potent IKur current blocker with selectivity versus hERG, Na and Ca channels, and an acceptable preclinical PK profile. Upon further characterization in vivo, compound 1 demonstrated an unacceptable level of brain penetration. In an effort to reduce the level of brain penetration while maintaining the overall profile, SAR was developed at the C2′ position for a series of close analogues by employing hydrogen bond donors. As a result, 5-[5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide (25) was identified as the lead compound in this series. Compound 25 showed robust effects in rabbit and canine pharmacodynamic models and an acceptable cross-species pharmacokinetic profile and was advanced as the clinical candidate. Further optimization of 25 to mitigate pH-dependent absorption resulted in identification of the corresponding phosphoramide prodrug (29) with an improved solubility and pharmacokinetic profile.