64614-49-9Relevant academic research and scientific papers
Structure-based drug design of RN486, a potent and selective Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis
Lou, Yan,Han, Xiaochun,Kuglstatter, Andreas,Kondru, Rama K.,Sweeney, Zachary K.,Soth, Michael,McIntosh, Joel,Litman, Renee,Suh, Judy,Kocer, Buelent,Davis, Dana,Park, Jaehyeon,Frauchiger, Sandra,Dewdney, Nolan,Zecic, Hasim,Taygerly, Joshua P.,Sarma, Keshab,Hong, Junbae,Hill, Ronald J.,Gabriel, Tobias,Goldstein, David M.,Owens, Timothy D.
supporting information, p. 512 - 516 (2015/03/03)
Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) (J. Pharmacol. Exp. Ther. 2012, 341, 90), which was selected for advanced preclinical characterization based on its favorable properties.
Development of a scalable synthesis of a Bruton's tyrosine kinase inhibitor via C-N and C-C bond couplings as an end game strategy
Hong, Jun Bae,Davidson, James P.,Jin, Qingwu,Lee, Gary R.,Matchett, Michael,O'Brien, Erin,Welch, Michael,Bingenheimer, Bill,Sarma, Keshab
, p. 228 - 238 (2014/05/20)
A scalable and convergent synthesis of a BTK (Bruton's tyrosine kinase) inhibitor has been developed. Synthetic routes to key intermediates were explored for the scale-up campaign, especially the process for 6-dimethylaminodihydroisoquinolinone, which was prepared via a regioselective cyclization of an isocyanate, mediated by AlCl3. Improved routes to key building blocks were demonstrated by expedient multikilogram productions. The target compound was assembled through a Pd-catalyzed amidation reaction followed by a Suzuki-Miyaura cross-coupling reaction.
BTK protein kinase inhibitors
-
Page/Page column 58, (2009/05/29)
This application discloses pyridine and pyrimidine compounds according to formula I wherein R1, R2, R3, R4, R5, X1 and A are as described herein which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of formula I and at least one carrier, diluent or excipient.
NOVEL IMIDAZO[1,2-A]PYRIDINE AND IMIDAZO[1,2-B]PYRIDAZINE DERIVATIVES
-
Page/Page column 88, (2009/07/18)
Imidazo[1,2-a]pyridine and imidazo[1,2-b]pyridazine derivatives which inhibit Btk and are useful for the treatment of auto-immune and inflammatory diseases caused by aberrant B-cell activation, e.g. arthritis.
A new class of potent non-imidazole H3 antagonists: 2-Aminoethylbenzofurans
Cowart, Marlon,Pratt, John K.,Stewart, Andrew O.,Bennani, Youssef L.,Esbenshade, Timothy A.,Hancock, Arthur A.
, p. 689 - 693 (2007/10/03)
2-Aminoethylbenzofurans constitute a new class of H3 antagonists that are more rotationally constrained than most previously reported H3 antagonists. They retain high potency at human and rat receptors, with efficient CNS penetration observed in 35. The SAR of the basic amine moiety was compared in three different series of analogues. The greatest potency was found in analogues bearing a 2-methylpyrrolidine, a 2,5-dimethylpyrrolidine, or a 2,6-dimethylpiperidine.
BENZO ‘ D!AZEPINE DERIVATIVES FOR THE TREATMENT OF NEUROLOGICAL DISORDERS
-
Page/Page column 18, (2010/02/07)
The present invention relates to benzazepine derivatives of formula ( I ) wherein: R1 represents -C3-7 cycloalkyl optionally substituted by C1-3 alkyl; having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.
Novel amines as histamine-3 receptor ligands and their therapeutic applications
-
, (2008/06/13)
Compounds of formula (I) or a pharmaceutically acceptable salts or prodrug thereof which are useful for the modulation of the histamine-3 receptors in mammals and which are useful for the treatment of disorders ameliorated by histamine-3 receptor ligands.
Novel amines as histamine-3 receptor ligands and their therapeutic applications
-
, (2008/06/13)
Compounds of formula (I) or a pharmaceutically acceptable salts or prodrug thereof which are useful for the modulation of the histamine-3 receptors in mammals and which are useful for the treatment of disorders ameliorated by histamine-3 receptor ligands.
