sb-1518 and Arthritis--Rheumatoid

sb-1518 has been researched along with Arthritis--Rheumatoid* in 1 studies

Other Studies

1 other study(ies) available for sb-1518 and Arthritis--Rheumatoid

Article	Year
Discovery of the macrocycle (9E)-15-(2-(pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a potent inhibitor of janus kinase 2/fms-like tyrosine kinase-3 (JAK Journal of medicinal chemistry, 2012, Mar-22, Volume: 55, Issue:6 Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization of a key aryl ring of the previously described SB1518 (pacritinib), the highly soluble 14l was selected as the optimal compound. Oral efficacy in the murine collagen-induced arthritis (CIA) model for rheumatoid arthritis (RA) supported 14l as a potential treatment for autoimmune diseases and inflammatory disorders such as psoriasis and RA. Compound 14l (SB1578) was progressed into development and is currently undergoing phase 1 clinical trials in healthy volunteers. Topics: Animals; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Line; Cell Membrane Permeability; Collagen Type II; Dogs; Female; fms-Like Tyrosine Kinase 3; Heterocyclic Compounds, 4 or More Rings; Humans; Janus Kinase 2; Macaca mulatta; Male; Mice; Mice, Nude; Microsomes; Models, Molecular; Rats; Signal Transduction; Solubility; Stereoisomerism; Structure-Activity Relationship; TYK2 Kinase	2012

Article

Year

Discovery of the macrocycle (9E)-15-(2-(pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a potent inhibitor of janus kinase 2/fms-like tyrosine kinase-3 (JAK

Journal of medicinal chemistry, 2012, Mar-22, Volume: 55, Issue:6

Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization of a key aryl ring of the previously described SB1518 (pacritinib), the highly soluble 14l was selected as the optimal compound. Oral efficacy in the murine collagen-induced arthritis (CIA) model for rheumatoid arthritis (RA) supported 14l as a potential treatment for autoimmune diseases and inflammatory disorders such as psoriasis and RA. Compound 14l (SB1578) was progressed into development and is currently undergoing phase 1 clinical trials in healthy volunteers.

Topics: Animals; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Line; Cell Membrane Permeability; Collagen Type II; Dogs; Female; fms-Like Tyrosine Kinase 3; Heterocyclic Compounds, 4 or More Rings; Humans; Janus Kinase 2; Macaca mulatta; Male; Mice; Mice, Nude; Microsomes; Models, Molecular; Rats; Signal Transduction; Solubility; Stereoisomerism; Structure-Activity Relationship; TYK2 Kinase

2012