Category: 1971920-73-6

Owens, Timothy D. published the artcilePhase 1 clinical trial evaluating safety, exposure and pharmacodynamics of BTK inhibitor tolebrutinib (PRN2246, SAR442168), Application of (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, the publication is Clinical and Translational Science (2022), 15(2), 442-450, database is CAplus and MEDLINE.

Bruton′s tyrosine kinase (BTK), expressed in B cells and cells of innate immunity, including microglia, is an essential signaling element downstream of the B-cell receptor and Fc-receptors. Tolebrutinib (PRN2246, SAR442168) is a potent BTK inhibitor that covalently binds the kinase, resulting in durable inhibition with the potential to target inflammation in the periphery and central nervous system (CNS). Tolebrutinib crosses the blood-brain barrier and potently inhibits BTK in microglial cells isolated from the CNS. A first-in-human randomized, double-blind, placebo-controlled study of tolebrutinib was conducted. The trial design consisted of five single ascending dose arms with oral administration of a single dose of 5, 15, 30, 60, and 120 mg (n = 6 per arm, n = 2 placebo), five multiple ascending dose arms with oral administration of 7.5, 15, 30, 60, and 90 mg (n = 8 per arm, n = 2 placebo) over 10 days, and one arm (n = 4) in which cerebral spinal fluid (CSF) exposure was measured 2 h after a single 120 mg dose. Tolebrutinib was well-tolerated in the study and all treatment-related treatment emergent adverse events were mild. Tolebrutinib was rapidly absorbed following oral administration with a rapid half-life of ∼ 2 h. Peripheral BTK occupancy was assessed at various timepoints by an ELISA-based readout using an irreversible probe. Assessments demonstrated extensive and prolonged peripheral BTK occupancy at steady-state with once daily doses as low as 7.5 mg. Further, CSF exposure was demonstrated 2 h after administration at 120 mg.

Clinical and Translational Science published new progress about 1971920-73-6. 1971920-73-6 belongs to piperidines, auxiliary class Other Aliphatic Heterocyclic,Piperidine,Alkenyl,Amine,Benzene,Ether,Inhibitor,Inhibitor, name is (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, and the molecular formula is C26H25N5O3, Application of (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Correale, Jorge published the artcileBruton’s tyrosine kinase inhibitors as potential therapies for multiple sclerosis, Computed Properties of 1971920-73-6, the publication is Lancet Neurology (2021), 20(9), 689-691, database is CAplus and MEDLINE.

A review. Over the past 30 years increasing numbers of mols. have been developed for treatment of multiple sclerosis. Bruton’s tyrosine kinase is a cytoplasmic tyrosine kinase expressed by B cells and myeloid cells. Both B cells and myeloid cells (particularly microglia) are important drivers of multiple sclerosis, suggesting that inhibitors of Bruton’s tyrosine kinase, such as the irreversible inhibitors evobrutinib, tolebrutininb, and orelabrutinib, and the reversible inhibitors fenebrutinib and BIIB091, might provide therapeutic benefits for patients. Bruton’s tyrosine kinase inhibitors could provide attractive therapeutic benefits for patients with multiple sclerosis, with potential advantages over monoclonal antibodies because they might be less likely to trigger antibody responses, allergic reactions,or neutralisation of their therapeutic actions. Addnl., these inhibitors, as small mols., might be able to access the CNS and inhibit microglial activation. However, whether Bruton’s tyrosine kinase inhibitors will be more efficacious than monoclonal antibodies remains to be established.

Lancet Neurology published new progress about 1971920-73-6. 1971920-73-6 belongs to piperidines, auxiliary class Other Aliphatic Heterocyclic,Piperidine,Alkenyl,Amine,Benzene,Ether,Inhibitor,Inhibitor, name is (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, and the molecular formula is C26H25N5O3, Computed Properties of 1971920-73-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Zheng, Jiamin published the artcileSmall molecule approaches to treat autoimmune and inflammatory diseases (Part I): Kinase inhibitors, Recommanded Product: (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, the publication is Bioorganic & Medicinal Chemistry Letters (2021), 127862, database is CAplus and MEDLINE.

Autoimmune and inflammatory diseases place a huge burden on the healthcare system. Small mol. (SM) therapeutics provide much needed complementary treatment options for these diseases. This digest series highlights the latest progress in the discovery and development of safe and efficacious SMs to treat autoimmune and inflammatory diseases with each part representing a class of SMs, namely: (1) protein kinases; (2) nucleic acid-sensing pathways; and (3) soluble ligands and receptors on cell surfaces. In this first part of the series, the focus is on kinase inhibitors that emerged between 2018 and 2020, and which exhibit increased target and tissue selectivity with the aim of increasing their therapeutic index.

Bioorganic & Medicinal Chemistry Letters published new progress about 1971920-73-6. 1971920-73-6 belongs to piperidines, auxiliary class Other Aliphatic Heterocyclic,Piperidine,Alkenyl,Amine,Benzene,Ether,Inhibitor,Inhibitor, name is (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, and the molecular formula is C22H38O2, Recommanded Product: (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Ringheim, Garth E. published the artcileBruton′s tyrosine kinase (BTK) inhibitors and autoimmune diseases: making sense of BTK inhibitor specificity profiles and recent clinical trial successes and failures, COA of Formula: C26H25N5O3, the publication is Frontiers in Immunology (2021), 662223, database is CAplus and MEDLINE.

Clin. development of BTK kinase inhibitors for treating autoimmune diseases has lagged behind development of these drugs for treating cancers, due in part from concerns over the lack of selectivity and associated toxicity profiles of first generation drug candidates when used in the long term treatment of immune mediated diseases. Second generation BTK inhibitors have made great strides in limiting off-target activities for distantly related kinases, though they have had variable success at limiting cross-reactivity within the more closely related TEC family of kinases. We investigated the BTK specificity and toxicity profiles, drug properties, disease associated signaling pathways, clin. indications, and trial successes and failures for the 13 BTK inhibitor drug candidates tested in phase 2 or higher clin. trials representing 7 autoimmune and 2 inflammatory immune-mediated diseases. We focused on rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic lupus erythematosus (SLE) where the majority of BTK nonclin. and clin. studies have been reported, with addnl. information for pemphigus vulgaris (PV), Sjogren′s disease (SJ), chronic spontaneous urticaria (CSU), graft vs. host disease (GVHD), and asthma included where available. While improved BTK selectivity vs. kinases outside the TEC family improved clin. toxicity profiles, less profile distinction was evident within the TEC family. Anal. of genetic associations of RA, MS, and SLE biomarkers with TEC family members revealed that BTK and TEC family members may not be drivers of disease. They are, however, mediators of signaling pathways associated with the pathophysiol. of autoimmune diseases. BTK in particular may be associated with B cell and myeloid differentiation as well as autoantibody development implicated in immune mediated diseases. Successes in the clinic for treating RA, MS, PV, ITP, and GVHD, but not for SLE and SJ support the concept that BTK plays an important role in mediating pathogenic processes amenable to therapeutic intervention, depending on the disease. Based on the data collected in this study, we propose that current compound characteristics of BTK inhibitor drug candidates for the treatment of autoimmune diseases have achieved the selectivity, safety, and coverage requirements necessary to deliver therapeutic benefit.

Frontiers in Immunology published new progress about 1971920-73-6. 1971920-73-6 belongs to piperidines, auxiliary class Other Aliphatic Heterocyclic,Piperidine,Alkenyl,Amine,Benzene,Ether,Inhibitor,Inhibitor, name is (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, and the molecular formula is C26H25N5O3, COA of Formula: C26H25N5O3.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem