PF-06751979

InvivoChem Cat #:V4442CAS #:1818339-66-0 (free base)Purity >=98%

Description: PF-06751979 is a novel, highly potent, brain penetrant, and selective inhibitor of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) with an IC50 of 7.3 nM in BACE1 binding assay. PF-06751979 displays excellent brain penetration, potent in vivo efficacy, and broad selectivity over related aspartyl proteases including BACE2. Chronic dosing of 64 for up to 9 months in dog did not reveal any observation of hair coat color (pigmentation) changes and suggests a key differentiator over current BACE1 inhibitors that are nonselective against BACE2 in later stage clinical development. A major challenge in the development of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors for the treatment of Alzheimer's disease is the alignment of potency, drug-like properties, and selectivity over related aspartyl proteases such as Cathepsin D (CatD) and BACE2. The potential liabilities of inhibiting BACE2 chronically have only recently begun to emerge as BACE2 impacts the processing of the premelanosome protein (PMEL17) and disrupts melanosome morphology resulting in a depigmentation phenotype. Herein, we describe the identification of clinical candidate

References: J Med Chem. 2018 May 24; 61(10):4476-4504

Related CAS: 1818339-67-1 (HCl)

-20C for 3 years in powder form

Synonym: PF-06751979; PF 06751979; PF06751979
IUPAC/Chemical Name: N-(2-((4aR, 6S, 8aR)-2-amino-6-methyl-4, 4a, 5, 6-tetrahydropyrano[3, 4-d][1, 3]thiazin-8a(8H)-yl)thiazol-4-yl)-5-(difluoromethoxy)picolinamide
InChi Key: ZLZUHACSRMOLLV-RAALSFIWSA-N
InChi Code: InChI=1S/C18H19F2N5O3S2/c1-9-4-10-6-30-17(21)25-18(10, 8-27-9)15-24-13(7-29-15)23-14(26)12-3-2-11(5-22-12)28-16(19)20/h2-3, 5, 7, 9-10, 16H, 4, 6, 8H2, 1H3, (H2, 21, 25)(H, 23, 26)/t9-, 10-, 18-/m0/s1
SMILES Code: [H][C]12[C](CO[CH](C)C2)(C3=NC(NC(C4=NC=C(OC(F)F)C=C4)=O)=CS3)N=C(N)SC1