Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• derivatives as potent anti-Alzheimer agents (171, 172) by a Buchwald coupling of the corresponding C3-substituted amines 170 and indole 5/6-bromides 169 (Scheme 23) [113]. Cyano, 4-piperidinyl and N-methylpiperidinyl substitutions at the indole and 7-azaindoles were necessary to improve the brain penetration

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• 1 (or 17) which combines Notum inhibition with CNS penetration would be a valuable chemical probe for investigating the role of Notum in disease models. Keywords: brain penetration; 1-chloro-1,2-benziodoxol-3-one; electrophilic chlorination; LP-922056; Notum inhibitor; Introduction The Wnt

• contains an essential carboxylic acid and acids tend to have low passive brain penetration [8][9][10][11][12]. We are investigating the role of Notum in modulating Wnt signalling in the central nervous system (CNS) [13] and wished to establish if 1 would serve as a peripherally restricted control compound

• ; cpKa 3.1). Pharmacokinetic (PK) data for 1 was generated in vivo in mouse to evaluate brain penetration (Table 1; Figure 2) (see Supporting Information File 1, Tables S1–S3). The route of administration and dose were selected to most closely match relevant published mouse disease model studies [5][7

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• . Two arm lengths of two or three carbons were envisioned, on the C2 for the myo-series and on the C1 for the scyllo-series, ending with a hydroxy group or a fluorine atom. Indeed the addition of fluorine could improve chemical properties including lipophilicity, brain penetration, enhanced binding

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• chalcone and flavone derivatives, [Re]- and [99mTc]-labeled aurone complexes 33a and 33b were also prepared [18]. The high affinity for Aβ aggregates observed with the [99mTc]-labeled aurone 33b was hampered by its weak brain penetration, which made it unsuitable for in vivo application [18]. Stilbene and

• . While 57 was able to label amyloid deposits in APP/PS1 mice, its brain penetration was not as high as that of [11C]56c. Besides [11C], other radiolabels have been investigated for benzothiazole imaging agents. Two of the earliest [125I]-labeled imaging agents reported were [125I]TZDM (58a) and [125I