4-Substituted Cubylcarbinylamines:  A New Class of Mechanism-Based Monoamine Oxidase B Inactivators

Abstract

Cubylcarbinylamine (1a), (4-cyclopropylcubyl)carbinylamine (1b), and (4-phenylcubyl)carbinylamine (1c) were synthesized and shown to be time-dependent, irreversible inactivators of monoamine oxidase B (MAO B). Substrate protects the enzyme from inactivation, but beta-mercaptoethanol does not, suggesting that these compounds are mechanism-based inactivators. All three compounds were also substrates for MAO B with partition ratios ranging from 152 to 536. The 4-substituted analogues were more potent inactivators than the unsubstituted analogue, indicating a benefit to 4-substitution in this class of inactivators.

New oxapolycyclic cage amines with NMDA receptor antagonist and trypanocidal activities

“…1). 12 Moreover, heteroatom substituted polycyclic cage amines are an interesting and highly promising group of compounds that are receiving intense scrutiny as potential scaffolds for the development of new drugs. For example, a series of oxapentacycloundecylamines, such as NGP1-01 and related compounds, has showed neuroprotective properties through NMDA receptor 0968-0896/$ -see front matter Ó 2009 Elsevier Ltd. All rights reserved.…”

Synthesis of 4-bromocubane-1-carbaldehyde

“…139-140 °C. 1 Synthesis of 4 bromocubane 1 carbaldehyde (2) by the reduction of methyl 4 bromocubane 1 carboxylate (6b) with bis(N methylpiperazinyl)aluminum hydride (7). A solution of es ter 6b (243 mg, 1.01 mmol) in anhydrous THF (15 mL) was added dropwise for 5 min to a stirred (and cooled on an ice bath) solution of hydride 7 (664 mg, 2.8 mmol) in THF (10 mL).…”

Three-Membered-Ring-Based Molecular Architectures

“…Protonation of the latter afforded cyclopropylcubane 947, a stable material under ordinary conditions, in 63% yield after purification by preparative gas chromatography, 599 while reaction of 946 with carbon dioxide gave the corresponding acid 948 in essentially the same yield (62%) (Scheme 157). 600 Both transformations of 944 to 947 and to 948 could be performed in single-pot operations. The acid 948 was used for the preparation of [(4-cyclopropylcubyl)methyl]lamine, which was shown to be a time-dependent, irreversible inhibitor of monoamine oxidase B.…”

“…The acid 948 was used for the preparation of [(4-cyclopropylcubyl)methyl]lamine, which was shown to be a time-dependent, irreversible inhibitor of monoamine oxidase B. 600 It is obvious that the introduction of multiple cyclopropyl substituents by such methods will be difficult or at best proceed with very low yields. It ought to be more efficient to transform appropriate functional substituents preexisting on the skeleton into cyclopropyl moieties.…”