60462-14-8

Upstream product

• 53578-15-7 cubane-1-carboxylic acid 
• 60462-18-2 4-methoxycarbonylcubane-1-carbonyl chloride 
• 29412-63-3 monocarbomethoxycubane 

Downstream Products

• 59346-69-9 bromocubane 
• 74725-77-2 Iodocubane 
• 119696-06-9 1-cubanecarboxamide 
• 80606-52-6 (cubyl)(methyl)methanone 
• 150234-60-9 pentacyclo[4.2.0.0^2,5.0^3,8.0^4,7]octane-1-methanamine 

Relevant academic research and scientific papers

SYNTHESIS OF IODOCUBANES BY DECARBOXYLATIVE IODINATION

An efficient method is described for the preparation of iodocubanes from the corresponding carboxylic acids utilizing thiohydroxamic ester methodology with 2,2,2-trifluoroiodoethane as the iodide source.

Synthesis and chemistry of 1,3,5,7-tetranitrocubane including measurement of its acidity, formation of o-nitro anions, and the first preparations of pentanitrocubane and hexanitrocubane

Nitro groups on alternate corners of cubane enhance the acidity of cubyl hydrogen (pK(a) ~21) and provide sufficient activation for ready anion formation. The sodium salt of 1,3,5,7-tetranitrocubane reacts easily with electrophiles and leads thereby to yet more highly substituted cubanes, like carbomethoxy- and (trimethylsilyl)tetranitrocubane. Anions from these species are also easily formed and are useful for further substitution on the cubane nucleus. Dinitrogen tetraoxide reacts with the anion of tetranitrocubane to give 1,2,3,5,7-pentanitrocubane, the first cubane to contain vicinal nitro groups. The reaction probably involves oxidation of the anion to the corresponding radical. Similarly, the anion of pentanitrocubane is used to prepare 1,2,3,4,5,7-hexanitrocubane, the most highly nitrated cubane made to date. Single-crystal X-ray structural information is given for both penta- and hexanitrocubane.

Cyclooctatetraenes through Valence Isomerization of Cubanes: Scope and Limitations

The scope and limitations of Eaton's rhodium(I)-catalyzed valence isomerization of cubane to cyclooctatetraene (COT) were investigated in the context of functional group tolerability, multiple substitution modes and the ability of cubane-alcohols to undergo one-pot tandem Ley–Griffith Wittig reactions in the absence of a transition metal catalyst.

Cyclooctatetraene: A Bioactive Cubane Paradigm Complement

Cubane was recently validated as a phenyl ring (bio)isostere, but highly strained caged carbocyclic systems lack π character, which is often critical for mediating key biological interactions. This electronic property restriction associated with cubane has been addressed herein with cyclooctatetraene (COT), using known pharmaceutical and agrochemical compounds as templates. COT either outperformed or matched cubane in multiple cases suggesting that versatile complementarity exists between the two systems for enhanced bioactive molecule discovery.

Enantioselective synthesis of (: R)-2-cubylglycine including unprecedented rhodium mediated C-H insertion of cubane

The first enantioselective synthesis of (R)-2-cubylglycine, an analogue of (R)-2-phenylglycine in which the phenyl ring has been replaced by cubane, is disclosed. The key step was a telescoped Strecker reaction using (S)-2-amino-2-phenylethanol as a chiral auxiliary. Exploration of an alternative synthetic approach resulted in unprecedented cubane C-H insertion.

Thermal and Sensitiveness Determination of Cubanes: Towards Cubane-Based Fuels for Infrared Countermeasures

As infrared seeking technology evolves, threats are better able to distinguish defensive infrared (IR) flares from true targets. Spectrally matched flares, which generally employ carbon-based fuels, are better able to decoy some advanced missiles by more closely mimicking the IR emission of the target. Cubane is a high-energy carbon-based scaffold which may be suitable for use as a fuel in spectrally matched flares. The enthalpy of formation and strain energy of a series of cubanes was predicted in silico, and their thermal and impact stability examined. All were found to undergo highly exothermic decomposition in sealed cell differential scanning calorimetry, and two cubanes subsequently underwent quantitative sensitiveness testing. Despite their F of I values being in the secondary explosive range, cubane-1,4-dicarboxylic acid (F of I=70) and 4-carbamoylcubane-1-carboxylic acid (F of I=90) were identified as potentially useful fuels for pyrotechnic infrared countermeasure flare formulations.

The cubane paradigm in bioactive molecule discovery: Further scope, limitations and the cyclooctatetraene complement

The cubane phenyl ring bioisostere paradigm was further explored in an extensive study covering a wide range of pharmaceutical and agrochemical templates, which included antibiotics (cefaclor, penicillin G) and antihistamine (diphenhydramine), a smooth muscle relaxant (alverine), an anaesthetic (ketamine), an agrochemical instecticide (triflumuron), an antiparasitic (benznidazole) and an anticancer agent (tamibarotene). This investigation highlights the scope and limitations of incorporating cubane into bioactive molecule discovery, both in terms of synthetic compatibility and physical property matching. Cubane maintained bioisosterism in the case of the Chagas disease antiparasitic benznidazole, although it was less active in the case of the anticancer agent (tamibarotenne). Application of the cyclooctatetraene (COT) (bio)motif complement was found to optimize benznidazole relative to the benzene parent, and augmented anticancer activity relative to the cubane analogue in the case of tamibarotene. Like all bioisosteres, scaffolds and biomotifs, however, there are limitations (e.g. synthetic implementation), and these have been specifically highlighted herein using failed examples. A summary of all templates prepared to date by our group that were biologically evaluated strongly supports the concept that cubane is a valuable tool in bioactive molecule discovery and COT is a viable complement.

POLYCYCLIC MOLECULAR COMPOUNDS

This invention relates to compounds of Formula (I), wherein A is a carboaromatic or heteroaromatic ring having one or more substituents; R6 Formula (A) is optionally substituted with one or more substituents; and n is 0, 1 or an integer greater than 1 and when n is 1 or greater the bond or bonds between the carbon atoms may be saturated or unsaturated, which bind the P2X7 receptor with high affinity. This invention also relates to methods for the diagnosis, treatment or monitoring of disorders in which the P2X7 receptor is implicated, in particular the diagnosis, treatment or monitoring of (the progression of) neuroinflammatory and neurodegenerative disorders in a subject.

Cubyl amides: Novel P2X7 receptor antagonists

Polycyclic amides 2 and 5-9 were successfully synthesised and their lipophilicity profiles were evaluated using reverse-phase HPLC. All synthesised compounds possessed P2X7R antagonistic properties when tested on rat spinal cord microglia cells. Extensive screening for binding to other neuroreceptor subtypes demonstrated their P2X7 selectivity.

4-Substituted cubylcarbinylamines: A new class of mechanism-based monoamine oxidase B inactivators

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 inactiva