Tertiary prototypes

Methylbutynol. 2-Methyl-3-butyn-2-ol [115-19-5] prepared by ethynylation of acetone, is the simplest of the tertiary ethynols, and serves as a prototype to illustrate their versatile reactions. There are three reactive sites, ie, hydroxyl group, triple bond, and acetylenic hydrogen. Although the triple bonds and acetylenic hydrogens behave similarly in methylbutynol and in propargyl alcohol, the reactivity of the hydroxyl groups is very different. 

Amines. One of the most ubiquitous classes of reductants for photoreducible dyes is that of amines, especially tertiary amines. Oster described the use of hydrazine as a reductant in his original report (7). The first comprehensive studies of amine reductants were reported by Chen (17). Chen examined as a prototype the system methylene blue (MB)/triethanolamine (TEOA) (17a). Methylene blue is 3,9-dimethylaminophenazothion-ium chloride, a dye of the phenazine class. Those results will be considered in some detail. 

Removal of one of the ethylene portions of the piperidine ring leaves the phenyl-propylamine skeleton of the phenyl piperidines. These are the most simplified structures still to have opioid receptor activity. The phenylpropylamines still follow the SAR of morphine on the basis that they possess a basic nitrogen which is two carbons away from a central quaternary carbon atom having a benzene ring attached [18]. In the case of methadone (29 Fig. 11.16) [65], the prototype phenyl-propylamine, the quaternary carbon contains another benzene ring and a propio-nyl moiety. The basic nitrogen is still tertiary with two methyl groups present. 

Analyses of NH2-terminated PAMAM dendrimers by titration and concurrent 13C-NMR monitoring of carbons attached to primary and tertiary amino groups were very interesting. Usually, tertiary amines are assumed to be more basic than primary amines. With the present prototypes, the opposite was true. Titrations with hydrochloric acid showed that neutralizations occurred to give rather sharp breaks at pH = 6.85 and pH = 3.86 (Fig. 43), which were in very close agreement with theoretical values for terminal primary amino groups and interior tertiary amino groups, respectively [2, 79]. The distinctive endpoints exhibited by these... 

Imipramine Dibenzapine tertiary amine Prototype compound... 

The first prototype chiral nematic phase change devices were demonstrated with a tertiary mixture of cholesteryl chloride (12), nonanoate (13) and oleyl... 

Table 3.2 Transition temperatures (°C) for chiral nematic derivatives of cholesterol (12-14) and a tertiary mixture (30%I56%I14%. respectively) for a CNPC-LCD prototype ...

Although formation of the diaUcyl peroxide is shown in the prototype reaction (Scheme 9), hydroperoxides, alcohols, aldehydes, and acids also have been isolated. The extent of these secondary paths depends on the choice of solvent and reaction conditions. Secondary and tertiary halides also give substantial quantities of alkenes from dehydrohalogenation by... 

The search for better tolerated folate antagonist antitumor agents continues to produce yet more variants on methotrexate [see pemetrexed (46) for structure]. The analogue pralatrexate (202) retains most of the features of the prototype, but replaces the side-chain tertiary amine by a... 

Branching ratios for specific reactions are much harder to determine in real-time experiments and investigations have tended to concentrate on measuring the overall rates of reactions of prototypical compounds. Measurements of the rates of abstraction from ethane or neopentane determine rate coefficients per primary bond. Related measurements can then be used to calculate the rates of secondary or tertiary abstraction assuming that the overall rate coefficient is of the form... 

Atropine is the prototype drug of this group and will be described first. Other named agents will be mentioned only in so far as they differ from atropine. All act as non-selective and competitive antagonists of the various muscarinic receptor subtypes (Ml-3). Atropine is a simple tertiary amine certain others (see Summary) are quaternary nitrogen compounds, a modification that is important as it intensifies antimuscarinic potency in the gut, imparts ganglionblocking effects and reduces CNS penetration. 

II trials as an anxiolytic. SAR studies showed that the 5-methoxy group, a tertiary amine, and a four carbon linker provide the optimum compromise between 5HT-1A affinity and selectivity vs. adrenergic and dopaminergic sites (447). The aminobenzopyran moiety, which is derived from the prototypical 5HT-1A ligand 8-OH-DPAT, contributes more to the 5HT-1A affinity, whereas the carbon linker has a greater impact on selectivity than on affinity. The (+) enantiomers are consistently more potent and selective than the (-) antipodes. Alnespirone binds with higher affinity (0.3 nM) and selectivity than that of either buspi-rone or ipsapirone (447,448), is a full agonist at pre- and postsynaptic 5HT-1A sites, and is active in animal models at low doses (<4 mg/ kg, ip) with no sedative effects. 

Several ofher lipocalins whose tertiary structures have been elucidated adopt a very similar fold. These were dubbed prototypic lipocalins [21] in order to distinguish fhem from more distantly related members of fhe family [18]. Wifhin fhis subset, especially fhe / -barrel with the attached a-helix is highly conserved. In contrast, fhe four loops that form fhe entrance to fhe ligand pocket vary considerably in sequence, conformation, and length, fhus effecting fhe differing ligand specificities (Fig. 8.2). 

Atropine is the prototype of the class. As a tertiary amine, it enters CNS, where it acts as an M receptor antagonist. 

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