Aminoindans, conformers

In another work, a series of substituted 2-aminoindans was analyzed using MM2-85108. The calculated potential energy surface for rotation around the CH—CH—CH2— N and CH—CH2—N—lp in model compound 70 is presented in Figure 9 and shows 9 minima. These were scrutinized as potential candidates for dopamine receptor agonists, according to several criteria The highest-energy conformation f (Erei = 7.3 kcalmol-1)... 

The constrained bis(oxazolines) 9a and 9b can be constructed beginning with malononitrile 32 as shown by Ghosh and co-workers. Thus, treatment of 32 with anhydrous hydrochloric acid in dioxane, as shown by Lehn and co-workers, yielded imidate salt 33 (Fig. 9.9). Condensation of the imidate salt with commercially available (15,2/ )-l-aminoindan-2-ol afforded the conformationally constrained bis(oxazoline) inda-box 9a. Alkylation at the bridging methylene of 9a was carried out by Davies and co-workers.Treatment of 9a with lithium diisopropylamide followed by alkylation with methyl iodide afforded 9b. Alternatively, alkylation with diiodoalkanes incorporated ring systems at the bridging position (structures 34a-d). 

Mosberg and co-workers utilized a similar type of approach for constraining the flexibility of Tyr in JOM-13 [69]. In an effort to better determine the binding conformation of the Tyr1 residue, a series of conformationally constrained analogues of Tyr (FlO-Tic 7-hydroxy-1,2,3,4-tetrahydroisoquin-oline-3- carboxylic acid Flai 6-hydroxy-2-aminoindan-2-carboxylic acid Hat 6-hydroxy-2-aminotetralin-2-carboxylic acid, and c-Hpp and t-Hpp ... 

Aminoindane and related ring systems have also been employed as conformational restraints of enkephalins. The analog 24 in which 1-aminoindane replaces residues 4 and 5 of the pentapeptide retains half the GPI activity of DADL,(45) while the peptide 25 modified at the Tyr residue exceeds Leu-enkephalin in potency seven to eight times, but is 30 times less effective at MVD sites.(183) The last derivative showed no activity in mice, using the... 

Conformational constraint of Phe by incorporation of 2-aminoindan-2-carboxylic acid (Aic, Fig. 7.43) into the relatively nonselective peptide [K ratio (S/ju,) = 3] Tyr-cycZo[D-Orn-Phe-GluJNHa markedly enhances /x-re-ceptor selectivity (see Table 7.18) (834). This is a direct consequence of conformational restriction because incorporation of the acyclic derivatives a-methylphenylalanine or 2 -methylphenylalanine in position 3 does not significantly change preceptor selectivity. Interestingly, the peptides containing l- and d-2-... 

Davies and coworkers , for example, used iV-enoyl derivatives of a cw-l-aminoindan-2-ol based L3-oxazolidin-2-one (222) as chiral dienophiles in the Diels-Alder reactions with isoprene (91a) and piperylene (91b) which give 223 (equation 62). Their results have been summarized in Table 6. The reactions proceeded with high endo/exo and regioselectivities. Bidentate co-ordination of the catalyst to both carbonyl groups kept the dienophile in a rigid conformation, which gave rise to the high de values observed. 

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