Rigid analogues

The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

Thus, there has been much interest in preparation of rigid analogues both for their utility in mapping receptors and because it was felt that an intrinsically correct fit would maximize intrinsic potency. 

Molecular modelling studies using small molecules, which have been con-formationally investigated before they are compared and fitted, can be performed by using a potent and rigid analogue as a template molecule. Alter-... 

Perhaps following up the rigid analogue concept, an epinephrine analogue with a cyclized side chain is the rimiterol (38). Reaction... 

Retro-Claisen reaction, 49 Rigid analogues, 50, 223, 284, 296, 451 Rimantadine, 19 Rimiterol, 278... 

A.S. Horn, S.H. Snyder, Steric requirements for catecholamine uptake by rat brain synaptosomes, studies with rigid analogues of amphetamine, J. Pharmacol. Exp. Ther. 180 (1972) 523-530. 

Scheme 2.2.5.20 Formation of rigid analogues of oligosaccharide structures by tandem aldolization of appropriately functionalized cyclic precursors.

The synthesis of 614, a conformationally rigid analogue of the tricylic antidepressant imipramine, also begins with an A,A-diisopropyl nicotinamide ortho metalation (Scheme 181) [87H(26)3165]. Thus, LiTMP depro-... 

A number of 4-oxoquinoline-3-carboxylic acids are commercially very important antibacterials and there is continuous research to extend the range of clinically useful products. As part of a programme on the synthesis of conformationally rigid analogues of the basic system it was found that heating of the amide 1 in acetic anhydride at 80°C for 4 hours gave a 92% yield of the tetracyclic analogue 2. 

Qiu J, Silverman RB. A new class of conformationally-rigid analogues of 4-amino-5-halopentanoic acids, potent inactivators of y-aminobutyric acid aminotransferase. J. Med. Chem. 2000 43 706-720. 

Three-Dimensional Quantitative Structure-Activity Relationship Approaches An early study by Seidel et al. showed that a certain 3D feature, such as a torsion angle, can be used to help explain calcium channel activity of a series of DHPs [123], For a set of rigid analogues of nifedipine, their calcium channel affinities (log A)) were correlated with the deviation from 90° of the torsion angle between the two rings (Aa) ... 

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