Conformational restriction analysis

Cromakalim (137) is a potassium channel activator commonly used as an antihypertensive agent (107). The rationale for the design of cromakalim is based on P-blockers such as propranolol (115) and atenolol (123). Conformational restriction of the propanolamine side chain as observed in the cromakalim chroman nucleus provides compounds with desired antihypertensive activity free of the side effects commonly associated with P-blockers. Enantiomerically pure cromakalim is produced by resolution of the diastereomeric (T)-a-meth5lben2ylcarbamate derivatives. X-ray crystallographic analysis of this diastereomer provides the absolute stereochemistry of cromakalim. Biological activity resides primarily in the (—)-(33, 4R)-enantiomer [94535-50-9] (137) (108). In spontaneously hypertensive rats, the (—)-(33, 4R)-enantiomer, at dosages of 0.3 mg/kg, lowers the systoHc pressure 47%, whereas the (+)-(3R,43)-enantiomer only decreases the systoHc pressure by 14% at a dose of 3.0 mg/kg. 

Kemp and Carter142 described the synthesis of the conformationally restricted y-turn mimetic tert-butyl A- 6-(benzyloxycarbonyl)-3-cyano-6-azabicyclo[3.2.1]oct-3-en-4-yl alanin-ate (22) (Scheme 13). No conformational analysis or biological evaluation of this system has been reported. 

Dynamic two-dimensional and NMR studies of the conformationally restricted amide iV-(l-naphthoyl)-d5-2,6-dimethylpiperidine reveal correlated rotation about the aryl-CO and amide bonds. 9-(l-Adamantylamino-methyl)-9,10-dihydroanthracene was prepared via condensation of 1-adaman-tylnitrile with 9-anthryllithium and its hydride reduction. An NMR study confirmed a boat conformation for the central ring, with the substituent of C9 in a pseudo-axial position. The structure of bis[(l,3)2-oxaadamantano]-18-crown-6 (I) and its potassium picrato complex were studied using NMR, X-ray structure analysis and molecular mechanics calculations. In the gas phase and in CDCI3 solution, in both I and the corresponding complex cation the most stable conformation of C2h symmetry is found. 

Kamphuis, J., Lelj, F., Tancredi, T., Toniolo, C., and Temussi, P.A. (1992). SAR of sweet molecules, conformational analysis of two hypersweet and two conformationally restricted aspartame analogues. QSAR 11,486-491. 

From extensive conformational analysis of gastrin-17, big-gastrin and their related fragments by CD techniques it was concluded that in aqueous solution these peptides are essentially unordered (80). According to the dichroic properties of the chimeric compounds the gastrin-related components and the hinge portion retain their own conformational properties in water without reciprocal interferences and conformational restrictions. This fact could account for the surprising observation... 

Ono S, Ogawa K, Yamashita K, et al. Conformational analysis of the NMDA receptor antagonist (1S,2R)-1-phenyl-2-[S-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (PPDC) designed by a novel conformational restriction method based on the structural feature of cyclopropane ring. Chem Pharm Bull (Tokyo). 2002 50 966-968. 

Rehbein H, Sotelo CG, Perez-Martin RI, et al. (2002). Differentiation of raw or processed eel by PCR-based techniques restriction fragment length polymorphism analysis (RFLP) and single strand conformation polymorphism analysis (SSCP). Eur. Food Res. Technol, 214 171-177. 

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