ABSTRACT
In this study, we synthesized some novel N-(tetrazol-1H-5-yl)-6,14-endoethenotetrahydrothebaine 7α-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives as potential analgesic agents. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C NMR, 2D NMR, and high-resolution mass spectral data. The analgesic activity was evaluated by a rat-hot plate test model and a rat tail-flick model. Compound 12 showed analgesic activity higher than that of morphine. In addition to a histopathological and biochemical evaluation, the LD50 dose for the most active compound 12 was determined.
Subject(s)
Oxadiazoles/pharmacology , Thebaine/pharmacology , Thiadiazoles/pharmacology , Analgesics/chemical synthesis , Analgesics/chemistry , Analgesics/pharmacology , Animals , Disease Models, Animal , Lethal Dose 50 , Magnetic Resonance Spectroscopy/methods , Male , Morphine/pharmacology , Oxadiazoles/chemical synthesis , Oxadiazoles/chemistry , Pain/drug therapy , Rats , Rats, Wistar , Thebaine/analogs & derivatives , Thebaine/chemical synthesis , Thiadiazoles/chemical synthesis , Thiadiazoles/chemistryABSTRACT
IN THE TITLE COMPOUND (SYSTEMATIC NAME: methyl 17-cyano-3,6-dimeth-oxy-4,5α-ep-oxy-6,14-endo-ethenomorphinan-7-carboxyl-ate), C(23)H(24)N(2)O(5), the dihydro-furan ring adopts a twist conformation, while the piperidine ring is in a chair conformation. The benzene-fused cyclo-hexene ring adopts an envelope conformation. An intra-molecular C-Hâ¯O hydrogen bond is observed. Inter-molecular C-Hâ¯N and C-Hâ¯O hydrogen bonds form C(5) chains along the a and b axes, respectively, and together they form a three-dimensional network.
ABSTRACT
In the title compound, C(14)H(16)BrNO(5), the isoxazolidine ring adopts an envelope conformation, with the N atom at the flap. In the crystal, inter-molecular C-Hâ¯N and C-Hâ¯O hydrogen bonds generate R(3) (3)(18) ring motifs which are fused into a ribbon-like structure extending along the b axis.
ABSTRACT
In the title compound, C(18)H(18)N(2)O, the cyclo-hexene and cyclo-hexane rings of the bicyclo-[2.2.2]oct-5-ene unit adopt distorted boat conformations. In the crystal, mol-ecules exist as C-Hâ¯N hydrogen-bonded centrosymmetric R(2) (2)(14) dimers, which are further linked by C-Hâ¯π inter-actions.
ABSTRACT
In the mol-ecule of the title compound, C(23)H(27)NO(5), the furan ring adopts an envelope conformation. Intra-molecular C-Hâ¯O inter-actions result in the formation of S(5) and S(6) motifs. In the crystal structure, weak inter-molecular C-Hâ¯O hydrogen bonds link the mol-ecules through C(6) and C(8) chains along the [100] and [010] directions, generating a two-dimensional network.