Molecular structure and antiaggregating activity of the potent local anaesthetic (-)-4-[2-hydroxy-3-(N-isopropylamino)-propoxyimino]-cis-carane .
The molecular structure of (-)-4-[-2-hydroxy-3-(N-isopropylamino)- propoxyimino]-cis-carane (C16H30O2N2.HCl), a recently synthesized potent local anaesthetic, including the absolute configuration at 4 chirality centres was determined using X-ray diffraction method. The substance crystallizes in diastereoisomeric form in lowest symmetry (triclinic P1 space group). Determined intermolecular close contacts between chlorine atoms and nitrogen and hydroxyl oxygen are the main determinants of crystal packing. In the crystalline state nitrogen of the isopropylamine group has quaternary coordination. The influence of the title compound on blood platelets aggregation induced by adenosine diphosphate was studied. The results of parallel tests conducted for lidocaine and bupivacaine show that the antiaggregating activity of the title compound is much stronger. This property could be attributed to the monoterpene part of its molecule, in analogy to the observed cyclic adenosine monophosphate inhibitory action of forskolin (diterpene).
Czarnecki
R
R
Chair of Pharmacodynamics, Medical Academy, Kraków, Poland.
Czerwińska
K
K
Grochowska
K
K
Grochowski
J
J
Librowski
T
T
Serda
P
P
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000081008:Bicyclic Monoterpenes; D002045:Bupivacaine / Q000494:pharmacology; D003460:Crystallization; D003514:Cyclohexylamines / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008968:Molecular Conformation; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D014961:X-Ray Diffraction
D000081008:Bicyclic Monoterpenes; D003514:Cyclohexylamines; D010975:Platelet Aggregation Inhibitors; C079300:4-(2-hydroxy-3-(N-isopropylamino)propoxyimino)carane; D000244:Adenosine Diphosphate; D008012:Lidocaine; D002045:Bupivacaine