Design and synthesis of aryloxyalkylamines as h5-HT1B agonists with potential analgesic activity. A. M.Ismaiel, L. M. Gad , Salah A. Ghareib, F. H. Bamanie & M. A.Moustafa Pharmaceutical chemistry department, *Pharmacology &Toxicology department, Faculty of Pharmacy. King Abdulaziz University,Jeddah,KSA.
It has been proposed that h5-HT and
receptors agonists are targeted for the
development of novel analgesic and antimigraine agents, because h5-HT1B receptors might be
primarily involved in neurogenic inflammation due to their preponderance in neuronal tissues, whereas h5-HT1D receptors might be involved more in vasoconstriction that occurred during
migraine attack. Most of h5-HT1B serotonin sub receptors agonists bind with high affinity but
with low selectivity. Aryloxyalkylamines are curious exception. In the present investigation new series of aryloxyalkylamines ( III : target compounds 4-7,10&11 ) were designed and synthesized in which structure modifications of the well-known analgesic β-blockers; propranolol (I) had been done aiming to obtain new agonist series of aryloxyalkylamine with enhanced affinity for human h5-5HT1B serotonin receptors and possess analgesic with possible
The naphthyl moiety in propranolol (I) is replaced by substituted phenyl group, in addition
the alkyl side chain is ethyl or α-substituted ethyl thus keeping the distance between O and N atoms not changed as the case in (II) . The structures of the new compounds were confirmed by microanalyses and 1H-and 13C-NMR spectroscopy. Some of them were subjected to 3D studies and were found to be superimposed on compound (II).The binding affinity, for most of the new compounds, at 5-HT1B and 5-HT1D were determined and some were found to bind with
high affinity and selectivity compared to (I) and with comparable affinity and selectivity to (II). The analgesic activity of selected compounds were performed on experimental animals and proved to be in the range of 66-100% activity compared to aspirin. R : H , CH3 , C6H5 Target Compounds 4(a-e) , 5 , 6( a, b) ,7 (a, b),10 (a-f) &11 Synthesis of Piperazino and Morpholino Derivatives of Aryloxypropane with Potential Analgesic and Possible Antimigraine Activity. A. M.Ismaiel, L. M. Gad , Salah A. Ghareib, F. H. Bamanie & M. A.Moustafa Pharmaceutical chemistry department, *Pharmacology &Toxicology department, Faculty of Pharmacy. King Abdulaziz University,Jeddah,KSA.
Development of drugs acting on h5-HT serotonin subreceptors represents an exciting new
area of research as a result of the increasing attention of the involvement of these receptors in psychiatric disorders. Modeling studies demonstrate that aryl piperazines (I), Aryloxyalkylamines (II), phenylalkykamines (III) and indolylalkylamines (VI) might interact at 5-HT receptors in a similar manner. Inspection of these structures (I-VI) reveals that all possess an aromatic moiety and terminal amine binding sites. In the present investigation new series of aryloxyalkylamines (V,VI) were designed and synthesized, in which the aromatic moiety is phenyl group substituted at 2,3-, 2,4-, 2,5-, or 2,6- positions by halogens and the terminal amine is N-methylpiperazine or morpholine . In addition the alkyl side chain is ethyl or substituted ethyl at α- or β-carbon by methyl group .The length of the alkyl chain that separate the terminal amine from the ether oxygen atom of the aryloxy group is of major importance and two-carbon chain appears optimal. The structures of the new compounds were assessed by microanalyses, IR and NMR .The binding affinity for some of the new compounds at 5-HT1B and 5-HT1D were determined. The analgesic activity of selected compounds were
performed on experimental animals and proved to be in the range of 85-100% activity compared to aspirin. X: O, N,CH3 X: O, N,CH3 Target compounds A Target compounds B (4 a-c), (5a-f) (8a,b) and (9a-g)
Test Report No. SH9088202-1/CHEM DONGJUE SILICONE (NANJING) CO., LTD. NO.196, FUYIN EASTERN STREET, QIAOLIN, PUKOU DISTRICT, NANJING CITY, JIANGSU PROVINCE, CHINA THIS REPORT IS TO SUPERSEDE TEST REPORT NO.SH9088202/CHEM DATE: 2009/05/18 The following sample(s) was/were submitted and identified by/on behalf of the client as: Sample Name Sample May Cover : NE-20, NE-131, NE-141, NE-
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