- Oxadiazole and its salts, their use in treating dementia
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The compound (3R, 4R)-3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[2.2.1]heptane and its salts behave as a functionally selective muscarinic agonist and are useful in the treatment of neurological and mental disorders, preferably in a pharmaceutical formulation comprising the active compound in association with a pharmaceutically acceptable carrier. The compound can be prepared by methods analogous to those known in the art via suitable chiral intermediates and cyclopropyl carboxamide oxime.
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- ENANTIOSELECTIVE SYNTHESIS OF 3-SUBSTITUTED 1-AZABICYCLO(2.2.1)HEPTANES
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A process for preparing a substantially pure enantiomer of a compound formula (I) STR1 wherein X is O or S; andR. sup.2 represents hydrogen,--CF 3,--OR 7,--SR 7,--NR 7 R 8,--CN,--COOR 7,--CONR 7 R 8, or a saturated or unsaturated, substituted or unsubstituted hydrocarbon group, wherein R. sup.7 and R. sup.8 are independently selected from hydrogen and C 1-2 alkyl provided that--NR 7 R 8 is other than NH 2 ; which process comprises cyclization of a compound of formula (10) or salt thereof: STR2 wherein X and R 2 are as defined in formula (I); and R 4 is a labile leaving group and optionally epimerizing the endo-diastereomer so prepared to produce the corresponding exo-diastereomer.
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- Substituted oxadiazoles and thiadiazoles for use in the treatment of glaucoma
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The use of compounds for formula (I): STR1 or a salt or prodrug thereof; wherein one of X, Y, or Z is an oxygen or sulphur atom and the other two are nitrogen atoms, and the dotted circle represents two double bonds thus forming a 1,3,4-oxadiazole, 1,2,4-oxadiazole, 1,3,4-thiadiazole or 1,2,4-thiadiazole nucleus; R1 represents a non-aromatic azacyclic or azabicyclic ring system selected from STR2 wherein the broken line represents an optional chemical bond; the substituents R3 and R4 may be present at any position, including the point of attachment to the oxa- or thia-diazole ring, and independently represent hydrogen, C1-4 alkyl, halo, C1-4 alkoxy, hydroxy or carboxy, or R3 and R4 together represent carbonyl; the group R5 represents hydrogen or C1-4 alkyl; and R2 represents hydrogen, C1-8 hydrogen, C1-8 alkyl optionally substituted by hydroxy or fluoro, C2-8 alkenyl, OR7, SR7, NR7 R8, CN, CO2 R7, CONR7 R8 OR NHCONHR9 where R9 is C1-4 alkyl; wherein R7 and R8 independently represent hydrogen or saturated or unsaturated C1-4 alkyl provided that, when R7 and R8 in NR7 R8 are both hydrogen, at least one of R3 and R4 is C1-4 alkyl, in the treatment of glaucoma, novel compounds having such use, formulations containing them and their synthesis.
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- Synthesis, Physicochemical and Conformational Properties of (3R,4R)-3-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)-1-azabicycloheptane, a Novel M1 Selective Muscarinic Partial Agonist
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The cyclopropyloxadiazole derivative described in the title has been shown to be a functionally selective M1 partial agonist with antagonist properties in M2 and M3 muscarinic receptor assays; conformational studies indicate free rotation around the oxadiazole-azanorbornane bond, whilst X-ray studies reveal that the cyclopropyl group is in conjugation with the oxadiazole C=N bond.
- Baker, Raymond,Showell, Graham A.,Street, Leslie J.,Saunders, John,Hoogsteen, Karst,et al.
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p. 817 - 819
(2007/10/02)
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