Patent EA-003937-B1 (EA)
Title: Novel aryloxy-alkyl-dialkylamines
Inventor: RAVEENDRANATH PANOLIL
IPC: A61K31/404
Filed: 1998-10-14
Abstract: 1. A compound of the formula: wherein: R<1> and R<2> are, independently, selected from H; X selected from halogen; A is -O-; m is 1; R<3>, R<4>, R<5>, and R<6> are independently selected from H; and Y is selected from: a) the moiety: wherein R<7> and R<8> are independently C1-C6 alkyl; b) a six-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two nitrogen heteroatoms; c) a seven-membered saturated, unsaturated or partially unsaturated heterocycle containing up to two nitrogen heteroatoms, and the pharmaceutically acceptable salts thereof. 2. A compound of Claim 1 which is (4-Chloromethyl-phenoxy)-ethylpiperidin-1-yl hydrochloride. 3. A compound of Claim 1 which is (4-Chloromethyl-phenoxy)-ethylhexamethyleneimine - 1-yl hydrochloride. 4. A compound of Claim 1 which is (4-Chloromethyl-phenoxy)-ethyldimethylamino hydrochloride. 5. A process for preparing a compound of the formula (I) as claimed in any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof, which comprises converting an alcohol of formula wherein m, A, Y and R<1-6> are as defined in claim 1 to give a corresponding compound of formula (I) wherein X is a leaving group by appropriate means; e.g using a halogenating, sulphonylating or acylating agent containing the leaving group X as defined in claim 1, and if necessary, oxidising a compound of formula (I) wherein A is S to give a corresponding compound of formula (I) wherein A is -SO- or -SO2-; and optionally converting a compound of formula (I) to a pharmaceutically acceptable salt thereof. 6. A process for preparing a compound of Claim 1 wherein A is -O- comprising the steps of: a) alkylating a hydroxybenzaldehyde of the formula: wherein R<3-6> are as defined in Claim 1, with an alkyl halide of the formula: R<1> and R<2> are as defined in Claim 1, m is 1 and halo is selected from Cl, F, Br or I, to produce an aldehyde of the formula: b) reducing the aldehyde product of step a), to yield an alcohol of the formula: c) converting the alcohol of step b) to its hydrochloride salt; and d) converting the alcohol in the compound of step c) to a leaving group. 7. A process for preparing a compound of Claim 1 wherein A is S, the process comprising the steps of: a) alkylating a compound of the following formula: wherein R<3-6> are as defined in claim 1 with an alkylating agent of the formula: wherein Y, R<1>, R<2> and m are as defined in Claim 1, halo can be Cl, F, Br or I, to 5 produce an aldehyde of the formula: b) reduction of the aldehyde, such as with sodium borohydride, to an alcohol of the formula; c) treatment of the alcohol of step b) with gaseous HCl to generate its hydrochloride; and d) converting the alcohol hydrochloride product of step c) to a leaving group. 8. The process of Claim 7 further comprising the step of controlled oxidation of the sulfur in the alcohol hydrochloride of step d) to a sulfoxide or to a sulfone. 9. A process according to any one of claims 5 to 8 wherein the alcohol is converted to a leaving group through treatment with methanesulfonyl chloride, toluenesulfonyl chloride, or trifluoroacetic anhydride in the presence of pyridine or triethylamine. 10. A process according to any one of Claims 5 to 9 wherein halo is Cl and m is 1. 11. A process for producing compounds of the formula: wherein Y represents: a) the moiety wherein R<7> and R<8> are independently H; or b) a six-, or seven-membered unsaturated or partially unsaturated heterocyclic ring containing one or two nitrogen atoms, the heterocyclic ring being bound to the ethoxy bridge at a nitrogen atom in the ring and being optionally substituted by from 1 to 3 groups selected from C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, -CF3, or -NO2, the process comprising reacting, in an alkaline medium, 4-hydroxybenzyl alcohol with a salt of a compound of the formula: wherein Y is as defined above. 12. The process of Claim 11 wherein the alkaline medium is maintained at a pH of 9 or greater. 13. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutical acceptable salt thereof as claimed in any one of claims 1 to 4 and a pharmaceutically acceptable carrier.