Syntex (u.s.a.) Inc.

Belig M Berkoz

Stefan H Unger

Brian Lewis

Karl G Untch

Joseph M Muchowski

1-Alkylamino-3-(4-[(endobicyclo[3.1.0]hex-6-yl)alkylure ido]-1-phenoxy)-2-propanol and substituted derivatives thereof; 1-alkylamino-3-(4-[(endobicyclo[3.1.0]hex-6-yl)-alkylcarbonylamino]-1-phen oxy)-2-propanol and substituted derivatives thereof; and 1-alkylamino-3-(4-[(endobicyclo-[3.1.0]hex-6-yl)alkoxycarbonylamino]-1-phe noxy)-2-propanol and substituted derivatives thereof as well as methods for preparing such compounds are disclosed. 5-(4-[(Endobicyclo[3.1.0]hex-6-yl)alkylureido]-1-phenoxy) methyl-3-alkyl-2-optionally substituted oxazolidine and derivatives thereof; 5-(4-[(endobicyclo[3.1.0]hex-6-yl alkylcarbonylamino]-1-phenoxy)methyl-3-alkyl-2-optionally substituted oxazolidine and derivatives thereof; and 5-(4-[(endobicyclo[3.1.0]hex-6-yl)alkoxycarbonylamino]-1-phenoxy)methyl-3- alkyl-2-optionally substituted oxazolidine and derivatives thereof and methods for preparing these compounds are also disclosed. These compounds exhibit cardiovascular activity and are useful in the treatment of abnormal heart conditions as well as hypertension in mammals. The bicyclo-2-propanols are prepared by treatment of the corresponding 1,2-epoxy-3-(4-[(endobicyclo[3.1.0]hex-6-yl)alkylureido, alkylcarbonylamino or alkoxycarbonylamino-1-phenoxypropane, with the desired alkylamine or by base or acid hydrolysis of the corresponding 5-(4-[(endobicyclo[3.1.0]-hex-6-yl)alkylureido, alkylcarbonylamino or alkoxycarbonylamino]-1-phenoxy)-methyloxazolidine. The lattercompounds are prepared from the corresponding 1-alkylamino-3-(4-[(endobicyclo[3.1.0]-hex-6-yl)alkylureido, alkylcarbonylamino or alkoxycarbonylamino]-1-phenoxy)-2-propanol by treatment with an aldehyde having the desired optional substituent.

Bicyclo[3.1.0]hexyl-substituted carbonylaminophenoxy cardiovascular

Processes and intermediates for preparing 1-alkylamino-3-(5-substitutedaminocarbonylthiazol-2-yloxy)-2-propanols and 5-(5-substitutedaminocarbonylthiazol-2-yloxymethylene)-N-alkyloxazolidine and 2-substituted oxazolidine derivatives thereof and intermediates therefore. The present processes, and intermediates, reduce the number of transformations necessary to produce these products as compared with the prior processes. The products are useful to treat abnormal heart conditions and/or hypertension in mammals. The intermediates are 2-alkylsulfinyl-5-substitutedaminocarbonylthiazoles and 2-alkylsulfonyl-5-substitutedaminocarbonylthiazoles.

Certain thiazole-5-carboxamide compounds

1-Alkylamino-3-(5-alkynylaminocarbonylthiazol-2-yloxy)-2-propanol; 5-(5-alkynylaminocarbonyl-thiazol-2-yloxymethylene)-N-alkyloxazolidine and/or 2-substituted oxazolidine derivatives thereof, and methods of making such compounds. The compounds exhibit cardiovascular activity and are useful in the treatment of abnormal heart conditions in mammals. The compounds are also useful in the treatment of hypertension in mammals. The 5-(5-alkynyl-aminocarbonylthiazol-2-yloxymethylene)-N-alkyloxazolidines and derivatives are also intermediates for the 1-alkylamino-3-(5-alkynylaminocarbonylthiazol-2-yloxy)-2-propanols. The 1-alkylamino-3-(5-alkynylaminocarbonylthiazol-2-yloxy)-2-propanols can be prepared by base or acid hydrolysis of the corresponding 5-(5-alkynylaminocarbonylthiazol-2-yloxymethylene)-N-alkyloxazolidine or derivative; or by treatment of the corresponding 3-(5-alkynylaminocarbonylthiazol-2-yloxy)-2,3-epoxypropane with the desired alkylamine. Similarly the 5-(5-alkynylaminocarbonylthiazol-2-yloxymethylene)-N-alkyloxazolidine or derivative can be prepared from the corresponding 1-alkylamino-3-(5-alkynylaminocarbonylthiazol-2-yloxy)-2-propanols via treatment with an aldehyde or ketone.

Thiazole cardiovascular agents

1-Alkylamino-3-(5-alkenylaminocarbonylthiazol-2-yloxy)-2-propanol; 5-(5-alkenylaminocarbonylthiazol-2-yloxymethylene)-N-alkyloxazolidine and/or 2-substituted oxazolidine derivatives thereof, and methods of making such compounds. The compounds exhibit cardiovascular activity and are useful in the treatment of abnormal heart conditions in mammals. The compounds are also useful in the treatment of hypertension in mammals. The 5-(5-alkenylaminocarbonylthiazol-2-yloxymethylene)-N-alkyloxazolidines and derivatives are also intermediates for the 1-alkylamino-3-(5-alkenylaminocarbonylthiazol-2-yloxy)-2-propanols. The 1-alkylamino-3-(5-alkenylaminocarbonylthiazol-2-yloxy)-2-propanols can be prepared by base or acid hydrolysis of the corresponding 5-(5-alkenylaminocarbonylthiazol-2-yloxymethylene)-N-alkyloxazolidine or derivative; or by treatment of the corresponding 3-(5-alkenylaminocarbonylthiazol-2-yloxy)-2,3-epoxypropane with the desired alkylamine. Similarly the 5-(5-alkenylaminocarbonylthiazol-2-yloxymethylene)-N-alkyloxazolidine or derivative can be prepared from the corresponding 1-alkylamino-3-(5-alkenylaminocarbonylthiazol-2-yloxy)-2-propanols via treatment with an aldehyde or ketone.

Growing community of inventors

Los Altos, CA, United States of America

Belig M Berkoz