ω-Substituted alkyl carboxylic acids as antidiabetic and lipid-lowering agents
摘要:
In screening experiments certain omega-substituted alkyl carboxylic acids were found to produce an increase in insulin-stimulated C-14-acetate incorporation into triglycerides, which may indicate an improvement in the action of insulin. Antidiabetic and lipid-lowering properties in genetically diabetic ob/ob mice demonstrated the in vivo relevance of the insulin-potentiating effects seen in vitro. The chemical structures of the w-substituted alkyl carboxylic acids with insulin-potentiating effects correspond to the general formula ring-spacer-COOH. A close structure-activity relationship was observed. The most potent compound in ob/ob mice was 3e, which normalized blood glucose as well as hyperinsulinaemia and lowered serum triglycerides and cholesterol by 52% and 37%, respectively. On the basis of these results, omega-substituted alkyl carboxylic acids are interesting as a new class of oral antidiabetic agents with insulin-sensitizing and lipid-lowering activity. (C) Elsevier, Paris.
2,2-Dichloroalkanecarboxylic acids, processes for their production and
申请人:Roche Diagnostics GmbH
公开号:US05968982A1
公开(公告)日:1999-10-19
Pharmaceutical agents for treating diabetus mellitus which contain a compound of formula I ##STR1## as the active substance, in which A, B, A' and W have the meanings stated in the claims, new compounds of formula I as well as processes for their production.
Phenethanolamine derivatives are disclosed of formula ##STR1## wherein m is 2 to 8; n is 1 to 7 provided that m+n is 4 to 12; Ar is phenyl or phenyl substituted by one or two halogen atoms, alkyl or alkoxy groups or by an alkylenedioxy group; R.sup.1 and R.sup.2 are hydrogen or alkyl provided that the sum total of carbon atoms in R.sup.1 and R.sup.2 is not more than 4; and the physiologically acceptable salts and solvates thereof. The compounds have a selective stimulant action at .beta..sub.2 -adrenoreceptors and may be used inter alia in the treatment of diseases associated with reversible airways obstructions such as asthma and chronic bronchitis. The compounds may be formulated in conventional manner as pharmaceutical compositions with physiologically acceptable carriers or excipients. The compounds may be prepared, for example by alkylation of an amine: ##STR2## where R.sup.3, R.sup.5 and R.sup.6 is hydrogen or a protecting group, followed by removal of any protecting group.