17019-27-1

A series of substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones was synthesized from amino alcohols or amino thiols and keto acids. A pharmacological model based on the results obtained with these compounds led to the synthesis and evaluation of a series of isoxazoles and other monocyclic compounds. These were evaluated for their ability to enhance glucose utilization in cultured L6 myocytes. The in vivo hypoglycemic efficacy and potency of these compounds were evaluated in a model of type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus), the ob/ob mouse. 25a(2S) (SDZ PGU 693) was selected for further pharmacological studies.

Compounds of formula I STR1 and N-oxides thereof, in which Ar is aryl; R1 and R2 are the same or different and are hydrogen, alkyl, alkenyl or alkynyl, each of which is optionally substituted, aryl, heterocyclyl, cyano, halogen, nitro, XR3, S(O)2 NR4 R5, CHO and functional derivatives thereof, NR4 R5 or CYNR4 R5 ; R3 is hydrogen or optionally substituted alkyl or alkenyl; R4 and R5 are the same or different and are hydrogen, optionally substituted alkyl, acyl or aryl, or together with the nitrogen to which they are attached, form a 5 to 7 membered ring which can contain other hetero atoms; X is O, S, S(O)n, OSO2, YCO or COO; Y is O or S; and n is 1 or 2; have pesticidal activity and especially insecticidal and acaricidal activity. Many of the compounds are novel.

α-Oximo-α-haloketones were readily synthesized in good yields by treating α-haloketone with alkyl thionitrites under mild conditions.