Abstract: This invention is directed to sorbitol dehydrogenase inhibitory compounds of the formula I, wherein R1, R2 and R3 are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds and methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, diabetic macroangiopathy and diabetic cardiomyopathy by administering such compounds to a mammal suffering from diabetes and therefore at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of this invention with an aldose reductase inhibitor and to methods of treating or preventing diabetic complications therewith.

Abstract: This invention is directed to sorbitol dehydrogenase inhibitory compounds of the formula I, wherein R1, R2 and R3 are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds and methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, diabetic macroangiopathy and diabetic cardiomyopathy by administering such compounds to a mammal suffering from diabetes and therefore at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of compound of formula I of this invention with an aldose reductase inhibitor and to methods of treating or preventing diabetic complications therewith.

Abstract: This invention is directed to sorbitol dehydrogenase inhibitory compounds of the formula I, 1

Abstract: This invention is directed to sorbitol dehydrogenase inhibitory compounds of the formula I, wherein R1, R2 and R3 are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds and methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, diabetic macroangiopathy and diabetic cardiomyopathy by administering such compounds to a mammal suffering from diabetes and therefore at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of this invention with an aldose reductase inhibitor and to methods of treating or preventing diabetic complications therewith.

Abstract: This invention is directed to sorbitol dehydrogenase inhibitory compounds of the formula I, wherein R1, R2 and R3 are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds and methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, diabetic macroangiopathy and diabetic cardiomyopathy by administering such compounds to a mammal suffering from diabetes and therefore at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of this invention with an aldose reductase inhibitor and to methods of treating or preventing diabetic complications therewith.

Abstract: This invention is directed to sorbitol dehydrogenase inhibitory compounds of the formula I, 1

Abstract: This invention is directed to sorbitol dehydrogenase inhibitory compounds of the formula I, wherein R1, R2 and R3 are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds and methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, diabetic macroangiopathy and diabetic cardiomyopathy by administering such compounds to a mammal suffering from diabetes and therefore at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of this invention with an aldose reductase inhibitor and to methods of treating or preventing diabetic complications therewith.

Abstract: This invention relates to methods of inhibiting sorbitol dehydrogenase, lowering fructose levels, and treating or preventing diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic microangiopathy or diabetic macroangiopathy in a mammal using pyrimidine derivatives of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are defined as below, and to pharmaceutical compositions containing such derivatives. It also relates to certain novel substituted pyrimidines having the above formula. It also relates to mutual prodrugs of compounds of the formula I and aldose reductase inhibiting compounds, and to pharmaceutical compositions comprising a compound of the formula I and an aldose reductase inhibitor.

Abstract: This invention relates to methods of inhibiting sorbitol dehydrogenase, lowering fructose levels, and treating or preventing diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic microangiopathy or diabetic macroangiopathy in a mammal using pyrimidine derivatives of formula (I) wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are defined as below, and to pharmaceutical compositions containing such derivatives. It also relates to certain novel substituted pyrimidines having the above formula. It also relates to mutual prodrugs of compounds of above formula (I) and aldose reductase inhibiting compounds, and to pharmaceutical compositions comprising a compound of above formula (I) and an aldose reductase inhibitor.

Abstract: Certain 1H-indazole-3-acetic acid derivatives, and their pharmaceutically-acceptable esters and salts, are inhibitors of the aldose reductase enzyme, and so are useful in the treatment of diabetic complications.

Abstract: Abstract Certain 1H-indazole-3-acetic acid derivatives, and their pharmaceutically-acceptable esters and salts, are inhibitors of the aldose reductase enzyme, and so are useful in the treatment of diabetic complications.

Abstract: Oxophthalazinyl acetic acids having benzothiazole side chains are prepared by reacting an oxophthalazinyl thioacetamide acetate with hydrogen sulfide and a nitrophenyl compound having a reactive group such that the benzothiazole side chain may be formed by ring closure involving the thioacetamide group. The oxophthalazinyl thioacetamide may be prepared by reacting the corresponding cyanomethyloxophthalazinyl acetate with hydrogen sulfide in the presence of tertiary amines. Analogous indazole and oxopyridopyridazinone acetic acids may be prepared similarly, as well as oxophthalazinyl, indazole and oxopyridopyridazinone acetic acids having thiazoloyridinyl side chains.

Abstract: Oxophthalazinyl acetic acids having benzothiazole side chains are prepared by reacting an oxophthalazinyl thioacetamide acetate with hydrogen sulfide and a nitrophenyl compound having a reactive group such that the benzothiazole side chain may be formed by ring closure involving the thioacetamide group. The oxophthalazinyl thioacetamide may be prepared by reacting the corresponding cyanomethyloxophthalazinyl acetate with hydrogen sulfide in the presence of tertiary amines. Analogous indazole and oxopyridopyridazinone acetic acids may be prepared similarly, as well as oxophthalazinyl, indazole and oxopyridopyridazinone acetic acids having thiazolopyridinyl side chains.

Abstract: Oxophthalazinyl acetic acids having benzothiazole side chains are prepared by reacting an oxophthalazinyl thioacetamide acetate with hydrogen sulfide and a nitrophenyl compound having a reactive group such that the benzothiazole side chain may be formed by ring closure involving the thiocaetamide group. The oxophthalazinyl thioacetamide may be prepared by reacting the corresponding cyanomethyloxophthalazinyl acetate with hydrogen sulfide in the presence of tertiary amines. Analogous indazole and oxopyridopyridazinone acetic acids may be prepared similarly, as well as oxophthalazinyl, indazole and oxopyridopyridazinone acetic acids having thiazolopyridinyl side chains.

Abstract: A series of novel 6-substituted-5-oxo-6H-pyrido[2,3-d]pyridazine-8-ylacetic acid and 7-substituted-8-oxo-7H-pyrido[2,3-d]pyridazine-5-ylacetic acid compounds have been prepared, including their C.sub.1 -C.sub.6 alkyl ester derivatives, as well as the base salts of said acids with pharmacologically acceptable cations. Typical member compounds include those acids wherein the ring substitutent is always attached to the available ring-nitrogen atom and is either a lower aralkyl group or a lower heteroaralkyl group. These compounds are useful in therapy as aldose reductase inhibitors for the control of certain chronic diabetic complications. Methods for preparing these compounds from known starting materials are provided.

Abstract: Oxophthalazinyl acetic acids having benzothiazole side chains are prepared by reacting an oxophthalazinyl thioacetamide acetate with hydrogen sulfide and a nitrophenyl compound having a reactive group such that the benzothiazole side chain may be formed by ring closure involving the thioacetamide group. The oxophthalazinyl thioacetamide may be prepared by reacting the corresponding cyanomethyloxophthalazinyl acetate with hydrogen sulfide in the presence of tertiary amines. Analogous indazole and oxopyridopyridazinone acetic acids may be prepared similarly, as well as oxophthalazinyl, indazole and oxopyridopyridazinone acetic acids having thiazolopyridinyl side chains.

Abstract: A process for the preparation of oxophthalazinyl acetic acids having benzothiazole or other heterocyclic side chains comprising reacting an oxophthalizinyl acetic acid ester with an aniline derivative is disclosed. Also disclosed are processes for the preparation of such oxopthalizinyl esters.

Abstract: Oxophthalazinyl acetic acids having aldose reductase inhibitory properties of the formula ##STR1## wherein Z is hydrogen or methyl, U is S, CH.sub.2 or a covalent bond, and R.sup.1, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are as herein defined, are prepared by reacting an intermediate oxophthalazinyl acetic acid ester having a cyano or alkylamido group with an aniline derivative of the formula ##STR2## Processes for the preparation of the intermediate oxophthalazinyl acetic esters are disclosed.

Abstract: The 2-chloro-1,1,1-tri(C.sub.1 -C.sub.6)alkoxyethanes are prepared from the corresponding tri(C.sub.1 -C.sub.6)alkoxyethanes by chlorination with N-chlorosuccinimide or with chlorine in pyridine and a chlorohydrocarbon cosolvent.

Abstract: Chloromethyl group substituted heterocyclic compounds of the formulae ##STR1## wherein X is O or S;Y together with the two carbons to which Y is attached forms phenyl, pyridyl or pyrimidyl, each of which may be substituted by R;R is one of iodo or trifluoromethylthio or one or two of fluoro, chloro, bromo, (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxy, (C.sub.1 -C.sub.4)alkylthio, (C.sub.1 -C.sub.4)alkylsulfinyl, (C.sub.1 -C.sub.4)alkylsulfonyl or trifluoromethyl; andR.sup.1 is hydrogen or R, are prepared by reacting a bifunctional compound of the formulae ##STR2## with a 2-chloro-1,1,1-tri(C.sub.1 -C.sub.6)alkoxyethane. Most of the compounds of formulae I and II are novel. These compounds are intermediates of use in the preparation of compounds having pharmaceutical activity. The 2-chloro-1,1,1-tri(C.sub.1 -C.sub.6)alkoxyethanes are prepared from the corresponding tri(C.sub.1 -C.sub.6)alkoxyethanes by chlorination with N-chlorosuccinimide or with chlorine in pyridine and a chlorohydrocarbon cosolvent.