Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a compound comprising: 
wherein M is N or CR 4 ; Q 1 and Q 2 are each independently selected from the group consisting of CO, SO, SO 2 , and C═NR 9 ; and each L, X, R 1 , R 2 , and R 3 are as defined herein.

Dipeptidyl peptidase inhibitors

Pharmaceutical compositions comprising 2-[6-(3-Amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-4-fluoro-benzonitrile and pharmaceutically acceptable salts thereof are provided as well as kits and articles of manufacture comprising the pharmaceutical compositions as well as methods of using the pharmaceutical compositions.

Administration of dipeptidyl peptidase inhibitors

Compositions comprising the succinate salt of 2-[6-(3-Amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-4-fluoro-benzonitrile (referred to herein as Compound I) which has the formula: (I) wherein the Compound I is present in one or more polymorphic forms. Also provided are novel methods for the preparation of the polymorphs of Compound I, and kits and articles of manufacture of the compositions, and methods of using the compositions to treat various diseases.

Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2h-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor

Weekly administration of dipeptidyl peptidase inhibitors

Quinazoline (I) is the building stone for approximately fifty naturally occurring alkaloids isolated from a number of different families of the plant kingdom, from microorganisms and animals [1]. The best known quinazoline alkaloids are peganine (vasicine) (II, R=H) and febrifugine (III).

Search for pharmaceutically interesting quinazoline derivatives: Efforts and results (1969–1980)

The effect of centpiperalone [2-piperazino-4(3H)-quinazolinone monoacetate], a potent hypoglycemic compound on glucose and oxygen uptake, and lactic acid formation by rat hemidiaphragms suspended in glucose-phosphate buffer in Warburg bath at 37 degrees C and 80 shakes/min was studied in vitro. Although centpiperalone enhanced glucose and oxygen uptake by itself, no increment in the above parameters was seen when insulin was added simultaneously along with centpiperalone. Preincubation of hemidiaphragms with centpiperalone and their subsequent incubation with insulin did not indicate any potentiation of insulin action as indicated by uptake of oxygen and glucose. However when 16 times diluted serum from centpiperalone-treated rats was added to hemidiaphragms suspended in glucose-phosphate buffer, significant increase in glycogen content was observed compared to that seen in hemidiaphragms after addition of serum from normal untreated and alloxanized centpiperalone-fed rats. Definite degranulation of B-cells was seen in centpiperalone-fed rats using the aldehyde fuchsin staining technique. These data strongly suggest that centpiperalone induces hypoglycemia through liberation of insulin from B-cells.

Subal S. Mukherjee

Papers

Studies on the mechanism of centpiperalone-induced hypoglycemia.