Enteropeptidase is a serine protease that converts trypsinogen secreted from the pancreas after meal to trypsin. Trypsin in a state activated by enteropeptidase then activates protease precursors such as chymotrypsinogen, procarboxypeptidase, and proelastase. These activated proteases decompose dietary proteins into amino acid units. The resulting amino acids are absorbed into the small intestine. Thus, enteropeptidase inhibitors are capable of suppressing the degradation or absorption of proteins and is useful as a drug for treating obesity.
Examples of heterocyclic compounds include the following:
(1) A compound which has a trypsin inhibitory effect and is useful in the treatment or prevention of a renal disease or a disease involving trypsin, the compound being represented by the following formula:
wherein
ring A represents

R1 represents halogen, lower alkyl, or OH;
R2 represents H, optionally substituted cycloalkyl, optionally substituted aryl, an optionally substituted aromatic heterocyclic ring, an optionally substituted nonaromatic heterocyclic ring, —C(O)-lower alkylene-optionally substituted aryl, or lower alkyl optionally substituted by halogen or the like;
L1 represents —Y1-lower alkylene-Y2—, or —C(O)—N(R6)—;
Y1 represents a bond or —C(O)—;
Y2 represents a bond, —N(R6)—, or —C(O)—N(R6)—;
L2 represents -(lower alkylene optionally substituted by CO2H or the like)-, —Y3-cyclohexanediyl-Y4—, or —Y3-phenylene-Y4—, and L2 optionally forms optionally substituted cyclic amino together with R2;
Y3 represents a bond or lower alkylene;
Y4 represents a bond, lower alkylene, or —C(O)—;
R3 represents H, lower alkyl optionally substituted by halogen, halogen, OH, —O-lower alkyl, cycloalkyl, aryl, or the like;
R4 represents lower alkyl optionally substituted by halogen, halogen, OH, —O-lower alkyl, cycloalkyl, aryl, or the like;
R5 and R6 each represent H or lower alkyl;
X1, X2, and X3 each represent CH or N (except that at least one of X1, X2, and X3 is N);
m represents an integer of 0 to 4;
p represents an integer of 0 to 3; and
q represents an integer of 0 to 4
(Patent Literature 1).
(2) A compound which has a serine protease inhibitory effect and is useful in the treatment or prevention of obesity, hyperlipidemia, diabetes mellitus, diabetic complications, or metabolic syndrome, the compound being represented by the following formula:
wherein
R1, R2, R3, and R4 each represent H or the like;
HetAr represents an optionally substituted heteroaromatic ring;
X represents optionally substituted lower alkylene or the like;
Y represents carbonyl or the like;
A represents
or the like; and
R6 and R7 each represent H, optionally substituted lower alkyl, or the like
(Patent Literature 2).
(3) A compound which has a serine protease inhibitory effect and is useful in the treatment or prevention of obesity, hyperlipidemia, diabetes mellitus, diabetic complications, or metabolic syndrome, the compound being represented by the following formula:
wherein
D represents a benzene ring, a naphthalene ring, or a pyridine ring;
Het represents a heterocyclic ring;
R1 represents H or the like;
R2 represents nitro, lower alkyl, or the like;
X represents optionally substituted lower alkylene;
Z represents —N(R3)-(wherein R3 represents H, optionally substituted lower alkyl, optionally substituted lower cycloalkyl, or the like);
Y represents a single bond or —(CH2)p-C(R4a) (R4b)-(CH2)q- (wherein R4a and R4b each represent H, lower alkyl, or aralkyl, and p and q each represents an integer of 0 to 5); and
A represents —CO2R6 (wherein R6 represents H or lower alkyl) or
wherein Q represents optionally substituted lower alkylene, and R7 represents H or lower alkyl(Patent Literature 3).
(4) A compound which has an enteropeptidase inhibitory effect and is useful in the treatment or prevention of a disease related to obesity or abnormal fat metabolism, the compound being represented by the following formula:
wherein
B represents boron;
W represents a nitrogen-containing functional group (

X represents a linker (CX1X2)p;
Y and Z each represent OH, OR (R represents alkyl), a homocyclic ring, a heterocyclic ring, or the like;
R2 represents aminoacyl, acyl, or the like; and
R2 represents H, alkyl, or OR (R represents H or alkyl)
(Patent Literature 4).
(5) A compound which has a serine protease inhibitory effect and is useful in the treatment or prevention of obesity, diabetes mellitus, or the like, the compound being represented by the following formula:
wherein
R1 and R2 each represent alkyl or the like; and
X represents —OR3, —NR4R5, or the like
(Patent Literature 5).