Calcium receptor modulating compound and use thereof

A compound of the formula (III):

• wherein R1 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted thiol group, an optionally substituted amino group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- is —CO—, —CS—, —SO— or —SO2—, and Z2 is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group);
• R3 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above);
• Y is C, CR4 (wherein R4 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above)) or N;
• R8 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above);
• Ar is an optionally substituted cyclic group;
• R9 and R10 are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above), or R9 and R10 may be combined to form an oxo group, methylene group or a ring;
• X3 is a bond, oxygen atom, an optionally oxidized sulfur atom, N, NR7′ (wherein R7′ is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula -Z1′-Z2 (wherein -Z1′- is —CS—, —SO— or —SO2—, and Z2 is as defined above)), or an optionally substituted bivalent C1-2 hydrocarbon group;
• and
• is a single bond or a double bond;
• provided that at least one of R9 and R10 is CHR15R16 (wherein R15 and R16 are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above)) and the other is other than an optionally substituted phenyl group;
• or a salt thereof.

A compound of the formula (IIIa):

• wherein R1a is (1) an optionally substituted heterocyclic group, or
• (2) a group of the formula:
• -Z1a-Z2a (wherein -Z1a- is —CO—, —CS—, —SO— or —SO2—, and
• Z2, is (i) an optionally substituted heterocyclic group,
• (ii) —NR20a(CR21aR22aR23a) (wherein
• (a) R20a is H or an optionally substituted hydrocarbon group;
• and R21a is an optionally substituted heterocyclic group which may be fused with an optionally substituted benzene ring, or an optionally substituted phenyl group which may be fused with an optionally substituted aromatic heterocyclic ring and R22a and R23a are the same or different and are an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group or R22a and R23a may be combined to form a ring, or
• (b) R20a is H or an optionally substituted hydrocarbon group;
• and R21a, R22a and R23a are the same or different and are an optionally substituted C1-8 aliphatic hydrocarbon group, provided that the sum total of the number of carbon atoms is 7 or more),
• (iii)-NR20aR25a (wherein R20a is as defined above and R25a is an optionally substituted C6-10 aryl-C2-4 alkyl, C6-10 aryloxy-C2-4 alkyl, C6-10 arylamino-C2-4 alkyl, C7-14 aralkylamino-C2-4 alkyl, heterocyclic ring-C2-4 alkyl or heterocyclic group),
• (iv) a substituted 5- to 7-membered cyclic amino group, or
• (v) —OR24a (wherein R24a is
• (a) an optionally substituted C7-14 aralkyl group,
• (b) an optionally substituted C3-7 alicyclic hydrocarbon group,
• (c) an optionally substituted C7-24 aliphatic hydrocarbon group, or
• (d) an optionally substituted heterocyclic group);
• R3 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- is —CO—, —CS—, —SO— or —SO2—, and Z2 is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group);
• Y is C, CR4 (wherein R4 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above)) or N;
• R8 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above);
• Ar is an optionally substituted cyclic group;
• R9 and R10 are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above);
• or R9 and R10 may be combined to form an oxo group, methylene group or a ring;
• X3 is a bond, oxygen atom, an optionally oxidized sulfur atom, N, NR7′ (wherein R7′ is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula -Z1′-Z2 (wherein -Z1′- is —CS—, —SO— or —SO2—, and Z2 is as defined above)), or an optionally substituted bivalent C1-2 hydrocarbon group;
• and
• is a single bond or a double bond;
• provided that at least one of R9 and R10 is CHR15R16 (wherein R15 and R16 are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above)) and the other is other than an optionally substituted phenyl group;
• or a salt thereof.

N-(1-ethyl-1-(4-methylphenyl)propyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,

• N-(1-ethyl-1-(4-methylphenyl)propyl)-5-(2-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
• N-(1-ethyl-1-(4-methylphenyl)propyl)-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
• N-(1-ethyl-1-(4-ethylphenyl)propyl)-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
• N-(1-ethyl-1-(4-methylphenyl)propyl)-5-(2-fluorophenyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
• N-(1-ethyl-1-(4-ethylphenyl)propyl)-5-(2-fluorophenyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
• 5-(2-chlorophenyl)-N-(1-ethyl-1-(4-methylphenyl)propyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
• N-(1-(4-(dimethylamino)phenyl)-1-ethylpropyl)-5-(2-fluorophenyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
• N-(1,1-diethylbutyl)-5-(2-fluorophenyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
• N-(1-ethyl-1-phenylpropyl)-5-(2-fluorophenyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
• 3-(5-(1-ethyl-1-(4-methylphenyl)propyl)-1,3,4-oxadiazol-2-yl)-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine or a salt thereof,
• 3-(5-(1-ethyl-1-(4-methylphenyl)propyl)-1,3,4-thiadiazol-2-yl)-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine or a salt thereof,
• 3-((4-(benzyloxy)-2,2-diethyl-1-pyrrolidinyl)carbonyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine or a salt thereof,
• 3-((2,2-diethyl-4-methoxy-1-pyrrolidinyl)carbonyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine or a salt thereof, or
• 3-((2,2-diethyl-4-fluoro-1-pyrrolidinyl)carbonyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine or a salt thereof.

A composition for modulating calcium receptor which comprises a compound of the formula (I):

• wherein ring A is an optionally substituted 5- to 7-membered ring;
• ring B is an optionally substituted 5- to 7-membered heterocyclic ring;
• X1 is CR1 (wherein R1 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- is —CO—, —CS—, —SO— or —SO2—, and Z2 is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group)), CR1R2 (wherein R1 is as defined above, R2 is H or an optionally substituted hydrocarbon group), N or NR13 (wherein R13 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above));
• X2 is N or NR3 (wherein R3 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above);
• Y is C, CR4 (wherein R4 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above)) or N;
• Z is CR5 (wherein R5 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above)), CR5R6 (wherein R5 and R6 are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above)), N or NR7 (wherein R7 is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula:
• -Z1-Z2 (wherein -Z1- and Z2 are as defined above));
• Ar is an optionally substituted cyclic group;
• R is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, an optionally substituted sulfonyl group or an optionally substituted sulfinyl group, or R and Z may be combined to form a ring B;
• and is a single bond or a double bond;
• or a salt thereof or a prodrug thereof.