JP2008285464A - PYRAZOLO[1,5-a]PYRIMIDINE COMPOUND - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a pyrazolo[1,5-a]pyrimidine compound having a CB1 receptor antagonistic activity. <P>SOLUTION: This compound is expressed by general formula [I] [wherein, R<SP>1</SP>, R<SP>2</SP>are each an aryl which may have a substituent, or the like; R<SP>0</SP>is H, an alkyl or the like; E is a group expressed by formula: -C(=O)- or -SO<SB>2</SB>-; and R is a group expressed by formula [i], [ii], [iii], or the like]. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a novel pyrazolo [1,5-a] pyrimidine compound or a pharmacologically acceptable salt thereof which has an excellent central cannabinoid (CB1) receptor antagonistic activity and is useful as a medicament.

  It is well known that cannabis can cause various neuropsychiatric reactions such as confusion in time and space, euphoria, memory impairment, decreased pain, and hallucinations. Many of these actions are due to compounds collectively referred to as cannabinoids, including delta 9-tetrahydrocannabinol (delta 9-THC). The effects of cannabinoids are thought to be due to interactions with specific high affinity receptors present in the body. So far, two cannabinoid receptors (CB1 receptor, CB2 receptor) have been identified and cloned, and CB1 receptors are distributed in the central nervous system (CNS) such as the brain (Non-patent Document 1). Receptors are distributed in immune tissues such as the spleen (Non-patent Document 2).

  Substances having an affinity for these cannabinoid receptors (agonists, antagonists, and inverse agonists) exhibit various pharmacological actions similar to cannabis, and in particular, substances having affinity for the central CB1 receptor are psychological. It is useful for the treatment of CNS diseases such as disorders and neurological disorders.

  Examples of compounds having affinity for the CB1 receptor include pyrazole-3-carboxamide derivatives such as SR141716 (Non-patent Document 3), 4,5-dihydro-1H-pyrazole derivatives such as SLV-319 (Non-patent Document 4), Dihydropyrazolo [3,4-c] pyridin-7-one derivative or 2H-pyrazolo [4,3-d] pyrimidin-7 (6H) -one derivative (Patent Document 1), 1- [2 and / or 3 Various compounds including -arylpyrazolo [1,5-a] pyrimidin-7-yl] piperidine derivatives and the like (Patent Document 2) are known. In addition, the applicant has filed a patent application separately for pyrazolo [1,5-a] pyrimidine-3-carboxamide or sulfonamide derivatives (Patent Document 3). Of these compounds, at least SR141716 and SLV-319 have been clinically tested for their effectiveness as appetite suppressants (anti-obesity agents).

WO2004 / 094417 WO2004 / 069838 WO2007 / 046548 Nature, Vol. 346, pp561-564 (1990) Nature, Vol. 365, pp61-65 (1993) Similand, J .; et al, Life Science, Vol. 63, PL113-PL117 (1998) Lange, JH, et al, Journal of Medicinal Chemistry, Vol. 47 (3), p627-643 (2004)

  An object of the present invention is to provide a novel pyrazolo [1,5-a] pyrimidine compound having an excellent CB1 receptor antagonistic activity and useful as a medicine.

  The present invention relates to general formula [I]:

[Wherein, R ¹ and R ² are the same or different and each may have an aryl group which may have a substituent or a saturated or unsaturated heterocyclic group which may have a substituent,
R ⁰ is (a) a hydrogen atom; (b) an alkyl group optionally substituted with 1 to 3 halogen atoms; (c) an alkyloxyalkyl group; (d) Formula: —CON (R ^e ) (R ^f ) a group represented by: (e) an aminoalkyl group (the amino group portion of the group may be substituted with 1 to 2 alkyl groups); (f) an alkyl group, an alkylcarbonyl group, and an alkylsulfonyl group An amino group which may be substituted with a group selected from: (g) a 4- to 6-membered nitrogen-containing aliphatic heterocyclic group; (h) a formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ) A group; (i) a group represented by the formula: -NHCONHR ⁰³ ; (j) an alkyloxy group optionally substituted with a hydroxyl group; (k) a hydroxyalkyl group; or (l) a carboxyl group, R ^e and R ^f are , Same or different, hydrogen atom, alkyl group Dialkylamino group, R ⁰¹ and R ⁰² are the same or different and represent a hydrogen atom, an alkyl group or carbamoyl group, R ⁰³ is a hydrogen atom or an alkyl group,
E is a group represented by the formula: —C (═O) — or —SO ₂ —;
R represents (A) R ⁰ is (a) a hydrogen atom; (b) an alkyl group optionally substituted with 1 to 3 halogen atoms; (c) an alkyloxyalkyl group; (e) an aminoalkyl group ( The amino group portion of the group may be substituted with 1 to 2 alkyl groups); (f) an amino group optionally substituted with a group selected from an alkyl group, an alkylcarbonyl group and an alkylsulfonyl group; (G) a 4- to 6-membered nitrogen-containing aliphatic heterocyclic group; or (j) an alkyloxy group that may be substituted with a hydroxyl group, the following formula [i], [ii], or [iii]:

And (B) R ⁰ is a group represented by the formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ), a formula: —NHCONHR ⁰³ , a formula: —CON (R ^e ) (R ^f ), A carboxyl group or a hydroxyalkyl group, it represents (a) an alkyloxy group or (b) a group represented by the formula: —N (R ⁵ ) (R ⁶ ),
Ring A is a C _3-8 cycloalkyl group (which may be condensed with a benzene ring) or a benzene ring, Q is a single bond or a methylene group,
Ring B is a 4- to 7-membered aliphatic heterocyclic group bonded to the adjacent nitrogen atom via the ring-constituting carbon atom, X is a sulfur atom, —SO—, —SO ₂ —, an oxygen atom or —NR ^k —. The group shown, R ^k is an alkyl group, an alkylcarbonyl group, an alkyloxycarbonyl group, an alkylsulfonyl group, an aminosulfonyl group optionally substituted with 1 to 2 alkyl groups, or 1 to 2 alkyl groups. An optionally substituted carbamoyl group,
R ³ is (a) an alkyl group optionally substituted with a group selected from a hydroxyl group, an amino group, an acylamino group, a dialkylcarbamoylamino group, an alkylsulfonylamino group, and a dialkylsulfamoylamino; (b) a cyano group; c) carboxyl group; (d) alkyloxycarbonyl group; (e) formula: —N (R ^a ) (R ^b ) group; (f) formula: —CON (R ^a ) (R ^b ) (G) the following formula:

A group represented by: or (h) a hydroxyl group,
R ^a and R ^b are the same or different and are a hydrogen atom, hydroxyl group, cyano group, alkyl group, cyanoalkyl group, trihalogenoalkyl group, hydroxyalkyl group, alkyloxyalkyl group, cycloalkyl group, acyl group, alkylsulfonyl group or Represents an aminoalkyl group (the amino group portion of the group may be substituted with 1 to 2 alkyl groups), or both R ^a and R ^b are bonded to each other at the end to contain a saturated or unsaturated group; Nitrogen heterocyclic group (this heterocyclic group may contain a hetero atom selected from sulfur atom and oxygen atom in addition to nitrogen atom)
R ⁴ represents (a) a hydrogen atom; (b) an alkyl group; (c) a cyano group; (d) a carboxyl group; (e) an alkylcarbonyl group; (f) an alkyloxycarbonyl group; (g) a formula: —CON ( R ^c ) a group represented by (R ^d ); (h) a phenyl group; (i) a benzyl group; or (j) an acylamino group, R ^c and R ^d are the same or different and are a hydrogen atom or an alkyl group,
One of R ^A and R ^B is (a) an alkyl group (which may be substituted with a hydroxyl group, an alkyloxy group, an amino group, an alkylamino group or a dialkylamino group); (b) a phenyl group (the phenyl group is Optionally substituted by 1 to 2 groups selected from a halogen atom, an alkyloxy group and a trihalogenoalkyl group); (c) a benzyl group; (d) a heteroaryl group; or (e) a cycloalkyl group And the other is (a) a hydrogen atom; or (b) an alkyl group (which may be substituted with a hydroxyl group, an alkyloxy group, an amino group, an alkylamino group, or a dialkylamino group),
In R ⁵ and R ⁶ , (A) one is a hydrogen atom or an alkyl group, and the other is (a) substituted with a halogen atom, a hydroxyl group, a cyano group, an alkyloxy group, a cycloalkyl group, or one or two alkyl groups. An amino group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, an acyl group, an aryl group which may have a substituent, and a saturated or unsaturated heterocyclic group which may have a substituent An alkyl group which may be substituted with 1 to 3 groups selected from the group; (b) a cycloalkyl group which may have a substituent; (c) a formula: —N (R ⁸ ) (R ⁹ (D) an aryl group optionally having substituent (s); or (e) a saturated or unsaturated heterocyclic group optionally having substituent (s), or (B) together both R ⁵ and ^{R 6} at the end Combined represent to form adjacent nitrogen atom together may be substituted saturated or unsaturated nitrogen-containing heterocyclic group,
One of R ⁸ and R ⁹ is a hydrogen atom or an alkyl group, and the other is (a) an alkyl group which may be substituted with 1 to 3 groups selected from a halogen atom, a cyano group and an aryl group; b) a cycloalkyl group optionally having a substituent; (c) an aryl group optionally having a substituent; (d) an acyl group; or (e) a saturated optionally having a substituent. Or represents an unsaturated heterocyclic group. ]
A compound represented by the formula (However, 6-phenyl-7- (4-chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyano-4-tetrahydrothiopyranyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-dimethylbenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-methylbenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine; 6- (2 -Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyanobenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine; and 6- (2-chlorophenyl) -7- (4-chlorophenyl) ) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2- (hydroxymethyl) pyrazolo [1,5-a] pyrimidine) or a pharmaceutically acceptable salt thereof Regarding salt.

  Since the compound [I] of the present invention has a high affinity for the CB1 receptor, it is useful as a CB1 receptor ligand (particularly a CB1 receptor antagonist), and the receptor is involved based on its antagonistic action. It is useful for the prevention and treatment of various diseases (for example, psychosis including schizophrenia, appetite disorders (bulimia, anorexia), etc.). In addition, the compound [I] of the present invention is useful for chronic treatment and withdrawal from alcohol or drug abuse (for example, opioids). Furthermore, the compound [I] of the present invention is useful as an analgesic activity enhancer or a smoking cessation aid.

  In addition, the compound [I] of the present invention or a pharmacologically acceptable salt thereof has a feature of low toxicity and high safety as a medicine.

  The compound [I] of the present invention includes compounds that can be useful as selective antagonists for peripheral CB1 from the viewpoint of central migration.

  One embodiment of the present invention is, for example, the general formula [II]:

[Wherein, R ^0A represents (a) a hydrogen atom; (b) an alkyl group optionally substituted with 1 to 3 halogen atoms; (c) an alkyloxyalkyl group; (d) an aminoalkyl group (the group (The amino group portion of may be substituted with 1 to 2 alkyl groups); (e) an amino group optionally substituted with a group selected from an alkyl group, an alkylcarbonyl group and an alkylsulfonyl group; ) A 4-6 membered nitrogen-containing aliphatic heterocyclic group; or (g) an alkyloxy group optionally substituted with a hydroxyl group,
R ′ represents the following formula [i], [ii] or [iii]:

The other symbols have the same meaning as described above. ]
A compound represented by the formula (However, 6-phenyl-7- (4-chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyano-4-tetrahydrothiopyranyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-dimethylbenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-methylbenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine; and 6- ( 2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyanobenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine; or a pharmaceutically acceptable salt thereof. To do.

  In addition, the present invention can be used as another embodiment, for example, represented by the general formula [I-II]:

[Wherein, R ^0B represents a group represented by the formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ), a group represented by the formula: —NHCONHR ⁰³ , and a formula: —CON (R ^e ) (R ^f ) Group, carboxyl group or hydroxyalkyl group, R ⁰¹ and R ⁰² are the same or different from each other, hydrogen atom, alkyl group or carbamoylalkyl group, R ⁰³ is a hydrogen atom or alkyl group, and R ^e and R ^f are the same or different from each other. An atom, an alkyl group or a dialkylamino group,
R ″ represents an alkyloxy group or a group represented by the formula: —N (R ⁵ ) (R ⁶ ), and other symbols have the same meaning as described above.]
Or a pharmaceutically acceptable salt thereof (provided that 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) Carbamoyl] -2- (hydroxymethyl) pyrazolo [1,5-a] pyrimidine).

In the compound [I] of the present invention, when R ¹ and / or R ² is an aryl group, examples of the aryl group include 6 to 10-membered monocyclic or bicyclic aryl such as phenyl group and naphthyl group. And a phenyl group is preferable.

When R ¹ and / or R ² is a saturated or unsaturated heterocyclic group, the heterocyclic group contains, for example, 1 to 3 heteroatoms selected from a sulfur atom, an oxygen atom and a nitrogen atom And a saturated or unsaturated 5- to 7-membered heteromonocyclic group. More specifically, a 5- or 6-membered oxygen-containing heterocyclic group such as a furyl group, a tetrahydrofuranyl group, a pyranyl group, or a tetrahydropyranyl group, a thienyl group, a tetrahydrothienyl group, a thiopyranyl group, or a tetrahydrothiopyranyl group. Saturated or unsaturated 5- to 6-membered sulfur-containing heterocyclic group, or pyrrolidinyl group, imidazolyl group, pyrazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, pyridyl group, piperidyl group, pyrimidinyl group, pyrazinyl group, pyridazinyl A saturated or unsaturated 5- to 7-membered nitrogen-containing heterocyclic group such as a group, morpholinyl group, thiomorpholinyl group and azacycloheptyl group, and among them, a saturated or unsaturated group such as thienyl group, pyrrolidinyl group, piperidyl group or pyridyl group Unsaturated 5-6 membered sulfur-containing or nitrogen-containing double Monocyclic groups are preferred.

The aryl group in R ¹ and / or R ² may be substituted with a halogen atom, a cyano group, an alkyl group that may be substituted with 1 to 3 halogen atoms, or 1 to 3 halogen atoms. It may be substituted with 1 to 3 groups selected from an alkyloxy group, an amino group optionally substituted with 1 to 2 alkyl groups, an alkylthio group, an alkylsulfinyl group and an alkylsulfonyl group.

The saturated or unsaturated heterocyclic group in R ¹ and / or R ² is a halogen atom, a cyano group, an oxo group, an alkyl group optionally substituted with 1 to 3 halogen atoms, an alkyloxyalkyl group, Alkyloxy group optionally substituted with 1 to 3 halogen atoms, alkyloxyalkyloxy group, amino group optionally substituted with 1 to 2 alkyl groups, alkylthio group, alkylsulfinyl group and alkylsulfonyl It may be substituted with 1 to 3 groups selected from the group.

In the compound [I] of the present invention, when R ⁰ or R ^0A is a 4-6 membered nitrogen-containing aliphatic heterocyclic group, examples of the aliphatic heterocyclic group include azetidinyl group, pyrrolidinyl group, imidazolidinyl Group, piperidyl group, piperazinyl group, morpholinyl group and the like.

As the saturated or unsaturated nitrogen-containing heterocyclic group in R ³ [the group represented by the formula: —N (R ^a ) (R ^b ) or the group represented by the formula: —CON (R ^a ) (R ^b )] For example, a saturated or unsaturated 5- or 6-membered nitrogen-containing heteromonocyclic group such as a pyrrolyl group, a pyrrolidinyl group, a piperidino group, a piperazino group, a morpholino group, or a thiomorpholino group, among which a pyrrolidinyl group or a morpholino group Is preferred.

When R ^A or R ^B is a heteroaryl group, examples of the heteroaryl group include a 5- to 6-membered nitrogen-containing monocyclic heteroaryl group such as a pyridyl group.

When R ⁵ , R ⁶ , R ⁸ or R ⁹ is a cycloalkyl group, the cycloalkyl group is (a) a cyano group, (b) an alkyl group, (c) a carboxyl group, (d) an alkyloxycarbonyl group, (E) an amino group (the amino group may be substituted with 1 to 2 alkyl groups) and (f) a carbamoyl group (the carbamoyl group may be substituted with 1 to 2 alkyl groups). ) May be substituted with 1 to 2 groups selected from

Examples of the aryl group in R ⁵ , R ⁶ , R ⁸ or R ⁹ include 6 to 10-membered monocyclic or bicyclic aryl groups such as a phenyl group and a naphthyl group, and among these, a phenyl group is preferable. The aryl group may be substituted with 1 to 2 halogen atoms.

When R ⁵ , R ⁶ , R ⁸ or R ⁹ is a saturated or unsaturated heterocyclic group, the heterocyclic group includes (a) a saturated or unsaturated 4- to 7-membered heteromonocyclic group (including The heteromonocyclic group includes 1 to 4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom); (b) the heteromonocyclic group, a 3 to 8 membered cycloalkyl group, and 5 to 6 From a member monocyclic aryl group and a saturated or unsaturated 4- to 7-membered heteromonocyclic group (the heteromonocyclic group contains 1 to 4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom) 8- to 15-membered saturated or unsaturated nitrogen-containing bicyclic or tricyclic heterocyclic group formed by condensation of 1 to 2 selected cyclic groups; or (c) saturated or unsaturated 8 to 11 members And nitrogen-containing spiroheterocyclic groups.

Examples of the saturated or unsaturated heterocyclic group for R ⁵ , R ⁶ , R ⁸ or R ⁹ include:
(A) Furyl group, tetrahydrofuranyl group, pyranyl group, tetrahydropyranyl group, thiacyclobutyl group, thienyl group, tetrahydrothienyl group, thiopyranyl group, tetrahydrothiopyranyl group, benzofuranyl group, dihydrobenzofuranyl group, isobenzo Saturated or unsaturated oxygen-containing or sulfur-containing heterocyclic group selected from furanyl group, chromanyl group, isochromanyl group, chromenyl group, isochromenyl group, benzothienyl group and dihydrobenzothienyl group, or (B) azetidyl group, pyrrolidinyl group Pyrrolinyl group, imidazolidinyl group, imidazolinyl group, pyrazolidinyl group, pyrazolinyl group, pyrrolyl group, 2H-pyrrolyl group, imidazolyl group, pyrazolyl group, dihydropyrazolyl group, thiazolidinyl group, thiazolyl group, isothiazolyl group, Soxazolyl group, oxazolidinyl group, pyridyl group, dihydropyridyl group, tetrahydropyridyl group, piperidyl group, pyrazinyl group, piperazinyl group, pyrimidinyl group, tetrahydropyrimidinyl group, pyridazinyl group, morpholinyl group, azosinyl group, azacycloheptyl group, indolizinyl group, Benzimidazolyl group, benzotriazolyl group, indolyl group, isoindolyl group, 3H-indolyl group, indolinyl group, isoindolinyl group, 1H-indazolyl group, pyrrolopyridyl group, pyrrolopyrimidinyl group, tetrazolyl group, purinyl group, pteridinyl group, 4H- Quinolidinyl group, quinolyl group, dihydroquinolyl group, tetrahydroquinolyl group, isoquinolyl group, dihydroisoquinolyl group, tetrahydroisoquinolyl group, phthalazinyl , Dihydrophthalazinyl group, naphthyridinyl group, dihydronaphthyridinyl group, tetrahydronaphthyridinyl group, quinoxalinyl group, quinazolinyl group, dihydrobenzothiazinyl group, dihydrobenzoxazinyl group, cinnolinyl group, pteridinyl group, xanthenyl group, carbazolyl Group, β-carbolinyl group, phenanthridinyl group, acridinyl group, 5H-dihydrodibenzazepinyl group and the general formula:

[Wherein, R ^G and R ^H are the same or different and represent a hydrogen atom or an alkyl group, and q and r each represent an integer of 1 or 2. ]
And a saturated or unsaturated nitrogen-containing heterocyclic group selected from spiroheterocyclic groups represented by the formula:

  Among the above, preferred saturated or unsaturated heterocyclic groups include, for example, tetrahydrofuranyl group, pyrrolyl group, pyrrolidinyl group, piperidyl group, azacycloheptyl group, tetrahydropyranyl group, piperazinyl group, morpholinyl group, thiomorpholinyl group, Examples include a thiacyclobutyl group, a tetrahydrothienyl group, a tetrahydrothiopyranyl group, a thiazolyl group, a pyridyl group, a pyrimidinyl group, an indolinyl group, a pyrrolopyridyl group, and a tetrahydronaphthyridinyl group.

Examples of the saturated or unsaturated nitrogen-containing heterocyclic group formed by combining R ⁵ and R ⁶ with each other include:
(A) a saturated or unsaturated 4- to 7-membered nitrogen-containing heteromonocyclic group (the heteromonocyclic group may contain two or more nitrogen atoms, and in addition to the nitrogen atom, an oxygen atom and a sulfur atom) And may contain 1 to 2 heteroatoms selected from:
(B) the heteromonocyclic group, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered monocyclic aryl group, and a saturated or unsaturated 4- to 7-membered heteromonocyclic group (the heteromonocyclic group is 8- to 15-membered saturated or unsaturated nitrogen-containing bicyclic ring formed by condensation of 1 to 2 cyclic groups selected from oxygen atoms, sulfur atoms and nitrogen atoms (including 1 to 4 heteroatoms) And a cyclic or tricyclic heterocyclic group; or (c) a saturated or unsaturated 8- to 11-membered nitrogen-containing spiro heterocyclic group.

  Specific examples of the saturated or unsaturated nitrogen-containing heterocyclic group include, for example, azetidyl group, pyrrolidinyl group, pyrrolinyl group, imidazolidinyl group, imidazolinyl group, pyrazolidinyl group, pyrazolinyl group, pyrrolyl group, imidazolyl group, pyrazolyl group, Dihydropyrazolyl group, thiazolidinyl group, oxazolidinyl group, dihydropyridyl group, tetrahydropyridyl group, piperidyl group, piperazinyl group, tetrahydropyrimidinyl group, morpholinyl group, azacycloheptyl group, benzimidazolyl group, benzotriazolyl group, indolyl group, isoindolyl Group, indolinyl group, isoindolinyl group, 1H-indazolyl group, purinyl group, dihydroquinolyl group, tetrahydroquinolyl group, dihydroisoquinolyl group, tetrahydroisoquinolyl group, Hydro lid pyrazinyl group, dihydroquinazolinyl group, dihydro-benzothiazinyl group, dihydro benzoxazinyl group, carbazolyl group, beta-carbolinyl group, 5H-dihydrodibenz dithienoazepinyl groups and the general formula:

[Wherein, R ^G and R ^H are the same or different and represent a hydrogen atom or an alkyl group, and q and r each represent an integer of 1 or 2. ]
And a saturated or unsaturated nitrogen-containing heterocyclic group selected from spiroheterocyclic groups represented by the formula:

  Among the above, preferred saturated or unsaturated nitrogen-containing heterocyclic groups include, for example, saturated 5- to 7-membered nitrogen-containing heterocyclic monocyclic groups such as morpholino group, thiomorpholino group, piperidino group, piperazino group or azacycloheptyl group. Group.

Furthermore, the saturated or unsaturated heterocyclic group (and the nitrogen-containing heterocyclic group formed by combining R ⁵ and R ⁶ ) in R ⁵ , R ⁶ , R ⁸ or R ⁹ is a halogen atom, a hydroxyl group , Cyano group, oxo group, alkyl group, alkyl group substituted with 1 to 3 halogen atoms, alkyloxyalkyl group, aminoalkyl group, cycloalkyl group, arylalkyl group, alkyloxy group, 1 to 3 An alkyloxy group substituted with a halogen atom, an acyl group, an amino group optionally substituted with 1 to 2 alkyl groups, an acylamino group, an alkylsulfonyl group, or an alkyl group substituted with 1 to 2 alkyl groups 1-4 selected from a good aminosulfonyl group, an aryl group optionally substituted by 1 to 2 halogen atoms, and a saturated or unsaturated 5- to 6-membered nitrogen-containing heterocyclic group It may be substituted with the group.

Examples of the acyl group in R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁸ or R ⁹ include the following general formula:
R ^X -COOH [Ac-1]
[In the formula, R ^X represents (a) a hydrogen atom, (b) an alkyl group optionally substituted with 1 to 3 groups selected from a halogen atom, a cyano group, an alkylsulfonyl group and a pyridyl group, (c 1) or 2 groups selected from an alkyloxy group optionally substituted with an aryl group, (d) a cycloalkyl group, (e) a halogen atom, a cyano group, an alkyl group, a trihalogenoalkyl group and an alkyloxy group An aryl group optionally substituted with (f) an amino group optionally substituted with 1 to 2 alkyl groups, or (g) a halogen atom, a cyano group, an alkyl group and a trihalogenoalkyl group. It represents a saturated or unsaturated 5- to 7-membered heterocyclic group which may be substituted with 1 to 2 groups. ]
In groups formed by removing one hydroxyl group from a carboxylic acid represented (i.e., formula group represented by R X ^CO-) and the like. Specific examples of such an acyl group include, for example, (a1) formyl group, (b1) acetyl group, C _1-6 alkyl-carbonyl group such as propionyl group, and trihalogeno C _1-6 alkyl such as trifluoroacetyl group. - carbonyl group, such as cyano _{C 1-6} alkyl cyanoacetyl group - carbonyl group, such as pyridyl _{-C 1-6} alkyl pyridyl acetyl - carbonyl group, (c1) methoxycarbonyl group, an ethoxycarbonyl group, tert- butoxycarbonyl such _{C 1-6} alkyloxy group - carbonyl group, such as an aryl _{-C 1-6} alkyloxy benzyloxycarbonyl group - carbonyl group, (d1) cyclopropylcarbonyl group, such as _{C 3-8} cycloalkyl cyclopentyl group -Carbonyl group, (e1) benzoy Aryl-carbonyl groups such as chlorobenzoyl groups, chlorobenzoyl groups, fluorobenzoyl groups, mono- or dihalogenoaryl-carbonyl groups such as difluorobenzoyl groups, cyanoaryl-carbonyl groups such as cyanobenzoyl groups, trihalogeno groups such as trifluoromethylbenzoyl groups. C _1-6 alkyl - aryl - carbonyl group, such as _{C 1-6} alkyloxy methoxybenzoyl group - aryl - carbonyl group, (f1) carbamoyl group, _{N-(C 1-6} alkyl) carbamoyl group, or (g1) 5- to 6-membered groups such as furoyl, thenoyl, bromothenoyl, cyanothenoyl, pyridylcarbonyl, chloropyridylcarbonyl, cyanopyridylcarbonyl, trifluoromethylpyridylcarbonyl or pyrazinylcarbonyl Roariru - carbonyl group (the heteroaryl portion of the group is a halogen atom, a cyano group, an alkyl group and may be substituted with one to two groups selected from trihalogenoalkyl group) and the like.

  As a more specific embodiment of the present invention, the following general formula [I-IA]:

[Wherein R ¹⁰ and R ²⁰ are the same or different and (i) a 6 to 10-membered monocyclic or bicyclic aryl group (the aryl group is substituted with a halogen atom, a cyano group, or 1 to 3 halogen atoms An alkyl group that may be substituted, an alkyloxy group that may be substituted with 1 to 3 halogen atoms, an amino group that may be substituted with 1 to 2 alkyl groups, an alkylthio group, an alkylsulfinyl group, and Optionally substituted with 1 to 3 groups selected from alkylsulfonyl groups); or (ii) saturated or unsaturated sulfur-containing, oxygen-containing or nitrogen-containing 4- to 7-membered heteromonocyclic group (the heterocyclic ring) The formula group is a halogen atom, a cyano group, an oxo group, an alkyl group which may be substituted with 1 to 3 halogen atoms, an alkyloxy group which may be substituted with 1 to 3 halogen atoms, 1 to 2 Pieces Alkyl amino group which may be substituted with a group, or an alkylthio group, optionally substituted with 1 to 3 groups selected from alkylsulfinyl group and alkylsulfonyl group),
R ^S represents the following formula [ia], [ii-a] or [iii-a]:

A group represented by
R ³⁰ is (a) an alkyl group (the alkyl group may be substituted with a group selected from a hydroxyl group, an amino group, an acylamino group, a dialkylcarbamoylamino group, an alkylsulfonylamino group, and a dialkylsulfamoylamino group); (B) a cyano group; (c) a carboxyl group; (d) an alkyloxycarbonyl group; (e) a group represented by the formula: —N (R ^aa ) (R ^bb ); (f) a formula: —CON (R ^aa ) A group represented by (R ^bb ); (g)

Or (h) a hydroxyl group, R ^aa and R ^bb are the same or different and are a hydrogen atom, a hydroxyl group, a cyano group, an alkyl group, a cyanoalkyl group, a trihalogenoalkyl group, a hydroxyalkyl group, an alkyloxyalkyl group, A cycloalkyl group, a group represented by the formula: R ^xa CO—, an alkylsulfonyl group or an aminoalkyl group (the amino group part of the group may be substituted with 1 to 2 alkyl groups), or R ^aa and R ^bb are both bonded to each other at the end to form a saturated or unsaturated nitrogen-containing heterocyclic group (the heterocyclic group further contains a hetero atom selected from an oxygen atom and a sulfur atom in addition to a nitrogen atom). R ^xa is (a) a hydrogen atom, (b) an alkyl group (the alkyl group is a halogen atom, a cyano group, an alkylsulfonyl group, and a pyridyl group). (C) an alkyloxy group (the alkyloxy group may be substituted with a 6 to 10-membered monocyclic or bicyclic aryl group). (D) a cycloalkyl group, (e) a 6 to 10-membered monocyclic or bicyclic aryl group (the aryl group is selected from a halogen atom, a cyano group, an alkyl group, a trihalogenoalkyl group, and an alkyloxy group) (Optionally substituted with 1 to 2 groups), (f) amino group (the amino group may be substituted with 1 to 2 alkyl groups) or (g) saturated or unsaturated sulfur-containing An oxygen-containing or nitrogen-containing 4- to 7-membered heteromonocyclic group (the heteromonocyclic group is substituted with 1 to 2 groups selected from a halogen atom, a cyano group, an alkyl group and a trihalogenoalkyl group) You may)
R ⁴⁰ represents (a) a hydrogen atom; (b) an alkyl group; (c) a cyano group; (d) a carboxyl group; (e) an alkylcarbonyl group; (f) an alkyloxycarbonyl group; (g) a formula: —CON ( A group represented by R ^cc ) (R ^dd ); (h) a phenyl group; (i) a benzyl group or (j) a group represented by the formula: R ^xa CONH—, R ^cc and R ^dd are the same or different, and An atom or an alkyl group,
One of R ^Aa and R ^Ba is (a) an alkyl group (the alkyl group may be substituted with a hydroxyl group, an alkyloxy group, an amino group, an alkylamino group, or a dialkylamino group); The phenyl group may be substituted with 1 to 2 groups selected from a halogen atom, an alkyloxy group and a trihalogenoalkyl group); (c) a benzyl group; (d) a 5- to 6-membered nitrogen-containing heteroaryl group Or (e) a cycloalkyl group and the other is (a) a hydrogen atom; or (b) an alkyl group (the alkyl group is substituted with a hydroxyl group, an alkyloxy group, an amino group, an alkylamino group, or a dialkylamino group); Other symbols have the same meaning as described above. ]
(Wherein 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyanobenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine, 6- (2 -Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyano-4-tetrahydrothiopyranyl) carbamoyl] pyrazolo [1,5-a] pyrimidine, 6-phenyl-7- (4- Chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5-a] pyrimidine; 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5 -A] pyrimidine; 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-dimethylbenzyl) carbamoyl] pyrazo [1,5-a] pyrimidine; 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-methylbenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine; (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine; 6- (2-chlorophenyl) -7 -(4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine; and 6- (2-chlorophenyl) -7- (4 -Chlorophenyl) -3- [N- (4-cyanobenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine) or a pharmaceutically acceptable salt thereof.

  As a more specific embodiment regarding the compound [I-IA] of the present invention, the following general formula [I-I-a]:

[Wherein, R ^1A represents (a) a phenyl group which may be substituted with one or two groups selected from a halogen atom, a difluoroalkyl group, a trifluoroalkyl group and a dialkylamino group, or (b) an alkyl group, A saturated or unsaturated 5- to 6-membered nitrogen-containing heterocyclic group which may be substituted with a group selected from a trifluoroalkyl group and an alkyloxy group;
R ^2A is a phenyl group optionally substituted by 1 to 2 groups selected from a halogen atom and a cyano group;
R ^S1 represents the following formula [ib], [ic], [id], [ii-b], [iii-b] or [iii-c]:

A group represented by
Ring A ^a is (a) a C _3-8 cycloalkyl group or (b) a C _5-6 cycloalkyl group condensed with a benzene ring, Q is a single bond or a methylene group,
Ring B ^a 4 to 7 membered aliphatic heteromonocyclic group bonded to the adjacent nitrogen atom through the ring-constituting carbon atoms,
R ³¹ represents a cyano group, an alkyl group, a hydroxyalkyl group, an aminoalkyl group (the amino part of the group may be substituted with an alkylcarbonyl group, a dialkylsulfamoyl group, an alkylsulfonyl group or a dialkylcarbamoyl group), carboxy An alkyl group, a carboxyl group, an alkyloxycarbonyl group, a carbamoyl group (the amino group portion of the group may be substituted with one or two groups selected from an alkyl group and a dialkylaminoalkyl group), or the following:

A group represented by
R ⁴¹ is a hydrogen atom, an amino group, or a group represented by the formula: R ^xa CONH—
R ³² represents a hydroxyl group, a carboxyl group, an alkyloxycarbonyl group, an amino group, or a group represented by the formula: R ^xa CONH—
R ³³ is a carboxyl group or an alkyloxycarbonyl group,
R ³⁴ is a cyano group, an alkyl group, a hydroxyalkyl group, an aminoalkyl group, a carboxyalkyl group, a carboxyl group, an alkyloxycarbonyl group, a carbamoyl group (the amino group portion of the group is an alkyl group, a hydroxyalkyl group, a cyanoalkyl group, A trihalogenoalkyl group, an alkyloxyalkyl group, a cycloalkyl group, an alkylsulfonyl group and a dialkylaminoalkyl group which may be substituted with 1 to 2 groups), a formula:

Or a group represented by

The ring J is a saturated or unsaturated 4- to 7-membered nitrogen-containing heteromonocyclic group (the heterocyclic group may contain an oxygen atom as a hetero atom other than the nitrogen atom),
R ³⁵ is a hydroxyalkyl group, a carboxyl group, an alkyloxycarbonyl group or a carbamoyl group (the amino group portion of the group may be substituted with 1 to 2 alkyl groups),
R ^A1 is an alkyl group, a cycloalkyl group, a phenyl group (the phenyl group may be substituted with 1 to 2 groups selected from a halogen atom, an alkyloxy group and a trihalogenoalkyl group) or a benzyl group;
R ^B1 represents a hydrogen atom or an alkyl group,
R ³⁶ represents an alkyl group or a carbamoyl group,
R ^B2 represents a hydrogen atom or an alkyl group, and other symbols have the same meaning as described above. ]
(Wherein 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyano-4-tetrahydrothiopyranyl) carbamoyl] pyrazolo [1,5-a]) Pyrimidine, 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine and 6- (2- Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine) or pharmacologically acceptable Examples of the salt that can be obtained.

  Further, the present invention is more specifically described as another embodiment of the following general formula [I-II-i]:

[Where,
R ^5A represents a hydrogen atom or an alkyl group,
R ^6A represents (A) an alkyl group (the group is (a) a halogen atom, (b) a hydroxyl group, (c) a cyano group, (d) an alkyloxy group, (e) a carboxyl group, (f) a carbamoyl group (this group May be substituted with 1 to 2 alkyl groups), (g) an alkylthio group, (h) an alkylsulfonyl group (i) a cycloalkyl group (the group is 1 to 2 groups selected from an alkyl group and a hydroxyl group) (J) an amino group optionally substituted with 1 to 2 alkyl groups, and (k) a saturated or unsaturated 4- to 10-membered, monocyclic or bicyclic group. Optionally substituted with 1 to 3 groups selected from nitrogen, sulfur-containing or oxygen-containing heterocyclic groups);
(B) a cycloalkyl group (the cycloalkyl group may be condensed with a benzene ring, and (a) an alkyl group optionally substituted with a group selected from a hydroxyl group, a carboxyl group, and an amino group; (b) (C) carboxyl group; (d) formula: group represented by R ^xa CO—; (e) formula: —N (R ^a1 ) (R ^b1 ) group; (f) formula: —CON (R ^a1 ) a group represented by (R ^b1 ); (g) a 6 to 10-membered monocyclic or bicyclic aryl group; (h) an alkyl group substituted with a 6 to 10-membered monocyclic or bicyclic aryl group And (i) optionally substituted with 1 to 2 groups selected from saturated or unsaturated 4 to 7-membered nitrogen-containing heteromonocyclic group which may be substituted with 1 to 2 oxo groups; ^{), R a1} and ^{R b1} are the same or different and represent a hydrogen atom, a hydroxyl group, a cyano , An alkyl group, the formula: a group represented by R ^{xa CO-,} an alkylsulfonyl group, an aminoalkyl group, a monoalkylamino group or dialkylamino group;
(C) 6 to 10-membered monocyclic or bicyclic aryl group (the aryl group may be substituted with 1 to 2 groups selected from a cyano group, a trihalogenoalkyl group, an alkyloxy group and a carboxyl group) );
(D) a saturated or unsaturated 4- to 10-membered monocyclic or bicyclic heterocyclic group (the heterocyclic group contains at least one heteroatom selected from a sulfur atom, an oxygen atom and a nitrogen atom, and (A) halogen atom, (b) hydroxyl group, (c) oxo group, (d) cyano group, (e) alkyl group, (f) trihalogenoalkyl group, (g) hydroxyalkyl group, (h) alkyloxyalkyl Group, (i) alkyloxy group, (j) group represented by formula: R ^xa CO—, (k) cycloalkyl group, (l) alkylsulfonyl group, (m) substituted with 1 to 2 alkyl groups An optionally substituted aminosulfonyl group, (n) a phenylsulfonyl group, (o) an amino group, (p) a group represented by the formula: R ^xa CONH-, (q) substituted with 1 to 2 alkyl groups Good carbamoyl group, ( r) 6 to 10-membered monocyclic or bicyclic aryl group optionally substituted with a halogen atom and (s) optionally substituted with 1 or 2 groups selected from an alkyl group and a trihalogenoalkyl group Saturated or unsaturated sulfur-containing, oxygen-containing or nitrogen-containing optionally substituted with 1 to 4 groups selected from 4 to 7-membered heteromonocyclic groups);
(E) a group represented by the formula: —N (R ⁸¹ ) (R ⁹¹ ), R ⁸¹ is a hydrogen atom or an alkyl group, R ⁹¹ is (a) an alkyl group (the alkyl group is a halogen atom, a cyano group and 6 to 6 Optionally substituted with 1 to 3 groups selected from 10-membered monocyclic or bicyclic aryl groups); (b) cycloalkyl groups; (c) 6-10 membered monocyclic or bicyclic aryl groups (The aryl group is a group selected from a halogen atom, a cyano group, an alkyl group, a trihalogenoalkyl group, an alkyloxy group, a trihalogenoalkyloxy group, an alkylthio group, an alkylsulfonyl group, and a group represented by the formula: R ^xa CO—. (D) a group represented by the formula: R ^xa CO—; or (e) a saturated or unsaturated sulfur-containing, oxygen-containing or nitrogen-containing 4- to 7-membered heterocyclic monocyclic group Heterocyclic groups are Optionally substituted with a group selected from a halogen atom, an alkyl group, a trihalogenoalkyl group and an alkyloxy group); or (F) R ^5A and R ^6A are bonded to each other and saturated or unsaturated together with the adjacent nitrogen atom 4- to 10-membered monocyclic or bicyclic nitrogen-containing heterocyclic group (this nitrogen-containing heterocyclic group has 1 to 2 heteroatoms selected from sulfur atom and oxygen atom in addition to nitrogen atom) And may be substituted with one or two groups selected from a halogen atom, an oxo group, an alkyl group, a group represented by the formula: R ^xa CO— and a dialkylaminosulfonyl group). The other symbols have the same meaning as described above. ]
Embedded image wherein 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2- (hydroxymethyl) ) Except for pyrazolo [1,5-a] pyrimidine) or a pharmaceutically acceptable salt thereof; and the following general formula [I-II-ii]:

[Wherein, R ⁿ represents an alkyl group, and other symbols have the same meaning as described above. ]
Or a pharmaceutically acceptable salt thereof.

Regarding the above-mentioned present invention, as another specific embodiment,
1) In the general formula [I-II-i], R ¹⁰ is substituted with 1 to 2 groups selected from (a) a halogen atom, an alkyl group, a difluoroalkyl group, a trifluoroalkyl group, and a dialkylamino group. and a phenyl group, or even (b) an alkyl group, a trifluoromethyl group, and alkyloxy substituted with a group selected from the group optionally may be saturated or unsaturated 5- to 6-membered nitrogen-containing heterocyclic group, R ²⁰ is halogen A phenyl group ^optionally substituted by 1 to 2 groups selected from an atom and a cyano group, R ^6A is an (A) alkyl group (the alkyl group is 1 to 3 halogen atoms, a hydroxyl group, a cyano group, a carboxyl group) Or a group selected from an alkyloxycarbonyl group); or (B) the following formula:

In cyclic groups wherein shown, ring ^{A b} is _{(a) C 3-8} cycloalkyl group or (b) a benzene ring fused with _{C 5-6} cycloalkyl ^{group, R 37} is a hydrogen atom, a cyano group, An alkyl group, a hydroxyalkyl group, an aminoalkyl group, a carboxyalkyl group, a carboxyl group, an alkyloxycarbonyl group, a carbamoyl group (the amino group portion of the group is one or two groups selected from an alkyl group and a dialkylaminoalkyl group); Optionally substituted) or the following formula:

R ⁴³ represents a hydrogen atom, an amino group, an alkyloxycarbonylamino group, or a benzyloxycarbonylamino group]; or (C) a phenyl group (the phenyl group is a halogen atom, an alkyloxy group, a trihalogeno group) (Which may be substituted with one or two groups selected from an alkyl group, a carboxyl group and an alkyloxycarbonyl group); or (D)

In cyclic groups wherein shown, Ring B ^b is the ring structure 4-7 membered aliphatic heteromonocyclic group bonded to the adjacent nitrogen atom via a carbon atom, ring B ^c is 4-7 membered aliphatic A nitrogen-containing heteromonocyclic group, X ¹ is a sulfur atom, a group represented by the formula: —SO—, a group represented by the formula: —SO ₂ —, an oxygen atom or a group represented by the formula: —NR ^m —, R ^m is an alkyl group, an alkylcarbonyl group, an alkyloxycarbonyl group, an alkylsulfonyl group, an aminosulfonyl group which may be substituted with 1 to 2 alkyl groups, or an alkyl group which may be substituted with 1 to 2 alkyl groups. a carbamoyl group, R ³⁸ is a hydrogen atom, a cyano group, an alkyl group, a hydroxyalkyl group, an aminoalkyl group, a carboxyalkyl group, a carboxyl group, an alkyloxycarbonyl group, an amino group moiety of the carbamoyl group (said group alkyl 1-2 may be substituted with a group) or the following formula selected from the group and dialkylamino group:

Or (E) a group represented by the formula: —N (R ^8a ) (R ^9a ), wherein R ^8a is a hydrogen atom or an alkyl group, R ^9a is an alkyl group, or a trihalogenoalkyl. Group, cyanoalkyl group, benzyl group, cycloalkyl group, phenyl group (the phenyl group is a halogen atom, cyano group, alkyl group, trihalogenoalkyl group, alkyloxy group, trihalogenoalkyloxy group, alkylthio group, alkylsulfonyl group) Represents an alkyloxycarbonyl group, a benzyloxycarbonyl group, or a 5- to 6-membered nitrogen-containing heteroaryl group], or (F), which may be substituted with a group selected from an alkyloxycarbonyl group and a benzyloxycarbonyl group); The following formula:

In the radical represented [wherein ring A ^c is a benzene ring condensed with C _3-8 optionally the cycloalkyl group, the ring B ^d is (a) phenyl group (said phenyl group is a halogen atom, a cyano group, an alkyl (Which may be substituted with an oxy group, a trihalogenoalkyl group or a carboxyl group) or (b) a pyridyl group, R ^S11 is a hydrogen atom or an alkyl group, R ^S12 is a hydrogen atom, an alkyl group, a carboxyl group, a carbamoyl group or a mono group Or a dialkylcarbamoyl group, R ³⁹ is a hydrogen atom, halogen atom, cyano group, alkyl group, hydroxyalkyl group, trihalogenoalkyl group, aminoalkyl group, alkyloxy group, carboxyalkyl group, carboxyl group, carbamoyl group (of the group) The amino group moiety is one or two groups selected from an alkyl group and a dialkylaminoalkyl group Or an amino group, an alkyloxycarbonylamino group or a benzyloxycarbonylamino group, k represents an integer of 0 to 2]; or 2) a compound represented by the general formula [I-II-ii] Wherein R ¹⁰ is (a) a phenyl group which may be substituted with one or two groups selected from a halogen atom, a difluoroalkyl group, a trifluoroalkyl group and a dialkylamino group, or (b) an alkyl group, trifluoro A saturated or unsaturated 5- to 6-membered nitrogen-containing heterocyclic group which may be substituted with a group selected from an alkyl group and an alkyloxy group, and R ²⁰ is a group of 1 to 2 selected from a halogen atom and a cyano group The compound which is the phenyl group which may be substituted is mention | raise | lifted.

Among the compounds [I] of the present invention, preferred compounds include, for example, in the general formula [I-I], R ¹ and R ² are the same or different, and (a) a halogen atom, a cyano group, 1 to 3 A phenyl group optionally substituted with 1 to 3 groups selected from an alkyl group optionally substituted with a halogen atom and an amino group optionally substituted with 1 to 2 alkyl groups, or (b A saturated or unsaturated 5- to 7-membered nitrogen-containing heterocyclic group which may be substituted with a group selected from an alkyl group optionally substituted with 1 to 3 halogen atoms and an alkyloxy group,
A1) R ′ is a group represented by the formula [i], R ³ is an alkyl group which may be substituted with a group selected from (a) a hydroxyl group and an amino group, (b) a cyano group, (c) a carboxyl group, (D) an alkyloxycarbonyl group, (e) a group represented by the formula: —CON (R ^e ) (R ^f ), or (f) an acylamino group, R ^e and R ^f are the same or different, and a hydrogen atom, an alkyl group or A dialkylaminoalkyl group, R ⁴ is a hydrogen atom or an acylamino group, or;
A2) R ′ is a group represented by the formula [ii], X is a sulfur atom, SO ₂ , an oxygen atom or a group ^represented by the formula: N—R ^k , R ^k is an alkyloxycarbonyl group, an alkylsulfonyl group, an alkylcarbonyl A group or a dialkylaminosulfonyl group, R ³ is (a) an alkyl group optionally substituted with a hydroxyl group, (b) a carboxyl group, (c) an alkyloxycarbonyl group or (d) a formula: —CON (R ^e ) ( A group represented by R ^f ), R ^e and R ^f are the same or different and are a hydrogen atom, an alkyl group or a trihalogenoalkyl group, R ⁴ is a hydrogen atom; or A3) R ′ is represented by the formula [iii] Group, R ^A is an alkyl group optionally substituted with a hydroxyl group, a phenyl group (the phenyl group may be substituted with a halogen atom or a trihalogenoalkyl group), or nitrogen-containing 5-6 A membered heteroaryl group, R ^B is a hydrogen atom or an alkyl group, R ³ is an alkyl group, a carboxyl group or a group represented by the formula: —CON (R ^a ) (R ^b ), R ^a and R ^b are a hydrogen atom or an alkyl group R ^0A is a hydrogen atom, an alkyl group optionally substituted with 1 to 3 halogen atoms, an alkyloxy group optionally substituted with a hydroxyl group, a hydroxyalkyl group, an amino group (the amino group). May be substituted with one or two groups selected from an alkyl group, an alkylcarbonyl group and an alkylsulfonyl group) or a compound which is a 4- to 6-membered nitrogen-containing aliphatic heterocyclic group.

Among the preferable compounds [I-I], more preferable compounds include, for example,
A1) R ′ is a group represented by the formula [i], R ³ is (a) a C _1-6 alkyl group, (b) a hydroxy-C _1-6 alkyl group, (c) an amino-C _1-6 alkyl group (D) a cyano group, (e) a carboxyl group, (f) a C _1-6 alkyloxy-carbonyl group, (g) a carbamoyl group, (h) a mono- or di (C _1-6 alkyl) carbamoyl group, (i A di (C _1-6 alkyl) amino-C _1-6 alkyl-carbamoyl group or (j) a C _1-6 alkyloxy-carbonylamino group, and R ⁴ is a hydrogen atom or phenyl-C _1-6 alkyloxy. A compound which is a carbonylamino group; or A2) a group represented by the formula [ii], R ′ is a group represented by X, a sulfur atom, SO ₂ , an oxygen atom or N—R ^k , and R ^k is C _1-6 alkyloxy - _{group, C 1-} Alkylsulfonyl _{group, C 1-6} alkyl - carbonyl or gripping _{(C 1-6} alkyl) aminosulfonyl group, ^{R 3} is (a) carbamoyl group, (b) mono- or di _{(C 1-6} alkyl) - carbamoyl groups (C) mono (trihalogeno C _1-6 alkyl) carbamoyl group, (d) C _1-6 alkyloxy-carbonyl group, (e) C _1-6 alkyl group or (f) hydroxy-C _1-6 alkyl group , R ⁴ is a hydrogen atom; or A3) R ′ is a group represented by the formula [iii], R ^A is a C _1-6 alkyl group, a hydroxy-C _1-6 alkyl group, a phenyl group, a halogenophenyl group. , trihalogeno _{(C 1-6} alkyl) - phenyl group or pyridyl group, ^{R B} is a hydrogen atom or a _{C 1-6} alkyl group, ^{R 3} is _{C 1-6} alkyl group, carboxyl groups, C _-6 alkyloxy - compound is a carbonyl group or a carbamoyl group.

Among the compounds [I-I] of the groups A1 to A3, more preferable compounds include, for example, R ¹ is a halogen atom, a dihalogeno-C _1-6 alkyl group, a trihalogeno-C _1-6 alkyl group and a di (C _1-6 alkyl) phenyl group, C _1-6 alkyloxy-pyrrolidinyl group, C _1-6 alkyl-piperidyl group or C _1-6 alkyloxypiperidyl group substituted with 1-2 groups selected from amino groups , R ² is a phenyl group substituted with 1 to 2 halogen atoms, a cyanophenyl group or a trihalogeno-C _1-6 alkyl-pyridyl group, R ^0A is a hydrogen atom, a C _1-6 alkyl group, a dihalogeno-C _{1 -6} alkyl group, trihalogeno-C _1-6 alkyl group, C _1-6 alkyloxy group, hydroxy-C _1-6 alkyloxy group, amino group, C _1-6 Examples thereof include an alkyl-carbonylamino group, a mono (C _1-6 alkyl) carbamoyl group, or a 4- to 6-membered nitrogen-containing aliphatic heterocyclic group.

Among the above compounds [I-I], particularly preferred compounds include, for example,
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-cyanocyclohexyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-cyanocyclopentyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-methylcyclohexyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-methylcyclopropyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (1-cyanocyclopentyl) carbamoyl] -7- (4-trifluoromethylphenyl) -2-methylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (1-cyanocyclohexyl) carbamoyl] -7- (4-trifluoromethylphenyl) -2-methylpyrazolo [1,5-a] pyrimidine;
3- [N- (4-Carbamoyl-1,1-dioxo-tetrahydrothiopyran-4-yl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] Pyrimidine;
2-acetylamino-6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine ;
6- (2-chlorophenyl) -7- (4-chloro-2-fluorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] -2- (1-pyrrolidinyl) pyrazolo [1,5- a] pyrimidine;
3- [N- (1-carbamoylcyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
3- [N- (4-Carbamoyl-1,1-dioxo-tetrahydrothiopyran-4-yl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5 -A] pyrimidine;
3- [N- (1-carboxycyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3-[[1- [N- [2- (N, N-dimethylamino) ethyl] carbamoyl] cyclohexyl] carbamoyl] pyrazolo [1, 5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (N-methylcarbamoyl) cyclohexyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (N, N-dimethylcarbamoyl) cyclohexyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
(S) -3- [N- (1-carboxy-2-methylpropyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine;
(S) -3- [N- (1-carboxy-2-phenylethyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
(S) -3- [N- (1-carboxy-2-methylpropyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
(S) -3- [N- (α-carboxybenzyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
(S) -3- [N- (1-carboxy-2-methylpropyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -2-methylpyrazolo [1,5-a] pyrimidine;
3- [N- (1-carboxy-1-methylethyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -2-methylpyrazolo [1,5-a] pyrimidine;
3- [N- (α-carboxybenzyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine;
3- [N- (1-carboxy-1-methylethyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
3- [N- (1-carboxy-2-phenylethyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine;
3- [N- (4-carboxy-1-cyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
3- [N- (4-carboxybenzyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
3- [N- (3-carboxybenzyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (1-cyanocyclohexyl) carbamoyl] -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-methoxycarbonylcyclohexyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (methylsulfonylamino) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine ;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- [N-methyl-N- (methylsulfonyl) amino] -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-methylpiperidin-1-yl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] Pyrimidine;
6- (2-Chlorophenyl) -7- (4-methoxypiperidin-1-yl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] Pyrimidine;
6- (2-Chlorophenyl) -7- (3-methoxypyrrolidin-1-yl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] Pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (1-methoxycarbonylcyclohexyl) sulfamoyl] -2-methylpyrazolo [1,5-a] pyrimidine;
3- [N- (1-carboxycyclohexyl) sulfamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -2-methylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (4-methoxycarbonyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1, 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5 -A] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2-methyl-3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1, 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2-methyl-3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (3-hydroxy-2-methylprop-2-yl) carbamoyl] -2-methylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (4-hydroxymethyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1, 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2-trifluoromethyl-3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [ 1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2-ethoxy-3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1, 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (2-fluoro-4-trifluoromethylphenyl) -3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (3-methoxycarbonyl-1,1-dioxothietan-3-yl) carbamoyl] pyrazolo [1,5-a] Pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-cyanocyclohexyl) carbamoyl] -2-methylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (2-hydroxyethoxy) -3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl) carbamoyl] Pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2- (2-hydroxyethoxy) -3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl ) Carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl) carbamoyl] pyrazolo [1,5- a] pyrimidine;
6- (2-Chlorophenyl) -2- (difluoromethyl) -7- (4-trifluoromethylphenyl) -3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl) carbamoyl ] Pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (trifluoromethyl) -3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [4- (N-methylcarbamoyl) -1,1-dioxotetrahydrothiopyran-4-yl] carbamoyl] Pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -3- [N- [4- [N- (2,2,2-trifluoroethyl) carbamoyl] -1,1-dioxotetrahydrothiopyran-4-yl] carbamoyl]- 7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine; and 6- (2-chlorophenyl) -3- [N- [4- [N- (2,2,2-trifluoroethyl) ) Carbamoyl] -1,1-dioxotetrahydrothiopyran-4-yl] carbamoyl] -7- (4-trifluoromethylphenyl) -2-methylpyrazolo [1,5-a] pyrimidine or pharmacology thereof Salts which are acceptable.

As another preferable compound in the present invention, for example, in the general formula [I-II],
B1) a phenyl group in which R ¹ and R ² are the same or different and may be substituted with one or two groups selected from a halogen atom, a cyano group, an alkyl group, a dihalogenoalkyl group and a trihalogenoalkyl group; ”Is a group represented by the formula: —N (R ⁵ ) (R ⁶ ), R ⁵ is a hydrogen atom or an alkyl group, R ⁶ is (a) an alkyl group (the alkyl group is a halogen atom, a hydroxyl group, a cyano group, an alkyl group) An oxy group, a C _3-8 cycloalkyl group, a hydroxy-C _3-8 cycloalkyl group, an amino-C _3-8 cycloalkyl group, a C _3-8 cycloalkyl group substituted with 1 to 2 halogen atoms, Dialkylamino group, carboxyl group, carbamoyl group optionally substituted with 1 to 2 alkyl groups, phenyl group substituted with 1 to 2 halogen atoms, trihalogenoalkyl group N group, alkyloxyphenyl group, carboxyphenyl group and 1 to 3 groups selected from a saturated or unsaturated 5- or 6-membered nitrogen-containing or oxygen-containing heterocyclic group), (b) C _3-8 cycloalkyl group [the cycloalkyl group may be condensed with a benzene ring, and a cyano group, an alkyl group, a hydroxyalkyl group, a carboxyalkyl group, an aminoalkyl group, an alkylcarbonylamino-alkyl group, (Alkyl) carbamoyl-amino-alkyl group, alkylsulfonylaminoalkyl group, dialkylsulfamoylaminoalkyl group, carboxyl group, alkyloxycarbonyl group, phenylalkyloxycarbonyl group, formula: -CON (R ^a1 ) (R ^b1 ) group (wherein shown ^{in, R a1} and ^{R b1} are the same or different (Which represents a hydrogen atom, an alkyl group or a dialkylaminoalkyl group) and a tetrazolyl group may be substituted with 1 to 2 groups], (c) a saturated or unsaturated 4- to 6-membered nitrogen-containing group, A sulfur-containing or oxygen-containing heterocyclic group [the heterocyclic group is an oxo group, a hydroxyl group, a cyano group, an alkyl group, a hydroxyalkyl group, a carboxyl group, an alkyloxycarbonyl group, an alkylsulfonyl group, a formula: —CON (R ^a2 ) (R ^b2 ) (wherein R ^a2 and R ^b2 are the same or different and are a hydrogen atom, an alkyl group, a trihalogenoalkyl group, a cyanoalkyl group, a hydroxyalkyl group, an alkyloxyalkyl group, an alkylsulfonyl group) or an C _3-8 cycloalkyl group), selected from pyrrolidinylcarbonyl group and a morpholinocarbonyl group Or (d) an amino group (the amino group may be substituted with 1 to 2 groups selected from an alkyl group and a pyridyl group) (which may be substituted with ~ 3 groups). However, 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2- (hydroxymethyl) pyrazolo [1, 5-a] except for pyrimidine); or B2) R ¹ and R ² are the same or different and are substituted with 1 to 2 groups selected from a halogen atom, a cyano group, a dihalogenoalkyl group and a trihalogenoalkyl group And an ^{optionally substituted} phenyl group, R ^0B is a group represented by the formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ), and R ″ is an alkyloxy group.

  Among the compounds [I-II], more preferable compounds include compounds in which E is a group represented by the formula: —C (═O) —.

Among the compounds [I-II], more preferable compounds include, for example,
B1-1) R ¹ and R ² may be the same or different and may be substituted with 1 to 2 groups selected from a halogen atom, a cyano group, an alkyl group, a dihalogenoalkyl group and a trihalogenoalkyl group A group, R ^0B is a group represented by the formula: —NHCONHR ⁰³ , E is a group represented by —C (═O) —, R ″ is a group represented by the formula: —N (R ⁵ ) (R ⁶ ), R ⁵ is a hydrogen atom, R ⁶ is (a) alkyl group, (b) trihalogenoalkyl group, (c) C _3-8 cycloalkyl group, (d) dialkylamino group or (e) oxo group, alkyl group and carbamoyl A compound which is a saturated or unsaturated 5- to 6-membered sulfur-containing heterocyclic group which may be substituted with 1 to 3 groups selected from the group;
B1-2) R ¹ and R ² are the same or different, and (i) one or two groups selected from a halogen atom, a cyano group, an alkyl group, a dihalogenoalkyl group, a trihalogenoalkyl group and an alkyloxy group An optionally substituted phenyl group or (ii) a saturated or unsaturated 5- to 6-membered nitrogen-containing ^{heteromonocyclic} group, a group in which R ^0B is represented by the formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ), R ⁰¹ is a hydrogen atom or an alkyl group, R ⁰² is a hydrogen atom, an alkyl group or a carbamoylalkyl group, E is a group represented by —C (═O) —, R ″ is a formula: —N (R ⁵ ) (R ⁶ ), R ⁵ is a hydrogen atom or an alkyl group, R ⁶ is (a) a halogen atom, a hydroxyl group, a cyano group, an alkyloxy group, or C _{3 -3} which may be substituted with 1 to 2 halogen atoms. ₈ cycloalkyl, 1-2 An alkyl group optionally substituted with 1 to 3 groups selected from an amino group and a pyridyl group optionally substituted with an alkyl group, (b) substituted with a group selected from an alkyl group and a carbamoyl group Or a C _3-8 cycloalkyl group, (c) an amino group optionally substituted with one or two groups selected from an alkyl group and a pyridyl group, or (d) an oxo group, an alkyl group and a carbamoyl group. A compound which is a saturated or unsaturated 5- or 6-membered nitrogen-containing or sulfur-containing heterocyclic group optionally substituted by 1 to 3 groups;
B1-3) R ¹ and R ² are the same or different, and a phenyl group which may be substituted with one or two groups selected from a halogen atom and a trihalogenoalkyl group, R ^0B is represented by the formula: —CON (R ^e ) a group represented by (R ^f ), R ^e is a hydrogen atom or an alkyl group, R ^f is a hydrogen atom, an alkyl group or a dialkylamino group, E is a group represented by —C (═O) —, and R ″ is A group represented by the formula: —N (R ⁵ ) (R ⁶ ), R ⁵ is a hydrogen atom, R ⁶ is (a) an alkyl group optionally substituted with 1 to 3 halogen atoms, (b) C _A compound which is a saturated or unsaturated 4- to 6-membered sulfur-containing heterocyclic group which may be substituted with 1 to 3 groups selected from a _3-8 cycloalkyl group or (c) an oxo group and an alkyl group;
B1-4) R ¹ and R ² are the same or different and may be substituted with one or two groups selected from a halogen atom and a trihalogenoalkyl group, R ^0B is a hydroxyalkyl group, and E is A group represented by —C (═O) —, R ″ is a group represented by the formula: —N (R ⁵ ) (R ⁶ ), R ⁵ is a hydrogen atom, R ⁶ is (a) 1 to 3 halogen atoms An alkyl group optionally substituted with an atom, (b) an alkyl group substituted with a pyridyl group, (c) a C _3-8 cycloalkyl group _optionally substituted with a group selected from a cyano group and carbamoyl, or ( d) A compound which is a saturated or unsaturated 4- to 6-membered nitrogen-containing or sulfur-containing heterocyclic group optionally substituted with 1 to 3 groups selected from an oxo group and an alkyl group (provided that 6- (2 -Chlorophenyl) -7- (4-chloropheny R) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2- (hydroxymethyl) pyrazolo [1,5-a] pyrimidine); or B1-5) R ¹ and R ² are the same or different and may be substituted with 1 to 2 groups selected from a halogen atom and a trihalogenoalkyl group, R ^0B is a carboxyl group, and E is —C (═O). A group represented by —, R ″ is a group represented by the formula: —N (R ⁵ ) (R ⁶ ), R ⁵ is a hydrogen atom, R ⁶ is one to three groups selected from an oxo group and an alkyl group. A compound which is a saturated or unsaturated 5- or 6-membered sulfur-containing heterocyclic group which may be substituted; or B2-1) R ¹ and R ² are the same or different and have a halogenophenyl group or 1 to 2 R ^0B groups Sulfur optionally substituted with an alkyl group of Moil group, E is -C (= O) - group represented by the compounds wherein R "is an alkyloxy group.

Among the above compounds [I-II], particularly preferable compounds include, for example,
B1-a) R ¹ may be substituted with 1 to 2 groups selected from (i) a halogen atom, a C _1-6 alkyl group, a dihalogeno C _1-6 alkyl group and a trihalogeno C _1-6 alkyl group A good phenyl group or (ii) a piperidino group, R ² is a phenyl group optionally substituted by 1 to 2 groups selected from a halogen atom and a cyano group, and R ^0B is represented by the formula: —SO ₂ N (R ⁰¹ ) A group represented by (R ⁰² ), R ⁰¹ is a hydrogen atom or a C _1-6 alkyl group, R ⁰² is a hydrogen atom, a C _1-6 alkyl group or a carbamoyl-C _1-6 alkyl group, R ⁵ is a hydrogen atom, R ⁶ is (a) a halogen _{atom, C 1-6} alkyloxy _{group, C 3-8} cycloalkyl group and one to three _{C 1-6} alkyl group optionally substituted by a group selected from a pyridyl group, _{(b) C 1-6} Al Le optionally substituted C _3-8 also be a cycloalkyl group with a group, (c) C _1-6 alkyl group and one to two amino groups which may be substituted by a group selected from a pyridyl group, or (d ) A compound which is a saturated or unsaturated 5- or 6-membered nitrogen-containing or sulfur-containing heterocyclic group optionally substituted by 1 to 2 oxo groups;
B1-b) R ¹ is a trihalogeno C _1-6 alkyl-phenyl group, R ² is a halogenophenyl group, R ^0B is a group represented by the formula: —CON (R ^e ) (R ^f ), and R ^e is a hydrogen atom or A C _1-6 alkyl group, R ^f is a hydrogen atom or a C _1-6 alkyl group, R ⁵ is a hydrogen atom, and R ⁶ is (a) C _{1-6 optionally} substituted by 1 to 3 halogen atoms. A compound which is an alkyl group, or (b) a saturated or unsaturated 5- to 6-membered sulfur-containing heterocyclic group which may be substituted with 1 to 3 groups selected from an oxo group and a C _1-6 alkyl group;
B1-c) R ¹ is a trihalogeno C _1-6 alkyl-phenyl group, R ² is a halogenophenyl group, R ^0B is a hydroxy C _1-4 alkyl group, R ⁵ is a hydrogen atom, and R ⁶ is (a) trihalogeno C _{1. -6} alkyl group, (b) pyridyl-C _1-6 alkyl group, (c) C _5-7 cycloalkyl group substituted with a group selected from cyano group and carbamoyl, or (d) oxo group and C _1-6 A compound which is a saturated or unsaturated 5- or 6-membered sulfur-containing heterocyclic group optionally substituted with 1 to 3 groups selected from alkyl groups (provided that 6- (2-chlorophenyl) -7- (4 -Chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2- (hydroxymethyl) pyrazolo [1,5-a] pyrimidine); or B2-a) R ^Examples thereof include compounds in which ¹ and R ² are the same or different halogenophenyl groups, R ^0B is a C _1-6 alkyl-sulfamoyl group, and R ″ is a C _1-6 alkyloxy group.

Particularly preferred compounds [I-II] above include, for example:
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3-ethoxycarbonyl-2- (N-methylsulfamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3-ethoxycarbonyl-2- (N, N-dimethylsulfamoyl) pyrazolo [1,5-a] pyrimidine;
(R) -6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (N-methylsulfamoyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) Carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclopentyl) carbamoyl] -2- (N-methylsulfamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] -2- (N-methylsulfamoyl) pyrazolo [ 1,5-a] pyrimidine;
(R) -6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (N, N-dimethylsulfamoyl) -3- [N- (1,1-dioxotetrahydrothien-3- Yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclopentyl) carbamoyl] -2- (N, N-dimethylsulfamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (N, N-dimethylsulfamoyl) -3- [N- (1-pyrrolidinyl) carbamoyl] pyrazolo [1,5-a] pyrimidine ;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] -2- (N, N-dimethylsulfamoyl) Pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -2- (N-methylsulfamoyl) -3- [N- (1-pyrrolidinyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
(R) -6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2-sulfamoylpyrazolo [ 1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-pyrrolidinyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] -2-sulfamoylpyrazolo [1,5- a] pyrimidine;
(S) -6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2-sulfamoylpyrazolo [ 1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclopentyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] -2-sulfamoylpyrazolo [1,5 -A] pyrimidine;
(R) -6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2-sulfamoyl Pyrazolo [1,5-a] pyrimidine;
(S) -6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2-sulfamoyl Pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (cyclopentyl) carbamoyl] -7- (4-trifluoromethylphenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
(R) -7- (4-Chlorophenyl) -6- (2-cyanophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
7- (4-chlorophenyl) -6- (2-cyanophenyl) -3- [N- (cyclopentyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
7- (4-Chlorophenyl) -6- (2-cyanophenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] -2-sulfamoylpyrazolo [1,5 -A] pyrimidine;
(R) -2- [N- (carbamoylmethyl) sulfamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) ) Carbamoyl] pyrazolo [1,5-a] pyrimidine;
2- [N- (carbamoylmethyl) sulfamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclopentyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
2- [N- (carbamoylmethyl) sulfamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] pyrazolo [1,5-a] pyrimidine;
2- [N- (carbamoylmethyl) sulfamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-pyrrolidinyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
3- [N- (1-carboxycyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -2- (N-methylsulfamoyl) pyrazolo [1,5-a] Pyrimidine;
3- [N- (1-carbamoylcyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2-hydroxymethyl-3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5 -A] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2-hydroxymethyl-3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (1-cyanocyclohexyl) carbamoyl] -7- (4-trifluoromethylphenyl) -2-hydroxymethylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2-hydroxymethyl-3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] Pyrazolo [1,5-a] pyrimidine;
2-carbamoyl-6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2- (N-methylcarbamoyl) -3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4- Yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (2,2-dimethylpropyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclohexylmethyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine ;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (3-methylpropyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (2,2-difluoroethyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclopropylmethyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-methylcyclopropyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -7- (4-trifluoromethylphenyl) -2-hydroxymethylpyrazolo [1,5-a ] Pyrimidine;
6- (2-chlorophenyl) -7- (4-difluoromethylphenyl) -3- [N- (isobutyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
2-carbamoyl-6- (2-chlorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine ;
6- (2-Chlorophenyl) -7- (4-chloro-2-fluorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -2-sulfamoylpyrazolo [1, 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-difluoromethylphenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a ] Pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (n-propyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (isobutyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (1-methylpropyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (3-methoxyprop-2-yl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] Pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (1-methylcyclopropyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -7- (4-fluorophenyl) -2-sulfamoylpyrazolo [1,5-a] Pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] -2-sulfamoylpyrazolo [1 , 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -2- (dimethylcarbamoyl) pyrazolo [1,5- a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] -2-sulfamoylpyrazolo [1 , 5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (3-methoxyprop-2-yl) carbamoyl] -7- (4-methylphenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -7- (4-methylphenyl) -2-sulfamoylpyrazolo [1,5-a] Pyrimidine;
6- (2-chlorophenyl) -3- [N- (isobutyl) carbamoyl] -7- (4-methylphenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine; and 6- (2- A compound selected from chlorophenyl) -3- [N-cyclopentylcarbamoyl] -7- (4-methylphenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine or a pharmaceutically acceptable salt thereof. Is included.

  When the compound [I] of the present invention has an asymmetric carbon atom in the molecule, it can exist as a plurality of stereoisomers (diastereoisomers, optical isomers) based on the asymmetric carbon atom. The invention includes any one of these stereoisomers or mixtures thereof.

  Since the compound [I] of the present invention has a high affinity for the CB1 receptor, it is useful as a CB1 receptor ligand (particularly a CB1 receptor antagonist), and the receptor is involved based on its antagonistic action. Various diseases such as psychosis including schizophrenia, anxiety disorder, stress, depression, epilepsy, neurodegeneration, cerebellar and old cerebellum (Spinocerebell) disorder, cognitive impairment, cranial trauma, panic attack, peripheral neuropathy, glaucoma, fragment Headache, Parkinson's disease, Alzheimer's disease, Huntington's disease, Raynaud's syndrome, tremor, obsessive compulsive disorder, amnesia, senile dementia, thymic disorder, Tourette syndrome, tardive dyskinesia, bipolar disorder, cancer, drug-induced movement disorder , Including ataxia, endotoxemic shock, hemorrhagic shock, hypotension, insomnia, inflammation Immunological diseases, multiple sclerosis, vomiting, diarrhea, asthma, appetite disorders (bulimia, anorexia), obesity, non-insulin dependent diabetes mellitus (NIDDM), impaired glucose tolerance, hyperinsulinemia, hyperlipidemia Disease, hypercholesterolemia, hypertriglyceridemia, dyslipidemia, arteriosclerosis, hypertension, coronary disease, memory disorder, urological disease, cardiovascular disease, infertility, infection, demyelinating disease, neuritis, viral It is useful for the prophylaxis and treatment of gastrointestinal diseases including encephalitis, cerebrovascular disorder, cirrhosis, or intestinal transit disorder.

  In addition, the compound [I] of the present invention is useful for chronic treatment and withdrawal from substances (such as alcohol) or drug abuse (eg, opioid, barbiturate, cannabis, cocaine, amphetamine, phencyclide, hallucinogen, benzodiazepine). .

  Furthermore, the compound [I] of the present invention is also useful as an analgesic activity enhancer of an analgesic agent or an anesthetic and non-anesthetic drug, or a smoking cessation aid (withdrawal from smoking).

  The compound [I] of the present invention or a pharmacologically acceptable salt thereof has a feature of low toxicity and high safety as a medicine.

  The compound [I] of the present invention includes compounds that can be useful as selective antagonists for peripheral CB1 from the viewpoint of central migration.

  The compound [I] of the present invention can be used for pharmaceutical use either in a free form or in the form of a pharmaceutically acceptable salt thereof. Examples of pharmaceutically acceptable salts include inorganic acid salts such as hydrochloride, sulfate, phosphate or hydrobromide, acetate, fumarate, oxalate, citrate, methanesulfone, and the like. And organic acid salts such as acid salts, benzenesulfonate, tosylate and maleate. In addition, when the compound has a carboxyl group in the molecule, the pharmacologically acceptable salt includes a salt with a base (for example, an alkali metal salt such as a sodium salt or a potassium salt, or an alkaline earth such as a calcium salt). Metal salts).

  The compound [I] of the present invention or a pharmacologically acceptable salt thereof includes any of its internal salts and adducts, solvates or hydrates thereof.

  The compound [I] of the present invention or a pharmacologically acceptable salt thereof can be administered orally or parenterally, and tablets, granules, capsules, powders, injections, inhalants, etc. Can be used as a conventional pharmaceutical preparation (a pharmaceutical composition comprising compound [I] or a pharmaceutically acceptable salt thereof as an active ingredient).

  The dose of the compound [I] of the present invention or a pharmacologically acceptable salt thereof varies depending on the administration method, the age, body weight and condition of the patient. 1.0 mg / kg, especially about 0.001 to 0.1 mg / kg, orally, usually about 0.001 to 100 mg / kg per day, especially about 0.01 to 10 mg / kg Is preferred.

  Compound [I] of the present invention can be produced by the following method, but is not limited thereto.

[Method A]
Among the compounds [I] of the present invention, the following general formula [IA]:

[Wherein R ^M is the following formula:

Or a group represented by the formula: —N (R ⁵ ) (R ⁶ ), and other symbols have the same meaning as described above. ]
The compound represented by the general formula [II-A]:

[Wherein, R ^a represents a hydrogen atom, an alkyl group or a benzyl group, and other symbols have the same meaning as described above. ]
And a compound of the general formula [III]:
HR ^M [III]
[Wherein the symbols have the same meaning as described above. ]
It can manufacture by making it react with the amine compound or its salt shown by these.

When R ^a is a hydrogen atom, this reaction can be carried out in a solvent in the presence of a condensing agent, in the presence or absence of an activator, in the presence or absence of a base. Any solvent may be used as long as it does not affect the reaction. For example, methylene chloride, chloroform, dimethylformamide, dimethylacetamide, tetrahydrofuran, dioxane, toluene, benzene, 1,2-dichloroethane, 1-methylpyrrolidinone, 1,2 -Dimethoxyethane and the like. Examples of the condensing agent include dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSC.HCl), diphenylphosphoryl azide (DPPA), carbonyldiimidazole (CDI), diethyl Cyanophosphonate (DEPC), diisopropylcarbodiimide (DIPCI), benzotriazol-1-yl-oxytrispyrrolidinophosphonium hexafluorophosphate (PyBOP), carbonylditriazole, N-cyclohexylcarbodiimide-N'-propyloxymethylpolystyrene (PS- Carbodiimide), N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), hexafluorophosphate 2- (7-azabenzo) Triazol-1-yl) -1,1,3,3-tetramethyluronium (HATU), 2- (1H-benzotriazol-1-yl) -1,1,3,3-tetramethyl hexafluorophosphate Uronium (HBTU), bromotrispyrrolidinophosphonium hexafluorophosphate (PyBroP), 2- (1H-benzotriazol-1-yl) -1,1,3,3-tetramethyluronium (TBTU) tetrafluoroborate ), Chloro-1,1,3,3-tetramethyluronium hexachloroantimonate (ACTU), and the like. Examples of the activator include 1-hydroxybenzotriazole (HOBt), hydroxysuccinimide (HOSu), dimethylaminopyridine (DMAP), 1-hydroxy-7-azabenzotriazole (HOAt), hydroxyphthalimide (HOPht), pentafluoro Examples thereof include phenol (Pfp-OH), 1-hydroxybenzotriazole-6-sulfonamidomethylpolystyrene (PS-HOBt) and the like. Examples of the base include pyridine, triethylamine, diisopropylethylamine, 4-methylmorpholine, 1,8-diazabicyclo [5,4,0] -undecene (DBU) and the like.

  In the above reaction, the amount of compound [II-A] used can be 0.33 to 1.5 equivalents, preferably 0.5 to 1.2 equivalents, relative to compound [III]. The amount of the condensing agent to be used can be 1.0 to 3.0 equivalents, preferably 1.0 to 1.2 equivalents, relative to compound [II-A] or [III]. The amount of the base to be used can be 1.0 to 3.0 equivalents, preferably 1.0 to 1.2 equivalents, relative to compound [II-A] or [III]. The usage-amount of an activator can be 0.01-2.0 equivalent with respect to compound [II-A] or [III], Preferably it can be 0.1-1.0 equivalent. This reaction can be carried out at 0 to 150 ° C, preferably 20 to 80 ° C.

In the general formula [II-A], when R ^a is a hydrogen atom, the compound is converted to a reactive derivative such as a corresponding acid halide (for example, acid chloride) or a mixed acid anhydride, and then the reactivity is changed. Compound [IA] can also be produced by reacting the derivative with compound [III] in the presence or absence of a solvent in the presence of the above base.

In the general formula [II-A], when R ^a is an alkyl group or a benzyl group, this reaction may be carried out by subjecting the ester compound to hydrolysis, hydrochloric acid, formic acid, trifluoroacetic acid or the like, or The corresponding carboxylic acid compound by the reduction reaction, that is, the following general formula [II-Aa]:

[Wherein the symbols have the same meaning as described above. ]
The compound [II-Aa] and the compound [III] may be treated in the same manner as described above after conversion to the compound represented by

[Method B]
Among the compounds [I] of the present invention, compounds in which E is a group represented by the formula: —SO ₂ — (compound [IB]) include, for example, the following general formula [II-B]:

[Wherein W ⁰⁰ represents a halogen atom, and other symbols have the same meaning as described above. ]
It can manufacture by making the sulfonyl halide compound shown by and amine compound [III] react. This reaction can be carried out in a solvent in the presence of a base. The solvent is not particularly limited as long as it does not affect this reaction, and examples thereof include chloroform, dichloromethane, tetrahydrofuran and the like. Examples of the base include pyridine, triethylamine, diisopropylethylamine and the like. The amount of amine compound [III] to be used can be 0.5 to 5.0 equivalents, preferably 0.8 to 1.5 equivalents, relative to compound [II-B]. The amount of the base used can be 1.0 to 5.0 equivalents, preferably 1.0 to 1.5 equivalents, relative to compound [II-B]. This reaction can be carried out at −10 to 100 ° C., preferably 0 to 40 ° C.

[Method C]
Among the compounds [I] of the present invention, the general formula [I-C]:

[Wherein the symbols have the same meaning as described above. ]
For example, the compound represented by the following general formula [II-C]:

[Wherein the symbols have the same meaning as described above. ]
And a compound represented by the general formula:
R ⁰³ NCO
[Wherein the symbols have the same meaning as described above. ]
Can be produced by reacting with an alkyl isocyanate represented by The amount of alkyl isocyanate used may be a large excess with respect to compound [II-C] in consideration of the function as a solvent. This reaction can be carried out at 20 to 120 ° C, preferably 50 to 90 ° C. In addition, you may use chloroform, a dichloromethane, tetrahydrofuran etc. as another solvent, for example.

The target compound [I] of the present invention can also be produced by further converting the substituents on R ¹ and R ² of the compound obtained as described above into other desired substituents. . Such a substituent conversion method may be appropriately selected according to the type of the target substituent, and can be carried out, for example, as in the following methods a to h.

(Method a)
The compound [I] of the present invention having a cyano group (or a group containing cyano) as a substituent is, for example, a corresponding compound having a halogen atom or an alkylsulfonyl group (or a group containing a halogen atom or an alkylsulfonyl group) as a substituent. It can be produced by reacting [I] with a cyanide compound (such as zinc cyanide, copper cyanide, trimethylsilane cyanide or potassium cyanide) in the presence or absence of a catalyst, a base and an additive. Examples of the base include triethylamine, N-methylpiperidine, diisopropylethylamine and the like. Examples of the catalyst include palladium catalysts such as palladium acetate, tris (dibenzylideneacetone) dipalladium, trans-dichlorobis (tricyclohexylphosphine) palladium or tetrakis (triphenylphosphine) palladium or nickel catalysts such as dibromobis (triphenylphosphine) nickel. Etc. Examples of the additive include triphenylphosphine, 1,1′-bis (diphenylphosphino) ferrocene, racemic-2,2′-bis (diphenylphosphino) -1,1′-binaphthyl, 2- (di-tert Phosphine compounds such as -butylphosphino) biphenyl, 2- (dicyclohexylphosphino) biphenyl, 2-dicyclohexylphosphino-2 '-(N, N'-dimethylamino) biphenyl, and tri-tert-butylphosphine. .

(Method b)
The compound [I] of the present invention having an alkylamino group or a cycloalkylamino group (or a group containing an alkylamino group or a cycloalkylamino group) as a substituent is, for example, a halogen atom (or a group containing a halogen atom) as a substituent. ) And the corresponding compound [I] having a monovalent or dialkylamine or cycloalkylamine in a solvent in the presence of a catalyst, an additive and a base. Examples of the catalyst include a palladium catalyst or a copper catalyst used in the method (a). Examples of the additive include phosphine compounds used in the method (a), and examples of the base include potassium acetate, potassium carbonate, cesium carbonate, potassium tert-butoxide and the like.

(Method c)
The compound [I] of the present invention having an alkyloxy group (or a group containing an alkyloxy group) as a substituent includes, for example, (1) the corresponding compound [I] having a hydroxyl group (or a group containing a hydroxyl group) as a substituent. , Alkyl halide is reacted in a suitable solvent, or (2) the corresponding compound [I] having a hydroxyl group (or a group containing a hydroxyl group) as a substituent and an alkanol in a solvent in a base (potassium carbonate, cesium carbonate, In the presence of sodium hydride or the like, or in the presence of an activator (diethyl azodicarboxylate or the like) and a trisubstituted phosphine, or (3) an alkylsulfonyl group (or a group containing an alkylsulfonyl group) as a substituent. It can be obtained by reacting the corresponding compound [I] having a alkoxide with an alkali metal alkoxide in an appropriate solvent.

(Method d)
The compound [I] of the present invention having an alkylsulfinyl group or alkylsulfonyl group (or a group containing an alkylsulfinyl group or an alkylsulfonyl group) as a substituent includes, for example, an alkylthio group (or a group containing an alkylthio group) as a substituent. The corresponding compound [I] can be prepared by treating with an oxidizing agent such as 3-chloroperbenzoic acid in a suitable solvent.

(Method e)
The compound [I] of the present invention having an acylamino group (a group containing an acylamino group) such as an alkylcarbonylamino group as a substituent includes, for example, the corresponding compound [I] having an amino group (or a group containing an amino group) as a substituent. ] And the following general formula:
R ^X COOH [Ac-1]
[Wherein, R ^X has the same meaning as described above. ]
Or a reactive derivative thereof (such as a corresponding acid anhydride or a corresponding acid halide). This reaction can be carried out in a solvent in the presence of a base (such as triethylamine) or a condensing agent (such as water-soluble carbodiimide) and in the presence or absence of an activating agent (such as 1-hydroxybenzotriazole).
The removal of the acyl group from the compound [I] can be carried out by a conventional method such as acid treatment or catalytic reduction depending on the kind of the acyl group.

(Method f)
The compound [I] of the present invention having a substituted or unsubstituted carbamoyl group (or a group containing a substituted or unsubstituted carbamoyl group) represented by the formula: —CON (R ^e ) (R ^f ) as a substituent is The corresponding compound [I] having a carboxyl group or an alkyloxycarbonyl group (or a group containing a carboxyl group or an alkyloxycarbonyl group) in an appropriate solvent is an amine compound represented by the formula: HN (R ^e ) (R ^f ) Ammonia, mono- or dialkylamine, etc.).

(G method)
The compound [I] of the present invention having an alkylcarbamoylamino group (or a group containing an alkylcarbamoylamino group) as a substituent is preferably a corresponding compound [I] having an amino group (or a group containing an amino group) as a substituent. It can be produced by reacting with an alkyl isocyanate in a solvent.

(Method h)
The following formula as a substituent:

[Wherein, ring A ¹ represents a 5- to 7-membered aliphatic nitrogen-containing heteromonocyclic group. ]
The compound [I] of the present invention having the group shown above and the corresponding compound [I] having an amino group as a substituent have the formula:
X ⁰¹ -Alk ¹ -X ⁰²
[Wherein, X ⁰¹ and X ⁰² represent a halogen atom, and Alk ¹ represents an alkylene group. ]
Can be produced by reacting in a solvent (acetonitrile, etc.) in the presence or absence of a base (potassium carbonate, etc.) and in the presence or absence of an additive (potassium iodide, etc.). it can. As the 5- to 7-membered aliphatic nitrogen-containing heteromonocyclic group represented by A ^1, e.g., 1-pyrrolidinyl group, a 1-piperidyl group.

(I method)
The compound [I] of the present invention having a carboxyl group as a substituent is obtained by converting the corresponding compound [I] having a hydroxymethyl group as a substituent with an oxidizing agent (such as pyridinium dichromate) in a suitable solvent such as dimethylformamide. It can be manufactured by processing.

  The desired compound [I] of the present invention obtained as described above can be converted into a pharmaceutically acceptable salt according to a conventional method, if desired.

[Production of Intermediate Compound]
(I) Of the intermediate compound [II-A] in the present invention, the following general formula [II-A1]:

[Wherein the symbols have the same meaning as described above. ]
Can be produced, for example, according to the following reaction schemes A1 to A3.

  (Reaction Scheme A1)

  (Reaction Scheme A2)

(Reaction Scheme A3)

[Among the above reaction scheme A1, A2 and A3, R ⁰⁰¹ is an alkyl group, R ¹¹ and R ²¹ are optionally substituted aryl group, an optionally substituted heteroaryl group or an optionally substituted aliphatic A nitrogen-containing heterocyclic group, R ¹² and R ²² are an optionally substituted aryl group or an optionally substituted heteroaryl group, and R ¹³ and R ²³ are an optionally substituted aliphatic nitrogen-containing heterocyclic ring The formula groups R ⁰⁰² and R ⁰⁰³ are the same or different and each represents a hydrogen atom or an alkyl group, or both are bonded to each other to form an alkylene group, t-Bu is a tert-butyl group, W ⁰¹ and W ⁰² Represents a halogen atom, and other symbols have the same meaning as described above. ]
Examples of the aryl group in R ¹¹ , R ¹² , R ²¹ or R ²² include 6 to 10-membered monocyclic or bicyclic aryl groups such as a phenyl group and a naphthyl group, and among these, a phenyl group is preferable. .

Examples of the heteroaryl group in R ¹¹ , R ¹² , R ^21, or R ²² include, for example, a 5- to 10-membered monocyclic or bicyclic compound containing 1 to 3 hetero atoms selected from an oxygen atom, a sulfur atom, and a nitrogen atom. A cyclic heteroaryl group is mentioned, Among these, a furyl group, a thienyl group, or a pyridyl group is preferable.

Examples of the aliphatic nitrogen-containing heterocyclic group for R ¹¹ , R ¹² , R ²¹ or R ²² include a 5- to 7-membered aliphatic nitrogen-containing heterocyclic monocyclic group. The heterocyclic group may further contain 1 to 2 hetero atoms selected from an oxygen atom, a sulfur atom and a nitrogen atom. Of such heterocyclic groups, a 1-pyrrolidinyl group, 1-piperidyl group, morpholino group or thiomorpholino group is preferable.

The aryl group, heteroaryl group and aliphatic nitrogen-containing heterocyclic group in R ¹¹ , R ¹² , R ²¹ or R ²² may be substituted with a halogen atom, a cyano group, or 1 to 3 halogen atoms. It may be substituted with 1 to 3 groups selected from an alkyl group, an alkyloxy group which may be substituted with 1 to 3 halogen atoms, and an alkylsulfonyl group.

Examples of the alkylene group formed by combining R ⁰⁰² and R ⁰⁰³ with each other include linear or branched C _2-6 such as ethylene group, trimethylene group, 1,1,2,2-tetramethylethylene group. Examples of the substituent on the alkylene group include an alkyl group such as a methyl group.

  Each reaction described in the above schemes A1 to A3 can be carried out, for example, as follows.

Reaction step A1-1:
The reaction of compound [VI] and compound [VII] can be carried out in a solvent under heating. Any solvent that does not affect the reaction may be used, and examples thereof include dimethylformamide, dimethylacetamide, dioxane, 1,2-dichloroethane, toluene, and xylene. The amount of compound [VII] to be used can be 1.0 to 10 equivalents, preferably 1.0 to 3.0 equivalents, relative to compound [VI]. This reaction can be carried out at 50 to 200 ° C, preferably 80 to 150 ° C.

Reaction step A1-2:
The reaction of compound [VIII] and compound [i] can be carried out in a solvent in the presence or absence of a base. Examples of the base include piperidine, morpholine, N-methylpiperazine, diethylamine and the like. Any solvent that does not affect the reaction may be used, and examples include acetic acid, methanol, ethanol, isopropanol, and ethylene glycol. The amount of compound [i] to be used can be 0.5 to 2.0 equivalents, preferably 0.8 to 1.2 equivalents, relative to compound [VIII]. The amount of the base used can be 0.01 to 2.0 equivalents, preferably 0.1 to 1.0 equivalents, relative to compound [VIII]. This reaction can be carried out at 50 to 150 ° C, preferably 70 to 100 ° C. This reaction can also be carried out in a solvent in the presence or absence of an acid. Examples of the acid include hydrogen bromide, hydrogen chloride, acetic acid and the like. Any solvent that does not affect the reaction may be used, and examples include acetic acid, methanol, ethanol, isopropanol, and ethylene glycol. The amount of compound [i] to be used can be 0.5 to 2.0 equivalents, preferably 0.8 to 1.2 equivalents, relative to compound [VIII]. The amount of the acid to be used can be 0.1 to 3.0 equivalents, preferably 0.3 to 1.0 equivalents, relative to compound [VIII]. This reaction can be carried out at 0 to 150 ° C., preferably 60 to 100 ° C.

Reaction step A2-1:
The reaction of compound [VI-a] and compound [VII] can be carried out in the same manner as in reaction step A1-1.

Reaction step A2-2:
The reaction of compound [VIII-a] and compound [i] can be carried out in the same manner as in reaction step A1-2. Moreover, compound [Xa] can be obtained by implementing this reaction in acetic acid, without implementing reaction process A2-3.

Reaction step A2-3:
The intramolecular ring closure reaction of compound [IX-a] can be carried out in a solvent in the presence of a base. Any solvent that does not affect the reaction may be used, and examples thereof include ethanol, acetonitrile, chloroform, tetrahydrofuran, dioxane, toluene, N, N-dimethylformamide and the like. Examples of the base include sodium carbonate, cesium carbonate, triethylamine, diisopropylethylamine, dimethylaminopyridine and the like. The amount of the base used can be 1.0 to 10.0 equivalents, preferably 1.2 to 3.0 equivalents, relative to compound [IX-a]. This reaction can be carried out at 30 to 150 ° C, preferably 60 to 100 ° C.

Reaction step A2-4:
Conversion of compound [Xa] to compound [XII-a] can be carried out in a solvent in the presence of a halogenating agent and in the presence or absence of a base. Any solvent that does not affect the reaction may be used, and examples thereof include acetonitrile, chloroform, tetrahydrofuran, dioxane, toluene, N, N-dimethylformamide and the like. Examples of the halogenating agent include phosphorus oxychloride, thionyl chloride, phosphorus pentachloride, oxalyl chloride and the like. Examples of the base include N, N-dimethylaniline, diisopropylethylamine, N-methylmorpholine and the like. The amount of the halogenating agent to be used can be 1.1 to 5.0 equivalents, preferably 1.2 to 1.5 equivalents, relative to compound [X-a]. The amount of the base to be used can be 1.2 to 10.0 equivalents, preferably 1.5 to 2.0 equivalents, relative to compound [X-a]. This reaction can be carried out at 50 to 200 ° C, preferably 80 to 150 ° C.

Reaction step A2-5:
(1) The reaction of the compound [XII-a] and the boronic acid compound [XIII-a] can be carried out in a solvent in the presence of a catalyst and a base. As the boronic acid compound [XIII-a], a compound in which R ⁰⁰² and R ⁰⁰³ are a hydrogen atom or an alkyl group (such as a methyl group, an ethyl group, an isopropyl group), or an alkylene group (R ⁰⁰² and R ⁰⁰³ are bonded to each other) Examples thereof include compounds that form an ethylene group, a propylene group, a 1,1,2,2-tetramethylethylene group, and the like. Among these, compounds in which R ⁰⁰² and R ⁰⁰³ are hydrogen atoms (or the following formula:

[Wherein the symbols have the same meaning as described above. ]
And the corresponding boroxine compound) is preferred. Any solvent may be used as long as it does not affect the reaction, and examples thereof include dioxane, toluene, dimethoxyethane, ethanol, N, N-dimethylformamide, tetrahydrofuran, water and the like. Examples of the catalyst include tetrakis (triphenylphosphine) palladium (0), palladium (II) acetate, bis (dibenzylideneacetone) palladium (0), bis (triphenylphosphine) palladium (II) dichloride, bis (tri- palladium catalysts such as o-tolylphosphine) palladium (II) dichloride, bis (tricyclohexylphosphine) palladium (II) dichloride, [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride, Examples thereof include nickel catalysts such as 3-bis (diphenylphosphino) propane nickel (II) dichloride and bis (triphenylphosphine) nickel (II) dichloride. Examples of the base include potassium phosphate, sodium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium fluoride, triethylamine, lithium chloride and the like. The amount of compound [XIII-a] to be used in this reaction can be 1.0 to 5.0 equivalents, preferably 1.1 to 2.0 equivalents, relative to compound [XII-a]. The amount of the catalyst to be used can be 0.001 to 0.5 equivalent, preferably 0.01 to 0.05 equivalent, relative to compound [XII-a]. The amount of the base to be used can be 1.0 to 10.0 equivalents, preferably 2.0 to 5.0 equivalents, relative to compound [XII-a]. This reaction can be carried out at 20 to 150 ° C, preferably 60 to 120 ° C.

  (2) The reaction of the compound [XII-a] and the nitrogen-containing heterocyclic compound [XIII-b] can be carried out in a solvent in the presence of a base. Any solvent may be used as long as it does not affect the reaction. Examples thereof include dimethylformamide, toluene, dioxane, and tetrahydrofuran. Examples of the base include potassium carbonate, sodium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium fluoride, triethylamine, diisopropylethylamine, dimethylaminopyridine and the like. The amount of compound [XIII-b] used in this reaction can be 0.8 to 5.0 equivalents, preferably 1.0 to 1.5 equivalents, relative to compound [XII-a]. The amount of the base to be used can be 1.0 to 10.0 equivalents, preferably 2.0 to 5.0 equivalents, relative to compound [XII-a]. This reaction can be carried out at 80 to 200 ° C, preferably 120 to 180 ° C.

Reaction step A3-1:
The reaction of compound [VI-b] and compound [VII-b] can be carried out in a solvent or without a solvent. Any solvent may be used as long as it does not affect the reaction, and examples thereof include dimethylformamide, toluene, dioxane, tetrahydrofuran, and dimethoxyethane. The amount of compound [VII-b] used in this reaction can be 0.5 to 5.0 equivalents, preferably 0.9 to 1.5 equivalents, relative to compound [VI-b]. This reaction can be carried out at 0 to 150 ° C, preferably 50 to 80 ° C.

Reaction step A3-2:
The halogenation of compound [VIII-b] can be carried out in a solvent in the presence of a halogenating agent and in the presence or absence of a base. Any solvent may be used as long as it does not affect the reaction. Examples thereof include methylene chloride, carbon tetrachloride, chloroform, acetic acid, and tetrahydrofuran. Examples of the halogenating agent include bromine, N-bromosuccinimide, N-chlorosuccinimide and the like. Examples of the base include triethylamine, diisopropylethylamine, potassium carbonate, sodium carbonate and the like. The amount of the halogenating agent to be used can be 0.5 to 10.0 equivalents, preferably 1.0 to 3.0 equivalents, relative to compound [VIII-b]. This reaction can be carried out at -40 to 100 ° C, preferably -5 to 20 ° C.

Reaction step A3-3:
The reaction of compound [IX-b] and compound [i] can be carried out in the same manner as in reaction step A1-2.

Reaction step A3-4:
The reaction of compound [Xb] with boronic acid compound [XIII-c] or nitrogen-containing heterocyclic compound [XIII-d] is carried out in the same manner as in reaction step A2-5 (1) or (2), respectively. be able to.

  (Ii) Of the intermediate compound [II-A], the following general formula [II-A3]:

[Wherein the symbols have the same meaning as described above. ]
Can be produced, for example, according to the following reaction scheme A4.

  (Reaction Scheme A4)

[In the above scheme, Bzl represents a benzyl group, and other symbols have the same meaning as described above. ]
Each reaction described in the above scheme A4 can be carried out, for example, as follows.

Reaction step A4-1:
This reaction can be carried out in the same manner as in Step A1-2.

Reaction step A4-2:
The reaction of compound [II-A5] with sodium hypochlorite can be carried out in a solvent in the presence of an acid (such as concentrated hydrochloric acid). Any solvent may be used as long as it does not affect the reaction, and examples thereof include methylene chloride and chloroform. The usage-amount of sodium hypochlorite in this reaction can be 0.5-10.0 equivalent with respect to compound [II-A5], Preferably it can be 1.0-3.0 equivalent. This reaction can be carried out at -40 to 100 ° C, preferably -5 to 20 ° C.

Reaction step A4-3:
The reaction of compound [II-A6] and compound [III-C] can be carried out in the same manner as in the aforementioned Method B.

(Iii) Among the above intermediate compounds [II-A], the compound in which R ⁰ is a hydroxyalkyl group is obtained by, for example, reacting the corresponding compound in which R ⁰ is an alkyl group in a suitable solvent such as carbon tetrachloride. After treatment with a brominating agent such as bromosuccinimide, the reaction product is then reacted with an acetic acid compound such as potassium acetate in a suitable solvent such as dimethylformamide, and the reaction product is further reacted with a suitable solvent such as ethanol-tetrahydrofuran. It can be produced by treating with a base such as an alkali metal alkoxide (such as sodium ethoxide) in a solvent.

  (Iv) The intermediate compound [II-B] is, for example, represented by the general formula:

[Wherein the symbols have the same meaning as described above. ]
And a compound of the general formula [XIV]:
Hal-SO ₃ H [XIV]
[In the formula, Hal represents a halogen atom. ]
Can be produced by treating the resulting product with a halogenating agent (thionyl halide such as thionyl chloride).

  In the present invention, “halogen atom” means a fluorine atom, a chlorine atom, an iodine atom or a bromine atom, and “alkyl” is a straight chain having 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms. The branched alkyl, “cycloalkyl” represents cycloalkyl having 3 to 8 carbon atoms, preferably 5 to 7 carbon atoms. “Alkylene” represents linear or branched alkylene having 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms.

  Specific examples (Examples) of the target compound of the present invention synthesized by each of the above exemplified methods are shown below, but the present invention is not limited thereby.

Example A1
58 mg of 3-carboxy-6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine (compound obtained in Reference Example 1 (4)) and 25 mg of 1-cyanocyclohexylamine hydrochloride 1-hydroxybenzotriazole monohydrate (0.5 M chloroform solution, containing amylene) 0.45 mL, 1- (3-dimethylaminopropyl) -3-ethyl Add 0.45 mL of carbodiimide hydrochloride (0.5 M, N, N-dimethylformamide solution) and 63 μL of triethylamine and stir at room temperature overnight. Add 2 mL of saturated aqueous sodium hydrogen carbonate solution, 2 mL of water and 4 mL of chloroform to the reaction solution, and vigorously stir for 15 minutes. After separating the organic layer, the aqueous layer is extracted with 3 mL of chloroform. The combined organic layers are washed successively with 3 mL of saturated aqueous sodium bicarbonate solution and 3 mL of saturated brine, and concentrated under reduced pressure. The resulting crude product was purified using a liquid chromatograph mass spectrometer (LCMS, column: XTerra MS C18, solvent: 10 mM aqueous ammonium carbonate solution / methanol = 40/60 to 10/90), and then freeze-dried. 6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-cyanocyclohexyl) carbamoyl] pyrazolo [1,5-a] pyrimidine (15.6 mg, 21% yield). Obtain as a powder.
MS (ESI) m / z; 490 [M + H] ^< +>.

Example A2
To a solution of 70 mg of the compound obtained in Example A1 in 1.0 mL of methylene chloride, 84 μL of methanesulfonic acid and a few drops of water are added, stirred at room temperature overnight, and further stirred at 35 ° C. for 4 hours. A saturated aqueous sodium hydrogen carbonate solution and methylene chloride are sequentially added to the reaction mixture and stirred, and then the organic layer is separated and concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (chloroform / methanol = 100: 0 to 95: 5) to give 3- [N- (1-carbamoylcyclohexyl) carbamoyl] -6- (2- Chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine (18 mg, 25% yield) is obtained as a pale yellow solid.
MS (APCI) m / z; 508/510 [M + H] ^< +>.

Example A3
(1) Treat 77 mg of the compound obtained in Reference Example A1 (4) and 34 mg of 4-amino-4-cyanotetrahydrothiopyran hydrochloride (compound obtained in Reference Example A3 (1)) in the same manner as in Example A1. 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyanotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine (50.8 mg Yield 50%) as a powder.
MS (APCI) m / z; 508/510 [M + H] ^< +>.

(2) 47 mg of the compound obtained in (1) above is dissolved in 1 mL of methylene chloride and 18 μL of methanesulfonic acid, 53 mg of metachloroperbenzoic acid is added, and the mixture is stirred at room temperature for 3 hours. Saturated aqueous sodium hydrogen carbonate solution is added to the reaction mixture and stirred, and then the organic layer is separated and concentrated, and the resulting crude product is purified by silica gel column chromatography (chloroform / methanol = 98: 2-95: 5). 3- [N- (4-carbamoyl-1,1-dioxo-tetrahydrothiopyran-4-yl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5- a] Pyrimidine (18 mg, 35% yield) is obtained as a solid.
MS (APCI) m / z; 558/560 [M + H] ^< +>.

Example A4
(1) To a solution of 300 mg of the compound obtained in Reference Example A1 (4) and 181 mg of 1-methoxycarbonylcyclohexylamine hydrochloride in 4 mL of dichloromethane, 179 mg of 1-hydroxybenzotriazole monohydrate, 1- (3-dimethylaminopropyl) ) Add 224 mg of 3-ethylcarbodiimide hydrochloride and 328 μL of triethylamine and stir at room temperature overnight. Add methylene chloride and saturated aqueous sodium hydrogen carbonate solution to the reaction mixture and stir vigorously for 10 minutes. The organic layer is separated and concentrated under reduced pressure, and the resulting crude product is purified by NH silica gel column chromatography (Chromatorex NH silica gel; manufactured by Fuji Silysia Chemical, solvent; hexane / ethyl acetate = 70: 30 to 50:50). 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-methoxycarbonylcyclohexyl) carbamoyl] pyrazolo [1,5-a] pyrimidine (380 mg, 93%) obtain.
MS (APCI) m / z; 523/525 [M + H] ^< +>.

(2) To a solution of 200 mg of the compound obtained in (1) above in ethanol (2.0 mL) is added 2N aqueous sodium hydroxide solution (0.38 mL), and the mixture is stirred at room temperature overnight and further at 50 ° C. for 5 hours. After cooling the reaction solution to room temperature, 2N hydrochloric acid (0.38 mL) is added, and then saturated brine and methylene chloride are added. The organic layer is separated and concentrated under reduced pressure, and the resulting crude product is purified by silica gel column chromatography (chloroform / methanol = 99: 1 to 92: 8) to give 3- [N- (1-carboxycyclohexane]. Xyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine (180 mg, 92% yield) is obtained as a powder.
MS (APCI) m / z; 509/511 [M + H] ^< +>.

Example A5
1 mL of 1-hydroxybenzotriazole monohydrate and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide were added to 1 mL of a methylene chloride solution of the compound (50 mg) obtained in Example A4 and methylamine hydrochloride (8 mg). Add 29 mg of hydrochloride and 21 μL of triethylamine and stir at room temperature overnight. Add methylene chloride and saturated aqueous sodium hydrogen carbonate solution to the reaction mixture and stir vigorously for 10 minutes. The organic layer is separated and concentrated under reduced pressure. The resulting crude product is purified by silica gel column chromatography (solvent; chloroform / methanol = 100: 0 to 95: 5) and then powdered with hexane to give 6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (N-methylcarbamoyl) cyclohexyl] carbamoyl] pyrazolo [1,5-a] pyrimidine (25 mg, 61% yield) )
MS (APCI) m / z; 522/524 [M + H] ^< +>.

Example A6
(1) Compound (2-amino-6- (2-chlorophenyl) -3-ethoxycarbonyl-7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine) obtained in Reference Example A6 By treating 0 g in the same manner as in Reference Example A1 (4), 2-amino-3-carboxy-6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] Pyrimidine is obtained as a powder.

  (2) By treating 200 mg of the compound obtained in the above (1) and 73 mg of 1- (2-pyridyl) ethylamine in the same manner as in Example A1, 2-amino-6- (2-chlorophenyl) -7- (4 -Trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine (112 mg, 45% yield) is obtained as a powder.

(3) A mixture of 59 mg of the compound obtained in (2) above, 156 μL of acetyl chloride, 304 μL of triethylamine and 5 mL of terahydrofuran is stirred at 60 ° C. overnight. Saturated sodium hydrogen carbonate is added to the reaction mixture at 0 ° C., and the mixture is stirred and extracted with chloroform. The extract is dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by NH silica gel column chromatography (Chromatorex NH silica gel, solvent; hexane / ethyl acetate = 50 / 50-30 / 70) to give 2-acetylamino-6. -(2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine (50.8 mg, yield) 80%) is obtained as a pale yellow powder.
MS (APCI) m / z; 579/581 [M + H] ^< +>.

Example A7
(1) 2.9 g of 1,4-dichlorobutane, 3.2 g of potassium carbonate, and 2.7 g of sodium iodide are added to a solution of 2.1 g of the compound obtained in Reference Example A6 in 21 mL of water / 84 mL of acetonitrile, and the mixture is added to 5 Reflux for days. After cooling the reaction solution to room temperature, ethyl acetate and water are added to the residue and stirred. The organic layer is separated, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 85/15 to 70:30) to give 6- (2-chlorophenyl) -3-ethoxy. Carbonyl-7- (4-trifluoromethylphenyl) -2- (1-pyrrolidinyl) pyrazolo [1,5-a] pyrimidine (0.61 g, 26% yield) is obtained as a yellow oil.
MS (APCI) m / z; 515/517 [M + H] ^< +>.

(2) The compound (610 mg) obtained in (1) above was treated in the same manner as in Reference Example A1 (4) to give 3-carboxy-6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl)- 2- (Pyrrolidin-1-yl) pyrazolo [1,5-a] pyrimidine (449 mg) was prepared and then the compound (70 mg) was treated in the same manner as in Example A1 to give 6- (2-chlorophenyl) -7- (4-Trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] -2- (pyrrolidin-1-yl) pyrazolo [1,5-a] pyrimidine (15 .2 mg).
MS (APCI) m / z; 591/593 [M + H] ^< +>.

Example A8
(1) 3-carboxy-7- (4-chloro-2-fluorophenyl) -6- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidine (the compound obtained in Reference Example A11, 39 mg) and 4- Amino-1,1-dioxotetrahydrothiopyran-4-carboxylic acid methyl ester (20 mg) was treated in the same manner as in Example A1 to give 7- (4-chloro-2-fluorophenyl) -6- (2 -Chlorophenyl) -3- [N- (4-methoxycarbonyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine (45 mg, 79% yield) Obtained as a yellow powder.
MS (APCI) m / z; 591/593 [M + H] ^< +>.

(2) The compound (352 mg) obtained in (1) above is treated in the same manner as in Example A4 (2) to give 3- [N- (4-carboxy-1,1-dioxotetrahydrothiopyran-4 -Yl) carbamoyl] -7- (4-chloro-2-fluorophenyl) -6- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidine (301 mg, 88% yield) is obtained as a pale yellow powder. .
MS (APCI) m / z; 577/579 [M + H] ^< +>.

(3) The compound (70 mg) obtained above (2) and ammonium chloride (32 mg) are treated in the same manner as in Example A1 to give 3- [N- (4-carbamoyl-1,1-dioxotetrahydrothio]. Pyran-4-yl) carbamoyl] -7- (4-chloro-2-fluorophenyl) -6- (2-chlorophenyl) pyrazolo [1,5-a] pyrimidine (40 mg, 57% yield) as pale yellow powder Get as a body.
MS (APCI) m / z; 576/578 [M + H] ^< +>.

Examples A9-A15
The corresponding starting materials are treated in the same manner as in Example A1 to give the compounds shown in Table 1 below.

Examples A16-A18
The corresponding starting material compounds are treated in the same manner as in Example A5 to give the compounds shown in Table 2 below.

Examples A19 to A30
The corresponding starting material compounds are treated in the same manner as in Example A4 to give the compounds listed in Table 3 below.

Examples A31-A32
The corresponding starting materials are treated in the same manner as in Example A1 to give the compounds listed in Table 4 below.

Example A34
(1) By treating the corresponding starting material compound in the same manner as in Reference Example A6, 2-amino-6- (2-chlorophenyl) -7- (4-chlorophenyl) -3-ethoxycarbonylpyrazolo [1,5-a Pyrimidine is obtained as a yellow powder.
MS (APCI) m / z; 427/429 [M + H] ^< +>.

(2) To a solution of the compound (2.64 g) obtained in the above (1) in 50 mL of tetrahydrofuran were added 5.17 mL of triethylamine and 2.83 g of methanesulfonyl chloride at 0 ° C. Stir for 1 hour. The reaction mixture is diluted with ethyl acetate, water is added at 0 ° C., and the mixture is stirred. After separating the organic layer, the aqueous layer is extracted with ethyl acetate. The combined organic layers are dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by NH silica gel column chromatography (Chromatorex NH silica gel, solvent; chloroform) to give 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3. -Ethoxycarbonyl-2- [bis (methylsulfonyl) amino] pyrazolo [1,5-a] pyrimidine (2.91 g, 81% yield) is obtained as a pale yellow solid.
MS (APCI) m / z; 583/585 [M + H] ^< +>.

(3) Add 3.15 g of tetrabutylammonium fluoride trihydrate to a 60 mL tetrahydrofuran solution of the compound (2.91 g) obtained in (2) above and stir at room temperature for 30 minutes. Water is added to the reaction solution and stirred, and then the organic layer is separated. Extract the aqueous layer with chloroform. The combined organic layers were concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 70/30 to 50/50) to give 6- (2-chlorophenyl) -7. -(4-Chlorophenyl) -3-ethoxycarbonyl-2- (methylsulfonylamino) pyrazolo [1,5-a] pyrimidine (2.20 g, 87% yield) is obtained as a pale yellow solid.
MS (APCI) m / z; 505/507 [M + H] ^< +>.
(4) To a solution of 0.8 g of the compound obtained in (3) above in ethanol-tetrahydrofuran (10 mL / 20 mL) is added 4.8 mL of 2N aqueous sodium hydroxide solution, and the mixture is stirred at 40 ° C. overnight. The precipitated solid was collected by filtration to give 3-carboxy-6- (2-chlorophenyl) -7- (4-chlorophenyl) -2- (methylsulfonylamino) pyrazolo [1,5-a] pyrimidine (0.86 g). Is obtained as a crude product.
MS (APCI) m / z; 477/479 [M + H] ^< +>.
(5) By treating 70 mg of the compound obtained in the above (4) and 23 mg of 1- (2-pyridyl) ethylamine in the same manner as in Example A1, 6- (2-chlorophenyl) -7- (4-chlorophenyl)- 2- (Methylsulfonylamino) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine (27 mg, 32% yield) is obtained as a colorless powder.
MS (APCI) m / z; 581/583 [M + H] ^< +>.

Example A35
(1) A mixture of the compound (1.0 g) obtained in Example A34 (3), 1.35 g of sodium ethoxide and 40 mL of ethanol was stirred at 80 ° C. for 10 minutes, and 2.5 mL of methyl iodide was slowly added dropwise thereto. And the mixture is stirred for 3 days. The reaction mixture is concentrated, water and ethyl acetate are added to the residue, the organic layer is separated, and the aqueous layer is extracted with ethyl acetate. The combined organic layers are dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by NH silica gel column chromatography (Chromatorex NH silica gel, solvent; hexane / ethyl acetate = 75 / 25-40: 60) to give 6- (2-chlorophenyl). ) -7- (4-Chlorophenyl) -3-ethoxycarbonyl-2- [N-methyl-N- (methylsulfonyl) amino] pyrazolo [1,5-a] pyrimidine (1.06 g, 100% yield). Obtained as a colorless powder.
MS (APCI) m / z; 519/521 [M + H] ^< +>.

(2) To a solution of 1.06 g of the compound obtained in (1) above in ethanol (15 mL) and tetrahydrofuran (15 mL) is added 2N aqueous sodium hydroxide solution (4.1 mL), and the mixture is stirred at 40 ° C. overnight. The reaction mixture is made weakly acidic with 2N hydrochloric acid, concentrated under reduced pressure, and extracted with chloroform. The organic layer is dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the residue was triturated with diethyl ether to give 3-carboxy-6- (2-chlorophenyl) -7- (4-chlorophenyl) -2- [N-methyl-N- ( Methylsulfonyl) amino] pyrazolo [1,5-a] pyrimidine (0.75 g, 75% yield) is obtained as a pale yellow powder.
MS (APCI) m / z; 491/493 [M + H] +.

(3) By treating 60 mg of the compound obtained in the above (2) and 19 mg of 1- (2-pyridyl) ethylamine in the same manner as in Example A1, 6- (2-chlorophenyl) -7- (4-chlorophenyl)- 2- [N-methyl-N- (methylsulfonyl) amino] -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine (57 mg, 79% yield) Is obtained as a colorless powder.
MS (APCI) m / z; 595/597 [M + H] ^< +>.

Examples A36-A38
The corresponding starting material compounds are treated in the same manner as in Example A1 to give the compounds shown in Table 5 below.

Example A39
To a solution of 159 mg of the compound obtained in Reference Example A9 and 83 μL of pyridine in 5 mL of chloroform is added dropwise a solution of 200 mg of the compound obtained in Reference Example A17 in 2 mL of chloroform under ice cooling, and the mixture is stirred at room temperature for 17 hours. Add water to the reaction mixture and extract with chloroform. The organic layer was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80/20 to 65:35) to give 6- (2-chlorophenyl) -7- ( 4-Trifluoromethylphenyl) -3- [N- (1-methoxycarbonylcyclohexyl) sulfamoyl] -2-methylpyrazolo [1,5-a] pyrimidine (205 mg, 82% yield) is obtained as a powder.
MS (APCI) m / z; 607/609 [M + H] ^< +>.

Example A40
To a solution of the compound obtained in Example A39 (190 mg) in methanol (2 mL) is added 2N aqueous sodium hydroxide solution (0.39 mL), and the mixture is stirred at 70 ° C. for 15 hours. The reaction solution is cooled to room temperature, 2N hydrochloric acid water (400 μL) is added, and the mixture is diluted with water. The precipitated solid was collected by filtration to give 3- [N- (1-carboxycyclohexyl) sulfamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -2-methylpyrazolo [1,5- a] Pyrimidine (150 mg, 81% yield) is obtained as a powder.
MS (APCI) m / z; 593/595 [M + H] ^< +>.

Example A41
(1) By treating 200 mg of the compound obtained in Reference Example A10 and 63 mg of the compound obtained in Reference Example B15 in the same manner as in Example A1, 6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (4-Methyl-tetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine (153 mg, yield: 48%) is obtained as a powder.
MS (APCI) m / z; 531/533 [M + H] ^< +>.

(2) To a solution of 95 mg of the compound obtained in (1) above in 5 mL of methylene chloride is added 123 mg of metachloroperbenzoic acid under ice cooling, and the mixture is stirred at room temperature for 21 hours. Saturated aqueous sodium hydrogen carbonate solution is added to the reaction mixture, and the mixture is extracted with chloroform. The organic layer was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80/20 to 60:40) to give 6- (2-chlorophenyl) -7- ( 4-trifluoromethylphenyl) -3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine (68 mg, 68% yield) ) As a powder.
MS (APCI) m / z; 563/565 [M + H] ^< +>.

Examples A42 to A49
The corresponding starting material compounds are treated in the same manner as in Example A41 to give the compounds shown in Table 6 below.

Examples A50 to A64
The corresponding starting material compounds are treated in the same manner as in Example A1 to give the compounds listed in Table 7 below.

Example A65
(1) 11.9 mL of a trimethylsilyldiazomethane 2M-hexane solution is added dropwise to a 10 mL methanol solution of 2.29 g of 1- (tert-butoxycarbonylamino) cyclopentanecarboxylic acid under ice cooling. The reaction mixture is concentrated, hexane is added to the residue, and the precipitated crystals are collected by filtration. The filtrate was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 9/1 to 7/3) and combined with the above crystals to give 1- (tert-butoxycarbonylamino) cyclopentanecarboxylic acid methyl ester 2 .49 g is obtained.
MS (ESI) m / z; 244 [M + H] ^< +>.

  (2) To a solution of 2.49 g of the compound obtained in the above (1) in 12 mL of tetrahydrofuran is added dropwise 13.3 mL of methylmagnesium bromide 3M-diethyl ether solution under ice cooling and nitrogen atmosphere, and the mixture is stirred at room temperature overnight. Add water to the reaction mixture and extract with ethyl acetate. The organic layer was dried over magnesium sulfate and purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 8/1) to obtain [1- (1-hydroxy-1-methylethyl) cyclopentyl] carbamic acid tert- A mixture (0.57 g) of butyl ester and 1- (tert-butoxycarbonylamino) cyclopentanecarboxylic acid methyl ester is obtained as a powder.

  (3) 2 mL of trifluoroacetic acid is added to a solution of 0.56 g of the compound obtained in (2) above in 5 mL of chloroform and stirred at room temperature for 10 minutes. The reaction solution is concentrated, and the resulting residue is dissolved in 1.0 mL of methanol, and then 0.6 mL of concentrated hydrochloric acid is added and stirred for 1 minute. The reaction mixture is concentrated and the resulting residue is dissolved in ethanol. The solution is concentrated, an ethanol / diethyl ether mixed solvent is added to the residue, and the mixture is stirred overnight. The precipitated crystals were collected by filtration, washed with diethyl ether and dried to give a mixture of 1- (1-hydroxy-1-methylethyl) cyclopentylamine hydrochloride and 1-aminocyclopentanecarboxylic acid methyl ester hydrochloride (376 mg). ) As a powder.

(4) 56 mg of the compound obtained in (3) above and 100 mg of 3-carboxy-6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine were added to Example A4 (1) and Process in the same way. The reaction product is dissolved in 2 mL of ethanol, 0.2 mL of 2N aqueous sodium hydroxide solution is added thereto, and the mixture is stirred at 60 ° C. for 2.5 hours. The reaction mixture is cooled to room temperature, neutralized with 2N hydrochloric acid, and extracted with dichloromethane. The organic layer was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 70/30 to 50/50 → chloroform / methanol = 90/10). 2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (1-hydroxy-1-methylethyl) cyclopentyl] carbamoyl] pyrazolo [1,5-a] pyrimidine (65 mg, yield 49 %, Compound a) and 3- [N- (1-carboxycyclopentyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine (24 mg, yield 19 %, Compound b) is obtained as a powder.
Compound a: MS (APCI) m / z; 509/511 [M + H] ⁺
Compound b: MS (APCI) m / z; 495/497 [M + H] ⁺ .

Examples A66 to A72
The corresponding starting material compound is treated in the same manner as in Example A4 (1) to give the compound shown in Table 8 below.

Examples A73 to A74
The corresponding starting material compound is treated in the same manner as in Example A41 (2) to give the compound shown in Table 9 below.

Examples A75-A78
The corresponding starting material compound is treated in the same manner as in Example A4 (2) to give the compound shown in Table 10 below.

Examples A79-A106
The corresponding starting material compounds are treated in the same manner as in Example A4 (1) to (2) to give the compounds described in Table 11 below.

Example A107
(1) To a solution of 805 mg of the compound obtained in Example A64 in 10 mL of dioxane, 10 mL of 4N hydrochloric acid-dioxane solution is added and stirred at room temperature for 4 hours. The reaction solution was diluted with diisopropyl ether, and the precipitated solid was collected by filtration to give 4-carbamoyl-4- [6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a ] Pyrimidine-3-carboxamide] piperidine hydrochloride (784 mg, 100% yield) is obtained as a powder.
MS (APCI) m / z; 543/545 [M + H] ^< +>.

(2) 30 mg of potassium carbonate and 13 μL of isopropyl iodide are added to a solution of 50 mg of the compound obtained in (1) above in 1 mL of dimethylformamide, and the mixture is stirred at 40 ° C. for 20 hours. The reaction mixture is allowed to cool, water is added, the mixture is extracted with ethyl acetate, and the organic layer is concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (solvent; chloroform / methanol = 99/1 to 87/13) to give 4-carbamoyl-4- [6- (2-chlorophenyl) -7- (4 -Trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine-3-carboxamide] -1-isopropylpiperidine (27 mg, 55% yield) is obtained as a powder.
MS (APCI) m / z; 585/587 [M + H] ^< +>.

Example A108
To a solution of 45 mg of the compound obtained in Example A107 (1) in 2 mL of methylene chloride is added 32.5 μL of triethylamine and methanesulfonyl chloride (7.8 μL), and the mixture is stirred at room temperature for 15 hours. Water is added to the reaction mixture, and the mixture is extracted with chloroform. The organic layer is concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 30 / 70-0 / 100) to give 4-carbamoyl-4- [6- (2-chlorophenyl) -7- ( 4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine-3-carboxamide] -1-methylsulfonylpiperidine (36 mg, 75% yield) is obtained as a powder.
MS (APCI) m / z; 621/623 [M + H] ^< +>.

Examples A109-A121
The corresponding starting material compounds are treated in the same manner as in Example A5 to give the compounds shown in Table 12 below.

Examples A122 to A123
The corresponding starting material compounds are treated in the same manner as in Example A108 to give the compounds shown in Table 13 below.

Examples A124-A138
The corresponding starting material compounds are treated in the same manner as in Example A5 to give the compounds shown in Table 14 below.

Examples A139-A142
The corresponding starting material compounds are treated in the same manner as in Example A1 to give the compounds shown in Table 15 below.

Example A143
The compound obtained in Example A142 (175 mg) was treated in the same manner as in Example A4 (2) to give 3- [N- (1-carboxycyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7. -(4-Chlorophenyl) -2- (2-hydroxyethoxy) pyrazolo [1,5-a] pyrimidine (131 mg, 77% yield) is obtained as a powder.
MS (APCI) m / z; 569/571 [M + H] ^< +>.

Example A144
6- (2-Bromophenyl) -3-carboxy-7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine (the compound obtained in Reference Example A18; 500 mg) and the compound obtained in Reference Example A9 (293 mg ) As in Example A1, and then the reaction product as in Example A4 (2) to give 6- (2-bromophenyl) -3- [N- (1-carboxycyclo). Hexyl) carbamoyl] -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine (648 mg) is obtained as a powder.
MS (APCI) m / z; 553/555 [M + H] ^< +>.

Example A145
(1) The compound (100 mg) obtained in Example A144 and 19 mg of ammonium chloride were treated in the same manner as in Example A5 to give 6- (2-bromophenyl) -3- [N- (1-carbamoylcyclohexyl). ) Carbamoyl] -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine (84 mg) is obtained as a powder.
MS (APCI) m / z; 552/554 [M + H] ^< +>.

(2) A solution of the compound (83 mg) obtained in the above (1), 20 mg of zinc cyanide and 17 mg of tetrakistriphenylphosphine palladium in 1 mL of dimethylformamide is stirred at 110 ° C. for 13 hours under a nitrogen atmosphere. The reaction mixture is cooled to room temperature, water is added, and the mixture is extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 67/33 to 10/90) to give 3- [N- (1-carbamoylcyclohexane). Xyl) carbamoyl] -7- (4-chlorophenyl) -6- (2-cyanophenyl) pyrazolo [1,5-a] pyrimidine (22 mg, 30% yield) is obtained as a powder.
MS (APCI) m / z; 499/501 [M + H] ^< +>.

Examples A146-A147
The corresponding starting material compound is treated in the same manner as in Example A1, and then the product is treated in the same manner as in Example A145 to obtain the compounds described in Table 16 below.

Examples A148-A149
The corresponding starting material compound is treated in the same manner as in Example A6 to give the compound shown in Table 17 below.

Example A150
86 mg of sodium azide and 183 mg of triethylamine hydrochloride are added to a solution of the compound 106 mg obtained in Example A1 in 4 mL of toluene and 1.5 mL of dimethylformamide, and the mixture is stirred at 120 ° C. for 24 hours. To the reaction solution, 90 mg of sodium azide and 183 mg of triethylamine hydrochloride are further added and stirred for 21 hours. The reaction mixture is cooled to room temperature, insolubles are filtered off through celite, and the filtrate is concentrated under reduced pressure. The resulting crude product is purified by silica gel column chromatography (solvent; chloroform / methanol = 100/0 to 95/5), and then purified by gel permeation chromatography (solvent; chloroform). (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (1,2,3,4-tetrazol-5yl) cyclohexyl] carbamoyl] pyrazolo [1,5-a] Pyrimidine (95 mg, 83% yield) is obtained as a powder.
MS (APCI) m / z; 533/535 [M + H] ^< +>.

Example A151
180 mg of metachloroperbenzoic acid (75%) is added to 3 mL of a methylene chloride solution of 195 mg of the compound obtained in Example A70, and the mixture is stirred at room temperature for 1 hour. After adding an aqueous sodium thiosulfate solution and methylene chloride to the reaction solution, the organic layer is separated and concentrated. The resulting residue is purified by NH silica gel column chromatography (Chromatorex NH silica gel, solvent; hexane / ethyl acetate = 50 / 50-30 / 70) to give 6- (2-chlorophenyl) -7- (4-trifluoro Methylphenyl) -3- [N- (4-hydroxymethyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine (169 mg, 82% yield) was lightly added. Obtained as a yellow powder.
MS (APCI) m / z; 579/581 [M + H] ^< +>.

Example A152
Raney nickel is added to a solution of 50 mg of the compound obtained in Example A62 in tetrahydrofuran-methanol (1 mL / 1 mL), and the mixture is stirred at 50 ° C. for 1 hour and a half in a hydrogen atmosphere, and then stirred at room temperature for 3 days. The reaction solution is filtered and the filtrate is concentrated. The obtained residue was purified by NH silica gel column chromatography (Chromatorex NH silica gel, solvent; chloroform) to give 3- [N- [1- (aminomethyl) cyclohexyl] carbamoyl] -6- (2-chlorophenyl)- 7- (4-Chlorophenyl) -2-methylpyrazolo [1,5-a] pyrimidine (35 mg, 69% yield) is obtained as a pale yellow powder.
MS (APCI) m / z; 508/510 [M + H] ^< +>.

Example A153
69 μL of trifluoroacetic acid is added to 0.6 mL of a methylene chloride solution of the compound obtained in Example A71 (35 mg) and stirred at room temperature overnight. Saturated aqueous sodium hydrogen carbonate solution is added to the reaction mixture, and the mixture is stirred for 5 minutes, extracted with methylene chloride, and the organic layer is concentrated. The obtained residue was purified by NH silica gel column chromatography (Chromatorex NH silica gel, solvent; hexane / ethyl acetate = 60 / 40-30 / 70) to give 3- [N-[(1-aminocyclopentyl) methyl] Carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -2-methylpyrazolo [1,5-a] pyrimidine (14 mg, 48% yield) is obtained as a powder.
MS (APCI) m / z; 494/496 [M + H] ^< +>.

Example A154
9 μL of acetyl chloride is added dropwise to a solution of the compound 51m obtained in Example A152 and 28 μL of triethylamine in 4 mL of methylene chloride at room temperature, followed by stirring for 1 hour. Water and methylene chloride are added to the reaction solution, and the organic layer is separated and concentrated. The obtained crude product was purified by silica gel column chromatography (solvent: chloroform / methanol = 100/0 to 95/5) to give 3- [N- [1- (acetylaminomethyl) cyclohexyl] carbamoyl. ] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -2-methylpyrazolo [1,5-a] pyrimidine (36.5 mg, yield: 66%) is obtained as a powder.
MS (APCI) m / z; 550/552 [M + H] ^< +>.

Example A155
The compound (51 mg) obtained in Example A152 and dimethylcarbamoyl chloride (11 μL) were treated in the same manner as in Example A154 to give 6- (2-chlorophenyl) -7- (4-chlorophenyl) -2-methyl-3. -[N- [1-[(3,3-Dimethylureido) methyl] cyclohexyl] carbamoyl] pyrazolo [1,5-a] pyrimidine (25.3 mg, yield: 44%) is obtained as a powder.
MS (APCI) m / z; 579/581 [M + H] ^< +>.

Example A156
The compound (51 mg) obtained in Example A152 and 9 μL of methanesulfonyl chloride were treated in the same manner as in Example A154 to give 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1 -(Mesylaminomethyl) cyclohexyl] carbamoyl] -2-methylpyrazolo [1,5-a] pyrimidine (39.2 mg, yield: 67%) is obtained as a powder.
MS (APCI) m / z; 586/588 [M + H] ^< +>.

Example A157
The compound (51 mg) obtained in Example A152 and 13 μL of dimethylsulfamoyl chloride were treated in the same manner as in Example A154 to give 6- (2-chlorophenyl) -7- (4-chlorophenyl) -2-methyl-3. -[N- [1-[[(Dimethylsulfamoyl) amino] methyl] cyclohexyl] carbamoyl] pyrazolo [1,5-a] pyrimidine (12.3 mg, yield: 20%) is obtained as a powder.
MS (APCI) m / z; 615/617 [M + H] ^< +>.

Examples A158 to A159
The corresponding starting material compounds are treated in the same manner as in Example A1 to give the compounds shown in Table 18 below.

Examples A160 to A161
The corresponding starting material compounds are treated in the same manner as in Example A1 to give the compounds listed in Table 19 below.

Examples A162 to A163
The compound shown in Table 20 below is obtained by treating the compound obtained in Example A143 and the corresponding amine compound in the same manner as in Example A5.

Examples A164 to A174
The compound shown in Table 21 below is obtained by treating the compound obtained in Example A75 and the corresponding amine compound in the same manner as in Example A5.

Examples A175-A184
The corresponding starting compounds are treated as in Example A1, then the product is treated as in Example A4 (2), and the product is treated as in Example A5, as described in Table 22 below. A compound is obtained.

Example B1
To a solution of 70 mg of the compound obtained in Reference Example B3 in 2 mL of tetrahydrofuran is added 0.14 mL of 2M methylamine-tetrahydrofuran solution, and the mixture is stirred at room temperature for 10 minutes. The reaction mixture is concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate solution is added to the residue, and the mixture is extracted with chloroform. The organic layer was concentrated under reduced pressure, and the resulting crude product was purified by NH silica gel column chromatography (Chromatorex NH silica gel, solvent; hexane / ethyl acetate = 80 / 20-30: 70) to give 6- (2-chlorophenyl). ) -7- (4-Chlorophenyl) -3-ethoxycarbonyl-2- (N-methylsulfamoyl) pyrazolo [1,5-a] pyrimidine (75 mg, 100% yield) is obtained as a colorless powder.
MS (APCI) m / z; 505/507 [M + H] ^< +>.

Example B2
(1) To a solution of the compound 524 mg obtained in Example B1 in 7 mL of ethanol and 7 mL of tetrahydrofuran, 1.04 mL of 2N aqueous sodium hydroxide solution is added and stirred at room temperature for 2 hours. The reaction mixture is made weakly acidic with 2N hydrochloric acid, concentrated under reduced pressure, and extracted with chloroform. The organic layer is dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to obtain 543 mg of 3-carboxy-6- (2-chlorophenyl) -7- (4-chlorophenyl) -2- (N-methylsulfamoyl) pyrazolo [1,5-a] pyrimidine. Obtained as a crude product.

(2) By treating the compound obtained in (1) above in the same manner as in Example A1, 6- (2-chlorophenyl) -7- (4-chlorophenyl) -2- (N-methylsulfamoyl)- 3- [N- (1-pyrrolidinyl) carbamoyl] pyrazolo [1,5-a] pyrimidine (29 mg) is obtained as a pale yellow powder.
MS (APCI) m / z; 545/547 [M + H] ^< +>.

Example B3
To a solution of 600 mg of the compound obtained in Reference Example B3 in 12 mL of tetrahydrofuran is added 1.17 mL of 2M dimethylamine-tetrahydrofuran solution, and the mixture is stirred at room temperature for 30 minutes. The reaction mixture is concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate solution is added to the residue, and the mixture is extracted with chloroform. The organic layer was concentrated under reduced pressure, and the resulting crude product was purified by NH silica gel column chromatography (Chromatorex NH silica gel, solvent; hexane / ethyl acetate = 80/20 to 0: 100) to give 6- (2-chlorophenyl). ) -7- (4-Chlorophenyl) -3-ethoxycarbonyl-2- (N, N-dimethylsulfamoyl) pyrazolo [1,5-a] pyrimidine (566 mg, 93% yield) is obtained as a colorless powder. .
MS (APCI) m / z; 519/521 [M + H].

Example B4
To a solution of 300 mg of the compound obtained in Reference Example B3 in 10 mL of tetrahydrofuran is added 7 mL of 0.5 M ammonia-1,4-dioxane solution, and the mixture is stirred at room temperature overnight. The reaction mixture is concentrated under reduced pressure, tetrahydrofuran is added to the residue, and the precipitate is removed by filtration. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80/20 to 50:50) to give 6- (2-chlorophenyl) -7- ( 4-Chlorophenyl) -3-ethoxycarbonyl-2-sulfamoylpyrazolo [1,5-a] pyrimidine (242 mg, 84% yield) is obtained as a colorless powder.
MS (APCI) m / z; 491/493 [M + H] ^< +>.

Example B5
1 mL of ethyl isocyanate is added to a solution of 40 mg of the compound obtained in Reference Example B7 in 2 mL of chloroform, and the mixture is heated to reflux overnight. After cooling the reaction solution to room temperature, an aqueous sodium hydrogen carbonate solution and chloroform are added and stirred. The organic layer is separated and concentrated under reduced pressure, and the resulting crude product is purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80/20 to 60:40) to give 6- (2-chlorophenyl)- 7- (4-Chlorophenyl) -3- (N-cyclopentylcarbamoyl) -2- (3-ethylureido) pyrazolo [1,5-a] pyrimidine (33.3 mg, 72% yield) is obtained as a pale yellow solid. .
MS (APCI) m / z; 537/539 [M + H] ^< +>.

Examples B6 to B24
The corresponding starting material compound is treated in the same manner as in Example B2 (2) to give the compound shown in Table 23 below.

Examples B25-B28
The corresponding starting material compounds are treated in the same manner as in Example B2 to give the compounds listed in Table 24 below.

Example B29
(1) The corresponding starting material compound is treated in the same manner as in Example B2 (2) to give 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-methoxycarbonylcyclohexyl). ) Carbamoyl] -2- (N-methylsulfamoyl) pyrazolo [1,5-a] pyrimidine (185 mg) is obtained as a pale yellow powder.
MS (APCI) m / z; 616/618 [M + H] ^< +>.

(2) The compound (182 mg) obtained in (1) above is treated in the same manner as in Example A4 (2) to give 3- [N- (1-carboxycyclohexyl) carbamoyl] -6- (2- Chlorophenyl) -7- (4-chlorophenyl) -2- (N-methylsulfamoyl) pyrazolo [1,5-a] pyrimidine (5.6 mg) is obtained as a powder.
MS (APCI) m / z; 602/604 [M + H] ^< +>.

Example B30
3- [N- (1-carbamoylcyclohexyl) carbamoyl] was obtained by treating the compound obtained in Reference Example B5 (35 mg) and the compound obtained in Reference Example B10 (17.5 mg) in the same manner as in Example A1. -6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (sulfamoyl) pyrazolo [1,5-a] pyrimidine (3.6 mg, yield: 8%) is obtained as a colorless powder.
MS (APCI) m / z; 587/589 [M + H] ^< +>.

Example B31
(1) By treating the compound (200 mg) obtained in Example A6 (1) and the compound (137 mg) obtained in Reference Example B11 in the same manner as in Example A1, 2-amino-3- [N- (4 -Carbamoyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine (82 mg, Yield: 29%) as a pale yellow powder.
MS (APCI) m / z; 607/609 [M + H] ^< +>.

(2) By treating 39 mg of the compound obtained in the above (1) in the same manner as in Example B5, 3- [N- (4-carbamoyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] -6- (2-chlorophenyl) -2- (3-ethylureido) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine (15 mg, yield: 34%) was pale yellow powder Get as a body.
MS (APCI) m / z; 678/680 [M + H] ^< +>.

Example B32
By treating 500 mg of the compound obtained in Reference Example B17 in the same manner as in Example A1, and then treating the product in the same manner as in Example A41 (2), 6- (2-chlorophenyl) -7- (4-tri Fluoromethylphenyl) -2-hydroxymethyl-3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine (498 mg) was lightly added. Obtained as a yellow powder.
MS (APCI) m / z; 593/595 [M + H] +.

Example B33
1.28 g of pyridinium dichromate is added to a solution of 335 mg of the compound obtained in Example B32 in 3.5 mL of dimethylformamide, and the mixture is stirred at room temperature for 16 hours. The reaction solution is filtered through silica gel and washed with a chloroform / methanol = 9/1 solution. The mother liquor is concentrated under reduced pressure, diluted with ethyl acetate and water is added. The organic layer is separated, washed with water and saturated brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent: chloroform / methanol = 100/0 to 85/15) to give 2-carboxy-6- (2-chlorophenyl). -7- (4-trifluoromethylphenyl) -3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine (245 mg, 71% yield) is obtained as a colorless solid.
MS (APCI) m / z; 607/609 [M + H] +.

Example B34
The compound (45 mg) obtained in Reference Example B17 was treated in the same manner as in Example A1 to give 3- [N- (1-carbamoylcyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7- (4 -Trifluoromethylphenyl) -2- (hydroxymethyl) pyrazolo [1,5-a] pyrimidine (29 mg, yield: 50%) is obtained as a colorless powder.
MS (APCI) m / z; 572/574 [M + H] ^< +>.

Examples B35-B38
The compound described in Table 25 below is obtained by treating the compound obtained in Example B33 and the corresponding amine compound in the same manner as in Example A5.

Examples B39 to B51
The corresponding starting material compounds are treated in the same manner as in Example A1 to give the compounds shown in Table 26 below.

Examples B52 to B53
The corresponding raw material compound is treated in the same manner as in Example A41 to give the following compound.

Example B52: 2-carbamoyl-6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (1,1-dioxothiacyclobutan-3-yl) carbamoyl] pyrazolo [ 1,5-a] pyrimidine powder MS (APCI) m / z; 564/566 [M + H] ⁺ .

Example B53: 6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -2-hydroxymethyl-3- [N- (1,1-dioxothiacyclobutan-3-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine powder MS (APCI) m / z; 551/553 [M + H] ⁺ .

Examples B54-B120
The corresponding starting material compounds are treated in the same manner as in Example A1 to give the compounds described in Table 27 below.

Example B121
Under a nitrogen atmosphere, add 0.15 mL of a 2.0 M trimethylaluminum-toluene solution to 1.5 mL of toluene in 30 μL of cyclopentylamine, and stir at room temperature for 15 minutes. After adding 76 mg of the compound obtained in Reference Example B21 and stirring at room temperature for 1 hour, the mixture is stirred at 100 ° C. for 17 hours. The reaction mixture is cooled to room temperature, diluted with ethyl acetate, 20% aqueous Rochelle salt solution is added, and the mixture is extracted with chloroform. The organic layer was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent: chloroform / methanol = 100/0 to 96/4) to give 6- (2-chlorophenyl) -3- [N -(Cyclopentyl) carbamoyl] -7- (4-trifluoromethylphenyl) -2-ureidopyrazolo [1,5-a] pyrimidine (48 mg, yield: 59%) is obtained as a powder.
MS (APCI) m / z; 543/545 [M + H] ^< +>.

Examples B122 to B125
The corresponding starting material compound is treated in the same manner as in Example B121 to give the compound shown in Table 28 below.

Reference Example A1
(1) To 250 mL of diethyl ether, 6.04 g of metal magnesium and a catalytic amount of iodine are added and stirred, and 20.0 g of 2-chlorobenzyl chloride is gradually added dropwise. After stirring the mixture for 1 hour, 18.8 g of 4-chlorobenzonitrile in tetrahydrofuran-diethyl ether (20 mL / 50 mL) is added to the reaction mixture and stirred for 3 hours. Under ice cooling, 150 mL of 2N hydrochloric acid is added to the reaction mixture, and the mixture is stirred at room temperature for 2 hours, followed by extraction with ethyl acetate. The organic layer is washed with water and saturated brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (hexane / ethyl acetate = 40: 1 to 20: 1) to give (2-chlorobenzyl) (4-chlorophenyl) methanone ( 24.40 g, 74% yield) is obtained as a powder.
MS (APCI) m / z; 265/267 [M + H] +.

  (2) A solution of 6.4 g of the compound obtained in (1) above and 6.4 mL of N, N-dimethylformamide dimethylacetal in 24 mL of N, N-dimethylformamide is stirred at 150 ° C. for 4 hours. The reaction mixture is cooled to room temperature, water is added, and the mixture is extracted 3 times with ethyl acetate-hexane. The organic layer is washed with saturated brine, dried over magnesium sulfate, and filtered. The filtrate is concentrated under reduced pressure to give 1- (4-chlorophenyl) -2- (2-chlorophenyl) -3- (N, N-dimethylamino) -2-propen-1-one as an oil.

(3) The oily compound obtained in the above (2) is dissolved in 8 mL of acetic acid, 3.75 g of 3-amino-4-ethoxycarbonyl-1H-pyrazole and 0.48 mL of piperidine are added, and the mixture is heated at 80 ° C. for 16 hours. After cooling the reaction solution to room temperature, water and ethyl acetate are added and stirred. The organic layer is washed with saturated brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (hexane / ethyl acetate = 17 / 3-67 / 33) to give 6- (2-chlorophenyl) -7- (4- Chlorophenyl) -3-ethoxycarbonylpyrazolo [1,5-a] pyrimidine (5.02 g, total yield of steps (2) to (3) 50%) is obtained as a powder.
MS (APCI) m / z; 412/414 [M + H] +.

(4) 6 mL of 2N aqueous sodium hydroxide solution is added to 30 mL of an ethanol solution of 2.5 g of the compound obtained in (3) above, and the mixture is stirred at room temperature for 5 hours. 2N Hydrochloric acid is added to the reaction mixture, and the mixture is stirred and concentrated under reduced pressure. The organic layer is washed with saturated brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give 3-carboxy-6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine (2.1 g, yield 90%) as a powder. obtain.
MS (APCI) m / z; 384/386 [M + H] +.

Reference Example A2
(1) To 100 mL of dimethoxyethane was added 4.1 g of 4-chlorobenzyl bromide, 2.56 mL of 4-chlorobenzoyl chloride, 702 mg of bis (triphenylphosphine) palladium dichloride and 2.6 g of zinc dust, and the mixture was added under nitrogen atmosphere. Stir for hours. The reaction mixture is filtered, the filtrate is concentrated under reduced pressure, and the residue is extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 49/1 to 9/1) to give (2-chlorobenzyl) (4-chlorophenyl). Methanone (4.85 g, 91% yield) is obtained as a powder.
MS (GC-EI) m / z; 264 [M] ^<+> .

  (2) 3-carboxy-6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo is obtained by treating the compound obtained in (1) in the same manner as in Reference Example A1 (2) to (4). [1,5-a] pyrimidine is obtained.

Reference Example A3
(1) A solution of 5.6 g of potassium cyanide and 5.06 g of ammonium chloride in 17 mL of water is added with a solution of 10 g of tetrahydro-4H-thiopyran-4-one in 22 mL of methanol and refluxed overnight. The reaction mixture is cooled to room temperature, 1N aqueous sodium hydroxide solution is added, and the mixture is extracted with diethyl ether. The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. 4N Hydrochloric acid ethyl acetate solution is added to the diethyl ether solution of the residue, and the precipitate is collected by filtration to give 4-aminotetrahydrothiopyran-4-carbonitrile (13.6 g, yield 88%) as a colorless solid.
MS (APCI) m / z; 143 [M + H] ^< +>.

(2) Reflux overnight with 500 mL of a 6N aqueous hydrochloric acid solution of the compound (10.5 g) obtained in (1) above. The reaction mixture is cooled to room temperature, concentrated under reduced pressure, and the residue is dried to give 4-aminotetrahydrothiopyran-4-carboxylic acid (10.6 g) as a crude product.
MS (APCI) m / z; 162 [M + H] ^< +>.

(3) 5.7 mL of thionyl chloride is gradually added dropwise to 70 mL of a methanol solution of the compound (10.6 g) obtained in (2) above, and the mixture is refluxed overnight. The reaction mixture is cooled to room temperature and concentrated under reduced pressure. The residue is washed with ethyl acetate-diethyl ether, 1N aqueous sodium hydroxide solution is added, and the mixture is extracted with chloroform. The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure to give 4-aminotetrahydrothiopyran-4-carboxylic acid methyl ester (3.83 g, yield 39%) as a brown oil. .
MS (APCI) m / z; 176 [M + H] ^< +>.

(4) 394 mg of metachloroperbenzoic acid is gradually added to a solution of the compound obtained in (3) (100 mg) in 4 mL of methylene chloride and stirred at room temperature for 30 minutes. After adding 4 mL of methanol to the reaction solution, 0.9 g of PL-HCO ₃ MP resin (manufactured by Polymer Labs) is gradually added, and the mixture is stirred overnight. The reaction solution is filtered, and the filtrate is concentrated under reduced pressure. The resulting crude product is purified by silica gel column chromatography (hexane / ethyl acetate = 30: 70-0: 100) to give 4-amino-1,1-dioxotetrahydrothiopyran-4-carboxylic acid methyl ester (38 mg, 32% yield) is obtained as a colorless solid.
MS (ESI) m / z; 208 [M + H] ^< +>.

Reference Example A4
A solution of 40 g of 2-cyano-3,3-bismethylthioacrylic acid ethyl ester, 12.6 g of hydrazine hydrochloride and 22.6 g of sodium acetate in ethanol (700 mL) is stirred at 90 ° C. for 2 hours. The reaction mixture is cooled to room temperature, concentrated under reduced pressure, and water and ethyl acetate are added to the residue. The organic layer is separated, dried over magnesium sulfate, filtered, and the filtrate is concentrated under reduced pressure. Ethyl acetate and hexane are added to the residue, and the precipitated solid is collected by filtration and dried to give 3-amino-4-ethoxycarbonyl-5-methylthiopyrazole (17.4 g, yield 47%) as a colorless solid.
MS (APCI) m / z; 202 [M + H] ^< +>.

Reference Example A5
(1) By treating 50 g of 2-chlorobenzyl chloride and 53.1 g of 4-trifluoromethylbenzonitrile in the same manner as in Reference Example A1 (1), (2-chlorobenzyl) (4-trifluoromethylphenyl) methanone (42.5 g, 46% yield) is obtained as a powder.

  (2) By treating the compound (15.1 g) obtained in (1) above and N, N-dimethylformamide dimethyl acetal (12.1 g) in the same manner as in Reference Example A1 (2), 2- (2- Chlorophenyl) -1- (4-trifluoromethylphenyl) -3- (N, N-dimethylamino) -2-propen-1-one (17.7 g) is obtained as an oily crude product.

(3) By treating the compound (17.7 g) obtained in (2) above and the compound (10.2 g) obtained in Reference Example A4 in the same manner as in Reference Example A1 (3), 6- (2-chlorophenyl) ) -3-Ethoxycarbonyl-7- (4-trifluoromethyl) -2-methylthiopyrazolo [1,5-a] pyrimidine (12.2 g, 46% yield) is obtained as a powder.
MS (APCI) m / z; 492/494 [M + H] +.

Reference Example A6
(1) 6- (2-Chlorophenyl) -3-ethoxycarbonyl-7- (4-trifluoromethylphenyl) -2-methylthiopyrazolo [1,5-a] pyrimidine (compound obtained in Reference Example A5, 11 Of 1 g of m-chloroperbenzoic acid at 400C to 400 mL of a solution of 0.0 g) of methylene chloride and the mixture is stirred at room temperature for 3 hours. To the reaction solution, an aqueous sodium thiosulfate solution is added dropwise at 0 ° C. with stirring, and the mixture is extracted with ethyl acetate. The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The resulting crude product is washed with ethanol to give 6- (2-chlorophenyl) -3-ethoxycarbonyl-7- (4-trifluoromethylphenyl) -2-methylsulfonylpyrazolo [1,5-a]. Pyrimidine (10.7 g, 91% yield) is obtained as a powder.

  (2) To a solution of 10.7 g of the compound obtained in (1) above in 120 mL of dimethylformamide is added 5.3 g of sodium azide, and the mixture is stirred at 110 ° C. for 3 hours. The reaction mixture is cooled to room temperature, water is added, and the mixture is stirred and extracted with ethyl acetate. The organic layer is washed with water and concentrated under reduced pressure, and the resulting crude product is purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80/20 to 65:35) to give 2-azido-6- (2 -Chlorophenyl) -3-ethoxycarbonyl-7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine (9.7 g, 98% yield) is obtained as a pale yellow solid.

  (3) Add 10.5 g of triphenylphosphine to a solution of the compound (9.7 g) obtained in (2) above in 150 mL of tetrahydrofuran and stir at 60 ° C. for 1 hour. The reaction solution is cooled to room temperature and concentrated under reduced pressure, and the resulting crude product is purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 90/10 to 0/100) to give 6- (2-chlorophenyl). -3-Ethoxycarbonyl-7- (4-trifluoromethylphenyl) -2- (N-triphenylphosphoranylideneamino) pyrazolo [1,5-a] pyrimidine (11.1 g, 77% yield) yellow Obtain as a solid.

(4) A mixed solution of the compound (11.1 g) obtained in (3) above in 28 mL of tetrahydrofuran, 70 mL of acetic acid and 42 mL of water is stirred at 100 ° C. overnight. The reaction mixture is cooled to room temperature and concentrated under reduced pressure. The resulting crude product is purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 85/15 to 60/40) to give 2-amino-6- ( 2-Chlorophenyl) -3-ethoxycarbonyl-7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine (5.2 g, 73% yield) is obtained as a yellow solid.
MS (APCI) m / z; 461/463 [M + H] ^< +>.

Reference Example A7
(1) 7.58 mL of diphenylphosphoric acid azide and 4.90 mL of triethylamine are added to a solution of 3.52 g of 1-methylcyclopropanecarboxylic acid in 50 mL of tert-butanol and stirred at 80 ° C. for 15 hours. The reaction mixture is cooled to room temperature, concentrated under reduced pressure, water and saturated aqueous sodium hydrogen carbonate are added to the residue, and the mixture is extracted with diethyl ether. The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 90/10 to 87/13) to give 1-methyl-1- (N-tert-butoxycarbonyl) aminocyclopropane ( 4.66 g, 77% yield) is obtained as a colorless solid.
MS (APCI) m / z; 172 [M + H] ^< +>.

(2) To a solution of 4.66 g of the compound obtained in (1) above in 10 mL of 1,4-dioxane, 10 mL of 4N hydrochloric acid-dioxane solution is added and stirred overnight at room temperature. Diisopropyl ether is added to the reaction mixture, and the precipitated crystals are collected by filtration to give 1-methylcyclopropylamine (2.69 g, yield 92%) as a colorless solid hydrochloride.
MS (APCI) m / z; 72 [M + H] ^< +>.

Reference Example A8
Under a nitrogen atmosphere, a solution of anhydrous cerium chloride (5.0 g) in tetrahydrofuran (40 mL) is stirred at room temperature overnight. Under cooling with dry ice-acetone, 19 mL of a 1.04 M methyllithium-diethyl ether solution is added dropwise to the reaction mixture over 20 minutes, and the mixture is stirred at the same temperature for 30 minutes. A solution of 2-cyanopyridine (685 mg) in tetrahydrofuran (1 mL) is added dropwise to the reaction solution, and the temperature is raised to room temperature over 5 hours. 12.5 mL of 28% aqueous ammonia solution is added to the reaction mixture under ice cooling, and the insoluble material is filtered through Celite. The filtrate is dried over sodium sulfate and filtered, and the filtrate is concentrated under reduced pressure to give 1-methyl-1- (2-pyridyl) ethylamine (863 mg) as a brown oil.
MS (APCI) m / z; 137 [M + H] ^< +>.

Reference Example A9
To 600 mg of 1-aminocyclohexanecarboxylic acid in tetrahydrofuran-methanol solution, 4.2 mL of trimethylsilyldiazomethane is added dropwise with stirring under ice cooling, and the mixture is stirred overnight. The reaction mixture is concentrated, and diethyl ether / hexane (1/1) and 1.05 mL of 4N hydrochloric acid-ethyl acetate are sequentially added to the residue. The precipitated solid is collected by filtration and dried to give 1-aminocyclohexanecarboxylic acid methyl ester (423 mg, yield 52%) as a white powder.
MS (APCI) m / z; 158 [M + H] ^< +>.

Reference Examples A10 to A13
The corresponding starting material compounds are treated in the same manner as in Reference Example A1 to give the compounds listed in Table 29 below.

Reference Example A14
(1) Add 14.4 mL of N, N-dimethylformamide dimethyl acetal to 150 mL of dimethylformamide in 10 g of 2-chlorophenylacetic acid methyl ester, and stir at 85 ° C. overnight. After cooling the reaction solution to room temperature, ethyl acetate and water are added and stirred. The organic layer is extracted, dried over sodium sulfate and filtered. The filtrate is concentrated under reduced pressure, and the residue is diluted with 18 mL of acetic acid. Then, 8.4 g of 3-amino-4-ethoxycarbonyl-1H-pyrazole and 1.1 mL of piperidine are added, and the mixture is stirred at 80 ° C. for 3.5 hours. After cooling the reaction solution to room temperature, ethyl acetate and water are added and stirred, followed by filtration. The obtained solid is dried to obtain 3- [2- (2-chlorophenyl) -2-methoxycarbonylvinylamino] -4-ethoxycarbonyl-1H-pyrazole (11.8 g, yield 62%) as a powder. .
MS (APCI) m / z; 350/352 [M + H] ^< +>.

(2) To a solution of 10.7 g of the compound obtained in (1) above in 250 mL of ethanol is added 3.24 g of sodium carbonate and heated to reflux for 4 days. The reaction solution is cooled to room temperature and then filtered, and the filtrate is concentrated under reduced pressure. Water is added to the residue, stirred, and filtered (the filtration operation is repeated 5 times). The resulting solid was dried to give 6- (2-chlorophenyl) -3-ethoxycarbonyl-7-oxo-4,7-dihydropyrazolo [1,5-a] pyrimidine (8.5 g, 87% yield). ) As a powder.
MS (APCI) m / z; 318/320 [M + H] ^< +>.

(3) Add 319 μL of N, N-dimethylaniline and 270 μL of phosphorus oxychloride to a solution of 300 mg of the compound obtained in (2) above in 2 mL of acetonitrile, and heat to reflux for 1 day. The reaction mixture is cooled to room temperature, poured into ice water, and extracted with methylene chloride. The extract is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80/20 to 60/40) to give 7-chloro-6- (2-chlorophenyl) -3-ethoxycarbonylpyrazolo. [1,5-a] pyrimidine (108 mg, 34% yield) is obtained as a powder.
MS (APCI) m / z; 336/338 [M + H] ^< +>.

(4) 210 μL of 4-pipecoline and 412 mg of potassium carbonate are added to a 6 mL solution of 500 mg of the compound obtained in (3) above in dimethylformamide, and the mixture is stirred at 80 ° C. for 2 hours and 30 minutes. The reaction mixture is cooled to room temperature, water is added, and the mixture is extracted with ethyl acetate. The organic layer is washed with water and saturated brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80/20 to 50/50) to give 6- (2-chlorophenyl) -3-ethoxy. Carbonyl-7- (4-methylpiperidin-1-yl) pyrazolo [1,5-a] pyrimidine (593 mg, 99% yield) is obtained as an oil.
MS (APCI) m / z; 399/401 [M + H] ^< +>.

(5) By treating 593 mg of the compound obtained in (4) above in the same manner as in Reference Example 1 (4), 3-carboxy-6- (2-chlorophenyl) -7- (4-methylpiperidin-1-yl) ) Pyrazolo [1,5-a] pyrimidine (500 mg, 91% yield) is obtained as a colorless solid.
MS (APCI) m / z; 371/373 [M + H] ^< +>.

Reference Example A14B
36 mL of N, N-dimethylformamide dimethylacetal is added to a solution of 25 g of 2-chlorophenylacetic acid methyl ester in 400 mL of dimethylformamide, and stirred at 90 ° C. overnight. After cooling the reaction solution to room temperature, ethyl acetate and water are added and stirred. The organic layer is dried over magnesium sulfate and then filtered. The filtrate is concentrated under reduced pressure, and the residue is diluted with 60 mL of acetic acid. To this is added 19.7 g of 3-amino-4-ethoxycarbonyl-5-methyl-1H-pyrazole, and the mixture is stirred at 120 ° C. overnight. After cooling the reaction solution to room temperature, the precipitate is collected by filtration, washed with ethyl acetate / diisopropyl ether (= 1/1) and dried to give 6- (2-chlorophenyl) -3-ethoxycarbonyl-2-methyl. -7-oxo-4,7-dihydropyrazolo [1,5-a] pyrimidine (26.0 g, 62% yield) is obtained as a powder.
MS (APCI) m / z; 332/334 [M + H] ^< +>.

Reference examples A15 to A16
By treating the corresponding starting compound in the same manner as in Reference Example A14 or Reference Example A14B, and then treating each reaction product in the same manner as in Reference Example A14 (3) to (4), the compounds described in Table 30 below were obtained. obtain.

Reference Example A17
(1) The corresponding starting material compound is treated in the same manner as in Reference Example A1 (1) to give (2-chlorobenzyl) (4-trifluoromethylphenyl) methanone.

(2) The compound obtained in the above (1) (3.0 g) and N, N-dimethylformamide dimethyl acetal were treated in the same manner as in Reference Example A1 (2), and then the resulting product and 3-amino-5-methyl By treating 977 mg of pyrazole in the same manner as in Reference Example A1 (3), 6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -2-methylpyrazolo [1,5-a] pyrimidine (2. 63 g, 67% yield) is obtained as a brown oil.
MS (APCI) m / z; 388/390 [M + H] +.

(3) 1.35 mL of chlorosulfonic acid is gradually added dropwise to a solution of the compound 2.27 g obtained in (2) above in 50 mL of chloroform, and the mixture is stirred at 70 ° C. for 3.5 hours. The reaction mixture is concentrated under reduced pressure, 20 mL of thionyl chloride is added to the residue, and the mixture is heated to reflux for 2 hours. The reaction mixture is concentrated under reduced pressure, ice water is added to the residue, and the mixture is extracted with chloroform. The organic layer is dried over sodium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The obtained crude product is purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 85 / 15-60 / 40) to give 6- (2-chlorophenyl) -3-chlorosulfonyl-7- (4- Trifluoromethylphenyl) -2-methylpyrazolo [1,5-a] pyrimidine (2.71 g, 95% yield) is obtained as a pale yellow solid.
MS (APCI) m / z; 486/488 [M + H] +.

Reference examples A18 to A20
The corresponding starting material compounds are treated in the same manner as in Reference Example A1 to obtain the compounds described in Table 31 below.

Reference examples A21 to A22
The corresponding starting material compounds are treated in the same manner as in Reference Example A2 to obtain the compounds described in Table 32 below.

Reference Example A23
(1) To a solution of 7.4 g of 2-chlorophenylacetic acid methyl ester in 110 mL of dimethylformamide, 10.6 mL of N, N-dimethylformamide dimethylacetal is added and stirred at 90 ° C. overnight. The reaction mixture is cooled to room temperature, water is added, and the mixture is extracted once with 200 mL of ethyl acetate: hexane (4: 1) and twice with 100 mL. The organic layers are combined, washed with water and saturated brine, dried over magnesium sulfate, and filtered. The filtrate is concentrated under reduced pressure, and the residue is diluted with 18 mL of acetic acid, and 6.2 g of 3-amino-4-ethoxycarbonyl-1H-pyrazole is added thereto, followed by stirring at 110 ° C. overnight. After cooling the reaction solution to room temperature, the precipitate is collected by filtration, washed with ethyl acetate and then with diisopropyl ether and dried to give 6- (2-chlorophenyl) -3-ethoxycarbonyl-7-oxo-4,7- Dihydropyrazolo [1,5-a] pyrimidine (9.9 g, 2-step yield 78%) is obtained as a powder.
MS (APCI) m / z; 318/320 [M + H] ^< +>.

(2) By treating 4.8 g of the compound obtained in (1) in the same manner as in Reference Example A14 (3), 7-chloro-6- (2-chlorophenyl) -3-ethoxycarbonylpyrazolo [1, 5-a] pyrimidine (4.2 g, 85% yield) is obtained as a powder.
MS (APCI) m / z; 336/338 [M + H] ^< +>.

(3) 840 mg of the compound obtained in the above (2), 61 mg of [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride-methylene chloride complex, 1.6 g of potassium phosphate and 2-fluoro-4 A solution of 462 mg of formylphenylboronic acid in 25 mL of 1,4-dioxane is stirred at 80 ° C. overnight under a nitrogen atmosphere. Cool the reaction to room temperature and add ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer is separated, washed successively with water and saturated brine, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 70/30 to 50/50) to give 6- (2-chlorophenyl) -3-ethoxy. Carbonyl-7- (2-fluoro-4-formylphenyl) pyrazolo [1,5-a] pyrimidine (665 mg, 63% yield) is obtained as a powder.
MS (APCI) m / z; 424/426 [M + H] ^< +>.

(4) To a solution of 660 mg of the compound obtained in (3) above in 0.7 mL of methylene chloride, 783 μL of bis (2-methoxyethyl) aminosulfur trifluoride (trade name: Deoxo-Fluor, manufactured by Scott) was added, and 1 at room temperature was added. Stir for days. The reaction mixture is ice-cooled, saturated aqueous sodium hydrogen carbonate solution is added, and the mixture is stirred for 10 min and extracted with methylene chloride. The organic layer is concentrated under reduced pressure, and the resulting crude product is purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 75 / 25-60 / 40) to give 6- (2-chlorophenyl) -3-ethoxy. Carbonyl-7- (2-fluoro-4-difluoromethylphenyl) pyrazolo [1,5-a] pyrimidine (295 mg, 42% yield) is obtained as a powder.
MS (APCI) m / z; 446/448 [M + H] ^< +>.

(5) By treating 290 mg of the compound obtained in the above (4) in the same manner as in Reference Example A1 (4), 3-carboxy-6- (2-chlorophenyl) -7- (2-fluoro-4-difluoromethyl) Phenyl) pyrazolo [1,5-a] pyrimidine (208 mg, 77% yield) is obtained as a solid.
MS (APCI) m / z; 418/420 [M + H] ^< +>.

Reference Example A24
The corresponding starting material compound is treated in the same manner as in Reference Example A23 (1) to (3), and then the resulting product is treated in the same manner as in Reference Example A23 (5) to give 3-carboxy-6- (2-chlorophenyl). ) -2-Methyl-7-phenylpyrazolo [1,5-a] pyrimidine (250 mg, 94% yield) is obtained as a solid.
MS (APCI) m / z; 364/366 [M + H] ^< +>.

Reference Example A25
(1) In a nitrogen atmosphere, 4.7 mL of ethyl cyanoacetate is added dropwise to a solution of 14.32 g of sodium ethoxide in 20 mL of ethanol, and the mixture is stirred at room temperature for 1 hour. 4.85 mL of difluoroacetic acid is added to the reaction mixture, and the mixture is stirred at room temperature for 4 hours, and further stirred at an external temperature of 60 ° C. for 17 hours. The reaction mixture is concentrated under reduced pressure, 10 mL of toluene and 3.2 g of phosphorus chloride are added to the resulting residue, and the mixture is stirred at 45 ° C. for 1 hour. 1.9 g of phosphorus chloride is further added to the reaction solution, and the mixture is stirred at 55 ° C. for 2 hours. The reaction mixture is ice-cooled, filtered through Celite, and the filtrate is concentrated under reduced pressure. Ethanol 20mL, hydrazine monohydrate 0.8mL, and triethylamine 3.0mL are added to the obtained residue, and it stirs at 60 degreeC for 2 hours. The reaction mixture is cooled to room temperature, saturated aqueous sodium hydrogen carbonate solution and water are added, and the mixture is extracted with chloroform (4 times). The organic layer is dried over sodium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The resulting crude product is purified by silica gel column chromatography (solvent; chloroform / methanol = 100/0 to 94/6) and washed with chloroform to give 3-amino-4-ethoxycarbonyl-5-difluoromethylpyrazole. (1.26 g, 41% yield) is obtained as a colorless solid.
MS (APCI) m / z; 206 [M + H] ^< +>.

(2) By treating the compound (400 mg) obtained in the above (1) in the same manner as in Reference Example A1 (2) to (3), 3-carboxy-6- (2-chlorophenyl) -7- (4- Chlorophenyl) -2-difluoromethylpyrazolo [1,5-a] pyrimidine (405 mg, 48% yield) is obtained as a powder.
MS (APCI) m / z; 434/436 [M + H] ^< +>.

Reference Example A26
(1) Add 37.2 g of trifluoroacetic anhydride to a methylene chloride 260 m solution of 14.6 g of methyl cyanoacetate and stir at room temperature. To this mixture, 51.7 mL of triethylamine is slowly added dropwise at 0 ° C., and the mixture is stirred at room temperature overnight. Add water to the reaction mixture and extract with methylene chloride. The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure to give methyl 2-cyano-2- (2-trifluoroacetyl) acetate (Compound 2a) and 2-cyano-4,4,4. A mixture (55.3 g) of methyl trifluoro-3-trifluoromethoxycarbonyl-2-butenoate (compound 2b) is obtained.
Compound 2a: MS (APCI) m / z; 196 [M + H] ⁺
Compound 2b: MS (APCI) m / z; 292 [M + H] ^< +>.

  (2) 31.6 mL of oxalyl chloride is gradually added dropwise to a solution of 27.6 g of the compounds 2a and 2b (mixture) obtained in (1) above in 200 mL of methylene chloride (added together with several drops of pyridine). After the mixture is heated to reflux for 4 hours, the reaction mixture is poured slowly into water and extracted with methylene chloride. The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure to obtain methyl 3-chloro-2-cyano-4,4,4-trifluoro-2-butenoate as a crude product.

(3) Add 20 mL of water to the compound obtained in (2) above, and gradually drop 6.74 g of hydrazine monohydrate (80%) at 0 ° C. Add 2 mL of triethylamine to the mixture at room temperature and stir for 1 hour. Add water to the reaction mixture and extract with ethyl acetate. The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. Chloroform is added to the residue, and the precipitate is collected by filtration to give 3-amino-5-trifluoromethyl-4-methoxycarbonylpyrazole (3.96 g) as an orange solid.
MS (APCI) m / z; 210 [M + H] ^< +>.

(4) By treating the compound (2.37 g) obtained in (3) in the same manner as in Reference Example A1 (2) to (3), 3-carboxy-6- (2-chlorophenyl) -7- ( 4-Chlorophenyl) -2-trifluoromethylpyrazolo [1,5-a] pyrimidine (1.81 g) is obtained as a crude product (powder).
MS (APCI) m / z; 452/454 [M + H] ^< +>.

Reference examples A27 to A28
The corresponding starting material compounds are treated in the same manner as in Reference Example A25 or Reference Example A26 to obtain the compounds described in Table 33 below.

Reference examples A29 to A30
The corresponding starting material compound is treated in the same manner as in Reference Example A6, and then the product is treated in the same manner as in Reference Example A1 (4) to obtain the compounds described in Table 34 below.

Reference Example A31
(1) Add 748 mg of hydrazine hydrochloride and 1.34 g of sodium acetate to 20 mL of ethanol in 2.0 g of 2-[(cyano) (ethoxycarbonyl) vinyl] -1,3-dioxolane, and stir at 80 ° C. for 1 hour. . The reaction mixture is cooled to room temperature, filtered through celite, and the filtrate is concentrated under reduced pressure. The resulting crude product is purified by silica gel column chromatography (solvent; chloroform / methanol = 100/0 to 85/15) to give 3-amino-4-ethoxycarbonyl-5-[(2-hydroxy) ethoxy]. -1H-pyrazole (2.01 g, 86% yield) is obtained as a pale pink solid.
MS (APCI) m / z; 216 [M + H] ^< +>.

(2) By treating 2.65 g of the compound obtained in (1) above in the same manner as in Reference Example A1 (2) to (4), 3-carboxy-6- (2-chlorophenyl) -7- (4- Chlorophenyl) -2- (2-hydroxyethoxy) pyrazolo [1,5-a] pyrimidine is obtained as a powder.
MS (ESI) m / z; 444/446 [M + H] ^< +>.

Reference Example A32
(1) To a 15 mL acetic acid solution of 3.78 g of methyl 2-pyridylacetate is added dropwise a 5 mL aqueous solution of 1.75 g of sodium nitrite under ice cooling, and the mixture is stirred for 30 minutes at room temperature. The reaction mixture is neutralized with aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (hexane / ethyl acetate = 75 / 25-25 / 75) to give methyl (hydroxyimino) (2-pyridyl) acetate (3.72 g). Yield 83%) as a colorless solid.
MS (APCI) m / z; 181 [M + H] ^< +>.

(2) Add 200 mg of 10% palladium on carbon to a solution of 1.64 g of the compound obtained in (1) above in 32 mL of methanol and shake for 6 hours in a hydrogen atmosphere and under pressure (50 Parr). The reaction mixture is filtered, and the filtrate is concentrated under reduced pressure to give methyl (amino) (2-pyridyl) acetate (1.52 g, yield 93%) as an oil.
MS (APCI) m / z; 167 [M + H] ^< +>.

(3) To a solution of the compound 659 mg obtained in (2) above in chloroform (10 mL) is added di-tert-butyl dicarbonate (908 mg) in chloroform (10 mL), and the mixture is stirred at room temperature for 1.5 hours. A saturated aqueous sodium hydrogen carbonate solution is added to the reaction mixture, and the organic layer is separated and concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane / ethyl acetate = 85 / 15-60 / 40) to give methyl (tert-butoxycarbonylamino) (2-pyridyl) acetate (123 mg, yield 12 %) As a yellow oil.
MS (APCI) m / z; 267 [M + H] ^< +>.

(4) To a solution of 122 mg of the compound obtained in (3) above in 3 mL of methanol is added 460 μL of a 2N aqueous sodium hydroxide solution, and the mixture is stirred at room temperature for 1 hour. The reaction solution is concentrated under reduced pressure, and the residue and 25 mg of ammonium chloride are treated in the same manner as in Example A5. The reaction product is then treated in the same manner as in Reference Example A7 (2) to give 2-amino-2- (2-pyridyl) acetamide (92 mg, yield 89%) as a yellow powder.
MS (APCI) m / z; 152 [M + H] ^< +>.

Reference Example A33
The corresponding starting material compound is treated in the same manner as in Reference Example A23 (1) to (3), and then the resulting product is treated in the same manner as in Reference Example A23 (5) to give 3-carboxy-6- (2-chlorophenyl). ) -7- (4-Dimethylaminophenyl) pyrazolo [1,5-a] pyrimidine (230 mg, 86% yield) is obtained as a solid.
MS (APCI) m / z; 393/395 [M + H] ^< +>.

Reference example B1
(1) Under a nitrogen atmosphere, 6.77 g of sodium hydride (60%) was added to 75 mL of dimethylformamide, and then cooled (internal temperature of about 10 ° C.), a solution of 9.57 g of ethyl cyanoacetate in 15 mL of dimethylformamide Add dropwise over 15 minutes. After stirring the mixture at room temperature for 10 minutes, under cooling (internal temperature of 10 ° C. or less), a solution of 5.09 mL of carbon disulfide in 12 mL of dimethylformamide is added dropwise over 20 minutes. The mixture is stirred at room temperature overnight, and then a solution of benzylformamide in 20.1 mL of dimethylformamide in 23 mL is added dropwise under cooling (internal temperature of 25 ° C. or lower). The mixture is stirred at 70 ° C. for 7 hours and then at room temperature overnight. The reaction mixture is poured into ice water and stirred. The precipitate is collected by filtration and recrystallized from hot ethanol. The obtained crystals are washed with cold ethanol to give 2-cyano-3,3-bisbenzylthioacrylic acid ethyl ester (25.63 g, yield 82%) as a colorless solid.
MS (APCI) m / z; 370 [M + H] ^< +>.

(2) A solution of 15.0 g of the compound obtained in (1) above in 16 mL of tetrahydrofuran and 41 mL of ethanol is added with a solution of 2.04 g of hydrazine monohydrate in 18 mL of ethanol over 5 minutes and stirred overnight at room temperature. The reaction mixture is concentrated under reduced pressure, the residue is crystallized with diisopropylpropyl ether / hexane, and the crystals are washed with hexane / diisopropyl ether (4/1) to give 5-amino-3-benzylthio-4-ethoxycarbonyl- 1H-pyrazole (9.45 g, 84% yield) is obtained as a colorless solid.
MS (APCI) m / z; 278 [M + H] ^< +>.

Reference example B2
8.15 g of the compound obtained in Reference Example B1 and (2-chlorobenzyl) (4-chlorophenyl) methanone (the compound obtained in Reference Example A1 (1), 9.78 g) were treated in the same manner as in Reference Example A1 (3). 2-benzylthio-6- (2-chlorophenyl) -7- (4-chlorophenyl) -3-ethoxycarbonylpyrazolo [1,5-a] pyrimidine (8.24 g, yield 51%) Obtained as a yellow solid.
MS (APCI) m / z; 534/536 [M + H] ^< +>.

Reference example B3
To a reaction solution of the compound (100 mg) obtained in Reference Example B2, a 1.5 mL solution of methylene chloride is cooled to 0 ° C., and 0.8 mL of water and 0.05 mL of concentrated hydrochloric acid are added. To the mixture, 0.4 mL of 4% aqueous sodium hypochlorite solution (antiformin) is added and stirred for 2 hours. Extract with methylene chloride. The organic layer was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80/20 to 65/35) to give 6- (2-chlorophenyl) -7- (4-Chlorophenyl) -2-chlorosulfonyl-3-ethoxycarbonylpyrazolo [1,5-a] pyrimidine (78 mg, 82% yield) is obtained as a colorless solid.
MS (APCI) m / z; 510/512 [M + H] ^< +>.

Reference example B4
The compound (546 mg) obtained in Reference Example B3 was treated in the same manner as in Example B2 (1) to give 3-carboxy-6- (2-chlorophenyl) -7- (4-chlorophenyl) -2- (N, N-dimethylsulfamoyl) pyrazolo [1,5-a] pyrimidine (558 mg) is obtained as a crude product.

Reference example B5
The compound (240 mg) obtained in Reference Example B4 is treated in the same manner as in Example B2 (1) to give 3-carboxy-6- (2-chlorophenyl) -7- (4-chlorophenyl) -2-sulfamoyl. Pyrazolo [1,5-a] pyrimidine (239 mg) is obtained as a crude product.

Reference Example B6
An ethanol solution of 40 g of 2-cyano-3,3-bismethylthioacrylic acid ethyl ester, 12.6 g of hydrazine hydrochloride and 22.6 g of sodium acetate is stirred at 90 ° C. for 2 hours. The reaction mixture is cooled to room temperature, concentrated under reduced pressure, and water and ethyl acetate are added to the residue. The organic layer is separated, dried over magnesium sulfate, filtered, and the filtrate is concentrated under reduced pressure. Ethyl acetate and hexane were added to the residue, and the precipitated solid was collected by filtration and dried to give 5-amino-4-ethoxycarbonyl-3-methylthio-1H-pyrazole (17.4 g, yield 47%) as a colorless solid. Get as.

Reference Example B7
(1) 6.8 g of 5-amino-4-ethoxycarbonyl-3-methylthio-1H-pyrazole (compound obtained in Reference Example B6), 1- (4-chlorophenyl) -2- (2-chlorophenyl) -3- A solution of 10.9 g of (dimethylamino) -2-propen-1-one and 578 mg of piperidine in 13 mL of acetic acid is stirred at 80 ° C. overnight. After cooling the reaction solution to room temperature, water and ethyl acetate are added. The organic layer is washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 85/15 to 70/30) to give 6- (2-chlorophenyl) -7- ( 4-Chlorophenyl) -3-ethoxycarbonyl-2-methylthiopyrazolo [1,5-a] pyrimidine (5.88 g, 38% yield) is obtained as a pale yellow solid.

(2) 3-carboxy-6- (2-chlorophenyl) -7- (4-chlorophenyl) -2 by treating the compound (600 mg) obtained in (1) above in the same manner as in Reference Example A1 (4). -Methylthiopyrazolo [1,5-a] pyrimidine (502 mg) is obtained as a pale yellow powder.
MS (APCI) m / z; 430/432 [M + H] ^< +>.

(3) 260 mg of cyclopentylamine, 620 mg of water-soluble carbodiimide hydrochloride and 540 mg of 1-hydroxybenzotriazole are added to a solution of 1.0 g of the compound obtained in (2) above in 20 mL of chloroform and stirred overnight at room temperature. An aqueous sodium hydrogen carbonate solution and chloroform are added to the reaction solution and stirred, and then the organic layer is concentrated under reduced pressure. The obtained crude product is purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 82/18 to 67/33) to give 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- (N-cyclopentylcarbamoyl) -2-methylthiopyrazolo [1,5-a] pyrimidine (940 mg, 81% yield) is obtained as a pale yellow solid.
MS (APCI) m / z; 497/499 [M + H] ^< +>.

(4) To a solution of 940 mg of the compound obtained in (3) above in 40 mL of methylene chloride is added 1.09 g of 3-chloroperbenzoic acid under ice cooling, and the mixture is stirred at room temperature for 3 hours. To the reaction solution is added an aqueous sodium thiosulfate solution, and the mixture is stirred and extracted with chloroform. The organic layer is concentrated under reduced pressure, and the resulting crude product is purified by silica gel column chromatography (Chromatorex NH silica gel, solvent; hexane / ethyl acetate = 50 / 50-0 / 100) to give 6- (2-chlorophenyl). -7- (4-Chlorophenyl) -3- (N-cyclopentylcarbamoyl) -2-methylsulfonylpyrazolo [1,5-a] pyrimidine (1.0 g, 100% yield) is obtained as a colorless solid.
MS (APCI) m / z; 529/531 [M + H] ^< +>.

(5) 1.11 g of sodium azide is added to a 20 mL solution of 1.5 g of the compound obtained in (4) above in dimethylformamide, and the mixture is stirred at 110 ° C. overnight. The reaction mixture is cooled to room temperature, saturated brine is added, and the mixture is stirred and extracted with ethyl acetate. The organic layer is washed with water and concentrated under reduced pressure, and the resulting crude product is purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80/20 to 30:70) to give 2-azido-6- (2 1.15 g of -chlorophenyl) -7- (4-chlorophenyl) -3- (N-cyclopentylcarbamoyl) pyrazolo [1,5-a] pyrimidine are obtained as a yellow solid. To a solution of 870 mg of the compound in 16 mL of tetrahydrofuran is added 869 mg of triphenylphosphine, and the mixture is stirred at 40 ° C. for 1 hour. The reaction solution is cooled to room temperature and concentrated under reduced pressure, and the resulting crude product is purified by silica gel column chromatography (solvent; chloroform / methanol = 100/0 to 97/3) to give 6- (2-chlorophenyl)- 7- (4-Chlorophenyl) -3- (N-cyclopentylcarbamoyl) -2-triphenylphosphoranylideneaminopyrazolo [1,5-a] pyrimidine (942 mg, 58% yield) is obtained as a yellow solid.
MS (APCI) m / z; 726/728 [M + H] ^< +>.

(6) 7 mL of acetic acid is added to a solution of 1.1 g of the compound obtained in (5) above in 2.8 mL of tetrahydrofuran / 4.2 mL of water, and the mixture is stirred at 100 ° C. for 1 hour in a microwave reactor. The reaction mixture is cooled to room temperature, 2N aqueous sodium hydroxide solution is added, and the mixture is extracted with chloroform. The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The resulting crude product is purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80 / 20-60: 40) to give 2-amino-6- (2-chlorophenyl) -7- (4-chlorophenyl). ) -3- (N-cyclopentylcarbamoyl) pyrazolo [1,5-a] pyrimidine (529 mg, 75% yield) is obtained as a yellow solid.
MS (APCI) m / z; 466/468 [M + H] ^< +>.

Reference Example B8
(1) The corresponding starting material compound is treated in the same manner as in Reference Example B2, and then the reaction product is treated in the same manner as in Reference Example B3 to give 6- (2-chlorophenyl) -2-chlorosulfonyl-3-ethoxycarbonyl. -7- (4-Trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine is obtained as a colorless powder.
MS (APCI) m / z; 544/546 [M + H] ^< +>.

(2) The compound (2.2 g) obtained in (1) above is treated in the same manner as in Example B4, and then the reaction product is treated in the same manner as in Example B2 (1) to give 3-carboxy- 6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine (0.45 g) is obtained as a pale yellow powder.
MS (APCI) m / z; 497/499 [M + H] ^< +>.

Reference Example B9
(1) The corresponding starting material compound is treated in the same manner as in Example B2 (1) to give 6- (2-bromophenyl) -3-carboxy-7- (4-chlorophenyl) -2-sulfamoylpyrazolo [ 1,5-a] pyrimidine (897 mg) is obtained as a pale yellow powder.
MS (APCI) m / z; 507/509 [M + H] ^< +>.

(2) The compound (150 mg) obtained in (1) above and cyclopentylamine (33 mg) are treated in the same manner as in Example A1 to give 6- (2-bromophenyl) -7- (4-chlorophenyl) -3. -(N-cyclopentylcarbamoyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine (170 mg, 100% yield) is obtained as a pale yellow powder.
MS (APCI) m / z; 574/576 [M + H] ^< +>.

(3) To a solution of the compound (166 mg) obtained in (2) above in 2 mL of dimethylformamide is added 37 mg of zinc cyanide and 33 mg of tetrakis (triphenylphosphine) palladium (0), and the mixture is stirred at 110 ° C. overnight under a nitrogen atmosphere. After cooling the reaction solution to room temperature, water and ethyl acetate are added and stirred. The organic layer was separated and concentrated under reduced pressure, and the resulting crude product was subjected to silica gel column chromatography (solvent; hexane / ethyl acetate = 60 / 40-50 / 50) to give 7- (4-chlorophenyl) -6. -(2-Cyanophenyl) -3- (N-cyclopentylcarbamoyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine (24 mg, 16% yield) is obtained as a pale yellow powder.
MS (APCI) m / z; 521/523 [M + H] ^< +>.

Reference Example B10
(1) To a solution of 5 g of 1-aminocyclohexanecarboxylic acid in dioxane (70 mL), an aqueous sodium hydroxide solution (4.19 g of sodium hydroxide / 70 mL of water) is added, and 16.7 g of di-tert-butyl dicarbonate is added thereto. The mixture is stirred overnight at room temperature. Concentrate the reaction and add water and ethyl acetate to the residue. The pH is made slightly acidic with 2N hydrochloric acid, and the mixture is extracted with ethyl acetate. The combined organic layers are washed with water and saturated brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting solid was washed with diethyl ether and dried under reduced pressure to give 1- (tert-butoxycarbonylamino) cyclohexanecarboxylic acid (5.8 g, yield 69%) as a colorless solid. obtain.
MS (APCI) m / z; 244 [M + H] ^< +>.

(2) The compound obtained in the above (1) and ammonium chloride (6.4 g) were treated in the same manner as in Example A1 to give 1- (tert-butoxycarbonylamino) cyclohexane-1-carboxamide (5. 4 g, 92% yield) is obtained as a colorless solid.
MS (APCI) m / z; 243 [M + H] ^< +>.

(3) A 4N hydrochloric acid / dioxane solution (22.1 mL) is added to a dioxane (80 mL) solution of the compound obtained in the above (2), and the mixture is stirred at room temperature overnight. Diethyl ether is added to the reaction mixture and stirred, and then the precipitated solid is collected by filtration to give 1-aminocyclohexane-1-carboxamide (3.35 g, yield 85%) as a colorless powder.
MS (APCI) m / z; 143 [M + H] ^< +>.

Reference example B11
(1) By treating the compound (8 g) obtained in Reference Example A3 (2) in the same manner as in Reference Example B10 (1), 4- (tert-butoxycarbonylamino) -tetrahydrothiopyran-4-carboxylic acid ( 10.8 g, 69% yield) is obtained as a pale yellow solid.
MS (APCI) m / z; 262 [M + H] ^< +>.

(2) The compound obtained in the above (1) and ammonium chloride (11.1 g) were treated in the same manner as in Example A1 to give 4- (tert-butoxycarbonylamino) -tetrahydrothiopyran-4-carboxamide (3 .3 g, 30% yield) is obtained as a colorless solid.
MS (APCI) m / z; 261 [M + H] ^< +>.

(3) To a solution of 3.3 g of the compound obtained in (2) above in 100 mL of methylene chloride, 8.7 g of metachloroperbenzoic acid is added little by little, and the mixture is stirred at room temperature for 3 hours. The reaction solution is extracted with chloroform, and the organic layer is washed with a saturated aqueous solution of sodium bicarbonate. The aqueous layer is extracted with ethyl acetate, and the combined organic layer is dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; chloroform / methanol = 98/2 to 90:10) to give 4- (tert-butoxycarbonylamino) -1, 1-Dioxotetrahydrothiopyran-4-carboxamide (3.3 g, 90% yield) is obtained as a colorless powder.
MS (APCI) m / z; 293 [M + H] ^< +>.

(4) By treating 3.3 g of the compound obtained in (3) in the same manner as in Reference Example B10 (3), 4-amino-1,1-dioxotetrahydrothiopyran-4-carboxamide (2.0 g 77%) as a colorless powder.
MS (APCI) m / z; 193 [M + H] ^< +>.

Reference example B12
(1) A mixture of 4.95 g of (R) -methioninol, 8.3 mL of benzonitrile and 250 mg of zinc bromide is stirred at 120 ° C. for 90 hours under a nitrogen atmosphere. The reaction solution is cooled to room temperature and then filtered. The filtrate is washed with water and brine, dried over magnesium sulfate and filtered again. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 5 / 1-3 / 1) to give (R) -4- (2-methylthioethyl). ) -2-Phenyl-4,5-dihydrooxazole (3.94 g, 48.6% yield) is obtained as a colorless oil.
MS (APCI) m / z; 222 [M + H] ^< +>.

(2) Add 7.7 mL of concentrated hydrochloric acid to a solution of 3.94 g of the compound obtained in (1) above in 65 mL of acetic acid, and heat to reflux overnight. The reaction mixture is cooled to room temperature and concentrated under reduced pressure. Add 50 mL of aqueous sodium hydroxide and 100 mL of chloroform to the residue and stir. Magnesium sulfate and silica gel are added to the organic layer, and the mixture is stirred and then filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was washed with isopropyl ether and dried to give (R) -N- (tetrahydrothien-3-yl) benzamide (2.80 g, yield 76%) colorless. Obtain as a solid.
MS (APCI) m / z; 208 [M + H] ^< +>.

(3) 10 g of 3-chloroperbenzoic acid (75%) is gradually added to 70 mL of methylene chloride containing 3.59 g of the compound obtained in the above (2) under ice cooling, and the mixture is stirred at room temperature overnight. Water (35 mL), sodium sulfite (3.5 g) and saturated aqueous sodium hydrogen carbonate solution (100 mL) are added to the reaction mixture, and the mixture is stirred for 30 minutes and extracted with chloroform. The extract is washed with an aqueous sodium hydrogen carbonate solution, and the organic layer is dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting solid was washed with ethyl acetate to give (R) -N- (1,1-dioxotetrahydrothien-3-yl) benzamide (3.5 g, yield 85%). Obtained as a colorless solid.
MS (APCI) m / z; 240 [M + H] ^< +>.

(4) To a solution of 3.51 g of the compound obtained in (3) above in 13 mL of ethanol is added 52 mL of 6N aqueous hydrochloric acid, and the mixture is heated to reflux for 1 day. The reaction mixture is cooled to room temperature, and the aqueous layer is washed with ethyl acetate and concentrated under reduced pressure. The precipitated solid was washed with ethanol / diethyl ether, collected by filtration, and further washed with diethyl ether to give (R) -N- (1,1-dioxo-tetrahydrothien-3-yl) amine hydrochloride (2. 52 g, 100% yield) is obtained as a colorless solid.
MS (APCI) m / z; 136 [M + H] ^< +>.

Reference Example B13
(S) -Methioninol (4.83 g) was treated in the same manner as in Reference Example B12 to give (S) -N- (1,1-dioxo-tetrahydrothien-3-yl) amine hydrochloride (3.86 g). Is obtained as a colorless solid.
MS (APCI) m / z; 136 [M + H] ^< +>.

Reference Example B14
To a methanol solution of 2 g of 4-amino-4-carboxytetrahydropyran hydrochloride is added dropwise 33 mL of a 2M trimethylsilyldiazomethane diethyl ether solution under ice cooling, and the mixture is stirred at room temperature for 4 days. The reaction solution is concentrated under reduced pressure, and the resulting crude product is dissolved in hexane-diethyl ether (1 mL / 1 mL). 4N hydrochloric acid is added to the solution, and the precipitated solid is collected by filtration to give 4-amino-4-methoxycarbonyltetrahydropyran (2.13 g, yield 99%) as white crystals.
MS (ESI) m / z; 160 [M + H] ^< +>.

Reference example B15
(1) A 3M methylmagnesium bromide-diethyl ether solution is added dropwise to a solution of 25.0 g of tetrahydrothiopyran-4-one in 500 mL of diethyl ether under an argon atmosphere at 0 ° C. and stirred at the same temperature for 30 minutes. To the reaction solution is added 200 mL of saturated aqueous ammonium chloride solution, and the mixture is extracted three times with ethyl acetate. The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 9/1 to 6/1) to give 4-methyl-tetrahydrothiopyran-4-ol (14.7 g, yield). 52%) is obtained as a solid.

(2) To a solution of 13.7 g of the compound obtained in (1) above in 100 mL of toluene, 14.3 g of trimethylsilyl azide and 17.6 g of boron trifluoride diethyl ether complex are added and stirred overnight at room temperature. The reaction mixture is poured into water, and the organic layer is separated and washed successively with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine. The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 10/1) to give 4-azido-4-methyl-tetrahydrothiopyran (6.84 g, yield 42%). Obtained as an oil.
MS (APCI) m / z; 130 [M + H-N 2] +.

(3) To a solution of 370 mg of the compound obtained in (2) above in 12 mL of diethyl ether, 446 mg of lithium aluminum hydride is added at 0 ° C., and the mixture is stirred at room temperature. To the reaction solution, 442 μL of water, 442 μL of 15% aqueous sodium hydroxide solution and 884 μL of water are added and stirred, and then the insoluble material is removed by filtration through Celite. The filtrate is concentrated under reduced pressure to give 1-methyl-tetrahydrothienylamine (221 mg, yield 72%) as an oil.
MS (APCI) m / z; 132 [M + H] ^< +>.

Reference Example B16
(1) 9.46 g of sodium sulfide is added to a 200 mL solution of 1,3-dibromo-2,2-dimethoxypropane in 26.45 g of dimethyl sulfoxide, and the mixture is stirred at an external temperature of 110 ° C. to 140 ° C. for 30 minutes. The reaction mixture is diluted with diethyl ether under ice-cooling, saturated aqueous sodium hydrogen carbonate solution and water are added, and the mixture is extracted twice with diethyl ether. The organic layer is washed with saturated brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / diethyl ether = 100/0 to 15/1) to give 3,3-dimethoxythiacyclobutane (10.55 g). Yield 78%) as a pale yellow liquid.
MS (APCI) m / z; 103 [M + H-MeOH] ^<+> .

  (2) 3.5 g of ion exchange resin (Amberlyt 15E) is added to a solution of 9.0 g of the compound obtained in (1) above in 70 mL of acetone, and the mixture is stirred at room temperature for 21 hours. The reaction mixture is filtered through celite, and the residue is washed with acetone. Combine the filtrate and washings and concentrate under reduced pressure. The precipitate is collected and washed with cold hexane to give 3-oxothiacyclobutane (1.58 g, yield 27%) as colorless crystals.

(3) To a 10 mL aqueous solution of 0.80 g of potassium cyanide and 0.62 g of ammonium chloride, add 3.59 g of ammonium carbonate and a solution of 1.0 g of the compound obtained in (2) above in 10 mL of methanol and stir at 60 ° C. overnight. To the reaction solution is added 5 mL of 1N aqueous sodium hydroxide solution and 50 mL of water, and the mixture is extracted with ethyl acetate. The organic layer is washed successively with water and saturated brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was washed with diisopropyl ether to give 2-thia-5,7-diaza-spiro [3,4] octane-6,8-dione (0.79 g, 44% yield) is obtained as a powder.
MS (ESI) m / z; 157 [M-H] -.

(4) 10 mL of 1N aqueous sodium hydroxide solution of 0.75 g of the compound obtained in (3) above is heated to reflux for 15 hours. The reaction mixture is ice-cooled, 3 mL of concentrated hydrochloric acid is added, and the mixture is concentrated under reduced pressure to give 3-aminothietane-3-carboxylic acid (1.54 g) as a solid.
MS (APCI) m / z; 134 [M + H] ^< +>.

(5) Add 0.50 mL of thionyl chloride to a suspension of 1.54 g of the compound obtained in (4) above in 20 mL of methanol under ice cooling, and heat to reflux for 5 hours. The reaction mixture is neutralized with ice water and sodium hydrogen carbonate, and extracted with chloroform. The organic layer is dried over sodium sulfate and filtered, and the filtrate is concentrated under reduced pressure. To the resulting residue was added 4N hydrochloric acid-ethyl acetate (2 mL), and the precipitated solid was collected by filtration and washed successively with diisopropyl ether and ethyl acetate to give 3-aminothietane-3-carboxylic acid methyl ester (0.53 g, yield). 61%) is obtained as a powder.
MS (APCI) m / z; 148 [M + H] ^< +>.

Reference Example B17
(1) 6- (2-Chlorophenyl) -3-ethoxycarbonyl-7- (4-trifluoromethylphenyl) -2-methylpyrazolo [1,5-a] pyrimidine (corresponding ethyl ester of the compound obtained in Reference Example A12) ) 6.23 g of N-bromosuccinimide and 96 mg of 2,2′-azobisisobutyronitrile are added to a solution of 5.35 g of carbon tetrachloride in 73 mL, and the mixture is stirred at an external temperature of 85 ° C. for 18 hours. The reaction mixture is cooled to room temperature, filtered through celite, and the filtrate is concentrated under reduced pressure. The resulting crude product is purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80/20 to 65/35) to give 2-bromomethyl-6- (2-chlorophenyl) -3-ethoxycarbonyl-7. -(4-Trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine (4.72 g, 75% yield) is obtained as a pale yellow solid.
MS (APCI) m / z; 538/540 [M + H] ^< +>.

(2) To a solution of 4.72 g of the compound obtained in (1) above in 50 mL of dimethylformamide is added 2.58 g of potassium acetate, and the mixture is stirred at 60 ° C. for 1 hour. The reaction mixture is cooled to room temperature, diluted with ethyl acetate, and water is added to separate the organic layer. The organic layer is washed successively with water and saturated brine, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 80 / 20-60 / 40) to give 2-acetoxymethyl-6- (2-chlorophenyl). ) -3-Ethoxycarbonyl-7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine (1.86 g, 41% yield) is obtained as a colorless powder.
MS (APCI) m / z; 518/520 [M + H] ^< +>.

(3) To a solution of 1.86 g of the compound obtained in (2) above in 30 mL of ethanol-30 mL of tetrahydrofuran, 2.5 mL of 21% sodium ethoxide-ethanol solution is added and stirred at 60 ° C. for 30 minutes. The reaction solution is cooled to room temperature, diluted with ethyl acetate, diluted aqueous hydrochloric acid is added, and the organic layer is separated. The organic layer is washed with saturated brine, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 85/15 to 55/45) to give 6- (2-chlorophenyl) -3-ethoxy. Carbonyl-7- (4-trifluoromethylphenyl) -2-hydroxymethylpyrazolo [1,5-a] pyrimidine (1.05 g, 62% yield) is obtained as a colorless solid.
MS (APCI) m / z; 476/478 [M + H] ^< +>.

(4) By treating 1.03 g of the compound obtained in the above (3) in the same manner as in Reference Example A1 (4), 3-carboxy-6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) 2-Hydroxymethylpyrazolo [1,5-a] pyrimidine (894 mg, 92% yield) is obtained as a pale yellow solid.
MS (APCI) m / z; 448/450 [M + H] ^< +>.

Reference examples B18 to B20
The compound obtained in Reference Example B17 (3) is treated in the same manner as in Example B33, then the reaction product and the corresponding amine compound are treated in the same manner as in Example A5, and the reaction product is further treated as in Reference Example A1 (4 ) To give the compounds shown in Table 35 below.

Reference example B21
To a solution of 1.00 g of the compound obtained in Reference Example A30 and 1.33 mL of triethylamine in 20 mL of methylene chloride is added 350 mg of triphosgene under ice-cooling, and the mixture is stirred at room temperature for 1.5 hours. Add 20 mL of 0.5 M ammonia-dioxane solution to the reaction mixture and stir at room temperature for 30 minutes. Add water to the reaction mixture and extract with chloroform. The organic layer is dried over magnesium sulfate and filtered, and the filtrate is concentrated under reduced pressure. The obtained crude product is purified by silica gel column chromatography (solvent: hexane / ethyl acetate = 65 / 35-20 / 80) to give 6- (2-chlorophenyl) -3-ethoxycarbonyl-7- (4- Trifluoromethylphenyl) -2-ureidopyrazolo [1,5-a] pyrimidine (0.70 g, 64% yield) is obtained as a colorless powder.
MS (APCI) m / z; 504/506 [M + H] ^< +>.

Reference Example B22
(1) To a solution of 100 mg of the compound obtained in Reference Example B16 (2) in 3 mL of ethanol, 236 mg of hydroxylamine hydrochloride and 360 mg of sodium carbonate are added, and the mixture is heated to reflux for 17 hours. The reaction mixture is cooled to room temperature, saturated aqueous sodium hydrogen carbonate solution and water are added, and the mixture is extracted with chloroform. The organic layer was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 90 / 10-50 / 50) to give 3-hydroxyiminothiacyclobutane (93 mg, yield). 80%) is obtained as a colorless solid.

(2) Under a nitrogen atmosphere, to a solution of 58 mg of lithium aluminum hydride in tetrahydrofuran (2 mL) is added dropwise a solution of 93 mg of the compound obtained in (1) above in 1.5 mL of tetrahydrofuran under ice cooling, and the mixture is stirred at room temperature for 1 hour. . Under ice cooling, 60 μL of water, 60 μL of 15% aqueous sodium hydroxide and 120 μL of water are sequentially added to the reaction mixture, and the mixture is stirred at room temperature. The reaction solution is filtered through Celite, and the filtrate is concentrated under reduced pressure to give 3-aminothiacyclobutane as a crude product.
Reference Example B23
(1) The compound obtained in Reference Example B1 is treated in the same manner as Reference Example A14B and then Reference Example A14 (3) to give 2-benzylthio-7-chloro-6- (2-chlorophenyl) -3-ethoxycarbonylpyrazolo. [1,5-a] pyrimidine is obtained as a powder.
MS (APCI) m / z; 458/460 [M + H] ^< +>.

(2) 1.0 g of the compound obtained in the above (1), 63 mg of [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride-methylene chloride complex, 1.4 g of potassium phosphate and 4-fluoro A solution of 339 mg of phenylboronic acid in 25 mL of 1,4-dioxane is stirred at 80 ° C. for 16 hours under a nitrogen atmosphere. The reaction mixture is cooled to room temperature, water is added, and the mixture is extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (solvent; hexane / ethyl acetate = 2/1 to 1/1) to give 2-benzylthio-6- (2-chlorophenyl). -3-Ethoxycarbonyl-7- (4-fluorophenyl) pyrazolo [1,5-a] pyrimidine (865 mg, 76% yield) is obtained as a powder.
MS (APCI) m / z; 518/520 [M + H] ^< +>.

(3) By treating 854 mg of the compound obtained in the above (2) in the same manner as in Reference Example B3 and then treating the product in the same manner as in Example B4, 6- (2-chlorophenyl) -3-ethoxycarbonyl- 7- (4-Fluorophenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine (670 mg, 78% yield) is obtained as a powder.
MS (APCI) m / z; 475/477 [M + H] ^< +>.

(4) By treating 660 mg of the compound obtained in (3) above in the same manner as in Example B2 (1), 3-carboxy-6- (2-chlorophenyl) -7- (4-fluorophenyl) -2- Sulfamoylpyrazolo [1,5-a] pyrimidine (318 mg, 56% yield) is obtained as a powder.
MS (APCI) m / z; 447/449 [M + H] ^< +>.

Reference examples B24 to B28
1) Reference examples B24 to B25
The corresponding starting material compounds are treated in the same manner as in Reference Examples B1 to B3, Example B4, and Example B2 (1) to obtain the compounds described in Table 36 below.

2) Reference examples B26 to B27
The corresponding starting material compounds are treated in the same manner as in Reference Example B23 to give the compounds described in Table 36 below.

3) Reference example B28
The corresponding starting material compound is treated in the same manner as in Reference Example B23 (1), and then the resulting product is treated in the same manner as in Reference Example A14 (4) to (5) to obtain the compounds described in Table 36 below.

Experimental example 1
[Human CB1 receptor binding test]
(1) Preparation of CB1 receptor cell membrane fraction (Material)
Human CB1 receptor-expressing cell line: hCB1 / CHO (# ES-110-C, manufactured by Euroscreen)
Medium: F-12 (GIBCO # 11765-062), [containing 10% fetal bovine serum, geneticin (400 μg / mL), penicillin (100 units / mL), streptomycin (100 μg / mL)]
Buffer A: 50 mM Tris-HCl (pH 7.5) [containing ethylenediaminetetraacetic acid (EDTA, 2.5 mM) and MgCl ₂ (5 mM) sucrose (200 mM)]
(Method)
The receptor-expressing cells cultured in the above medium are washed twice with a phosphate buffer (9.57 mM, pH 7.5), and then cooled on ice or at 4 ° C. (the following operations are also performed at the same temperature). 2 mL) was added, and the cells were recovered with a cell scraper. The cells were treated with a microchip ultrasonic device for 20 seconds (pulse on: 2 seconds, pulse off: 1 second), and then centrifuged at 500 × g for 15 minutes. The supernatant was collected and further centrifuged at 43000 × g for 60 minutes. Buffer A was added to the precipitate, homogenized with a potter homogenizer, an equal amount of 80% glycerol solution was added, and the mixture was stored at -80 ° C.

(2) Measurement of human CB1 receptor binding activity (Material)
Buffer B: 50 mM Tris-HCl (pH 7.5) [containing MgCl ₂ (5 mM), EDTA (2.5 mM) and bovine serum albumin (2 mg / mL, fatty acid free)]
Buffer C: 50 mM Tris-HCl (pH 7.5) [containing MgCl ₂ (5 mM), EDTA (2.5 mM) and bovine serum albumin (2 mg / mL)]
Coating solution: 0.3% ethyleneimine polymer Labeled ligand: [ ³ H] -CP55940 [30 nM (7992 dpm / μL); prepared by diluting an 8.3 μM solution with buffer B. ]
(Method)
In a 96-well plate (Costar Code # 3371), 140 μL of the above reaction buffer, sample (20 μL, dimethyl sulfoxide solution, final concentration 0.1%), labeled ligand (20 μL) and cell membrane fraction prepared in (1) above ( 20 μL, 0.5-8.0 μg / 20 μL) and incubated at room temperature for 90 minutes, and then the reaction mixture was filtered through a filter (Unifilter GF / B, # 6005177, Packard) treated with the above coating solution. The membrane fraction was collected. The filter was washed with buffer C (200 μL × 10 times), dried at 50 ° C. for 1 hour, then added with Microscinti 40 (40 μL) to each well, and then used with a scintillation counter (Top Count NXT; manufactured by Packard). Radioactivity was measured. The IC ₅₀ value of each specimen for the binding of the labeled ligand to the human CB1 receptor was calculated using Microsoft Excel 2000 (manufactured by Microsoft) based on the radioactivity measurement results.

(3) Results The IC ₅₀ values of each specimen are shown in Table 37 below. In addition, the symbol (++ and +++) in a table | surface represents the following meaning.

++: 10 nM <IC ₅₀ <100 nM
+++: 10 nM> IC ₅₀

Experimental example 2
[Selectivity of analyte compound for human CB1 receptor]
(1) Method a) Human CB1 receptor binding activity:
The title binding activity was measured in the same manner as in Experimental Example 1.

b) Human CB2 receptor binding activity:
Using human CB2 receptor-expressing CHO cells (hCB2 / CHO) instead of human CB1 receptor-expressing cells, the binding activity (IC ₅₀ value) of each sample compound to the human CB2 receptor was determined in the same manner as in Experimental Example 1. The selectivity for human CB1 receptor was evaluated by human CB2 receptor binding activity (IC ₅₀ value) / human CB1 receptor binding activity (IC ₅₀ value). The IC ₅₀ value and selectivity for the human CB1 receptor of each specimen are shown in Table 38 below. The symbols (++ and +++) in the table have the same meaning as in Experimental Example 1.

  Compound [I] of the present invention is useful for the prevention and treatment of various diseases involving CB1 receptor (for example, psychosis including schizophrenia). Also, the compound [I] of the present invention is useful for chronic treatment and withdrawal from alcohol or drug abuse. Furthermore, the compound [I] of the present invention is useful as an analgesic activity enhancer or a smoking cessation aid.

Claims (37)

Formula [I]:

[Where,
R ¹ and R ² are the same or different and may have a substituted aryl group or a saturated or unsaturated heterocyclic group which may have a substituent,
R ⁰ is (a) a hydrogen atom; (b) an alkyl group optionally substituted with 1 to 3 halogen atoms; (c) an alkyloxyalkyl group; (d) Formula: —CON (R ^e ) (R ^f ) a group represented by: (e) an aminoalkyl group (the amino group portion of the group may be substituted with 1 to 2 alkyl groups); (f) an alkyl group, an alkylcarbonyl group, and an alkylsulfonyl group An amino group which may be substituted with a group selected from: (g) a 4- to 6-membered nitrogen-containing aliphatic heterocyclic group; (h) a formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ) A group; (i) a group represented by the formula: -NHCONHR ⁰³ ; (j) an alkyloxy group optionally substituted with a hydroxyl group; (k) a hydroxyalkyl group; or (l) a carboxyl group, R ^e and R ^f are , Same or different, hydrogen atom, alkyl group Dialkylamino group, R ⁰¹ and R ⁰² are the same or different and represent a hydrogen atom, an alkyl group or carbamoyl group, R ⁰³ is a hydrogen atom or an alkyl group,
E is a group represented by the formula: —C (═O) — or —SO ₂ —;
R represents (A) R ⁰ is (a) a hydrogen atom; (b) an alkyl group optionally substituted with 1 to 3 halogen atoms; (c) an alkyloxyalkyl group; (e) an aminoalkyl group ( The amino group portion of the group may be substituted with 1 to 2 alkyl groups); (f) an amino group optionally substituted with a group selected from an alkyl group, an alkylcarbonyl group and an alkylsulfonyl group; (G) a 4- to 6-membered nitrogen-containing aliphatic heterocyclic group; or (j) an alkyloxy group that may be substituted with a hydroxyl group, the following formula [i], [ii], or [iii]:

And (B) R ⁰ is a group represented by the formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ), a formula: —NHCONHR ⁰³ , a formula: —CON (R ^e ) (R ^f ), A carboxyl group or a hydroxyalkyl group, it represents (a) an alkyloxy group or (b) a group represented by the formula: —N (R ⁵ ) (R ⁶ ),
Ring A is a C _3-8 cycloalkyl group (which may be condensed with a benzene ring) or a benzene ring, Q is a single bond or a methylene group,
Ring B is a 4- to 7-membered aliphatic heterocyclic group bonded to the adjacent nitrogen atom via the ring-constituting carbon atom, X is a sulfur atom, —SO—, —SO ₂ —, an oxygen atom or —NR ^k —. The group shown, R ^k is an alkyl group, an alkylcarbonyl group, an alkyloxycarbonyl group, an alkylsulfonyl group, an aminosulfonyl group optionally substituted with 1 to 2 alkyl groups, or 1 to 2 alkyl groups. An optionally substituted carbamoyl group,
R ³ is (a) an alkyl group optionally substituted with a group selected from a hydroxyl group, an amino group, an acylamino group, a dialkylcarbamoylamino group, an alkylsulfonylamino group, and a dialkylsulfamoylamino; (b) a cyano group; c) carboxyl group; (d) alkyloxycarbonyl group; (e) formula: —N (R ^a ) (R ^b ) group; (f) formula: —CON (R ^a ) (R ^b ) (G) the following formula:

A group represented by: or (h) a hydroxyl group,
R ^a and R ^b are the same or different and are a hydrogen atom, hydroxyl group, cyano group, alkyl group, cyanoalkyl group, trihalogenoalkyl group, hydroxyalkyl group, alkyloxyalkyl group, cycloalkyl group, acyl group, alkylsulfonyl group or Represents an aminoalkyl group (the amino group portion of the group may be substituted with 1 to 2 alkyl groups) or both R ^a and R ^b are bonded together at the ends and saturated with the adjacent nitrogen atom Or an unsaturated nitrogen-containing heterocyclic group (the heterocyclic group may contain a hetero atom selected from a sulfur atom and an oxygen atom in addition to a nitrogen atom);
R ⁴ represents (a) a hydrogen atom; (b) an alkyl group; (c) a cyano group; (d) a carboxyl group; (e) an alkylcarbonyl group; (f) an alkyloxycarbonyl group; (g) a formula: —CON ( R ^c ) a group represented by (R ^d ); (h) a phenyl group; (i) a benzyl group; or (j) an acylamino group, R ^c and R ^d are the same or different and are a hydrogen atom or an alkyl group,
One of R ^A and R ^B is (a) an alkyl group (which may be substituted with a hydroxyl group, an alkyloxy group, an amino group, an alkylamino group or a dialkylamino group); (b) a phenyl group (the phenyl group is Optionally substituted by 1 to 2 groups selected from a halogen atom, an alkyloxy group and a trihalogenoalkyl group); (c) a benzyl group; (d) a heteroaryl group; or (e) a cycloalkyl group And the other is (a) a hydrogen atom; or (b) an alkyl group (which may be substituted with a hydroxyl group, an alkyloxy group, an amino group, an alkylamino group, or a dialkylamino group),
In R ⁵ and R ⁶ , (A) one is a hydrogen atom or an alkyl group, and the other is (a) substituted with a halogen atom, a hydroxyl group, a cyano group, an alkyloxy group, a cycloalkyl group, or one or two alkyl groups. An amino group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, an acyl group, an aryl group which may have a substituent, and a saturated or unsaturated heterocyclic group which may have a substituent An alkyl group which may be substituted with 1 to 3 groups selected from the group; (b) a cycloalkyl group which may have a substituent; (c) a formula: —N (R ⁸ ) (R ⁹ (D) an aryl group optionally having substituent (s); or (e) a saturated or unsaturated heterocyclic group optionally having substituent (s), or (B) together both R ⁵ and ^{R 6} at the end Combined to form a contiguous nitrogen atom together may be substituted saturated or unsaturated nitrogen-containing heterocyclic group,
One of R ⁸ and R ⁹ is a hydrogen atom or an alkyl group, and the other is (a) an alkyl group which may be substituted with 1 to 3 groups selected from a halogen atom, a cyano group and an aryl group; ) An optionally substituted cycloalkyl group; (c) an optionally substituted aryl group; (d) an acyl group; or (e) an optionally substituted saturated or It represents an unsaturated heterocyclic group. ]
A compound represented by the formula (However, 6-phenyl-7- (4-chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyano-4-tetrahydrothiopyranyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-dimethylbenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-methylbenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine; 6- (2 -Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyanobenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine; and 6- (2-chlorophenyl) -7- (4-chlorophenyl) ) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2- (hydroxymethyl) pyrazolo [1,5-a] pyrimidine) or a pharmaceutically acceptable salt thereof salt. General formula [II]:

[Where,
R ¹ and R ² are the same or different and each may have an aryl group which may have a substituent or a saturated or unsaturated heterocyclic group which may have a substituent,
R ^0A is (a) a hydrogen atom; (b) an alkyl group optionally substituted with 1 to 3 halogen atoms; (c) an alkyloxyalkyl group; (d) an aminoalkyl group (the amino group portion of the group). May be substituted with 1 to 2 alkyl groups); (e) an amino group optionally substituted with a group selected from an alkyl group, an alkylcarbonyl group and an alkylsulfonyl group; (f) 4-6 A nitrogen-containing aliphatic heterocyclic group; or (g) an alkyloxy group optionally substituted with a hydroxyl group,
E is a group represented by the formula: —C (═O) — or —SO ₂ —;
R ′ represents the following formula [i], [ii] or [iii]:

A group represented by
Ring A is a C _3-8 cycloalkyl group (which may be condensed with a benzene ring) or a benzene ring, Q is a single bond or a methylene group,
Ring B is a 4- to 6-membered aliphatic heterocyclic group bonded to the adjacent nitrogen atom via its ring-constituting carbon atom, X is a sulfur atom, —SO—, —SO ₂ —, an oxygen atom, or —NR ^k —. The group shown, R ^k is an alkyl group, an alkylcarbonyl group, an alkyloxycarbonyl group, an alkylsulfonyl group, an aminosulfonyl group optionally substituted with 1 to 2 alkyl groups, or 1 to 2 alkyl groups. An optionally substituted carbamoyl group,
R ³ is (a) an alkyl group optionally substituted with a group selected from a hydroxyl group, an amino group, an acylamino group, a dialkylcarbamoylamino group, an alkylsulfonylamino group, and a dialkylsulfamoylamino group; (b) a cyano group; (C) carboxyl group; (d) alkyloxycarbonyl group; (e) group represented by formula: —N (R ^a ) (R ^b ); (f) formula: —CON (R ^a ) (R ^b ) The group shown; (g)

Or (h) a hydroxyl group, R ^a and R ^b are the same or different and are a hydrogen atom, a hydroxyl group, a cyano group, an alkyl group, a cyanoalkyl group, a trihalogenoalkyl group, a hydroxyalkyl group, an alkyloxyalkyl group, Represents a cycloalkyl group, an alkylsulfonyl group or an aminoalkyl group (the amino group portion of the group may be substituted with 1 to 2 alkyl groups), or R ^a and R ^b are both terminated with respect to each other; To form a saturated or unsaturated nitrogen-containing heterocyclic group (the heterocyclic group may contain a hetero atom selected from a sulfur atom and an oxygen atom in addition to a nitrogen atom),
R ⁴ represents (a) a hydrogen atom; (b) an alkyl group; (c) a cyano group; (d) a carboxyl group; (e) an alkylcarbonyl group; (f) an alkyloxycarbonyl group; (g) a formula: —CON ( R ^c ) a group represented by (R ^d ); (h) a phenyl group; (i) a benzyl group; or (j) an acylamino group, R ^c and R ^d are the same or different and are a hydrogen atom or an alkyl group,
One of R ^A and R ^B is (a) an alkyl group (which may be substituted with a hydroxyl group, an alkyloxy group, an amino group, an alkylamino group or a dialkylamino group); (b) a phenyl group (the phenyl group is Optionally substituted by 1 to 2 groups selected from a halogen atom, an alkyloxy group and a trihalogenoalkyl group); (c) a benzyl group; (d) a heteroaryl group; or (e) a cycloalkyl group And the other is (a) a hydrogen atom; or (b) an alkyl group (which may be substituted with a hydroxyl group, an alkyloxy group, an amino group, an alkylamino group or a dialkylamino group). ]
A compound represented by the formula (However, 6-phenyl-7- (4-chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyano-4-tetrahydrothiopyranyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-dimethylbenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-methylbenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine; and 6- ( 2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyanobenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine) or a pharmaceutically acceptable salt thereof. General formula [I-II]:

[Where,
R ¹ and R ² are the same or different and each may have an aryl group which may have a substituent or a saturated or unsaturated heterocyclic group which may have a substituent,
R ^0B is a group represented by the formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ), a group represented by the formula: —NHCONHR ⁰³ , a group represented by the formula: —CON (R ^e ) (R ^f ), carboxyl Group or hydroxyalkyl group, R ⁰¹ and R ⁰² are the same or different and are a hydrogen atom, alkyl group or carbamoylalkyl group, R ⁰³ is a hydrogen atom or an alkyl group, R ^e and R ^f are the same or different and are a hydrogen atom or an alkyl group Or a dialkylamino group,
E is a group represented by the formula: —C (═O) — or —SO ₂ —;
R ″ represents an alkyloxy group or a group represented by the formula: —N (R ⁵ ) (R ⁶ ),
R ⁵ and R ⁶ are (A) one is a hydrogen atom or an alkyl group, and the other is (a) substituted with a halogen atom, a hydroxyl group, a cyano group, an alkyloxy group, a cycloalkyl group, or 1 to 2 alkyl groups. An amino group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, an acyl group, an aryl group which may have a substituent, and a saturated or unsaturated heterocyclic group which may have a substituent An alkyl group which may be substituted with 1 to 3 groups selected from: (b) an optionally substituted cycloalkyl group; (c) a formula: —N (R ⁸ ) (R ⁹ ) (D) an aryl group optionally having substituent (s); or (e) a saturated or unsaturated heterocyclic group optionally having substituent (s), or (B) R ⁵ and mutually sintering both at the end of the R ⁶ To form adjacent nitrogen atom together may be substituted saturated or unsaturated nitrogen-containing heterocyclic group,
One of R ⁸ and R ⁹ is a hydrogen atom or an alkyl group, and the other is (a) an alkyl group which may be substituted with 1 to 3 groups selected from a halogen atom, a cyano group and an aryl group; b) a cycloalkyl group optionally having a substituent; (c) an aryl group optionally having a substituent; (d) an acyl group; or (e) a saturated optionally having a substituent. Or it represents that it is an unsaturated heterocyclic group. ]
Or a pharmaceutically acceptable salt thereof (provided that 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) ) Except carbamoyl] -2- (hydroxymethyl) pyrazolo [1,5-a] pyrimidine. R ¹ and R ² may be the same or different and (i) a halogen atom, a cyano group, an alkyl group which may be substituted with 1 to 3 halogen atoms, or a substituent with 1 to 3 halogen atoms A good alkyloxy group, an amino group optionally substituted with 1 to 2 alkyl groups, an alkylthio group, an alkylsulfinyl group and an alkylsulfonyl group optionally substituted with 1 to 3 groups 10-membered monocyclic or bicyclic aryl group, or (ii) halogen atom, cyano group, oxo group, alkyl group optionally substituted with 1 to 3 halogen atoms, substituted with 1 to 3 halogen atoms An alkyloxy group which may be substituted, an amino group which may be substituted with one or two alkyl groups, an alkylthio group, an alkylsulfinyl group and an alkylsulfonyl group A compound according to any one of 1-3 optionally substituted saturated or unsaturated oxygen-containing a group barrel is sulfur-containing or nitrogen-containing 5- to 7-membered heteromonocyclic group claims 1-3. A saturated or unsaturated heterocyclic group in R ⁵ , R ⁶ , R ⁸ or R ⁹ is
(A) a saturated or unsaturated 4- to 7-membered heteromonocyclic group (the heteromonocyclic group includes 1 to 4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom);
(B) the heteromonocyclic group, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered monocyclic aryl group, and a saturated or unsaturated 4- to 7-membered heteromonocyclic group (the heteromonocyclic group is 8- to 15-membered saturated or unsaturated nitrogen-containing 2-condensation product having 1 to 2 cyclic groups selected from oxygen atoms, sulfur atoms and 1 to 4 heteroatoms selected from nitrogen atoms) The compound according to claim 1 or 3, which is a cyclic or tricyclic heterocyclic group; or (c) a saturated or unsaturated 8- to 11-membered nitrogen-containing spiro heterocyclic group. A saturated or unsaturated nitrogen-containing heterocyclic group formed by combining R ⁵ and R ⁶ is
(A) a saturated or unsaturated 4- to 7-membered nitrogen-containing heteromonocyclic group (the heteromonocyclic group may contain two or more nitrogen atoms, and in addition to the nitrogen atom, an oxygen atom and a sulfur atom) And may contain 1 to 2 heteroatoms selected from:
(B) the heteromonocyclic group, a 3- to 8-membered cycloalkyl group, a 5- to 6-membered monocyclic aryl group, and a saturated or unsaturated 4- to 7-membered heteromonocyclic group (the heteromonocyclic group is 8- to 15-membered saturated or unsaturated nitrogen-containing 2-condensation product having 1 to 2 cyclic groups selected from oxygen atoms, sulfur atoms and 1 to 4 heteroatoms selected from nitrogen atoms) The compound according to claim 1 or 3, which is a cyclic or tricyclic heterocyclic group; or (c) a saturated or unsaturated 8- to 11-membered nitrogen-containing spiro heterocyclic group. An alkyl group in which a saturated or unsaturated heterocyclic group in R ⁵ , R ⁶ , R ⁸ or R ⁹ is substituted with a halogen atom, a hydroxyl group, a cyano group, an oxo group, an alkyl group, or 1 to 3 halogen atoms; Alkyloxyalkyl group, aminoalkyl group, cycloalkyl group, arylalkyl group, alkyloxy group, alkyloxy group substituted with 1 to 3 halogen atoms, acyl group, substituted with 1 to 2 alkyl groups An amino group, an acylamino group, an alkylsulfonyl group, an aminosulfonyl group which may be substituted with 1 to 2 alkyl groups, an aryl group which may be substituted with 1 to 2 halogen atoms, and saturated or 6. A saturated or unsaturated heterocyclic group substituted with 1 to 4 groups selected from unsaturated 5 to 6-membered nitrogen-containing heterocyclic groups. Compound. A saturated or unsaturated nitrogen-containing heterocyclic group formed by R ⁵ and R ⁶ is a halogen atom, a hydroxyl group, a cyano group, an oxo group, an alkyl group, an alkyl group substituted with 1 to 3 halogen atoms, Alkyloxyalkyl group, aminoalkyl group, cycloalkyl group, arylalkyl group, alkyloxy group, alkyloxy group substituted with 1 to 3 halogen atoms, acyl group, substituted with 1 to 2 alkyl groups Saturated or unsaturated substituted with 1 to 3 groups selected from amino group, acylamino group, alkylsulfonyl group, aminosulfonyl group optionally substituted with 1 to 2 alkyl groups and aryl group The compound according to claim 6, which is a nitrogen-containing heterocyclic group. The saturated or unsaturated heterocyclic group in R ⁵ , R ⁶ , R ⁸ or R ⁹ is (A) furyl group, tetrahydrofuranyl group, pyranyl group, tetrahydropyranyl group, thiacyclobutyl group, thienyl group, tetrahydrothienyl. Group, thiopyranyl group, tetrahydrothiopyranyl group, benzofuranyl group, dihydrobenzofuranyl group, isobenzofuranyl group, chromanyl group, isochromanyl group, chromenyl group, isochromenyl group, benzothienyl group and dihydrobenzothienyl group Or unsaturated oxygen-containing or sulfur-containing heterocyclic group, or (B) azetidyl group, pyrrolidinyl group, pyrrolinyl group, imidazolidinyl group, imidazolinyl group, pyrazolidinyl group, pyrazolinyl group, pyrrolyl group, 2H-pyrrolyl group, imidazolyl group, pyrazolyl Group, Jihi Lopyrazolyl, thiazolidinyl, thiazolyl, isothiazolyl, isoxazolyl, oxazolidinyl, pyridyl, dihydropyridyl, tetrahydropyridyl, piperidyl, pyrazinyl, piperazinyl, pyrimidinyl, tetrahydropyrimidinyl, pyridazinyl, morpholinyl Azosinyl group, azacycloheptyl group, indolizinyl group, benzimidazolyl group, benzotriazolyl group, indolyl group, isoindolyl group, 3H-indolyl group, indolinyl group, isoindolinyl group, 1H-indazolyl group, pyrrolopyridyl group, pyrrolopyrimidinyl group , Tetrazolyl group, purinyl group, pteridinyl group, 4H-quinolidinyl group, quinolyl group, dihydroquinolyl group, tetrahydroquinolyl group, isoquinolyl , Dihydroisoquinolyl group, tetrahydroisoquinolyl group, phthalazinyl group, dihydrophthalazinyl group, naphthyridinyl group, dihydronaphthyridinyl group, tetrahydronaphthylidinyl group, quinoxalinyl group, quinazolinyl group, dihydrobenzothiazinyl group, dihydrobenzo Oxazinyl group, cinnolinyl group, pteridinyl group, xanthenyl group, carbazolyl group, β-carbolinyl group, phenanthridinyl group, acridinyl group, 5H-dihydrodibenzazepinyl group and general formula:

[Wherein, R ^G and R ^H are the same or different and represent a hydrogen atom or an alkyl group, and q and r each represent an integer of 1 or 2. ]
The compound according to claim 7, which is a saturated or unsaturated nitrogen-containing heterocyclic group selected from spiroheterocyclic groups represented by: The saturated or unsaturated heterocyclic group in R ⁵ , R ⁶ , R ⁸ or R ⁹ is a tetrahydrofuranyl group, a pyrrolyl group, a pyrrolidinyl group, a piperidyl group, an azacycloheptyl group, a tetrahydropyranyl group, a piperazinyl group, or a morpholinyl group. The compound according to claim 7, which is a thiomorpholinyl group, a thiacyclobutyl group, a tetrahydrothienyl group, a tetrahydrothiopyranyl group, a thiazolyl group, a pyridyl group, a pyrimidinyl group, an indolinyl group, a pyrrolopyridyl group, or a tetrahydronaphthyridinyl group. A saturated or unsaturated nitrogen-containing heterocyclic group formed by bonding R ⁵ and R ⁶ to each other is an azetidyl group, pyrrolidinyl group, pyrrolinyl group, imidazolidinyl group, imidazolinyl group, pyrazolidinyl group, pyrazolinyl group, pyrrolyl group, Imidazolyl, pyrazolyl, dihydropyrazolyl, thiazolidinyl, oxazolidinyl, dihydropyridyl, tetrahydropyridyl, piperidyl, piperazinyl, tetrahydropyrimidinyl, morpholinyl, azacycloheptyl, benzimidazolyl, benzotriazolyl Group, indolyl group, isoindolyl group, indolinyl group, isoindolinyl group, 1H-indazolyl group, tetrazolyl group, purinyl group, dihydroquinolyl group, tetrahydroquinolyl group, dihydroisoquinolyl group, Trahydroisoquinolyl group, dihydrophthalazinyl group, dihydroquinazolinyl group, dihydrobenzothiazinyl group, dihydrobenzoxazinyl group, carbazolyl group, β-carbolinyl group, 5H-dihydrodibenzazepinyl group and general formula:

[Wherein, R ^G and R ^H are the same or different and represent a hydrogen atom or an alkyl group, and q and r each represent an integer of 1 or 2. ]
The compound according to claim 8, which is a saturated or unsaturated nitrogen-containing heterocyclic group selected from spiroheterocyclic groups represented by: General formula [I-I-A]:

[Wherein R ¹⁰ and R ²⁰ are the same or different and (i) a 6 to 10-membered monocyclic or bicyclic aryl group (the aryl group is substituted with a halogen atom, a cyano group, or 1 to 3 halogen atoms An alkyl group that may be substituted, an alkyloxy group that may be substituted with 1 to 3 halogen atoms, an amino group that may be substituted with 1 to 2 alkyl groups, an alkylthio group, an alkylsulfinyl group, and Optionally substituted with 1 to 3 groups selected from alkylsulfonyl groups); or (ii) saturated or unsaturated sulfur-containing, oxygen-containing or nitrogen-containing 4- to 7-membered heteromonocyclic group (the heterocyclic ring) The formula group is a halogen atom, a cyano group, an oxo group, an alkyl group which may be substituted with 1 to 3 halogen atoms, an alkyloxy group which may be substituted with 1 to 3 halogen atoms, 1 to 2 Pieces Alkyl amino group which may be substituted with a group, or an alkylthio group, optionally substituted with 1 to 3 groups selected from alkylsulfinyl group and alkylsulfonyl group),
R ^0A is (a) a hydrogen atom; (b) an alkyl group optionally substituted with 1 to 3 halogen atoms; (c) an alkyloxyalkyl group; (d) an aminoalkyl group (the amino group portion of the group). May be substituted with 1 to 2 alkyl groups); (e) an amino group optionally substituted with a group selected from an alkyl group, an alkylcarbonyl group and an alkylsulfonyl group; (f) 4-6 A nitrogen-containing aliphatic heterocyclic group; or (g) an alkyloxy group optionally substituted with a hydroxyl group,
E is a group represented by the formula: —C (═O) — or —SO ₂ —;
R ^S represents the following formula [ia], [ii-a] or [iii-a]:

A group represented by
Ring A is a C _3-8 cycloalkyl group (which may be condensed with a benzene ring) or a benzene ring, Q is a single bond or a methylene group,
Ring B is a 4- to 7-membered aliphatic heterocyclic group bonded to the adjacent nitrogen atom via the ring-constituting carbon atom, X is a sulfur atom, —SO—, —SO ₂ —, an oxygen atom or —NR ^k —. The group shown, R ^k is an alkyl group, an alkylcarbonyl group, an alkyloxycarbonyl group, an alkylsulfonyl group, an aminosulfonyl group optionally substituted with 1 to 2 alkyl groups, or 1 to 2 alkyl groups. An optionally substituted carbamoyl group,
R ³⁰ is (a) an alkyl group (the alkyl group may be substituted with a group selected from a hydroxyl group, an amino group, an acylamino group, a dialkylcarbamoylamino group, an alkylsulfonylamino group, and a dialkylsulfamoylamino group); (B) a cyano group; (c) a carboxyl group; (d) an alkyloxycarbonyl group; (e) a group represented by the formula: —N (R ^aa ) (R ^bb ); (f) a formula: —CON (R ^aa ) A group represented by (R ^bb ); (g)

Or (h) a hydroxyl group,
R ^aa and R ^bb are the same or different and each represents a hydrogen atom, a hydroxyl group, a cyano group, an alkyl group, a cyanoalkyl group, a trihalogenoalkyl group, a hydroxyalkyl group, an alkyloxyalkyl group, a cycloalkyl group, a formula: R ^xa CO— Or an alkylsulfonyl group or an aminoalkyl group (the amino group portion of the group may be substituted with 1 to 2 alkyl groups), or both R ^aa and R ^bb are terminated with ^respect to each other. To form a saturated or unsaturated nitrogen-containing heterocyclic group (the heterocyclic group may further contain a hetero atom selected from an oxygen atom and a sulfur atom in addition to a nitrogen atom), and R ^xa (A) a hydrogen atom, (b) an alkyl group (the alkyl group is substituted with 1 to 3 groups selected from a halogen atom, a cyano group, an alkylsulfonyl group and a pyridyl group) (C) an alkyloxy group (the alkyloxy group may be substituted with a 6 to 10-membered monocyclic or bicyclic aryl group), (d) a cycloalkyl group, (e) 6 to 10-membered monocyclic or bicyclic aryl group (the aryl group may be substituted with 1 to 2 groups selected from a halogen atom, a cyano group, an alkyl group, a trihalogenoalkyl group and an alkyloxy group) ), (F) an amino group (the amino group may be substituted with 1 to 2 alkyl groups) or (g) a saturated or unsaturated sulfur-containing, oxygen-containing or nitrogen-containing 4- to 7-membered heteromonocyclic ring A formula group (the heteromonocyclic group may be substituted with 1 to 2 groups selected from a halogen atom, a cyano group, an alkyl group and a trihalogenoalkyl group),
R ⁴⁰ represents (a) a hydrogen atom; (b) an alkyl group; (c) a cyano group; (d) a carboxyl group; (e) an alkylcarbonyl group; (f) an alkyloxycarbonyl group; (g) a formula: —CON ( A group represented by R ^cc ) (R ^dd ); (h) a phenyl group; (i) a benzyl group; or (j) a group represented by the formula: R ^xa CONH-, R ^cc and R ^dd are the same or different, A hydrogen atom or an alkyl group,
One of R ^Aa and R ^Ba is (a) an alkyl group (the alkyl group may be substituted with a hydroxyl group, an alkyloxy group, an amino group, an alkylamino group, or a dialkylamino group); The phenyl group may be substituted with 1 to 2 groups selected from a halogen atom, an alkyloxy group and a trihalogenoalkyl group); (c) a benzyl group; (d) a 5- to 6-membered nitrogen-containing heteroaryl group Or (e) a cycloalkyl group and the other is (a) a hydrogen atom; or (b) an alkyl group (the alkyl group is substituted with a hydroxyl group, an alkyloxy group, an amino group, an alkylamino group, or a dialkylamino group); It may be)
(Wherein 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyanobenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine, 6- (2 -Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyano-4-tetrahydrothiopyranyl) carbamoyl] pyrazolo [1,5-a] pyrimidine, 6-phenyl-7- (4- Chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5-a] pyrimidine; 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- (N-isopropylcarbamoyl) pyrazolo [1,5 -A] pyrimidine; 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-dimethylbenzyl) carbamoyl] pyrazo [1,5-a] pyrimidine; 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (α-methylbenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine; (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine; 6- (2-chlorophenyl) -7 -(4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine; and 6- (2-chlorophenyl) -7- (4 -Chlorophenyl) -3- [N- (4-cyanobenzyl) carbamoyl] pyrazolo [1,5-a] pyrimidine) or a pharmaceutically acceptable salt thereof. General formula [I-I-a]:

[Wherein, R ^1A represents (a) a phenyl group which may be substituted with one or two groups selected from a halogen atom, a difluoroalkyl group, a trifluoroalkyl group and a dialkylamino group, or (b) an alkyl group, A saturated or unsaturated 5- to 6-membered nitrogen-containing heterocyclic group which may be substituted with a group selected from a trifluoroalkyl group and an alkyloxy group;
R ^2A is a phenyl group optionally substituted by 1 to 2 groups selected from a halogen atom and a cyano group;
R ^0A is (a) a hydrogen atom; (b) an alkyl group optionally substituted with 1 to 3 halogen atoms; (c) an alkyloxyalkyl group; (d) an aminoalkyl group (the amino group portion of the group). May be substituted with 1 to 2 alkyl groups); (e) an amino group optionally substituted with a group selected from an alkyl group, an alkylcarbonyl group and an alkylsulfonyl group; (f) 4-6 A nitrogen-containing aliphatic heterocyclic group; or (g) an alkyloxy group optionally substituted with a hydroxyl group,
E is a group represented by the formula: —C (═O) — or —SO ₂ —;
R ^S1 represents the following formula [ib], [ic], [id], [ii-b], [iii-b] or [iii-c]:

A group represented by
Ring A ^a is (a) a C _3-8 cycloalkyl group or (b) a C _5-6 cycloalkyl group condensed with a benzene ring, Q is a single bond or a methylene group,
Ring ^{B a} 4 to 7 membered aliphatic heteromonocyclic group bonded to the adjacent nitrogen atom through the ring-constituting carbon atoms, X is a sulfur _{atom, -SO -, - SO 2 -} , an oxygen atom or -NR ^k A group represented by-, ^Rk is an alkyl group, an alkylcarbonyl group, an alkyloxycarbonyl group, an alkylsulfonyl group, an aminosulfonyl group optionally substituted by 1 to 2 alkyl groups, or 1 to 2 alkyls A carbamoyl group optionally substituted by a group,
R ³¹ represents a cyano group, an alkyl group, a hydroxyalkyl group, an aminoalkyl group (the amino part of the group may be substituted with an alkylcarbonyl group, a dialkylsulfamoyl group, an alkylsulfonyl group or a dialkylcarbamoyl group), carboxy An alkyl group, a carboxyl group, an alkyloxycarbonyl group, a carbamoyl group (the amino group portion of the group may be substituted with one or two groups selected from an alkyl group and a dialkylaminoalkyl group), or the following:

A group represented by
R ⁴¹ is a hydrogen atom, an amino group or a group represented by the formula: R ^xa CONH—, R ^xa is (a) a hydrogen atom, (b) an alkyl group (the alkyl group is a halogen atom, a cyano group, an alkylsulfonyl group and a pyridyl group) Or (c) an alkyloxy group (the alkyloxy group may be substituted with a 6 to 10-membered monocyclic or bicyclic aryl group). ), (D) a cycloalkyl group, (e) a 6 to 10-membered monocyclic or bicyclic aryl group (the aryl group is selected from a halogen atom, a cyano group, an alkyl group, a trihalogenoalkyl group and an alkyloxy group) ~ Optionally substituted with 2 groups), (f) an amino group (the amino group may be substituted with 1 to 2 alkyl groups) or (g) a saturated or unsaturated sulfur-containing, Oxygenated Or a nitrogen-containing 4- to 7-membered heteromonocyclic group (the heteromonocyclic group may be substituted with 1 to 2 groups selected from a halogen atom, a cyano group, an alkyl group and a trihalogenoalkyl group) Good),
R ³² represents a hydroxyl group, a carboxyl group, an alkyloxycarbonyl group, an amino group, or a group represented by the formula: R ^xa CONH—
R ³³ is a carboxyl group or an alkyloxycarbonyl group,
R ³⁴ is a cyano group, an alkyl group, a hydroxyalkyl group, an aminoalkyl group, a carboxyalkyl group, a carboxyl group, an alkyloxycarbonyl group, a carbamoyl group (the amino group portion of the group is an alkyl group, a hydroxyalkyl group, a cyanoalkyl group, A trihalogenoalkyl group, an alkyloxyalkyl group, a cycloalkyl group, an alkylsulfonyl group and a dialkylaminoalkyl group which may be substituted with 1 to 2 groups), a formula:

Or a group represented by

The ring J is a saturated or unsaturated 4- to 7-membered nitrogen-containing heteromonocyclic group (the heterocyclic group may contain an oxygen atom as a hetero atom other than the nitrogen atom),
R ³⁵ represents a hydroxyalkyl group, a carboxyl group, an alkyloxycarbonyl group or a carbamoyl group (the amino group portion of the group may be substituted with 1 to 2 alkyl groups), and R ^A1 represents an alkyl group or a cycloalkyl group. A phenyl group (the phenyl group may be substituted with 1 to 2 groups selected from a halogen atom, an alkyloxy group and a trihalogenoalkyl group) or a benzyl group, R ^B1 is a hydrogen atom or an alkyl group,
R ³⁶ represents an alkyl group or a carbamoyl group, and R ^B2 represents a hydrogen atom or an alkyl group. ]
Embedded image wherein 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (4-cyano-4-tetrahydrothiopyranyl) carbamoyl] pyrazolo [1,5-a] Pyrimidine, 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine and 6- (2- Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine) or pharmacologically acceptable thereof. Get salt. General formula [I-II-i]:

[Wherein R ¹⁰ and R ²⁰ are the same or different and (i) a 6 to 10-membered monocyclic or bicyclic aryl group (the aryl group is substituted with a halogen atom, a cyano group, or 1 to 3 halogen atoms An alkyl group that may be substituted, an alkyloxy group that may be substituted with 1 to 3 halogen atoms, an amino group that may be substituted with 1 to 2 alkyl groups, an alkylthio group, an alkylsulfinyl group, and Optionally substituted with 1 to 3 groups selected from alkylsulfonyl groups); or (ii) saturated or unsaturated sulfur-containing, oxygen-containing or nitrogen-containing 4- to 7-membered heteromonocyclic group (the heterocyclic ring) The formula group is a halogen atom, a cyano group, an oxo group, an alkyl group which may be substituted with 1 to 3 halogen atoms, an alkyloxy group which may be substituted with 1 to 3 halogen atoms, 1 to 2 Pieces Alkyl amino group which may be substituted with a group, or an alkylthio group, optionally substituted with 1 to 3 groups selected from alkylsulfinyl group and alkylsulfonyl group),
R ^0B is a group represented by the formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ), a group represented by the formula: —NHCONHR ⁰³ , a group represented by the formula: —CON (R ^e ) (R ^f ), carboxyl Group or hydroxyalkyl group, R ⁰¹ and R ⁰² are the same or different and are a hydrogen atom, alkyl group or carbamoylalkyl group, R ⁰³ is a hydrogen atom or an alkyl group, R ^e and R ^f are the same or different and are a hydrogen atom or an alkyl group Or a dialkylamino group,
E is a group represented by the formula: —C (═O) — or —SO ₂ —;
R ^5A represents a hydrogen atom or an alkyl group,
R ^6A is (A) an alkyl group (the group is (a) a halogen atom, (b) a hydroxyl group, (c) a cyano group, (d) an alkyloxy group, (e) a carboxyl group, (f) a carbamoyl group (this group May be substituted with 1 to 2 alkyl groups), (g) an alkylthio group, (h) an alkylsulfonyl group (i) a cycloalkyl group (the group is 1 to 2 groups selected from an alkyl group and a hydroxyl group) (J) an amino group optionally substituted with 1 to 2 alkyl groups, and (k) a saturated or unsaturated 4- to 10-membered, monocyclic or bicyclic group. Optionally substituted with 1 to 3 groups selected from nitrogen, sulfur-containing or oxygen-containing heterocyclic groups);
(B) a cycloalkyl group (the cycloalkyl group may be condensed with a benzene ring, and (a) an alkyl group optionally substituted with a group selected from a hydroxyl group, a carboxyl group, and an amino group; (b) (C) carboxyl group; (d) formula: group represented by R ^xa CO—; (e) formula: —N (R ^a1 ) (R ^b1 ) group; (f) formula: —CON (R ^a1 ) a group represented by (R ^b1 ); (g) a 6 to 10-membered monocyclic or bicyclic aryl group; (h) an alkyl group substituted with a 6 to 10-membered monocyclic or bicyclic aryl group And (i) optionally substituted with 1 to 2 groups selected from saturated or unsaturated 4 to 7-membered nitrogen-containing heteromonocyclic group which may be substituted with 1 to 2 oxo groups; ^{), R a1} and ^{R b1} are the same or different and represent a hydrogen atom, a hydroxyl group, a cyano , An alkyl group, the formula: a group represented by R ^{xa CO-,} an alkylsulfonyl group, an aminoalkyl group, a monoalkylamino group or dialkylamino group;
(C) 6 to 10-membered monocyclic or bicyclic aryl group (the aryl group may be substituted with 1 to 2 groups selected from a cyano group, a trihalogenoalkyl group, an alkyloxy group and a carboxyl group) );
(D) a saturated or unsaturated 4- to 10-membered monocyclic or bicyclic heterocyclic group (the heterocyclic group contains at least one heteroatom selected from a sulfur atom, an oxygen atom and a nitrogen atom, and (A) halogen atom, (b) hydroxyl group, (c) oxo group, (d) cyano group, (e) alkyl group, (f) trihalogenoalkyl group, (g) hydroxyalkyl group, (h) alkyloxyalkyl Group, (i) alkyloxy group, (j) group represented by formula: R ^xa CO—, (k) cycloalkyl group, (l) alkylsulfonyl group, (m) substituted with 1 to 2 alkyl groups An optionally substituted aminosulfonyl group, (n) a phenylsulfonyl group, (o) an amino group, (p) a group represented by the formula: R ^xa CONH-, (q) substituted with 1 to 2 alkyl groups Good carbamoyl group, ( r) 6 to 10-membered monocyclic or bicyclic aryl group optionally substituted with a halogen atom, and (s) 1 to 2 groups optionally saturated selected from an alkyl group and a trihalogenoalkyl group Alternatively, it may be substituted with 1 to 4 groups selected from unsaturated sulfur-containing, oxygen-containing or nitrogen-containing 4 to 7-membered heteromonocyclic groups);
(E) a group represented by the formula: —N (R ⁸¹ ) (R ⁹¹ ), R ⁸¹ is a hydrogen atom or an alkyl group, R ⁹¹ is (a) an alkyl group (the alkyl group is a halogen atom, a cyano group and 6 to 6 Optionally substituted with 1 to 3 groups selected from 10-membered monocyclic or bicyclic aryl groups); (b) cycloalkyl groups; (c) 6-10 membered monocyclic or bicyclic aryl groups (The aryl group is a group selected from a halogen atom, a cyano group, an alkyl group, a trihalogenoalkyl group, an alkyloxy group, a trihalogenoalkyloxy group, an alkylthio group, an alkylsulfonyl group, and a group represented by the formula: R ^xa CO—. (D) a group represented by the formula: R ^xa CO—; or (e) a saturated or unsaturated sulfur-containing, oxygen-containing or nitrogen-containing 4- to 7-membered heterocyclic monocyclic group Heterocyclic groups are Optionally substituted with a group selected from a halogen atom, an alkyl group, a trihalogenoalkyl group and an alkyloxy group); or (F) R ^5A and R ^6A are bonded to each other and saturated or unsaturated together with the adjacent nitrogen atom 4- to 10-membered monocyclic or bicyclic nitrogen-containing heterocyclic group (this nitrogen-containing heterocyclic group has 1 to 2 heteroatoms selected from sulfur atom and oxygen atom in addition to nitrogen atom) And may be substituted with one or two groups selected from a halogen atom, an oxo group, an alkyl group, a group represented by the formula: R ^xa CO— and a dialkylaminosulfonyl group). Represents
R ^xa is (a) a hydrogen atom, (b) an alkyl group (the alkyl group may be substituted with 1 to 3 groups selected from a halogen atom, a cyano group, an alkylsulfonyl group and a pyridyl group), c) an alkyloxy group (the alkyloxy group may be substituted with a 6-10 membered monocyclic or bicyclic aryl group), (d) a cycloalkyl group, (e) a 6-10 membered monocyclic or bicyclic group. A cyclic aryl group (the aryl group may be substituted with one or two groups selected from a halogen atom, a cyano group, an alkyl group, a trihalogenoalkyl group and an alkyloxy group), (f) an amino group ( The amino group may be substituted with 1 to 2 alkyl groups) or (g) a saturated or unsaturated sulfur-containing, oxygen-containing or nitrogen-containing 4- to 7-membered heteromonocyclic group (the heteromonocyclic Group is halogen atom, shear Group, an alkyl group, and an alkyl group may be substituted with 1 to 2 groups selected from a trihalogenoalkyl group. ]
Embedded image wherein 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2- (hydroxymethyl) ) Excluding pyrazolo [1,5-a] pyrimidine) or a pharmaceutically acceptable salt thereof. General formula [I-II-ii]:

[Wherein R ¹⁰ and R ²⁰ are the same or different and (i) a 6 to 10-membered monocyclic or bicyclic aryl group (the aryl group is substituted with a halogen atom, a cyano group, or 1 to 3 halogen atoms An alkyl group that may be substituted, an alkyloxy group that may be substituted with 1 to 3 halogen atoms, an amino group that may be substituted with 1 to 2 alkyl groups, an alkylthio group, an alkylsulfinyl group, and Optionally substituted with 1 to 3 groups selected from alkylsulfonyl groups); or (ii) saturated or unsaturated sulfur-containing, oxygen-containing or nitrogen-containing 4- to 7-membered heteromonocyclic group (the heterocyclic ring) The formula group is a halogen atom, a cyano group, an oxo group, an alkyl group which may be substituted with 1 to 3 halogen atoms, an alkyloxy group which may be substituted with 1 to 3 halogen atoms, 1 to 2 Pieces Alkyl amino group which may be substituted with a group, or an alkylthio group, optionally substituted with 1 to 3 groups selected from alkylsulfinyl group and alkylsulfonyl group),
R ^0B is a group represented by the formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ), a group represented by the formula: —NHCONHR ⁰³ , a group represented by the formula: —CON (R ^e ) (R ^f ), carboxyl Group or hydroxyalkyl group, R ⁰¹ and R ⁰² are the same or different and are a hydrogen atom, alkyl group or carbamoylalkyl group, R ⁰³ is a hydrogen atom or an alkyl group, R ^e and R ^f are the same or different and are a hydrogen atom or an alkyl group Or a dialkylamino group,
R ⁿ represents an alkyl group. ]
Or a pharmaceutically acceptable salt thereof. R ¹⁰ is (i) a phenyl group which may be substituted with one or two groups selected from a halogen atom, an alkyl group, a difluoroalkyl group, a trifluoroalkyl group and a dialkylamino group, or (ii) an alkyl group, Saturated or unsaturated 5- to 6-membered nitrogen-containing heterocyclic group which may be substituted with a group selected from a fluoroalkyl group and an alkyloxy group, or one or two groups wherein R ²⁰ is selected from a halogen atom and a cyano group A phenyl group optionally substituted by
R ^6A is (A) an alkyl group (the alkyl group may be substituted with a group selected from 1 to 3 halogen atoms, a hydroxyl group, a cyano group, a carboxyl group, and an alkyloxycarbonyl group);
(B) The following formula:

In cyclic groups wherein shown, ring ^{A b} is _{(a) C 3-8} cycloalkyl group or (b) a benzene ring fused with _{C 5-6} cycloalkyl ^{group, R 37} is a hydrogen atom, a cyano group, An alkyl group, a hydroxyalkyl group, an aminoalkyl group, a carboxyalkyl group, a carboxyl group, an alkyloxycarbonyl group, a carbamoyl group (the amino group portion of the group is one or two groups selected from an alkyl group and a dialkylaminoalkyl group); Optionally substituted) or the following formula:

R ⁴³ represents a hydrogen atom, an amino group, an alkyloxycarbonylamino group, or a benzyloxycarbonylamino group];
(C) a phenyl group (the phenyl group may be substituted with 1 to 2 groups selected from a halogen atom, an alkyloxy group, a trihalogenoalkyl group, a carboxyl group and an alkyloxycarbonyl group);
(D) The following formula:

In cyclic groups wherein shown, Ring B ^b is the ring structure 4-7 membered aliphatic heteromonocyclic group bonded to the adjacent nitrogen atom via a carbon atom, ring B ^c is 4-7 membered aliphatic A nitrogen-containing heteromonocyclic group, X ¹ is a sulfur atom, a group represented by the formula: —SO—, a group represented by the formula: —SO ₂ —, an oxygen atom or a group represented by the formula: —NR ^m —, R ^m is an alkyl group, an alkylcarbonyl group, an alkyloxycarbonyl group, an alkylsulfonyl group, an aminosulfonyl group which may be substituted with 1 to 2 alkyl groups, or an alkyl group which may be substituted with 1 to 2 alkyl groups. a carbamoyl group, R ³⁸ is a hydrogen atom, a cyano group, an alkyl group, a hydroxyalkyl group, an aminoalkyl group, a carboxyalkyl group, a carboxyl group, an alkyloxycarbonyl group, an amino group moiety of the carbamoyl group (said group alkyl 1-2 may be substituted with a group) or the following formula selected from the group and dialkylamino group:

Represents a group represented by
(E) Formula: a group represented by —N (R ^8a ) (R ^9a ), wherein R ^8a is a hydrogen atom or an alkyl group, R ^9a is an alkyl group, a trihalogenoalkyl group, a cyanoalkyl group, a benzyl group, Cycloalkyl group, phenyl group (the phenyl group is a halogen atom, cyano group, alkyl group, trihalogenoalkyl group, alkyloxy group, trihalogenoalkyloxy group, alkylthio group, alkylsulfonyl group, alkyloxycarbonyl group, and benzyloxycarbonyl) An alkyloxycarbonyl group, a benzyloxycarbonyl group, or a 5- or 6-membered nitrogen-containing heteroaryl group, which may be substituted with a group selected from a group]; or (F)

In the radical represented [wherein ring A ^c is a benzene ring condensed with C _3-8 optionally the cycloalkyl group, the ring B ^d is (a) phenyl group (said phenyl group is a halogen atom, a cyano group, an alkyl (Which may be substituted with an oxy group, a trihalogenoalkyl group or a carboxyl group) or (b) a pyridyl group, R ^S11 is a hydrogen atom or an alkyl group, R ^S12 is a hydrogen atom, an alkyl group, a carboxyl group, a carbamoyl group or a mono group Or a dialkylcarbamoyl group, R ³⁹ is a hydrogen atom, halogen atom, cyano group, alkyl group, hydroxyalkyl group, trihalogenoalkyl group, aminoalkyl group, alkyloxy group, carboxyalkyl group, carboxyl group, carbamoyl group (of the group) The amino group moiety is one or two groups selected from an alkyl group and a dialkylaminoalkyl group The compound according to claim 14, which may be substituted with an amino group, an alkyloxycarbonylamino group, or a benzyloxycarbonylamino group, and k represents an integer of 0 to 2. R ¹⁰ is (i) a phenyl group which may be substituted with one or two groups selected from a halogen atom, an alkyl group, a difluoroalkyl group, a trifluoroalkyl group and a dialkylamino group, or (ii) an alkyl group, Saturated or unsaturated 5- to 6-membered nitrogen-containing heterocyclic group which may be substituted with a group selected from a fluoroalkyl group and an alkyloxy group, or one or two groups wherein R ²⁰ is selected from a halogen atom and a cyano group The compound according to claim 15, which is a phenyl group which may be substituted with. R ¹ and R ² may be the same or different and may be (a) a halogen atom, a cyano group, an alkyl group that may be substituted with 1 to 3 halogen atoms, and a substituent that is substituted with 1 to 2 alkyl groups. A phenyl group optionally substituted by 1 to 3 groups selected from good amino groups, or (b) a group selected from an alkyl group and alkyloxy group optionally substituted by 1 to 3 halogen atoms A saturated or unsaturated 5- to 7-membered nitrogen-containing heterocyclic group optionally substituted by
A1) R ′ is a group represented by the formula [i], R ³ is an alkyl group which may be substituted with a group selected from (a) a hydroxyl group and an amino group, (b) a cyano group, (c) a carboxyl group, (D) an alkyloxycarbonyl group, (e) a group represented by the formula: —CON (R ^e ) (R ^f ), or (f) an acylamino group, R ^e and R ^f are the same or different, and a hydrogen atom, an alkyl group or A dialkylaminoalkyl group, R ⁴ is a hydrogen atom or an acylamino group, or;
A2) R ′ is a group represented by the formula [ii], X is a sulfur atom, SO ₂ , an oxygen atom or a group ^represented by the formula: N—R ^k , R ^k is an alkyloxycarbonyl group, an alkylsulfonyl group, an alkylcarbonyl A group or a dialkylaminosulfonyl group, R ³ is (a) an alkyl group optionally substituted with a hydroxyl group, (b) a carboxyl group, (c) an alkyloxycarbonyl group or (d) a formula: —CON (R ^e ) ( A group represented by R ^f ), R ^e and R ^f are the same or different and are a hydrogen atom, an alkyl group or a trihalogenoalkyl group, R ⁴ is a hydrogen atom; or A3) R ′ is represented by the formula [iii] Group, R ^A is an alkyl group optionally substituted with a hydroxyl group, a phenyl group (the phenyl group may be substituted with a halogen atom or a trihalogenoalkyl group), or nitrogen-containing 5-6 A membered heteroaryl group, R ^B is a hydrogen atom or an alkyl group, R ³ is an alkyl group, a carboxyl group or a group represented by the formula: —CON (R ^a ) (R ^b ), R ^a and R ^b are a hydrogen atom or an alkyl group R ^0A is a hydrogen atom, an alkyl group optionally substituted with 1 to 3 halogen atoms, an alkyloxy group optionally substituted with a hydroxyl group, a hydroxyalkyl group, an amino group (the amino group 3. The compound according to claim 2, which is a 4- to 6-membered nitrogen-containing aliphatic heterocyclic group which may be substituted with 1 or 2 groups selected from an alkyl group, an alkylcarbonyl group and an alkylsulfonyl group. R ′ is a group represented by the formula [i], R ³ is (a) a C _1-6 alkyl group, (b) a hydroxy-C _1-6 alkyl group, (c) an amino-C _1-6 alkyl group, d) cyano group, (e) carboxyl group, (f) C _1-6 alkyloxy-carbonyl group, (g) carbamoyl group, (h) mono- or di (C _1-6 alkyl) carbamoyl group, (i) di (C _1-6 alkyl) amino-C _1-6 alkyl-carbamoyl group or (j) C _1-6 alkyloxy-carbonylamino group, R ⁴ is a hydrogen atom or phenyl-C _1-6 alkyloxy-carbonyl The compound according to claim 18, which is an amino group. R ′ is a group represented by the formula [ii], X is a sulfur atom, SO ₂ , an oxygen atom or a group ^represented by N—R ^k , R ^k is a C _1-6 alkyloxy-carbonyl group, C _1-6 alkyl A sulfonyl group, a C _1-6 alkyl-carbonyl group or a di (C _1-6 alkyl) aminosulfonyl group, R ³ is (a) a carbamoyl group, (b) a mono- or di (C _1-6 alkyl) -carbamoyl group, (C) a mono (trihalogeno C _1-6 alkyl) carbamoyl group, (d) a C _1-6 alkyloxy-carbonyl group, (e) a C _1-6 alkyl group or (f) a hydroxy-C _1-6 alkyl group, The compound according to claim 18, wherein R ⁴ is a hydrogen atom. R ′ is a group represented by the formula [iii], R ^A is a C _1-6 alkyl group, a hydroxy-C _1-6 alkyl group, a phenyl group, a halogenophenyl group, a trihalogeno (C _1-6 alkyl) -phenyl group or The compound according to claim 18, wherein R 1 is a pyridyl group, R ^B is a hydrogen atom or a C _1-6 alkyl group, and R ³ is a C _1-6 alkyl group, a carboxyl group, a C _1-6 alkyloxy-carbonyl group or a carbamoyl group. A phenyl group in which R ¹ is substituted with one or two groups selected from a halogen atom, a dihalogeno-C _1-6 alkyl group, a trihalogeno-C _1-6 alkyl group and a di (C _1-6 alkyl) amino group; A C _1-6 alkyloxy-pyrrolidinyl group, a C _1-6 alkyl-piperidyl group or a C _1-6 alkyloxypiperidyl group, a phenyl group in which R ² is substituted with 1 to 2 halogen atoms, a cyanophenyl group, or a trihalogeno group -C _1-6 alkyl-pyridyl group, R ^0A is a hydrogen atom, C _1-6 alkyl group, dihalogeno-C _1-6 alkyl group, trihalogeno-C _1-6 alkyl group, C _1-6 alkyloxy group, hydroxy -C _1-6 alkyl group, amino _{group, C 1-6} alkyl - carbonyl amino group, a mono _{(C 1-6} alkyl) carbamoyl group or a 4 Claim 19, 20 or 21 compound as described is membered nitrogen-containing aliphatic heterocyclic group. 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-cyanocyclohexyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-cyanocyclopentyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-methylcyclohexyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-methylcyclopropyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (1-cyanocyclopentyl) carbamoyl] -7- (4-trifluoromethylphenyl) -2-methylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (1-cyanocyclohexyl) carbamoyl] -7- (4-trifluoromethylphenyl) -2-methylpyrazolo [1,5-a] pyrimidine;
3- [N- (4-Carbamoyl-1,1-dioxo-tetrahydrothiopyran-4-yl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] Pyrimidine;
2-acetylamino-6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine ;
6- (2-chlorophenyl) -7- (4-chloro-2-fluorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] -2- (1-pyrrolidinyl) pyrazolo [1,5- a] pyrimidine;
3- [N- (1-carbamoylcyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
3- [N- (4-Carbamoyl-1,1-dioxo-tetrahydrothiopyran-4-yl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5 -A] pyrimidine;
3- [N- (1-carboxycyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3-[[1- [N- [2- (N, N-dimethylamino) ethyl] carbamoyl] cyclohexyl] carbamoyl] pyrazolo [1, 5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (N-methylcarbamoyl) cyclohexyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (N, N-dimethylcarbamoyl) cyclohexyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
(S) -3- [N- (1-carboxy-2-methylpropyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine;
(S) -3- [N- (1-carboxy-2-phenylethyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
(S) -3- [N- (1-carboxy-2-methylpropyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
(S) -3- [N- (α-carboxybenzyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
(S) -3- [N- (1-carboxy-2-methylpropyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -2-methylpyrazolo [1,5-a] pyrimidine;
3- [N- (1-carboxy-1-methylethyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -2-methylpyrazolo [1,5-a] pyrimidine;
3- [N- (α-carboxybenzyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine;
3- [N- (1-carboxy-1-methylethyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
3- [N- (1-carboxy-2-phenylethyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) pyrazolo [1,5-a] pyrimidine;
3- [N- (4-carboxy-1-cyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
3- [N- (4-carboxybenzyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
3- [N- (3-carboxybenzyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (1-cyanocyclohexyl) carbamoyl] -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-methoxycarbonylcyclohexyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (methylsulfonylamino) -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine ;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- [N-methyl-N- (methylsulfonyl) amino] -3- [N- [1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-methylpiperidin-1-yl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] Pyrimidine;
6- (2-Chlorophenyl) -7- (4-methoxypiperidin-1-yl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] Pyrimidine;
6- (2-Chlorophenyl) -7- (3-methoxypyrrolidin-1-yl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5-a] Pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (1-methoxycarbonylcyclohexyl) sulfamoyl] -2-methylpyrazolo [1,5-a] pyrimidine;
3- [N- (1-carboxycyclohexyl) sulfamoyl] -6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -2-methylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (4-methoxycarbonyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1, 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5 -A] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2-methyl-3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1, 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2-methyl-3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (3-hydroxy-2-methylprop-2-yl) carbamoyl] -2-methylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (4-hydroxymethyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1, 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2-trifluoromethyl-3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [ 1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2-ethoxy-3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1, 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (2-fluoro-4-trifluoromethylphenyl) -3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (3-methoxycarbonyl-1,1-dioxothietan-3-yl) carbamoyl] pyrazolo [1,5-a] Pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-cyanocyclohexyl) carbamoyl] -2-methylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (2-hydroxyethoxy) -3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl) carbamoyl] Pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2- (2-hydroxyethoxy) -3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl ) Carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl) carbamoyl] pyrazolo [1,5- a] pyrimidine;
6- (2-Chlorophenyl) -2- (difluoromethyl) -7- (4-trifluoromethylphenyl) -3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl) carbamoyl ] Pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (trifluoromethyl) -3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [4- (N-methylcarbamoyl) -1,1-dioxotetrahydrothiopyran-4-yl] carbamoyl] Pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -3- [N- [4- [N- (2,2,2-trifluoroethyl) carbamoyl] -1,1-dioxotetrahydrothiopyran-4-yl] carbamoyl]- 7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine; and 6- (2-chlorophenyl) -3- [N- [4- [N- (2,2,2-trifluoroethyl) ) Carbamoyl] -1,1-dioxotetrahydrothiopyran-4-yl] carbamoyl] -7- (4-trifluoromethylphenyl) -2-methylpyrazolo [1,5-a] pyrimidine or pharmacology thereof Acceptable salt. R ¹ and R ² may be the same or different and may be substituted with one or two groups selected from a halogen atom, a cyano group, an alkyl group, a dihalogenoalkyl group and a trihalogenoalkyl group, R ″ is A group represented by the formula: —N (R ⁵ ) (R ⁶ ), R ⁵ is a hydrogen atom or an alkyl group, R ⁶ is (a) an alkyl group (the alkyl group is a halogen atom, a hydroxyl group, a cyano group, an alkyloxy group) C _3-8 cycloalkyl group, hydroxy-C _3-8 cycloalkyl group, amino-C _3-8 cycloalkyl group, C _3-8 cycloalkyl group substituted with 1 to 2 halogen atoms, dialkylamino Group, carboxyl group, carbamoyl group optionally substituted with 1 to 2 alkyl groups, phenyl group substituted with 1 to 2 halogen atoms, trihalogenoalkylphenyl , Alkyloxy phenyl group, optionally substituted with 1 to 3 groups selected from carboxyphenyl group and a saturated or unsaturated 5- to 6-membered nitrogen-containing or oxygen-containing heterocyclic group), (b) C _{3 -8} cycloalkyl group [this cycloalkyl group may be condensed with a benzene ring, and cyano group, alkyl group, hydroxyalkyl group, carboxyalkyl group, aminoalkyl group, alkylcarbonylamino-alkyl group, di (alkyl ) Carbamoyl-amino-alkyl group, alkylsulfonylaminoalkyl group, dialkylsulfamoylaminoalkyl group, carboxyl group, alkyloxycarbonyl group, phenylalkyloxycarbonyl group, represented by the formula: —CON (R ^a1 ) (R ^b1 ) group (wherein ^{which, R a1} and ^{R b1} are the same or different (Which may be substituted with 1 to 2 groups selected from an elementary atom, an alkyl group or a dialkylaminoalkyl group) and a tetrazolyl group], (c) a saturated or unsaturated 4- to 6-membered nitrogen-containing, sulfur-containing Or an oxygen-containing heterocyclic group [the heterocyclic group is an oxo group, a hydroxyl group, a cyano group, an alkyl group, a hydroxyalkyl group, a carboxyl group, an alkyloxycarbonyl group, an alkylsulfonyl group, a formula: —CON (R ^a2 ) ( R ^b2 ) (wherein R ^a2 and R ^b2 are the same or different and are a hydrogen atom, an alkyl group, a trihalogenoalkyl group, a cyanoalkyl group, a hydroxyalkyl group, an alkyloxyalkyl group, an alkylsulfonyl group or C _3-8 represents a cycloalkyl group), 1 selected from pyrrolidinylcarbonyl group and a morpholinocarbonyl group Or (d) an amino group (the amino group may be substituted with 1 to 2 groups selected from an alkyl group and a pyridyl group). Described compounds (provided that 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2- (hydroxymethyl)) Except for pyrazolo [1,5-a] pyrimidine). R ¹ and R ² are the same or different, a halogen atom, a cyano group, di-halogenoalkyl group and trihalogenoalkyl 1-2 phenyl group which may be substituted by a group selected from an alkyl group, R ^0B has the formula: 4. The compound according to claim 3, wherein the group represented by —SO ₂ N (R ⁰¹ ) (R ⁰² ), R ″ is an alkyloxy group. The compound according to claim 24 or 25, wherein E is a group represented by the formula: -C (= O)-. R ¹ and R ² are the same or different, and a phenyl group which may be substituted with one or two groups selected from a halogen atom, a cyano group, an alkyl group, a dihalogenoalkyl group and a trihalogenoalkyl group, R ^0B Is a group represented by the formula: —NHCONHR ⁰³ , E is a group represented by —C (═O) —, R ″ is a group represented by the formula: —N (R ⁵ ) (R ⁶ ), and R ⁵ is a hydrogen atom. , R ⁶ is selected from (a) alkyl group, (b) trihalogenoalkyl group, (c) C _3-8 cycloalkyl group, (d) dialkylamino group or (e) oxo group, alkyl group and carbamoyl group The compound according to claim 3, which is a saturated or unsaturated 5- to 6-membered sulfur-containing heterocyclic group which may be substituted with 1 to 3 groups. R ¹ and R ² are the same or different and (i) substituted with 1 to 2 groups selected from a halogen atom, a cyano group, an alkyl group, a dihalogenoalkyl group, a trihalogenoalkyl group and an alkyloxy group. A suitable phenyl group or (ii) a saturated or unsaturated 5- to 6-membered nitrogen-containing ^{heteromonocyclic} group, R ^0B is a group represented by the formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ), and R ⁰¹ is hydrogen. An atom or an alkyl group, R ⁰² is a hydrogen atom, an alkyl group or a carbamoylalkyl group, E is a group represented by —C (═O) —, R ″ is represented by the formula: —N (R ⁵ ) (R ⁶ ) Group, R ⁵ is a hydrogen atom or an alkyl group, R ⁶ is (a) a halogen atom, a hydroxyl group, a cyano group, an alkyloxy group, or a C _3-8 cycloalkyl group _optionally substituted by 1 to 2 halogen atoms. 1 to 2 alkyls An alkyl group which may be substituted with 1 to 3 groups selected from an amino group and a pyridyl group which may be substituted with (b) may be substituted with a group selected from an alkyl group and a carbamoyl group 1 selected from a C _3-8 cycloalkyl group, (c) an amino group optionally substituted by 1 to 2 groups selected from an alkyl group and a pyridyl group, or (d) an oxo group, an alkyl group and a carbamoyl group 4. The compound according to claim 3, which is a saturated or unsaturated 5- or 6-membered nitrogen-containing or sulfur-containing heterocyclic group which may be substituted with 3 groups. R ¹ and R ² are the same or different, and a phenyl group which may be substituted with one or two groups selected from a halogen atom and a trihalogenoalkyl group, R ^0B is represented by the formula: —CON (R ^e ) (R ^f ), a group represented by R ^e is a hydrogen atom or an alkyl group, R ^f is a hydrogen atom, an alkyl group or a dialkylamino group, E is a group represented by -C (= O)-, and R "is a formula: -N (R ⁵ ) a group represented by (R ⁶ ), R ⁵ is a hydrogen atom, R ⁶ is (a) an alkyl group _optionally substituted with 1 to 3 halogen atoms, (b) C _3-8 cyclo The compound according to claim 3, which is a saturated or unsaturated 4- to 6-membered sulfur-containing heterocyclic group which may be substituted with 1 to 3 groups selected from an alkyl group or (c) an oxo group and an alkyl group. R ¹ and R ² are the same or different and may be substituted with one or two groups selected from a halogen atom and a trihalogenoalkyl group, R ^0B is a hydroxyalkyl group, and E is —C (= O) —, R ″ is a group represented by the formula: —N (R ⁵ ) (R ⁶ ), R ⁵ is a hydrogen atom, and R ⁶ is (a) substituted with 1 to 3 halogen atoms. An optionally substituted alkyl group, (b) an alkyl group substituted with a pyridyl group, (c) a C _3-8 cycloalkyl group _optionally substituted with a group selected from a cyano group and carbamoyl, or (d) an oxo group And a saturated or unsaturated 4- to 6-membered nitrogen-containing or sulfur-containing heterocyclic group which may be substituted with 1 to 3 groups selected from alkyl groups; 2-chlorophenyl) -7- (4-chloroph Enyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2- (hydroxymethyl) pyrazolo [1,5-a] pyrimidine). R ¹ and R ² are the same or different and may be substituted with one or two groups selected from a halogen atom and a trihalogenoalkyl group, R ^0B is a carboxyl group, and E is —C (═O ) —, R ″ is a group represented by the formula: —N (R ⁵ ) (R ⁶ ), R ⁵ is a hydrogen atom, R ⁶ is an oxo group and an alkyl group. 4. The compound according to claim 3, which is a saturated or unsaturated 5- to 6-membered sulfur-containing heterocyclic group which may be substituted with. R ¹ and R ² are the same or different and a halogenophenyl group, R ^0B is a sulfamoyl group optionally substituted by 1 to 2 alkyl groups, E is a group represented by —C (═O) —, R ″ The compound according to claim 3, wherein is an alkyloxy group. R ¹ is (i) a phenyl group which may be substituted with one or two groups selected from a halogen atom, a C _1-6 alkyl group, a dihalogeno C _1-6 alkyl group and a trihalogeno C _1-6 alkyl group; (Ii) a piperidino group, R ² is a phenyl group optionally substituted by one or two groups selected from a halogen atom and a cyano group, and R ^0B is a formula: —SO ₂ N (R ⁰¹ ) (R ⁰² ) R ⁰¹ is a hydrogen atom or a C _1-6 alkyl group, R ⁰² is a hydrogen atom, a C _1-6 alkyl group or a carbamoyl-C _1-6 alkyl group, R ⁵ is a hydrogen atom, and R ⁶ is ( a) a halogen _{atom, C 1-6} alkyloxy _{group, C 3-8} cycloalkyl group and one to three _{C 1-6} alkyl group optionally substituted by a group selected from a pyridyl group, (b) C stand at _1-6 alkyl group Which may be _{C 3-8} cycloalkyl groups, _{(c) C 1-6} alkyl group and one to two amino groups which may be substituted by a group selected from a pyridyl group, or (d) 1-2 29. The compound according to claim 28, which is a saturated or unsaturated 5- or 6-membered nitrogen-containing or sulfur-containing heterocyclic group which may be substituted with one oxo group. R ¹ is a trihalogeno C _1-6 alkyl-phenyl group, R ² is a halogenophenyl group, R ^0B is a group represented by the formula: —CON (R ^e ) (R ^f ), R ^e is a hydrogen atom or C _1-6 An alkyl group, R ^f is a hydrogen atom or a C _1-6 alkyl group, R ⁵ is a hydrogen atom, R ⁶ is (a) a C _1-6 alkyl group _optionally substituted by 1 to 3 halogen atoms, or (B) The compound according to claim 29, which is a saturated or unsaturated 5- to 6-membered sulfur-containing heterocyclic group which may be substituted with 1 to 3 groups selected from an oxo group and a C _1-6 alkyl group. . R ¹ is a trihalogeno C _1-6 alkyl-phenyl group, R ² is a halogenophenyl group, R ^0B is a hydroxy C _1-4 alkyl group, R ⁵ is a hydrogen atom, R ⁶ is (a) a trihalogeno C _1-6 alkyl group (B) a pyridyl-C _1-6 alkyl group, (c) a C _5-7 cycloalkyl group substituted with a group selected from a cyano group and carbamoyl, or (d) an oxo group and a C _1-6 alkyl group. 31. The compound according to claim 30, wherein the compound is a saturated or unsaturated 5- to 6-membered sulfur-containing heterocyclic group optionally substituted by 1 to 3 groups (provided that 6- (2-chlorophenyl) -7- ( 4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2- (hydroxymethyl) pyrazolo [1,5-a] pyrimidine). The compound according to claim 32, wherein R ¹ and R ² are the same or different halogenophenyl groups, R ^0B is a C _1-6 alkyl-sulfamoyl group, and R ″ is a C _1-6 alkyloxy group. 6- (2-chlorophenyl) -7- (4-chlorophenyl) -3-ethoxycarbonyl-2- (N-methylsulfamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3-ethoxycarbonyl-2- (N, N-dimethylsulfamoyl) pyrazolo [1,5-a] pyrimidine;
(R) -6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (N-methylsulfamoyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) Carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclopentyl) carbamoyl] -2- (N-methylsulfamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] -2- (N-methylsulfamoyl) pyrazolo [ 1,5-a] pyrimidine;
(R) -6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (N, N-dimethylsulfamoyl) -3- [N- (1,1-dioxotetrahydrothien-3- Yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclopentyl) carbamoyl] -2- (N, N-dimethylsulfamoyl) pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -2- (N, N-dimethylsulfamoyl) -3- [N- (1-pyrrolidinyl) carbamoyl] pyrazolo [1,5-a] pyrimidine ;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] -2- (N, N-dimethylsulfamoyl) Pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -2- (N-methylsulfamoyl) -3- [N- (1-pyrrolidinyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
(R) -6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2-sulfamoylpyrazolo [ 1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-pyrrolidinyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] -2-sulfamoylpyrazolo [1,5- a] pyrimidine;
(S) -6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2-sulfamoylpyrazolo [ 1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclopentyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] -2-sulfamoylpyrazolo [1,5 -A] pyrimidine;
(R) -6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2-sulfamoyl Pyrazolo [1,5-a] pyrimidine;
(S) -6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2-sulfamoyl Pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (cyclopentyl) carbamoyl] -7- (4-trifluoromethylphenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
(R) -7- (4-Chlorophenyl) -6- (2-cyanophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
7- (4-chlorophenyl) -6- (2-cyanophenyl) -3- [N- (cyclopentyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
7- (4-Chlorophenyl) -6- (2-cyanophenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] -2-sulfamoylpyrazolo [1,5 -A] pyrimidine;
(R) -2- [N- (carbamoylmethyl) sulfamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1,1-dioxotetrahydrothien-3-yl) ) Carbamoyl] pyrazolo [1,5-a] pyrimidine;
2- [N- (carbamoylmethyl) sulfamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclopentyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
2- [N- (carbamoylmethyl) sulfamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] pyrazolo [1,5-a] pyrimidine;
2- [N- (carbamoylmethyl) sulfamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-pyrrolidinyl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
3- [N- (1-carboxycyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -2- (N-methylsulfamoyl) pyrazolo [1,5-a] Pyrimidine;
3- [N- (1-carbamoylcyclohexyl) carbamoyl] -6- (2-chlorophenyl) -7- (4-chlorophenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2-hydroxymethyl-3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] pyrazolo [1,5 -A] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2-hydroxymethyl-3- [N- (3-methyl-1,1-dioxotetrahydrothien-3-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (1-cyanocyclohexyl) carbamoyl] -7- (4-trifluoromethylphenyl) -2-hydroxymethylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2-hydroxymethyl-3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] Pyrazolo [1,5-a] pyrimidine;
2-carbamoyl-6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4-yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -2- (N-methylcarbamoyl) -3- [N- (4-methyl-1,1-dioxotetrahydrothiopyran-4- Yl) carbamoyl] pyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (2,2-dimethylpropyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclohexylmethyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-chlorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine ;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (3-methylpropyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (2,2-difluoroethyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (cyclopropylmethyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-chlorophenyl) -3- [N- (1-methylcyclopropyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -7- (4-trifluoromethylphenyl) -2-hydroxymethylpyrazolo [1,5-a ] Pyrimidine;
6- (2-chlorophenyl) -7- (4-difluoromethylphenyl) -3- [N- (isobutyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
2-carbamoyl-6- (2-chlorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -7- (4-trifluoromethylphenyl) pyrazolo [1,5-a] pyrimidine ;
6- (2-Chlorophenyl) -7- (4-chloro-2-fluorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -2-sulfamoylpyrazolo [1, 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-difluoromethylphenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a ] Pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (n-propyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (isobutyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (1-methylpropyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (3-methoxyprop-2-yl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] Pyrimidine;
6- (2-chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (1-methylcyclopropyl) carbamoyl] -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -7- (4-fluorophenyl) -2-sulfamoylpyrazolo [1,5-a] Pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3-[[N′-methyl-N ′-(2-pyridyl) hydrazino] carbonyl] -2-sulfamoylpyrazolo [1 , 5-a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -2- (dimethylcarbamoyl) pyrazolo [1,5- a] pyrimidine;
6- (2-Chlorophenyl) -7- (4-trifluoromethylphenyl) -3- [N- [1-methyl-1- (2-pyridyl) ethyl] carbamoyl] -2-sulfamoylpyrazolo [1 , 5-a] pyrimidine;
6- (2-chlorophenyl) -3- [N- (3-methoxyprop-2-yl) carbamoyl] -7- (4-methylphenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine;
6- (2-Chlorophenyl) -3- [N- (2,2,2-trifluoroethyl) carbamoyl] -7- (4-methylphenyl) -2-sulfamoylpyrazolo [1,5-a] Pyrimidine;
6- (2-chlorophenyl) -3- [N- (isobutyl) carbamoyl] -7- (4-methylphenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine; and 6- (2- A compound selected from chlorophenyl) -3- [N-cyclopentylcarbamoyl] -7- (4-methylphenyl) -2-sulfamoylpyrazolo [1,5-a] pyrimidine, or a pharmaceutically acceptable salt thereof.