JPH0632734A - Therapeutic agent for thrombocytopenia and optically active pyrazolopyridine compound - Google Patents

Abstract

PURPOSE:To obtain a therapeutic agent for thrombocytopenia comprising a condensation type pyrazole compound containing a partially new optically active substance, its optical isomer or its pharmaceutically permissible salt as an active ingredient. CONSTITUTION:This therapeutic agent for thrombocytopenia comprises a condensation type pyrazole compound of formula I [X is N or CH; R is H, alkyl, alkoxy or halogen; Y<1> is group of formula II or phenyl; Y<2> is group of formula III (A<1> and A<2> are alkylene; B<1> and B<2> are carboxyl, alkoxycarbonyl, phenylalkoxycarbonyl, etc.; Z<1> and Z<2> are O, S, etc.; L<1> and L<2> are H, halogen, alkyl or alkoxy)], its optical isomer or its pharmaceutically permissible salt as an active ingredient. (+)-3-[4-(2-Dimethylamino-1-methylethoxy)phenyl]-1H- pyrazolo[3,4-b]pyridine-1-acetic acid, its ester or its pharmaceutically permissible salt is a new compound.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a medicine, especially a therapeutic agent for reducing the number of platelets and an optically active pyrazolopyridine compound.

[0002]

2. Description of the Related Art Most cancer patients are treated with chemotherapy such as anticancer drugs and radiation. However, heavy use of anticancer agents causes side effects such as blood disorders, which has become a problem in the medical field. In recent years, therapeutic agents for leukopenia such as human granulocyte colony stimulating factor have been marketed, and it has become possible to restore the white blood cell count to a normal level. In addition, in cases where platelets are destroyed by antibodies, such as idiopathic thrombocytopenic purpura, it is possible to indirectly recover the platelet count by administering an adrenocortical hormone that has a function of suppressing antibody production. Has been done. However, since an effective drug for directly recovering the decrease in the number of platelets, which is a cause of bleeding, etc., has not been marketed yet, it is the current situation that component transfusion of platelets is exclusively performed. On the other hand, Japanese Unexamined Patent Publication (Kokai) No. 2-85258 discloses a condensed pyrazole compound having a leukocyte number recovering ability or a pharmaceutically acceptable salt thereof.

[0003]

[Problems to be Solved by the Invention] Platelet transfusion has a limited supply amount of fresh platelets. Further, in terms of safety, there is a risk that various viruses are mixed in blood and this virus triggers exposure to new infection. There is a continuing need for the development of drugs that restore the platelet count.

[0004]

[Means for Solving the Problems] The inventors of the present invention have conducted diligent research in order to solve the above-mentioned problems.
It was found that the compound disclosed in Japanese Patent No. 5258 and a novel optically active substance thereof also promote recovery of platelet number, and have completed the present invention.

That is, the present invention provides (1) general formula

[0006]

[Chemical 8]

[Wherein, X is ═N— or ═CH—, R represents hydrogen, an alkyl group, an alkoxy group, or halogen, and Y ¹ is a formula:

[0008]

[Chemical 9]

Represents a group represented by phenyl, or phenyl substituted by 1 to 3 halogens, alkyl groups or alkoxy groups. Y ² is the formula:

[0010]

[Chemical 10]

A group represented by the formula: a group represented by the formula: --A ² --B ² , hydrogen, an alkyl group, a phenylalkyl group, and a phenyl nucleus substituted with 1 to 3 halogen, alkyl group or alkoxy group. And a phenylalkyl group, a phenyl group or a phenyl group substituted by 1 to 3 halogen, an alkyl group or an alkoxy group, an alkoxyalkyl group, a hydroxyalkyl group, an alkoxycarbonylalkyl group, a carboxyalkyl group and an acyloxyalkyl group. However, of Y ¹ and Y ² ,
Either or both are expressions:

[0012]

[Chemical 11]

Or the formula:

[0014]

[Chemical 12]

Is a group represented by here,
Z ¹ and Z ² are the same or different and each represents —O—, —S— or —NR ³ — (wherein R ³ represents hydrogen or an alkyl group), and A ¹ and A ² are the same or different. Represents an alkylene group, and B ¹ and B ² are the same or different and are a carboxyl group, an alkoxycarbonyl group, a phenylalkoxycarbonyl group (the phenyl may be substituted with 1 to 3 halogen, alkyl group or alkoxy group) , An acyl group, a hydroxyl group, an acyloxy group or a formula:

[0016]

[Chemical 13]

Or

[0018]

[Chemical 14]

(Here, R ¹ and R ² are the same or different and each is hydrogen, an alkyl group, a dialkylaminoalkyl group or a hydroxyalkyl group, or R ¹ and R ² form a heterocycle with the adjacent nitrogen atom. A group represented by L ¹ and L ² are the same or different and each represents hydrogen, halogen, an alkyl group or an alkoxy group. ] A condensed pyrazole compound represented by the following, a therapeutic agent for thrombocytopenia containing an optical isomer thereof or a pharmaceutically acceptable salt thereof as an active ingredient,

(2) (+)-3- [4- (2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid and its ethyl ester or those A therapeutic agent for thrombocytopenia containing a pharmaceutically acceptable salt of

(3) (+)-3- [4- (2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid and its ethyl ester or its It relates to a pharmaceutically acceptable salt.

In the present specification, the halogen means chlorine, bromine, fluorine and iodine, and the alkyl group has 1 to 1 carbon atoms.
8 straight or branched alkyl, meaning methyl,
Examples thereof include ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, isopentyl and hexyl. The alkoxy group means a linear or branched alkoxy having 1 to 8 carbon atoms, and is methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tertiary butoxy, pentyloxy, isopentyloxy, hexyloxy. And so on. The alkylene group means a linear or branched alkylene having 1 to 8 carbon atoms, methylene, ethylene, 1,1-dimethylethylene, trimethylene, propylene, 2-methyltrimethylene, 2-ethyltrimethylene. , Tetramethylene, pentamethylene, heptamethylene and the like. Phenylalkyl group has 1 carbon atom
~ 4 straight chain or branched alkyl, benzyl, 1-phenylethyl, 2-phenylethyl, 3-
Phenylpropyl, 4-phenylbutyl, etc., and 1 to 3 halogen groups on their phenyl rings,
It may be substituted with a linear or branched alkyl group having 1 to 8 carbon atoms or a linear or branched alkoxy group having 1 to 8 carbon atoms. The alkoxyalkyl group is a linear or branched alkoxy or alkyl group having 1 to 4 carbon atoms, and the alkoxy group and the alkyl group are 2-methoxyethyl, 2-ethoxyethyl, 3-
Methoxypropyl, 3-ethoxypropyl, methoxymethyl, 4-ethoxybutyl and the like can be mentioned. The hydroxyalkyl group is a linear or branched alkyl group having 1 to 4 carbon atoms, and is 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 2-hydroxy-1-. Methyl ethyl, 2,3-dihydroxypropyl and the like can be mentioned.

The alkoxycarbonylalkyl group has an alkoxy group and an alkyl group each having 1 to 4 carbon atoms.
A straight-chain or branched alkoxy and alkyl, such as methoxycarbonylmethyl, ethoxycarbonylmethyl, 2-methoxycarbonylethyl, 3-ethoxycarbonylpropyl and the like. The carboxyalkyl group is a linear or branched alkyl group having 1 to 4 carbon atoms, which is carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3
-Examples include carboxypropyl. The acyloxyalkyl group is a straight-chain or branched alkanoyl having 2 to 5 carbon atoms or benzoyl.
The alkyl group is a linear or branched alkyl group having 1 to 4 carbon atoms, and examples thereof include 2-acetyloxyethyl, 3-acetyloxypropyl, 1-benzoyloxymethyl and the like. The dialkylaminoalkyl group is a linear or branched alkyl group having 1 to 4 carbon atoms, each of which is 2-dimethylaminoethyl, 2-diethylaminoethyl, 3-dimethylaminopropyl, 3-
Examples include diethylaminopropyl. The alkoxycarbonyl group is a straight-chain or branched alkoxy group having 1 to 4 carbon atoms, which is methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
Isopropoxycarbonyl, butoxycarbonyl, third
Examples include butoxycarbonyl and the like. The phenylalkoxycarbonyl group is an alkoxy group having 1 to 1 carbon atoms.
It is four linear or branched alkoxy and includes benzyloxycarbonyl, 2-phenylethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl and the like. The acyl group is a linear or branched alkanoyl having 2 to 5 carbon atoms (acetyl, propionyl, butyryl, pivaloyl, valeryl etc.) or benzoyl.

The acyloxy group is a straight-chain or branched alkanoyl or benzoyl having 2 to 5 carbon atoms, and examples thereof include acetoxy, propionyloxy, butyryloxy, pivaloyloxy, valeryloxy and benzoyloxy. The heterocycle formed by combining R ¹ and R ² with the adjacent nitrogen atom has at least one nitrogen, oxygen or sulfur which may be substituted with an alkyl group or a hydroxyalkyl group as a hetero atom. 5-7 membered ring which may be
Pyrrolidinyl, piperidino, 1-piperazinyl, 4-methyl-1-piperazinyl, morpholino, thiomorpholino, 4-ethyl-1-piperazinyl, 4- (2-hydroxyethyl) -1-piperazinyl, 1-homopiperazinyl, 4-methyl- 1-homopiperazinyl, 2-oxo-
1-pyrrolidinyl and the like can be mentioned.

Pharmaceutically acceptable salts of the compounds of general formula (I) are hydrochlorides, sulphates, hydrobromides, phosphates, formates, acetates, fumarates, maleates, citrates. Acid salt,
Acid addition salts such as tartrate, malate, mandelate, methanesulfonate, toluenesulfonate, metal salts such as sodium salt, potassium salt, lithium salt, magnesium salt, calcium salt, ammonium salt, triethylamine salt Examples thereof include salts with amino acids such as amine salts (including quaternary ammonium salts), arginine salts, lysine salts, ornithine salts and the like. In addition, hydrates (monohydrate, hemihydrate, 3/2 hydrate, etc.) and other solvates are also included in the present invention.

The compounds of the present invention contained in the general formula (I) include the compounds shown below.

1- [4- (3-Dimethylaminopropoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 133-
136 ° C ◎ 3- (4-Bromophenyl) -1- [4- (2-diethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 135-
140 ° C. ◎ 1- [3- (3-Dimethylamino-2-methylpropoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 134-
136 ° C. ◎ 3- [4- (3-dimethylaminopropoxy) phenyl] -1- (4-methylphenyl) -1H-pyrazolo [3,4-b] pyridine maleate, melting point 138-
140 ° C ◎ 3- (4-fluorophenyl) -1- [3- (3-
Dimethylaminopropoxy) phenyl] -1H-indazole maleate, melting point 110-112 ° C

◎ N, N-diethyl-3- [3- (4-
Fluorophenyl) -1H-pyrazolo [3,4-b] pyridin-1-yl] phenoxyacetic acid amide, melting point 102
~ 105 ° C ◎ 1- [4- (2-dimethylaminoethoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 123-126 ° C ◎ 1- [4- (4-Dimethylaminobutoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 112-115 ° C. 1- [4- (2-diethylaminoethoxy) phenyl]- 3-Phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 110-115 ° C. ◎ 1- [4- (3-dimethylamino-2-methylpropoxy) phenyl] -3-phenyl-1H -Pyrazolo [3,4-b] pyridine maleate, melting point 143-
146 ° C

◎ 3- (4-chlorophenyl) -1-
[4- (3-dimethylaminopropoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine maleate, melting point 162-165 ° C. ◎ 3- (4-bromophenyl) -1- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [ 3,4-b] Pyridine maleate, melting point 162-
165 ° C. ◎ 1- [3- (2-dimethylaminoethoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine dimaleate, melting point 117-120 ° C. ◎ 1- [3- (3-Dimethylaminopropoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b]
Pyridine maleate, melting point 120-123 ° C ◎ 1- [3- (2-morpholinoethoxy) phenyl]
-3-Phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 140-142 ° C

◎ 3- (4-chlorophenyl) -1-
[3- (2-dimethylaminoethoxy) phenyl] -1
H-pyrazolo [3,4-b] pyridine maleate,
Melting point 140-143 ° C ◎ 1- [2- (2-dimethylaminoethoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 153-157 ° C ◎ 1- [ 2- (3-Dimethylaminopropoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b]
Pyridine maleate, melting point 123-125 ° C ◎ 3- (4-fluorophenyl) -1- [3- (2-
Piperidinoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 149-
151 ° C. ◎ 3- (4-fluorophenyl) -1- [3- (3-
Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate hemihydrate, melting point 102-105 ° C

◎ 3- (4-chlorophenyl) -1-
[3- (3-dimethylamino-2-methylpropoxy)
Phenyl] -1H-pyrazolo [3,4-b] pyridine
Maleate, melting point 150-152 ° C. 1- [3- (2-diethylaminoethoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate hemihydrate , Melting point 86-90
° C ◎ 3- (4-fluorophenyl) -1- [3- (3-
Piperidinopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine fumarate, mp 73-75
° C ◎ 3- (4-fluorophenyl) -1- [3- (3-
Dimethylamino-2-methylpropoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine maleate hemihydrate, melting point 128 to 130 ° C. ◎ 3- (4-fluorophenyl) -1- [3- (3-
Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 110
~ 112 ℃

◎ 3- (4-chlorophenyl) -1-
[3- (3-Dimethylaminopropoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine fumarate,
Mp 170-172 ° C ◎ 1- [3- (4-dimethylaminobutoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine fumarate monohydrate, mp 140-143 ° C ◎ 3- [4- (3-dimethylaminopropoxy) phenyl] -1-phenyl-1H-pyrazolo [3,4-b]
Pyridine maleate, melting point 132-135 ° C ◎ 3- [4- (2-dimethylaminoethoxy) phenyl] -1-phenyl-1H-pyrazolo [3,4-b] pyridine maleate, melting point 137- 141 ° C ◎ 4- {3- [3- (4-fluorophenyl) -1H
-Pyrazolo [3,4-b] pyridin-1-yl] phenoxyacetyl} morpholine, melting point 141-143 ° C.

◎ 1- (4-methylphenyl) -3-
[4- (3-dimethylamino-2-methylpropoxy)
Phenyl] -1H-pyrazolo [3,4-b] pyridine
Maleate, melting point 170-171 ° C ◎ 1-methyl-3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 128-129 ° C. ◎ 6-methyl-1- [3- (3-dimethylamino-2
-Methylpropoxy) phenyl] -3-phenyl-1H
-Pyrazolo [3,4-b] pyridine maleate, melting point 123-125 ° C 1- [3- (3-dimethylamino-2-methylpropoxy) phenyl] -3-phenyl-1H-indazole maleic acid Salt / 2/5 ethyl acetate solvate, melting point 58-
63 ° C. 1- [4- (3-hydroxypropoxy) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine, melting point 135-138 ° C.

◎ N- (2-dimethylaminoethyl)-
4- (1-phenyl-1H-pyrazolo [3,4-b] pyridin-3-yl) phenoxyacetic acid amide maleate, melting point 169-171 ° C. N- (2-hydroxyethyl) -3- [3 -(4-
Fluorophenyl) -1H-pyrazolo [3,4-b] pyridin-1-yl] phenoxyacetic acid amide, melting point 161
~ 163 ° C ◎ N- (2-diethylaminoethyl) -3- [3-
(4-Fluorophenyl) -1H-pyrazolo [3,4-
b] pyridin-1-yl) phenoxyacetic acid amide, melting point 137-138 ° C. ◎ 1- {3- [3- (4-fluorophenyl) -1H
-Pyrazolo [3,4-b] pyridin-1-yl] phenoxyacetyl} -4-methylpiperazine, melting point 132-
135 ° C. N- (2-diethylaminoethyl) -4- (1-phenyl-1H-pyrazolo [3,4-b] pyridine-3-
Il) Phenoxyacetic acid amide fumarate, melting point 152
~ 154 ° C

4-methyl-1- [4- (1-phenyl-1H-pyrazolo [3,4-b] pyridin-3-yl) phenoxyacetyl] piperazine maleate,
Mp 187-189 ° C ◎ 3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, melting point 176-177 ° C ◎ 3- [4- (2-dimethylaminoethyl) Amino) phenyl] -1H-pyrazolo [3,4-b] pyridine, melting point 165 to 167 ° C. ◎ 1-methyl-3- [4- (2-dimethylaminoethylamino) phenyl] -1H-pyrazolo [3,4] -B]
Pyridine maleate, melting point 88-90 ° C ◎ 3- [4- (2-dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, melting point 1
32-134 ° C

◎ 1- (4-chlorobenzyl) -3-
[4- (3-dimethylaminopropoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine maleate, melting point 136-138 ° C. ◎ 3- [4- (2-dimethylaminoethoxy) phenyl] -1- (2-methoxyethyl) -1H-pyrazolo [ 3,4-b] Pyridine maleate, melting point 115-
117 ° C. N, N-dimethyl-3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-
b] Pyridin-1-yl acetic acid amide maleate, melting point 165 to 167 ° C. ◎ 1- (2,4-dichlorobenzyl) -3- [4-
(2-Dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 1
36-138 ° C ◎ 1-Butyl-3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine maleate, melting point 112-113 ° C.

3- [4- (3-Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate maleate, melting point 108-
110 ° C. ◎ 1-acetonitrile-3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4]
-B] Pyridine maleate, melting point 119 to 121 ° C ◎ 1- (4-fluorophenacyl) -3- [4- (3
-Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine / 3/2 fumarate, mp 165-169 ° C 1- (2-chlorobenzyl) -3- [4- (2- Dimethylaminoethylamino) phenyl] -1H-pyrazolo [3,4-b] pyridine fumarate, mp 155-
157 ° C. ◎ 1- (2-dimethylaminoethyl) -3- [4-
(2-Dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine dimaleate, melting point 96-98 ° C

1- [3- (3-Dimethylaminopropoxy) phenyl] -3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-
b] Pyridine difumarate, melting point 145 to 148 ° C. ◎ 1- (3-dimethylaminopropyl) -3- [4-
(3-Dimethylaminopropoxy) phenyl] -1H-
Pyrazolo [3,4-b] pyridine dimaleate, melting point 127-130 ° C ◎ 1- [3- (2-dimethylaminoethoxy) phenyl] -3- [4- (2-dimethylaminoethoxy) phenyl] -1H-Pyrazolo [3,4-b] pyridine difumarate, melting point 115-118 ° C ◎ 1- (4-methylphenyl) -3- [4- (2-dimethylamino-1-methylethoxy) phenyl ] -1H
-Pyrazolo [3,4-b] pyridine maleate, melting point 139-140 ° C ◎ 6-methyl-1- (4-methylphenyl) -3-
[4- (3-dimethylaminopropoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine

6-Methyl-1- (4-methylphenyl) -3- [4- (3-dimethylamino-2-methylpropoxy) phenyl] -1H-pyrazolo [3,4-b]
Pyridine ◎ 1- (3-methylphenyl) -3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine ◎ 1- (3-methylphenyl) -3- [ 4- (3-Dimethylamino-2-methylpropoxy) phenyl] -1
H-pyrazolo [3,4-b] pyridine ◎ 1- (2-methylphenyl) -3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine ◎ 1- (2-Methylphenyl) -3- [4- (3-dimethylamino-2-methylpropoxy) phenyl] -1
H-pyrazolo [3,4-b] pyridine

◎ 1- [3- (2-dimethylamino-1
-Methylethoxy) phenyl] -3-phenyl-1H-
Pyrazolo [3,4-b] pyridine maleate, melting point 118-120 ° C ◎ 2- (4-methylphenyl) -3- [4- (2-dimethylamino-2-methylethoxy) phenyl] -1H
-Pyrazolo [3,4-b] pyridine maleate, melting point 126-128 ° C 1- [3- (2-dimethylamino-2-methylethoxy) phenyl] -3-phenyl-1H-pyrazolo [3,3] 4-b] pyridine-3 / 2 fumarate, melting point 13
9-142 ° C ◎ 3- (4-fluorophenyl) -1- [3- (2-
Dimethylamino-1-methylethoxy) phenyl] -1
H-pyrazolo [3,4-b] pyridine fumarate, melting point 148-149 ° C ◎ 3- (4-fluorophenyl) -1- [3- (2-
Dimethylamino-2-methylethoxy) phenyl] -1
H-pyrazolo [3,4-b] pyridine / 3/2 fumarate, mp 174-176 ° C

◎ 3- (4-chlorophenyl) -1-
[3- (2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine fumarate, melting point 150-152 ° C ◎ 3- (4-chlorophenyl) -1- [ 3- (2-Dimethylamino-2-methylethoxy) phenyl] -1H
-Pyrazolo [3,4-b] pyridine / 3/2 fumarate, mp 148-150 ° C ◎ 1- [3- (3-dimethylamino-2-methylpropoxy) phenyl] -1-phenyl-1H-pyrazolo [3,4-b] Pyridine maleate salt / 2/5 ethyl acetate solvate, melting point 58-60 ° C ◎ 1- (2-hydroxyethyl) -3- [4- (3-
Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine.1 / 2 fumarate, melting point 1
62-163 ° C ◎ 1- (2-acetoxyethyl) -3- [4- (3-
Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine fumarate, melting point 122-
124 ° C

N-Methyl-3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridin-1-ylacetic acid amide difumarate, mp 102-105 ° C ◎ 6- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridin-1-yl} methyl hexanoate, NMR (CDCl ₃ ) δ: 1.33-2.70 (m, 12H), 2.24 (s, 6H), 3.60
(s, 3H), 4.07 (t, 2H), 4.53 (t, 2H), 6.93-8.51 (7H) ◎ 3- [4- (2-dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4- b] Pyridine-1-ethyl acetate maleate, melting point 138-140 ° C. ◎ 4- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1 -Yl} ethyl butyrate difumarate, melting point 121
˜124 ° C. ◎ 3- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridin-1-yl} propionate ethyl fumarate, melting point 105-107 ℃

2-Methyl-2- {3- [4- (3-
Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridin-1-yl} propionate ethyl, NMR (CDCl ₃ ) δ: 1.10 (t, 3H), 2.03 (s, 6H), 1.96- 2.40 (m,
2H), 2.30 (s, 6H), 2.52 (t, 2H), 4.01 (t, 2H), 4.12 (q, 2
H), 6.98-8.51 (7H) ◎ 3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate, NMR (CDCl ₃ ) δ: 1.25 (t, 3H), 1.33 (d, 3H), 2.33 (s, 6H),
2.34-2.78 (m, 2H), 4.21 (q, 2H), 4.55 (q, 1H), 5.26 (s, 2
H), 6.98 to 8.51 (7H) ◎ 4- (1-phenyl-1H-pyrazolo [3,4-
b] Pyridin-3-yl) phenoxyethyl acetate, melting point 118-120 ° C ◎ 4- (1-phenyl-1H-pyrazolo [3,4-
b] Pyridin-3-yl) phenoxyacetic acid, melting point 220
~ 222 ° C ◎ 3- [3- (4-fluorophenyl) -1H-pyrazolo [3,4-b] pyridin-1-yl] phenoxyacetate ethyl, melting point 130-131 ° C.

◎ 3- [3- (4-fluorophenyl)
-1H-Pyrazolo [3,4-b] pyridin-1-yl]
Phenoxyacetic acid, melting point 225-226 ° C ◎ 4- (3-phenyl-1H-pyrazolo [3,4-
b] Pyridin-1-yl) phenoxyethyl acetate ◎ 4- (3-phenyl-1H-pyrazolo [3,4-
b] pyridin-1-yl) phenoxyacetic acid ◎ 3- [4- (3-dimethylaminopropoxy) phenyl] -1-propionyl-1H-pyrazolo [3,4-
b] Pyridine / 3/2 fumarate, melting point 155-157
° C ◎ 3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-
Acetic acid, melting point 221-223 ° C

◎ 3- [4- (3-Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid, melting point 221-223 ° C ◎ 3- [4- (2-dimethyl Amino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, melting point 130-132 ° C ◎ 3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate NMR (CDCl ₃ ) δ: 1.25 (t, 3H), 1.33 (d, 3H), 2.33 (s, 6H),
2.34-2.78 (m, 2H), 4.21 (q, 2H), 4.55 (q, 1H), 5.26 (s, 2
H), 6.98 to 8.51 (7H) ◎ 3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid, melting point 210-211 ° C. ◎ 2-methyl-2- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-
b] Pyridin-1-yl} propionic acid, melting point 187-
190 ° C

3- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-
b] Pyridin-1-yl} propionic acid hemihydrate, melting point 86 to 90 ° C. ◎ 6- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4- b] pyridin-1-yl} hexanoic acid, melting point 96 to 100 ° C. ◎ 3- [4- (2-dimethylaminoethylamino) phenyl] -1H-pyrazolo [3,4-b] pyridine-1
-Acetic acid NMR (CDCl ₃ ) δ: 1.20 (t, 3H), 2.40 (s, 6H), 2.56 (t, 2H),
3.20 (t, 2H), 4.20 (q, 2H), 5.30 (s, 2H), 6.63 to 8.56 (7H) ◎ 3- [4- (2-dimethylaminoethylamino) phenyl] -1H-pyrazolo [3. 4-b] pyridine-1
-Acetic acid, melting point 240-242 ° C ◎ 3-phenyl-1- (4-trifluoroacetylaminophenyl) -1H-pyrazolo [3,4-b] pyridine, melting point 172-174 ° C.

1- [4- (2-dimethylaminoethylamino) phenyl] -3-phenyl-1H-pyrazolo [3,4-b] pyridine maleate hemihydrate, melting point 80- 88 ° C ◎ 1- [4- (3-dimethylaminopropylamino)
Phenyl] -3-phenyl-1H-pyrazolo [3,4-
b] Pyridine dimaleate, melting point 145-146 ° C

In the general formula (I), a compound in which X is ═N— and / or at least one of Z ¹ and Z ² is oxygen is preferable. The following compounds are exemplified as more preferable compounds of the compound of the general formula (I) and pharmaceutically acceptable salts thereof.

◎ 3- [4- (2-dimethylamino-1
-Methylethoxy) phenyl] -1H-pyrazolo [3,3
4-b] pyridine-1-acetic acid, ◎ 3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate, ◎ 3- [4- (3-Dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-
Acetic acid, ◎ 3- [4- (2-dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate, ◎ 1- [4- (3-dimethylaminopropoxy) phenyl] -3-Phenyl-1H-pyrazolo [3,4-b]
Pyridine,

◎ 1- [3- (3-dimethylamino-2
-Methylpropoxy) phenyl] -3-phenyl-1H
-Pyrazolo [3,4-b] pyridine, ◎ 1- (4-methylphenyl) -3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, ◎ 1 -[3- (2-Dimethylaminoethoxy) phenyl] -3- [4- (2-dimethylaminoethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, ◎ N- (2-diethylaminoethyl) -3- [3-
(4-Fluorophenyl) -1H-pyrazolo [3,4-
b] pyridin-1-yl] phenoxyacetic acid amide and ◎ 3- {3- [4- (3-dimethylaminopropoxy) phenyl] -1H-pyrazolo [3,4-b] pyridin-1-yl} propionic acid and Its optical isomer,
Or a pharmaceutically acceptable salt thereof.

Most of the compounds (I) used in the present invention are produced by the method described in JP-A-2-85258, which is incorporated herein by reference. The optical isomer can be obtained by using an optically active raw material or optically resolving the obtained racemate. In order to achieve the object of the present invention, as an active ingredient compound, 3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-
b] Pyridine-1-acetic acid and its ethyl ester, their optically active forms or their pharmaceutically acceptable salts are preferred. Further, a novel (+)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] compound is useful as a compound useful for achieving the object of the present invention. Pyridine-1-acetic acid and its ethyl ester or their pharmaceutically acceptable salts are mentioned. These optically active substances can be produced by the following methods. That is, optically active (+)-1-dimethylamino-2-propanol and, for example, 2-chloro-3- (4-fluorobenzoyl) pyridine, which are known from JP-B-49-19252, are added to benzene, toluene, xylene, Pyridine, ethanol, isopropyl alcohol,
Deoxidizing agent such as sodium hydroxide, sodium hydride, potassium hydride, sodium hydrogen carbonate, sodium carbonate, potassium carbonate, triethylamine, etc. in a solvent inert to the reaction such as ethylene glycol dimethyl ether, dimethylformamide, dioxane, etc. 0 to
By reacting at a temperature of 250 ° C., (+)-2-chloro-3- [4- (2-dimethylamino-1-methylethoxy) benzoyl] pyridine was obtained, and then the above compound and hydrazine hydrate were added to benzene. , Toluene, xylene,
Dioxane, diethylene glycol dimethyl ether,
(+)-3 by refluxing in a suitable solvent such as pyridine with a suitable dehydrating agent or deoxidizing agent as necessary.
-[4- (2-Dimethylamino-1-methylethoxy)
Phenyl] -1H-pyrazolo [3,4-b] pyridine is obtained. The obtained pyrazolo [3,4-b] pyridine compound and ethyl chloroacetate were mixed with benzene, toluene, xylene, dimethylformamide, pyridine, chloroform,
Deoxidizing agent such as sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, sodium carbonate, potassium carbonate, triethylamine, etc. in a solvent inert to the reaction such as dichloromethane, dichloroethane, methanol, ethanol, etc. And reacting at a temperature of 0 to 250 ° C. to give (+)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine- 1-Ethyl acetate is obtained. Further, by hydrolyzing the above ethyl acetate compound in the presence of an acid or an alkali, (+)-3- [4
It can be-(2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid. 3-obtained in this way
[4- (2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1
-Acetic acid and its ethyl ester are inorganic materials such as hydrochloric acid, sulfuric acid, hydrobromic acid, phosphoric acid, formic acid, acetic acid, fumaric acid, maleic acid, citric acid, tartaric acid, malic acid, mandelic acid, methanesulfonic acid and toluenesulfonic acid. The corresponding acid addition salt can be obtained by treating with an acid or an organic acid by a conventional method.

In producing the drug of the present invention, the compound is preferably contained in a therapeutically effective amount, and the drug contains, in addition to these active ingredients, a pharmaceutically acceptable carrier, excipient, By mixing with diluents, solubilizers, disintegrants, binders, etc., to prepare tablets, powders, capsules, injections, suppositories, drops, etc., which can be safely administered orally or parenterally to patients. be able to. The dose is usually 2.5 to 100 mg by oral administration and 0.5 to 20 mg by intravenous administration to an adult per day. In particular, (+)-3
-[4- (2-Dimethylamino-1-methylethoxy)
Phenyl] -1H-pyrazolo [3,4-b] pyridine-
1-Acetic acid ethyl ester has a good absorption rate by oral administration, has a high bioavailability, and can be applied as an oral preparation.

[0053]

ACTION AND EFFECT OF THE INVENTION The compound of the general formula (I) and the specific optically active compound of the present invention have an action of recovering the number of platelets, unlike the adrenocortical hormone. Therefore, the pharmaceutical agent of the present invention is useful as a drug for promoting recovery of platelet number reduction due to bone marrow transplantation, anticancer agent, or irradiation, and idiopathic thrombocytopenic purpura, myelodysplastic syndrome, or congenital / idiopathic favorable. Used to prevent or treat hematopoietic disorders or hematopoietic disorders such as neutropenia.

[0054]

EXAMPLES The present invention will be described in more detail below with reference to examples, pharmaceutical formulation examples and experimental examples, but it goes without saying that the present invention is not limited thereto.

Example 1 (1) 60 ml of sodium hydride 60% in 150 ml of toluene
7 g is suspended, and a mixed liquid of 200 ml of toluene containing 75 g of (+)-1-dimethylamino-2-propanol is added to 50-
Add dropwise at 60 ° C. This was cooled, 200 ml of dimethylformamide was added, and 2-chloro-3 was added at -10 to -5 ° C.
182 g of-(4-fluorobenzoyl) pyridine is added in several times. It takes 3 hours and the temperature gradually increases to 40 ° C.
The reaction is completed by raising the temperature to 40 ° C. and further heating and stirring at 40 ° C. for 2 hours. Water is added, the toluene layer is separated and washed with water. The toluene layer is extracted with diluted hydrochloric acid.
The extract is made alkaline with potassium carbonate and the liberated oil is extracted with toluene. If toluene is distilled off, crude (+)-2-chloro-3- [4- (2-dimethylamino-1-methylethoxy) benzoyl] pyridine 190 will be obtained.
g is obtained as an oil.

(2) 190 g of the above crude product, 60 pyridine
0 ml and 92 g of hydrazine hydrate are refluxed and stirred for 12 hours. Pyridine was distilled off, and toluene was added to the residue 500 m.
1 is added and heated to 40 to 50 ° C. to dissolve. Wash with warm water and evaporate toluene. The residue was crystallized by adding isopropyl ether, filtered, and recrystallized from a mixed solution of isopropyl ether and isopropyl alcohol to obtain (+)-3- [4- (2-
Dimethylamino-1-methylethoxy) phenyl] -1
100.7 g of H-pyrazolo [3,4-b] pyridine are obtained. [Α] _D ²³ = + 15.3 ° (1%, methanol)

(3) 2.7 g of 60% sodium hydride was suspended in 46 ml of toluene, 31 ml of dimethylformamide was added under ice cooling, and then (+)-3- [4- (2
-Dimethylamino-1-methylethoxy) phenyl]-
18 g of 1H-pyrazolo [3,4-b] pyridine was added to 2-3
Put in dividedly. After stirring for 15 minutes, a mixed solution of 8.2 g of ethyl chloroacetate and 16 ml of toluene was added dropwise, and the mixture was reacted at room temperature for 1 hour and at 40 ° C. for 1 hour. After cooling, water is added and the toluene layer is collected, washed with water and dried. If toluene is distilled off, crude (+)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-ethyl acetate 20. 8 g are obtained as an oil.

(4) Crude (+)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H
-Pyrazolo [3,4-b] pyridine-1-ethyl acetate 2
0.8 g is dissolved in 150 ml of ethyl acetate, and 13 g of 15% hydrochloric acid-ethanol solution is added to give a hydrochloride. When the produced crystals were produced from a mixed solution of ethyl acetate-ethanol, (+)-3- [4- (2-
Dimethylamino-1-methylethoxy) phenyl] -1
17.2 g of H-pyrazolo [3,4-b] pyridine-1-ethyl acetate / hydrochloride is obtained. [Α] _D ²⁵ = + 16.1 °
(1%, ethanol)

Example 2 20.8 g of the crude product of Example 1 (3) above was added to methanol 4
Dissolved in 3 ml, sodium hydroxide 2.4 g, water 21 m
1 solution is added and stirred at room temperature for 1 hour. P with diluted hydrochloric acid
After adjusting to H7 and distilling off methanol, the residue is purified using DIAION PH-20. After being recrystallized from water-containing isopropyl alcohol (including water of crystallization), ethanol was added and heated to obtain (+)-3 with a melting point of 212 to 213 ° C.
-[4- (2-Dimethylamino-1-methylethoxy)
Phenyl] -1H-pyrazolo [3,4-b] pyridine-
1-acetic acid is obtained. [Α] _D ²² = + 25.7 ° (1%, methanol)

Example 3 (1) When (-)-1-dimethylamino-2-propanol was used to carry out the reaction treatment in the same manner as in (1) and (2) of Example 1, a melting point of 125-127 ° C. -)-3- [4- (2
-Dimethylamino-1-methylethoxy) phenyl]-
1H-pyrazolo [3,4-b] pyridine is obtained. [Α]
_D ²³ = -15.0 ° (1%, methanol)

(2) Using (-)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine, (3) of Example 1
If the reaction treatment is performed in the same manner as in Example 2, the melting point of 212 to
(-)-3- [4- (2-dimethylamino-
1-Methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid is obtained. [Α] _D ²³
= -25.0 ° (1%, methanol)

In the following formulation examples and experimental examples, compound A, compound B and compound C are as follows.

Compound A = (±) -3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-
Pyrazolo [3,4-b] pyridine-1-acetic acid

Compound B = (+)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-
Pyrazolo [3,4-b] pyridine-1-acetic acid

Compound C = (+)-3- [4- (2-dimethylamino-1-methylethoxy) phenyl] -1H-
Pyrazolo [3,4-b] pyridine-1-ethyl acetate / hydrochloride

Formulation Example 1

10 g of compound A and 9 g of sodium chloride
Is dissolved in 10 liters of water for injection, and after sterile filtration, 10 m
Take l, fill an ampoule, seal, and sterilize under high pressure steam to obtain an injection.

Formulation Example 2

An injection containing Compound B is produced in the same manner as in Production Formulation Example 1 using Compound B.

Formulation formulation example 3

Compound C (50 mg) is sufficiently kneaded with lactose (98 mg), corn starch (45 mg) and hydroxypropyl cellulose (3 mg) in a kneader. 200 kneaded products
Pass through a mesh screen, dry at 50 ° C, and then pass through a 24 mesh screen. Mix with 3 mg of talc and 1 mg of magnesium stearate and obtain a tablet with a weight of 200 mg using a 9 mm diameter punch. The tablets can be sugar-coated or film-coated, if necessary.

Experimental Example 1: Effect of promoting recovery of platelet count in bone marrow transplanted mice

Six to eight-week-old ICR mice were systemically irradiated with 8.0 Gy of radiation and then transplanted with 10 ⁷ syngeneic mouse bone marrow cells. Compound A or compound B was continuously administered intravenously for 9 days from the day after bone marrow transplantation. On day 11 after bone marrow transplantation, heparinized blood was collected from the mouse abdominal aorta, and the platelet count was measured by an automatic hemocytometer. The experiment was conducted with 5 animals per group.

[0074]

[Table 1] Table 1 ──────────────────────────────────── Pretreatment Subject Dose Platelet count ( mg / kg) (10 ⁴ / mm ³ ) ──────────────────────────────────── X-ray irradiation Only − 0 6.7 ± 2.9 X-ray irradiation + bone marrow transplant − 0 16.2 ± 4.4 X-ray irradiation + bone marrow transplant Compound A 0.01 27.4 ± 9.6 X-ray irradiation + bone marrow transplant Compound A 0.03 31.4 ± 11.4 X-ray irradiation + bone marrow transplant Compound A 0.1 42.3 ± 10.6 X-ray irradiation + bone marrow transplant Compound A 0.3 49.8 ± 9.7 No treatment − 0 53.0 ± 17.9 ──────────────────────────── ────────

As is clear from Table 1, it was found that administration of compound A to bone marrow-transplanted mice restored the platelet count to almost normal levels.

[0076]

[Table 2] Table 2 ──────────────────────────────────── Pretreatment Subject Dose Platelet count ( mg / kg) (10 ⁴ / mm ³ ) ──────────────────────────────────── X-ray irradiation Only − 0 5.1 ± 1.2 X-ray irradiation + bone marrow transplant − 0 9.4 ± 3.4 X-ray irradiation + bone marrow transplant Compound B 0.01 45.9 ± 6.7 X-ray irradiation + bone marrow transplant Compound B 0.03 54.8 ± 13.6 No treatment − 0 65.2 ± 13.2 ── ───────────────────────────────────

As is clear from Table 2, it was found that administration of compound B to bone marrow transplanted mice restored the platelet count to almost normal level.

Experimental Example 2: Recovery-promoting effect of reduction in platelet count in rats treated with anticancer drug

Nimustine hydrochloride 30 was added to 6-week-old SD rats.
mg / kg was administered intravenously, and the next day, 15 mg / kg was administered intravenously. Compound A is the first administration of nimustine hydrochloride,
It was administered intravenously for 4 days on 8, 9, 10, and 14 days. On a certain day after administration, heparinized blood was collected from the rat tail,
Platelet count was measured with an automated hemocytometer. Experiment 1 group 4
~ 6 animals.

[0080]

[Table 3] Table 3 ──────────────────────────────────── Pretreatment Subject Dose Platelet count ( mg / kg) (10 ⁴ / mm ³ ) ───────────── 25th day 44th day ───────────────────── ──────────────── Nimustine hydrochloride only − 0 8.8 ± 3.8 22.7 ± 12.8 Nimustine hydrochloride Compound A 1.0 17.7 ± 21.8 57.3 ± 20.2 ──────────── ────────────────────────

As is clear from Table 3, administration of compound A to nimustine hydrochloride-administered mice was found to promote recovery of the decrease in platelet count.

As is clear from the above experimental example, administration of compound A to bone marrow transplanted or nimustine hydrochloride-administered animals accelerates recovery of platelet counts.

Experimental Example 3: Acute toxicity experiment

When Compound A, Compound B and Compound C were orally administered to rats, each dose was 1000 mg / kg.
No cases of death were observed.

Claims (3)

[Claims] 1. A general formula: [In the formula, X is = N- or = CH-, R is hydrogen,
Represents an alkyl group, an alkoxy group, or halogen, and Y ¹ is represented by the formula: Represents a group represented by, a phenyl group, or a phenyl group substituted with 1 to 3 halogen, an alkyl group or an alkoxy group. Y ² has the formula: A group represented by the formula: a group represented by -A ² -B ^2, hydrogen, alkyl group, phenyl group, 1-phenyl nucleus is halogen, alkyl or alkoxy group
1 of phenylalkyl group, phenyl group or halogen, alkyl group or alkoxy group substituted by 3
It shows a phenyl group, an alkoxyalkyl group, a hydroxyalkyl group, an alkoxycarbonylalkyl group, a carboxyalkyl group, and an acyloxyalkyl group substituted by 3 to 3. However, ^one of Y ¹ and Y ²
Or both have the formula: Or the formula: Is a group represented by. Here, Z ¹ and Z ² are the same or different and are —O—, —S— or —NR ³ —.
(Wherein R ³ represents hydrogen or an alkyl group), A ¹ and A ² are the same or different and represent an alkylene group, and B ¹ and B ² are the same or different and a carboxyl group,
Alkoxycarbonyl group, phenylalkoxycarbonyl group (the phenyl may be substituted by 1 to 3 of halogen, alkyl group or alkoxy group), acyl group, hydroxyl group, acyloxy group or the formula: Or [Chemical 7] (Here, R ¹ and R ² are the same or different and each is hydrogen, an alkyl group, a dialkylaminoalkyl group, a hydroxyalkyl group, or a group in which R ¹ and R ² form a heterocycle with the adjacent nitrogen atom. Represents a group represented by. L ¹ and L ² are the same or different and each represents hydrogen, halogen, an alkyl group or an alkoxy group. ] A therapeutic agent for thrombocytopenia containing a fused pyrazole compound represented by the following formula, an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. 2. (+)-3- [4- (2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid and its ethyl ester or their A therapeutic agent for thrombocytopenia containing a pharmaceutically acceptable salt as an active ingredient. 3. (+)-3- [4- (2-Dimethylamino-1-methylethoxy) phenyl] -1H-pyrazolo [3,4-b] pyridine-1-acetic acid and its ethyl ester or its medicament. Top acceptable salt.