WO2019235571A1

WO2019235571A1 - Treatment agent and pharmaceutical composition for hematologic cancer

Info

Publication number: WO2019235571A1
Application number: PCT/JP2019/022539
Authority: WO
Inventors: 由紀子石井
Original assignee: 富士フイルム株式会社
Priority date: 2018-06-06
Filing date: 2019-06-06
Publication date: 2019-12-12

Abstract

The present invention addresses the problem of providing a treatment agent and a pharmaceutical composition that are for effective prevention or treatment of hematologic cancer. The present invention provides a treatment agent for hematologic cancer, the treatment agent including a compound represented by general formula (1) or a salt thereof.

Description

Hematological cancer treatment agent and pharmaceutical composition

The present invention relates to a treatment agent and a pharmaceutical composition for preventing or treating blood cancer.

There are blood cells such as red blood cells, white blood cells, and platelets in the blood, and they differentiate from the hematopoietic stem cells that are the source of the blood cells in the bone marrow inside the bone (the immature cells become mature cells). Made. Blood cancer occurs when a genetic abnormality occurs in myeloblasts, which are immature blood cells in the process of making blood, and cancerous cells (leukemia cells) proliferate indefinitely.

There are various treatment methods for hematological cancer such as chemotherapy, radiation therapy, molecular target therapy, and high-dose chemotherapy combined with hematopoietic stem cell transplantation. However, the number of deaths from blood cancer is increasing, and there are problems such as resistance to therapeutic drugs, and no cure has been established.

On the other hand, Patent Document 1 discloses a compound that has an excellent keratinocyte growth-inhibiting action and is useful for treatment such as prevention or treatment of diseases involving excessive proliferation of keratinocytes. There are no studies on treatment.

International Publication No. 2014/066951

As described above, various methods are known as methods for preventing or treating blood cancer, but the effects are not satisfactory, and therapeutic agents and pharmaceutical compositions for more effective prevention or treatment of blood cancer Things are desired.

Under such circumstances, as a result of intensive studies, the present inventors have found that the compound represented by the general formula (1) or a salt thereof can solve the above problems, and completed the present invention.

The present invention provides the following.
[1] A treatment for blood cancer comprising a compound represented by the general formula (1) or a salt thereof.

(Where
G ¹ is CH or a nitrogen atom;
R ¹ is a halogen atom, an optionally substituted C _1-6 alkyl group or an optionally substituted C _3-8 cycloalkyl group;
R ² is an optionally substituted bicyclic fused hydrocarbon ring group or an optionally substituted bicyclic heterocyclic group.
However,
(1) When R ² is an optionally substituted bicyclic fused hydrocarbon ring group, G ¹ is a nitrogen atom;
(2) When G ¹ is CH and R ¹ is a chlorine atom or an optionally substituted C _3-8 cycloalkyl group, R ² is represented by the general formula (2-1) or (2-2)

(Where
X ¹ , X ² and X ³ are the same or different and are CR ³ or a nitrogen atom;
R ³ is a hydrogen atom, a halogen atom, an optionally substituted C _1-6 alkyl group,
R ⁴ is an optionally substituted C _3-6 alkyl group, an optionally substituted C _3-8 cycloalkyl group, an _optionally substituted C _3-8 cycloalkyl C _1-6 alkyl group, An optionally substituted aryl group, an optionally substituted ar C _1-6 alkyl group, an optionally substituted acyl group, an optionally substituted heterocyclic group or an optionally substituted heterocyclic C _1-6 alkyl group. . ). )

[2] An agent for treating blood cancer, comprising the compound or a salt thereof according to [1], wherein R ¹ is a chlorine atom or an optionally substituted C _3-8 cycloalkyl group.
[3] R ² is represented by the general formula (3-1) or (3-2)

(Where
X ^1a , X ^2a , and X ^3a are the same or different and are CR ⁵ or a nitrogen atom;
X ⁴ is CH or a nitrogen atom;
R ^4a is an optionally substituted _{C 1-6} alkyl group, optionally substituted _{C 3-8} cycloalkyl _{C 1-6} alkyl group, an optionally substituted aryl group or an optionally substituted aralkyl _{C 1 A -6} alkyl group;
R ⁵ represents a hydrogen atom, a halogen atom, an optionally substituted C _1-6 alkyl group, an optionally substituted C _2-6 alkenyl group, an optionally substituted C _3-8 cycloalkyl group, a substituted which may C _3-8 cycloalkenyl group, optionally substituted C _3-8 cycloalkyl C _1-6 alkyl group, an optionally substituted aryl group, an optionally substituted heterocyclic group or optionally substituted A good ar C _1-6 alkyl group. )
Or a group represented by
Alternatively, when G ¹ is CH and R ¹ is a chlorine atom or an optionally substituted C _3-8 cycloalkyl group, R ² is represented by the general formula (4-1) or (4-2)

(Where
X ^1b , X ^2b and X ^3b are the same or different and are CH or a nitrogen atom;
R ^4b is a group represented by [1] or [2], or a salt thereof, which is a group represented by an optionally substituted aryl group or an optionally substituted ar C _1-6 alkyl group) Contains a treatment for blood cancer.

[4] R ² is represented by the general formula (5-1) or (5-2)

(Where
R ^4c is an optionally substituted C _1-6 alkyl group or an optionally substituted aryl group;
R ^5c is each independently a hydrogen atom, a halogen atom, an aryl group that may be substituted, or a heterocyclic group that may be substituted. )
Or a group represented by
Or
When G ¹ is CH and R ¹ is a chlorine atom or an optionally substituted C _3-8 cycloalkyl group, R ² is represented by the general formula (6)

(Wherein R ^4d is an ^optionally substituted aryl group, an optionally substituted ar C _1-6 alkyl group), any one of [1] to [3] A therapeutic agent for hematological cancer comprising the compound or a salt thereof described in 1.

[5] G ¹ is a nitrogen atom, and R ² is a group represented by the general formula (7)

(Where
R ^4c is an optionally substituted C _1-6 alkyl group or an optionally substituted aryl group;
R ^5c is each independently a hydrogen atom, a halogen atom, an aryl group that may be substituted, or a heterocyclic group that may be substituted. A therapeutic agent for blood cancer comprising the compound or a salt thereof according to any one of [1] to [4], which is a group represented by:

[6] A pharmaceutical composition comprising the treatment agent according to any one of [1] to [5].
[7] A method for treating blood cancer, comprising a step of administering to the subject the treatment agent according to any one of [1] to [5].
[8] The treatment agent according to any one of [1] to [5] for use in the treatment of blood cancer.
[9] A compound represented by the above general formula (1) or a salt thereof for use in the treatment of blood cancer.
[10] Use of the compound represented by the above general formula (1) or a salt thereof for the manufacture of a therapeutic agent for blood cancer.

The present invention is useful for treatment such as prevention or treatment of blood cancer.

Hereinafter, the present invention will be described in detail.

In the present invention, each term has the following meaning unless otherwise specified.
A halogen atom means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
C _3-6 alkyl group means a linear or branched C _3-6 alkyl group such as propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl and hexyl groups. To do.
The C _1-6 alkyl group is a linear or branched C _1-6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl and hexyl groups. Means a group.
Means a C _2-6 alkenyl group, straight chain or branched C _2-6 alkenyl group such as vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, 1,3-butadienyl, pentenyl and hexenyl groups .
C _3-8 cycloalkyl group means a C _3-8 cycloalkyl group such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl groups.
C _3-8 cycloalkenyl group means a C _3-8 cycloalkenyl group such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl and cyclohexanedienyl groups.
C _3-8 Cycloalkyl _{C 1-6} alkyl group, cyclopropylmethyl, 2- (cyclopropyl) ethyl, cyclobutylmethyl, 2- (cyclobutyl) ethyl, _{C 3-8,} such as cyclopentylmethyl and cyclohexylmethyl groups Means a cycloalkyl C _1-6 alkyl group.

An aryl group means a phenyl group, a bicyclic condensed hydrocarbon ring group, or a tricyclic condensed hydrocarbon ring group.
An ar C _1-6 alkyl group means a methoxy, ethoxy, propoxy or isopropoxy group.
Acyl group means formyl group, succinyl group, glutaryl group, maleoyl group, phthaloyl group, C _2-12 alkanoyl group, aroyl group, heterocyclic carbonyl group or (α-substituted) aminoacetyl group.

The C _2-12 alkanoyl group means a linear or branched C2-12 alkanoyl group such as acetyl, propionyl, valeryl, isovaleryl and pivaloyl groups.
An aroyl group means a benzoyl or naphthoyl group.
The heterocyclic carbonyl group means nicotinoyl, thenoyl, pyrrolidinocarbonyl or furoyl group.
The (α-substituted) aminoacetyl group is an amino acid (glycine, alanine, valine, leucine, isoleucine, serine, threonine, cysteine, methionine, aspartic acid, glutamic acid, asparagine, glutamine, arginine, lysine, histidine, hydroxylysine, phenylalanine. , Tyrosine, tryptophan, proline and hydroxyproline, etc.) means the N-terminus derived from (α-substituted) aminoacetyl groups which may be protected.

The bicyclic condensed hydrocarbon ring group means a bicyclic condensed hydrocarbon ring in which a part such as pentalenyl, indanyl, indenyl and naphthyl groups may be hydrogenated.
The tricyclic fused hydrocarbon ring group means a tricyclic fused hydrocarbon ring in which a part such as biphenylenyl, acenaphthenyl, acenaphthylenyl, fluorenyl, phenalenyl, phenanthrenyl and anthracenyl groups may be hydrogenated.

The heterocyclic group means a monocyclic heterocyclic group, a bicyclic heterocyclic group or a tricyclic heterocyclic group.
The monocyclic heterocyclic group is a monocyclic nitrogen-containing heterocyclic group, a monocyclic oxygen-containing heterocyclic group, a monocyclic sulfur-containing heterocyclic group, a monocyclic nitrogen-containing / oxygen heterocyclic group, or a monocyclic heterocyclic group. This means a nitrogen-containing / sulfur heterocyclic group.
The monocyclic oxygen-containing heterocyclic group means a tetrahydrofuranyl, furanyl, tetrahydropyranyl, dihydropyranyl or pyranyl group.
The monocyclic sulfur-containing heterocyclic group means a thienyl group.
The monocyclic nitrogen-containing / oxygen heterocyclic group is a monocyclic nitrogen-containing / oxygen heterocyclic group containing only a nitrogen atom and an oxygen atom as the hetero atoms forming the ring, such as oxazolyl, isoxazolyl, oxadiazolyl and morpholinyl groups. Means.
The monocyclic nitrogen-containing / sulfur heterocyclic group is a hetero atom forming the ring such as thiazolyl, isothiazolyl, thiadiazolyl, thiomorpholinyl, 1-oxidethiomorpholinyl and 1,1-dioxidethiomorpholinyl groups. Means a monocyclic nitrogen-containing / sulfur heterocyclic group containing only nitrogen and sulfur atoms.

Bicyclic heterocyclic groups are bicyclic nitrogen-containing heterocyclic groups, bicyclic oxygen-containing heterocyclic groups, bicyclic sulfur-containing heterocyclic groups, bicyclic nitrogen-containing and oxygen heterocyclic groups. Alternatively, it means a bicyclic nitrogen-containing / sulfur heterocyclic group.

Bicyclic nitrogen-containing heterocyclic groups are indolinyl, indolyl, isoindolinyl, isoindolyl, pyrrolopyridinyl, indazolyl, benzimidazolyl, benzotriazolyl, tetrahydroquinolinyl, dihydroquinolinyl, quinolinyl, tetrahydroquinolinyl, tetrahydroisoxyl. Bicycles containing only nitrogen atoms as heterogeneous atoms forming the ring, such as nolinyl, isoquinolinyl, dihydroquinazolinyl, cinnolinyl, phthalazinyl, quinazolinyl, dihydroquinoxalinyl, quinoxalinyl, naphthyridinyl, purinyl, pteridinyl and quinuclidinyl groups The nitrogen-containing heterocyclic group of the formula is meant.
Bicyclic oxygen-containing heterocyclic groups include 2,3-dihydrobenzofuranyl, benzofuranyl, isobenzofuranyl, chromanyl, chromanyl, isochromanyl, 1,3-benzodioxolyl, 1,3-benzodioxanyl And a bicyclic oxygen-containing heterocyclic group containing only an oxygen atom as a hetero atom forming the ring, such as a 1,4-benzodioxanyl group.
The bicyclic sulfur-containing heterocyclic group means a bicyclic sulfur-containing heterocyclic group containing only a sulfur atom as a hetero atom forming the ring, such as 2,3-dihydrobenzothienyl and benzothienyl groups. .
Bicyclic nitrogen-containing / oxygen heterocyclic groups include dihydrobenzoxazolyl, benzoxazolyl, benzisoxazolyl, benzoxdiazolyl, benzomorpholinyl, dihydropyranopyridyl, dihydrodioxynopyridyl and It means a bicyclic nitrogen-containing / oxygen heterocyclic group containing only a nitrogen atom and an oxygen atom as the hetero atoms forming the ring, such as a dihydropyridoxazinyl group.
Bicyclic nitrogen-containing / sulfur heterocyclic groups include dihydrobenzothiazolyl, benzothiazolyl, benzisothiazolyl and benzothiadiazolyl groups containing nitrogen and sulfur atoms as heterogeneous atoms forming the ring. This means a cyclic nitrogen-containing / sulfur heterocyclic group.

Heterocyclic C _1-6 alkyl group means azetidinylmethyl, azetidinylethyl, pyrrolidinylmethyl, pyrrolidinylethyl, piperidylmethyl, piperidylethyl, pyridylmethyl, pyridylethyl, imidazolylmethyl, imidazolylethyl, pipepe Monocyclic nitrogen-containing heterocyclic C _1-6 alkyl groups such as razinylmethyl and piperazinylethyl groups; monocyclic oxygen-containing heterocyclic C _1-6 alkyl groups such as tetrahydrofuranylmethyl and tetrahydropyranylmethyl; thienyl Monocyclic sulfur-containing heterocyclic C _1-6 alkyl group such as methyl group; oxazolylmethyl, oxazolylethyl, isoxazolylmethyl, isoxazolylethyl, morpholinylmethyl and morpholinylethyl groups nitrogen-containing, oxygen heterocycle C _1-6 alkyl group of one ring, such as; thiazolylmethyl Chiazoriruechiru, benzisothiazolyl methyl and iso-thiazolyl ethyl monocyclic nitrogen-containing sulfur heterocycles C _1-6 alkyl group such group; indolylmethyl, indolylethyl ethyl, benzimidazolyl methyl, benzimidazolyl ethyl, quinolylmethyl and quinolylethyl group Bicyclic nitrogen-containing heterocyclic C _1-6 alkyl group such as; bicyclic oxygen-containing heterocyclic C _1-6 alkyl group such as benzofuranylmethyl, isobenzofuranylmethyl and chromanylmethyl groups; benzothienyl A bicyclic sulfur-containing heterocyclic C _1-6 alkyl group such as a methyl group; a bicyclic nitrogen-containing / oxygen heterocyclic C _1-6 alkyl group such as a benzoxazolylmethyl and benzoisoxazolylmethyl group; Bicyclic nitrogen-containing and sulfur complex such as benzothiazolylmethyl and benzoisothiazolylmethyl groups C1-6 alkyl; tricyclic oxygen-containing heterocyclic C _1-6 alkyl group and a thianthrenyl such key Sante methylpropenylmethyl group; carbazolylphenyl tricyclic nitrogen-containing heterocyclic C _1-6 alkyl group such as methyl group It means a tricyclic sulfur-containing heterocyclic C _1-6 alkyl group such as a methyl group.

Examples of the salt of the compound of the general formula (1) include a salt in a basic group such as a commonly known amino group or an acidic group such as a phenolic hydroxyl group or a carboxyl group.

Examples of salts in basic groups include salts with mineral acids such as hydrochloric acid, hydrobromic acid, nitric acid and sulfuric acid; formic acid, acetic acid, citric acid, oxalic acid, fumaric acid, maleic acid, succinic acid, malic acid, Salts with organic carboxylic acids such as tartaric acid, aspartic acid, trichloroacetic acid and trifluoroacetic acid; and salts with sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, mesitylenesulfonic acid and naphthalenesulfonic acid Can be mentioned.

Salts in acidic groups include, for example, salts with alkali metals such as sodium and potassium; salts with alkaline earth metals such as calcium and magnesium; ammonium salts; and trimethylamine, triethylamine, tributylamine, pyridine, N, N— Nitrogen-containing organic bases such as dimethylaniline, N-methylpiperidine, N-methylmorpholine, diethylamine, dicyclohexylamine, procaine, dibenzylamine, N-benzyl-β-phenethylamine, 1-ephenamine and N, N′-dibenzylethylenediamine And a salt thereof.

Examples of blood cancer include acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia (CML). ), Chronic neutrophil leukemia (CNL), acute undifferentiated leukemia (AUL), undifferentiated large cell lymphoma (ALCL), prolymphocytic leukemia (PML), juvenile myelomonocytic leukemia (JMML), adult Examples include T cells (ALL), myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), lymphoblastic lymphoma (LBL), adult T cell leukemia / lymphoma (ATL).

The “treatment” of the present invention includes prevention or treatment. Prevention includes inhibition of onset, reduction of risk of onset, delay of onset. Treatment includes amelioration of the disease or condition of interest or suppression (maintenance or delay) of progression. The subject of treatment includes human or non-human animals in need of such treatment.

The “agent” of the present invention can be a composition in which formulation adjuvants such as excipients, carriers and diluents used in the formulation are appropriately mixed in addition to the active ingredient compound or a salt thereof. The “agent” may contain other active ingredients and can be used together with a medicine containing other active ingredients.

Among the compounds of the present invention, the following compounds are preferred.

G ¹ is CH or a nitrogen atom.

R ¹ is a halogen atom, an optionally substituted C _1-6 alkyl group or an optionally substituted C _3-8 cycloalkyl group, a chlorine atom or an optionally substituted C _3-8 cycloalkyl group It is preferably a chlorine atom or an optionally substituted cyclopropyl group, more preferably a chlorine atom or a cyclopropyl group.
_Examples of the substituent for the C _1-6 alkyl group and the C _3-8 cycloalkyl group represented by R ¹ include at least one group selected from the substituent group α.

R ² is an optionally substituted bicyclic fused hydrocarbon ring group or an optionally substituted bicyclic heterocyclic group. Examples of the substituent of the bicyclic condensed hydrocarbon ring group and the bicyclic heterocyclic group represented by R ² include at least one group selected from the substituent group α.
Provided that when R ² is an optionally substituted bicyclic fused hydrocarbon ring group, G ¹ is a nitrogen atom;
When G ¹ is CH and R ¹ is a chlorine atom or an optionally substituted C _3-8 cycloalkyl group, R ² is a group represented by the general formula (2-1) or (2-2) is there.

In the formula, X ¹ , X ² and X ³ are the same or different and are CR ³ or a nitrogen atom; R ³ is a hydrogen atom, a halogen atom or an optionally substituted C _1-6 alkyl group; R ⁴ is an optionally substituted C _3-6 alkyl group, an optionally substituted C _3-8 cycloalkyl group, an _optionally substituted C _3-8 cycloalkyl C _1-6 alkyl group, An optionally substituted aryl group, an optionally substituted ar C _1-6 alkyl group, an optionally substituted acyl group, an optionally substituted heterocyclic group or an optionally substituted heterocyclic C _1-6 alkyl group. .
_Examples of the substituent for the C _1-6 alkyl group represented by R ³ include at least one group selected from substituent group α.
R ⁴ C _3-6 alkyl group, C _3-8 cycloalkyl group, C _3-8 cycloalkyl C _1-6 alkyl group, aryl group, al C _1-6 alkyl group, acyl group, heterocyclic group and heterocycle Examples of the substituent of the ring C _1-6 alkyl group include at least one group selected from substituent group α.

R ² is preferably a group represented by the general formula (3-1) or (3-2).

In the formula, X ^1a , X ^2a and X ^3a are the same or different and are CR ⁵ or a nitrogen atom; X ⁴ is CH or a nitrogen atom; R ^4a is an optionally substituted C _1-6 An alkyl group, an optionally substituted C _3-8 cycloalkyl C _1-6 alkyl group, an optionally substituted aryl group or an optionally substituted ar C _1-6 alkyl group; R ⁵ represents a hydrogen atom; , A halogen atom, an optionally substituted C _1-6 alkyl group, an optionally substituted C _2-6 alkenyl group, an optionally substituted C _3-8 cycloalkyl group, an _optionally substituted C _3-8 A cycloalkenyl group, an optionally substituted C _3-8 cycloalkyl C _1-6 alkyl group, an optionally substituted aryl group, an optionally substituted heterocyclic group or an optionally substituted al C _1-6 It is an alkyl group.
Alternatively, when G ¹ is CH and R ¹ is a chlorine atom or an optionally substituted C _3-8 cycloalkyl group, R ² is represented by the general formula (4-1) or (4-2) It is preferably a group.

In the formula, X ^1b , X ^2b and X ^3b are the same or different and are CH or a nitrogen atom; R ^4b is an optionally substituted aryl group or an optionally substituted al C _1-6 alkyl group. It is a group represented.

The C _1-6 alkyl group for R ^4a is preferably a C _1-4 alkyl group, more preferably a methyl group, an ethyl group, or an isopropyl group, and even more preferably a methyl group or an isopropyl group.
The C _3-8 cycloalkyl C _1-6 alkyl group for R ^4a is preferably a C _3-6 cycloalkyl C _1-3 alkyl group, more preferably a cyclobutylmethyl group, a cyclopentylmethyl group, or a cyclohexylmethyl group.
The aryl group for R ^4a is preferably a phenyl group.
The al C _1-6 alkyl group for R ^4a is preferably a phenylmethyl group.
The substituent for the C _1-6 alkyl group, the C _3-8 cycloalkyl C _1-6 alkyl group, the aryl group and the ar C _1-6 alkyl group of R ^4a is at least one selected from the substituent group α. The group of is mentioned.

The halogen atom for R ⁵ is preferably a fluorine atom.
The C _1-6 alkyl group for R ⁵ is preferably a C _1-4 alkyl group, and more preferably a methyl group, an ethyl group, or a propyl group.
The C _2-6 alkenyl group for R ⁵ is preferably a C _2-4 alkenyl group, more preferably a 1-propenyl group or a 2-propenyl group, and even more preferably a 1-propenyl group. .
The C _3-8 cycloalkyl group for R ⁵ is preferably a C _3-6 cycloalkyl group.
The C _3-8 cycloalkenyl group for R ⁵ is preferably a C _3-6 cycloalkenyl group, and more preferably a cyclohexenyl group.
The C _3-8 cycloalkyl C _1-6 alkyl group for R ⁵ is preferably a C _3-6 cycloalkyl C _1-3 alkyl group.
The aryl group for R ⁵ is preferably a phenyl group.
The ar C _1-6 alkyl group for R ⁵ is preferably a phenyl C _1-6 alkyl group.
R ⁵ C _1-6 alkyl group, C _2-6 alkenyl group, C _3-8 cycloalkyl group, C _3-8 cycloalkenyl group, C _3-8 cycloalkyl C _1-6 alkyl group, aryl group, complex Examples of the substituent for the cyclic group and the ar C _1-6 alkyl group include at least one group selected from the substituent group α.

The aryl group for R ^4b is preferably a phenyl group.
The ar C _1-6 alkyl group for R ^4b is preferably a phenylmethyl group.
^Examples of the substituent of the aryl group of R ^4b and the al C _1-6 alkyl group include at least one group selected from the substituent group α.

R ² is more preferably a group represented by the general formula (5-1) or (5-2).

In the formula, R ^4c is an optionally substituted C _1-6 alkyl group or an optionally substituted aryl group; each R ^5c independently represents a hydrogen atom, a halogen atom, an optionally substituted aryl group or It is a heterocyclic group which may be substituted.
Alternatively, when G ¹ is CH and R ¹ is a chlorine atom or an optionally substituted C _3-8 cycloalkyl group, R ² is more preferably a group represented by the general formula (6).

In the formula, R ^4d is an ^optionally substituted aryl group or an optionally substituted ar C _1-6 alkyl group.

The C _1-6 alkyl group of R ^4c is preferably a C _1-4 alkyl group, more preferably a methyl group, an ethyl group, or an isopropyl group, and even more preferably a methyl group or an isopropyl group.
The aryl group for R ^4c is preferably a phenyl group.
^Examples of the substituent for the C _1-6 alkyl group and aryl group of R ^4c include at least one group selected from substituent group α.

The halogen atom for R ^5c is preferably a fluorine atom.
The aryl group for R ^5c is preferably a phenyl group.
^Examples of the substituent of the aryl group and heterocyclic group of R ^5c include at least one group selected from the substituent group α.

The aryl group for R ^4d is preferably a phenyl group.
The ar C _1-6 alkyl group for R ^4d is preferably a phenylmethyl group.
^Examples of the substituent of the aryl group of R ^4d and the al C _1-6 alkyl group include at least one group selected from the substituent group α.

R ² is more preferably a group represented by the general formula (7).

In the formula, R ^4c is an optionally substituted C _1-6 alkyl group or an optionally substituted aryl group; each R ^5c independently represents a hydrogen atom, a halogen atom, an optionally substituted aryl group or It is a heterocyclic group which may be substituted.
At this time, however, G ¹ is preferably a nitrogen atom.

Substituent group α: at least one selected from a halogen atom, a hydroxyl group that may be protected, a carboxyl group that may be protected, an amino group that may be protected, a nitro group, a cyano group, and a substituent group β A carbamoyl group which may be substituted with a group, a C _1-6 alkyl group which may be substituted with at least one group selected from substituent group β, and at least one group selected from substituent group β C _2-6 alkenyl group which may be substituted, C _3-8 cycloalkyl group which may be substituted with at least one group selected from substituent group β, at least one selected from substituent group β A C _1-6 alkoxy group that may be substituted with the above group, an acyl group that may be substituted with at least one group selected from substituent group β, and at least one group selected from substituent group β Is replaced with There alkoxycarbonyl group, at least one optionally substituted C _1-6 alkylamino group with a group selected from Substituent group beta, optionally substituted with at least one group selected from Substituent group beta A good di (C _1-6 alkyl) amino group, a C _1-6 alkylthio group optionally substituted with at least one group selected from substituent group β, and at least one selected from substituent group β A C _1-6 alkylsulfonyl group which may be substituted with a group, an aryl group which may be substituted with at least one group selected from substituent group β, and at least one group selected from substituent group β A heterocyclic group which may be substituted with an oxo group;

Substituent group β: halogen atom, optionally protected hydroxyl group, optionally protected carboxyl group, optionally protected amino group, carbamoyl group, C _1-6 alkyl group _optionally substituted with halogen atom, halogen An optionally substituted C _1-6 alkoxy group, a C _1-6 alkylamino group, a di (C _1-6 alkyl) amino group, a heterocyclic group, an oxo group;

Preferred compounds in the present invention include the following compounds.
5-chloro-2-((1-phenyl-1H-indol-5-yl) amino), 2-((1-benzyl-1H-indol-5-yl) amino) -5-cyclopropylbenzoic acid, 2 -((1-benzyl-1H-pyrrolo (2,3-b) pyridin-5-yl) amino) -5-cyclopropylbenzoic acid, 2-((1-benzyl-1H-indazol-5-yl) amino ) -5-cyclopropylbenzoate, 5-chloro-2-((1- (3- (trifluoromethyl) phenyl) -1H-indol-5-yl) amino) benzoic acid, 5-cyclopropyl-2- ((1-phenyl-1H-indol-5-yl) amino) benzoic acid, 2-((1-benzyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 5-cyclopropyl 2-((1-Phenyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1- (4- (trifluoromethyl) phenyl) -1H-indol-5-yl ) Amino) benzoic acid, 2-((3-benzyl-2-oxo-2,3-dihydrobenzo [d] thiazol-6-yl) amino) -5-cyclopropylnicotinic acid, 2-((1- ( Cyclohexylmethyl) -1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((1- (cyclobutylmethyl) -1H-indol-5-yl) amino) -5-cyclopropylnicotine Acid, 5-cyclopropyl-2-((5-phenylnaphthalen-1-yl) amino) nicotinic acid, 5-cyclopropyl-2- (1-methyl-3-phenyl-1H-i Dole-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((5-phenylnaphthalen-2-yl) amino) nicotinic acid, 5-cyclopropyl-2-((8-phenylnaphthalene-2- Yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl-7-phenyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1- (3 -Fluorophenyl) -1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1- (4-fluorophenyl) -1H-indol-5-yl) amino) nicotinic acid, 5 -Cyclopropyl-2-((1- (3-fluorobenzyl) -1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-phenyl-1 H-indol-4-yl) amino) nicotinic acid, 2-((1- (cyclohexylmethyl) -1H-indazol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((1-benzyl- 1H-pyrrolo (2,3-b) pyridin-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((1-benzyl-6-fluoro-1H-indol-5-yl) amino) -5 -Cyclopropylnicotinic acid, 5-cyclopropyl-2-((1- (3- (trifluoromethyl) benzyl) -1H-indol-5-yl) amino) nicotinic acid, 2-((1-benzyl-4 , 6-Difluoro-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((1- (3-chlorobenzyl) -1H-indol-5-yl) amino) 5-cyclopropylnicotinic acid, 5-cyclopropyl-2-((7- (2-fluorophenyl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2- ( (7- (3-Fluorophenyl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((7- (4-fluorophenyl) -1-methyl-1H -Indol-5-yl) amino) nicotinic acid, (E) -5-cyclopropyl-2-((7- (3-methoxyprop-1-en-1-yl) -1-methyl-1H-indole-5 -Yl) amino) nicotinic acid, 5-cyclopropyl-2-((7- (3-methoxypropyl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, (E) -5-cyclop Lopyl-2-((7- (2-cyclopropylvinyl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((7- (2-cyclopropylethyl) ) -1-Methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((7- (3,6-dihydro-2H-pyran-4-yl) -1-methyl- 1H-Indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-phenylisoquinolin-6-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl-7 -(2-trifluoromethyl) phenyl) -1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (3-trifluoromethyl) phenyl)- H-Indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (4-trifluoromethyl) phenyl) -1H-indol-5-yl) amino) nicotinic acid 5-cyclopropyl-2-((1-isobutyl-3-methyl-1H-indol-5-yl) amino) nicotinic acid, 2-((7- (2-cyanophenyl) -1-methyl-1H- Indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((7- (4-cyanophenyl) -1-methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid 2-((7- (3-chlorophenyl) -1-methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((7- (4-chlorophenyl)- -Methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (2- (trifluoromethoxy) phenyl) -1H-indole -5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (3- (trifluoromethoxy) phenyl) -1H-indol-5-yl) amino) nicotinic acid, 5 -Cyclopropyl-2-((1-methyl-7- (4- (trifluoromethoxy) phenyl) -1H-indol-5-yl) amino) nicotinic acid, 2-((7-cyclohex-1-ene) -1-yl) -1-methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((1-benzyl-6-methyl-1H-indole-5-yl) ) Amino) -5-cyclopropylnicotinic acid, 5-cyclopropyl-2-((1- (3,5-difluorobenzyl) -1H-indol-5-yl) amino) nicotinic acid, 2-((1- (Cyclopentylmethyl) -1H-indol-4-yl) amino) -5-cyclopropylnicotinic acid, 5-cyclopropyl-2-((2-oxo-1-phenyl-1,2-dihydroquinolin-5-yl) ) Amino) benzoic acid, 2-((1-benzyl-4-methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid.

The compounds of the present invention include 5-chloro-2-((1-phenyl-1H-indol-5-yl) amino), 2-((1-benzyl-1H-indol-5-yl) amino) -5 -Cyclopropylbenzoic acid, 2-((1-benzyl-1H-pyrrolo (2,3-b) pyridin-5-yl) amino) -5-cyclopropylbenzoic acid, 2-((1-benzyl-1H- Indazol-5-yl) amino) -5-cyclopropylbenzoate, 5-chloro-2-((1- (3- (trifluoromethyl) phenyl) -1H-indol-5-yl) amino) benzoic acid, 5-cyclopropyl-2-((1-phenyl-1H-indol-5-yl) amino) benzoic acid, 2-((1-benzyl-1H-indol-5-yl) amino) -5-cyclopropylnico Acid, 5-cyclopropyl-2-((1-phenyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1- (4- (trifluoromethyl) phenyl) -1H-indol-5-yl) amino) benzoic acid, 2-((1- (cyclohexylmethyl) -1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((1- ( Cyclobutylmethyl) -1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 5-cyclopropyl-2-((5-phenylnaphthalen-1-yl) amino) nicotinic acid, 5-cyclopropyl -2-((5-phenylnaphthalen-2-yl) amino) nicotinic acid, 5-cyclopropyl-2-((8-phenylnaphthalen-2-yl) amino) nicotine Acid, 5-cyclopropyl-2-((1-methyl-7-phenyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1- (3-fluorophenyl)- 1H-Indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1- (4-fluorophenyl) -1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2 -((1-phenyl-1H-indol-4-yl) amino) nicotinic acid, 2-((1- (cyclohexylmethyl) -1H-indazol-5-yl) amino) -5-cyclopropylnicotinic acid, 2 -((1-benzyl-1H-pyrrolo (2,3-b) pyridin-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((1-benzyl-6-fluoro-1H-i Dol-5-yl) amino) -5-cyclopropylnicotinic acid, 5-cyclopropyl-2-((1- (3- (trifluoromethyl) benzyl) -1H-indol-5-yl) amino) nicotinic acid 2-((1-benzyl-4,6-difluoro-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((1- (3-chlorobenzyl) -1H-indole- 5-yl) amino) -5-cyclopropylnicotinic acid, 5-cyclopropyl-2-((7- (2-fluorophenyl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, 5 -Cyclopropyl-2-((7- (3-fluorophenyl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((7- (4 Fluorophenyl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, (E) -5-cyclopropyl-2-((7- (3-methoxyprop-1-en-1-yl)- 1-methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((7- (3-methoxypropyl) -1-methyl-1H-indol-5-yl) amino) nicotine Acid, (E) -5-cyclopropyl-2-((7- (2-cyclopropylvinyl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2- ( (7- (2-Cyclopropylethyl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((7- (3,6-dihydro-2H-pyran- 4-I L) -1-Methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-phenylisoquinolin-6-yl) amino) nicotinic acid, 5-cyclopropyl-2- ((1-Methyl-7- (2-trifluoromethyl) phenyl) -1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (3-tri Fluoromethyl) phenyl) -1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (4-trifluoromethyl) phenyl) -1H-indole-5 Yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-isobutyl-3-methyl-1H-indol-5-yl) amino) nicotinic acid, 2-((7- (2-sia Phenyl) -1-methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((7- (4-cyanophenyl) -1-methyl-1H-indol-5-yl) Amino) -5-cyclopropylnicotinic acid, 2-((7- (3-chlorophenyl) -1-methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((7- (4-Chlorophenyl) -1-methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (2- (trifluoromethoxy ) Phenyl) -1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (3- (trifluoromethoxy) phenyl) -1H Indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (4- (trifluoromethoxy) phenyl) -1H-indol-5-yl) amino) nicotinic acid, 2-((7-Cyclohex-1-en-1-yl) -1-methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((1-benzyl-6- Methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 5-cyclopropyl-2-((1- (3,5-difluorobenzyl) -1H-indol-5-yl) amino) Nicotinic acid, 2-((1- (cyclopentylmethyl) -1H-indol-4-yl) amino) -5-cyclopropylnicotinic acid and 5-cyclopropyl-2-((2-oxo 5-phenyl-1,2-dihydro-quinolin yl) amino) is more preferably at least one compound or its salt selected from the acid.

The compounds of the present invention include 2-((1-benzyl-1H-indol-5-yl) amino) -5-cyclopropylbenzoic acid, 5-cyclopropyl-2-((1-phenyl-1H- Indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1- (4- (trifluoromethyl) phenyl) -1H-indol-5-yl) amino) benzoic acid, 5-cyclopropyl -2-((5-phenylnaphthalen-1-yl) amino) nicotinic acid, 5-cyclopropyl-2-((5-phenylnaphthalen-2-yl) amino) nicotinic acid, 5-cyclopropyl-2- ( (1-Methyl-7-phenyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1- (4-fluorophenyl) -1H-indo -5-yl) amino) nicotinic acid, 2-((1-benzyl-4,6-difluoro-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 5-cyclopropyl-2- ( (7- (2-Fluorophenyl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((7- (3-fluorophenyl) -1-methyl-1H -Indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((7- (4-fluorophenyl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclo Propyl-2-((7- (3,6-dihydro-2H-pyran-4-yl) -1-methyl-1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-(( 1 Methyl-7- (2-trifluoromethyl) phenyl) -1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (3-trifluoromethyl) phenyl ) -1H-Indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (4-trifluoromethyl) phenyl) -1H-indol-5-yl) amino) Nicotinic acid, 2-((7- (4-cyanophenyl) -1-methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((7- (3-chlorophenyl)- 1-methyl-1H-indol-5-yl) amino) -5-cyclopropylnicotinic acid, 2-((7- (4-chlorophenyl) -1-methyl-1H-indol-5-yl) Amino) -5-cyclopropylnicotinic acid, 5-cyclopropyl-2-((1-methyl-7- (2- (trifluoromethoxy) phenyl) -1H-indol-5-yl) amino) nicotinic acid, 5 -Cyclopropyl-2-((1-methyl-7- (3- (trifluoromethoxy) phenyl) -1H-indol-5-yl) amino) nicotinic acid, 5-cyclopropyl-2-((1-methyl -7- (4- (trifluoromethoxy) phenyl) -1H-indol-5-yl) amino) nicotinic acid and 2-((7-cyclohex-1-en-1-yl) -1-methyl-1H More preferred is at least one compound selected from -indol-5-yl) amino) -5-cyclopropylnicotinic acid or a salt thereof.

Preferred salts of the present invention include pharmacologically acceptable salts.
In the compound represented by the general formula (1), when isomers (for example, optical isomers, geometric isomers, tautomers and the like) exist, the present invention includes those isomers, It includes hydrates, hydrates and crystals of various shapes.

Next, the manufacturing method of this invention compound is demonstrated.
Although this invention compound can be manufactured in accordance with the manufacturing method of international publication 2014/066951, it is not limited to this.

The pharmaceutical composition means a composition obtained by appropriately mixing formulation adjuvants such as excipients, carriers and diluents used for formulation in addition to the compound of the present invention or a salt thereof as an active ingredient.

When the present invention is used as a pharmaceutical composition, formulation adjuvants such as excipients, carriers and diluents usually used for formulation may be appropriately mixed.
Examples of the additive include an excipient, a disintegrant, a binder, a lubricant, a corrigent, a colorant, a flavoring agent, a surfactant, a coating agent, and a plasticizer.
Examples of excipients include sugar alcohols such as erythritol, mannitol, xylitol, and sorbitol; sugars such as sucrose, powdered sugar, lactose, and glucose; α-cyclodextrin, β-cyclodextrin, and sulfobutyl ether β-cyclodextrin sodium Cyclodextrins such as; celluloses such as crystalline cellulose and microcrystalline cellulose; and starches such as corn starch, potato starch and pregelatinized starch.
Examples of the disintegrant include carmellose, carmellose calcium, croscarmellose sodium, carboxymethyl starch sodium, crospovidone, low-substituted hydroxypropylcellulose, and partially pregelatinized starch.
Examples of the binder include hydroxypropylcellulose, carmellose sodium and methylcellulose.
Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, talc, hydrous silicon dioxide, light anhydrous silicic acid, and sucrose fatty acid ester.
Examples of the corrigent include aspartame, saccharin, stevia, thaumatin, and acesulfame potassium.
Examples of the colorant include titanium dioxide, iron sesquioxide, yellow iron sesquioxide, black iron oxide, edible red No. 102, edible yellow No. 4, and edible yellow No. 5.
Examples of flavoring agents include essential oils such as orange oil, lemon oil, peppermint oil and pine oil; essences such as orange essence and peppermint essence; flavors such as cherry flavor, vanilla flavor and fruit flavor; apple micron, banana micron, Powder fragrances such as peach micron, strawberry micron and orange micron; vanillin; and ethyl vanillin.
Examples of the surfactant include sodium lauryl sulfate, dioctyl sodium sulfosuccinate, polysorbate, and polyoxyethylene hydrogenated castor oil.
Examples of the coating agent include hydroxypropyl methylcellulose, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, ethyl cellulose, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, methacrylic acid copolymer L, methacrylic acid copolymer LD, and methacrylic acid copolymer S. Is mentioned.
Examples of the plasticizer include triethyl citrate, macrogol, triacetin, and propylene glycol.
These additives may be used alone or in combination of two or more.

The blending amount is not particularly limited, and may be blended appropriately so that the effect is sufficiently exhibited according to each purpose.
These are tablets, capsules, powders, syrups, granules, pills, suspensions, emulsions, solutions, powder formulations, suppositories, eye drops, nasal drops, ear drops, It can be administered orally or parenterally in the form of a patch, ointment or injection. In addition, the administration method, the dose, and the number of administrations can be appropriately selected according to the age, weight and symptoms of the patient.
In general, for adults, 0.01 to 1000 mg / kg may be divided into 1 to several times a day by oral or parenteral administration.

The present invention will be described with reference to examples, but the present invention is not limited thereto.

[Production of Compound Nos. 1 to 53]
According to the production method described in International Publication No. 2014/066951, the compounds listed in Table 1 to Table 6 were produced.

[Blood cancer cell proliferation test]
Cell proliferation tests were performed using the human myeloid leukemia cell line HL60 (JCRB cell bank, IFO50022). 10% Fetal Bovine Serum (Thermo Fisher Scientific, 10427-028) and 5% penicillin streptomycin (Thermo Fisher Scientific, 15140-122) were added to RPMI1640 (Thermo Fisher Scientific, 11875-093). I used something. HL-60 cells were seeded on a 384 well plate (Corning, 8327) at 1000 cells / 20 μL / well. After overnight culture, add 5 μL of the compound at the specified concentration, and 4 days later, add 25 μL of Cell Titer-Glo (registered trademark) Luminescent Cell Viability Assay (Promega, G7572) and use Envision plate reader (PerkinElmer). The issue volume was measured. Since the amount of issuance is proportional to the intracellular adenosine triphosphate (ATP) concentration, the amount of luminescence was used as an index of the number of living cells. The growth inhibitory concentration at each test compound concentration was calculated by the following formula.

The growth inhibitory concentration was calculated from the following formula.
The growth inhibition rate at each compound concentration was determined, and a 50% growth inhibitory concentration [GI50 (μmol / L)] was calculated using XLfit.
Growth inhibition rate (%) = (luminescence amount of well added with test compound) / (luminescence amount of well added with DMSO) × 100

The results are shown in Tables 7 to 9.
The abbreviations in the table have the following meanings. Moreover, the numerical value in a table | surface represents the above-mentioned growth inhibitory concentration, and a unit is micromol / L.
A: GI50 value <0.1 μmol / L
B: 0.1 μmol / L ≦ GI50 value <1.0 μmol / L
C: 1.0 μmol / L ≦ GI50 value

Compound Nos. 1 to 53 showed an excellent cell growth inhibitory effect.

Since the compound of the present invention or a salt thereof has an excellent effect of inhibiting the growth of blood cancer cells, it is useful for treatment such as prevention or treatment of blood cancer.

Claims

A therapeutic agent for blood cancer comprising a compound represented by the general formula (1) or a salt thereof.

(Where
G 1 is CH or a nitrogen atom;
R 1 is a halogen atom, an optionally substituted C 1-6 alkyl group or an optionally substituted C 3-8 cycloalkyl group;
R 2 is an optionally substituted bicyclic fused hydrocarbon ring group or an optionally substituted bicyclic heterocyclic group.
However,
(1) When R 2 is an optionally substituted bicyclic fused hydrocarbon ring group, G 1 is a nitrogen atom;
(2) When G 1 is CH and R 1 is a chlorine atom or an optionally substituted C 3-8 cycloalkyl group, R 2 is represented by the general formula (2-1) or (2-2)

(Where
X 1 , X 2 and X 3 are the same or different and are CR 3 or a nitrogen atom;
R 3 is a hydrogen atom, a halogen atom, an optionally substituted C 1-6 alkyl group,
R 4 is an optionally substituted C 3-6 alkyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 3-8 cycloalkyl C 1-6 alkyl group, An optionally substituted aryl group, an optionally substituted ar C 1-6 alkyl group, an optionally substituted acyl group, an optionally substituted heterocyclic group or an optionally substituted heterocyclic C 1-6 alkyl group. . ). )
A therapeutic agent for blood cancer comprising the compound or a salt thereof according to claim 1, wherein R 1 is a chlorine atom or an optionally substituted C 3-8 cycloalkyl group.
R 2 is represented by the general formula (3-1) or (3-2)

(Where
X 1a , X 2a , and X 3a are the same or different and are CR 5 or a nitrogen atom;
X 4 is CH or a nitrogen atom;
R 4a is an optionally substituted C 1-6 alkyl group, optionally substituted C 3-8 cycloalkyl C 1-6 alkyl group, an optionally substituted aryl group or an optionally substituted aralkyl C 1 A -6 alkyl group;
R 5 represents a hydrogen atom, a halogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 3-8 cycloalkyl group, a substituted which may C 3-8 cycloalkenyl group, optionally substituted C 3-8 cycloalkyl C 1-6 alkyl group, an optionally substituted aryl group, an optionally substituted heterocyclic group or optionally substituted A good ar C 1-6 alkyl group. )
Or a group represented by
Alternatively, when G 1 is CH and R 1 is a chlorine atom or an optionally substituted C 3-8 cycloalkyl group, R 2 is represented by the general formula (4-1) or (4-2)

(Where
X 1b , X 2b and X 3b are the same or different and are CH or a nitrogen atom;
The blood containing the compound or a salt thereof according to claim 1 or 2, wherein R 4b is a group represented by an optionally substituted aryl group or an optionally substituted ar C 1-6 alkyl group). Cancer treatment.
R 2 is represented by the general formula (5-1) or (5-2)

(Where
R 4c is an optionally substituted C 1-6 alkyl group or an optionally substituted aryl group;
R 5c is each independently a hydrogen atom, a halogen atom, an aryl group that may be substituted, or a heterocyclic group that may be substituted. )
Or a group represented by
Or
When G 1 is CH and R 1 is a chlorine atom or an optionally substituted C 3-8 cycloalkyl group, R 2 is represented by the general formula (6)

4. The group according to claim 1, wherein R 4d is an optionally substituted aryl group or an optionally substituted ar C 1-6 alkyl group. 5. A treatment for blood cancer comprising the compound or a salt thereof.
G 1 is a nitrogen atom, and R 2 is a group represented by the general formula (7)

(Where
R 4c is an optionally substituted C 1-6 alkyl group or an optionally substituted aryl group;
R 5c is each independently a hydrogen atom, a halogen atom, an aryl group that may be substituted, or a heterocyclic group that may be substituted. The therapeutic agent of hematological cancer containing the compound or its salt as described in any one of Claim 1 to 4 which is group represented by these.
A pharmaceutical composition comprising the treatment agent according to any one of claims 1 to 5.