JP2002114684A - Therapeutic agent for uropathy - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new medicine excellent as a therapeutic agent and a prophylactic agent for uropathy diseases, especially urinary disturbance. SOLUTION: This medicine useful as the therapeutic agent and the prophylactic agent comprises a compound of formula (I) [A is a group represented by formula (II) or formula (III) (Ar1 ring is a benzene ring, or the like; Ar2 ring is a benzene ring, or the like; D is a group represented by the formula CH, or the like; R3 and R4 are each the same or different and hydrogen atom, or the like; R5 is hydrogen atom, or the like; R6 is hydrogen atom, or the like; R7 is hydrogen atom, or the like; R8 is a 1-6C alkyl which may be substituted, or the like; partial structure = is a single bond or double bond; (n) is an integer of 0 or 1-3; (p) is an integer of 0 or 1 to 6); X is nitrogen atom, or the like; R1 and R2 are each hydrogen atom or bonded to form an X-containing ring; (m) is an integer of 0 or 1 to 6], its salt or their hydrates.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a medicament of a compound having a binding property to a serotonin receptor, and more particularly to a therapeutic or preventive agent for urinary tract diseases.

[0002]

2. Description of the Related Art Urination is filtered and reabsorbed in nephron.
・ Urine produced by secretion passes through the ureter, bladder, and urethra
It is a series of mechanisms (urine collection / urination) that are discharged immediately. Urine collection
The mechanism is under sympathetic innervation and mainly consists of bladder neck and sphincter urine
The micturition is regulated by the smooth muscle of the tract, whereas the urination
It is known that it is a reflex through the sympathetic nerve (pelvic nerve, etc.)
Have been. Normal urination accumulates a certain amount of urine in the bladder
When urination occurs and you decide to urinate, the bow
Inhibition of the lower sacral center is released, and bladder wall smooth muscle
Muscles) contract, and at the same time, relaxation of the external urethral sphincter occurs due to reflexes.
It happens by doing. Dysuria is a series of these
A general term for conditions in which the urinary system has an abnormality.
Prohibition, urine output / urination frequency / urination status such as enuresis / urinary line / urination
Severe urinary tract disease with abnormalities. For example, if you have difficulty urinating
Is a disease that is prone to be present in patients with benign prostatic hyperplasia and neuropathic bladder.
Sickness, bladder or urethral vessels, regardless of willingness to urinate
Due to qualitative and functional impairment, urination becomes difficult. Frequent
In urine, the frequency of urination is increased,
Is constantly aware of urination, with or without organic disability
The patient shows frequent urination. Also, incontinence (involuntary urination, ureteral
Urinary incontinence, stress incontinence, reflex incontinence, overflow incontinence
Etc.), urine is involuntarily and unconsciously excreted
In the case of enuresis, urine is involuntarily caused mainly by psychological factors.
Be in a state of leaking. In recent years, with the aging of society, dysuria
Harm is a major problem in care and clinical settings
You. One of the factors is that the prostate gland
Increase in hypertrophy, but also cerebrovascular disorders and
Various factors such as neurodegenerative diseases are also intricately intertwined
It is thought to have led to the disease. Drugs for urinary disorders
Thus, some drugs are already in clinical use. An example
For example, as a treatment for dysuria, α ₁Receptor selective block
There are drugs such as tamsulosin hydrochloride and naftopidil.
Anticholinergics (eg, salt)
Acid oxybutynin, etc.), muscle relaxants (eg, baclofen
), Drugs acting on the central nervous system (such as imipramine)
is there. However, pharmacological activity, safety, etc. in clinical
At present, no drug has been found that satisfies the above points
Therefore, there is a long-awaited need to develop a new drug for treating dysuria.
You.

On the other hand, in recent years, serotonin (5-hydroxytrypt
(amine = 5-HT) There have been several reports suggesting a relationship between 5-HT _1A receptor, one of the receptors, and urinary tract disease. For example, it has been reported that the 5-HT _1A receptor is involved in the micturition reflex (J. Pharmacol. Exp. Therapeutic).
s, 262: 1, 181-189 (1992)). Also recently, WO9
6/05817 reports that compounds that interact with the serotonin 5-HT _1A receptor are useful for preventing urinary incontinence, and furthermore, WO97 / 31637 and US59.
90114 reports the use of a compound having affinity for the serotonin 5-HT _1A receptor in the treatment of lower urinary tract disorders. Serotonin is a bioactive amine known as a neurotransmitter. Conventionally, it is involved in various functions such as peripheral smooth muscle relaxation, platelet aggregation, gastrointestinal function, and central temperature control, appetite, sleep, pain, sexual behavior, anxiety, depression, cognition and memory. And there have been numerous reports of involvement in diseases associated with these functions, particularly psychosis. Required serotonin receptor bioactivity expression of serotonin, unprecedented 5-HT ₁ to be identified as the seven families of 5-HT _7, 5-HT ₁ is further classified into five subtypes (5 -HT _1A , 5-HT _1B , 5-HT
_1D , 5-HT _1E , 5-HT _1F ). The 5- _HT1A receptor functionally includes a presynaptic receptor and a postsynaptic receptor, and the former is widely distributed in serotonin-producing nerves, and the latter is widely distributed in the brain.

Compounds having 5-HT _1A receptor antagonistic activity are disclosed in JP-A-9-40648 and JP-A-10-27343.
7, JP-A-11-147871, JP-A-11-15
8179, JP-A-11-302279, and W
O98 / 43956, JP-A-2000-53647 and the like have been reported so far, but a compound known to be associated with urinary tract disease is represented by the formula [1]

Embedded image Wherein R ₁ and R ₂ independently represent a halogen atom or the like; R ₃ represents a C _1-4 alkyl group or the like; R ₄ and R ₅ independently represent a hydrogen atom or the like; Ar represents a phenyl group or the like. Or a pharmacologically acceptable salt thereof (US Pat. No. 5,387,593);

Embedded image Wherein a and b each represent 0, 1, etc .; a dotted line optionally represents a double bond; A represents an alkylene chain having 1 or 2 carbon atoms; R represents a monocyclic aryl radical or the like. R ¹ represents a monocyclic heteroaryl radical or the like;
R ² represents a cycloalkyl group or the like. Or a pharmacologically acceptable acid addition salt thereof (WO95)
/ 02592), Equation [3]

Embedded image [Wherein, R ₁ represents an n-propyl group or the like; R ₂ represents an isopropyl group or the like; R ₃ represents a hydrogen atom; R ₄ represents a hydrogen atom or the like. Or a pharmacologically acceptable salt thereof (WO95 / 1)
1891), equation [4]

Embedded image [Wherein, R ^a and R ^b represent a methyl group or the like; R ^c represents a hydrogen atom or the like. Or a pharmacologically acceptable acid addition salt thereof (WO95 / 33743).
O97 / 31637, a compound represented by the formula [5]

Embedded image Wherein R represents a hydrogen atom or the like; R ₁ represents a hydrogen atom or the like; R ₂ represents a halogen atom or the like; B represents a monocyclic aryl group or the like. Or a pharmacologically acceptable salt thereof (WO 99/06384).

[0005]

As described above, 5-HT
Compounds with _1A receptor binding properties can be expected as dysuric agents based on a novel mechanism of action, excellent 5-HT _1A has a receptor binding strength, and urinary tract disorders in addition clinical, In particular, a compound capable of exhibiting an excellent effect in treating and preventing dysuria has not yet been found.

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies in view of the above circumstances, and as a result, the present inventors have already succeeded in synthesizing, and have found the binding activity of 5-HT _1A receptor to WO9.
Compounds disclosed in 8/43956 and JP-A-2000-53647 have an excellent inhibitory effect on rhythmic bladder contraction, and are used as a therapeutic / prophylactic agent for dysuria, especially urinary frequency, urinary incontinence and the like. The present invention was found to be useful, and the present invention was completed.

That is, the first feature of the present invention is (1)
formula

Embedded image [Where A is the formula

Embedded image(Wherein, Ar¹The ring is benzene, pyridine, pyridazine,
Represents a pyrimidine or pyrazine ring; Ar^TwoRing is Benze
Represents a pyridine, pyridine, thiophene or furan ring; D is
A group represented by the formula> CH- or a nitrogen atom;^Three
And R^FourAre the same or different (1) a hydrogen atom,
(2) halogen atom, (3) hydroxyl group, (4) cyano group,
(5) nitro group, (6) (i) halogen atom, (ii) hydroxyl
Group, (iii) cyano group, (iv) C_1-6Alkylsulfonyl
Amino group, (v) hydroxypiperidylcarbonyl group,
(Vi) Hydroxy C_1-6Alkylamide group, (vii) halo
Genification C_1-6Alkylamide group, (viii) dihalogenation
C_1-6Alkylamide group, (ix) heteroarylamide
Group, (x) hydroxy C_1-6Alkylamide group, (xi) water
An acid group, (xii) an optionally substituted amino group, (xii
i) C optionally substituted with a nitrogen atom_1-6Acylamino
Group, (xiv) optionally substituted C_6-14Aromatic hydrocarbon
A cyclic group, (xv) an optionally substituted 5- to 14-membered group
Aromatic heterocyclic group, (xvi) C_3-8Cycloalkylcarbonyl
An amino group, (xvii) an optionally substituted ureido group,
(Xviii) succinimido-1-yl group, (xix) substituted
An optionally substituted carbamoyl group, (xx)
Thiocarbamoyl group, (xxi) pyrrolidinyl car
Bonyl group, (xxii) optionally substituted aminosulfo
Nyl group, (xxiii) carboxyl group and (xxix) C_1-6
One or more groups selected from alkylamide groups
Optionally substituted C_1-6Alkyl group, (7) 1-hydr
Roxy C_3-8Cycloalkyl group, (8) 1-hydroxy-
1- (methoxypyridyl) methyl group, (9) (i) hydro
A xyimino group, (ii) a 2-pyrrolidone-1-yl group,
(Iii) 2-piperidone-1-yl group, (iv) 2-imi
Dazolidinone-1-yl group, (v) 2,4-imidazoli
Zindione-3-yl group, (vi) 2-oxazolidone-
3-yl group, (vii) glutarimido-1-yl group, (v
iii) a 2,4-thiazolidinedione-3-yl group and
(Ix) selected from an optionally substituted 4-piperidyl group
Methyl group substituted with a group represented by the formula_{1- 6}Alkoxy
C which may be substituted with a group or a hydroxyl group_1-6Alkoki
Shi group, (11) C_1-6Alkylsulfonyloxy group, (1
2) C which may be substituted_6-14Aromatic hydrogen ring group, (1
3) 5- to 14-membered aromatic heterocyclic ring which may be substituted
Group, (14) (i) C_1-6Alkyl group, (ii) C_1-6Arco
A xycarbonyl group, (iii) C_1-6Alkylsulfonyl
Group, (iv) C_1-6Acyl group and (v) even if substituted
One or two selected from arylsulfonyl groups
An amino group optionally substituted with the above groups, formula (15)
-CO-R³⁶(Where R³⁶Is (i) C_1-6Alkyl group,
(Ii) C_2-6Alkenyl group, (iii) C_2-6Alkynyl
Group, (iv) methoxypyridyl group, (v) C_6-14Aromatic coal
Hydrogenated ring group or (vi) 5- to 14-membered aromatic heterocyclic group
(16) 2-pyrrolidinone-1
-Yl group, (17) 1,3-propane sultam-2-yl
Group, (18) C_1-6Alkylsulfonyl group, (19) amide
Group, (20) sulfonamide group, (21) even if substituted
Good carbamoyl group, (22) urethane which may be substituted
Id group, (23) succinimide group or (24) formyl
Represents a group or R^ThreeAnd R^FourAre joined together by
Alicyclic ring which may be substituted, may be substituted
Heterocyclic or optionally substituted alkylenedio
R may form a xy group;^FiveIs (1) a hydrogen atom,
(2) halogen atom, (3) hydroxyl group, (4) (i) hydroxyl group
Or (ii) a sulfamo optionally substituted with a nitrogen atom
C optionally substituted with an yl group_1-6Alkyl group, (5)
C which may be substituted with a hydroxyl group_1-6An alkoxy group,
(6) formyl group, (7) optionally substituted aralkyl
Roxy group or (8) sulfa which may be substituted
Represents a moyl group; R⁶Is a hydrogen atom, a halogen atom, C_1-6
Alkyl group or C_1-6Represents an alkoxy group; R⁷Is hydrogen
Atom, halogen atom, C_1-6Alkyl group or C_1-6Al
Represents a oxy group; R⁸Is (1) (i) hydroxyl group, (ii) C
_6-14Aromatic hydrocarbon ring group and (iii) nitrogen atom are substituted
One selected from the group consisting of amino groups which may be
Or C which may be substituted with two or more groups._1-6Archi
Group, (2) optionally substituted C_{6- 14}Aromatic hydrocarbon
An aromatic ring or an optionally substituted 5- to 14-membered aromatic
C optionally substituted with a heterocyclic group_2-6Alkenyl
Group, (3) optionally substituted C_{6- 14}Aromatic hydrocarbon
Cyclic group, optionally substituted 5- to 14-membered heteroaromatic
C optionally substituted with a cyclic group or an aromatic acyl group
_2-6Alkynyl group, (4) (i) aromatic acyl group, (ii)
C_6-14Arylsulfonyl group, (iii) C_1-6Alkoxy
C _6-14Arylsulfonyl group, (iv) even when substituted
Good C_6-14Aromatic hydrocarbon ring group and (v) substituted
Substituted with a group selected from an aralkyl group which may be
An optionally substituted amino group, (5) an optionally substituted C_6-14
Aromatic hydrocarbon ring group, (6) 5 which may be substituted
14-membered aromatic heterocyclic group, (7) optionally substituted
Aralkyloxy group, (8) hydroxy C_1-6Alkoki
Cystyryl group, (9) C_1-6Alkoxyaryloxy
Group, (10) 4-phenylpiperidin-1-yl group, (1
1) 4-pyridylpiperidin-1-yl group or (12)
formula

Embedded imageWherein M represents a nitrogen atom or a methine group;⁹, R
^TenAnd R¹¹Are the same or different (1) a hydrogen atom,
(2) halogen atom, (3) cyano group, (4) (i) hydroxyl
Group, (ii) halogen atom, (iii) cyano group, (iv) C
_1-6May be substituted with an alkoxy group or (v) a hydroxyl group
C_6-14Aromatic hydrocarbon ring group, (vi) 5- to 14-membered aromatic
Group heterocyclic group, (vii) hydroxyimino group, (viii) C
_3-8Cycloalkyl group, (ix) C_1-6Alkylsulfonyl
Amino group, (x) NC_1-6Alkylaminosulfonyl
Group, (xi) N, N-di C_1-6Alkylaminosulfonyl
Group, (xii) C_1-6Acyl group, (xiii) C_1-6Acylami
No group, (xiv) C_1-6Alkylsulfonyl group, (xv) N-
C_1-6Alkylamide group, (xvi) thiazol-2-yl
Group, (xvii) trifluoro group, (xviii) ω, ω-lower
Alkylenedioxy group and (xix) 1,3-dioxo
One or more groups selected from the group consisting of ranyl groups
C optionally substituted with_1-6Alkyl group, (5) hydroxyl group
C optionally substituted with_2-6Alkenyl group, (6) hydroxyl
C optionally substituted with a group_2-6Alkynyl group, (7)
Droxy C_3-8Cycloalkyl group, (8) hydroxy C
_3-8Cycloalkenyl group, (9) (i) hydroxyl group, (ii) c
A halogen atom, (iii) a cyano group, (iv) C_{1 -6}Alkoxy
Group, (v) C_1-6Thioalkoxy group, (vi) C_1-6Archi
Rusulfonyl group, (vii) hydroxy C_1-6Alkyl group,
(Viii) a 5- to 14-membered aromatic heterocyclic group, (ix) ω, ω
Lower alkylenedioxy group, (x) pyridyl group, (x
i) C_{1 -6}Alkylpyridyl group, (xii) trifluoro
Group, (xiii) amino group, (xiv) NC_1-6Alkylam
No group, (xv) N, N-diC_1-6Alkylamino group, (xv
i) C_1-6Acyl group, (xvii) C_1-6Acylaminoalco
A xy group, (xviii) (1,3-dioxolanyl) C_1-6A
Lucoxy group, (xix) amide group and (xx) imidazoly
At least one group selected from the group consisting of
C which may be replaced _1-6Alkoxy group, (10) hydro
Kishi C_3-8Substituted with cycloalkyloxy group, (11) hydroxyl group
C which may be replaced_1-6Thioalkoxy group, (12)
Reelthio group, (13) heteroarylthio group, (14) formula
 −N (R³⁷) R³⁸(Where R³⁷And R³⁸Are the same or
Differently hydrogen atom, C_1-6Alkyl group, hydroxy C
_1-6Alkyl group, C_1-6Acyl group, hydroxy C_1-6Reed
Group or C_1-6It represents an alkylsulfonyl group. )
Amino group, (15) (i) C_1-6Alkyl group, (i
i) C_3-8Cycloalkyl group, (iii) C_1-6Alkyl group,
(Iv) N-hydroxy C_1-6Alkyl group and (v) C
_6-14One or more selected from the group consisting of aromatic hydrocarbon ring groups
Is an amide group optionally substituted by two groups, (16) C
_1-6Alkyl group and hydroxy C_1-6From an alkyl group
Even if it is substituted with one or two groups selected from the group
Good carbamoyl group, (17) (i) C_1-6Alkyl group,
(Ii) hydroxy C _1-6Alkyl group, (iii) halogenation
C_1-6Alkyl group, (iv) C_1-6Alkoxyalkyl group,
(V) amino group, (vi) C_1-6Alkylamino group, (vi
i) C_3-8Cycloalkylamino group, (viii) di C_1-6A
Alkylamino group, (ix) N-hydroxy C_1-6Alkyl
Amino group, (x) NC_1-6Alkoxy C_1-6Alkyria
Amino group, (xi) arylamino group, (xii) 5 to 1
4-membered nitrogen-containing heterocyclic group, (xiii) 5- to 14-membered aromatic compound
A ring group, (xiv) 4-morpholinyl group, (xv) 4-oxo
Cythiomorpholinyl group and (xvi) 4-dioxythio
One or two members selected from the group consisting of morpholinyl groups
A sulfonyl group which may be substituted with a group, (18)
OR³⁹(Where R³⁹Is C_1-6Alkyl group, C_2-6Arche
Nyl group, C_2-6Alkynyl group or 5- to 14-membered nitrogen
Represents an elementary heterocyclic group. ), (19) Tetrahi
Dropyranyl group, hydroxytetrahydropyranyl group,
Hydroxy C _1-6Alkyltetrahydropyranyl group, (2
0) C_6-14Aromatic hydrocarbon ring group, (21) 5 to 14 members
Aromatic heterocyclic group, (22) 4-hydroxypiperidyl group,
(23) 4-C_1-6Alkoxypiperidyl group, (24) ant
Oxy group, (25) 4- (hydroxyalkyl) tetra
Lahydropyran-4-yl group, (26) 2,3-dihydro
Benzofuranyl group, (27) 2-hydroxy-2-alkyl
-2,3-dihydrobenzofuranyl group, (28)
Nonyl group, (29) hydroxyindanyl group, (30)
Silimide group or (31) 2-oxazolidone-3-yl
Represents a group or (31) R⁷Is a hydrogen atom and R⁸You
And R⁹Are linked together by cyclopentanone
Ring, hydroxycyclopentane ring, hydroxyalkyl
Cyclopentane ring, cyclohexanone ring, hydroxy
Clohexane ring, hydroxyalkylcyclohexane
Ring, 2-hydroxymethyl-2-methylcyclopentano
Ring, 1,2-ethylenedioxy ring or methylenedi
May form a xy ring; q represents 0 or 1;
r and s are the same or different and each is an integer of 0, 1 to 6
R;¹², R¹⁴, R^Fifteen, R¹⁶, R¹⁷, R¹⁸, R¹⁹,
R²⁰, R^{twenty one}, R^{twenty two}, R^{twenty three}, R^{twenty four}, R^{twenty five}, R²⁷, R²⁹And
And R³¹Are the same or different and are each a hydrogen atom, halo
Gen atom, hydroxyl group, C which may be substituted with a hydroxyl group
_1-6C which may be substituted with an alkyl group or a hydroxyl group_1-6A
Represents a alkoxy group or a tetrahydropyranyl group;¹³
Represents a hydrogen atom, a halogen atom, a hydroxyl group, C_1-6Alkyl group
Or C_1-6Represents an alkoxy group; R²⁶Is a hydrogen atom or
Is C_1-6Represents an alkyl group; R²⁸Is a hydrogen atom or a hydride
Roxy C_1-6Represents an alkyl group; R³⁰Is a hydrogen atom or
C_1-6Represents an alkyl group; R³²Is a hydrogen atom, C_1-6Archi
Group, C_1-6Alkoxy group, hydroxy C_1-6Alkyl group
Or hydroxy C_3-8Represents a cycloalkoxy group; W
Represents a sulfur atom or an oxygen atom; partial structure--- Is simply
Indicates a bond or a double bond. Selected from the group consisting of
Indicates any group; partial structure---- Is a single bond or two
Represents a heavy bond; n represents an integer of 0, 1 to 3;
It represents an integer of 0, 1 to 6. ) Represents a group represented by
And further [1] A is the formula

Embedded image (Wherein, Ar ¹ ring, R ³ , R ⁴ , R ⁵ , D and n have the same meanings as defined above), and X represents a nitrogen atom or a formula

Embedded image Wherein R ¹ and R ² are taken together by a bond to form a group containing X

Embedded image(Wherein X and Y are the same or different, and
R represents a group of the same meaning; R³³Is (1) hydrogen atom, (2) water
Acid group or (3) (i) hydroxyl group, (ii) C_1-6Alkoxy
A group, (iii) an optionally substituted aryloxy group and
And (iv) an optionally substituted aralkyloxy group
Substituted with one or more groups selected from the group consisting of
May be C_1-6Represents an alkyl group; R³⁴Is C_1-6Al
Kill group, C_1-6Acyl group, C_1-6Alkoxycarbonyl
Group, aromatic acyl group or formula -Q¹− (CH_Two)_s−Q^Two−
R⁴⁰(Where Q¹And Q^TwoAre the same or different
Is represented by an oxygen atom, a carbonyl group, or the formula -NHCO-
Group represented by the formula —NHSO_TwoA group or formula represented by-
> CH-R⁴¹(Where R ⁴¹Is a hydroxyl group, C_1-6Alkyl group
Or a halogen atom. ) Represents a group represented by
And Q¹And Q^TwoOne of the two represents a single bond; s is
R represents 0 or an integer of 1 to 6;⁴⁰Is a cyano group, substituted
C that may be_6-14Aromatic hydrocarbon ring group, substituted
An optionally substituted 5- to 14-membered aromatic heterocyclic group,
A benzoheteroaryl group, 1,4-benzo
Dioxanyl group, 1,3-benzodioxolyl group or
Shows a benzthiazolyl group. ));
t represents an integer of 1 to 3. ) Represents a group represented by
And m represents 0 or an integer of 1 to 6, and [2]
A is the formula

Embedded image (Wherein, Ar ² ring, R ⁶ , R ⁷ , R ⁸ and p have the same meanings as defined above), X represents a nitrogen atom, and R ¹ and R ² are the same. Or a different group consisting of (1) a hydrogen atom or (2) (i) an N, N-diC _1-6 alkylamino group and (ii) an optionally substituted 5- to 14-membered aromatic heterocyclic group. A C _1-6 alkyl group which may be substituted with one or more groups selected from the group _{consisting of}

Embedded image(Wherein E is a nitrogen atom or a group represented by the formula> CH-
R;³⁵Is (1) hydrogen atom, (2) (i) hydroxyl group, (i
i) halogen atom, (iii) cyano group, (iv) carbamoy
And (v) C_6-14Selected from aromatic hydrocarbon ring groups
C which may be substituted with_1-6Alkyl group, (3) C
_2-6Alkenyl group, (4) 1-piperidyl group, (5) C_3-8
Cycloalkyl group or formula (6) -CO-R⁴²(Where
R⁴²Is C _1-6Alkyl group, C_2-6Alkenyl group, C_2-6A
Rukinyl group, C_1-6Alkoxy group, C_6-14Aromatic hydrocarbon
Heterocyclic group, 5- to 14-membered aromatic heterocyclic group, aryloxy
It represents a cyclo group or an aralkyloxy group. )
Represents a group. ) And m represents 0
You. Or a salt thereof or a compound thereof
A therapeutic or prophylactic agent for urinary tract diseases comprising a hydrate of
(2) In the above (1), the agent is a compound represented by the formula

Embedded image [Wherein, Ar ¹ ring, R ³ , R ⁴ , R ⁵ , R ³³ , R ³⁴ , D,
n, t and partial structure ---- have the same meanings as defined above; X and Y are the same or different and are each a nitrogen atom or a formula

Embedded image And m represents 0 or an integer of 1 to 6. [3] In the above (2), the compound represented by the formula (2)

Embedded image [Wherein, the Ar ¹ ring, R ³ , R ⁴ , R ⁵ , D and n have the same meaning as defined above. Is a group represented by the formula

Embedded image [Wherein, R ³ , R ⁴ and R ⁵ have the same meanings as defined above; the partial structure --- represents a single bond or a double bond. ]
(4) In the above (2), the Ar ¹ ring may be a benzene ring, and (5)
In the above (2), the Ar ¹ ring is a benzene ring,
May be a nitrogen atom, and n may be 0. (6) In the above (2), the m may be 0. (7) In the above (2), the m may be 1 to 6 (8) In the above (2), the t may be 2, (9) in the above (2), X is a methine group, and Y is a nitrogen atom. (10) In the above (2), the X may be a methine group, Y may be a nitrogen atom, and t may be 2. (11) In the above (2), The partial structure --- may be a double bond, (12) in the above (2), R ³³ may be a hydrogen atom, and (13) in the above (2), R ³⁴ may be a group represented by the formula -Q ^1- (CH ₂ ) _s -Q ² -R
⁴⁰ [wherein Q ¹ , Q ² , R ⁴⁰ and s are as defined above. (14) In the above (1), the agent is a group represented by the formula

Embedded image [Wherein, R ³ , R ⁴ , R ⁵ , R ³³ and R ³⁴ have the same meaning as defined above. Or a salt thereof or a hydrate thereof.
(15) In the above (1), the agent is a compound represented by the formula

Embedded image [Wherein, the Ar ² ring, R ⁶ , R ⁷ , R ⁸ and p have the same meanings as defined above; R ¹ and R ² are the same or different and are (1) a hydrogen atom or (2) (i) It may be substituted with one or more groups selected from the group consisting of an N, N-diC _1-6 alkylamino group and (ii) an optionally substituted 5- to 14-membered aromatic heterocyclic group. or represents an C _1-6 alkyl group, or formula together by coupling

Embedded image(Wherein E is a nitrogen atom or a group represented by the formula> CH-
R;³⁵Is (1) hydrogen atom, (2) (i) hydroxyl group, (i
i) halogen atom, (iii) cyano group, (iv) carbamoy
And (v) C_6-14Selected from aromatic hydrocarbon ring groups
C which may be substituted with_1-6Alkyl group, (3) C
_2-6Alkenyl group, (4) 1-piperidyl group, (5) C_3-8
Cycloalkyl group or formula (6) -CO-R³⁸(Where
R³⁸Is C _1-6Alkyl group, C_2-6Alkenyl group, C_2-6A
Rukinyl group, C_1-6Alkoxy group, C_6-14Aromatic hydrocarbon
Heterocyclic group, 5- to 14-membered aromatic heterocyclic group, aryloxy
It represents a cyclo group or an aralkyloxy group. )
Represents a group. ). A compound represented by the formula:
Or an agent comprising a salt thereof or a hydrate thereof
(16) In (15) above,
R^ThreeMay be a hydrogen atom, and (17) the above (15)
In the above, the Ar^TwoThe ring may be a benzene ring,
(18) In the above (15), the formula

Embedded image [Wherein the Ar ² ring and R ⁶ have the same meaning as defined above. The group represented by the formula

Embedded image Wherein R ⁶ is as defined above. (19) In the above (15),
formula

Embedded image Wherein X, R ¹ and R ² have the same meaning as defined above. Is a group represented by the formula

Embedded image [Wherein, R ³⁵ has the same meaning as defined above. (20) In the above (15),
R ³⁵ may be a C _1-6 alkyl group, (21)
In the above (15), R ³⁵ may be an ethyl group, (22) in the above (15), R ⁶ may be a hydrogen atom, and (23) in the above (15),
R ⁷ may be a hydrogen atom, and (24) the above (1)
In 5), the R ⁸ may be each optionally substituted C _{6-1 4} aromatic hydrocarbon ring group or 5- to 14-membered aromatic heterocyclic group and (25) above (15) And R ⁸ may be a phenyl group which may be substituted. (26) In the above (15), p may be 0. As a second feature of the present invention, (2)
7) The therapeutic / prophylactic agent for urinary tract disease in (1) may be a therapeutic / prophylactic agent for dysuria, and (28) In (1), the agent may be an agent for dysuria associated with prostatic hypertrophy. (29) The above-mentioned (1)
In the above, the agent may be a therapeutic / prophylactic agent for pollakiuria or urinary incontinence. Urinary frequency due to bladder irritation due to chronic prostatitis It may be a therapeutic / prophylactic agent for urinary incontinence associated with a stimulating state, urinary incontinence associated with a bladder stimulating state due to chronic prostatitis, nocturia, psychogenic voiding disorder or enuresis. A third feature of the present invention resides in (31) use of the compound described in (1) above, a salt thereof, or a hydrate thereof for the manufacture of a therapeutic agent for dysuria.

Hereinafter, the meanings of symbols, terms, and the like described in the specification of the present application will be described, and the present invention will be described in detail.

In the specification of the present application, the structural formula of a compound may represent a certain isomer for convenience, but the present invention is based on all geometric isomers and asymmetric carbons occurring in the structure of the compound. It includes isomers such as optical isomers, stereoisomers, tautomers, and isomer mixtures, and is not limited to the description of formulas for convenience, and may be either one isomer or a mixture. Accordingly, an optically active compound and a racemic compound having an asymmetric carbon atom in the molecule may exist, but the present invention is not limited thereto, and any of them is included. Further, there may be crystal polymorphs, but it is not similarly limited,
It may be any single crystal form or a mixture thereof, and may be a hydrate other than the anhydride.

[0010] The term "urinary tract disease" as used herein refers to
A general term for diseases associated with disorders in the urine storage mechanism and disorders in the urination mechanism.

[0011] In the present specification, "urinary disorders"
(1) "Urine volume abnormality" such as polyuria, oliguria, and anuria; (2) "Urination frequency abnormality" such as pollakiuria and rare urine; (3) "Urination difficulty"; (4) "Urine" (Closed), (5) "urinary incontinence", (6) "urinary abnormalities" such as enuresis, (7) "urinary abnormalities" such as small urinary line, decreased output, abortion, and two-stage urination Show various "disorders / abnormalities" that impair normal urination, and
It is a word that also indicates a lower concept disease classified into each category with the “disorder / abnormality” of the above (1) to (7) as a higher concept. For example, neuropathic bladder, nervous frequency, unstable bladder,
Urinary frequency associated with bladder irritation due to chronic cystitis, urinary frequency associated with bladder irritation due to chronic prostatitis, urgency, urge incontinence, reflex incontinence, stress urinary incontinence, overflow urinary incontinence, chronic bladder Diseases such as urinary incontinence due to bladder irritation due to inflammation, urinary incontinence due to bladder irritation due to chronic prostatitis, nocturia, psychogenic dysuria, enuresis, etc. are naturally included in the “urinary dysfunction”.

The compound represented by the formula (I) contained in the therapeutic or prophylactic agent for urinary tract diseases according to the present invention is a compound represented by the formula (I)
It is a compound group including the compounds represented by I) and (III). That is, they are classified as follows according to the pattern of the group represented by A.

[In the formulas (I), (II) and (III)
Signs, Significance of Formula and Structure] In the compound represented by the formula (I), [1]

Embedded image Wherein, Ar ^{1 ring, R 3, R 4, R} 5, D, n and the partial structure --- have the same meanings as defined above. ] The group represented by the formula

Embedded image [Wherein, Ar ¹ ring, R ³ , R ⁴ , R ⁵ , R ³³ , R ³⁴ , D,
n, t and the partial structure --- have the same meanings as defined above;
X and Y are the same or different and each represents a nitrogen atom or a formula

Embedded image And m represents 0 or an integer of 1 to 6. And [2] A is a compound represented by the formula

Embedded image (Wherein, Ar ² ring, R ⁶ , R ⁷ , R ⁸ and p have the same meanings as defined above).

Embedded image [Wherein, the Ar ² ring, R ⁶ , R ⁷ , R ⁸ and p have the same meanings as defined above; R ¹ and R ² are the same or different and are (1) a hydrogen atom or (2) (i) It may be substituted with one or more groups selected from the group consisting of an N, N-diC _1-6 alkylamino group and (ii) an optionally substituted 5- to 14-membered aromatic heterocyclic group. or represents an C _1-6 alkyl group, or formula together by coupling

Embedded image(Wherein E is a nitrogen atom or a group represented by the formula> CH-
R;³⁵Is (1) hydrogen atom, (2) (i) hydroxyl group, (i
i) halogen atom, (iii) cyano group, (iv) carbamoy
And (v) C_6-14Selected from aromatic hydrocarbon ring groups
C which may be substituted with_1-6Alkyl group, (3) C
_2-6Alkenyl group, (4) 1-piperidyl group, (5) C_3-8
Cycloalkyl group or formula (6) -CO-R³⁸(Where
R³⁸Is C _1-6Alkyl group, C_2-6Alkenyl group, C_2-6A
Rukinyl group, C_1-6Alkoxy group, C_6-14Aromatic hydrocarbon
Heterocyclic group, 5- to 14-membered aromatic heterocyclic group, aryloxy
It represents a cyclo group or an aralkyloxy group. )
Represents a group. ). A compound represented by the formula:
Is shown.

In the above formula, the ring represented by Ar ¹ represents a benzene, pyridine, pyridazine, pyrimidine or pyrazine ring, preferably a benzene or pyridine ring, and more preferably a benzene ring.

D represents a group represented by the formula> CH- or a nitrogen atom, and is preferably a nitrogen atom.

The ring represented by Ar ² represents a benzene, pyridine, thiophene or furan ring, preferably a benzene or thiophene ring, and more preferably a benzene ring.

The term "halogen atom" as used herein means an atom such as a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and is preferably a fluorine atom, a chlorine atom or a bromine atom. Hereinafter, "halogen atom" in the present specification
Means the same as defined above.

"C _1-6 alkyl group" in the present specification
Means an alkyl group having 1 to 6 carbon atoms, preferably a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, a tert-butyl group, -Pentyl, i-pentyl, neopentyl, n-hexyl, 1-methylpropyl, 1,2-dimethylpropyl, 2-ethylpropyl, 1-methyl-2-ethylpropyl, 1-ethyl -2-methylpropyl group, 1,1,2-trimethylpropyl group, 1-methylbutyl group, 2-methylbutyl group, 1,1-dimethylbutyl group, 2,2-dimethylbutyl group, 2-ethylbutyl group, 3-dimethylbutyl group, 2-
It is a linear or branched alkyl group such as a methylpentyl group and a 3-methylpentyl group. In the specification of the present application, "C
_The " _2-6 alkenyl group" refers to an alkenyl group having 2 to 6 carbon atoms, preferably a vinyl group, an allyl group, or a 1-alkenyl group.
Propenyl group, isopropenyl group, 1-buten-1-yl group, 1-buten-2-yl group, 1-buten-3-yl group, 2-
It is a linear or branched alkenyl group such as a buten-1-yl group and a 2-buten-2-yl group. As used herein, the term “C _2-6 alkynyl group” refers to an alkynyl group having 2 to 6 carbon atoms, preferably ethynyl, 1-propynyl, 2-propynyl, butynyl, pentynyl, hexynyl. Linear or molecular alkynyl group such as a group; Hereinafter, “C _1-6 alkyl group”, “C _2-6 alkenyl group”, and “C _2-6 alkynyl group” in the present specification have the same meanings as defined above.

In the "C _1-6 alkoxy group" in the present specification, preferred groups are a methoxy group, an ethoxy group, an n-propoxy group, an i-propoxy group, a sec-propoxy group, an n-butoxy group and an i-butoxy group. Group, sec-butoxy group, tert-butoxy group, n-pentoxy group, i-pentoxy group, sec-pentoxy group, tert-pentoxy group, n-hexoxy group, i-hexoxy group, 1,2-dimethylpropoxy group, 2-ethylpropoxy group, 1-methyl-2-ethylpropoxy group, 1-ethyl-2-methylpropoxy group, 1,
1,2-trimethylpropoxy group, 1,1,2-trimethylpropoxy group, 1,1-dimethylbutoxy group, 2,2-dimethylbutoxy group, 2-ethylbutoxy group, 1,3-dimethylbutoxy group, 2- Examples include a methylpentoxy group, a 3-methylpentoxy group, and a hexyloxy group. Also,
“C _1-6 alkoxyalkoxy group” refers to a group in which a C _1-6 alkoxy group having the same meaning as defined above is further substituted with a C _1-6 alkoxy group, for example, a methoxymethoxy group, 1-
Methoxyethoxy group, 2-methoxyethoxy group, n-
(3-methoxy) propoxy group and the like. Less than,
As used herein, “C _1-6 alkoxy group” has the same meaning as defined above.

In the present specification, preferred examples of the “C _1-6 thioalkoxy group” include a methylthio group, an ethylthio group, an n-propylthio group, an i-propylthio group,
n-butylthio group, i-butylthio group, tert-butylthio group, n-pentylthio group, i-pentylthio group, neopentylthio group, n-hexylthio group, 1-methylpropylthio group and the like. Hereinafter, "C
_“1-6 thioalkoxy group” has the same meaning as defined above.

The term "C _3-8 cycloalkyl group" as used herein means a cyclic alkyl group having 3 to 8 carbon atoms.
Preferred examples of the group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group and the like. Preferred _{examples of} the “C _3-8 cycloalkenyl group” include those represented by the formula

Embedded image And the group represented by Hereinafter, “C _3-8 cycloalkyl group” and “C _3-8 cycloalkenyl group” in the specification of the present application have the same meanings as defined above, respectively.

The term "C _6-14 aromatic hydrocarbon ring group" as used herein means a monocyclic, bicyclic or tricyclic aromatic hydrocarbon ring group having 6 to 14 carbon atoms. Examples of preferred groups include, for example, phenyl, indenyl, naphthyl, azulenyl, heptalenyl, biphenyl, indacenyl, acenaphthyl, fluorenyl, phenalenyl,
Monocyclic such as phenanthrenyl, anthracenyl, cyclopentacyclooctenyl, benzocyclooctenyl group,
Bicyclic or tricyclic C _6-14 aromatic hydrocarbon ring groups are exemplified. Hereinafter, the “C _6-14 aromatic hydrocarbon ring group” in the specification of the present application has the same meaning as the above definition. The “aryl group” in the specification of the present application is a group having the same meaning as the above “C _6-14 aromatic hydrocarbon ring group”.

Preferred examples of the “5- to 14-membered aromatic heterocyclic group” in the present specification include (1) pyrrolyl, pyridyl, pyridazyl, pyrimidyl,
Pyrazyl, pyrazolyl, imidazolyl, indolyl, isoindolyl, indolizyl, purinyl, indazolyl, quinolyl, isoquinolyl, quinolidyl, phthalidyl, naphthyridyl, quinoxalyl, quinazolyl, cinnolyl, pteridyl, imidazotriazyl, pyrazinopyridazyl, acridil, phenanthryl Nitrogen-containing aromatic heterocyclic groups such as carbazolyl, carbazolyl, perimidyl, phenanthrolyl and phenacyl groups; (2) sulfur-containing aromatic heterocyclic groups such as thienyl and benzothienyl groups;
(3) Oxygen-containing aromatic heterocyclic groups such as furyl, pyranyl, cyclopentapyranyl, benzofuranyl, and isobenzofuranyl groups; A nitrogen atom such as, pyrazolooxazolyl, imidazothiazolyl, thienofuryl, flopyrrolyl, pyridoxazinyl group, etc.
An aromatic heterocyclic group containing two or more hetero atoms selected from the group consisting of a sulfur atom and an oxygen atom is exemplified. Hereinafter, the “5- to 14-membered aromatic heterocyclic group” in the present specification has the same meaning as the above definition. In addition, the "heteroaryl group" in the specification of the present application is a group having the same meaning as the above "5- to 14-membered aromatic heterocyclic group".

Preferred _examples of the "C _2-6 acyl group" in the present specification include an acetyl group, a propionyl group and a butyryl group.

As used herein, the term "optionally substituted amino group" refers to an amino group in which a nitrogen atom may be substituted by one or two identical or different groups. Is 1 or 2 selected from (1) an unsubstituted amino group, (2) (i) a C _1-6 alkyl group, and (ii) an optionally substituted C _6-14 aromatic hydrocarbon ring group. And an amino group substituted with a single group.

Preferred examples of the "C _1-6 alkylsulfonyl group" in the present specification include, for example, a methanesulfonyl group, an ethanesulfonyl group and the like.

The term "sulfonylamido group" as used herein refers to a group represented by the formula -SO ₂ NH ₂ .

[0028] "Hydroxy C _1-6 alkyl group" in the present specification, 1 or shows at least two hydroxyl groups in the substituted C _1-6 alkyl group as defined in the definition-out preferably in the group Examples thereof include a hydroxymethyl group, a 1-hydroxyethyl group, a 2-hydroxyethyl group, and an n- (1-hydroxy) propyl group.

Preferred examples of the "C _1-6 alkylsulfonylamino group" in the present specification include, for example, methanesulfonylamino group, ethanesulfonylamino group, n-propanesulfonylamino group, n-butanesulfonylamino group, N- And a methylmethanesulfonylamino group.

The term "C _1-6 acylamino group" as used herein means an amino group to which a lower fatty acid having 2 to 6 carbon atoms is bonded. And the like.

In the specification of the present application, the "lower acylaminoalkyl group optionally substituted with a nitrogen atom" includes, for example, those described above such as acetamidomethyl group, acetamidoethyl group, propionamidomethyl group and butyrylamidomethyl group. Examples thereof include a group in which a lower acyl group is bonded to an amino lower alkyl group, and the nitrogen atom may be further substituted with a lower alkyl group or the like.

In the specification of the present application, "optionally substituted arylsulfonylamino group"
For example, an aryl group such as a benzenesulfonylamino group and a toluenesulfonylamino group may be substituted with a sulfonylamino group (-S
A group to which O ₂ NH—) is bonded or a group in which the aryl group is further substituted,

More specifically, the term “C _1-6 alkylsulfonyloxy group” as used herein means a group in which a sulfonyloxy group (—SO ₃ —) is bonded to the lower alkyl group.

The term "optionally substituted amino C _1-6 alkyl group" as used herein means a C _1-6 alkyl group having an _optionally substituted amino group as a substituent. The preferred group in the “optionally substituted amino group” is, for example, a group in which the nitrogen atom is selected from a C _1-6 alkyl group, a C _1-6 alkylsulfonyl group and the like.
Or an amino group which may be substituted with two or more groups.

In the present specification, the “aralkyl group” in the “optionally substituted aralkyl group” is
_6-14 represents a C _1-6 alkyl group substituted with an aromatic hydrocarbon ring group, for example, benzyl group, phenethyl group, phenylpropyl group and the like, and the “aralkyl group” further has a substituent. You may. In the present specification, the “heteroaryl C _1-6 alkyl group” in the “optionally substituted heteroaryl C _1-6 alkyl group” is a C _1- substituted with a 5- to 14-membered aromatic heterocyclic group. _{6 represents} an alkyl group, for example, pyridylmethyl group, pyridylethyl group, pyrazylethyl group, pyridonemethyl group, pyrrolidonemethyl group, pyrrolylmethyl group, imidazolylmethyl group,
And a triazolylmethyl group, a thiazolylmethyl group, and the like. Further, the "heteroaryl C _1-6 alkyl group"
May have a substituent. Further, the present application as "C _3-8 cycloalkyl alkylcarbonylamino C _1-6 alkyl group" in the specification, the definition carbonyl C _3-8 cycloalkyl group as defined linked to a carbonyl group to an amino C _1-6 Shows an alkyl group.

Preferred examples of the “optionally substituted carbamoyl C _1-6 alkyl group” in the present specification include, for example, a carbamoylmethyl group represented by the formula —CH ₂ CONH ₂ and a nitrogen atom of the carbamoylmethyl group. And a group substituted with a C _1-6 alkyl group and the like. In the specification of the present application, preferred examples of the “optionally substituted thiocarbamoyl C _1-6 alkyl group” include, for example, a thiocarbamoylmethyl group represented by the formula —CH ₂ CSNH ₂ , A group in which an atom is substituted with a C _1-6 alkyl group and the like.

Preferred examples of the "heteroarylcarbonyl group" in the present specification include, for example, a pyridylcarbonyl group, a pyrrolylcarbonyl group, a thiazolylcarbonyl group and the like.

In the present specification, "halogenated C"_1-6A
"Alkyl group" means one or more identical or different
Halogen atom (fluorine atom, chlorine atom, bromine atom,
C substituted with an iodine atom, etc._1-6Represents an alkyl group,
Preferred groups in the group include a chloromethyl group and a chloromethyl group.
Examples thereof include a fluoromethyl group and a fluoroethyl group. Ma
In addition, "hetero which may be substituted"
Arylhydroxy C _1-6Alkyl group "
Groups include, for example, a pyridylhydroxymethyl group,
Azolylhydroxymethyl group, pyrimidylhydroxymethyl
Examples include a tyl group and a pyrrolylhydroxymethyl group.

[The compound of the formula (II)
Preferred Embodiment] In the above formula (II), the formula

Embedded image (Wherein, Ar ¹ ring, R ³ , R ⁴ , R ⁵ , D and n have the same meanings as defined above).

Embedded image [Wherein, R ³ , R ⁴ and R ⁵ have the same meanings as defined above; the partial structure --- represents a single bond or a double bond. ]
And any group selected from the group consisting of

Embedded image [Wherein, R ³ , R ⁴ and R ⁵ have the same meanings as defined above; the partial structure --- represents a single bond or a double bond. ]
Is a group represented by

In the formula (II), m represents 0 or an integer of 1 to 6, and the most preferred value of m is 0.

In the above formula (II),

Embedded image [Wherein, R ³³ , R ³⁴ , A, Y and t have the same meanings as defined above. As a preferred embodiment of the group represented by the formula (1), a group in which t is 2 is mentioned, and more preferably, a group in which X is a methine group, Y is a nitrogen atom and t is 2 (that is, a piperidyl group).

In the compound represented by the formula (II)
Specific examples of preferred embodiments include, for example, (1) 1-
[1- (4-Fluorophenyl) piperidine-4-i
Ru] Indoline, (2) 1- [1- (4-fluoroben
Jill) piperidin-4-yl] indoline, (3) 1-
(1-phenethylpiperidin-4-yl) indoline,
(4) 1- [1- (4-bromophenethyl) piperidine
-4-yl] indoline, (5) 1- [1- (3-chloro
Rophenethyl) piperidin-4-yl] indoline,
(6) 1- [1- (4-chlorophenethyl) piperidine
-4-yl] indoline, (7) 1- [1- (2-full)
Orophenethyl) piperidin-4-yl] indoline,
(8) 1- [1- (3-fluorophenethyl) piperidi
N-4-yl] indoline, (9) 1- [1- (4-F
Fluorophenethyl) piperidin-4-yl] indori
, (10) 1- [1- (2,4-difluorophenethylene)
Ru) piperidin-4-yl] indoline, (11) 1-
[1- (3,4-difluorophenethyl) piperidine-
4-yl] indoline, (12) 1- [1- (3,5-di
Fluorophenethyl) piperidin-4-yl] indori
, (13) 1- [1- (4-fluorophenylpropyl)
Ru) piperidin-4-yl] indoline, (14) 1-
{1- [2- (4-fluorophenyl) propyl] pipe
Lysin-4-yl @ indoline, (15) 1- [1- (4
-Fluorophenylbutyl) piperidin-4-yl] i
Ndrin, (16) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] methylindoline, (17)
1- {2- [1- (4-fluorophenethyl) piperidi
N-4-yl] ethyl @ indoline, (18) 1- [1-
(4-methoxyphenethyl) piperidin-4-yl] i
Ndrin, (19) 1- [1- (3-methoxyphenethylene)
Ru) piperidin-4-yl] indoline, (20) 1-
[1- (4-Hydroxyphenethyl) piperidine-4-
Yl] indoline, (21) 1- [1- (4-cyanofe)
Netyl) piperidin-4-yl] indoline, (22) 1
-[1- (3-hydroxymethylphenethyl) piperidi
N-4-yl] indoline, (23) 1- [1- (4-H
Droxymethylphenethyl) piperidin-4-yl] i
Ndrin, (24) 1- {1- [4- (2-hydroxyd
Tyl) phenethyl] piperidin-4-yl @ indori
, (25) 1- {4-[(1-hydroxyethyl) phenyl
Netyl] piperidin-4-yl @ indoline, (26) 1
-｛1- [4- (2-hydroxyethoxy) phenethyl
Ru] piperidin-4-yl @ indoline, (27) 1-
[1- (4-trifluoromethylphenethyl) piperidi
N-4-yl] indoline, (28) 1- [1- (4-me
Tansulfonylphenethyl) piperidin-4-yl] i
Ndrin, (29) 1- [1- (4-nitrophenethyl)
Piperidin-4-yl] indoline, (30) 1- [1-
(4-Aminophenethyl) piperidin-4-yl] in
Dolin, (31) 1- [1- (4-methylsulfonylamido)
Nophenethyl) piperidin-4-yl] indoline and
And 1- {1- [4-bis (methylsulfonyl) aminophen]
Enetyl] piperidin-4-yl @ indoline, (32)
1- [1- (4-acetamidophenethyl) piperidine
-4-yl] indoline, (33) 1- [1- (4-ethyl
Ruaminophenethyl) piperidin-4-yl] indori
, (34) 1- [1- (4-hydroxyiminomethylf
Phenethyl) piperidin-4-yl] indoline, (35)
1- [1- (4-aminomethylphenethyl) piperidine
-4-yl] indoline, (36) 1- [1- (4-ace
Toamidomethylphenethyl) piperidin-4-yl] i
Ndrin, (37) 1- [1- (4-chloroacetamide)
Methylphenethyl) piperidin-4-yl] indori
, (38) 1- [1- (4-methanesulfonylaminomethyl)
Tilphenethyl) piperidin-4-yl] indoline,
(39) 1- [1- (4-propionylaminomethylphen)
Netyl) piperidin-4-yl] -3-methylindori
, (40) 1- [1- (4-carbamoylphenethyl)
Piperidin-4-yl] indoline, (41) 1- [1-
(4-N-isopropylcarbamoylmethylphenetici
Ru) piperidin-4-yl] indoline, (42) 1-
[1- (4-Sulfamoylphenethyl) piperidine-
4-yl] indoline, (43) 1- {3-[(2-hydr)
Roxyethoxy) phenethyl] piperidin-4-yl}
Indoline, (44) 1- {1- [4- (2-dimethyla)
Minoethoxy) phenethyl] piperidin-4-ylpyi
Ndrin, (45) 1- {1- [3,4-di (hydroxy
Methyl) phenethyl] piperidin-4-yl} indori
, (46) 1- {1- [3,4- (methylenedioxy)
Phenethyl] piperidin-4-yl @ indoline, (4
7) 1- {1- [2- (4-chlorophenylsulfonyl)
Amino) ethyl] piperidin-4-yldiindoline,
(48) 1- {1- [2- (4-methoxyphenylsulfo)
Nylamino) ethyl] piperidin-4-ylindolin
, (49) 1- {1- [2- (4-pyridyl) ethyl]
Piperidin-4-yl} indolin, (50) 1- {1-
[2- (2-pyridyl) ethyl] piperidine-4-i
Rudoindoline, (51) 1- {1- [2- (3-pyridi)
Ru) ethyl] piperidin-4-yl @ indoline, (5
2) 1- {1- [2- (2-methoxy-5-pyridyl)]
Ethyl] piperidin-4-yl @ indoline, (53) 1
-{1- [2- (3-methoxypyridin-5-yl) e
Tyl] piperidin-4-yl @ indoline, (54) 1-
{1- [2- (2-cyanopyridin-5-yl) ethyl]
Ru] piperidin-4-yl @ indoline, (55) 1-
{1- [2- (2-hydroxymethylpyridine-5-i)
Ru) ethyl] piperidin-4-yl @ indoline, (5
6) 1- {1- [2- (3-hydroxymethylpyridine)
-5-yl) ethyl] piperidin-4-yl @ indori
, (57) 1- [1- (2,6-difluoro-3-pyri)
Zylethyl) piperidin-4-yl] indoline, (5
8) 1- {1- [2- (2-thienyl) ethyl] piperi
Zin-4-yl @ indoline, (59) 1- {1- [2-
(3-thienyl) ethyl] piperidin-4-yldiyne
Dolin, (60) 1- [1- (2-thiazolylethyl) pi
Peridin-4-yl] indoline, (61) 1- [1-
(4-methyl-5-thiazolylethyl) piperidine-4
-Yl] 1drin, (62) 1- ｛1-[(indole
-3-yl) ethyl] piperidin-4-yl @ indori
, (63) 1- {1- [2- (6-benzothiazolyl)
Ethyl] piperidin-4-yl @ indoline, (64) 1
-[1- (5-methoxy-2-thienyl) ethylpiperi
Zin-4-yl] indoline, (65) 1- [1- (2-
Methoxy-5-thiazoyl) ethylpiperidine-4-i
Ru] Indoline, (66) 1- [1- (2-cyano-5
Thiazolyl) ethylpiperidin-4-yl] indori
, (67) 1- (1-pyrazinylethylpiperidine-4)
-Yl) indoline, (68) 1- {1- [2- (4-B
Lomopyrazol-1-yl) ethyl] piperidine-4-
Il @ indoline, (69) 1- {1- [3- (4-full)
Orophenoxy) propyl] piperidin-4-ylpyi
Ndrin, (70) 1- {1- [3- (4-hydroxymeth
Tylphenoxy) propyl] piperidin-4-ylpy
Ndrin, (71) 1- {1- [3- (4-hydroxyd
Tylphenoxy) propyl] piperidin-4-ylpy
Ndrin, (72) 1- {1- [4- (4-fluorophene)
Nil) -4-oxobutyl] piperidin-4-yldiy
Ndrin, (73) 1- {1- [4- (4-fluorophene)
Nyl) -4-hydroxybutyl] piperidin-4-i
Rudoindoline, (74) 1- [1- (phthalimido-1
-Yl) ethylpiperidin-4-yl] indoline,
(75) 1- [1- (4-Fluorobenzamido) ethylpi
Peridin-4-yl] indoline, (76) 1- {1-
[1- (3,4-Dimethoxyphenyl) propane-2-
Il] piperidin-4-yl @ indoline, (77) 1-
{1-[(1,4-benzodioxan-2-yl) methyl]
Ru] piperidin-4-yl @ indoline, (78) 1-
[1- [3- (3,4-methylenedioxyphenoxy)
Propyl] piperidin-4-yl] indoline, (79)
1- [1- (4-fluorophenethyl) -3-methylpi
Peridin-4-yl] indoline, (80) 1- (1-B
Benzyl-3-hydroxymethylpiperidin-4-yl)
Indoline, (81) 1- [1- (4-fluorophenetici)
L) -3-Hydroxymethylpiperidin-4-yl] i
Ndrin, (82) 1- [1- (4-fluorophenetici)
L) -3-Hydroxymethylpiperidin-4-yl] i
Ndrin, (83) 1- [2- (4-acetamidomethyl)
Phenyl) ethyl] -4- (indan-1-yl) pipe
Lysine-1-oxide, (84) 1- [1-ethyl-3-
(4-fluorophenoxymethyl) piperidine-4-i
Indoline, (85) 1- [1-ethyl-3- (4-
Fluorobenzyloxymethyl) piperidine-4-i
Indolin, (86) 1- [1-ethyl-3- (4-
Fluorobenzyloxymethyl) piperidine-4-i
Ru] indoline, (87) 1- (1-acetylpiperidine)
-4-yl) indoline-7-carbaldehyde, (88)
1- [1- (4-t-butoxycarbonyl) piperidine
-4-yl] -6-bromoindoline, (89) 1- [1
-(4-t-butoxycarbonyl) piperidine-4-i
Ru] -6-hydroxymethylindoline, (90) 1-
[1- (4-t-butoxycarbonyl) piperidine-4
-Yl] -6-aminomethylindoline, (91) 1-
(1-benzylpiperidin-4-yl) -6-bromoy
Ndrin, (92) 1- (1-benzylpiperidine-4-
Yl) -6-fluoroindoline, (93) 1- (1-
Ndylpiperidin-4-yl) -6-formylindori
, (94) 1- (1-benzylpiperidin-4-yl)
-6-hydroxyiminomethylindoline, (95) 1-
(1-benzylpiperidin-4-yl) -6-aminomethyl
Tilindolin, (96) 1- (1-benzylpiperidine)
-4-yl) -6-acetamidomethylindoline,
(97) 1- [1- (4-methoxyphenethyl) piperidi
4-yl] -6-acetamidomethylindoline,
(98) 1- [1- (4-Chlorophenethyl) piperidine
-4-yl] -6-acetamidomethylindoline,
(99) 1- [1- (4-Fluorophenethyl) piperidi
N-4-yl] -5-methoxyindoline, (100) 1
-[1- (4-Fluorophenethyl) piperidine-4-
Yl] -6-bromoindoline, (101) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6-bromoindoline, (102) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6-chloro
Indoline, (103) 1- [1- (4-fluorophene)
Tyl) piperidin-4-yl] -6-fluoroindoli
, (104) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6-hydroxyindoline,
(105) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -4-methoxyindoline, (106)
1- [1- (4-fluorophenethyl) piperidine-4
-Yl] -6-methoxyindoline, (107) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
] -7-methoxyindoline, (108) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6,7-dimethoxyindoline, (109) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6-nitroindoline, (110) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6-amino
Indoline, (111) 1- [1- (4-fluorophene)
Tyl) piperidin-4-yl] -6-methylaminoin
Dolin, (112) 1- [1- (4-fluorophenethylene)
Ru) piperidin-4-yl] -6-ethylaminoindo
Phosphorus, (113) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6-isopropylaminoin
Dolin, (114) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6-dimethylaminoin
Dolin, (115) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6-acetamidoindo
Phosphorus, (116) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6-methanesulfonylamino
Indoline, (117) 1- [1- (4-fluorophene)
Tyl) piperidin-4-yl] -6-ethanesulfonyl
Aminoindoline, (118) 1- [1- (4-fluoro
Phenethyl) piperidin-4-yl] -6-propanes
Ruphonylaminoindoline, (119) 1- [1- (4-
Fluorophenethyl) piperidin-4-yl] -6
(4-fluorobenzenesulfonylamino) indori
, (120) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6- (N-methylmethanesulfo
Nylamino) indoline, (121) 1- [1- (4-F
Fluorophenethyl) piperidin-4-yl] -6-hydr
Roxyethoxyindoline, (122) 1- [1- (4-
Fluorophenethyl) piperidin-4-yl] -6-meth
Tansulfonyloxyindoline, (123) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
7-hydroxyethoxyindoline, (124) 1- [1
-(4-Fluorophenethyl) piperidin-4-yl]
-6-cyanoindoline, (125) 1- [1- (4-f
Fluorophenethyl) piperidin-4-yl] -6-cal
Bamoyl indoline, (126) 1- [1- (4-fluoro
Lophenethyl) piperidin-4-yl] -6- (1-pi
(Lorylcarbonyl) indoline, (127) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6-acetylindoline, (128) 1- [1- (4-f
Fluorophenethyl) piperidin-4-yl] -6-meta
Sulfonylindoline, (129) 1- [1- (4-f
Fluorophenethyl) piperidin-4-yl] -6-thio
Carbamoylmethylindoline, (130) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6-formylindoline, (131) 1- [1- (4-f
Fluorophenethyl) piperidin-4-yl] -6-hydr
Roximinomethylindoline, (132) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6-aminomethylindoline, (133) 1- [1- (4
-Fluorophenethyl) piperidin-4-yl] -6
Acetamidomethylindoline, (134) 1- [1-
(2-Fluorophenethyl) piperidin-4-yl]-
6-acetamidomethylindoline, (135) 1- [1
-(3-Fluorophenethyl) piperidin-4-yl]
-6-acetamidomethylindoline, (136) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
Ru] -6-hydroxymethylindoline, (137) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
Ru] -6- (1-hydroxyethyl) indoline, (13
8) 1- [1- (4-Fluorophenethyl) piperidine
-4-yl] -6- (1-hydroxypropyl) india
Phosphorus, (139) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6- (1-hydroxy-1-
Methylethyl) indoline, (140) 1- [1- (4-
Fluorophenethyl) piperidin-4-yl] -6
(1-hydroxycyclobutyl) indoline, (141)
1- [1- (4-fluorophenethyl) piperidine-4
-Yl] -6- (1-hydroxycyclopentyl) in
Dolin, (142) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6-chloromethylindo
Phosphorus, (143) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6-fluoromethylindori
, (144) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6- (1-fluoroethyl) i
Ndrin, (145) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6-cyanomethylindo
Phosphorus, (146) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6-carboxymethylindo
Phosphorus, (147) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6-carbamoylmethylin
Dolin, (148) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6- (methylcarbamoy
(Methyl) indoline, (149) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6- (ethyl
Rucarbamoylmethyl) indoline, (150) 1- [1
-(4-Fluorophenethyl) piperidin-4-yl]
-6- (n-propylcarbamoylmethyl) indori
, (151) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6- (isopropylcarbamoy
(Methyl) indoline, (152) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6- (iso
(Butylcarbamoylmethyl) indoline, (153) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
] -6- (t-butylcarbamoylmethyl) indori
, (154) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6- (cyclopropylcarbamo
Ylmethyl) indoline, (155) 1- [1- (4-f
Fluorophenethyl) piperidin-4-yl] -6- (te
Tramethylenecarbamoylmethyl) indoline, (15
6) 1- [1- (4-fluorophenethyl) piperidine
-4-yl] -6-propionylaminomethylindori
, (157) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6- (n-butyryl) aminometh
Chilindoline, (158) 1- [1- (4-fluorofuran)
Enetyl) piperidin-4-yl] -6-isobutyryl
Aminomethylindoline, (159) 1- [1- (4-F
Fluorophenethyl) piperidin-4-yl] -6-cyclo
Lopropanecarboxamide methylindoline, (160)
1- [1- (4-fluorophenethyl) piperidine-4
-Yl] -6-methylsulfonylaminomethylindori
, (161) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6-ureidomethylindori
, (162) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6-N-methylaminomethyli
Ndrin, (163) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6-N-methylacetoa
Midomethylindoline, (164) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6- (N-
Methylsulfamoylmethyl) indoline, (165) 1
-[1- (4-Fluorophenethyl) piperidine-4-
Yl] -6- (1-acetamidoethyl) indoline,
(166) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6-acetamidoethylindori
, (167) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6-[(piperidin-4-i
L) methyl] indoline, (168) 1- [1- (4-f
Fluorophenethyl) piperidin-4-yl] -6
[(1-acetylpiperidin-4-yl) methyl] in
Dolin, (169) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6-[(1-ethylpipe
Lysin-4-yl) methyl] indoline, (170) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
] -6-[(1-Methylpiperidin-4-yl) methyl
Ru] Indoline, (171) 1- [1- (4-fluorofuran)
Enetyl) piperidin-4-yl] -6- (2-pyridi
Ru) Indoline, (172) 1- [1- (4-fluorofuran)
Enetyl) piperidin-4-yl] -6- (2-thiazo
Ryl) indoline, (173) 1- [1- (4-fluoro
Phenethyl) piperidin-4-yl] -6- (1-methyl
Rupyrol-2-yl) indoline, (174) 1- [1
-(4-Fluorophenethyl) piperidin-4-yl]
-6- [1-hydroxy-1- (2-pyridyl) methyl
Ru] Indoline, (175) 1- [1- (4-fluorofuran)
Enetyl) piperidin-4-yl] -6- [1- (2-
Pyridyl) methyl] indoline, (176) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6- [1-hydroxy-1- (3-pyridyl) methyl]
Indoline, (177) 1- [1- (4-fluorophene)
Tyl) piperidin-4-yl] -6- [1- (3-pyri)
(Jill) methyl] indoline, (178) 1- [1- (4-
Fluorophenethyl) piperidin-4-yl] -6
(1-hydroxy-4-pyridylmethyl) indoline,
(179) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6- (4-pyridylmethyl) india
Phosphorus, (180) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6- (2-pyridylcarboni
Ru) Indoline, (181) 1- [1- (4-fluorofuran)
Enetyl) piperidin-4-yl] -6- [1-hydro
Xy-1- (2-pyridyl) ethyl] indoline, (18
2) 1- [1- (4-Fluorophenethyl) piperidine
-4-yl] -6- [1- (2-pyridyl) ethyl] i
Ndrin, (183) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6- (3-pyridylcar
Bonyl) indoline, (184) 1- [1- (4-fluoro)
Lophenethyl) piperidin-4-yl] -6- [1-h
Droxy-1- (2-methoxypyridin-3-yl) meth
Tyl] indoline, (185) 1- [1- (4-fluoro
Phenethyl) piperidin-4-yl] -6- [1- (2
-Methoxypyridin-3-yl) methyl] indoline,
(186) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6- [1-hydroxy-1- (2-
Methoxypyridin-6-yl) methyl] indoline,
(187) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6- [1- (2-methoxypyridine)
-6-yl) methyl] indoline, (188) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6- [1-hydroxy-1- (2-methoxypyridine-
5-yl) methyl] indoline, (189) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6- [1- (2-methoxypyridin-5-yl) methyl
Ru] Indoline, (190) 1- [1- (4-fluorofuran)
Enetyl) piperidin-4-yl] -6- [1-hydro
Xy-1- (2-pyridone-5-yl) methyl] india
Phosphorus, (191) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6- [1-hydroxy-1-
(2-dimethylaminopyridin-5-yl) methyl] i
Ndrin, (192) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6- [1-hydroxy-
1- (2-chloropyridin-5-yl) methyl] india
Phosphorus, (193) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6- [1- (2-thiazoly
Ru) -1-Hydroxymethyl] indoline, (194) 1
-[1- (4-Fluorophenethyl) piperidine-4-
Yl] -6- (2-thiazolylcarbonyl) indori
, (195) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6- [1- (4-thiazolyl)
-1-hydroxymethyl] indoline, (196) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
] -6- [1- (5-Thiazolyl) -1-hydroxy
Methyl] indoline, (197) 1- [1- (4-fluoro)
Lophenethyl) piperidin-4-yl] -6- [1-h
Droxy-1- (pyrimidin-2-yl) methyl] yne
Dolin, (198) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6- [1-hydroxy-
1- (pyrimidin-5-yl) methyl] indoline,
(199) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6- [1-hydroxy-1- (2-
Pyrrolyl) methyl] indoline, (200) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6-N, N-dimethylaminomethylindoline, (20
1) 1- [1- (4-Fluorophenethyl) piperidine
-4-yl] -6- (4-fluorophenyl) indori
, (202) 1- [1- (4-Fluorophenethyl) pi
Peridin-4-yl] -6- (2-pyrrolidone-1-i
M) methylindoline, (203) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6- (2-
Piperidone-1-yl) methylindoline, (204) 1
-[1- (4-Fluorophenethyl) piperidine-4-
Yl] -6- (succinimid-1-yl) methylindo
Phosphorus, (205) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6- (glutarimide-1-
Yl) methylindoline, (206) 1- [1- (4-f
Fluorophenethyl) piperidin-4-yl] -6- (2
-Imidazolidonyl) methylindoline, (207) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
Ru] -6- (2,4-Imidazolidinedione-3-i
M) methylindoline, (208) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6- (2-
Oxazolidone-3-yl) methylindoline, (20
9) 1- [1- (4-Fluorophenethyl) piperidine
-4-yl] -6- (2,4-thiazolidinedione-3
-Yl) methylindoline, (210) 1- [1- (4-
Fluorophenethyl) piperidin-4-yl] -6
(Pyrrole-1-yl) methylindoline, (211) 1
-[1- (4-Fluorophenethyl) piperidine-4-
Yl] -6- (imidazol-1-yl) methylindo
Phosphorus, (212) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6- (1,2,3-triazo
1-yl) methylindoline and 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6- (1,2,3-triazol-2-yl) methyli
Ndrin, (213) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6- (1,2,4-tri
Azol-2-yl) methylindoline, (214) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
Ru] -6- (2-thiazolyl) methylindoline, (21
5) 1- [1- (4-fluorophenethyl) piperidine
-4-yl] -3- (4-methoxybenzyl) indori
, (216) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -3-methylindoline, (21
7) 1- [1- (4-fluorophenethyl) piperidine
-4-yl] -5-chloro-6-aminoindoline,
(218) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -5-chloro-6-methanesulfonyl
Aminoindoline, (219) 1- [1- (4-fluoro
Phenethyl) piperidin-4-yl] -5-chloro-6
-Methoxyindoline, (220) 1- [1- (2,4-
Difluorophenethyl) piperidin-4-yl] -6
Aminoindoline, (221) 1- [1- (2,4-diph
Fluorophenethyl) piperidin-4-yl] -6-meta
Sulfonylaminoindoline, (222) 1- [1-
(2,4-difluorophenethyl) piperidine-4-i
] -6-acetamidoindoline, (223) 1- [1
-(2,4-difluorophenethyl) piperidine-4-
Yl] -6-bromoindoline, (224) 1- [1-
(2,4-difluorophenethyl) piperidine-4-i
] -6-acetamidomethylindoline, (225) 1
-[1- (2,4-difluorophenethyl) piperidine
-4-yl] -6-carbamoylmethylindoline,
(226) 1- {1- [3- (4-fluorophenyl) p]
Ropyl] piperidin-4-yl} -6-acetamidometh
Chilindoline, (227) 1- {1- [4- (4-full)
Orophenyl) butyl] piperidin-4-yl} -6
Acetamidomethylindoline, (228) 1- [1-
(4-methoxyphenethyl) piperidin-4-yl]-
6-methoxyindoline, (229) 1- [1- (4-me
Toxiphenethyl) piperidin-4-yl] -6-fur
Oroindoline, (230) 1- [1- (4-sulfamo)
Ilphenethyl) piperidin-4-yl] -6-methoxy
Shindoline, (231) 1- [1- (4-fluorophene)
Noxypropyl) piperidin-4-yl] -6-bromo
Indoline, (232) 1- [1- (4-fluoropheno)
Xypropyl) piperidin-4-yl] -6-acetoa
Midomethylindoline, (233) 1- {1- [2- (6
-Benzothiazolyl) ethyl] piperidin-4-yl}
-6-methoxyindoline, (234) 1- [1- (4-
Fluorophenethyl) piperidin-4-yl] thiazolo
[5,4-f] indoline, (235) 1- [1- (4-
Fluorophenethyl) piperidin-4-yl] -6-a
Minothiazolo [5,4-f] indoline, (236-1) 1
-[1- (4-Fluorophenethyl) piperidine-4-
Yl] -7-hydroxy- (4a, 7a) -cyclohexyl
Sanoindoline, (236-2) 1- [1- (4-fluoro
Phenethyl) piperidin-4-yl] -4-hydroxy
-(3b, 6a) -cyclohexanoindoline, (23
7) 1- (1-Methylpiperidin-4-yl) -6
(4-fluorobenzenesulfonylamino) indori
, (238) 1- (1-ethylpiperidin-4-yl)
-6- (4-fluorobenzenesulfonylamino) in
Dolin, (239) 1- (1-ethylpiperidinyl) -4
-(4-fluorophenyl) indoline, (240) 1-
(1-ethylpiperidin-4-yl) -3- (4-fur
(Orophenyl) indoline, (241) 1- (1-ethyl)
Piperidin-4-yl) -3- (4-methoxyphenyl)
Ru) Indoline, (242) 1- (1-ethylpiperidine)
-4-yl) -3- (4-methoxybenzyl) indori
(243) 1-[(1-ethylpiperidin-4-i
Ru) methyl] -3- (4-methoxybenzyl) indori
, (244) 1- (1-ethylpiperidin-4-yl)
-3- (4-Fluorobenzyl) indoline, (245)
1- (1-ethylpiperidin-4-yl) -3- (3-
Pyridylmethyl) indoline, (246) 1- (1-ethyl)
Lupiperidin-4-yl) -3- (3-methoxyphenene
Chill) indoline, (247) 1- (1-ethylpiperidi)
N-4-yl) -3- (3-fluorophenethyl) in
Dolin, (248) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] indan, (249) 1-
[1- (4-methoxyphenethyl) piperidine-4-i
Indane, (250) 1- {4- [2- (4-fluoro)
Rophenyl) ethyl] piperazin-1-yl {-6-me
Toxiindane, (251) 1- (4-ethylpiperazine
-1-yl) -6-methoxyindane, (252) 1-
(4-ethylpiperazin-1-yl) -2-ethoxyca
Ruboxyaminoindan, (253) 1- (4-ethylpi
Perazin-1-yl) -2-methylaminoindan;
(254) 1- (4-ethylpiperazin-1-yl) -2
-[Methyl- (4-trifluorobenzyl) amino] i
And (255) 7- [4-hydroxy-1- (4-f
Fluorophenethyl) piperidin-4-yl] -5,6-
Dihydro-7H-pyringin, (256) 7- [1- (4
-Fluorophenethyl) piperidine-4-ylidene]-
5,6-dihydropyringin, (257) 7- [1- (4
-Fluorophenethyl) piperidin-4-yl] -5.
6-dihydro-7H-pyringin, (258) 7- [4-
(4-Fluorophenethyl) piperazin-1-yl]-
5,6-dihydro-7H-pyringin, (259) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
] -6-chloro-7-azaindoline, (260) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
] -7-Azaindoline, (261) 1- [1- (4-
Fluorophenethyl) piperidin-4-yl] -6-fu
Ruoro-7-azaindoline, (262) 1- [1-
(2,4-difluorophenethyl) piperidine-4-i
] -6-chloro-7-azaindoline, (263) 1-
[1- (4-methoxyphenethyl) piperidine-4-i
] -6-chloro-7-azaindoline, (264) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
] -6-azaindoline, (265) 5- [1- (4-
Fluorophenethyl) piperidine-4-ylidene] -7
-Methyl-5,6-dihydrocyclopentapyrazine,
(266) 5- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -7-methyl-5,6-dihydro-5
H-cyclopentapyrazine, (267) 1- {1- [2-
(4-methoxyphenyl) ethyl] piperidin-4-i
Ru-7-methoxy-1,2,3,4-tetrahydroxy
Norin, (268) 1- {1- [2- (4-fluorophene)
Nyl) ethyl] piperidin-4-yl} -7-methoxy
-1,2,3,4-tetrahydroquinoline, (269) 1
-[1- (4-cyanopropyl) piperidine-4-i
Ru] -7-methoxy-1,2,3,4-tetrahydroxy
Norin, (270) 1- {1- [2- (2-thienyl) e
Tyl] piperidin-4-yl} -7-methoxy-1,
2,3,4-tetrahydroquinoline, (271) 1- {1
-[2- (4-fluorophenyl) ethyl] piperidine
-4-yl} -7,8-dimethoxy-1,2,3,4-
Tetrahydroquinoline, (272) 1- {1- [2- (4
-Fluorophenyl) ethyl] piperidin-4-yl}
-7,8-Methylenedioxy-1,2,3,4-tetra
Hydroquinoline, (273) 1- {1- [2- (4-fur
Orophenyl) ethyl] piperidin-4-yl} -7-
Methoxy-8-methyl-1,2,3,4-tetrahydro
Quinoline, (274) 1- {1- [2- (4-fluorofuran)
Enyl) -2-oxoethyl] piperidin-4-yl}
-7-methoxy-1,2,3,4-tetrahydroquinol
, (275) 1- {1- [2- (4-fluorophenyl)
L) -2-Hydroxyethyl] piperidin-4-yl}
-7-methoxy-1,2,3,4-tetrahydroquinol
, (276) 1- {1- [2- (4-fluorophenyl)
Ru) -2-fluoroethyl] piperidin-4-yl}-
7-methoxy-1,2,3,4-tetrahydroquinol
, (277) 1- [2- (4-fluorophenyl) ethyl
L] -4- (6-Methoxy-1,2,3,4-tetrahi
Dronaphthalen-1-yl) piperidine, (278) 1-
[2- (4-fluorophenyl) ethyl] -4- [6-
(2-hydroxy) ethoxy-1,2,3,4-tetra
Hydronaphthalen-1-yl] piperidine, (279)
Lance-1- (4-ethylpiperazin-1-yl) -7
-Methoxy-2- (4-trifluoromethylphenoxy)
B) -1,2,3,4-tetrahydronaphthalene, (28
0) 1- {4- [2- (4-fluorophenyl) ethyl
Ru] piperazin-1-yl} -7-methoxy-1,2,2,
3,4-tetrahydronaphthalene, (281) 1- {4-
[2- (4-fluorophenyl) -2-oxoethyl]
Piperazin-1-yl} -7-methoxy-1,2,3,
4-tetrahydronaphthalene, (282) 1- (4-fur
Orophenethyl) -4- (2-methoxybenzocyclohe
(Ptan-9-yl) piperazine, (283) 5- {4-
[2- (4-fluorophenyl) ethyl] piperazine-
1-yl} -5,6,7,8-tetrahydroisoquinolyl
, (284) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -5,6-methylenedioxyin
Dolin, (285) 1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6-acetamidomethyl
Indole, (286) 1- [1- (4-fluorophene)
Tyl) piperidin-4-yl] -6- (N-isopropyl
Rucarbamoylmethyl) indole, (287) 1- [1
-(4-Fluorophenethyl) piperidin-4-yl]
-6- (1-methylpyrrol-2-yl) indole,
(288) 1- [1- (4-acetamidomethylphenethylene)
Ru) piperidin-4-yl] indole, (289) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
] -6-cyanoindole, (290) 1- [1- (4
-Fluorophenethyl) -3-methylpiperidine-4-
Yl] indole, (291) 1- [1- (4-fluoro
Phenethyl) homopiperidin-4-yl] -6-methoxy
Shindoline, (292) 1- [1- (4-fluorophene)
Netyl) pyrrolidin-3-yl] -6-methoxyindo
Phosphorus, (293) 3,3-dimethyl-1- [1- (4-f
Fluorophenethyl) piperidin-4-yl] -6-bro
Mindoline, (294) 1- [1- (4-fluorophene)
Netyl) piperidin-4-yl] -6- (ethylcarba
Moylmethyl) indole, (295) 1- [1- (4-
Fluorophenethyl) piperidin-4-yl] -6
[N- (cyclopropylcarbamoyl) methyl] india
, (296) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6- [N- (isobutylcarb
Bamoyl) methyl] indole, (297) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6- (n-propylcarbamoylmethyl) indole,
(298) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6- (tetramethylenecarbamoyl
Methyl) indole, (299) 1- [1- (2,4-di
Fluorophenethyl) piperidin-4-yl] -6-ca
Rubamoylmethylindole, (300) 1- [1- (4
-Fluorophenethyl) piperidin-4-yl] -6
(2-hydroxyethyl) carbamoylmethylindole
, (301) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6-dimethylcarbamoylmethyl
Ruindole, (302) 1- [1- (4-fluorophene)
Netyl) piperidin-4-yl] -6- (4-hydroxy
Cipiperidin-1-ylcarbonylmethyl) indole
, (303) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6- [bis (2-hydroxy
Tyl] carbamoylmethylindole, (304) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
Ru] -6- (1,3-dihydroxypropane-2-i
L) carbamoylmethylindole, (305) 1- [1
-(4-Fluorophenethyl) piperidin-4-yl]
-6-carbamoylmethylindole, (306) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
Ru] -6- (carbamoylmethyl) carbamoylmethyl
Indole, (307) 1- [1- (4-fluorophene)
Tyl) piperidin-4-yl] -6- (2-dimethyla
Minoethyl) carbamoylmethylindole, (308)
1- [1- (4-fluorophenethyl) piperidine-4
-Yl] -6-cyanomethylcarbamoylmethylindo
, (309) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6- (2-methoxyethyl)
Carbamoylmethylindole, (310) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6- (2-fluoroethyl) carbamoylmethylindia
, (311) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6- [2- (ethylcarbamo
Il) ethyl] indole, (312) 1- [1- (4-
Fluorophenethyl) piperidin-4-yl] -6
[2- (pyrrolidin-1-yl) ethyl] carbamoyl
Methylindole, (313) 1- [1- (4-fluoro
Phenethyl) piperidin-4-yl] -6- [2- (mo
Ruphorin-4-yl) ethyl] carbamoylmethylin
Dole, (314) 1- [1- (4-fluorophenethyl)
Ru) piperidin-4-yl] -6- (pyridin-4-i
G) Methylcarbamoylmethylindole, (315) 1
-[1- (4-Fluorophenethyl) piperidine-4-
Yl] -6- [2- (pyridin-2-yl) ethyl] ca
Rubamoylmethylindole, (316) 1- [1- (4
-Fluorophenethyl) piperidin-4-yl] -6
Methylcarbamoylmethylindole, (317) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
] -6- (2-methoxypyridin-5-ylcarboni
Le) indole, (318) 1- [1- (4-fluorofuran)
Enetyl) piperidin-4-yl] -6-[(2-meth
Xypyridin-5-yl) hydroxymethyl] indoh
, (319) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6- (1-hydroxypropyl
Le) indole, (320) 1- [1- (4-fluorofuran)
Enetyl) piperidin-4-yl] -6- (1-hydro
(Xy-1-methylethyl) indoline, (321) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
Ru] -6- (3-hydroxypropyl) indole,
(322) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6-methanesulfonamidomethyli
Ndole, (323) 1- [1- (4-fluorophenethyl)
Ru) piperidin-4-yl] -6-isopropylsulfo
Amidomethylindole, (324) 1- [1- (4-
Fluorophenethyl) piperidin-4-yl] -6-
n-propylsulfonamidomethylindole, (32
5) 1- [1- (4-fluorophenethyl) piperidine
-4-yl] -6- (3-chloropropyl) sulfone
Midomethylindole, (326) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6- (1,
3-propanesultam-2-yl) methylindole,
(327) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6-propionylaminomethylin
Dole, (328) 3-chloro-1- [1- (4-fluoro)
Lophenethyl) piperidin-4-yl] -6-acetoa
Midomethylindole, (329) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6- (4-
(Hydroxybutyroamidomethyl) indole, (33
0) 1- [1- (4-Fluorophenethyl) piperidine
-4-yl] -6-hydroxyethoxyindole,
(331) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6-methanesulfonylindole,
(332) 1- [1- (2,6-difluoro-3-pyridi
Ruethyl) piperidin-4-yl] indole, (33
3) 1- [1- (4-Fluorophenethyl) piperidine
-4-yl] -6-fluoroindole, (334) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
Ru] thiazolo [5,4-f] indole, (335) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
] -6- (N-methylmethanesulfonylamino) yne
Dole, (336) 1- [1- (4-fluorophenethyl)
Ru) piperidin-4-yl] -6-methanesulfonylo
Xindole, (337) 1- [1- (4-fluorofuran)
Enetyl) piperidin-4-yl] -6-carbamoyl
Indole, (338) 1- [1- (4-fluorophene)
Tyl) piperidin-4-yl] -6- (N-methylsul
Famoylmethyl) indole, (339) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6-acetamidoindole, (340) 1- [1- (4
-Fluorophenethyl) piperidin-4-yl] -6
(1,2-dihydroxypropan-3-yl) carbamo
Ilmethylindole, (341) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6- (pyri
Zin-2-yl) methylcarbamoylmethylindole
, (341) 1- [1- (2-fluorophenethyl) pi
Peridin-4-yl] -6-methylcarbamoylmethyl
Indole, (343) 1- [1- (2-fluorophene)
Tyl) piperidin-4-yl] -6- (1-acetylpi
Peridin-4-yl) methylcarbamoylmethylindo
, (344) 1- [1- (2-fluorophenethyl)
Piperidin-4-yl] -6-ethylcarbamoylmethyl
Ruindole, (345) 1- [1- (4-fluorophene)
Netyl) piperidin-4-yl] -6- (1-ethylpi
Peridin-4-yl) methylcarbamoylmethylindo
346, 1- [1- (2-fluorophenethyl)
Piperidin-4-yl] -6- (2-hydroxyethyl
B) carbamoylmethylindole, (347) 1- [1
-(4-Fluorophenethyl) piperidin-4-yl]
-6- (1,3-dioxolan-2-ylmethyl) cal
Bamoylmethylindole, (348) 1- [1- (2-
Fluorophenethyl) piperidin-4-yl] -6-a
Minomethylindole, (349) 1- [1- (4-chloro
Lophenethyl) piperidin-4-yl] -6-acetoa
Midomethylindole, (350) 1- [1- (3-fur
Orophenethyl) piperidin-4-yl] -6-aceto
Amidomethylindole, (351) 1- [1- (4-me
Toxiphenethyl) piperidin-4-yl] -6-ace
Toamidomethylindole, (352) 1- [1- (2-
Fluorophenethyl) piperidin-4-yl] -6-a
Cetamidomethylindole, (353) 1- [1- (4
-Fluorophenethyl) piperidin-4-yl] -6
(2,4-Imidazolidinedione-3-yl) methyli
Ndole, (354) 1- [1- (4-fluorophenethyl)
Ru) piperidin-4-yl] -6-isobutyrylamino
Methylindole, (355) 1- [1- (4-fluoro
Phenethyl) piperidin-4-yl] -6- (2-imi
(Dazolidonyl) methylindole, (356) 1- {1-
[4- (4-fluorophenyl) butyl] piperidine-
4-yl} -6-acetamidomethylindole, (35
7) 1- [1- (2,4-difluorophenethyl) pipe
Lysin-4-yl] -6-acetamidomethylindole
, (358) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6- (2-pyrrolidone-1-i
M) methylindole, (359) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6-N-meth
Tilacetamide methyl indole, (360) 1- {1
-[3- (4-fluorophenyl) propyl] piperidi
N-4-yl} -6-acetamidomethylindole,
(361) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6-N-methylaminomethylindo
, (362) 1- [1- (4-fluorophenethyl)
Piperidin-4-yl] -6- (n-butyryl) amino
Methylindole, (363) 1- [1- (4-fluoro
Phenethyl) piperidin-4-yl] -6-cyclopro
Pancarboxamide methyl indole, (364) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
Ru] -6-hydroxyacetamidomethylindole,
(365) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6-difluoroacetamidomethyl
Indole, (366) 1- [1- (4-fluorophenene)
Tyl) piperidin-4-yl] -6-fluoroacetoa
Midomethylindole, (367) 1- [1- (4-fur
Orophenethyl) piperidin-4-yl] -6- (3-
Chloropropionylamino) methylindole, (36
8) 1- [1- (4-Fluorophenethyl) piperidine
-4-yl] -6-imidazocarbonylaminomethyli
And (369) 1- [1- (4-fluorophenethyl)
Ru) piperidin-4-yl] -6- (3-hydroxyp
(Ropionylamino) methylindole, (370) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
] -3-formyl-6-acetamidomethylindole
, (371) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -3-hydroxyimino-6-a
Cetamidomethylindole, (372) 1- [1- (4
-Fluorophenethyl) piperidin-4-yl] -3-
Hydroxymethyl-6-acetamidomethylindole
, (373) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6-chloroacetamidomethyl
Indole, (374) 1- [1- (4-fluorophene)
Tyl) piperidin-4-yl] -6-bromoacetamido
Domethylindole, (375) 1- [1- (4-fluoro
Rophenethyl) piperidin-4-yl] -6- (N, N
-Dimethylaminoacetamido) methylindole,
(376) 1- [1- (4-Fluorophenethyl) piperi
Zin-4-yl] -6-[(piperidin-1-yl) a
Cetamido] methylindole, (377) 1- [1-
(4-Fluorophenethyl) piperidin-4-yl]-
6- (3-bromopropionylamino) methylindole
, (378) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6- (3-N, N-dimethyla
Minopropionyl) aminomethylindole, (379)
1- [1- (4-fluorophenethyl) piperidine-4
-Yl] -6- [3- (piperidin-1-yl) propyl
Onylamino] methylindole, (380) 1- [1-
(2-Fluorophenethyl) piperidin-4-yl]-
6-propionylaminomethylindole, (381) 1
-[1- (2-Fluorophenethyl) piperidine-4-
Yl] -6-fluoroacetamidomethylindole,
(382) 1- [1- (2-Fluorophenethyl) piperi
Zin-4-yl] -6- (3-hydroxypropionyl
Amino) methylindole, (383) 1- [1- (2-
Fluorophenethyl) piperidin-4-yl] -6-h
Droxyacetamidomethylindole, (384) 1-
[1- (4-Fluorophenethyl) piperidine-4-i
Ru] -6-methoxycarbonylaminomethylindole
, (385) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6-N, N-dimethylaminoca
Rubonylaminomethylindole, (386) 1- {1-
[2- (3-pyridyl) ethyl] piperidine-4-i
Ru-6-acetamidomethylindole, (387) 3
-Cyano-1- [1- (4-fluorophenethyl) pipe
Lysin-4-yl] -6-acetamidomethylindole
, (388) 1- {4-[(1-hydroxyethyl)
Enetyl] piperidin-4-yl} -6-acetamide
Methylindole, (389) 1- [1- (4-bromofu)
Enetyl) piperidin-4-yl} -6-acetamide
Methylindole, (390) 1- [1- (2-fluoro
Phenethyl) piperidin-4-yl] -6-formylui
And (391) 1- [1- (2-fluorophenethyl)
Ru) piperidin-4-yl] -6-hydroxymethyli
And (392) 1- [1- (4-fluorophenethyl)
Ru) piperidin-4-yl] -6- (1-hydroxyd
Tyl) indole, (393) 1- [1- (4-fluoro
Phenethyl) piperidin-4-yl] -6-ureidome
Chilindole, (394) 1- [1- (4-fluorofuran)
Enetyl) piperidin-4-yl] -6- (3-methyl
Ureido) methylindole, (395) 3,3-dimethyl
Ru-1- [1- (4-fluorophenethyl) piperidine
-4-yl] -6-acetamidoindoline, (396)
2,2-dimethyl-1- [1- (4-fluorophenetici)
Ru) piperidin-4-yl] -6-methoxyindoli
, (397) 1- [1- (4-fluorophenethyl) pi
Peridin-4-yl] -6- (3-methylureido) me
Chill indole and the like.

[In the compound represented by the formula (III)
Preferred Embodiment] In the above formula (III),

Embedded image [Wherein the Ar ² ring and R ⁶ have the same meaning as defined above. Examples of the possible form of the group represented by the formula

Embedded image Wherein R ⁶ is as defined above. The preferred is the case where the Ar ² ring is a benzene or thiophene ring.

In the above formula (III),

Embedded image Wherein X, R ¹ and R ² have the same meaning as defined above. As a more preferred embodiment of the group represented by the formula

Embedded image [Wherein, R ³⁵ has the same meaning as defined above. And a piperazinyl group represented by the formula:

In the compound represented by the formula (II)
Specific examples of preferred embodiments include, for example, (1) 3-
(4-benzyloxybutyl) -1- (4-ethylpipe
(Razin-1-yl) isoquinoline, (2) 1- (1-me
Cylpiperazin-4-yl) -3- (4-methoxyfe
Nyl) isoquinoline, (3) 1- (1-methylpiperazi)
N-4-yl) -3- [4- (2-hydroxyethoxy)
C) phenyl] isoquinoline, (4) 1- (4-ethyl)
Piperazin-1-yl) -3- (4-trifluoromethyl
Ruphenyl) isoquinoline, (5) 1- (4-ethyl
Perazin-1-yl) -3- [4- (1-fluoropro
Pyl) phenyl] isoquinoline, (6) 1- (4-ethyl
Rupiperazin-1-yl) -3- (2-hydroxyfe
Nyl) isoquinoline, (7) 1- (4-ethylpiperazine)
1-yl) -3- (4-hydroxyphenyl) iso
Quinoline, (8) 1- (4-ethylpiperazine-1-i
L) -3- (2-methoxyphenyl) isoquinoline,
(9) 1- (4-ethylpiperazin-1-yl) -3-
(3-methoxyphenyl) isoquinoline, (10) 1-
(4-ethylpiperazin-1-yl) -3- (4-metho
(Xyphenyl) isoquinoline, (11) 3- (2,3-di
Methoxyphenyl) -1- (4-ethylpiperazine-1
-Yl) isoquinoline, (12) 3- (2,4-dimethoxy)
Cyphenyl) -1- (4-ethylpiperazine-1-i
L) isoquinoline, (13) 3- (2,5-dimethoxyphenyl)
Enyl) -1- (4-ethylpiperazin-1-yl) i
Soquinoline, (14) 3- (3,4-dimethoxyphenyi)
1) -1- (4-ethylpiperazin-1-yl) isoki
Norin, (15) 3- (3,5-dimethoxyphenyl)-
1- (4-ethylpiperazin-1-yl) isoquinoli
, (16) 1- (4-ethylpiperazin-1-yl)-
3- (2,4,5-trimethoxyphenyl) isoquinol
, (17) 1- (4-ethylpiperazin-1-yl)-
3- (4-hydroxymethylphenyl) isoquinoline,
(18) 3- [2- (2-hydroxyethoxy) phenyl
1]-(4-ethylpiperazin-1-yl) isoki
Norin, (19) 1- (4-ethylpiperazine-1-i
) -3- [4- (1-hydroxypropyl) phenyl
Ru] isoquinoline, (20) 1- (4-ethylpiperazine
-1-yl) -3- [4- (3-hydroxypropyl)
Phenyl] isoquinoline, (21) 1- (4-ethylpipe
Lazin-1-yl) -3- [4- (1-hydroxybuty)
Ru) phenyl] isoquinoline, (22) 1- (4-ethyl)
Piperazin-1-yl) -3- [4- (3-hydroxy
Butyl) phenyl] isoquinoline, (23) 3- [4-
(4-Hydroxybutyl) phenyl] -1- (4-ethyl
Rupiperazin-1-yl) isoquinoline, (24) 3-
[4- (1,3-dihydroxypropyl) phenyl]-
1- (4-ethylpiperazin-1-yl) isoquinoli
, (25) 3- [4- (1,3-dihydroxy-3-meth
Butyl) phenyl] -1- (4-ethylpiperazine
-1-yl) isoquinoline, (26) 3- [4- (3-h
Droxy-1-methoxybutyl) phenyl] -1- (4
-Ethylpiperazin-1-yl) isoquinoline, (27)
1- (1-ethylpiperazin-4-yl) -3- [4-
(3-hydroxy-1-fluoropropyl) phenyl]
Isoquinoline, (28) 1- (4-ethylpiperazine-1)
-Yl) -3- [4- (4-hydroxymethyl-3-f
Fluoro) phenyl] isoquinoline, (29) 1- (4-E
Cylpiperazin-1-yl) -3- [3-fluoro-4
-(1-hydroxypropyl) phenyl] isoquinolyl
, (30) 3- [3-chloro-4- (3-hydroxyp
Ropyl) phenyl] -1- (4-ethylpiperazine-1
-Yl) isoquinoline, (31) 3- [3-carboxya
Mid-4- (3-hydroxypropyl) phenyl] -1
-(4-ethylpiperazin-1-yl) isoquinoline,
(32) 3- [3-cyano-4- (3-hydroxypropyl
L) phenyl] -1- (4-ethylpiperazine-1-i
L) isoquinoline, (33) 1- (4-ethylpiperazine)
-1-yl) -3- [4- (3-hydroxypropyl)
-3-methoxyphenyl] isoquinoline, (34) 3-
[3- (3-hydroxypropyl) -4-methoxyfe
Nil] -1- (4-ethylpiperazin-1-yl) iso
Quinoline, (35) 3- [3- (4-hydroxybutyl)
-4-methoxyphenyl] -1- (4-ethylpiperazine
1-yl) isoquinoline, (36) 1- (4-ethyl)
Piperazin-1-yl) -3- [4- (2-hydroxy
(Ethoxy) phenyl] isoquinoline, (37) 3- [3,
4-di (2-hydroxyethoxy) phenyl] -1-
(4-ethylpiperazin-1-yl) isoquinoline,
(38) 3- [3,5-di (2-hydroxyethoxy) phenyl
Enyl] -1- (4-ethylpiperazin-1-yl) i
Soquinoline, (39) 3- [3-chloro-4- (2-hydrido)
Roxyethoxy) phenyl] -1- (4-ethylpipera
Zin-1-yl) isoquinoline, (40) 3- [3-methyl
4- (2-hydroxyethoxy) phenyl] -1-
(4-ethylpiperazin-1-yl) isoquinoline,
(41) 3- [3-isopropyl-4- (2-hydroxy
Ethoxy) phenyl] -1- (4-ethylpiperazine-
1-yl) isoquinoline, (42) 1- (4-ethylpipe)
Razin-1-yl) -3- [4- (2-methoxyethoxy)
C) phenyl] isoquinoline, (43) 3- [3,4-di
(2-methoxyethoxy) phenyl] -1- (4-ethyl
(Lupiperazin-1-yl) isoquinoline, (44) 3-
[4- (2-hydroxyethoxy) methylphenyl]-
1- (4-ethylpiperazin-1-yl) isoquinoli
, (45) 1- (4-ethylpiperazin-1-yl)-
3- [4- (2-fluoroethoxy) phenyl] isoki
Norin, (46) 3- (3,4-methylenedioxyphenyl)
1) -1- (4-ethylpiperazin-1-yl) isoki
Norin, (47) 1- (1-ethylpiperazine-4-i
) -3- (4-acetonyloxyphenyl) isoquino
Phosphorus, (48) 3- [4- (3-aminopropoxy) fe
Nil] -1- (4-ethylpiperazin-1-yl) iso
Quinoline, (49) 1- (1-ethylpiperazine-4-i
) -3- [4- (2-Dimethylaminoethoxy) fe
Nyl] isoquinoline, (50) 3- [4- (3-acetoa
Midopropoxy) phenyl] -1- (4-ethylpipera
Zin-1-yl) isoquinoline, (51) 3- (4-sia
Nomethoxyphenyl) -1- (4-ethylpiperazine-
1-yl) isoquinoline, (52) 3- [4- (2-sia
Noethoxy) phenyl] -1- (4-ethylpiperazine
-1-yl) isoquinoline, (53) 3- [4- (3-cy
Anopropoxy) phenyl] -1- (4-ethylpipera
Zin-1-yl) isoquinoline, (54) 3- [4- (3
-Methylthiopropoxy) phenyl] -1- (4-ethyl
(Lupiperazin-1-yl) isoquinoline, (55) 3-
[4- (3-methylsulfonylpropoxy) phenyl]
-1- (4-ethylpiperazin-1-yl) isoquinol
, (56) 3- {4- [2- (1-Imidazonyl) ethoate
[Xy] phenyl} -1- (4-ethylpiperazine-1-
Yl) isoquinoline, (57) 3- {4- [3- (4-pi
Ridyl) propoxy] phenyl} -1- (4-ethylpi
Perazin-1-yl) isoquinoline, (58) 3- {4-
[2- (2-methylpyridin-5-yl) ethoxy] f
Enyl} -1- (4-ethylpiperazin-1-yl) i
Soquinoline, (59) 1- (1-ethylpiperazine-4-
Yl) -3- [4- (N-ethylcarbamyl) phenyl
Ru] isoquinoline, (60) (Z) -1- (4-ethyl
Perazin-1-yl) -3- (4-hydroxyiminome
(Tylphenyl) isoquinoline, (61) (E) -1- (4
-Ethylpiperazin-1-yl) -3- (4-hydroxy
(Siminomethylphenyl) isoquinoline, (62) 3-
(4-cyanophenyl) -1- (4-ethylpiperazine
-1-yl) isoquinoline, (63) 1- (4-ethyl
Perazin-1-yl) -3- (4-N-propylamino
Carbonylphenyl) isoquinoline, (64) 3- [4-
(4-hydroxy-1-cyclohexen-1-yl)
Enyl] -1- (4-ethylpiperazin-1-yl) i
Soquinoline, (65) 3- (4-aminophenyl) -1-
(4-ethylpiperazin-1-yl) isoquinoline (66) 3- [4- (N, N-dimethylamino) phenyl
1]-(4-ethylpiperazin-1-yl) isoki
Norin, (67) 3- [4- (2-hydroxyethyl) a
Minophenyl] -1- (4-ethylpiperazine-1-i
L) isoquinoline, (68) 3- (4-acetamidophenyi)
1) -1- (4-ethylpiperazin-1-yl) isoki
Norin, (69) 3- (4-ethylcarbonylaminophen
Nyl) -1- (4-ethylpiperazin-1-yl) iso
Quinoline, (70) 3- (4-propylcarbonylamino
Phenyl) -1- (4-ethylpiperazin-1-yl)
Isoquinoline, (71) 3- (4-ethylsulfonylami
Nophenyl) -1- (4-ethylpiperazine-1-i
R) isoquinoline, (72) 3- (4-propylsulfoni)
L-aminophenyl) -1- (4-ethylpiperazine-1
-Yl) isoquinoline, (73) 3- (4-butylsulfo
Nylaminophenyl) -1- (4-ethylpiperazine-
1-yl) isoquinoline, (74) 3- (4-sulfonyl)
Amidophenyl) -1- (4-ethylpiperazine-1-
Yl) isoquinoline, (75) 3-[(4-morpholini)
Ru) sulfonylphenyl] -1- (4-ethylpiperazine
1-yl) isoquinoline, (76) 3-[(4-thio
Morpholinyl) sulfonylphenyl] -1- (4-ethyl
(Lupiperazin-1-yl) isoquinoline, (77) 3-
[(1,1-dioxythiomorpholinyl) sulfonylf
Enyl] -1- (4-ethylpiperazin-1-yl) i
Soquinoline, (78) 3- (4-ethylsulfonylamino)
Methylphenyl) -1- (4-ethylpiperazine-1-
Yl) isoquinoline, (79) 3- (4-ethylsulfoni)
L-aminoethylphenyl) -1- (4-ethylpiperazine
1-yl) isoquinoline, (80) 3- (4-ethyl
Aminosulfonylmethylphenyl) -1- (4-ethyl
(Piperazin-1-yl) isoquinoline, (81) 3- (4
-Propylaminosulfonylmethylphenyl) -1-
(4-ethylpiperazin-1-yl) isoquinoline,
(82) 3- [4- (N, N-diethylamino) sulfoni
Methylphenyl] -1- (4-ethylpiperazine-1
-Yl) isoquinoline, (83) 3- [4- (tetrahydrid
Ropyran-4-yl) phenyl] -1- (4-ethylpi
Perazin-1-yl) isoquinoline, (84) 3- [4-
(5,6-dihydro-2H-pyran-4-yl) phenyl
1]-(4-ethylpiperazin-1-yl) isoki
Norin, (85) 3- (4-ethylcarbonylaminomethyl)
Ruphenyl) -1- (4-ethylpiperazine-1-i
L) isoquinoline, (86) 3- (4-propyl carbonyl)
L-aminomethylphenyl) -1- (4-ethylpiperazine
1-yl) isoquinoline, (87) 3- (4-ethyl)
Aminocarbonylmethylphenyl) -1- (4-ethyl
Piperazin-1-yl) isoquinoline, (88) 3- (4
-Propylaminocarbonylmethylphenyl) -1-
(4-ethylpiperazin-1-yl) isoquinoline,
(89) 3- (4-butylaminocarbonylmethylphenyi)
1) -1- (4-ethylpiperazin-1-yl) isoki
Norin, (90) 3- (4-methylsulfonylmethylphen)
Nyl) -1- (4-ethylpiperazin-1-yl) iso
Quinoline, (91) 3- (3-chloro-4-ethylsulfo
Nylaminomethylphenyl) -1- (4-ethylpipera
Zin-1-yl) isoquinoline, (92) 3- (3-chloro
B-4-propylsulfonylaminomethylphenyl)-
1- (4-ethylpiperazin-1-yl) isoquinoli
, (93) 3- (4-morpholinylmethylphenyl)-
1- (4-ethylpiperazin-1-yl) isoquinoli
, (94) 3- (4-thiomorpholinylmethylphenyl)
1) -1- (4-ethylpiperazin-1-yl) isoki
Norin, (95) 3- [4- (3-oxazolidinone)
Enyl] -1- (4-ethylpiperazin-1-yl) i
Soquinoline, (96) 3- [4- (4,4-ethylenedi
Xipiperidin-1-yl) phenyl] -1- (4-d
Tylpiperazin-1-yl) isoquinoline, (97) 1-
(4-ethylpiperazin-1-yl) -3- [4- (4
-Hydroxypiperidin-1-yl) phenyl] isoqui
Norin, (98) 1- (4-ethylpiperazine-1-i
Ru) -3- [4- (4-Methoxypiperidin-1-i
L) phenyl] isoquinoline, (99) 3- [2- (4-
Acetylpiperazin-1-yl) pyridin-5-yl]
-1- (4-ethylpiperazin-1-yl) isoquinol
, (100) 3- [4- (4-acetylpiperazine-1)
-Yl) phenyl] -1- (4-ethylpiperazine-1
-Yl) isoquinoline, (101) 3- (2-methoxy)
Benzyl) -1- (4-ethylpiperazin-1-yl) i
Soquinoline, (102) 3- [α-methyl- (4-methoxy)
Cibenzyl)]-1- (4-ethylpiperazine-1-i
L) isoquinoline, (103) 3- [α-hydroxy-
(2-methoxybenzyl)]-1- (4-ethylpipera
Zin-1-yl) isoquinoline, (104) 3- [α-hi
Droxy- (4-methoxybenzyl)]-1- (4-d
Cylpiperazin-1-yl) isoquinoline, (105) 3
-[Α-methyl-α-hydroxy- (4-methoxybenz
Jill)]-1- (4-ethylpiperazin-1-yl) i
Soquinoline, (106) 1- (1-ethylpiperazine-4)
-Yl) -3- (4-methoxyphenethyl) isoquinolyl
, (107) 1- (1-ethylpiperazin-4-yl)
-3- [2- (2-hydroxyethoxy) phenethyl]
Isoquinoline, (108) 1- (1-ethylpiperazine-
4-yl) -3- [3- (2-hydroxyethoxy) phenyl
Enetyl] isoquinoline, (109) 1- (1-ethyl
Perazin-4-yl) -3- [4- (2-hydroxyd
Toxi) phenethyl] isoquinoline, (110) 1- (1
-Ethylpiperazin-4-yl) -3- {3- [2-
(2-Hydroxyethoxy) phenyl] propyl diiso
Quinoline, (111) 3- (2-methoxyphenylcarbo
Nyl) -1- (4-ethylpiperazin-1-yl) iso
Quinoline, (112) 3- (4-methoxyphenylcarbo)
Nyl) -1- (4-ethylpiperazin-1-yl) iso
Quinoline, (113) 3- (4-methoxyindane-1-
Yl) -1- (4-ethylpiperazin-1-yl) iso
Quinoline, (114) 3- (6-methoxyindane-1-
Yl) -1- (4-ethylpiperazin-1-yl) iso
Quinoline, (115) 3- [4- (2-hydroxyethoxy)
B) Indan-1-yl] -1- (4-ethylpiperazine
1-yl) isoquinoline, (116) 3- (8-meth
Xy-1,2-dihydronaphthalen-4-yl) -1-
(4-ethylpiperazin-1-yl) isoquinoline,
(117) 3- (7-methoxy-1,2-dihydronaphtha)
Ren-4-yl) -1- (4-ethylpiperazine-1-
Yl) isoquinoline, (118) 3- (6-methoxy-
1,2-dihydronaphthalen-4-yl) -1- (4-
Ethylpiperazin-1-yl) isoquinoline, (119)
3- (5-methoxy-1,2,3,4-tetrahydrona
Phthalen-1-yl) -1- (4-ethylpiperazine-
1-yl) isoquinoline, (120) 3- (6-methoxy)
-1,2,3,4-tetrahydronaphthalene-1-i
1) -1- (4-ethylpiperazin-1-yl) isoki
Norin, (121) 3- (7-methoxy-1,2,3,4
-Tetrahydronaphthalen-1-yl) -1- (4-e
Cylpiperazin-1-yl) isoquinoline, (122) 3
-(3-hydroxymethylchroman-6-yl) -1-
(4-ethylpiperazin-1-yl) isoquinoline,
(123) 1- (4-Ethylpiperazin-1-yl) -3
-(2-pyridyl) isoquinoline, (124) 1- (1-
Ethylpiperazin-4-yl) -3- [5- (2-hydr)
Roxyethoxy) pyridin-2-yl] isoquinoline,
(125) 1- (1-Ethylpiperazin-4-yl) -3
-[2- (2-hydroxyethoxy) pyridine-5-i
Ru] isoquinoline, (126) 1- (1-ethylpiperazine)
N-4-yl) -3- [2- (2-methoxyethoxy)
Pyridin-5-yl] isoquinoline, (127) 1- (1
-Ethylpiperazin-4-yl) -3- [5- (2-me
Toxiethoxy) pyridin-2-yl] isoquinoline,
(128) 3- (2-propylcarbonylaminopyridine
-5-yl) -1- (4-ethylpiperazine-1-i
L) isoquinoline, (129) 3-[(2-methylsulfo
Nilpyridin) -5-yl] -1- (4-ethylpipera
Zin-1-yl) isoquinoline, (130) 3-[(2-
Ethylsulfonylpyridine) -5-yl] -1- (4-
(Ethylpiperazin-1-yl) isoquinoline, (131)
1- (1-ethylpiperazin-4-yl) -3- (2-
(Butylpyridin-5-yl) isoquinoline, (132) 1
-(1-ethylpiperazin-4-yl) -3- [5-
(3-Fluoropropyl) pyridin-2-yl] isoki
Norin, (133) 1- (1-ethylpiperazine-4-i
) -3- [2- (3-Fluoropropyl) pyridine-
5-yl] isoquinoline, (134) 1- (1-ethylpi
Perazin-4-yl) -3- [5- (3-hydroxyp
Ropyl) pyridin-2-yl] isoquinoline, (135)
1- (1-ethylpiperazin-4-yl) -3- [2-
(3-Hydroxypropyl) pyridin-5-yl] iso
Quinoline, (136) 1- (1-ethylpiperazine-4-
Yl) -3- [2- (3-hydroxybutyl) pyridine
-5-yl] isoquinoline (137) 1- (1-ethylpiperazin-4-yl) -3
-[2- (4-hydroxybutyl) pyridine-5-i
Ru] isoquinoline, (138) 1- (1-ethylpiperazine)
N-4-yl) -3- [2- (3-hydroxy-3-me
Butyl) pyridin-5-yl] isoquinoline, (13
9) 1- (1-ethylpiperazin-4-yl) -3-
[2- (3-methoxypropyl) pyridin-5-yl]
Isoquinoline, (140) 1- (1-ethylpiperazine-
4-yl) -3- [3- (3-methoxypropyl) pyri
Zin-5-yl] isoquinoline, (141) 1- (1-E)
Cylpiperazin-4-yl) -3- [5- (3-methoxy
Cypropyl) pyridin-2-yl] isoquinoline, (14
2) 1- (1-ethylpiperazin-4-yl) -3-
[2- (3-ethoxypropyl) pyridin-5-yl]
Isoquinoline, (143) 1- (1-ethylpiperazine-
4-yl) -3- {2- [3- (2-propoxy) pro
[Pyr] pyridin-5-yl} isoquinoline, (144) 1
-(1-ethylpiperazin-4-yl) -3- [2-
(3-Methoxybutyl) pyridin-5-yl] isoquino
Phosphorus, (145) 1- (1-ethylpiperazine-4-i
) -3- {2- [2- (2-hydroxy-2-cyclo)
Hexyl) ethynyl] pyridin-4-yl {isoquinolyl
, (146) 1- (1-ethylpiperazin-4-yl)
-3- [2- (1-butynyl) pyridin-5-yl] i
Soquinoline, (147) 1- (4-ethylpiperazine-1)
-Yl) -3- [2- (morpholin-4-yl) pyridi
N-5-yl] isoquinoline, (148) 1- (4-ethyl
Rupiperazin-1-yl) -3- [5- (morpholine-
4-yl) pyridin-2-yl] isoquinoline, (14
9) 3- [2- (2,6-dimethylmorpholin-4-i
Ru) pyridin-5-yl] -1- (4-ethylpiperazine
1-yl) isoquinoline, (150) 1- (4-ethyl)
Lupiperazin-1-yl) -3- [2- (thiomorpholy
N-4-yl) pyridin-5-yl] isoquinoline,
(151) 1- (4-Ethylpiperazin-1-yl) -3
-[2- (S-oxythiomorpholin-4-yl) pyri
Zin-5-yl] isoquinoline, (152) 1- (4-E
Cylpiperazin-1-yl) -3- [2- (4-hydro
Xypiperidin-1-yl) pyridin-5-yl] iso
Quinoline, (153) 1- (4-ethylpiperazine-1-
Yl) -3- [2- (4-methoxypiperidine-1-i
Ru) pyridin-5-yl] isoquinoline, (154) 1-
(4-ethylpiperazin-1-yl) -3- [2- (4
-Hydroxymethylpiperidin-1-yl) pyridine-
5-yl] isoquinoline, (155) 3- [2- (5,6
-Dihydro-2H-pyran-4-yl) pyridine-5-
Yl] -1- (4-ethylpiperazin-1-yl) iso
Quinoline, (156) 3- [2- (tetrahydropyran-
4-yl) pyridin-5-yl] -1- (4-ethylpi
Perazin-1-yl) isoquinoline, (157) 3- {4
-[3- (3-pyridyl) propoxy] phenyl} -1
-(4-ethylpiperazin-1-yl) isoquinoline,
(158) 1- (1-Ethylpiperazin-4-yl) -3
-(1-phenylpiperazin-4-yl) isoquinolyl
, (159) 1- (1-ethylpiperazin-4-yl)
-3- [1- (2-Pyridyl) piperazin-4-yl]
Isoquinoline, (160) 3- [4- (4-morpholini)
L) phenyl] -1- (4-ethylpiperazine-1-i
L) isoquinoline, (161) 1- (1-ethylpiperazine)
N-4-yl) -3- (2-hydroxymethylthiophene
(4-N-yl) isoquinoline, (162) 1- (1-ethyl)
Lupiperazin-4-yl) -3- (2-hydroxymethyl)
(Luthiophen-5-yl) isoquinoline, (163) 1-
(1-ethylpiperazin-4-yl) -3- [2- (2
-Hydroxyethyl) thiophen-5-yl] isoquino
Phosphorus, (164) 1- (1-ethylpiperazine-4-i
) -3- [2- (1-hydroxypropyl) thiophene
4-N-yl] isoquinoline, (165) 1- (1-ethyl
Rupiperazin-4-yl) -3- [2- (1-hydroxy
Cypropyl) thiophen-5-yl] isoquinoline,
(166) 3- [2- (Tetrahydropyran-4-yl)
Thiophene-5-yl] -1- (4-ethylpiperazine
-1-yl) isoquinoline, (167) 1- (1-ethyl)
Piperazin-4-yl) -3- [4-methyl-5- (2
-Hydroxyethyl) thiazol-2-yl] isoquino
Phosphorus, (168) 1- (1-ethylpiperazine-4-i
L) -3- (2-Hydroxymethylthiazole-5-i
L) isoquinoline, (169) 1- (1-ethylpiperazine)
N-4-yl) -3- [1- (2-hydroxyethyl)
Pyrazol-3-yl] isoquinoline, (170) 1-
(1-ethylpiperazin-4-yl) -3-[(1-h
Droxypropyl) thiazol-5-yl] isoquinol
, (171) 1- (1-ethylpiperazin-4-yl)
-3- [2- (3-hydroxypropyl) thiazole-
5-yl] isoquinoline, (172) 1- (1-ethylpi
Perazin-4-yl) -3- [2- (3-methoxypro
Pill) thiazol-5-yl] isoquinoline, (173)
1- (1-ethylpiperazin-4-yl) -3- [2-
(4-morpholinyl) thiazol-5-yl] isoquino
Phosphorus, (174) 3- (2-propylcarbonylaminopi
Limidin-5-yl) -1- (4-ethylpiperazine-
1-yl) isoquinoline, (175) 3- [2- (5,6
-Dihydro-2H-pyran-4-yl) thiophene-4
-Yl] -1- (4-ethylpiperazin-1-yl) i
Soquinoline, (176) 3- [2- (5,6-dihydro-
2H-pyran-4-yl) thiophen-5-yl] -1
-(4-ethylpiperazin-1-yl) isoquinoline,
(177) 1- (1-ethylpiperazin-4-yl) -3
-(Phenylethynyl) isoquinoline, (178) 1-
(1-ethylpiperazin-4-yl) -3- (4-metho
(Xyphenyl) ethynylisoquinoline, (179) 1-
(1-ethylpiperazin-4-yl) -3- (2-pyri
(Zyl) ethynylisoquinoline, (180) 3- (3-mol
Folinyl-1-propynyl) -1- (4-ethylpipera
Zin-1-yl) isoquinoline, (181) 1- (1-E)
Tylpiperazin-4-yl) -3- (3-phenyl-1
-Propynyl) isoquinoline, (182) 1- (1-ethyl)
Rupiperazin-4-yl) -3- (4-phenyl-1-)
Butynyl) isoquinoline, (183) 1- (1-ethyl
Perazin-4-yl) -3- [4- (2-hydroxyd
Toxy) phenylethynyl] isoquinoline, (184) 1
-(1-ethylpiperazin-4-yl) -3-benzoi
Ruethynylisoquinoline, (185) 1- (1-ethylpi
Perazin-4-yl) -3- (2,4-dimethoxyfe
Nylethynyl) isoquinoline, (186) 1- (1-ethyl
Lupiperazin-4-yl) -3- [3- (3-methoxy
Propyl) -5-pyridyl] ethynylisoquinoline,
(187) 1- (1-ethylpiperazin-4-yl) -3
-[2- (2-hydroxyethoxy) phenyl] ethini
Luisoquinoline, (188) 1- (1-ethylpiperazine
-4-yl) -3- [3- (2-hydroxyethoxy)
-2-pyridyl] ethynylisoquinoline, (189) 1-
(1-ethylpiperazin-4-yl) -3- (trans
-2-phenylethenyl) isoquinoline, (190) 1-
(1-Ethylpiperazin-4-yl) -3- [trans
-2- (4-methoxyphenyl) ethenyl] isoquinolyl
, (191) 1- (1-ethylpiperazin-4-yl)
-3- [cis-2- (4-methoxyphenyl) etheni
Ru] isoquinoline, (192) 1- (1-ethylpiperazine)
N-4-yl) -3- (cis-1-methyl-2-phenyl)
(Ruethenyl) isoquinoline, (193) 1- (1-ethyl)
Piperazin-4-yl) -3- (trans-1-methyl)
-2-phenylethenyl) isoquinoline, (194) 1
-(1-ethylpiperazin-4-yl) -3- [tran
Su-2- (2-hydroxyethoxyphenyl) etheni
Ru] isoquinoline, (195) 1- (1-ethylpiperazine)
N-4-yl) -3- [trans-2- (2-methoxy)
Phenyl) ethenyl] isoquinoline, (196) 1- (1
-Ethylpiperazin-4-yl) -3- (trans-2
-Methyl-2-phenylethen-1-yl) isoquinolyl
, (197) 1- (1-ethylpiperazin-4-yl)
-3- [trans-2- (2-fluorophenyl) ether
Nyl] isoquinoline, (198) 1- (1-ethylpipera)
Zin-4-yl) -3-[(E) -4- (2-hydroxy
Ciethoxy) styryl] isoquinoline, (199) 1-
(1-ethylpiperazin-4-yl) -3- {trans
-2- [3- (2-hydroxyethoxy) phenyl] e
Thenyl {isoquinoline, (200) 3-{(E) -2-
[2- (4-morpholinyl) pyridin-5-yl] ether
Nil} -1- (4-ethylpiperazin-1-yl) iso
Quinoline, (201) 3-[(E) -2- (4-methyls)
Ruphonylphenyl) ethenyl] -1- (4-ethylpipe
(Razin-1-yl) isoquinoline, (202) 3-
[(E) -2- (2-methylsulfonylphenyl) ether
Nil] -1- (4-ethylpiperazin-1-yl) iso
Quinoline, (203) 3-[(E) -2- (4-methyls)
Rufonylmethylphenyl) ethenyl] -1- (4-ethyl
(Lupiperazin-1-yl) isoquinoline, (204) 3-
｛(E) -2- [3- (4-morpholinyl) phenyl]
Ethenyl} -1- (4-ethylpiperazin-1-yl)
Isoquinoline, (205) 3-{(E) -2- [4- (4
-Morpholinyl) phenyl] ethenyl} -1- (4-e
Cylpiperazin-1-yl) isoquinoline, (206) 3
-{(E) -2-methyl-2- [4- (4-morpholini)
Ru) phenyl] ethenyl} -1- (4-ethylpiperazine
1-yl) isoquinoline, (207) 3-{(E)-
2-methyl-2- [3- (4-morpholinyl) phenyl
Ru] ethenyl} -1- (4-ethylpiperazine-1-i
G) isoquinoline, (208) 3-[(E) -2-methoxy
Cimethyl-2-phenylethenyl] -1- (4-ethyl
Piperazin-1-yl) isoquinoline, (209) 1-
(1-Ethylpiperazin-4-yl) -3- [trans
-2- (2-pyridyl) ethenyl] isoquinoline, (21
0) 1- (1-Ethylpiperazin-4-yl) -3-
[Trans-2- (4-pyridyl) ethenyl] isoquino
Phosphorus, (211) 1- (1-ethylpiperazine-4-i
) -3- [3- (2-methoxy) phenyl-2-pro
Penyl] isoquinoline, (212) 1- (1-ethylpipe)
Lazin-4-yl) -3- [3- (2-hydroxyeth
[Xy) phenyl-1-propenyl] isoquinoline, (21
3) 3-{(E) -2- [2- (4-morpholinyl) pi
Lysin-5-yl] ethenyl} -1- (4-ethylpipe
(Razin-1-yl) isoquinoline, (214) 3-
｛(E) -2- [3- (4-morpholinyl) pyridazine
-6-yl] ethenyl} -1- (4-ethylpiperazine
-1-yl) isoquinoline, (215) 3-{(E) -2
-[4- (4-morpholinyl) pyrimidin-6-yl]
Ethenyl} -1- (4-ethylpiperazin-1-yl)
Isoquinoline, (216) 3-{(E) -2- [2- (4
-Morpholinyl) pyrazin-6-yl] ethenyl} -1
-(4-ethylpiperazin-1-yl) isoquinoline,
(217) 3- [1- (4-methoxyphenyl) etheni
1]-(4-ethylpiperazin-1-yl) isoki
Norin, (218) 1- (1-ethylpiperazine-4-i
) -N-phenyl-3-isoquinolinecarboxamido
, (219) 1- (1-ethylpiperazin-4-yl)
-3- (4-methoxyanilinomethyl) isoquinoline,
(220) 1- (1-Ethylpiperazin-4-yl) -3
-(4-methoxybenzylamino) isoquinoline, (22
1) 1- (1-ethylpiperazin-4-yl) -4-me
Toxic-3- (4-methoxyphenyl) isoquinoline,
(222) 1- (1-ethylpiperazin-4-yl) -5
-Methyl-3- (4-methoxyphenyl) isoquinol
, (223) 1- (4-ethylpiperazin-1-yl)
-3- [4- (2-hydroxyethoxy) phenyl]-
6-fluoroisoquinoline, (224) 1- (1-ethyl)
Piperazin-4-yl) -6-fluoro-3- (4-meth
(Toxiphenyl) isoquinoline, (225) 1- (1-E)
Cylpiperazin-4-yl) -6-methyl-3- (4-
(Methoxyphenyl) isoquinoline, (226) 1- (4-
Ethylpiperazin-1-yl) -6-methoxy-3-
(4-trifluoromethylphenyl) isoquinoline,
(227) 1- (4-ethylpiperazin-1-yl) -6
-Methoxy-3- (4-methoxyphenyl) isoquinol
, (228) 1- (1-ethylpiperazin-4-yl)
-7-methyl-3- (4-methoxyphenyl) isoquino
Phosphorus, (229) 1- (4-ethylpiperazine-1-i
L) -7-Fluoro-3- (4-methoxyphenyl) i
Soquinoline, (230) 1- (4-ethylpiperazine-1
-Yl) -3- [4- (2-hydroxyethoxy) fe
Nyl] -7-fluoroisoquinoline, (231) 1- (4
-Ethylpiperazin-1-yl) -7-methoxy-3-
Phenylisoquinoline, (232) 1- (4-ethylpipe
Razin-1-yl) -7-methoxy-3- (2-methoxy)
(Phenyl) isoquinoline, (233) 1- (1-ethyl)
Piperazin-4-yl) -8-fluoro-3- (4-meth
(Toxiphenyl) isoquinoline, (234) 1- (1-E)
Cylpiperazin-4-yl) -8-fluoro-3- [4
-(2-Hydroxyethoxy) phenyl] isoquinolyl
, (235) 1- (1-ethylpiperazin-4-yl)
-8-methoxy-3- (4-methoxyphenyl) isoki
Norin, (236) 1- (1-propylpiperazine-4-
Yl) -3- (4-methoxyphenyl) isoquinoline,
(237) 1- (1-propylpiperazin-4-yl)-
3- [4- (2-hydroxyethoxy) phenyl] iso
Quinoline, (238) 1- (1-isopropylpiperazine)
-4-yl) -3- (4-methoxyphenyl) isoquino
Phosphorus, (239) 1- (1-cyclopropylpiperazine-
4-yl) -3- (4-methoxyphenyl) isoquinolyl
, (240) 1- (1-allylpiperazin-4-yl)
-3- (4-methoxyphenyl) isoquinoline, (24
1) 1- [1- (2-Fluoroethyl) piperazine-4
-Yl] -3- (4-methoxyphenyl) isoquinolyl
, (242) 1- [4- (2-hydroxyethyl) pipe
Razin-1-yl] -3- (4-methoxyphenyl) i
Soquinoline, (243) 3- (4-ethylsulfonylamido)
Nomethylphenyl) -1- [4- (2-hydroxyethyl
Ru) piperazin-1-yl] isoquinoline, (244) 8
-(4-ethylpiperazin-1-yl) -6- (4-me
(Toxiphenyl) pyrido [2,3-c] pyridine, (24
5) 8- (1-Ethylpiperazin-4-yl) -6
[4- (2-hydroxyethoxy) phenyl] -1,7
-Naphthyridine, (246) 8- (1-ethylpiperazine
-4-yl) -6- {4-[(S) -2-hydroxyp
[Ropoxy] phenyl} -1,7-naphthyridine, (24
7) 8- (1-Ethylpiperazin-4-yl) -6
[4- (3-hydroxypropyl) phenyl] -1,7
-Naphthyridine, (248) 8- (1-ethylpiperazine
-4-yl) -6- [4- (3-hydroxybutyl) phenyl
Enyl] -1,7-naphthyridine, (249) 8- (1-
Ethylpiperazin-4-yl) -6- [4- (3-hydrido
Roxy-1-fluoropropyl) phenyl] -1,7-
Naphthyridine, (250) 8- (1-ethylpiperazine-
4-yl) -6- [4- (2-hydroxy-2-methyl
Propoxy) phenyl] -1,7-naphthyridine, (25
1) 1- (1-ethylpiperazin-4-yl) -3-
(4-methoxyphenyl) -2,6-naphthyridine,
(252) 5- (1-Ethylpiperazin-4-yl) -7
-(4-methoxyphenyl) -1,6-naphthyridine,
(253) 5- [4- (2-hydroxyethoxy) phenyl
Ru] -7- (4-Methylpiperazin-1-yl) thieno
[2,3-c] pyridine, (254) 7- (1-ethylpi
Perazin-4-yl) -5- [4- (1-hydroxype
Nthyl) phenyl] thieno [2,3-c] pyridine,
(255) 7- (1-ethylpiperazin-4-yl) -5
-[4- (1-hydroxy-3-methylbutyl) phenyl
Ru] thieno [2,3-c] pyridine, (256) 7- (1
-Ethylpiperazin-4-yl) -5- [4- (3-h
Droxy-1-fluoropropyl) phenyl] thieno
[2,3-c] pyridine, (257) 5- [4- (3-h
Droxypropyl) -3-chlorophenyl] -7- (4
-Ethylpiperazin-1-yl) thieno [2,3-c]
Pyridine, (258) 7- (1-ethylpiperazine-4-
Yl) -5- [3- (2-hydroxyethoxy) phenyl
Ru] thieno [2,3-c] pyridine, (259) 7- (4
-Ethylpiperazin-1-yl) -5- (4-hydroxy
Ciethoxyphenyl) thieno [2,3-c] pyridine,
(260) 7- (1-Ethylpiperazin-4-yl) -5
-[4- (2-hydroxy-2-methylpropoxy) phenyl
Enyl] thieno [2,3-c] pyridine, (261) 5-
[3- (3-hydroxypropyl) -4-methoxyfe
Nil] -7- (4-ethylpiperazin-1-yl) thie
No [2,3-c] pyridine, (262) 5- [4- (3-
Hydroxypropyl) -3-cyanophenyl] -7-
(4-ethylpiperazin-1-yl) thieno [2,3-
c] pyridine, (263) 5- [2- (4-morpholini)
Ru) pyridin-5-yl] -7- (4-ethylpiperazine
N-1-yl) thieno [2,3-c] pyridine, (26
4) 5- [2- (4-thiomorpholinyl) pyridine-5
-Yl] -7- (4-ethylpiperazin-1-yl) thio
Eno [2,3-c] pyridine, (265) 5- [2- (4
-Hydroxypiperidin-1-yl) pyridin-5-i
Ru] -7- (4-Ethylpiperazin-1-yl) thieno
[2,3-c] pyridine, (266) 5- [4- (5,6
-Dihydro-2H-pyran-4-yl) phenyl] -7
-(4-ethylpiperazin-1-yl) thieno [2,3
-C] pyridine, (267) 5- [2- (2-methoxy
Toxi-2-methyl) pyridin-5-yl] -7- (4
-Ethylpiperazin-1-yl) thieno [2,3-c]
Pyridine, (268) 5- [2- (2-hydroxyethoxy)
B) Pyridin-5-yl] -7- (4-ethylpiperazine
N-1-yl) thieno [2,3-c] pyridine, (26
9) 5- [2- (2-methoxyethoxy) pyridine-5
-Yl] -7- (4-ethylpiperazin-1-yl) thio
Eno [2,3-c] pyridine, (270) 5- [4- (4
-Hydroxycyclohexen-1-yl) phenyl]-
7- (4-ethylpiperazin-1-yl) thieno [2,
3-c] pyridine, (271) 7- (1-ethylpiperazine
-4-yl) -5- (4-Pentanoylphenyl) thio
Eno [2,3-c] pyridine, (272) 7- (1-ethyl
Lupiperazin-4-yl) -5- [4- (3-methylbutane
Tanoyl) phenyl] thieno [2,3-c] pyridine,
(273) 7- (1-Ethylpiperazin-4-yl) -5
-[4- (N-cyclohexylamido) phenyl] thie
No [2,3-c] pyridinecarboxamide, (274)
7- (1-ethylpiperazin-4-yl) -5- [4-
(Pyrrolidinyl-1-carbonyl) phenyl] thieno
[2,3-c] pyridine, (275) 5- [4- (2-H
Droxyethoxy) phenyl] -7- [4- (2-hydr)
Roxyethyl) piperazin-1-yl] thieno [3,2
-C] pyridine, (276) 5- (4-methoxyphenyl)
) -7- [4- (2-hydroxyethyl) piperazine
-1-yl] thieno [2,3-c] pyridine, (277)
4- (4-ethylpiperazin-1-yl) -6- (4-
Methoxyphenyl) thieno [3,4-c] pyridine,
(278) 4- (4-Ethylpiperazin-1-yl) -6
-[4- (2-hydroxyethoxy) phenyl] thieno
[3,4-c] pyridine, (279) 4- (4-methylpi
Perazin-1-yl) -6- [4- (2-hydroxyd
Toxy) phenyl] thieno [3,2-c] pyridine,
(280) 4- (4-Ethylpiperazin-1-yl) -6
-(4-hydroxyphenyl) thieno [3,2-c] pi
Lysine, (281) 4- (4-ethylpiperazine-1-i
) -6- [4- (1-hydroxyethyl) phenyl]
Thieno [3,2-c] pyridine, (282) 4- (4-E
Cylpiperazin-1-yl) -6- [4- (1-hydro
Xypropyl) phenyl] thieno [3,2-c] pyridi
, (283) 4- (4-ethylpiperazin-1-yl)
-6- [4- (1-hydroxybutyl) phenyl] thie
No [3,2-c] pyridine, (284) 4- (1-ethyl)
Piperazin-4-yl) -6- [3- (2-hydroxy)
Toxy) phenyl] thieno [3,2-c] pyridine,
(285) 4- (1-Ethylpiperazin-4-yl) -6
-[4- (3-hydroxybutyl) phenyl] thieno
[3,2-c] pyridine, (286) (4-ethylpipera
Zin-1-yl) -6- [4- (2-hydroxyethoxy)
C) phenyl] thieno [3,2-c] pyridine, (28
7) 4- (4-ethylpiperazin-1-yl) -6
[4- (2-hydroxypropoxy) phenyl] thieno
[3,2-c] pyridine, (288) 6- [4- (2-meth
Tyl-2-hydroxypropoxy) phenyl] -4-
(4-Methylpiperazin-1-yl) thieno [3,2-
c] pyridine, (289) 6- [4- (2-methyl-2-
Hydroxypropoxy) phenyl] -4- (4-propyl
Rupiperazin-1-yl) thieno [3,2-c] pyridi
, (290) 6- [4- (2-methyl-2-hydroxy
Propoxy) phenyl] -4- (4-ethylpiperazine
-1-yl) thieno [3,2-c] pyridine, (291)
4- (4-ethylpiperazin-1-yl) -6- [4-
(3-Hydroxy-3-methylbutyl) phenyl] thie
No [3,2-c] pyridine, (292) 6- [4- (4-
Methyl-4-hydroxypentyloxy) phenyl]-
4- (4-ethylpiperazin-1-yl) thieno [3,
2-c] pyridine, (293) 4- (4-propylpipera
Zin-1-yl) -6- [4- (2-hydroxyethoxy)
Cis) phenyl] thieno [3,2-c] pyridine, (29
4) 6- [4- (2-methyl-2-hydroxypropoxy)
C) phenyl] -4- [4- (2-fluoroethyl) pi
Perazin-1-yl] thieno [3,2-c] pyridine,
(295) 4- [4- (2-fluoroethyl) piperazine
-1-yl] -6- [4- (2-hydroxyethoxy)
Phenyl] thieno [3,2-c] pyridine, (296) 6
-[4- (2-methyl-2-hydroxypropoxy) phenyl
Enyl] -4- [4- (2-hydroxyethyl) pipera
Zin-1-yl] thieno [3,2-c] pyridine, (29
7) 6- [4- (2-methyl-2-hydroxypropoxy)
C) phenyl] -4- [4- (2-phenylethyl) pi
Perazin-1-yl] thieno [3,2-c] pyridine,
(298) 7- (1-Ethylpiperazin-4-yl) -5
-[3- (2-hydroxyethoxy) phenyl] furo
[2,3-c] pyridine, (299) 7- (1-ethylpi
Perazin-4-yl) -5- [4- (3-hydroxyp
[Ropyl) phenyl] furo [2,3-c] pyridine, (30
0) 7- (1-Ethylpiperazin-4-yl) -5-
[4- (3-hydroxybutyl) phenyl] furo [2,
3-c] pyridine, (301) 7- (1-ethylpiperazine
N-4-yl) -5- [4- (2-hydroxyethoxy)
C) phenyl] furo [2,3-c] pyridine, (302)
7- (1-ethylpiperazin-4-yl) -5- {4-
[(R) -2-hydroxy-1-methylethoxy] fe
Nyl @ furo [2,3-c] pyridine, (303) 7- (1
-Ethylpiperazin-4-yl) -5- {4-[(S)
-2-hydroxy-1-methylethoxy] phenyl
B [2,3-c] pyridine, (304) 7- (1-ethyl)
Piperazin-4-yl) -5- {4-[(S) -2-h
[Droxypropoxy] phenyl @ furo [2,3-c] pi
Lysine, (305) 7- (1-ethylpiperazine-4-i
) -5- {4-[(R) -2-hydroxypropoxy)
[Phenyl] furo [2,3-c] pyridine, (306)
7- (1-ethylpiperazin-4-yl) -5- [4-
(3-hydroxy-3-methylbutoxy) phenyl] f
B [2,3-c] pyridine, (307) 7- (1-ethyl)
Piperazin-4-yl) -5- {trans-2- [4-
(2-Hydroxyethoxy) phenyl] ethenyl difluoro
[2,3-c] pyridine, (308) 7- (1-ethylpi
Perazin-4-yl) -5- {trans-2- [2-
(2-Hydroxyethoxy) phenyl] ethenyl difluoro
[2,3-c] pyridine, (309) 1- (1-ethylpi
Perazin-4-yl) -3- [4- (2-hydroxy-
2-methylpropoxy) phenyl] isoquinoline, (31
0) 1- (1-Ethylpiperazin-4-yl) -3-
(3-phenyl-3-hydroxy-1-propynyl) i
Soquinoline, (311) 1- (1-ethylpiperazine-4)
-Yl) -8-methyl-3- (4-methoxyphenyl)
Isoquinoline (312) 1- (1-ethylpiperazin-4-yl) -4
-Methyl-3- (4-methoxyphenyl) isoquinol
, (313) 1- [1- (2-cyanoethyl) piperazine
4-Nyl] -3- (4-methoxyphenyl) isoalkyl
Norin, (314) 1- [1- (carbamoylmethyl) pi
Perazin-4-yl] -3- (4-methoxyphenyl)
Isoquinoline, (315) 1- (4-ethylsulfonylpy
Perazin-1-yl) -3- (4-methoxyphenyl)
Isoquinoline, (316) 4-piperazinyl-6- [4-
(2-methyl-2-hydroxypropoxy) phenyl]
Thieno [3,2-c] pyridine, (317) 7- (1-E
Cylpiperazin-4-yl) -5- [4- (3-hydro
Xypropoxy) phenyl] furo [2,3-c] pyridi
, (318) 1- (4-ethylpiperidin-1-yl)
-3- (4-methoxyphenyl) isoquinoline, (31
9) 1- {N- [2- (2-dimethylamino) ethyl]
-N-methylamino} -3- (4-methoxyphenyl)
Isoquinoline, (320) 1- (4-morpholinyl) -3
-(4-methoxyphenyl) isoquinoline, (321) 1
-(1-ethyl-2-pyrrolidinyl) methylamino-3
-(4-methoxyphenyl) isoquinoline, (322) 3
-(4-methoxyphenyl) -1- [2- (2-pyridi
Ru) ethyl] aminoisoquinoline, (323) 1- [2-
(4-morpholinyl) ethyl] amino-3- (4-metho
(Xyphenyl) isoquinoline, (324) 1- (1-imi)
Dazolyl) -3- (4-methoxyphenyl) isoquinol
, (325) 1- [4- (piperidin-1-yl) pipe
Lysin-1-yl] -3- (4-methoxyphenyl) i
Soquinoline, (326) 1- (1,4,5,6-tetrahi
Dropyrimidin-1-yl) -3- (4-methoxyfe
Nyl) isoquinoline, (327) 1- (1-ethylhomopi
Perazin-4-yl) -3- (4-methoxyphenyl)
Isoquinoline, (328) 3- (4-methoxyphenyl)
-1- (4-ethylpiperazin-1-yl) methyliso
Quinoline, (329) 1- (4-ethylpiperazine-1-
Yl) -3- [3- (2-hydroxyethoxy) phenyl
Ru] isoquinoline, (330) 1- (4-ethylpiperazine)
1-yl) -3- (4-ethoxyphenyl) isoquinone
Norin, (331) 1- (4-ethylpiperazine-1-i
) -3- [4- (3-Hydroxypropoxy) phenyl
Ru] isoquinoline, (332) 1- (4-ethylpiperazine)
1-yl) -3- (3,4-ethylenedioxyphene
Nyl) isoquinoline, (333) 1- (4-ethylpipera)
Zin-1-yl) -3- [4- (3-methoxypropyl
L) phenyl] isoquinoline, (334) 1- (4-ethyl
Rupiperazin-1-yl) -3- [4- (n-butyl)
Phenyl] isoquinoline, (335) 1- (4-ethylpi
Perazin-1-yl) -3- (4-methoxypyridine-
2-yl) isoquinoline, (336) 1- (4-ethylpi
Perazin-1-yl) -3- [4- (1,3-dioxo
Lan-2-ylmethyloxy) phenyl] isoquinolyl
, (337) 1- (4-ethylpiperazin-1-yl)
-3- [4- (2,3-dihydroxypropoxy) fe
Nyl] isoquinoline, (338) 1- (4-ethylpipera)
Zin-1-yl) -3- (4-carbamoylmethoxyph
Enyl) isoquinoline, (339) 1- (4-ethylpipe)
Razin-1-yl) -3- (4-trifluoromethoxy
Phenyl) isoquinoline, (340) 1- (4-ethyl
Perazin-1-yl) -3- [4- (2-hydroxyd
Toxy) -3-methoxyphenyl] isoquinoline, (34
1) 1- (4-Ethylpiperazin-1-yl) -3-
(4-methylthiophenyl) isoquinoline, (342) 1
-(4-ethylpiperazin-1-yl) -3- (4-me
(Tylsulfonylphenyl) isoquinoline, (343) 1-
(4-ethylpiperazin-1-yl) -3- [4- (2
-Hydroxy-3-methoxypropoxy) phenyl] i
Soquinoline, (344) 1- (4-ethylpiperazine-1)
-Yl) -3- (2-methoxypyridin-5-yl) i
Soquinoline, (345) 1- (4-ethylpiperazine-1
-Yl) -3- [4- (1-hydroxy-1-methyle
Tyl) phenyl] isoquinoline, (346) 1- (4-E
Cylpiperazin-1-yl) -3- {4- [N- (2-
Hydroxyethyl) carbamoyl] phenyl} isoquino
Phosphorus, (347) 1- (4-ethylpiperazine-1-i
) -3- {4- [N- (2-hydroxyethyl) sulfur
Famoyl] phenyl} isoquinoline, (348) 1-
(4-ethylpiperazin-1-yl) -3- [4- (1
-Hydroxyethyl) phenyl] isoquinoline, (34
9) 1- (4-ethylpiperazin-1-yl) -3-
[4- (propylsulfonyl) phenyl] isoquinolyl
, (350) 1- (4-ethylpiperazin-1-yl)
-3- {4-[(3-methoxypropyl) sulfonyl]
Phenyl diisoquinoline, (351) 1- (4-ethyl
Perazin-1-yl) -3- [4- (2-hydroxyd
Tyl) phenyl] isoquinoline, (352) 1- (4-E
Cylpiperazin-1-yl) -3- [4- (3-hydro
[Xypropyl) sulfonylphenyl] isoquinoline,
(353) 1- (4-ethylpiperazin-1-yl) -3
-[4- (N-propylsulfamoyl) phenyl] i
Soquinoline, (354) 1- (4-ethylpiperazine-1)
-Yl) -3- {4- [N- (2-methoxyethyl) s
Rufamoyl] phenyl} isoquinoline, (355) 1-
(4-ethylpiperazin-1-yl) -3- [4- (3
-Fluoropropyl) sulfonylphenyl] isoquinolyl
, (356) 1- (4-ethylpiperazin-1-yl)
-3- [4- (Pyrrolidin-1-yl) sulfonylfe
Nyl] isoquinoline, (357) 1- (4-ethylpipera)
Zin-1-yl) -3- [4- (N-ethylsulfamo
Yl) phenyl] isoquinoline, (358) 1- (4-E)
Cylpiperazin-1-yl) -3- [4- (N-methyl
-N-propylsulfamoyl) phenyl] isoquinolyl
, (359) 1- (4-ethylpiperazin-1-yl)
-3- [4- (N, N-diethylsulfamoyl) fe
Nyl] isoquinoline, (360) 1- (4-ethylpipera)
Zin-1-yl) -3- {4- [N- (1-methylpro
Pill) sulfamoyl] phenyl} isoquinoline, (36
1) 1- (4-Ethylpiperazin-1-yl) -3-
[4- (N-methylsulfamoyl) phenyl] isoki
Norin, (362) 1- (4-ethylpiperazine-1-i
) -3- [4- (N, N-dimethylsulfamoyl)
Phenyl] isoquinoline, (363) 1- (4-ethylpi
Perazin-1-yl) -3- [4- (N-cyclopropyl
Rusulfamoyl) phenyl] isoquinoline, (364)
1- (4-ethylpiperazin-1-yl) -3- [4-
(N-ethylcarbamoyl) phenyl] isoquinoline,
(365) 1- (4-ethylpiperazin-1-yl) -3
-[4- (N-methylcarbamoyl) phenyl] isoki
Norin, (366) 1- (4-ethylpiperazine-1-i
) -3- [4- (Ethylsulfonyl) phenyl] iso
Quinoline, (367) 1- (4-ethylpiperazine-1-
Yl) -3- (3-Fluoro-4-methoxyethoxyf
Enyl) isoquinoline, (368) 1- (4-ethylpipe)
Lazin-1-yl) -3- (3,5-difluoro-4-
(Methoxyethoxyphenyl) isoquinoline, (369) 1
-(4-ethylpiperazin-1-yl) -3- [3-f
Fluoro-4- (2-hydroxyethoxy) phenyl] i
Soquinoline, (370) 1- (4-ethylpiperazine-1
-Yl) -3- [3,5-difluoro-4- (2-hydrido)
Roxyethoxy) phenyl] isoquinoline, (371)
1- (4-ethylpiperazin-1-yl) -3- [3,
5-difluoro-4- (2-fluoroethoxy) phenyl
] Isoquinoline, (372) 1- [4- (2-hydroxy
Ciethyl) piperazin-1-yl] -3- [4- (N-
Ethylsulfamoyl) phenyl] isoquinoline, (37
3) 1- [4- (2-hydroxyethyl) piperazine-
1-yl] -3- [4- (propylsulfonyl) phenyl
Ru] isoquinoline, (374) 1- (4-ethylpiperazine)
1-yl) -3- (phenylthio) isoquinoline,
(375) 1- (4-ethylpiperazin-1-yl) -3
-[4- (2-oxopropyl) phenyl] isoquinolyl
, (376) 1- (4-ethylpiperazin-1-yl)
-3- [4- (2-hydroxypropyl) phenyl] i
Soquinoline, (377) 1- (4-ethylpiperazine-1
-Yl) -3- [4- (2-hydroxy-2-methylp
[Ropyl) phenyl] isoquinoline, (378) 1- (4-
Ethylpiperazin-1-yl) -3- (2-pyridylti
E) isoquinoline, (379) 1- (4-ethylpiperazine)
1-yl) -3- (4-butyrylphenyl) isoquinone
Norin, (380) 1- (4-ethylpiperazine-1-i
) -3- [4- (1-hydroxyiminobutyl) phenyl
Nyl] isoquinoline, (381) 1- (4-ethylpipera)
Zin-1-yl) -3- [4- (N-methyl-N-pro
Pyrcarbamoyl) phenyl] isoquinoline, (382)
1- (4-ethylpiperazin-1-yl) -3- {4-
[N- (2-hydroxyethyl) -N-methylcarbamo
Yl] phenyl} isoquinoline, (383) 1- (4-E
Cylpiperazin-1-yl) -3- [4- (3-hydro
Xy-1-methylpropyl) phenyl] isoquinoline,
(384) 1- (4-ethylpiperazin-1-yl) -3
-[4- (N-propylcarbamoyl) -3-fluoro
Phenyl] isoquinoline, (385) 1- (4-ethylpi
Perazin-1-yl) -3- [3-fluoro-4- (2
-Hydroxyethyl) phenyl] isoquinoline, (38
6) 1- (4-ethylpiperazin-1-yl) -3-
[4- (3-hydroxy-2-methylpropyl) pheni
Ru] isoquinoline, (387) 1- (4-ethylpiperazine)
1-yl) -3- [4- (1,2-dihydroxye
Tyl) phenyl] isoquinoline, (388) 1- (4-E
Cylpiperazin-1-yl) -3- [4- (3-hydro
[Xy-3-methylbutyl) phenyl] isoquinoline,
(389) 1- (4-ethylpiperazin-1-yl) -3
-[4- (3-hydroxy-2,2-dimethylpropyl
Ru) phenyl] isoquinoline, (390) 1- (4-ethyl)
Lupiperazin-1-yl) -3- [4- (3-hydroxy
[S-1,1-dimethylpropyl) phenyl] isoquinolyl
, (391) 1- (4-ethylpiperazin-1-yl)
-3- [4- (1,3-dihydroxy-2,2-dimethyl)
Propyl) phenyl] isoquinoline, (392) 1-
(4-ethylpiperazin-1-yl) -3- {4- [4
-(2-hydroxyethyl) tetrahydropyran-4-
Yl] phenyl} isoquinoline, (393) 1- (4-E)
Cylpiperazin-1-yl) -3- (2-hydroxyme
(Tilindan-5-yl) isoquinoline, (394) 1-
(4-ethylpiperazin-1-yl) -3-[(3,4
-Dihydroxymethyl) phenyl] isoquinoline, (39
5) 1- (4-ethylpiperazin-1-yl) -3-
[4- (1,4-dioxan-2-yl) phenyl] i
Soquinoline, (396) 1- (4-ethylpiperazine-1
-Yl) -3- [4- (tetrahydrofuran-2-i
L) phenyl] isoquinoline, (397) 1- (4-ethyl
Lupiperazin-1-yl) -3- [4- (cis-4-
Hydroxycyclohexyl) phenyl] isoquinoline,
(398) 1- (4-ethylpiperazin-1-yl) -3
-[4- (trans-4-hydroxycyclohexyl
Ru) phenyl] isoquinoline, (399) 1- (4-ethyl)
Lupiperazin-1-yl) -3- [4- (tetrahydro
Pyran-4-yl) methylphenyl] isoquinoline,
(400) 4-chloro-1- (4-ethylpiperazine-1
-Yl) -3- (4-methoxyphenyl) isoquinolyl
, (401) 1- (4-ethylpiperazin-1-yl)
-3- [4- (cis-4-hydroxytetrahydropi
Lan-2-yl) phenyl] isoquinoline, (402) 1
-(4-ethylpiperazin-1-yl) -3- [4-
(Trans-4-hydroxytetrahydropyran-2
-Yl) phenyl] isoquinoline, (403) 1- (4-
Ethylpiperazin-1-yl) -3- [4- (2-hydr)
Roxypropoxy) phenyl] isoquinoline, (404)
1- (4-ethylpiperazin-1-yl) -3- [4-
(2-hydroxy-1-methylethoxy) phenyl] i
Soquinoline, (405) 1- (4-ethylpiperazine-1)
-Yl) -3- (2-methoxypyridin-4-yl) i
Soquinoline, (406) 1- (4-ethylpiperazine-1
-Yl) -3- (2-benzyloxypyridine-4-i
L) isoquinoline and 1- (4-ethylpiperazine-
1-yl) -3- (2-chloropyridin-4-yl) i
Soquinoline, (407) 1- (4-ethylpiperazine-1
-Yl) -3- [2- (2-methoxyethoxy) pyridi
N-4-yl] isoquinoline, (408) 1- (4-ethyl
Lupiperazin-1-yl) -3- (4-carbamoylph
Enyl) isoquinoline, (409) 1- (4-ethylpipe)
Lazin-1-yl) -3- [4- (cyclohexyl hydride
Roxymethyl) phenyl] isoquinoline, (410) 1-
(4-ethylpiperazin-1-yl) -3- [4- (4
-Hydroxytetrahydropyran-4-yl) phenyl
Ru] isoquinoline, (411) 1- (4-ethylpiperazine)
1-yl) -3- {4- [bis (1,3-thiazole)
Ru-2-yl) hydroxymethyl] phenyl} isoquino
Phosphorus, (412) 1- (4-ethylpiperazine-1-i
) -3- [4- (1,3-thiazol-2-yl) hi
Droxymethylphenyl] isoquinoline, (413) 1-
(4-ethylpiperazin-1-yl) -3-[(3-pi
Lysyl) hydroxymethyl] isoquinoline, (414) 1
-(4-ethylpiperazin-1-yl) -3- (1-a
(Danon-5-yl) isoquinoline, (415) 1- (4
-Ethylpiperazin-1-yl) -3- (1-hydroxy
(Cyindan-5-yl) isoquinoline, (416) 1-
(4-ethylpiperazin-1-yl) -3- [4- (3
-Hydroxy-3-methylbutyl) -3-fluorophene
Nyl] isoquinoline, (417) 1- (4-ethylpipera)
Zin-1-yl) -3- [3-cyano-4- (2-hydr)
Roxyethoxy) phenyl] isoquinoline, (418) 1
-(4-ethylpiperazin-1-yl) -3- [3-
(3-hydroxypropyl) phenyl] isoquinoline,
(419) 1- (4-ethylpiperazin-1-yl) -3
-Benzylisoquinoline, (420) 1- (4-ethyl
Perazin-1-yl) -3- (2-hydroxy-2-f
Enylethyl) isoquinoline, (421) 3-benzami
Do-1- (4-ethylpiperazin-1-yl) isoquino
Phosphorus, (422) 3-benzenesulfonylamide-1-
(4-ethylpiperazin-1-yl) isoquinoline,
(423) 1- (4-ethylpiperazin-1-yl) -3
-(4-methoxybenzenesulfonylamide) isoquino
Phosphorus, (424) 1- (4-ethylpiperazine-1-i
) -3- (4-methoxyphenoxymethyl) isoquino
Phosphorus, (425) 1- (4-ethylpiperazine-1-i
) -3- [4- (2-Hydroxyethoxy) -2-me
Toxiphenyl] isoquinoline, (426) 1- (4-E
Cylpiperazin-1-yl) -3- [4- (2-hydro
[Xycyclohexyloxy) phenyl] isoquinoline,
(427) 4- (4-ethylpiperazin-1-yl) -2
-(4-methoxyphenyl) quinazoline, (428) 1-
(4-ethylpiperazin-1-yl) -3- (4-metho
(Xyphenyl) -7-azaisoquinoline, (429) 7-
(4-ethylpiperazin-1-yl) -5- [2- (3
-Hydroxypropyl) pyridin-5-yl] thieno
[2,3-c] pyridine, (430) 7- (4-ethylpi
Perazin-1-yl) -5- [3- (2-hydroxye
Toxy) styryl] thieno [2,3-c] pyridine,
(431) 7- (4-Ethylpiperazin-1-yl) -5
-[4- (2-hydroxyethoxy) styryl] thieno
[2,3-c] pyridine, (432) 7- (4-ethylpi
Perazin-1-yl) -5- [4- (3-hydroxyp
Ropyl) phenyl] thieno [2,3-c] pyridine,
(433) 7- (4-ethylpiperazin-1-yl) -5
-[4- (3-hydroxypropyl) -3-methoxyphenyl
Enyl] thieno [2,3-c] pyridine, (434) 7-
(4-ethylpiperazin-1-yl) -5- [4- (3
-Hydroxypropoxy) phenyl] thieno [2,3-
c] pyridine, (435) 7- (4-ethylpiperazine-
1-yl) -5- [4- (2-hydroxypropoxy)
Phenyl] thieno [2,3-c] pyridine, (436) 7
-(4-ethylpiperazin-1-yl) -5- [4-
(2-hydroxypropyl) phenyl] thieno [2,3
-C] pyridine, (437) 7- (4-ethylpiperazine
-1-yl) -5- [3-chloro-4- (2-hydroxy
Siethoxy) phenyl] thieno [2,3-c] pyridi
, (438) 7- (4-ethylpiperazin-1-yl)
-5- [4- (1-methyl-2-hydroxyethoxy)
Phenyl] thieno [2,3-c] pyridine, (439) 7
-(4-ethylpiperazin-1-yl) -5- [4-
(3-Hydroxy-3-methylbutyl) phenyl] thie
No [2,3-c] pyridine, (440) 7- (4-ethyl
Piperazin-1-yl) -5- [4- (3-hydroxy
Butyl) phenyl] thieno [2,3-c] pyridine,
(441) 7- (4-ethylpiperazin-1-yl) -5
-[4- (3-hydroxy-2-methylpropyl) fe
Nyl] thieno [2,3-c] pyridine, (442) 7-
(4-ethylpiperazin-1-yl) -5- [4- (3
-Hydroxy-2,2-dimethylpropyl) phenyl]
Thieno [2,3-c] pyridine, (443) 7- (4-E
Cylpiperazin-1-yl) -5- [4- (3-hydro
[Xy-1,1-dimethylpropyl) phenyl] thieno
[2,3-c] pyridine, (444) 7- (4-ethylpi
Perazin-1-yl) -5- [4- (2-hydroxyp
Ropirthio) phenyl] thieno [2,3-c] pyridi
, (445) 7- (4-ethylpiperazin-1-yl)
-5- (4-methanesulfonylphenyl) thieno [2,
3-c] pyridine, (446) 7- (4-ethylpiperazine
1-yl) -5- [4- (1-hydroxybutyl)
Phenyl] thieno [2,3-c] pyridine, (447) 7
-(4-ethylpiperazin-1-yl) -5- [4-
(N-methylcarbamoyl) phenyl] thieno [2,3
-C] pyridine, (448) 7- (4-ethylpiperazine
-1-yl) -5- [4- (N-ethylcarbamoyl)
Phenyl] thieno [2,3-c] pyridine, (449) 7
-(4-ethylpiperazin-1-yl) -5- [4-
(N-propylcarbamoyl) phenyl] thieno [2,
3-c] pyridine, (450) 7- (4-ethylpiperazine
1-yl) -5- (4-ethanesulfonylphenyi
Ru) thieno [2,3-c] pyridine, (451) 7- (4
-Ethylpiperazin-1-yl) -5- (4-propane
Sulfonylphenyl) thieno [2,3-c] pyridine,
(452) 7- (4-ethylpiperazin-1-yl) -5
-[4- (N-butylcarbamoyl) phenyl] thieno
[2,3-c] pyridine, (453) 7- (4-ethylpi
Perazin-1-yl) -5- [4- (N-cyclopentene
Rucarbamoyl) phenyl] thieno [2,3-c] pyri
Gin, (454) 7- (4-ethylpiperazine-1-i
) -5- [4- (cis-4-hydroxytetrahydrido)
[Ropyran-2-yl) phenyl] thieno [2,3-c]
Pyridine, (455) 7- (4-ethylpiperazine-1-
Yl) -5- [4- (trans-4-hydroxytet
Lahydropyran-2-yl) phenyl] thieno [2,3
-C] pyridine, (456) 7- (4-ethylpiperazine
-1-yl) -5- (2,3-dihydro-2-hydroxy
Cimethyl-2-methylbenzofuran-5-yl) thieno
[2,3-c] pyridine, (457) 7- (4-ethylpi
Perazin-1-yl) -5- [4- (cyclohexylhi)
Droxymethyl) phenyl] thieno [2,3-c] pyri
Gin, (458) 7- (4-ethylpiperazine-1-i
Ru) -5- [4- (cyclopentylhydroxymethyl)
Phenyl] thieno [2,3-c] pyridine, (459) 7
-(4-ethylpiperazin-1-yl) -5- (4-me
Toxiphenyl) thieno [2,3-c] pyridine, (46
0) 4- (4-Ethylpiperazin-1-yl) -6
[4- (1,3-dioxolan-2-yl) methoxyf
Enyl] thieno [3,2-c] pyridine, (461) 4-
(4-ethylpiperazin-1-yl) -6- [4- (2
-Hydroxyethoxy) phenyl] thieno [3,2-
c] pyridine, (462) 4- (4-ethylpiperazine-
1-yl) -6- [4- (3-hydroxypropoxy)
Phenyl] thieno [3,2-c] pyridine, (463) 4
-(4-ethylpiperazin-1-yl) -6- [4-
(2-hydroxy-1-methylethoxy) phenyl] thio
Eno [3,2-c] pyridine, (464) 4- (4-ethyl
Lupiperazin-1-yl) -6- [4- (3-hydroxy
[Ci-1-propynyl) phenyl] thieno [3,2-c]
Pyridine, (465) 4- (4-ethylpiperazine-1-
Yl) -6- [4- (3-hydroxypropyl) phenyl
Ru] thieno [3,2-c] pyridine, (466) 4- (4
-Ethylpiperazin-1-yl) -6- [4- (3-h
Droxy-3-methyl-1-butynyl) phenyl] thiye
No [3,2-c] pyridine, (467) 7- (4-ethyl
Piperazin-1-yl) -5- (4-methoxyphenyl)
F) Furo [2,3-c] pyridine, (468) 4- (4-
Ethylpiperazin-1-yl) -6- (4-methoxyph
Enyl) furo [3,2-c] pyridine and the like.

The above is a preferred embodiment of the compound represented by the above formula (I). However, the active ingredient of the medicament according to the present invention is not limited to the above compound, and the maximum of the range represented by the formula (I) is as follows. All aspects can be selected as far as possible.

The term "salt" as used herein refers to a pharmacologically acceptable salt, which is a compound contained in the therapeutic or prophylactic agent for urinary tract diseases according to the present invention and a pharmacologically acceptable salt. Although it is not particularly limited as long as it forms an acid salt, preferably, a hydrohalide (eg, hydrofluoride, hydrochloride, hydrobromide, hydroiodide, etc.), an inorganic acid salt (eg, sulfuric acid) Salt, nitrate, perchlorate, phosphate, carbonate,
Bicarbonate, etc.) organic carboxylate (eg, acetate, oxalate, maleate, tartrate, fumarate, citrate, etc.), organic sulfonate (eg, methanesulfonate, trifluoromethanesulfonic acid) Salt, ethanesulfonate, benzenesulfonate, toluenesulfonate,
Camphorsulfonate, etc.), amino acid salts (eg, aspartate, glutamate, etc.), quaternary amine salts, alkali metal salts (eg, sodium salt, potassium salt, etc.),
Alkaline earth metal salts (eg, magnesium salts and calcium salts). The “salt” is more preferably a hydrochloride, an oxalate or the like.

The compound represented by the above formula (I) or a salt thereof or a hydrate thereof contained in the therapeutic or prophylactic agent for urinary tract disease according to the present invention is produced by a known production method or a production method analogous thereto. can do. That is,
formula

Embedded image [Wherein each symbol and structure have the same meaning as in the above definition described for formula (II). Can be produced according to the production method described in WO 98/43956, a method analogous to the production method, or the like. Also, the formula

Embedded image [Wherein the symbols and formulas have the same meaning as in the above definition described for formula (III). Or a salt thereof or a hydrate thereof is disclosed in JP-A-2000-536.
It can be produced according to the production method described in JP-A-47-47, a method according to the production method, or the like. When the compound produced according to the production method is obtained as a free form, it can be converted to a salt state according to a conventional method,
Further, the isomer of the compound can be purified and isolated by using a usual separation means (for example, recrystallization, chromatography and the like).

The therapeutic or prophylactic agent for urinary tract disease according to the present invention comprises:
It can be formulated by a commonly used method, and preferred dosage forms include, for example, tablets, powders, fine granules, granules,
Examples include coated tablets, capsules, syrups, troches, inhalants, suppositories, injections, ointments, eye drops, eye ointments, nasal drops, ear drops, cataplasms, lotions and the like.
For formulation, commonly used excipients, binders, lubricants,
Coloring agents, flavoring agents, stabilizers and emulsifiers as needed,
An absorption enhancer, a surfactant, a pH adjuster, a preservative, an antioxidant and the like can be used, and a component generally used as a raw material of a pharmaceutical preparation can be blended to form a preparation by a conventional method. As these components, for example, soybean oil, tallow,
Animal and vegetable oils such as synthetic glycerides; hydrocarbons such as liquid paraffin, squalane, and solid paraffin; ester oils such as octyldodecyl myristate and isopropyl myristate; higher alcohols such as cetostearyl alcohol and behenyl alcohol; silicone resins; silicone oils; Surfactants such as ethylene fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene block copolymer; hydroxyethyl cellulose, polyacrylic acid, carboxyvinyl polymer,
Water-soluble polymers such as polyethylene glycol, polyvinylpyrrolidone and methylcellulose; lower alcohols such as ethanol and isopropanol; polyhydric alcohols such as glycerin, propylene glycol, dipropylene glycol and sorbitol; sugars such as glucose and sucrose; Examples include inorganic powders such as aluminum magnesium silicate and aluminum silicate, and purified water. As an excipient, for example, lactose, corn starch,
Sucrose, glucose, mannitol, sorbitol, crystalline cellulose, silicon dioxide and the like, as binders, for example, polyvinyl alcohol, polyvinyl ether, methyl cellulose, ethyl cellulose, gum arabic, tragacanth, gelatin, shellac, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinyl Pyrrolidone, polypropylene glycol / polyoxyethylene / block polymer, meglumine, etc., as disintegrants, for example, starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium hydrogencarbonate, calcium citrate, dextrin, pectin, carboxymethylcellulose Calcium and the like are used as lubricants, for example, magnesium stearate, talc, polyethylene glycol, silica, etc. , Hydrogenated vegetable oil and the like are those which are allowed to added to pharmaceuticals as coloring agents. Examples of the corrigent include cocoa powder, menthol, aromatic powder, peppermint oil, borneol, cinnamon powder and the like are used.

For example, in the case of oral preparations, a compound as an active ingredient or a salt thereof or a hydrate or excipient thereof, and if necessary, a binder, a disintegrant, a lubricant, a coloring agent, a flavoring agent, etc. After the addition, powders, fine granules, granules, tablets, coated tablets, capsules and the like are formed in a usual manner. In the case of tablets and granules, sugar coating or other appropriate coating may be used if necessary. In the case of syrups and injectable preparations, pH adjusters, solubilizers, tonicity agents, etc.
If necessary, a solubilizing agent, a stabilizing agent and the like are added, and the preparation is made by a conventional method. In the case of an external preparation, the production method is not particularly limited, and it can be produced by a conventional method. As base materials to be used, various raw materials usually used for pharmaceuticals, quasi-drugs, cosmetics, etc. can be used. For example, animal and vegetable oils, mineral oils, ester oils, waxes, higher alcohols, fatty acids , Silicone oil, surfactants, phospholipids, alcohols, polyhydric alcohols, water-soluble polymers, clay minerals, purified water and other raw materials. If necessary, pH adjusters, antioxidants , A chelating agent, an antiseptic / antifungal agent, a coloring agent, a fragrance and the like can be added. Further, if necessary, components having a differentiation inducing effect, components such as a blood flow promoter, a bactericide, an anti-inflammatory agent, a cell activator, vitamins, amino acids, a humectant, a keratolytic agent, and the like can be added. The dose of the sigma receptor binding agent according to the present invention varies depending on the degree of symptoms, age, sex, body weight, dosage form / type of salt, specific type of disease, and the like. About 30 μg to 10 g, preferably 100 μg to 5 g, more preferably 10 μg orally per day.
0 μg to 100 mg is administered by injection at about 30 μg to 1 g, preferably 100 μg to 500 mg, more preferably 100 μg to 30 mg, each in one or several divided doses.

The test examples and reference examples shown below are illustrative, and the therapeutic / prophylactic agent for urinary tract diseases according to the present invention is not limited to the following specific examples in any case. Those skilled in the art can make various modifications to the claims according to the present specification as well as the test examples or reference examples described below and can maximize the present invention, and such modifications are described in the present specification. It is included in such claims.

Test Example 1 [[ ³ H] -8-hydroxy-dipropylaminotetralin binding experiment] (1) Rat hippocampus was homogenized in 0.32 M sucrose and centrifuged at 1,000 xg for 10 minutes. The obtained supernatant was centrifuged at 20,000 × g for 20 minutes, and the operation of washing the precipitate with 50 mM Tris-HCl buffer (pH 7.5) was repeated three times. The final sediment was suspended in 100 times the initial wet weight of the same buffer to form a membrane fraction,
Stored at -80 ° C until use. The test compound and 0.1 to 1 nM [ ³ H] -8-hydroxy-dipropylaminotetralin were mixed with the membrane fraction and incubated at 37 ° C. for 20 minutes. This was filtered by suction with a glass filter, and the filter was washed with 50 mM Tris-HCl buffer (pH 7.5). Then, the radioactivity bound to the receptor was measured with a liquid scintillation counter. Non-specific binding was binding detected in the presence of 10 μM WAY-100,635. (2) Results: The agent according to the present invention and the compound or its salt or hydrate thereof contained in the agent showed an excellent receptor binding action.

Test Example 2 [5-HT _1A Receptor Antagonism Test] Human serotonin (5-HT _1A
It is well known that 5-HT _1A agonists inhibit forskolin-induced enhanced cAMP production in HEK293 cells expressing HT) 1A receptors. 5
-HT _1A antagonist antagonizes the inhibitory effect,
Using this as an index, the 5-HT _1A receptor antagonism of the test substance was examined. (1) First, 10% fetal calf serum, 0.6 mg
Using Dulbecco's modified Eagle's medium containing / mL Geneticin, the cells were cultured in a 48- or 96-well plate at 37 ° C. in the presence of 5% CO ₂ . Next, the test compound and the phosphodiesterase inhibitor were added dropwise, followed by incubation for a certain period of time. After that, the mixture was added dropwise to the medium together with forskolin and 8-hydroxy-dipropylaminotetralin.
Incubated for 0 minutes. After completion of the reaction, the medium was immediately removed by suction, and the cells were solubilized with a buffer containing 0.25% dodecyltrimethylammonium bromide. The resulting supernatant was used as a sample. (2) The amount of cAMP was determined by the enzyme antibody method. That is,
In a 96-well plate on which donkey anti-rabbit Ig antibody was immobilized,
A rabbit anti-cAMP antibody and a standard were added, followed by incubation at 4 ° C for 1 hour, and further addition of a cAMP-peroxidase conjugate and incubation at 4 ° C for 1 hour. Thereafter, the plate was washed with a buffer solution containing 0.05% Tween 20, and after adding tetramethylbenzidine, the mixture was stirred for 15 to 30 minutes at room temperature to cause a color reaction. After that, 1N sulfuric acid was added to stop the reaction. The amount of cAMP was calculated by measuring the absorbance at 450 nm. (3) Results: The agent according to the present invention and the compound or salt thereof or a hydrate thereof contained in the agent exhibited an excellent 5-HT _1A receptor binding action.

Test Example 3 Antagonism of 5-HT _1A receptor agonist-induced hypothermia in rats (1) 5-HT _1A receptor agonist (8-hydroxy-dipropylaminotetralin) 0.3 mg / The subcutaneous administration of 0.5 kg lowers the body temperature of rats.
-Has been found to be inhibited by HT _1A antagonists. In this test, the antagonism of the test substance to the 5-HT _1A receptor was evaluated using this as an index. That is, in the present study, by 3cm insertion probe into the rectum of the Sprague-Dawley strain female rats (200-250 g), were measured body temperature of the rat, for 5-HT _1A receptor agonist-induced body temperature lowering effect Antagonism was evaluated. The test substance was 30% at the time of administration of the 5-HT _1A agonist.
Administered one minute before. (2) Results: The agent according to the present invention and the compound or salt thereof or the hydrate thereof contained in the agent,
It exhibited excellent antagonism against HT _1A receptor agonist-induced hypothermia.

Test Example 4 [Inhibitory Action of Rhythmic Bladder Contraction in Rats] (1) In this test, Sprague-Dawley female rats (20
0-250 g). A midline incision was made in the abdomen under urethane (1 g / kg, subcutaneous administration) anesthesia, and then the ureters on both sides were ligated and cut on the kidney side. After the catheter was inserted into the bladder from the urethral opening to ligate the urethra, the other end of the catheter was connected to a pressure transducer and an infusion pump. Warm saline was injected into the bladder until rhythmic bladder contraction was induced, and changes in bladder pressure were recorded via a pressure transducer. The test substance was administered from a catheter previously placed in the jugular vein, and the effect of the test substance on the number of contractions for 15 minutes after administration was evaluated. (2) Results: The agent according to the present invention and the compound or salt thereof or a hydrate thereof contained in the agent showed a significant inhibitory effect on rhythmic bladder contraction. Excellent receptor binding action was demonstrated.

[0056]

According to the present invention, an excellent action as a medicine can be obtained.
A novel therapeutic and / or preventive agent for urinary tract disease that exerts an effect can be provided. The therapeutic or prophylactic agent for urinary tract disease according to the present invention is a medicament containing a compound having an affinity for 5-HT _1A receptor, a salt thereof or a hydrate thereof as an active ingredient, and particularly a dysuria (for example, prostate) In addition to being useful for the treatment and prevention of urination disorders caused by hypertrophy, etc., it can exert excellent effects in the treatment and prevention of pollakiuria and urinary incontinence. The therapeutic / prophylactic agent for urinary tract disease according to the present invention further comprises: Urinary frequency, urgency, urge incontinence, reflex incontinence, stress urinary incontinence, overflow incontinence, urinary incontinence associated with bladder irritation due to chronic cystitis, urinary incontinence associated with bladder irritation due to chronic prostatitis It is also useful for the treatment and prevention of nocturia, psychogenic dysuria, enuresis and the like.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Atsushi Sasaki, Inventor 4-15-2-2-203, Matsushiro, Tsukuba, Ibaraki (72) Inventor Keiko Takahashi 3-19-1, Minami, Ushiku-shi, Ibaraki Garden House K- N1 (72) Inventor Hiroki Kawano 2-1-7-201 Umezono, Tsukuba City, Ibaraki Prefecture (72) Inventor Tadashi Okabe 2-3-29 Minatomachi, Tsuchiura City, Ibaraki Prefecture Famiru Mitsuho A201 (72) Inventor Yuichi Suzuki Ibaraki 4930 Ino Windmill D302, Toride, Pref., Japan (72) Inventor Noboru Yamamoto 4-9-15, Matsushiro, Tsukuba, Ibaraki Pref. (72) Inventor Makoto Komatsu 3-8-10, Yoshiyuki, Fujisawa, Kanagawa Pref. 4C063 AA01 BB02 CC10 DD06 EE01 4C086 AA01 AA02 BC21 GA07 MA01 MA04 NA14 ZA81

Claims (31)

[Claims] (1) Formula (1)[Wherein A is a compound of the formula:(Wherein, Ar¹The ring is benzene, pyridine, pyridazine,
Represents a pyrimidine or pyrazine ring; Ar^TwoRing is Benze
Represents a pyridine, pyridine, thiophene or furan ring; D is
A group represented by the formula> CH- or a nitrogen atom;^Three
And R^FourAre the same or different (1) a hydrogen atom,
(2) halogen atom, (3) hydroxyl group, (4) cyano group,
(5) nitro group, (6) (i) halogen atom, (ii) hydroxyl
Group, (iii) cyano group, (iv) C_1-6Alkylsulfonyl
Amino group, (v) hydroxypiperidylcarbonyl group,
(Vi) Hydroxy C_1-6Alkylamide group, (vii) halo
Genification C_1-6Alkylamide group, (viii) dihalogenation
C_1-6Alkylamide group, (ix) heteroarylamide
Group, (x) hydroxy C_1-6Alkylamide group, (xi) water
An acid group, (xii) an optionally substituted amino group, (xii
i) C optionally substituted with a nitrogen atom_1-6Acylamino
Group, (xiv) optionally substituted C_6-14Aromatic hydrocarbon
A cyclic group, (xv) an optionally substituted 5- to 14-membered group
Aromatic heterocyclic group, (xvi) C_3-8Cycloalkylcarbonyl
An amino group, (xvii) an optionally substituted ureido group,
(Xviii) succinimido-1-yl group, (xix) substituted
An optionally substituted carbamoyl group, (xx)
Thiocarbamoyl group, (xxi) pyrrolidinyl car
Bonyl group, (xxii) optionally substituted aminosulfo
Nyl group, (xxiii) carboxyl group and (xxix) C_1-6
One or more groups selected from alkylamide groups
Optionally substituted C_1-6Alkyl group, (7) 1-hydr
Roxy C_3-8Cycloalkyl group, (8) 1-hydroxy-
1- (methoxypyridyl) methyl group, (9) (i) hydro
A xyimino group, (ii) a 2-pyrrolidone-1-yl group,
(Iii) 2-piperidone-1-yl group, (iv) 2-imi
Dazolidinone-1-yl group, (v) 2,4-imidazoli
Zindione-3-yl group, (vi) 2-oxazolidone-
3-yl group, (vii) glutarimido-1-yl group, (v
iii) a 2,4-thiazolidinedione-3-yl group and
(Ix) selected from an optionally substituted 4-piperidyl group
Methyl group substituted with a group represented by the formula_{1- 6}Alkoxy
C which may be substituted with a group or a hydroxyl group_1-6Alkoki
Shi group, (11) C_1-6Alkylsulfonyloxy group, (1
2) C which may be substituted_6-14Aromatic hydrogen ring group, (1
3) 5- to 14-membered aromatic heterocyclic ring which may be substituted
Group, (14) (i) C_1-6Alkyl group, (ii) C_1-6Arco
A xycarbonyl group, (iii) C_1-6Alkylsulfonyl
Group, (iv) C_1-6Acyl group and (v) even if substituted
One or two selected from arylsulfonyl groups
An amino group optionally substituted with the above groups, formula (15)
-CO-R³⁶(Where R³⁶Is (i) C_1-6Alkyl group,
(Ii) C_2-6Alkenyl group, (iii) C_2-6Alkynyl
Group, (iv) methoxypyridyl group, (v) C_6-14Aromatic coal
Hydrogenated ring group or (vi) 5- to 14-membered aromatic heterocyclic group
(16) 2-pyrrolidinone-1
-Yl group, (17) 1,3-propane sultam-2-yl
Group, (18) C_1-6Alkylsulfonyl group, (19) amide
Group, (20) sulfonamide group, (21) even if substituted
Good carbamoyl group, (22) urethane which may be substituted
Id group, (23) succinimide group or (24) formyl
Represents a group or R^ThreeAnd R^FourAre joined together by
Alicyclic ring which may be substituted, may be substituted
Heterocyclic or optionally substituted alkylenedio
R may form a xy group;^FiveIs (1) a hydrogen atom,
(2) halogen atom, (3) hydroxyl group, (4) (i) hydroxyl group
Or (ii) a sulfamo optionally substituted with a nitrogen atom
C optionally substituted with an yl group_1-6Alkyl group, (5)
C which may be substituted with a hydroxyl group_1-6An alkoxy group,
(6) formyl group, (7) optionally substituted aralkyl
Roxy group or (8) sulfa which may be substituted
Represents a moyl group; R⁶Is a hydrogen atom, a halogen atom, C_1-6
Alkyl group or C_1-6Represents an alkoxy group; R⁷Is hydrogen
Atom, halogen atom, C_1-6Alkyl group or C_1-6Al
Represents a oxy group; R⁸Is (1) (i) hydroxyl group, (ii) C
_6-14Aromatic hydrocarbon ring group and (iii) nitrogen atom are substituted
One selected from the group consisting of amino groups which may be
Or C which may be substituted with two or more groups._1-6Archi
Group, (2) optionally substituted C_{6- 14}Aromatic hydrocarbon
An aromatic ring or an optionally substituted 5- to 14-membered aromatic
C optionally substituted with a heterocyclic group_2-6Alkenyl
Group, (3) optionally substituted C_{6- 14}Aromatic hydrocarbon
Cyclic group, optionally substituted 5- to 14-membered heteroaromatic
C optionally substituted with a cyclic group or an aromatic acyl group
_2-6Alkynyl group, (4) (i) aromatic acyl group, (ii)
C_6-14Arylsulfonyl group, (iii) C_1-6Alkoxy
C _6-14Arylsulfonyl group, (iv) even when substituted
Good C_6-14Aromatic hydrocarbon ring group and (v) substituted
Substituted with a group selected from an aralkyl group which may be
An optionally substituted amino group, (5) an optionally substituted C_6-14
Aromatic hydrocarbon ring group, (6) 5 which may be substituted
14-membered aromatic heterocyclic group, (7) optionally substituted
Aralkyloxy group, (8) hydroxy C_1-6Alkoki
Cystyryl group, (9) C_1-6Alkoxyaryloxy
Group, (10) 4-phenylpiperidin-1-yl group, (1
1) 4-pyridylpiperidin-1-yl group or (12)
Formula 3Wherein M represents a nitrogen atom or a methine group;⁹, R
^TenAnd R¹¹Are the same or different (1) a hydrogen atom,
(2) halogen atom, (3) cyano group, (4) (i) hydroxyl
Group, (ii) halogen atom, (iii) cyano group, (iv) C
_1-6May be substituted with an alkoxy group or (v) a hydroxyl group
C_6-14Aromatic hydrocarbon ring group, (vi) 5- to 14-membered aromatic
Group heterocyclic group, (vii) hydroxyimino group, (viii) C
_3-8Cycloalkyl group, (ix) C_1-6Alkylsulfonyl
Amino group, (x) NC_1-6Alkylaminosulfonyl
Group, (xi) N, N-di C_1-6Alkylaminosulfonyl
Group, (xii) C_1-6Acyl group, (xiii) C_1-6Acylami
No group, (xiv) C_1-6Alkylsulfonyl group, (xv) N-
C_1-6Alkylamide group, (xvi) thiazol-2-yl
Group, (xvii) trifluoro group, (xviii) ω, ω-lower
Alkylenedioxy group and (xix) 1,3-dioxo
One or more groups selected from the group consisting of ranyl groups
C optionally substituted with_1-6Alkyl group, (5) hydroxyl group
C optionally substituted with_2-6Alkenyl group, (6) hydroxyl
C optionally substituted with a group_2-6Alkynyl group, (7)
Droxy C_3-8Cycloalkyl group, (8) hydroxy C
_3-8Cycloalkenyl group, (9) (i) hydroxyl group, (ii) c
A halogen atom, (iii) a cyano group, (iv) C_{1 -6}Alkoxy
Group, (v) C_1-6Thioalkoxy group, (vi) C_1-6Archi
Rusulfonyl group, (vii) hydroxy C_1-6Alkyl group,
(Viii) a 5- to 14-membered aromatic heterocyclic group, (ix) ω, ω
Lower alkylenedioxy group, (x) pyridyl group, (x
i) C_{1 -6}Alkylpyridyl group, (xii) trifluoro
Group, (xiii) amino group, (xiv) NC_1-6Alkylam
No group, (xv) N, N-diC_1-6Alkylamino group, (xv
i) C_1-6Acyl group, (xvii) C_1-6Acylaminoalco
A xy group, (xviii) (1,3-dioxolanyl) C_1-6A
Lucoxy group, (xix) amide group and (xx) imidazoly
At least one group selected from the group consisting of
C which may be replaced _1-6Alkoxy group, (10) hydro
Kishi C_3-8Substituted with cycloalkyloxy group, (11) hydroxyl group
C which may be replaced_1-6Thioalkoxy group, (12)
Reelthio group, (13) heteroarylthio group, (14) formula
 −N (R³⁷) R³⁸(Where R³⁷And R³⁸Are the same or
Differently hydrogen atom, C_1-6Alkyl group, hydroxy C
_1-6Alkyl group, C_1-6Acyl group, hydroxy C_1-6Reed
Group or C_1-6It represents an alkylsulfonyl group. )
Amino group, (15) (i) C_1-6Alkyl group, (i
i) C_3-8Cycloalkyl group, (iii) C_1-6Alkyl group,
(Iv) N-hydroxy C_1-6Alkyl group and (v) C
_6-14One or more selected from the group consisting of aromatic hydrocarbon ring groups
Is an amide group optionally substituted by two groups, (16) C
_1-6Alkyl group and hydroxy C_1-6From an alkyl group
Even if it is substituted with one or two groups selected from the group
Good carbamoyl group, (17) (i) C_1-6Alkyl group,
(Ii) hydroxy C _1-6Alkyl group, (iii) halogenation
C_1-6Alkyl group, (iv) C_1-6Alkoxyalkyl group,
(V) amino group, (vi) C_1-6Alkylamino group, (vi
i) C_3-8Cycloalkylamino group, (viii) di C_1-6A
Alkylamino group, (ix) N-hydroxy C_1-6Alkyl
Amino group, (x) NC_1-6Alkoxy C_1-6Alkyria
Amino group, (xi) arylamino group, (xii) 5 to 1
4-membered nitrogen-containing heterocyclic group, (xiii) 5- to 14-membered aromatic compound
A ring group, (xiv) 4-morpholinyl group, (xv) 4-oxo
Cythiomorpholinyl group and (xvi) 4-dioxythio
One or two members selected from the group consisting of morpholinyl groups
A sulfonyl group which may be substituted with a group, (18)
OR³⁹(Where R³⁹Is C_1-6Alkyl group, C_2-6Arche
Nyl group, C_2-6Alkynyl group or 5- to 14-membered nitrogen
Represents an elementary heterocyclic group. ), (19) Tetrahi
Dropyranyl group, hydroxytetrahydropyranyl group,
Hydroxy C _1-6Alkyltetrahydropyranyl group, (2
0) C_6-14Aromatic hydrocarbon ring group, (21) 5 to 14 members
Aromatic heterocyclic group, (22) 4-hydroxypiperidyl group,
(23) 4-C_1-6Alkoxypiperidyl group, (24) ant
Oxy group, (25) 4- (hydroxyalkyl) tetra
Lahydropyran-4-yl group, (26) 2,3-dihydro
Benzofuranyl group, (27) 2-hydroxy-2-alkyl
-2,3-dihydrobenzofuranyl group, (28)
Nonyl group, (29) hydroxyindanyl group, (30)
Silimide group or (31) 2-oxazolidone-3-yl
Represents a group or (31) R⁷Is a hydrogen atom and R⁸You
And R⁹Are linked together by cyclopentanone
Ring, hydroxycyclopentane ring, hydroxyalkyl
Cyclopentane ring, cyclohexanone ring, hydroxy
Clohexane ring, hydroxyalkylcyclohexane
Ring, 2-hydroxymethyl-2-methylcyclopentano
Ring, 1,2-ethylenedioxy ring or methylenedi
May form a xy ring; q represents 0 or 1;
r and s are the same or different and each is an integer of 0, 1 to 6
R;¹², R¹⁴, R^Fifteen, R¹⁶, R¹⁷, R¹⁸, R¹⁹,
R²⁰, R^{twenty one}, R^{twenty two}, R^{twenty three}, R^{twenty four}, R^{twenty five}, R²⁷, R²⁹And
And R³¹Are the same or different and are each a hydrogen atom, halo
Gen atom, hydroxyl group, C which may be substituted with a hydroxyl group
_1-6C which may be substituted with an alkyl group or a hydroxyl group_1-6A
Represents a alkoxy group or a tetrahydropyranyl group;¹³
Represents a hydrogen atom, a halogen atom, a hydroxyl group, C_1-6Alkyl group
Or C_1-6Represents an alkoxy group; R²⁶Is a hydrogen atom or
Is C_1-6Represents an alkyl group; R²⁸Is a hydrogen atom or a hydride
Roxy C_1-6Represents an alkyl group; R³⁰Is a hydrogen atom or
C_1-6Represents an alkyl group; R³²Is a hydrogen atom, C_1-6Archi
Group, C_1-6Alkoxy group, hydroxy C_1-6Alkyl group
Or hydroxy C_3-8Represents a cycloalkoxy group; W
Represents a sulfur atom or an oxygen atom; partial structure--- Is simply
Indicates a bond or a double bond. Selected from the group consisting of
Indicates any group; partial structure---- Is a single bond or two
Represents a heavy bond; n represents an integer of 0, 1 to 3;
It represents an integer of 0, 1 to 6. ) Represents a group represented by
And further [1] A is the formula(Wherein, Ar¹Ring, R^Three, R^Four, R^Five, D and n are as defined above.
We show the same meaning in righteousness. X) represents a group represented by
Nitrogen atom or formulaR represents a group represented by¹And R^TwoAre together by bonding
And a formula containing X(Wherein X and Y are the same or different, and
R represents a group of the same meaning; R³³Is (1) hydrogen atom, (2) water
Acid group or (3) (i) hydroxyl group, (ii) C_1-6Alkoxy
A group, (iii) an optionally substituted aryloxy group and
And (iv) an optionally substituted aralkyloxy group
Substituted with one or more groups selected from the group consisting of
May be C_1-6Represents an alkyl group; R³⁴Is C_1-6Al
Kill group, C_1-6Acyl group, C_1-6Alkoxycarbonyl
Group, aromatic acyl group or formula -Q¹− (CH_Two)_s−Q^Two−
R⁴⁰(Where Q¹And Q^TwoAre the same or different
Is represented by an oxygen atom, a carbonyl group, or the formula -NHCO-
Group represented by the formula —NHSO_TwoA group or formula represented by-
> CH-R⁴¹(Where R ⁴¹Is a hydroxyl group, C_1-6Alkyl group
Or a halogen atom. ) Represents a group represented by
And Q¹And Q^TwoOne of the two represents a single bond; s is
R represents 0 or an integer of 1 to 6;⁴⁰Is a cyano group, substituted
C that may be_6-14Aromatic hydrocarbon ring group, substituted
An optionally substituted 5- to 14-membered aromatic heterocyclic group,
A benzoheteroaryl group, 1,4-benzo
Dioxanyl group, 1,3-benzodioxolyl group or
Shows a benzthiazolyl group. ));
t represents an integer of 1 to 3. ) Represents a group represented by
And m represents 0 or an integer of 1 to 6, and [2]
A is the formula(Wherein, Ar^TwoRing, R⁶, R⁷, R⁸And p are as defined above
Show the same significance. X represents nitrogen
Represents an atom, R¹And R^TwoAre the same or different
(1) hydrogen atom or (2) (i) N, N-diC_1-6Archi
5-amino group and (ii) optionally substituted 5 to
1 or selected from the group consisting of a 14-membered aromatic heterocyclic group
C which may be substituted with two or more groups_1-6Alkyl group
Or together by a bond(Wherein E is a nitrogen atom or a group represented by the formula> CH-
R;³⁵Is (1) hydrogen atom, (2) (i) hydroxyl group, (i
i) halogen atom, (iii) cyano group, (iv) carbamoy
And (v) C_6-14Selected from aromatic hydrocarbon ring groups
C which may be substituted with_1-6Alkyl group, (3) C
_2-6Alkenyl group, (4) 1-piperidyl group, (5) C_3-8
Cycloalkyl group or formula (6) -CO-R⁴²(Where
R⁴²Is C _1-6Alkyl group, C_2-6Alkenyl group, C_2-6A
Rukinyl group, C_1-6Alkoxy group, C_6-14Aromatic hydrocarbon
Heterocyclic group, 5- to 14-membered aromatic heterocyclic group, aryloxy
It represents a cyclo group or an aralkyloxy group. )
Represents a group. ) And m represents 0
You. Or a salt thereof or a compound thereof
A therapeutic or prophylactic agent for urinary tract disease, comprising a hydrate of: (2) a compound represented by the formula: [Wherein, Ar ¹ ring, R ³ , R ⁴ , R ⁵ , R ³³ , R ³⁴ , D,
nitrogen atom or the formula: 10 wherein X and Y are the same or different and; n, t and partial structure ---- are showing the same meanings as defined above And m represents 0 or an integer of 1 to 6. The agent according to claim 1, which is represented by the formula: 3. A compound of the formula [Wherein, the Ar ¹ ring, R ³ , R ⁴ , R ⁵ , D and n have the same meaning as defined above. A group represented by the formula: [Wherein, R ³ , R ⁴ and R ⁵ have the same meanings as defined above; the partial structure --- represents a single bond or a double bond. ]
The agent according to claim 2, which is represented by the formula: 4. The agent according to claim 2, wherein the Ar ¹ ring is a benzene ring. 5. The agent according to claim 2, wherein the Ar ¹ ring is a benzene ring, D is a nitrogen atom, and n is 0. 6. The agent according to claim 2, wherein m is 0. 7. The agent according to claim 2, wherein m is an integer of 1 to 6. 8. The agent according to claim 2, wherein t is 2. 9. The agent according to claim 2, wherein X is a methine group and Y is a nitrogen atom. 10. The agent according to claim 2, wherein X is a methine group, Y is a nitrogen atom, and t is 2. Agent according to claim 2, wherein the partial structure --- is a double bond at 11. Formula (II). 12. The agent according to claim 2, wherein R ³³ is a hydrogen atom. 13. R ³⁴ has the formula _{^{-Q 1 - (CH 2) s}} -Q 2 -R 40
[Wherein Q ¹ , Q ² , R ⁴⁰ and s have the same meanings as defined above. 3. The agent according to claim 2, which is a group represented by the formula: (14) a compound represented by the formula: [Wherein, R ³ , R ⁴ , R ⁵ , R ³³ and R ³⁴ have the same meaning as defined above. The agent according to claim 1, which is represented by the formula: (15) a compound represented by the formula:[Wherein, Ar^TwoRing, R⁶, R⁷, R⁸And p are as defined above
Show the same meaning; R¹And R^TwoAre the same or different
(1) hydrogen atom or (2) (i) N, N-diC_1-6Archi
5-amino group and (ii) optionally substituted 5 to
1 or selected from the group consisting of a 14-membered aromatic heterocyclic group
C which may be substituted with two or more groups_{1- 6}Alkyl group
Or together by a bond with the formula(Wherein E is a nitrogen atom or a group represented by the formula> CH-
R;³⁵Is (1) hydrogen atom, (2) (i) hydroxyl group, (i
i) halogen atom, (iii) cyano group, (iv) carbamoy
And (v) C_6-14Selected from aromatic hydrocarbon ring groups
C which may be substituted with_1-6Alkyl group, (3) C
_2-6Alkenyl group, (4) 1-piperidyl group, (5) C_3-8
Cycloalkyl group or formula (6) -CO-R³⁸(Where
R³⁸Is C _1-6Alkyl group, C_2-6Alkenyl group, C_2-6A
Rukinyl group, C_1-6Alkoxy group, C_6-14Aromatic hydrocarbon
Heterocyclic group, 5- to 14-membered aromatic heterocyclic group, aryloxy
It represents a cyclo group or an aralkyloxy group. )
Represents a group. ). A compound represented by the formula:
The agent according to claim 1, which is 16. The agent according to claim 15, wherein R ³ is a hydrogen atom. 17. The method according to claim 15, wherein the Ar ² ring is a benzene ring.
Agents as described. 18. A compound of the formula [Wherein the Ar ² ring and R ⁶ have the same meaning as defined above. A group represented by the formula: Wherein R ⁶ is as defined above. 16. The agent according to claim 15, which is represented by the formula: 19. A compound represented by the formula: Wherein X, R ¹ and R ² have the same meaning as defined above. A group represented by the formula: [Wherein, R ³⁵ has the same meaning as defined above. 16. The agent according to claim 15, which is represented by the formula: 20. The method according to claim 1, wherein R ³⁵ is a C _1-6 alkyl group.
9. The agent according to 9. 21. The agent according to claim 19, wherein R ³⁵ is an ethyl group. 22. The agent according to claim 15, wherein R ⁶ is a hydrogen atom. 23. The agent according to claim 15, wherein R ⁷ is a hydrogen atom. 24. The C wherein R ⁸ is each optionally substituted
16. The agent according to claim 15, which is a _6-14 aromatic hydrocarbon ring group or a 5- to 14-membered aromatic heterocyclic group. (25) the agent according to the above (15), wherein R ⁸ is a phenyl group which may be substituted; 26. The agent according to claim 15, wherein p is 0. 27. The method according to claim 1, which is a therapeutic / prophylactic agent for dysuria.
Agents as described. 28. The agent according to claim 1, which is an agent for treating or preventing dysuria associated with benign prostatic hyperplasia. (29) The agent according to the above (1), which is a therapeutic / prophylactic agent for pollakiuria or urinary incontinence. 30. Urinary frequency associated with bladder irritation due to neuropathic bladder, neurogenic urinary frequency, unstable bladder, chronic cystitis, pollakiuria associated with bladder irritation due to chronic prostatitis, urgency, urgency incontinence , Reflex incontinence, stress urinary incontinence, overflow incontinence, urinary incontinence associated with bladder irritation due to chronic cystitis, urinary incontinence associated with bladder irritation due to chronic prostatitis, nocturia,
The agent according to claim 1, which is a therapeutic / prophylactic agent for psychogenic voiding disorder or enuresis. (31) Use of the compound according to (1), a salt thereof or a hydrate thereof for the manufacture of a therapeutic agent for dysuria.