Condensed heterocyclic ketone derivatives and their use

• US 5,462,934 A
• Filed: 03/04/1993
• Issued: 10/31/1995
• Est. Priority Date: 03/09/1992
• Status: Expired due to Fees

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Ishihara, Yuji, Miyamoto, Masaomi, Goto, Giichi
• Primary Examiner(s): Datlow, Philip I.
• Application Number:
  US08/026,041
• Time in Patent Office: 971 Days
• Field of Search: 540/542, 540/593, 540/594, 540/476, 514/213, 514/307, 514/311, 514/314, 514/253, 514/415, 514/416, 514/323, 514/183, 544/363, 544/373, 548/482, 548/491, 546/200, 546/201
• US Class Current: 514/183
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 215/08 with acylated ring nitrogen atom
• CPC Class Codes: C07D 223/16 Benzazepines; Hydrogenated benzazepines
• CPC Class Codes: C07D 225/06 condensed with one six-membered ring
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/10 Spiro-condensed systems

Abstract

A compound of the formula: ##STR1## wherein R¹ is H or an optionally substituted hydrocarbon or acyl group; ring A is an optionally further substituted benzene ring; n is an integer of 1 to 10; R², R³ and R⁴ are H or an optionally substituted hydrocarbon group; R³ and R⁴ may form an optionally substituted heterocyclic group, taken together with the adjacent nitrogen atom; k is an integer of 0 to 3; and m is an integer of 1 to 8; provided that when k=0 and m=2, n is an integer of not less than 2 or a pharmaceutically acceptable salt thereof, exhibiting excellent cholinesterase inhibitory activity and monoamine reuptake inhibitory activity, thus being useful as therapeutic/prophylactic medicaments of senile dementia.

Claims

1. A compound of the formula:

##STR1765## wherein R¹ is H, an optionally substituted hydrocarbon group or an optionally substituted acyl group;

ring A is an optionally further substituted benzene ring;

n is a whole number of 1 to 10;

R², is H or an optionally substituted hydrocarbon group;

R³ and R⁴ form an optionally substituted heterocyclic group, taken together with the adjacent nitrogen atom;

R² '"'"'s may be different from one another in the repetition of n;

k is a whole number of 0 to 3; and

m is a whole number of 1 to 8;

provided that when k=0 and m=2, n is a whole number of not less than 2, and provided that k+m=2 to 5;

or a pharmaceutically acceptable salt thereof.

2. A compound as claimed in claim 1, wherein R¹ is (1) a hydrogen atom, (2) a straight-chain or branched C_1-11 alkyl, C_2-4 alkenyl or C_2-4 alkynyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_1-4 alkylenedioxy and heterocyclic group, (3) a C_3-7 monocyclic cycloalkyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_1-4 alkylenedioxy and heterocyclic group, (4) a C_8-14 bridge ring saturated hydrocarbon group which may be substituted by 1 to 5 substituents selected from the group consisting of a halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_1-4 alkylenedioxy and heterocyclic group, (5) a phenyl or naphthyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a C_1-4 alkyl, halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_7-18 aralkyloxy, aminocarbonyloxy, mono- or di-C_1-4 alkyl-substituted aminocarbonyloxy, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, C_3-7 cycloalkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_3-7 cycloalkylsulfonyl and a phenyl, naphthyl, mono- or di-phenyl-C_1-3 alkyl, phenoxy, benzoyl, phenoxycarbonyl, benzylcarbonyl, phenyl-C_1-4 alkyl-carbamoyl, phenylcarbamoyl, phenyl-C_1-4 alkyl-carbonylamino, benzoylamino, phenyl-C_1-4 alkylsulfonyl, phenylsulfonyl, phenyl-C_1-4 alkylsulfinyl, phenyl-C_1-4 alkylsulfonylamino or phenylsulfonylamino group which may be substituted by 1 to 4 substituents selected from the group consisting of a C_1-4 alkyl, C_1-4 alkoxy, halogen, hydroxy, benzyloxy, amino, mono- or di-C_1-4 alkyl-substituted amino, nitro, C_1-6 alkyl-carbonyl and benzoyl, (6) a C_7-18 aralkyl, C_6-14 aryl-C_2-12 alkenyl, C_6-14 aryl-C_2-12 alkynyl or C_3-7 cycloalkyl-C_1-6 alkyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a C_1-4 alkyl, halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_7-18 aralkyloxy, aminocarbonyloxy, mono- or di-C_1-4 alkyl-substituted aminocarbonyloxy, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, C_3-7 cycloalkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_3-7 cycloalkylsulfonyl and a phenyl, naphthyl, mono- or di-phenyl-C_1-3 alkyl, phenoxy, benzoyl, phenoxycarbonyl, benzylcarbonyl, phenyl-C_1-4 alkyl-carbamoyl, phenylcarbamoyl, phenyl-C_1-4 alkyl-carbonylamino, benzoylamino, phenyl-C_1-4 alkylsulfonyl, phenylsulfonyl, phenyl-C_1-4 alkylsulfinyl, phenyl-C_1-4 alkylsulfonylamino or phenylsulfonylamino group which may be substituted by 1 to 4 substituents selected from the group consisting of a C.sub. 1-4 alkyl, C_1-4 alkoxy, halogen, hydroxy, benzyloxy, amino, mono- or di-C_1-4 alkyl-substituted amino, nitro, C_1-6 alkyl-carbonyl and benzoyl, (7) a C_1-8 alkyl-carbonyl or C_6-14 aryl-carbonyl group which may be substituted by 1 to 3 substituents selected from the group consisting of a halogen, amino, mono- or di-C_1-6 alkyl substituted amino and C_1-4 alkoxy, (8) a C_1-7 alkylsulfonyl or C_6-14 arylsulfonyl group which may be substituted by 1 to 3 substituents selected from the group consisting of a halogen, amino, mono- or di-C_1-6 alkyl substituted amino and C_1-4 alkoxy, (9) a C_1-7 alkylphosphonyl or C_6-14 arylphosphonyl group which may be substituted by 1 to 3 substituents selected from the group consisting of a halogen, amino, mono- or di-C_1-6 alkyl substituted amino and C_1-4 alkoxy, (10) a C_1-8 alkoxy-carbonyl or C_7-18 aralkyloxy-carbonyl group which may be substituted by 1 to 3 substituents selected from the group consisting of a halogen, amino, mono- or di-C_1-6 alkyl substituted amino and C_1-4 alkoxy, (11) heterocyclic-carbonyl group which may be substituted by 1 to 3 substituents selected from the group consisting of a halogen, amino, mono- or di-C_1-6 alkyl substituted amino and C_1-4 alkoxy, (12) carbamoyl group which may be substituted by 1 to 3 substituents selected from the group consisting of a halogen, amino, mono- or di-C_1-6 alkyl substituted amino and C_1-4 alkoxy, (13) mono- or di-C_1-4 alkyl-carbamoyl group which may be substituted by 1 to 3 substituents selected from the group consisting of a halogen, amino, mono- or di-C_1-6 alkyl substituted amino and C_1-4 alkoxy, or (14) formyl;

R² is (1'"'"') a hydrogen atom, (2'"'"') a straight-chain or branched C_1-11 alkyl, C_2-4 alkenyl or C_2-4 alkynyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1- 6 alkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_1-4 alkylenedioxy and heterocyclic group, (3'"'"') a C_3-7 monocyclic cycloalkyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1- 4 alkyl-carbonylamino, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_1-4 alkylenedioxy and heterocyclic group, (4'"'"') a C_8-14 bridge ring saturated hydrocarbon group which may be substituted by 1 to 5 substituents selected from the group consisting of a halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_1-4 alkylenedioxy and heterocyclic group, (5'"'"') a phenyl or naphthyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a C_1-4 alkyl, halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_7-18 aralkyloxy, aminocarbonyloxy, mono- or di-C_1-4 alkyl-substituted aminocarbonyloxy, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, C_3-7 cycloalkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_3-7 cycloalkylsulfonyl and a phenyl, naphthyl, mono- or di-phenyl-C_1-3 alkyl, phenoxy, benzoyl, phenoxycarbonyl, benzylcarbonyl, phenyl-C_1-4 alkyl-carbamoyl, phenylcarbamoyl, phenyl-C_1-4 alkyl-carbonylamino, benzoylamino, phenyl-C_1-4 alkylsulfonyl, phenylsulfonyl, phenyl-C_1-4 alkylsulfinyl, phenyl-C_1-4 alkylsulfonylamino or phenylsulfonylamino group which may be substituted by 1 to 4 substituents selected from the group consisting of a C_1-4 alkyl, C_1-4 alkoxy, halogen, hydroxy, benzyloxy, amino, mono- or di-C_1-4 alkyl-substituted amino, nitro, C_1-6 alkyl-carbonyl and benzoyl, (6'"'"') a C_7-18 aralkyl, C_6-14 aryl-C_2-12 alkenyl, C_6-14 aryl-C_2-12 alkynyl or C_3-7 cycloalkyl-C_1-6 alkyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a C_1-4 alkyl, halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_7-18 aralkyloxy, aminocarbonyloxy, mono- or di-C_1-4 alkyl-substituted aminocarbonyloxy, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, C_3-7 cycloalkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_3-7 cycloalkylsulfonyl and a phenyl, naphthyl, mono- or di-phenyl-C_1-3 alkyl, phenoxy, benzoyl, phenoxycarbonyl, benzylcarbonyl, phenyl-C_1-4 alkyl-carbamoyl, phenylcarbamoyl, phenyl-C_1-4 alkyl-carbonylamino, benzoylamino, phenyl-C_1-4 alkylsulfonyl, phenylsulfonyl, phenyl-C_1-4 alkylsulfinyl, phenyl-C_1-4 alkylsulfonylamino or phenylsulfonylamino group which may be substituted by 1 to 4 substituents selected from the group consisting of a C_1-4 alkyl, C_1-4 alkoxy, halogen, hydroxy, benzyloxy, amino, mono- or di-C_1-4 alkyl-substituted amino, nitro, C_1-6 alkyl-carbonyl and benzoyl, R³ and R⁴ taken together with the adjacent nitrogen atom, form a 3- to 13-membered heterocyclic group having, other than carbon atoms and one nitrogen atom, 1 to 3 nitrogen, oxygen and/or sulfur atoms as hetero atoms, which may be substituted by 1 to 5 substituents selected from the group consisting of (1") a straight-chain or branched C_1-11 alkyl, C_2-4 alkenyl or C_2-4 alkynyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_1-4 alkylenedioxy and heterocyclic group, (2") a C_3-7 monocyclic cycloalkyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a halogen, nitro, cyano, hydroxy, C_1- 4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_1-4 alkylenedioxy and heterocyclic group, (3") a C_8-14 bridge ring saturated hydrocarbon group which may be substituted by 1 to 5 substituents selected from the group consisting of a halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_1-4 alkylenedioxy and heterocyclic group, (4") a phenyl or naphthyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a C_1-4 alkyl, halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_7-18 aralkyloxy, aminocarbonyloxy, mono- or di-C_1-4 alkyl-substituted aminocarbonyloxy, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, alkyl-carbonyl, C_3-7 cycloalkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_3-7 cycloalkylsulfonyl, C_1-4 alkylenedioxy and a phenyl, naphthyl, mono- or di-phenyl-C_1-3 alkyl, phenoxy, benzoyl, phenoxycarbonyl, benzylcarbonyl, phenyl-C_1-4 alkyl-carbamoyl, phenylcarbamoyl, phenyl-C_1-4 alkyl-carbonylamino, benzoylamino, phenyl-C_1-4 alkylsulfonyl, phenylsulfonyl, phenyl-C_1-4 alkylsulfinyl, phenyl-C_1-4 alkylsulfonylamino or phenylsulfonylamino group which may be substituted by 1 to 4 substituents selected from the group consisting of a C_1-4 alkyl, C_1-4 alkoxy, halogen, hydroxy, benzyloxy, amino, mono- or di-C_1-4 alkyl-substituted amino, nitro, C_2-6 alkyl-carbonyl and benzoyl, (5") a C_7-18 aralkyl, C₆₁₄ aryl-C_2-12 alkenyl, C_6-14 aryl-C_2-12 alkynyl or C_3-7 cycloalkyl-C_1-6 alkyl group which may be substituted by 1 to 5 substituents selected from the group consisting of a C_1- 4 alkyl, halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_7-18 aralkyloxy, aminocarbonyloxy, mono- or di-C_1-4 alkyl-substituted aminocarbonyloxy, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, C_3-7 cycloalkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C.sub. 1-6 alkylsulfonyl, C_3-7 cycloalkylsulfonyl, C_1-4 alkylenedioxy and a phenyl, naphthyl, mono- or di-phenyl-C_1-3 alkyl, phenoxy, benzoyl, phenoxycarbonyl, benzylcarbonyl, phenyl-C_1-4 alkyl-carbamoyl, phenylcarbamoyl, phenyl-C_1-4 alkyl-carbonylamino, benzoylamino, phenyl-C_1-4 alkylsulfonyl, phenylsulfonyl, phenyl-C_1-4 alkylsulfinyl, phenyl-C_1-4 alkylsulfonylamino or phenylsulfonylamino group which may be substituted by 1 to 4 substituents selected from the group consisting of a C_1-4 alkyl, C_1-4 alkoxy, halogen, hydroxy, benzyloxy, amino, mono- or di-C_1-4 alkyl-substituted amino, nitro, C_1-6 alkyl-carbonyl and benzoyl, (6") halogen atom, (7") nitro group, (8") cyano group, (9") hydroxyl group, (10") C_1-4 alkoxy group, (11") C_1-4 alkylthio group, (12") amino group, (13") mono or di C_1-4 alkylamino group, (14") C_1-4 alkyl-carbonylamino group, (15") C_1-4 alkyl-sulfonylamino group, (16") C_1-4 alkoxy-carbonyl group, (17") carboxyl group, (18") formyl group, (19") C_1-6 alkyl-carbonyl group, (20") C_1-4 alkyl-carbonyloxy group, (21") ω

-oxo-ω

-(tetrahydrobenzazepinyl) C_1-6 alkyl group, (22") benzoyl group which may be substituted by 1 to 3 substituents selected from the group consisting of C_1-4 alkyl, halogen, C_1-4 alkoxy, mono- or di-C_1-4 alkylamino, 5- to 7-membered cyclic amino group, nitro and hydroxy, (23") carbamoyl group, (24") mono or di C_1-4 alkyl-carbamoyl group, (25") C_1-6 alkylsulfonyl group, (26") oxo group and (27") heterocyclic group selected from pyridinyl, pyrazinyl, pyrimidinyl, quinolinyl, isoquinolinyl, naphthylidinyl, benzothiazolyl, benzoxazolyl, furanyl and thiophenyl;

ring A is a benzene ring which may be further substituted by 1 to 3 substituents selected from the group consisting of a C_1-4 alkyl, halogen, nitro, cyano, hydroxy, C_1-4 alkoxy, C_1-4 alkylthio, amino, mono- or di-C_1-4 alkyl-substituted amino, 5 to 7-membered cyclic amino, C_1-4 alkyl-carbonylamino, C_7-18 aralkyloxy, aminocarbonyloxy, mono- or di-C_1-4 alkyl-substituted aminocarbonyloxy, C_1-4 alkylsulfonylamino, C_1-4 alkoxy-carbonyl, carboxyl, C_1-6 alkyl-carbonyl, C_3-7 cycloalkyl-carbonyl, carbamoyl, mono- or di-C_1-4 alkyl-substituted carbamoyl, C_1-6 alkylsulfonyl, C_3-7 cycloalkylsulfonyl and a phenyl, naphthyl, mono- or di-phenyl-C_1-3 alkyl, phenoxy, benzoyl, phenoxycarbonyl, benzylcarbonyl, phenyl-C_1-4 alkyl-carbamoyl, phenylcarbamoyl, phenyl-C_1-4 alkyl-carbonylamino, benzoylamino, phenyl-C_1-4 alkylsulfonyl, phenylsulfonyl, phenyl-C_1-4 alkylsulfinyl, phenyl-C_1-4 alkylsulfonylamino or phenylsulfonylamino which may be substituted by 1 to 4 substituents selected from the group consisting of a C_1-4 alkyl, C_1-4 alkoxy, halogen, hydroxy, benzyloxy, amino, mono- or di-C_1-4 alkyl-substituted amino, nitro, C_1-6 alkyl-carbonyl and benzoyl.

3. A compound as claimed in claim 1, wherein R¹ is

(i) hydrogen atom,

(ii) a C_1-4 alkyl group which may be substituted with a hydroxy group,

(iii) a C_2-4 alkynyl group,

(iv) a phenyl-C_1-3 alkyl group which may be substituted with one to three substituents selected from the group consisting of a halogen, nitro, cyano, C_1-4 alkyl, C_1-4 alkoxy, hydroxy and phenylmethoxy group,

(v) formyl group,

(vi) a C_1-4 alkyl-carbonyl group,

(vii) benzoyl group,

(viii) a C_1-4 alkoxy-carbonyl group,

(ix) pyridylcarbonyl group, or

(x) a mono- or di-C_1-4 alkylcarbamoyl group.

4. A compound as claimed in claim 1, wherein R¹ is (i) H, (ii) a straight-chain or branched C_1-4 alkyl group, (iii) a phenyl-C_1-3 alkyl group which may be substituted by 1 to 3 substituents selected from the group consisting of C_1-4 alkyl, halogen, nitro, cyano, hydroxy, C_1-4 alkoxy and C_7-18 aralkyloxy, (iv) a naphthyl-C_1-3 alkyl group, (v) a C_1-3 alkyl-carbonyl, (vi) a phenyloxycarbonyl or (vii) a C_1-4 alkoxy-carbonyl.

5. A compound as claimed in claim 1, wherein R¹ is (i) H, (ii) a straight-chain or branched C_1-4 alkyl group, (iii) a C_1-4 alkyl-carbonyl group or (iv) a phenyl-C_1-3 alkyl group which may be substituted by a C_1-4 alkoxy.

6. A compound as claimed in claim 1, wherein k is a whole number of 0 to 2 and m is a whole number of 2 to 5.

7. A compound as claimed in claim 1, wherein the moiety in the formula [I ] of ##STR1766## and R¹ is (i) H, (ii) a straight-chain or branched C_1-4 alkyl group, (iii) a C_1-3 alkyl-carbonyl group or (iv) a phenyl-C_1-3 alkyl group which may be substituted by a C_1-4 alkoxy.

8. A compound as claimed in claim 1, wherein the ring A is a benzene ring.

9. A compound as claimed in claim 1, wherein n is a whole number of 1 to 6.

10. A compound as claimed in claim 1, wherein R² is hydrogen atom or phenyl group.

11. A compound as claimed in claim 1, wherein R² is H.

12. A compound as claimed in claim 1, wherein R³ and R⁴, taken together with the adjacent nitrogen atom, form

(i'"'"') a piperidinyl group which may be substituted with a phenyl-C_1-3 alkyl group, a hydroxy group or oxo,

(ii'"'"') 4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]decan-8-yl,

(iii'"'"') 1,2,3,4-tetrahydroisoquinolin-2-yl,

(iv'"'"') pyrrolidinyl,

(v'"'"') morpholinyl,

(vi'"'"') a homopiperazinyl group which may be substituted with a phenyl-C_1-3 alkyl group, or

(vii'"'"') a piperazinyl group which may be substituted with (1) a phenyl-C_1-3 alkyl group which may be substituted with a halogen atom, a C_1-4 alkoxy group or a C_1-4 alkylenedioxy group, (2) pyridyl group, (3) a benzoyl group which may be substituted with a halogen atom, (4) a C_1-4 alkyl group which may be substituted with hydroxy group, 3-oxo-3[3-(phenylmethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]propyl, pyridyl, furyl or 2-methyl-thiazol-4-yl group, (5) formyl group, (6) a C_1-6 alkyl-carbonyl group, (7) a phenyl group which may be substituted with a halogen atom, (8) hydroxyl group or (9) a diphenyl-C_1-3 alkyl group.

13. A compound as claimed in claim 1, wherein R³ and R⁴ taken together with the adjacent nitrogen atom, form a pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl or 1,2,3,4-tetrahydroquinolinyl group which may be substituted by 1 or 2 substituents selected from the group consisting of (1) formyl, (2) C_1-4 alkylcarbonyl, (3) hydroxy, (4) oxo, (5) pyridyl, (6) benzoyl which may be substituted by 1 to 3 halogen atoms, (7) straight-chain or branched C_1-7 alkyl which may be substituted by 1 to 3 substituents selected from the group consisting of hydroxy, pyridyl, furyl, thiazol-4-yl and 2-methyl-thiazol-4-yl, (8) phenyl which may be substituted by 1 to 3 substituents selected from the group consisting of halogen, hydroxy and C_1-4 alkylenedioxy, (9) C_7-18 aralkyl which may be substituted by 1 to 3 substituents selected from the group consisting of halogen, hydroxy and C_1-4 alkylenedioxy and (10) ω

-oxo-ω

-(tetrahydrobenzazepinyl) C_1-6 alkyl.

14. A compound as claimed in claim 1, wherein R³ and R⁴ taken together with the adjacent nitrogen atom, form a 4-(phenylmethyl)-piperazin-1-yl or 4-[(2-methylthiazol-4-yl)methyl]-piperazin-1-yl.

15. A compound as claimed in claim 1, wherein n is a whole number of 2 to 5.

16. A compound as claimed in claim 1, which is a compound of the formula:

##STR1767## wherein R^1a is (i) a C_1-4 alkyl group or

(ii) a phenyl-C_1-3 alkyl group which may be substituted with a C_1-4 alkoxy group,

or a pharmaceutically acceptable salt thereof.

17. A compound as claimed in claim 1, which is 1-[3-[(4-methoxyphenyl)methyl]-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-3-[4-(phenylmethyl)piperazin-1-yl]-1-propanone or a pharmaceutically acceptable salt thereof.

18. A compound as claimed in claim 1, which is 1-[3-(2-phenylethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-3-[4-(phenylmethyl)piperazin-1-yl]-1-propanone or a pharmaceutically acceptable salt thereof.

19. A compound as claimed in claim 1, which is 1-[3-(2-methylpropyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-3-[4-(phenylmethyl)piperazin-1-yl]-1-propanone or a pharmaceutically acceptable salt thereof.

20. A compound as claimed in claim 1, which is 1-[3-(phenylmethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-3-[4-(phenylmethyl)piperazin-1-yl]-1-propanone or a pharmaceutically acceptable salt thereof.

21. A compound as claimed in claim 1, which is 1-[1-(phenylmethyl)-2,3-dihydro-1H-indol-5-yl]-3-[4-(phenylmethyl)piperazin-1-yl]-1-propanone or a pharmaceutically acceptable salt thereof.

22. A compound as claimed in claim 1, which is 1-[2-(phenylmethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl]-3-[4-(phenylmethyl)piperazin-1-yl]-1-propanone or a pharmaceutically acceptable salt thereof.

23. A compound as claimed in claim 1, which is 3-[4-[(2-methylthiazol-4-yl)methyl]piperazin-1-yl]-1-[3-(phenylmethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-1-propanone or a pharmaceutically acceptable salt thereof.

25. A pharmaceutical composition for a disease caused by acetylcholinesterase activity which contains an effective cholinesterase inhibiting amount of a compound of the formula as claimed in claim 1 or a pharmaceutically acceptable salt thereof and a pharmacologically acceptable carrier.

26. A pharmaceutical composition as claimed in claim 25, in which the disease is senile dementia and/or Alzheimer'"'"'s disease.

24. A compound of the formula:

##STR1768## wherein R¹ is H, an optionally substituted hydrocarbon group or an optionally substituted acyl group;

ring A is an optionally substituted benzene ring;

n is a whole number of 1 to 10;

R², R³ and R⁴ are independently H or an optionally substituted hydrocarbon group, provided one of R³ and R⁴ is H or a straight-chain or branched C_1-4 alkyl group and the other is a straight-chain or branched C_1-4 alkyl group, a phenyl-C_1-3 alkyl group or a naphthyl-C_1-3 alkyl group;

the R² '"'"'s may be different from one another in the repetition of n;

k is a whole number of 0 to 3; and

m is a whole number of 1 to 8;

provided that when k=0 and m=2, n is a whole number of not less than 2; and

provided that k+m=2 to 5;

or a pharmaceutically acceptable salt thereof.

27. A method of treating a disease caused by acetylcholinesterase activity which comprises administering a therapeutically effective amount of a compound of the formula:

##STR1769## wherein X¹ is R¹ --N (R¹ is H, an optionally substituted hydrocarbon group or an optionally substituted acyl group);

ring A is an optionally further substituted benzene ring;

n is a whole number of 1 to 10;

R², R³ and R⁴ are independently H or an optionally substituted hydrocarbon group;

R³ and R⁴ may form an optionally substituted heterocyclic group, taken together with the adjacent nitrogen atom;

R² '"'"'s may be different from one another in the repetition of n;

k is a whole number of 0 to 3; and

m is a whole number of 1 to 8, and provided that k+m=2 to 5;

or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier to a mammal suffering from such disease.