AU657424B2 - Oxytocin antagonist - Google Patents

Description

UPI DATE 31/01/94 APPIN. ID 43569/93 Illlll1111 111111111 AOJP DATE 28/04/94 PCT NUMBtER PCT/JP93/00835 I~~ll 111 ~lli i 11 AU9343569 (51) International Patent Classillcation 5 (It) International Publication Number: WO 94/01113 A61 K 31/537, 31/445 1495 (43) Intrnational Publication Date: 20 January 1994 (20.0194) (21) International Application Number: PCT/J P93/00835 (74) Agents: AQYAMA, Tamotsu et al.; Twin 21 Mid Tower.

(22) International Filing Date: 22 June 1993 (22 06.93) 1.61, Shiromi 2-clionie, Cliuo-ku, Osaka-shi, Osaka 540 Priority data:0 4/175563 2 July 1992 (02.07.92) 1 4/175566 2 July 1992 (02.07.92) P(81I) D~esignated States: AU, CA, KR, US, Europcan patent (71) Applkcant (for all d esit States excetU) TUA(T E H E K S R B R E T U PHARMACEUTICAL COMPANY LIMITED [3 CNP T S) JPJ; 9, Kandatsukasa-cho 2-chome, Chiyoda-ku, Tokyo 101 Published (72) Invent--s, andWihntnaia srcreo.

inventors/Applicants (for US otb) :OGAWA, Hidenori l'l nentoa eri eot Ii P/JPJ;, 25-18, Nakakiral-Aja Nakasenishinoko-shi, Matsushige-cho, Itano-gun. Tokushima 771-02 Ml- YAMOTO, Hisashi 3.16, Nakakirai-Aza Naka- 9 seteigai, Matsushige-cho, Itano-gun, Tokushima 771-02 KONDO, Kazumi [JP/Jl'j 55.11, Nukakiral-Aza YAMASHITA, Hiroshi liP/in; 57-1, Sasakino- Aza Hachikami, Matsushige-cho, Itano-gun, Tokushima 771.02 NAKAYA, Kenji lJP/JPJ:. 48, Kamibekkukita, Kawauchi-cho, Tokushima-shi, Tokushima 771-01 TANAKA, Michinori (JP/JPJ;, 211-1, Nakakirai- Aza Inamoto, Matsushig.'.cho, Itano-gun, Tokushima 771-02 KITANO, Kaziiyoslii [IP/JPI; KAN, Keizo IJP/JPI; 463-10, Kagasun-,, Kawauchi-cho, Tokushima.

shi, Tokushima 771-01 TOMINAGA, Michiaki liP/JP1; 310.6. Takaiso, Kamiita-cho, Itano-gun, Tokushima 771-13 YABUUCH-I, Yoichi [JP/JPI; 900-25, Omatsu, Kawauchi-cho, Tokushima-shi, Tokushima 771-01 (JP).

(54)TIe: OXYTOCIN ANTAGONIST KKN 0

R

(57) Abstract Oxytocin antagonist which comprises as an active ingredient the carbostyril derivative or formula or the benzohetero.

cyclic compound of formula or a pharmaceutically acceptable salt thereof, which shows excellent oxytocin antagonist activity and hence, is useful in the protection or treatment of oxytocin relating diseases, especially, for treatment of premature delivery, dysmenorrhea, endometritis, or for stopping labour preparatory to Caesarian delivery, WO 94/01113 PCT/JP93/00835

DESCRIPTION

OXYTOCIN ANTAGONIST Technical Field This invention relates to a novel oxytocin antagonist, which has excellent pharmacological activities, for example, inhibitory effect on uterin smooth muscle constriction, inhibitory effect on milk secretion, inhibitory effect on synthesis and secreation of prostaglandin, and vasodilation activity, and hence, are useful in the protection or treatment of oxytocin relating diseases, e.g. premature delivery, dysmenorrhea, endometritis, or in stopping labour preparatory to Caesarian delivery.

Background Art The carboxytril derivatives of the following formula and the benzohetrocyclic compounds of the following formula which are active ingredients of the present oxytocin antagonist, are known to have vasopressin antagonistic activity (cf. Japanese Patent First Publication (Kokai) No. 173870/1991, and European Patent No. 40097, respectively).

It is known that some heterocyclic compounds have oxytocin antagonistic activity. For example, EP-0421802-A2 discloses that 3-substituted-l,4-benzodiazepines of the following formula are antagonists of oxytocin and are useful in the treatment of preterm labour and dysmenorrhea and for WO 94/01113 PCT/JP93/uuai stoppage of labour preparatory to Caesarian delivery: R'

X

X1 N

R

R

2

(R'

1 3 wherein R 1 is H, C 1

-C

6 alkyl, lower alkenyl, lower alkynyl,

-X

1 2

COOR

6

-X

11 -cyclo(lower)alkyl, -X 12

NR

4

R

S

-X

12

CONR

4

R

5 12 CN or -X 11

C

10

R

2 is H, lower alkyl, substituted or unsubstituted phenyl, etc,; R 3 is H, -X 11

NR

1 8

X

11

R

7 etc.; R 9 and R 10 are each H, OH or CH 3

R

1 is H, lower alkyl, acyl, 0, cyclo(lower)alkyl, -X 11

COX

9

X

1 1

R

7 or -XlCOX 11

R

7

X

1 is H,

NO

2

CF

3 CN, OH, lower alkyl, halo, etc.; X 7 is 0, S, NH or

NR

15

X

11 is C!-C 4 alkylidene; and X 12 is C 1

-C

4 alkyl.

These compounds have a 1,4-benzodiazepine nucleus which is inclusive within the active compounds of the formula of the present invention, but are different in the substituen: at ?-position.

Some other European patent applications disclose also various oxytocin antagonists, such as spiro(indenepiperidine) compounds and analogues thereof (cf. EP-0444945- A2, EP-0450761-A1, and EP-0486280-A2), but these compounds are different from the active compounds of the formulae (1) and of the present invention in the chemical structure.

Disclosure of the Invention The present inventors have intensively studied the carbostyril derivatives of the formula and the WO 94/01113 -3- PCT/JP93/00835 benzohetrocyclic compounds of the formula and have found that these compounds and pharmaceutically acceptable salts thereof have excellent oxytocin antagonistic activity and have accomplished the present invention.

The carbostyril derivatives, which are one of active ingredients of the oxytocin antagonist of the present invention, have the following formula (1)

R

wherein R 1 is hydrogen atom; nitro; a lower alkoxy; a lower alkoxycarbonyl; a lower alkyl; a halogen atom; an amino having optionally one or two substituents selected from a lower alkanoyl, a lower alkyl, benozyl and a phenyl(lower)alkoxycarbonyl; hydroxy; cyano; carboxy; a lower alkanoyloxy; or hydrazinocarbonyl, q is an integer of 1 to 3, and R is a group of the formula: N-N R or (R)m wherein R 2 is hydrogen atom; a lower alkoxycarbonyl; a phenoxycarbonyl wherein the phenyl ring may optionally be substituted by one to three substituents selected from nitro and an amino having optionally one or two substituents selected from a lower alkanoyl, a lower alkyl and benzoyl; a phenyl(lower)alkenylcarbonyl; a phenyl(lower)alkanoyl wherein the lower alkanoyl moiety may optionally be 4 WO 94/01113 PCT/JP93/00835 substituted by an amino having optionally a lower alkoxycarbonyl subscicuent; an alkanoyl; an alkenylcarbonyl; a phenylsulfonyl wherein the phenyl ring may optionally be substituted by a lower alkoxy; a group of the formula:

-CONR

8

R

9 (wherein R 8 and R 9 are the same or different and are each hydrogen atom or a phenyl which may optionally have one to three substituents selected from a lower alkoxy, a lower alkyl, a halogen atom, an amino having optionally one or two substituents selected from a lower alkyl and a lower alkanoyl, and nicro); a heterocyclic group-substituted carbonyl wherein the heterocyclic group may optionally have one to three substituents selected from a phenyl(lower)alkoxycarbonyl, a phenyl(lower)alkoxy, oxo, a lower alkyl, and a lower alkylenedioxy; a group of the formula: -CO CH 3 I -CH 3 C H 3

CH

OH

3

OH

naphthylcarbonyl; a thienyl(lower)alkanoyl; a tricyclo- [3.3.1.1]decanyl(lower)alkanoyl; tricyclo[3.3.1.1]decanylcarbonyl; or a group of the formula: -CO (R13)p(wherein p is 0 or an integer of 1 to 3, and

R

13 is hydroxy; an alkoxy; an alkoxy which has one or two substituents selected from hydroxy, a lower alkanoyloxy, a tri(lower)alkylammonium, a lower alkoxy, and a group of the formula: -NF 1 4Ri 5 [wherein R 14 and R 15 are the same or different and are each hydrogen atom, a lower alkyl, a 5 WO 94/01113 PCT/JP93/00835 hydroxy-substituted lower alkyl, a lower alkanoyl, a tetrahydropyranyl(lower)alkyl, phenyl, a phenyl(lower)alkyl (wherein the alkyl moiety may optionally be substituted by hydroxy and the phenyl ring may optionally be substituted by a lower alkoxy), or a pyridyl(lower)alkyl; or R 14 and R 1 may bind with the nitrocen atom to which they bond to form a or 6-membered, saturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom (wherein the heterocyclic group may optionally be substituted by a member selected from carbamoyl, a lower alkyl, a phenyl(lower)alkyl, phenyl and a hydroxysubstituted lower alkyl)]; a carboxy-substituted alkoxy; a halogen-substituted lower alkoxy; a lower alkoxycarbonylsubstituted alkoxy; a lower alkanoyloxy-substituted lower alkoxy; a lower alkenyloxy-substituted lower alkoxy; a lower alkoxy(lower)alkoxy; a lower alkylsulfonyloxy-substituted lower alkoxy; a benzoyloxy-substituted lower alkoxy; tricyclo[3.3.1.1]decanyl-substituted lower alkoxy; a lower alkoxy(lower)alkoxy which is substituted by one or two substituents selected from hydroxy and an amino being optionally substituted by a lower alkyl; a morpholinylsubstituted lower alkoxy which may optionally be substituted by a lower alkvy or oxo; a benzimidazolylthio-substituted lower alkoxy; a benzimidazolylsulfinyl-substituted lower alkoxy; a group of the formula: -NR 4

R

5 (wherein A is an alkylene, is an integer of 0 or 1, E is a group of the formula: -CO- or -OCO-, R 4 and R 5 are the same or different and are each hydrogen atom; a lower alkyl which f 1 :i WO 94/01113 PCT/JP93/00835 may optionally be substituted by hydroxy or cyano; a lower alkenyl; a lower alkynyl; a phenyl(lower)alkyl; a lower alkanoyl which may optionally have one to three substituents of a halogen atom; a benzoyl wherein the phenyl ring may optionally be substituted by a member selected from nitro and an amino having optionally one or two substituents selected from a lower alkyl, a lower alkanoyl and a phenyl(lower)alkoxycarbonyl; phenyl; a lower alkoxycarbonyl; a lower alkoxycarbonyl(lower)alkyl wherein the lower alkyl moiety may optionally be substituted by hydroxy or an amino having optionally a phenyl(lower)alkoxycarbonyl substituent; an amido having optionally a lower alkyl substituent; a pyrrolidinyl-substituted carbonyl wherein the pyrrolidinyl ring may optionally be substituted by a phenyl(lower)alkoxycarbonyl; an amino-subscituted lower alkanoyl wherein the lower alkanoyl moiety may optionally be substituted by a member selected from phenyl(lower)alkoxycarbonylamino, hydroxy, a phenyl having optionally a hydroxy substitutent, carbamoyl, imidazolyl and a lower alkylthio, and tne amino group may optionally have a substituent selected from a lower alkyl having opvlonally a hydroxy substitutent, a lower alkenyl, a phenyl(lower)alkyl having optionally a lower alkoxy substituent on the phenyl ring, a lower alkylsulfonyl, a lower alkanoyl, and a phenyl(lower)alkoxycarbonyl; a hydroxy-substituted lower alkanoyl; a lower alkanoyloxy(lower)alkanoyl; a lower alkylsulfonyl; a phenylsulfonyl wherein the phenyl ring may optionally be substituted by a lower alkyl, nitro or an amino having 7 -c 3lrr~-- n~ WO 94/01113 7PCT/JP93/0OP optionally one or two substituents selected from a lower alkyl and a lower alkancyl; an amido-substituted lower alkyl wherein the lower alkyl moiety have optionally a substituent selected from a phenyl having optionally a hydroxy substituent, imidazolyl, carbamoyl and a lower alkylthio, and the amido group may optionally have a lower alkyl substituent; an amino-substituted lower alkyl which may optionally subs.-.uted by a lower alkyl or a lower alkanoyl; anilinocarbonyl; a piperidinyl which may optionally be substituted by a phenyl(lower)alkyl; a cycloalkyl, a cycloalkenylcarbonyl; a cycloalkylcarbonyl which may optionally have one to three substituents selected from hydroxy and a lower alkanoyloxy; a tetrahydropyranyl-substituted lower alkyl wherein the tetrahydropyranyl ring may optionally have one to four substituents selected from hydroxy and a lower alknxy; a lower alkanoyl which is substituted by a 5- or 6membered saturated hererocyclic group selected from pyrrolidinyl, piperazinyl, piperidinyl and morpholinyl wherein the heterocyclic group have optionally a substituent selected from a lower alkyl and phenyl; a piperidinylsubstituted carbonyl which may optionally be substituted by a lower alkanoyl; a lower alkanoyloxy(lower)alkyl; a pyridyl-substituted lower alkyl; or an amino acid residue which can form an amido group with its amino group, or R 4 and R 5 may bind together with the nitrogen atom to which they bond to form a 5- or 6-membered, saturated or unsaturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom, wherein the WO 94/01113 8 PCT/JP93/00835 heterocyclic group may optionally be substituted by a member selected from a phenyl having optionally a subsituent selected from a lower alkoxy and a halogen atom, oxo, hydroxy, a lower alkenyl, carboxy, a phenyl(lower)alkyl having optionally a hydroxy substituent on the lower alkyl moiety, a 3ower alkanoyl, a lower alkyl having optionally a hydroxy substituent, benzoyl, an amido having optionally a lower alkyl substituent, anilinocarbonyl, a benzoyl(lower)alkyl, a lower alkylsulfonyl, piperidinyl, pyrimidinyl, pyridyl, and a lower alkoxycarbonyl); a carbamoyloxysubstituted lower alkoxy; a lower alkylthio-substituted lower alkoxy; a lower alkylsulfonyl-substituted lower alkoxy; a lower alkylsulfinyl-substituted lower alkoxy; an alkenyloxy; phenoxy; a lower alkanoyloxy; a lower alkylsulfonyloxy; a lower alkynyloxy; a phenyl(lower)alkoxy; a cycloalkyl; a cycloalkyloxy; a cycloalkenyloxy; imidazoa group of the 'NR67 formula: NRR 7 (wherein t is as defined above, B is a lower alkylene or a group of and R 6 and R 7 are the same or different and are each hydrogen atom, a lower alkyl, a lower alkanoyl having optionally one to three halogen substituents, a carboxy(lower)alkyl, a lower alkoxycarbonyl, a lower alkoxycarbonyl(lower)alkyl, a lower alkenyl, an amido-substituted lower alkyl having optionally a lower alkyl substituent, or a phenyl(lower)alkoxycarbonyl, or R 6 and R 7 may bind together with nitrogen atom to which they bond to form a 5- or 6-membered, saturated or unsaturated heterocyclic group which may be intervened or not with 9 WO 94/01113 PCT/JP93/00835 nitrogen, oxygen or sulfur atom, wherein the heterocyclic group may optionally have a substituent selected from a lower alkoxycarbonyl, a lower alkyl, a lower alkylthio, and oxo); nitro; a halogen atom; a lower alkylsulfonyl; a lower alkyl which may optionally have one to three substituents selected from a halogen atom, hydroxy, phenyl and a lower alkoxy; a cyano-substituted lower alkoxy; an oxiranylsubstituted lower alkoxy; a phthalimido-substituted alkoxy; an amidino-substituted lower alkoxy, a pyrrolyl-substituted lower alkoxy; cyano; a lower alkoxycarbonyl; amidino; carbamoyl; carboxy; a lower alkanoyl; benzoyl; a lower alkoxycarbonyl(lower)alkyl; a carboxy(lower)alkyl; a lower alkoxy(lower)alkyl; a lower alkanoy' xy(lower)alkyl; hydroxyimino-substituted lower alkyl; phenyl; a lower alkylthio; a lower alkylsulfinyl; a lower alkenyl having optionally a hydroxy substituent; a lower alkylenedioxy, a lower alkylsilyl; a pyrimidylthio-substituted lower.alkoxy; a pyrimidylsulfinyl-substituted lower alkoxy; a pyrmidylsufonyl-substituted lower alkoxy; an imidazolylthiosubstituted lower alkoxy which may optionally have a lower alkyl substituent; an imidazolylsulfonyl-substituted lower alkoxy which may optionally have a lower alkyl substituent; an ammonium-lower alkoxy having three substituents selected from lower alkyl, lower alkenyl and oxo; a phenylthiosubstituted lower alkoxy wherein the phenyl ring may optionally have a substituent selected from nitro and amino; a phenylsulfonyl-substituted lower alkoxy wherein the phenyl ring may optionally have a substituent selected from nitro 10 WO 94/01113 PCT/JP93/00835 and an amino having optionally one or two substituents selected from a lower alkanoyl and lower alkyl; a pyridylthio-substituted lower alkoxy; or a pyridylsuflonylsubstituted lower alkoxy wherein the pyridyl ring may optionally be substituted by oxo), n is an integer of 1 or 2, m is 0 or an integer of 1 to 3, R 3 is a lower alkyl, R 1 0 is.a group of the formula: -NR 1 1

R

1 2 (wherein t is as defined above and R 11 and R 1 2 are the same or different and are each hydrogen atom, a lower alkyl, a phenyl(lower)alkyl a lower alkenyl, a benzoyl which may optionally have a lower alkoxy substituent, tricyclo[3.3.1.1decanyl, a phenyl which may optionally have a lower alkoxy substituent, or a cycloalkyl, or R 1 I and R 1 2 may bind together with the nitrogen atom to which they bond to form a saturated or unsaturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom, wherein the heterocyclic group may optionally have a substituent selected from a benzoyl, a lower alkanoyl, a phenyl(lower)alkyl and a phenyl which may optionally be substituted by a lower alkoxy or a.lower alkanoyl), the bond between 3- and 4-positions of the carbostyril ring is single bond or double bond, provided that when R 1 is hydrogen atom and the i in the formula: -NR 1 1

R

12 is 0 and R 11

R

1 2 are not simultaneously hydrogen atom The benzoheterocyclic compounds, which are also one of the active ingredient of the present oxytocin antagonist, have the following formula III~U-sll L I 11 WO 94/01113 PCT/JP93/00835 R'16 C=o (2)

IR

17 R18 wherein R 16 is hydrogen atom, a halogen atom, a lower alkyl, an amino having optionally a lower alkyl substituent, or a lower alkoxy,

R

17 is hydrogen atom, a halogen atom, a lower alkoxy, a phenyl(lower)alkoxy, hydroxy, a lower alkyl, an amino having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkoxy, an amino-substituted lower alkoxy having optionally a lower alkyl substituent, or a benzoyloxy which has optionally a halogen substituent on the phenyl ring,

R

18 is a group of the formula: -NR 19

R

20 or a group of the formula: -CONR 26

R

27

R

19 is hydrogen atom, a benzoyl which has optionally a halogen substituent on the phenyl ring, or a lower alkyl,

(R

31 )r

R

2 0 is a group of the formula: 0 [wherein R 31 is a halogen atom; a lower alkyl which has optionally a substituent selected from a halogen atom and hydroxy; hydroxy; a lower alkoxy; a lower alkanoyloxy; a lower alkylthio; a lower alkanoyl; carboxy; a lower alkoxycarbcnyl; cyano; nitro; an amino which has optionally a substituent selected from a lower alkyl and a lower WO 94/01113 12 PCT/JP93/00835 alkanoyl; phenyl; a cycloalkyl; a lower alkanoyloxysubstituted lower alkoxy; a carboxy-substituted lower alkoxy; a halogen-substituted lower alkoxy; a carbamoylsubstituted lower alkoxy; a hydroxy-substituted lower alkoxy; a lower alkoxycarbonyl-substituted lower alkoxy; a phthalimido-substituted lower alkoxy; an aminocarbonyl-lower alkoxy having a lower alkyl substituent; or a group of the formula: -O-F-N 21

R

22 (F is a lower alkylene, and R 21 and R 2 2 are the same or different and are each hydrogen atom, a lower alkyl having optionally a hvdroxy substituent, a lower alkanoyl, or benzoyl, or R 2 1 and R 22 may bind together with the nitrogen atom to which they bond to form a 5- or 6membered saturated heterocyclic group with or without being intervened with nitrogen or oxygen atom wherein the heterocyclic group has optionally a substituent selected from piperidinyl and a lower alkyl); and r is an ir'.eger of 0 to a phenyl-lower alkoxycarbonyl, a lower alkanoyl, a phenyl-lower alkanoyl, a cycloalkyl-lower alkanoyl, a cycloalkylcarbonyl, tricyclo[3.3.1.1]decanylcarbonyl, naphthylcarbonyl, pyridylcarbonyl, furoyl, thenoyl, a phenoxy-lower alkanoyl wherein the phenyl ring has optionally 1 to 3 substituents selected from a lower alkyl, a lower alkoxy and an amino having optionally a lower alkanoyl substituent, a phthalimido-substituted lower alkanoyl, a lower alkoxycarbonyl-lower alkanoyl, a carboxylower alkanoyl, a naphthyloxy-lower alkanoyl, a halogensubstituted lower alkanoyl, a group of the formula: -CO N-R 23 (wherein R 23 is hydrogen atom, a lower k_i WO 94/01113 13 PCT/JP93/00835 alkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, an amino-lower alkanoyl having optionally a lower alkyl siibstituent, or a lower alkanoyl), an anilinocarbonyl which has optionally a lower alkyl substituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonyl which has optionally a substituent selected from a halogen atom and a lower alkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula: -CO-G-(CO)s-NR 24

R

25 (wherein G is a lower alkylene, s is an integer of 0 or 1, and R 24 and R 25 are the same or different and are each hydrogen atom, a lower alkyl having optionally a hydroxy substituent, a cycloalkyl, a phenyllower alkyl, a lower alkanoyl, a lower alkenyl, a phenoxylower alkyl, a phenyl which has optionally 1 tc 3 substituents selected from an amino-lower alkyl having optionally a lower alkanoyl substituent, a lower alkyl, a lower alkoxy and a halogen atom, a phthalimido-substituted lower alkyl, an amino-lower alkyl having optionally a lower alka; o1 substituent, a lower alkynyl, or an amino-lower alkyl having optionally a lower alkyl substituent, or R 24 and R 25 may bind together with the nitrogen atom to whicn they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with nitrogen or oxygen atom wherein the heterocylic group has optionally a substituent selected from a lower alkyl, a lower alkoxycarboyl and piperidinyl),

R

26 is hydrogen atom or a lower alkyl,

R

27 is a cycloalkyl, or a phenyl which has optionally 1 to 3 substituents selected from a lower alkoxy, WO 94/01113 PCT/JP93/00835 a lower alkyl and a halogen atom, W is a group of the formula: -(CH 2 (t is an integer of 3 to or a group of the formula: -CH=CH-(CH2) v (v is an integer of 1 to the carbon atom of these groups: -(CH 2 and -CH=CH-(CH 2 being optionally replaced by oxygen atoi., sulfur atom, sulfinyl, sulfonyl, or a group of the formula: -NR 28

(R

28 is hydrogen atom, a cycloalkyl, or a lower alkyl), and further said -(CH2) t and -CH=CH-(CH 2 groups having optionally 1 to 3 substituents selected from a lower alkyl having optionally a hydroxy substituent, a lower alkoxycarbonyl, carboxy, hydroxy, oxo, a lower alkanoyloxy having optionally a halogen substituent, an amino-lower alkyl having optionally a substituent selected from a lower alkyl and a lower alkanoyl, a lower alkanoyloxy-substituted lower alkyl, a lower alkyl sulfonyloxy-lower alkyl, an azido-lower alkyl, a group of the formula: -OCH 2 an aminocarbonyloxy having optionally a lower alkyl substituent, a lower alkoxy, a lower alkoxycarbonyl-substituted lower alkoxy, a carboxysubstituted lower alkoxy, an aminocarbonyl-lower alkoxy having optionally a lower alkyl substituent, an amino-lower alkoxy having optionally a substituent selected from a lower alkyl and a lower alkanoyl, a phthalimido-substituted lower alkoxy, hydroxyimino, a lower alkanoyloxy-imino, a lower alkylidene, a haloge" atom, azido, sulfoxyimino, a group of the formula R3 -N T =0 (R 32 is hydrogen atom or a lower I I

/O

alkyl), hydrazino, pyrrolyl, an amino-lower alkanoyloxy WO 94/01113 PCT/JP93/00835 having optionally a lower alkyl substituent, a group of the formula: -O-F-CO-NR 33

R

34 (F is as defined above, and R 33 and

R

34 are the same or different and are each hydrogen atom, a lower alkyl, a carbamoyl-substituted lower alkyl, a hydroxysubstituted lower alkyl, or a pyridyl-lower alkyl, or R 33 and R 34 may bind together with nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with nitrogen, oxygen or sulfur atom wherein the heterocyclic group has optionally a substituent selected from oxo, a lower alkyl, a lower alkanoyl, and carbamoyl), or a group of the formula: -(CO)s-NR 29

N

30 (wherein s is as defined above, and R 29 and

R

30 are the same or different and are each hydrogen atom, a lower alkyl, a lower alkenyl, a lower alkanoyl, a cycloalkyl, an oxiranyl-substituted lower alkyl, a lower alkyl having optionally 1 to 2 substituents selected from a lower alkoxy, hydroxy and an amino having optionally a lower alkyl substituent, a phenyl-lower alkyl, a pyridyl-lower alkyl, a lower alkylsulfonyl, benzoyl, a lower alkoxycarbonyl, anilinocarbonyl, an aminocarbonyl having optionally a lower alkyl substituent, a cyano-substituted lower alkyl, a lower alkoxycarbonyl-substituted lower alkyl, a carbamoyl-substituted lower alkyl, a carboxy-substituted lower alkyl, a tecrahydropyranyloxy-substituted lower alky1, a lower alkanoyloxy-suostituted lower alkyl, a piperidinyl having optionally a phenyl-lower alkyl substituent on the piperidine ring, a halogen-substituted lower alkanoyl, an imidazolyl-substituted lower alkanoyl, an amino-lower 16 WO 94/01113 PT/JP93/00835 alkanoyl having optionally a substituent selected from a lower alkyl and a lower alkoxycarbonyl, an aminocarbonyllower alkyl having optionally a lower alkyl substituent, or a phenyl-lower alkoxycarbonyl, or R 29 and R 30 may bind together with nitrogen atom to which they bond to form a or 6-membered saturated heterocyclic group wi.h or without being intervened with nitrogen or oxygen, wherein the heterocyclic group may optionally have a substituent selected from a lower alkyl, a phenyl-lower alkyl and a lower alkanoyl).

The carbostyril derivatives of the formula and their salts, and the benzoheterocyclic compounds of the formula and their salts have excellent inhibitory effect on uterin smooth muscle constriction, inhibitory effect on milk secretion, innibitory effect on synthesis and secreation of prostaglandin, and vasodilation activity, and hence, they are useful in the protection or treatment of oxytocin relating diseases, expecially, for treatment of oremature delivery, dysmenorrhea, endometritis, or for stopping labour preparatory to Caearian delivery.

Each group in the above formulae and (2) includes specifically the following groups.

The "alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 12 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, and the like.

The "lower alkyl" includes a straight chain or I I ~bllli 17 WO 94/01113 PCT/J P93/00835 branched chain alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, tertbutyl, pentyl, hexyl, and the like.

The "halogen atom" includes fluorine atom, chlorine atom, bromine atom and iodine atome.

The "amino having optionally one or two substituents selected from a lower alkanoyl, a lower alkyl and benzoyl" includes an amino having optionally one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and benzoyl group, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tertbutylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino,

N-

methyl-N-butylamino, N-methyl-N-hexylamino, N-methyl-Nacetylamino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylamino, N-isobucyrylamino, N-pentanoylamino, N-tertbutylcarbonylamino, N-hexanoylamino, N-ethyl-N-acetylamino, benzoylamino, N-methyl-N-benzoylamino, N-ethyl-N-benzoylamino, and the like.

The "amino having optionally one or two substituents selected from a lower alkanoyl and a lower alkyl" includes an amino having optionally one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for WO 94/01113 1.8 PCT/JP93/00835 example, amino, niethylamino, ethylamino, Propylamino, isopropylamiio, butylamino, tert-butylanino, pentzylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N--ethylamino, N-ethyl-N-propylamino, N-methyl--N-butylamino, Ninethyl-N-hexylamino, N-inethyl-N-acetylamino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylaminot N- .isobutyrylamino, N-pentanoylamino, N-tert--butylcarbonylamino, N-hexanoylamino, N-ethyl-N-acetylamino, and the like.

The "phenyl(lower)alkyl" includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having I to 6 carbon atoms, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 1,1dimethvl-2-phenylethyl, 2-methyl-3-phenylpropyl, and the like.

The "amino having optionally one or two substirtuents selected from a lower alkyl, phenyl and a phenyl(lower)alkyl" includes an amino having optionally one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, phenyl and a pheny'lalkyl wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, amino, phenylamino, diphenylamino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tertbutylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexvlamino, N-methyl-N-ethylamino, Nq-ethyl-N-propylamino, N- WO 94/01113 PCT/JP93/00835 methyl-N-butylamino, N-methyl-N-hexylamino, N-methyl-Nphenylamino, N-ethyl-N-phenylamino, N-benzylamino, N-(2phenylethyl)amino, N-(l-phenylethyl)amino, 1-(3-phenylpropyl)amino, N-(4-phenylbutyl)amino, amino, N-(6-phenylhexyl)amino, N-(1,1-dimethyl-2-phenylethyl)amino, N-(2-methyl-3-phenylpropyl)amino, N-methyl-Nbenzylamino, N-ethyl-N-benzylamino, N-phenyl-N-benzylamino, and the like.

The "alkoxy which has one or two substituents selected from hydroxy, a lower alkanoyloxy, a tri(lower)alkylammonium, a lower alkoxy, and a group of the formula: -NR14R5n includes an alkoxy group having 1 to 10 carbon atoms which has one or two substituents selected from hydroxy, a straight chain or branched chain alkanoyloxy having 1 to 6 carbon atoms, a trialkylammonium group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, and a group of the formula: -NR 14

R

5 [wherein R 14 and R 15 are the same or different and are each hydrogen atom, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a hydroxy-substituted alkyl group wherein the alkyl moiety is a strainght chain or branched chain alkyl group having 1 to 6 carbon atoms, a tetrahydropyranylalkyl group wherein the alkyl moiety is straight chain or branched chain alkyl group having 1 to 6 carbon atoms, phenyl, a phenylalkyl (wherein the alkyl i- -I 20 WO 94/01113 PCT/JP93/00835 moiety is straight chain or branched chain alkyl group having 1 to 6 carbon atoms which may optionally be substituted by hydroxy and the phenyl ring may optionally be substituted by one to three of straight chain or branched chain alkoxy group having 1 to 6 carbon atoms), or a pyridylalkyl wherein the alkyl moiety is straight chain or branched chain alkyl group having 1 to 6 carbon atoms, or

R

14 and R 15 may bind with the nitrogen atom to which they bond to form a 5- or 6-membered, saturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom (wherein the heterocyclic group may optionally be substituted by one to three substituents selected from carbanoyl, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, phenyl and a hydroxy-substituted alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms)], for example, hydroxymethoxy, 2-hydroxyethoxy, l-hydroxyethoxy, 3-hydroxypropoxy, 2,3-dihydroxyethoxy, 4-hydroxybutoxy, 3,4-dihydroxybutoxy, 1,1-dimethyl- 2-hydroxyethoxy, 5,6-dihydroxyhexyloxy, 6-hydroxyhexyloxy, 7-hydroxyheptyloxy, 8-hydroxyoctyloxy, 9hydroxynonyloxy, 10-hydroxydecyloxy, 6-(3,4-dimethoxybenzyl- 6-(3-methoxybenzylamino)-5hydroxyhexyloxy, 6-[2-(2-pyridyl)ethylamino]-5-hydroxyhexyloxy, 6-[N-methyl-N-(2-pyridylethyl)amino-5-hydroxyhexyloxy, 6-(N-ethyl-N-2-(2-pyridylethyl)amino)-5-hydroxy- 21. WO 94/01113 PCr/J P93/00835 hexyloxy, 6-[N-ethyl-N-(4-pyridylmethyl)amino]-5-hydroxyhexyloxy, 6-(3-pyridylmethylamino)-5-hydroxyhexyloxy, 2- 6-(diethyl,methyl- 4-(trimethylammonium)-3hydroxyhexyloxy, 5-(dipropyl,ethylaminonium)-4-acetyloxypentyloxy, 7-C 2-ethoxybenzyJlamino )-6-ace tyloxyheptyloxy, 8- (3,4,5-trimethoxybenzylamino)-7-ethoxyoctyloxy, pyridyl)propyl]-4-acetyloxypentyloxy, 7-[4-(2I-pyridyl)butyl ]-6-propoxyheptyloxy, 2-methyl-3-hydroxypropoxy, aminomethoxy, 1-aminoethoxy, 2-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1dimethyl-2-aminoethoxy, 2-rethyl-3-aminopropoxy, methylaminomethoxy, ethylaminomethoxy, propylarninomethoxy, isopropylaminonethoxy, butylaininomethoxy, tert-butylaminomethoxy, pentylaminomethoxy, hexylaminomethoxy, dimethylaminonethoxy, diethylarninomethoxy, dipropyamino.methoxy, dibutylaminomethoxy, dipentyl aminomethoxy, dihexylarninomethoxy, N-methyl-N-ethylaminomethoxy, N-methyl- N-propylaminomethoxy, N-rnethyl-Nr--butylarninomethoxy, Nmethyl-N-hexylaminilethoxy, 1-inethylaminoethoxy, 2-ethylaminoethoxy, 3-propylaminopropoxy, 4-butyJlaminobutoxy, 1,1dimethyl-2-pentylaiinoethoxy, 5-hexylaminopentyloxy, 6dimethylaminohexyloxy, 7-rethylaminoheptyloxy, 8-~dimethylaminooctyloxy, 4-dimethylaminobutoxy, 2-diethylaminoethoxy, 1-(N-methyl-N-hexylamino)ethoxy, 3-dihexylarninopropoxy, 6diethylaminohexyloxy, 4-dibutylaminobutoxy, 9-(N-methvl-Npropylamino)nonyloxy, 2-(N-methyl-N-pentylamino)ethoxy, 7hydroxy-8-dimethylarninooctyloxy, 2-hydroxy-8-diethylamino- WO 94/01113 22 PCT/3P93/00835 propoxy, 7-hydroxy-8-diethylaninooctyloxy, 2-hydroxy-3-(Nphenyl-N-benzylamino)propoxy, 7-hydroxy-8-ethylarninooctyloxy, 3-hydroxy-4-nethylarninobutoxy, 5-hydroxy-6diethylaminohexyloxy, 3-hydroxy--4-phenylaminobutoxy, 8hydroxy-9-dimethylaminononyloxy, pentyJloxy, 9-hydroxy-1Q-diethylaminodecyloxy, 'ethylaminopentyloxy, phenylaminomethoxy, diphenylaminonethoxy, benzylarninomethoxy, 5-hydroxy-6-benzylarninohexyloxy, 5-hydroxy-6-[Nmethyl-N-(2-phenylethyl)aminolhexyloxy, 5-hydroxy-6-ethylaminohexyloxy, 5-hydroxy-6-isopropylaninohexyloxy, hydro::y-6-(N-nethy-Nbenzylamino)hexyloxy, S-hydroxy-6aminohexyloxy, (N-Iethyl-N-benzylamino)methoxy, (N-ethyl-NbenzyJlamino)methoxy, (N-phenyl-N--benzylamino)methoxy, 2- (phenylamino)ethoxy, 3-(2-p~hentylethylamino)propoxy, 4-(3phenylpropylamino)butoxy, l,l-dimethyl-2--(4-phenylbutylamino)ethoxy, 5-(5-phenylpentylamino)pentyloxy, 6-(6phenylhexylamino)hexyloxy, 7-hydroxy-8-(N-phenyl--N-benzylarnino)octyloxy, 8-hydroxy-9-[N-( 2-phenylethyl)arnino]nonyloxy, 9-hydroxy-lO-(N-ethyl-N-benzylamino)decyloxy, acetyloxyrnethoxy, 2-propionyloxyethoxy, l-butyryloxyethoxy, 3-acetyloxypropoxy, 4-isobutyryloxybutoxy, pentyloxy, 6'-tert-butylcarbonyloxyhexyloxy, 1,1-dimethyl-2hexanoyloxyethoxy, 2-methyl-3-acetyloxypropoxy, 7-acetyloxyheptyloxy, 8-acetyloxyoctyloxy, 9-acttyloxynonyloxy, acetyloxydecyloxy, (hvdroxymethyl)aminomethoxy, l-[N,N-di-- (2-hydroxyethyl )aminolethoxy, 2- (3-hydroxypropyl )aminoethoxy, 3-(4--hydroxybutyl)aminopropoxy, WO 94/01113 23 PCT/JP93/00835 aminobutoxy, 5-(6-hydroxyhexylaminopenty.oxy, 6-EN--(2hydroxyethyl)--N-niethylarnino]hexyloxy, 5-hydroxy-6-[N-( 2hydroxyethyl)-N-methylamino~hexyloxy, 5-hydroxy-6-(N,N-di (2hydroxyethyl)arninolhexyloxy, 6-hydroxy-7-(N-(2-hydroxyethyl)-N-benzylaminolheptyloxy, 7-hdroxy-8--[N-( 3-hydroxypropyl)-N-phenylaminoloctyloxy, 7-hydroxy-9-{N-( 4-hydrox"butyl)-N-[ (tetrahydropy'ranyl-2-yl)methyllamino)nonyloxy, 8hydroxy-1O-[N-(2-hydroxyethyl)-N-acetylaninoldecyloxy, acetylaminomethoxy, 2-(formylamino)ethoxy, 1-(propionvlamino)ethoxy, 3-(butyrylamino)propoxy, 4-(isobutyrylamino)butyloxy, 3-(pentanoylamino)pentyloxy, 6-(hexanoylarnino)hexyloxy, 5-acetyloxy-6-acetylaminohexyloxy, 5-hydvoxy-6acetylaminohexyloxy, 6-hydroxy-7-(N-methyl-'N-acetylznino)heptyloxy, 7-hydroxy-8-(N-berizyl-N acetylaraino)octyloxy, 8hydroxy-9-(N-phenyl-Ni-acetylamiio)nonyloxy, 9-acetvloxy-1O- [Nl-(tetrahydro-2-pyranylmethyl)-N-acetylarninojdecyloxy, (tetrahydro-2-pyranyl)nethylaninonethoxy, 2-(tetrahydro-3pyranylmethylamino)ethoxy, 1-(tetrahydro-4--pyranylmethylamino)ethoxy, 3-[2-(tetrahydro-2-pyranyl)ethylaniinojpropoxy, 4-[3-(tetrahydro-2-pyranyl)propylamino~butoxy, 5-4- (tetrahydro-2-pyranyl)butylamino~pentyloxy, 5-hydroxv-6-[Nethvl-N-tetrahydro-2-pyranylmethylaminolhexyloxy, 6-hydroxy- 7-(N-phenyl-N-t5-(tetrahydro-2-pyranyl)pentylamino)heptyloxy, 7-hydroxy-8-(N-benzyl-N-[6-(tetrahydro2-pyranyl)hexylamino~octyloxy, (2-hydroxy-2-phenylethyl)amiiomethoxy, (3-hyaroxy-3-phenylpropyl)aminolethoxy, (2-hydroxy-4phenylbutyl)aminolpropoxy, 4-f (6-hydroxy-6-phenylhexyl)aminolbutoxy, (2-hvdroxy-2-phenylethyl)amiinolpentyloxy, WO 94/01113 24 PCr/JP93/00835 5-hydroxy-6-[ (2-hydroxy-2-phenylethyl~amino~hexyloxy, 6hydroxy-7-[N-(2-hydroxy-2-phenylethyl)-N-nethylaminojheptyloxy, 7-hydroxy-8- (2-hydroxy-2-phenylethyl phenylamino Ioctyloxy, 8-hydroxy-9- (2-hydroxy-2-phenylethyl)-N-benzylaminolnonyloxy, 9-hydroxy-1O-[N-( 2-hydroxy-2phenylethyl)-N-acetylamino~decyloxy, (piperazin-1-yl)methoxy, 2-(pyrrolidin-1-yl)ethoxy, 3-(piperidin-1-yl)propoxy, 4-morphoJlinobutoxy, 5-thiomorpholinopeityloxy, 6- (piperazin-l-yl)hexyloxy, 5-hydroxy-6-(4-beizyl-lpiperazinyl)hexyloxy, 5-hydroxy-6-(1-pir~erazinyl)hexyloxy, 5-hydroxy-6- (4-methyl-l-piperazinyl )hexyloxy, (1-pyrrolidinyl)pentyloxy, pentyloxy, 4-hydroxy-5-morpholinopentyloxy, 5-hydroxy-6-(lpyrrolidiriyl)hexyloxy, 5-hydroxy-6-(1-piperidinyl)hexyloxy, 5-hydroxy-6-(4-phenyl-l-piperazinyl)hexyloxy, 5-hydroxy-6- (2-carbamoyl-l-pyrrolidinyl )hexyloxy, 7-hydroxy-8- (1pyrrolidinyl)octyloxy, 5-hydroxy-6-(2-hydroxymethyl-lpyrrolidinyl)hexyloxy, 2-carbamoylmorpholino)-6hydroxyheptyloxy, 8-hydroxy-9-(4-benzyl-l-piperazinyl)nonyloxy, 4-(3-carbamoyl-l-piperidinyl)-3-hydroxybutoxy, 9hydroxy-1O- (4-ethyl-l-oiperazinyl.) decyloxy, 6- (4-carbamoyland the like.

The "carboxy-substituted alkoxy" includes a carboxy-substituted alkoxy group wherein the alkoxy moiety is a straight chain or branched chain aJlkoxy group having 1 to 12 carbon atoms, for example, carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxv, 3-carboxypropoxy, 4-carboxybutoxy, rboxypentyloxy, 6-ca rboxyhexyloxy, 1,1-dime thyl-2- WO 94/01113 25 PCTIJP93/00835 carboxyethoxy, 2-methyl-3--carboxypropoxy, 7-carboxyheptyloxy, 8-carboxyoctyloxv, 9-carboxynonyloxy, lO-carboxydecyloxy, 1l-carboxyundecyloxy, 12-carboxydodecyloxy, and the like.

The "lower alkoxycarbonyl-substituted alkoxy" includes an alkoxycarbonyl-substituted straight chain or branched chain alkoxy group having 1 to 12 carbon atoms wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, rethoxycarbonylmethoxy, 3-methoxycarbonvipropoxy, ethoxycarbonylmethoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, pentyloxy, 6-propoxycarbonylhexyloxy, l,l-dimethyl--2-butoxycarbonylethoxy, 2-methyl-3-tert-butoxycarbonylDropoxy, 2pentvloxycarbonylethoxy, hexyloxycarbonylmethoxy, 7-methoxycarbonylhepotyloxy, 8-ethoxycarbonyloctyloxy, 9-propoxycarbonylnonyloxy, lO-butoxycarbonyldecyloxy, il-methoxycarbonylundecyloxy, 12-ethoxycarbonyldodecyloxyt and the l ike.

The "lower alkanoyloxy-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, for example, acetyloxymethoxy, 2propionyloxvethoxy, l-butyryloxyethoxy, 4-acetyloxybutoxy, 3-acetyloxypropoxy, 4-isobutyryloxybutoxy, oxypentyloxy, 6-acetyloxyhexyloxy, 6-tert-butvlcarbonyloxyhexyloxy, l,l-dirnethyl-2-hexanoyloxyethoxy, 2-methyl-3- WO 94/01113 6-PCT/JFP93/ 00835 acetyloxypropoxy, and the like.

The "lower alkinyloxy-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkenyloxy roup having 2 to 6 carbon atoms, for example, vinyloxymethoxy, 2-allyloxyethoxy, l-(2-butenyloxy)ethoxy, 3-allyloxypropoxy, 4-(3butenyloxy)butoxy, 5-(l-methylallyloxy)pentyloxy, 6-(2pentenyloxy)hexyloxy, l,l.-dimethyl-2-(2--hexenyloxy)ethoxy, 2-methyl-3-allyloxypropoxy, and the like.

The "lower alkoxy (lower) alkoxy" includes a siraight chain or branched chain aJlkoxy group having I to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, rnethoxymethoxy, 3-methoxypropoxy, 4-ethoxybutoxy, 6-propoxyhexyloxy, 5-isopropoxypentyloxy, 1,1-dimethy1l-2-butoxvethoxy, 2-methyl-3-tert-butoxypropoxy, 2-pentyloxyethoxy, hexyloxymethoxy, and the like.

The "lower alkylsulfonyloxy-substituted lov.er alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkylsulfonyloxy group having 1 to 6 carbon atoms, for example, methylsulfonyloxymethoxy, 3-methylsulfonyloxypropoxy, 4-e thylsulfonyloxybutoxy, 2-methylsulfoyloxyethoxy, 6-propylsulfonvioxvhexyloxy, 5-isopropv.Lsulfonyloxypentyloxy, 1 -dimethyl-2-butylsulfonyloxyethoxy, 2-methyl-3-methlsulfonyloxypropoxy, and the like.

III^ n A A 27 uzAI. PCTIJ P93/00835 The "benzoyloxy-substituted lower alkoxy"l includes a benzoyloxyalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 6 carbon atoms, for example, benzoyloxymethoxy, 2-benzoylc. ethoxy, l-benzoyloxyethoxy, 3-benzoyloxypropoxy, 4-benzoy.oxybutoxy, 6-benzoyJloxyhexyloxy, 5-benzoyloxypentyloxy, 1,1dimethyl-2-benzoyloxyethoxy, 2-methyl-3-benzoyloxypropoxy, and the like.

The "tricyclo[3 3.l.1]decanyl-substituted lower alkoxy" includes a tricyclo[3.3.l.lldecanyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, tricyclo[3.3.1.lldecanylmethoxy, decanylethoxy, 3 -tricyclo[3.3.l.lldecanylpropoxy, 4tricyclo[3. 3.l.ljdecanylbutoxy, 5-tricyclo[3.3.1ldecanylpentyloxy, 6 -tricyclo[3.3.l.lldecanylhexyloxy, 1,1-dimethyl- 2 -tricyclo[3.3.l.l)decanylethoxy, 2-methyl--3-tricyclo- 3 1.3.l.lldecanylpropoxy, and the like.

The "lower alkylene" includes a straight chain or branched chain alkylene group having 1 Lc' 6 carbon atoms, for example, methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, l-methyltrir~ethylene, Bthylmethylene, ethylmethylene, tetramethylene, perztamethylene, hexamethylene, and the like.

The "lower alkanoyl" includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, formyl, acetyl, propionyl- butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl, hexanolyl, and the like.

-2 0 WO 94/01113 Pcrii P3/0083 S The "amino having optionally one or two substituents selected from a lower alkyl, a lower alkanoyl and a phenyl(lower)alko: ycarbonyl"I includes an amino having optionally one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straict .Kin or branched chain alkanoyl group having I to 6 carbon atoms and a phenylalkoxycarbonyl group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylarnino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylaminot, N-ethyl- N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-benzyloxycarbonylamino, 2-phenylethoxycarbonyl )amino, N- -phenylethoxycarbonyl )amino, N- (3-phenylpropoxycarbonyl)amino, N-(4-phenylbutoxycarbonyl)amino,

N-CS-

phenylpentyloxycarbonyl )amino, N- (6-phenyihexyloxycarbonyl)amino, N-(ll-dimethyl-2-phenylethoxycarbonyl)amino, 2-methyl-3-phenylpropoxycarbonyl)amino, N-methyl- N-benzyloxycarbonylamino, N-ethyl-N-benzyloxycarbonylamino, acetylamino, formylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert-butylcarbonylamino, hexanoylamino, N-methyl-N--acetylamino, N-ethyl-N-acetylamino, N-benzyloxycarbonyl-N-acetylamino, and the like.

The "benzoyl wherein the phenyl ring nay optionally has a substituent selected from nitro and an amino having optionally one or two substituents selected from a lower WO 94/01113 WO 9/0113 PIJPW3/0$35 alkyl, a lower alkanoyl and a phenyl(lower)alkoxycarbonyl" includes a ben2oyJ. group wherein the phenyl ring may optionally have one to three substituents selected from nitro and an amino optionally having one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and a phenylalkoxycarbonyl group wherein "the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, benzoyl# 2-aminobenzoyl, 4-aminobenzoyl, 4-methylaminobenzoyl, 3-ethylaminobenzoyl, 2- (Nmethyl-N-ethylamino)benzoyl, 3-(N-methyl-N-hexylamino)benzoyl, 4-dimethylaminobenzoyl, 4-dipentylaminobenzoyl, 2isopropylaminobenzoyl, 3-butylaminobenzoyl, 4-(N-methyl-Nbenzyloxycarbonylamino) ben zoyl, 2-f N- (2-phenylethoxycarbonyl)amino)benzoyl, 2,3-bis(dimethylamino)benzoyl, 3,4bis(methylamino)benzoyl, 3,4,5-tri(methylamino)benzoyl, 2,6di(N-methyl-N-benzyloxycarbonylamino)benzoy., 3-f N-(3phenylpropoxycarbonyl)aminobenzoyl, oxycarbonyl)amino)benzoyl, 2-f N-(6-phenylhexyloxycarbonyl)amino)benzoyl, 3-tN-(4-phenylbutoxycaroonyl )aminolbenzoyl, 4-acetylami4nobenzoyll 3-(N-methyl-N-acetylamino)ben-"oyl, 2- (N-benzyloxycarbonyl-N-acetylamino)benzoyl, 4-nitrobenzoyl, 4-nitro-3-methylaminobenzoyl, 2, 4-dinitrobenzoyl, 2,4 ,6trinitrobenzoyl, and the like.

The "lower aikoxycarbonyl" includes a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxy- WO 94/01113 -30 -IC/J P93/(X835 carbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbony., hexyloxycarboiyl, and the like.

The "lower alkoxycarbonyl(lower)alkyl" includes a straight chain or brarnched chain alkoxycarbonylalkyl group having 1 to 6 carbon atoms in the alkoxy moiety wherein the alkyl. moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, inethoxycarbonyirnethyl, 3-methoxycarbonyipropyl, 3-ethoxycarbonylpropyl, ethoxycarbonylnethyl, 4-ethoxycarbonylbutyl, Iethoxycarbonylethyl, l-m'ethoxy-arbonylethy1, 6-propoxycarbonylbexyl, 5-isopropoxycarbonylpentyl, -dimethyl-2butoxycarbonylethyl, 2-methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl, hexyloxycarbonylmethylt and the like.

The "amido ha=ving optionally a lower alky.

substituent" includes an amido having optionally one or two substituents of a straight chain or branched chain alkyl group having 2. to 6 carbon atoms, for example, carbamoyl, methylamido, ethylamido, propylamido, isopropylamido, butylamido, tert-butylamido, pentylarnido, hexylamido, dimethylamido, diethylainido, dipropylamido, dibutylamido, dipentylamido, dihexylamido, N-methyl-N-ethylamido, N-ethyl-Npropylamido, N-methyl-N-butylamido, N-niethyl-N-hexylamido, and the lii~e.

The "'lower alkylsulfonyl" includes a straight chain or branched chain alkylsulfonyl group having I to 6 carbon atoms, for example, iethylsulfonyl, ethylsulfonyl, propyl- ~fl W0 9 41Uu'5 -3 PCr/JP93/l0835 sulfonyl, isopropylsulfonyl, butylsulfonyl, tert-butylsulfonyl, pentyJlsulfonyl, hexylsulfonyl, and the like.

The or 6-membered, saturated or unsaturated heterocyclic group which is formed by binding the groups R and R 5 together with the nitrogen atom to which they bond and may be intervened or not with nitrogen, oxygen or sulfur atom" includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyrrolyl, pyrazolyl, imidazolyl, imidazolidinyl, 1,2,4-triazolyl, 1,2,3,4-tetrazolyl, pyrrolinyl, imidazolinyl, pyrazolinyl, pyrazolidinyl, oxazolinyl, oxazolidinyl, isoxazolinyl, isoxazolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, and the like.

The "phenyl which may optionally have a substituent selected from a lower alkoxy and a halogen atom" includes a phenyl group which may optionally have one to three substituents selected from a straight chain or branched chain alkoxy group having I to 6 carbon atoms and a halogen atom, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenvl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 4-penty2.oxypheny., 2,4dimethoxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3, 4-diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, dimethoxyphenyl, 3,4-dipentyloxyphenyl, 3,4, phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-b romophenyl, 3-bromophenyll 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4- WO 94/01113 32 PCT/JP93/00835 iodophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,6dichlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4difluorophenyl, 3,5-dibromophenyl, 3,4,5-trichlorophenyl, 2methoxy-3-chlorophenyl, and the like.

The "heterocyclic group which is substituted by a member selected from a phenyl having optionally a subsitutent selected from a lower alkoxy and a halogen atom, oxo, hydroxy, lower alkenyl, carboxy, a phenyl(lower)alkyl having optionally a hydroxy substituent on the lower alkyl moiety, a lower alkanoyl, a lower alkyl having optionally a hydroxy substituent, benzoyl, an amido having optionally a lower alkyl substituent, anilinocarbonyl, a benzoyl(lower)alkyl, a lower alkylsulfonyl, piperidinyl, pyrimidinyl, pyridyl, and a lower alkoxycarbonyl" includes the abovementioned heterocyclic groups which is substituted by one to three substituents selected from a phenyl having optionally one to three subsitutents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and a halogen atom, an oxo group, a hydroxy group, a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, carboxy, a phenylalkyl wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and having optionally a hydroxy substituent, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and having optionall one to three hydroxy substituents, benzoyl, an amido croup having optionally one or two substituents of a straight WO 94/01113 pCr1JP93/00835 chain or branched chain al~kyl. group~ having 1 to 6 carbon atoms, anilinocarbony., a benzoyJlalkyl group wherein the alkyl. moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain aJlkylsulfonyl group having 21 to 6 carbon atoms in the alkyl moiety, piperidiny., pyrimidinyl, pyridyl, and a straight chain or branched chain alkoxycarbonyl group having 2. to 6 carbon atoms, for example, 4phenylpiperazinyl, 4-(4-methoxyphenyl)piperazinyl, 4-(4chloro~henyl)piperazinyl, 3-(2-ethoxyphenyl)pyrrolidinyl, 2- (4-isopropoxyphen. yrrolidinyl, 4-(4-pentyloxyphenyl)piperidinyl, 3-(4-hexyloxyphenyl)piperidinyl, 3-12,3dimethoxyphenyl)morpholino, 2-(2-methoxyphenyl)morpholino, 3-(3-ethoxyphenyl)thiomorpholino, 2-(3,4,5--trimethoxyphenyl)thiomorpholino, 4-(3,4-dimethoxyphenyl)piperazinyl, 4-(3,4,5-trimethoxyphenyl)piperazinyl, 3-(2-fluorophenyl)pyrrolidinyl, 2-'3--broiophenyl)pyrro2.idinyl, 4-(3-iodophenyl)piperidinyl, 3-(4-bromoohenyl)piperidiny., 2-(3,4dichlorophenyl)morpholino, 3-(3--chlorophenyl)morpho.ino, 3- (2-bromophenyl)thiomorpholino, 2-(4-fluorophenyl)thiomorpholino, 4-(3,4,5a-trichloropheny.)piperazinyl, 4-(2,6dichlorophenyl)piperazinyl, 4-benzy2.piperazinyl, 3-(2phenylethyl)pyrro.idinyl, 2-(3-phenylpropy2.)pyrrolidinyl, 4- (4-phenylbutyl)piperidinyl, 3-(5-pheny2.pentyl)morpho.ino, 2- (6-p~henyihexyl.) thiomorpholino, 2-phenyl-2-hydroxyethyl piperazinyl, 3-(l-hydroxy-l--phenylmethyl)pyrrolidinyl, 2-(3hydroxy-3-phenvlpropyl)pyrrolidinyl, 4-(2--hydroxy-4-phenylbutyl )piperidinvl, 5-hydroxy-5-phenylpentyl) thio- WO 94/01113 4- PGT/JP93/00835 morphol4no, 6-hydro y,-6-phenylhexyl)norpholino, 4acetylpiperazinyi, 3-forinylpyrrolidinyl, 2-propionylpyrrolidinyl, 4-butyrylpiperidinyl, 3-pentanov-,lthiornorpholino, 2-hexanoylmorpholino, 4-methylpiperazinyl, 3,4dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidiny., 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentyJlmorpholino, 2-hexylthiornorpholino, 4benzoylpiperazinyl, 3-benzoylpyrrolidinyl, 3-benzoylmor~ho.ino, 2-be-i~.oylthiomoroholino, 3-benzoylpiperidinyl, 4-anilinocarbonvipiperazinyl, 2-anilinocarbonylpyrrolidinyl, 3-anilinocarbonylpiperidinyl, 2-anili.nocarbonyirnorpholino, 3-aniJlinocarbonylthiomorpholino, 4-(benzoylmethyl)piperazinyl, 3-(l-benzoylethyl)pyrrolidinyl, 2-(3-benzoylpropyJ.)pyrrolidinyl, 4-(4-benzoylbutyl)piperidinyl, benzovlpentyl)rnorpholino, 6-benzoy.hexyl.) thiomorpho.ino, 3-methyl-4-benzoylpiperazinyl, 3-ethyl-4--acetylpiperidinyl, 3-methyl--4-benzylpyrrolidinyl, 3-propyl-4-anilinocarbonylpyrrolidinyl, 3-methyl-5-(benizoylmethyl)morpholino, 3methyl-5-(2-phenyl-2-hydroxyethyl)thionorpholino, 4-methy1lsulfonylpiperazinyl, 4-methoxycarbonylpiperazinyl, 3-ethylsulfonylpyrrolidiiyl, 3-ethoxycarbonylpyrrolidinyl, 4propylsulfonylpiperidinyl, 3-propoxycarbonylpiperidinyl, 3butylsulfonylmorpholino, 2-pentyloxycarbonyirnorpholino, 2hex-ylsulfony2.thiomorpholino, 3-hexyloxycarbonylthiomorpholino, 4-allylpiperazinyl, 4-ethoxycarbonylpiperidinyl, 4-carboxypiperidinyl, 4-6irnethylamidopiperidinyl, 4carbarnoylpiperidinyl, 4-(l-piperidinyljpiperidinyl, 3hydroxypiperidinyl, 2-carbamoylpyrrolidinyl, 2-hydroxy- WO 94/01113 5-PC1'/JP93/00835 methylpiperidinyl, 2-hydroxymethylpyrrolidinyl, 3-hydroxymethylpiperidinyl, 3-hydroxypyrrolidinyl, 4-(2-hydroxyethyl)pi,peridinyl, 2-methoxycarbonylpyrrolidinyl, 2-(2hydroxyethyl)piperidinvl, (2-pyrimidyl)piperazinyl, (2pyridyl)piperazinyl, 4-oxothiomorpholino, 4,4-dioxothiomorpholino; 2-methylimidazolyl, 3-methyl-l,2,4--triazolyl, methyl-l,2,3,4-tetrazolyl, 4-hydroxymethylimidazolyl, 3allyl-l,2,4-triazolyl, 5-phenyl-1,2,3,4-tetrazolyl, 3carboxypyrrolyl, 2-hydroxyoxazolidinyl, 2-carbamoylthiazolidinyl, and the like.

The "phenyl(lower)alkyl having optionally a hydroxy-substituent on the alkyl moiety and having optionally a lower alkoxy substituent on the phenyl ring" includes a phenylalky. group wherein the alkyl mnoi ety is a straight chain or branched chain- alkyl group having 1 to 6 carbon atoms and having optionally a hydroxy-substituent and the phenyl ring has optionally one to three substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, in addition to the abovementioned phenyl(lower)alkyl groups, l-hydroxy-l-phenylmethyl, l-phenyl-2-hydroxyethyl, 2-phenyl-2-hydroxyethyl, 3hydroxv-3-phenylpropyl, 2-hydroxy--4-phenylbutyl, 6-hydroxy- 6-pheny'.hexyl, 3,4-dimethoxybenzyl, 3-methoxybenzyl, 1-12methoxyphenyl)etiyl, 2-(4-methoxyphenyl)ethyl, 3-(2-ethoxyphenyl)propyl, 4-(13-ethoxyphenyl.)butyl, 5-(4-ethoxyphenyl)pentyl, 6-(4-isopropoxyphenyl)hexyl, l,l-dimethyl-2-(4pentyloxyphenyl.)ethyl, 2-methyl-3-(4-hexyloxyphenvl)propyl, 3-ethoxy-4-methoxybenzyl, 2,3-dimethoxybenzyl, 3,4-diethoxy- WO 94/01113 36 PCTIJP93/00835 benzyl, 3,4,5-trimethoxybenzyl, l-hydroxy-l-(3--methoxyphenyl)methyl, l-(2,5-dimethoxyphenyl)-2-hydroxyethyl, 2- (2,6-dirnethoxyphenyl)-2-hydroxyethyl, 5-hydroxy-5-(3,4dipentyloxyphenyl)pentyl, and the like.

The "benzoyl(lower)alkyl" includes a benzoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzoylmethyl, l-benzoylethyl, 2-benzoylethyl, 3benzoylpropyl, 4-benzoylbutyl, 5-benzoylpentyl, 6-benzoylhexvl, l,1-dimethyl-2-benzoylethyl, 2-methvl-3-benzoylpropyl, and the like.

The "carbamoyloxy-substituted lower alkoxy" includes a carbamoyloxy-substituted alkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having I to 6 carbon atoms, for example, carbamoyloxymethoxy, 2-carbamoyloxyethoxy, l-carbarnoyloxyethoxy, 3carbamoyloxypropoxy, 4-carbarnoyloxybutoxy, pentyloxy, 6-carbamoyloxyhexyloxy, 1,l-dimethyl-2-carbamoyloxyethoxy, 2-methyl-3-carbamoyloxypropoxy, and the like.

The "lower alkylthio-substituted alkoxy"l includes a alkylthio-substituted straight chain or branched chain alkoxv group having 1 to 6 carbon atoms wherein the alkylthio moiety is a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, methylthiomethoxy, 3-ethylthiopropoxy, 4-methylthiobutoxy, 2-methylthioethoxy, 6-propylthiohexyloxy, pentylsxy, 1 ,l-dimethyi--2-butylthioethoxy, 2-methyl-3methylthiopropoxy, and the like.

WO 94/01113 7-PCT/JP93/00835 The "lower alkylsulfonyl-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkylsulfonyl group having I to 6 carbon atoms, for example, methylsulfonylmethoxy, 3ethyJlsulfonylpropoxy, 4-methylsulfonylbutoxy, 2-methylsulfonylethoxy, 6-Dropylsulfonylhexyloxy, sulfonylpentyloxy, l,1-dimethyl-2-butylsu'fonylethoxy, 2methyl-3-methylsulfonylpropoxy, and the like.

The "lower alkylsulfinyl-substituted lower alkoxy"l includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkylsulfinyl group having 1 to 6 carbon atoms, for example, methylsulfinylmethoxy, 3ethylsulfinylpropoxy, 4-methylsulfinylbutoxy, 2-methylsulfinylethoxy, 6-propylsulfinylhexyloxy, sulfinvlpentyloxy, 1, l-dimethyl-2-butylsulfinylethoxy, 2methyl-3-methylsulfinylpropoxy, and the like.

The "alkenvloxy" includes a straight chain or branched chain alkenyl group having 2 to 12 carbon atoms and containing one to three double bonds, for ,xample, vinyloxy, allyloxy, 3-methyl-2-butenyloxy, 2-butenyloxy, 3-butenyloxy, 1-methylallyloxy, 2-pentenyloxy, 2-hexenyloxy, 1-heptenyloxy, 1-octenyloxy, 1-nonenyloxy, 1-decenyloxy, 1-undecenyloxy, 1-dodecenyloxy, 2-heptenyloxy, 3-heptenyloxy, 2-methyl- 4-heptenyloxy, 2-methyl-5-heptenyloxy, 4-methyl-2-heptenyloxy, 3-methyl-l-heptenyloxy, l.3-heptadienyloxy, I,A-heptadienyloxy, 1,5-heptLadienyloxy, 1,6-heptadienyloxy, 2,4- WO 94/01113 -cm 3- f/P93/00835 heptadienyloxy, 2-rnethyl-2, 4-heptadienyloxy, 2,6-dimethyl- 2,4-heptadienyloxy, 2,5-dimethyl-1,3-heptadienyloxy, 2,4,6trimethyl-2,4-heptadienyloxy, 2-octenyloxy, 3-octeriyloxy, 4octenyloxy, 2-rnethyl-5-octenyloxy, 2-methyl-6--octenyloxy, 2methyl-7-octenyloxy, 1,3-octadienyloxy, 1,4-octadienyloxy, 1,6-octadienyloxy, 1,7-octadienyloxy, 2,4-octadienyloxy, 3,7-octadienyloxy, 4,8-diniethyl-3,7octadienyloxy, 2,4,6-trimethyl-3,7--octadienyloxy, 3,4- 3,7-dirnethyl-2,6-octadierr.Loxy, 4 ,8-dirnethyl-2 ,6-octadieriyloxy, 2-nonenyloxy, 3-noneriyloxy, 4-nonenyloxy, 2-methyl-5-nonenyloxy, 2-methyJ.-6-nonenyloxy, 2-methyl-7-nonenyloxy, 2-methyl-8-nonenyloxy, 1,3-nonadienyloxy, 1,4-nonadienyloxy, 1,5-nonadienyloxy, 1,6-nonadienyloxy, 1,7-nonadienyloxy, J,8-nonadienyloxy, 2,4-nonadienyloxy, 3,7-nonadienyloxy, 4,8-dimethyl--3,7-nonadi4enyloxy, 2,4,6-trimethyl--3,7-nonadienyloxy, 3,4-dimethyl-2,Snonadienyloxy, 4, 8-dirnethyl-2, 6-nonadienyloxy, 2-decenyJloxy, 3-decenyloxy, 4-decenyloxy, 5-decenyloxy, 2-methyl-6decenyloxy, 3-methyl-7-decenvloxy, 4-xnethyl-8-decenyioxy, methyl-9-decenylox-y, 1,3-decadienyloxy, 1,4-decadi;enyioxy, 1,6-decadienyloxy, L,7-decadienyloxy, 1,8-decadienyloxy, 1,9-decadienyloxy, 2-methyl-2,4' decadienyloxy, 3-methyl-2,5-decadienyloxy, 4,8-dimethyl-2,6decadienyloxy, 2,4,6-trimethyl-3,7-decadienyloxy, 2,9diiethyl-3,7-decadienyloxy, 2-undecenyloxy, 3-undecenyioxy, 4-undecenyloxy, 5-undecenyloxy, 2-methyl-6--undecenyloxy, 3methvl-7-unaecenyloxyi 4-methyl-8-undecenyloxy, 5-znethyl-9undecenyloxy, 2-methyl-1O-undecenyloxy, 1,3-undecadienvloxy, WO 94/01113 3 P~/JP93/00835 1,4-undecadienyloxy, 1,5-undecadienyloxy, 1,6-undecadienyloxy, 1,7-undecadienyloxy, 1,8-undecadienyloxy, 1,9-undecadienyloxy, 1,10-undecadienyloxy, 2-methyl-2..4-undecadienyloxy, 3-methyl-2, 5-undecadienyloxy, 4, 8-dirnethyl-2, 6-undecadienyloxy, 2,4,6-trimethyl-3,8-undecadienyloxy, 2,9dimethyl-3,8-undecadienyloxy, 2-dodecenyloxy, 3-dodecenyloxy, 4-dodecenyloxy, 5-dodecenyloxy, 6-dodecenyloxy, 2methyl-7-dodecenyloxy, 3-methyl-8--dodecenyloxy, 4-rnethyl-9dodecenyloxy, 5-methyl--lO-dodecenyloxy, 6-methvl-ildodecenyloxy, 2-methyl-2, 4-dodecadienyloxy, 3-methyl-2, dodecadienyloxy, 4,8-dimethyl-2,6-dodecadienyloxy, 2,4,6trimethyl-2,7-dodecadienyloxy, 2,1Q-dimethyl-2,8-dodecadienyloxy, 2,5-dimethyl-3,7-dodecadienyloxy,, 4,8,12trimethyl-3,7,11-dodecatrienyloxy, 1,3,5-heptatrienyloxy, 2,4,6-octatrienyloxy, 1,3,6-nonatrienyloxy, 2,6,8-dodecatrienyloxy, 1,5,7-undecatrienyloxy, and the like.

The "lower alkanoyloxy" includes a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, for example, formyloxy, acetyloxy, propionyloxy, burvryloxy, isobutyryioxy, pentanoyloxy, tert-butylcarbonyloxy, hexanoyloxy, and the like.

The "lower alkylsulfonyloxy" includes a straight chain or branched chain alkylsulfonyloxy group having 2. to 6 carbon atoms, for example, methylsulfonyloxy, ethylsulfonyloxy, isopropylsulionyloxy, butylsulfonyloxy, tert-butylsulfonyloxy, pentylsulfonyloxy, hexylsulfonyloxy, and the like.

The "lower alkynyloxy" includes a straight chain or branched chain alkynyloxy group having 2 to 6 carbon atoms, WO 94/01113 40 -PTJ9/03 for example, ethynyl,,:xy, 2-propynyloxy, 2-butynyloxy, 3butynyloxy, 1-methyl-2-proeynyloxy, 2-pentynyloxy, 2'hexynyloxy, and the like.

The "pheny'L(lower)alkoxy" includes a phenylalkoxv group wherein the alko-y moiety is a straight chain or branched chain alkoxy group having 1. to 6 carbon atoms, for example, benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy, 6phenylhexyloxy, l,l-dimethyl-2-phenylethoxy, 2-methyl-3phenylpropoxy, and the like.

The "cycloalkyloxy" includes a cycloalkyloxy group having 3 to 8 carbon atoms, for example, cyclopropyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, and the like.

The "cvcloalkenyloxy" includes a cycloalkenyloxy group having 3 to 8 carbon at--s, for example, cyclopropenyloxy, cyclobutenyloxy, cyclopentenyloxy, cyclohexenyloxy, cycloheptenyloxy, cyclooctenyloxy, and the like.

The "lower alkanoyl which may optionally have one to three substituents of a halogen atom" includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms which may optionally have one to three substituents of a halogen atom, for example, in addition to the above mentioned lower alkanoyl groups, 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2fluoroacetyl, 2-iodoacetyl, 2, 2-ditluoroacetyl, 2, 2-dibromoacetyl, 3,3,3-trifluoropropionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl, 2,3-dichlopropionyl, 4,4,4-trichloro- II_ WO 94/01113 41 -PCT/JP93/00835 butyryl, 4-fluorobutyryl, 5-chloropentanoyl, 3-chloro-2methylpropionyl, 6-bromohexanoyl, 5,6-dibromohexanoyl, and the like.

The "lower alkenyl" includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, for example, vinyl, ally', 2-butenyl, 3-butenyl, 1-methylallyl, 2-pentenyl, 2-hexenyl, and the like.

The "lower alkylthio" includes a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, methylthio, ethylthio, propylthio, isopropyithio, butylthio, tert-butylthio, pentylthio, hexylthio, and the like.

The or 6-membered, saturated or unsaturated heterocyclic group which is formed by binding R 6 and R 7 :ogether with the nitrogen atom o which they bond and may be intervened or not with nitrogen, oxygen or sulfur atom" includes, for example, pyrrclidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyrrolyl, pyrazolyl, imidazolyl, imidazolidinyl, pyrrolyl, imidazolinyl, pyrazolinyl, pyrazolidinyl, oxazolinyl, oxazolidinyl, isoxazolinyl, isoxazolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, and the like.

The "heterocyclic group having a substituent selected from a lower alkoxycarbonyl, lower alkyl, lower alkylthio and oxo" includes the above heterocyclic groups which have a substituent selected fr .m a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having I WO 94101113 4 2 /.W3/OO00835 1 to 6 carbon atoms, a straight chain' or branched chain alkylthio group having 1 to 6 carbon atoms, and an oxo group, for example, 4 -tert-butoxycarbonylpiperazinylI 4methylpiperazinyl, 2-ethylthioimidazolyll 2-oxopyrrolidinyl, 2-oxo-okazolidinylt 3-oxopiperazinyl, 4-rethoxycarbonylpiperazinyl, 3-ethoxycarbonylpiperidinyl, 2-propoxycarbonylpyrrolidinyl, 3-pentyloxycarbonylthiomorpholino, 2-hexyloxycarbonylthiornorpholino, 3-ethoxycarbonylpyrrolylt 3-methoxycarbonylimidazolyl, 3-ethylpiperidinyl, 3-propylpyrrolidinyl, 3-butylpyrrolyl, 2-pentylimidazolyl, 3-hexylmorpholino, 2-me thyithiomorpholino, 2-methyloxazolidinyl, 2-ethylthiazolinyl, 3-methylisoxazolinyl, 2-metnylthioimidazolyl, 2-propylthioimidazolinyl, 2-butylthioimidazolidinyl, 3pentyithiopyrrolyl, 3-hexylthiopyrroliny'L, 3-methylthiopyrrolidinyl, 3-ethyithiomorpholino, 2-methyithiomorpholino, 2-methylthioisoxazolidinyl, and the like.

The "lower alkyl which may optionally have one to three substituents selected from a halogen atom, hydroxy, phenyl and a lower alkoxyll includes a straight chain c: branched chain alkyl group having I to 6 carbon atoms which may optionally have one to three substituents selected from a halogen atom, hydroxy, phenyl and a straight chain or branched chain alkoxy group hay ng I to 6 carbon atoms, for example, in addition to the above-mentioned iower alkyl groups, hydroxymethyl, 2-hydroxyethyl, l-hydroxyethyll 3hydroxypropyl, 213-dihyroxypropyl, 4-hydroxybutyl, 111dimethyl-2-h~jroxyethyl, 5,5,4-trihydroxypentyl, pentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3- WO 94/01113 t 4 3 c' Mr/3P93/00035 hydroxypropyl, trifluoromethyl, trichioromethyl, chioromethyl, bromornethyl, fluoromethyl, iodomethyll difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichioroethy3., 3-chloropropyl, 2,3-dichlorcnpropyl, 4,4#4-trichiorobutyl, 4-flukirobutyl, 5-chioropentyl, 3chloro-2-methylpropyl, 5-bromohexyl, 5, 6-dichlorohexyl, benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenyipropyl, 4phenylbutyl, l,l-dimethyl-2-phenylethyl, 5-phenylpentyl, 6phenyihexyl, 2-methyl-3-phenylpropyl, methoxyrnethyl, 3methoxypropyl, 4-ethoxybutyl, 6-propoxyhexyl, pentyl, 1,l-dimethyl-2-butoxyethyl, 2-zethyl-3-tert-butoxypropyl, 2-pentyloxyethyl, hexyloxymethyl, dirnethoxyrnethyl, 2,3-dimethoxyethyl, 6,6,5-trimethoxyhexyl, 1-hydroxv-lphenylmethyl, l-hydroxy-2-phenylethyl, 1-hydroxy-3-phenylpropyl, 1-methoxy-1-phenylnethyl, and the like.

The "cy&ano-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having I to 6 carbon atoms which is substituted by cyano group, for example, cyanomethoxy, 2-cyanoethoxy, 1-cyanoethoxy, 3cyanopropc xy, 4-cyanobutoxy, 5-cyanopentyloxy, 6-cyanohexyloxy, l,1-dimethyl-2-cyanoethoxy, 2-methyl-3-cyanopropoxy, and the like.

The "oxiranyl-substituted lower alkoxyl" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by oxiranyl group, for example, glycidcxy, 2-oxiranylethoxy, 1-oxiranylethoxy, 3oxiranyipropoxy, 4-oxiranylbutoxy, 5-oxiranylpentyloxy, 6-* oxiranylhexyloxy, ltl-dimethyl-2-oxiranylethoxy, 2-methyl-3- WO 94/01113 C vMf/93/OO835 oxiranyipropoxy, and the like.

The "phthalirnido-substituted alkoxyll includes a straight cha~in or branched Chain alkoxy group having I to 12 carbon atoms which is substituted by phthalirnido group, for example, phthalimidomethoxy, 2-phthalimidoethoxy, 1-phthalimidoethoxy, 3-phthalimidopropoxy, 4-phthaliinidobutoxy, Sphthalimidopentyloxy, 6-phthalimidohexyloxy, 1 ,1-dimethyJ.-2phthalimidoethoxyt 2-methyl-3-phthalimidopropoxy, 7-phthalimidoheptyloxy, 8-phthalimidooctyloxy, 9-phthalimidononyloxy, lQ-phthalimidodecyloxy, ll-phthalimidoundecyloxy, 12phthalimidododecyloxy, and the like.

The "pyrrolyl-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by pyrrolyl group, for example, (l-pyrrolyl)methoxyt 2-(2--pyrrolyl)ethoxy, 1-(3pyrrolyl)ethoxy, 3-(1-pyrrolyl)propoxyo 4-(l-pyrrolyl)butoxy, 5-(2-pyrrolyl)pentyloxy, 6-(3-pyrrolyl)hexvloxy, .L,1-dimethyl-2-(l-pyrrolyl)ethoxy, 2-methyl-3-(1-pyrrolyl)propoxy, and the like.

The tamidino-.substituted lower alkoxy"l includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by amidino group, for example, amidinomethoxy, 2-amidinoethoxy, I-amidinoethoxy, 3-amidinopropoxy, 2-amidinobutoxy, 5-amidinopentyloxy, 6amidinohexyloxy, 1,l-dimethyl-2-amidino2thoxy, 2-methyl-'3amidinopropoxy, and the like.

The "lower alkanoyloxy(lower)alkyl" includes a straight chain or branched chain alkyl group having 1 to 6 WO 94/01113 PCir P913/0O835 carbon atoms which is substituted by a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, for example, acetyloxymethyl, 2-propionyloxyethyl, 1butyryloxyethyl, 3-acetyloxypropyl, 4-isobutyryloxybutyl, pentanoyloxypentyl, 6-tert-butylcarbonyloxyhexyl, 1,1dimethyl-2-hexanoyloxyeth:1l, 2-methyl-3-acetyloxypropyl, and the like.

The "lower alkylsulfinyl" includes a straight chain or branched chain alkylsulfinyl group having 1 to 6 carbon atoms, for example, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, butylsulfiyl, tert-butylsulfinyl, pentylsulfinyl, hexylsulfinyl, and the like.

The "lower alkenyl having optionally a hydroxysubstituent" include a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms and having optionally a hydroxy-substituent, for example, in addition to the above-mentioned lower alkenyl groups, 1-hydroxyallyl, 4-hydroxy-l-butenyl, 4-hydroxy-2-butenyl, 2-hydroxy-3-butenyl, 5-hydroxy-2-pentenyl, 6-hydroxy-2-hexenyl, and the like.

The "lower alkylenedioxy" includes a straight chain or branched chain alkylenedioxy group having 1 to 4 carbon atoms, for example, methylenedioxy, ethylenedioxy, trimethylenedioxy, tetramethylenedioxy, and the like.

The "lower alkylsilyl" includes a silyl group having one to three substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methylsilyl, ethylsilyl, propylsilyl, isopropylsilyl, butylsilyl, tert-butylsilyl, pentylsilyl, 48 WO 94/01113 46 Pr/P93/0083 PCT/J3/00835 hexylsilyl, dimethylsilyl, trimethylsilyl, dimethyl-tertbutylsilyl, and the like.

The "amino which may optionally be substituted by a lower alkanoyl" includes an amino which may optionally be substituted by a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, amino, formylamino, acetylamino, propionylamino, butyrylaminc, isobutyrylamino, pentanoylamino, tert-butylcarbonylamino, hexanoylamino, and the like.

The "phenoxycarbonyl which may optionally have one to three substituents selected from nitro and an amino having optionally one or two substituents selected from a lower alkanoyl, lower alkyl and benzoyl" includes a phenoxycarbonyl group which may optionally have one to three substituents selected from nitro group and an amino group having optionally one or two substituents selected from a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and benzoyl group, for example, phenoxycarbonyl, 2-nitrophenoxycarbonyl, 3-nitrophenoxycarbonyl, 4-nitrophenoxycarbonyl, 3,4-dinitrophenoxycarbonyl, 2,5-dinitrophenoxycarbonyl, 2,6-dinitrophenoxycarbonyl, 3,4,5-trinitrophenoxycarbonyl, 2-aminophenoxycarbonyl, 3-aminophenoxycarbonyl, 4-aminophenoxycarbonyl, 3acetylaminophenoxycarbonyl, 4-formylaminophenoxycarbonyl, 4isobutyrylaminophenoxycarbonyl, 2-pentanoylaminophenoxycarbonyl, 3-hexanoylaminophenoxycarbonyl, 3,4-diacetylaminophenoxycarbonyl, 3,4-diaminophenoxycarbonyl, 2,6-diaminophe- WO 9/0113 7 "PCr/J P93/00835 noxycarbonyl, 2, 5-diaminophenoxycarbonyl, 2,4 ,6-triaminophenoxycarbonyl, 4-acetylaminophenoxycarbonyl, 4-dimethylaminophenoxycarbonyl, 4-benzoylaminophenoxycarbonyl, 3- (Nmethyl-N-benzoylamino)phenoxycarbonyl, 2-(N-ethyl-N-acetylamino)phenoxycarbonyl, and the like.

The "phenyl(lower)alkenylcarbonyl"I includes a phenylalkenylcarbonyl group wherein the alkenylcarbonyl moiety is a straight chain or branched chain alkenylcarbonyl group having 3 to 6 carbon atoms, for example, cinnamoy., 4pnhenyl-3-butenoyl, 4-phenyl-2-butenoyl, 5-phenyl-4pentenoyl, 5-phenyl-3-pentenoyl, 5-phenyl--2-pentenoyl, 6- 6-phenyl-4-hexenoyl, 6-phenyl-3-hexenoyl, 6-phenyl--2-hexenoyl, 2-methyl-4-phenyl-3-butenoyl, and the like.

The "amino having optionally a lower alkoxycarbonyl substituent" includes an amino being optionally substituted hy a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, amino, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, tert-butoxvcarbonylamino, pentyloxycarbonylamino, hexyloxycarbonylamino, and the like.

The "phenyl(lower)alkanoyl wherein the lower alkanoyl moiety may optionally be substituted by an amino having optionally a lower alkoxycarbonyl substituent" includes a phenylalkanoyl wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms and may optionally be substituted by an amino WO 94/01113 48 PCT/JP93/00835 group which may optionally be substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, phenylacetyl, 3-piienylpropionyl, 2-phenyipropionyl, 4-phenylbutyryl, 2,2-dimethyl-3-phenylpropionyl, 5-phenylpentanoyl, 6-phenyihexanoyl, 3-methyl-4phenylbutyryl, 2-amino-4--phenylacetyl, 2-tert--butoxycarbonylamino-2-phenylacetyl, 2-methoxycarbonylamino-2phenylacetyl, 2-ethoxycarbonylarnino-3-phenylpropionyl, 2uropooxvcarbonylamino-4-phenylbutyryl, 2-pentyloxycarbonl- 2-hexyloxycarbonylamino-6-phenylhexanoyl, and the like.

The "alkanoyl" includes a straight chain or branched chain alkanoyl group having 1 to 12 carbon atoms, for example, in addition to the above-mentioned lower alkanoyl groups, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, neopentanoyl, and the like.

The "alkenylcarbonyl" includes a straight chain or branched chain alkenylcarbonyl group having 2 to 12 carbon atoms and having one to three double bonds, for example, vinylcarbonyl, acrylcarbonyl, 3-methyl-2--butenylcarbonyl, 2butenylcarbonyl, 1-methylallylcarbonyl, 2-pentenylcarbonyl, 2-hexenylcarbonyl, 1-heptenylcarbonyl, 1-octenylcarbonyl, 1nonenylcarbonyl, 1-decenylcarbonyl, 1-undecenylcarbonyl, 1dodecenylcarbonyl, 2-heptenylcarbonyl, 3-heptenylcarbonyl, 2-methyl-4-heptenylcarbonyl, 2-methyl-5-heptenylcarbonyl, 4methyl-2-heptenylcarbonyl, 3-methyl-l-heptenylcarbonyl, 1, 3heptadienylcarbonyl, 1, 4-heptadienylcarbonyl, 1, dienvlcarbonyl, 1, 6-heptadienylcarbonyl, 2, 4-heptadienyl- 49 WO 94/01113 PCT/JP93/00835 carbonyl, 2-methy.-2, 4-heptadienylcarbonyl, 2, 6-dimethyl- 2,4-heptadienylcarbonyl, 2,6-dimethyl-1,5-heptadienylcarbonyl, 2,5-dimethyl-1,3-heptadienylcarbonyl, 2,4,6trimethyl-2,4-heptadienylcarbonyl, 2-octenylcarbonyl, 3octenylcarbonyl, 4-octenylcarbonyl, carbonyl, 2-methyl-6-octenylcarbonyl, 2-methyl-7-octenylcarbonyl, 3-octadienylcarbonyl, 1, 4-octadienylcarbanyl, J,6-octadienylcarbonyl, 1,7octadienylcarbonyl, 2,4-octadienylcarbonyl, 3,7-octadienylcarbonyl, 4,8-diinethyl-3,7-octadienylcarbonyl, 2,4,6trirethyl-3,7-octadienylcarbonyl, 3,4-dimethyl--2,5octadienylcarbonyl, 4,8-dimethyl-2,6--octadienylcarbonyl, 2nonenylcarbonyl, 3-noneriylcarbonyl, 4-nonenylcarbonyl, 2- 2-methyl-6-nonenylcarbonyl, 2methyl-7-rionenylcarbonyl, 2-methyl-8-nonenylcarbonyl, 1, 3nonadienylcarbonyl, 1,4-nonadienylcarbonyl, carbonyl, 1, 6-nonadienylcarbonyl, 1, 7-nonadienylcarboiyl, 1,8-nonadienylcarbonyl, 2,4-nonadienylcarbonyl, 3,7nonadienylcarbonyl, 4 ,8-dimethyl-3 ,7-nonadienylcarbonyl, 2,4,6-trimethvl-3,7-nonadieniylcarbonyl, 3,4-dimethyl--2,5nonadienylcarbonyl, 4 ,8-dimethyl-2, 6-nonadienylcarbonyl, 2decenylcarbonyl, 3-decenylcarbonyl, 4-decenylcarbonyl, decenylcarbonyl, 2-methyl-6-decenylcarbonyl, 3-xnethy2.-7decenylcarbonyl, 4-methyl-8-decenylcarbonyl, 5-methyl-9decenylcarbonyl, 1,3-decadienylcarbonyl, 1,4-decadienylcarbonyl, 1,5-decadienylcarbonyl, lt6-decadienylcarbony'1, 1,7-decadienylcarbonyl, 1,8-decadienylcarbonyl, 1,9decadienylcarbonyl, 2-methyl-2, 4-decadienylcarbonyl, 3- WO 94/01113 PCT/3P93/00835 4,8-dimethyJ.-2,6-decadienylcarbonyl, 2,4,6-trimethyl-3,7-decadienylcarbonyl, 2,9dimethyl-3,7-decadienylcarbonyl, 2-undecenylcarbonyl, 3undecenylcarbonyl, 4-undecenylcarbonyl, 2-methyl-6-undecenylcarbonyl, 3-methyl-7-undecenylcarbony.l, 4-methyl-8-undeceny.carbonyl, 5-methyl-9-undecenylcarbonyl, 2-methyl-lO-undecenylcarbonyl, 1,3-undecadienylcarbonyl, l,4-undecadienylcarbony., 1,5-undecadienylcarbonyl, 1,6undecadienylcarbonyl, 1, 7-undecadienylcarbonyl, 1, Bundecadienylcarbonyl, 1,9-undecadienvicarbonyl, 1,10undecadienylcarbonyl, 2-rnethyl-2 ,4-undecadienylcarboiyl, 3-rethyl-2,5-undecadienylcarbonyl, 4,8-dimethyvl-2,6undecadienylcarbonyl, 2,4,6-trimethvl-3,8-undecadienylcarbonyl, 2,9-dimethyl-3,8-undecadienylcarbonyl, 2dodecenvicarbonyl, 3-dodecenvlcarbony., 4-dodecenylcarbonvl, 6-dodecenylcarbon.l, 2-tnethyl-7dodecenylcarbonyl, 3-methyl-8-dodecenylcarbonyl, 4-methyl-9dodeceny2.carbonyl, 5-methyl-10-dodecenylcarbonvl, 6-methy-- 12-dodecenylcarbonvi, 2-methyl-2,4-dodecadienylcarbony., 3- 4,8-dirnethyl-2,6dodecadienylcarbonyl, 2,4,6-trimethvL-2,7-dodecadienylcarbonyl, 2,1O-dimethyl-2,8-dodecadienvlcarbon2.-, dimethyl-3,7-dodecadienylcarbonyl, 4,B,12-trimethyl-3,7,1ldodecatrienylcarbonyl, l,3,5-heptatrienylcarbonyl, 2,4,6octatrienylcarbonv., 1,3,6-nonatrienylcarbonyl, 216,8dodecatrienylcarbonyl, 1,5,7-undecatr-renvlcarbonyl, and the like.

The "phenylsulfony. wherein the phenyl. ring may 111 52 WO 94/01113 PCT/JP93/00835 optionally have a lower alkoxy substituent" includes a phenylsulfonyl group wherein the phenyl ring may optionally have one to three substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, phenylsulfonyl, 2-methoxyphenylsulfonyl, 3-methoxyphenylsulfonyl, 4-methoxyphenylsulfonyl, 2-ethoxyphenylsulfonyl, 3-ethoxyphenylsulfonyl, 4-ethoxyphenylsulfonyl, 4isopropoxyphenylsulfonyl, 4-pentylcxyphenylsulfonyl, 4hexyloxyphenylsulfonyl, 3,4-dimethoxyphenylsulfonyl, 3ethoxy-4-methoxyphenylsulfonl, 2,3-dimethoxyphenylsulfonyl, 3,4-diethoxyphenylsulfonyl, 2, 6-dimethoxyphenylsulfonyl, 3,4-dipentyloxyphenylsulfonyl, 3,4,5-trimethoxyphenylsulfonyl, and the like.

The "phenyl which may optionally have one to three substituents selected from a lower alkoxy, a lower alkyl, a halogen atom, an amino having optionally one or two substituents selected from a lower alkyl and a lower alkanoyl, and nitro" includes a phenyl group which may optionally have one to three substituents selected frci a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a halogen atom, an amino group having optionally one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, and a nitro group, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4- WO 94/01113 PCT/J P93/00835 methoxyphenyl, 2-ethoxypheny.1, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3, 4-dimethoxyphenyl, 3-ethoxy-4methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxypheiyl, 3,4-dipentyox~yphenyl, 3,4,5-trimethoxyphenyl, 2-methylphenyl, 3-methyJlphenyl, 4-methylphenyl, 2-ethyiphenyl, 3-ethylphenyl, 4-ethyiphenyl, 4isopropyiphenyl, 3-butylpheiyl, 4-pentyiphbenyl, 4-hexylphenyl, 3,4-dimethyiphenyl, 3,4-diethylphenyl, phenyl, 2,6-dimethylpheiyl, 3,4,5-trirnethylphenyl, 2-chiorophenyl, 3-chiorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodoiphenyl, 3,4-dichiorophenyl, 3,5-dichlorophienyl, 2,6-dichlorophenyl, 2,3-dichJlorophenyl, 2,4-dichioropbenyl, 3,4-difluorophenyl, 3,4,5-trichiororhenyl, 2-nitrophenyl, 3nitrophenyl, 4-nitroprnenyl, 3,4-dinitrophenyl, phenyl, 2,6-dinitrophenyl, 3,4,5-trinitrophenyl, 2-aminophenyl, 3-aminophenyl, 4-aminophenyl, 3-(N--acetylamino)phenyl, 4-(N-fornylamino)phenyl, 4-(N-isobutyrylamino)phenyl, 2-(N-pentanoylamino)phenyl, 3,4-diaminophenyl, 3,4di(N-acetylamino)phenyl, 3,4,5-triaminophenyl, 2,6-diarninophenyl, 2, 5-diaminopheiyl, 3, 5-di-t-butyl-4-hydroxvphenyl, 3-hydroxy-4-pentyloxyphenyl, 2-hydroxy-5-t-butylphenyj1, dichloro-4-arninophenyl, 3-amino-4-hydroxyphenyl, 3-acetvlamino-4-methoxyphenyl, 3-nitro-4-acetylaminophenyl, 3-nitro- 4-chlorophenyl, 3-chloro-4-methylphenyl, 3-rethoxy-4-methyl- WO 94/01113 PCTIJP93/00835 3, 4-dimethoxy-5-bromophenyl, 3, 5-diiodo-4methoxyphenyl, 4-dime thylaminophenyl, 3-me thylaminophenyl, 2-butylaminophenyl, 4-diethylaminophenyl, 3-dipropylaminophenyl, 2-(N-methyl-N-hexaylamino)phenyl, 4-(N-methyl-Nacetylamino)phenyl, 2,4-dimethylamino~henyl, and the like.

The "heterocyclic group-substituted carbonyl" includes a carbonyl group which is substituted by a 5- to lO-membered, monocyclic or dicyclic heterocyclic groups containing one or two hetero atoms selected from nitrogen atom, oxygen atom and/or sulfur atom, for example, 2pyrrolidinylcarbonyl, 3-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl, 1-piperazinylcarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl, 2-tetrahydrofurylcarbonyl, 2thienylcarbonyl, 3-thienylcarbonyl, 2-pyrrolylcarbonyl, 3pyrrolylcarbonyl, 2-furoyl, 3-furoyl, 2-pyridylc-arbonyl, 3pyridylcarbonyl, 4-pyridylcarbonyl, 3-pyridazylcarbonyl, 2thiazolyicarbonyl, 2-oxazolylcarbonyl, 2-imidazolylcarbonyl, 4-pyridazylcarbonyl, 5-pyridazylcarbonyl, 6-pyridazylcarbonyl, 2-pyrimidylcarbonyl, 4- pyrimidylcarbonyl, pyrimidylcarbonyl, 6-pyrimidylcarbonyl, 2-pyradylcarbonyl, 3-pyradylcarbonyl, 6-quinolylcarbonyl, 5-indolylcarbonyl, 6isoauinolylcarbonyl, 4-cinnolylcarbonyl, 3-auinoxalylcarbonyl, 4-phthalazylcarbonyl, 5-quinazolylcarbonyl, 3benzofblfuranylcarbonyl, 5-benzo~b]thiophenylcarbonyl, 2oxo-6-quinolylcarbonyl, 2-oxo-4-quinolylcarbonyl, and the like.

The above "heterocyclic group-substituted carbonyl which has one to th-ree substitutents selected from a phenyl- WO 94/01113 PCr/JP93/00835 (lower)alkoxycarbonyl, a phenyl(lower)alkoxy, oxo, a lower alkyl and a lower alkylenedioxy" includes the abovementioned heterocyclic group-substituted carbonyl groups which have one to three substituents selected from a phenylalkoxycarbonyl group wherein the alkoxycarbony. moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, a phenylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, an oxo group, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and a straight chain or branched chain alkylenedioxy group having 1 to 4 carbon atoms, for example, l-benzyloxycarbonyl-2-pyrrolidinylcarbonyl, 3-benzyloxycarbonyl-4, (1,1-dimethylmethylene)-2-tetrahydrofurylcarbonyl, 4-(2phenylethoxycarbonyl)-l-piperazinylcarbonyl, 3-methyl-2thienylcarbonyl, 3-ethyl-2-pyrrolylcarbonyl, 3-pro-pyl-2furoyl, 4-butyl-2-oxo-6-quinolylcarbonyl, 6-pentyl-2-oxo-4quinolylcarbonyl, 5-hexyl-2-pyrazylcarbonyl, l,3-dioxo-2methyl-6-quinazolylcarbonyl, 4, 5-methylenedioxy-3-indolylcarbonyl, 3-(3-phenylpropoxy)morpholinocarbonyl, and the like.

The "thienyl(lower)alkanoyl" includes a thienylalkanoyl wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2to 6 carbon atoms! for example, 2-(2-thienyl)acetyl, 3-(3-thienyl)propionyl, 2- (3-thienyl)propionyl, 4-(2-thienyl)butyryl, 2,2-dimethyl-3- (3-thienyl)propionyl, 5-(2-thienyl)pentanoyl, 6-(3-thienyl)hexanoyl, 3-methyl-4-(2-thienyl)butyryl, and the like.

WO~ 94/01113 Pr.JP93/00835 The "tricyclo[3.3.l.lldecanyl(lower)alkanoyl"I includes a tricyclo[3.3.l.lldecanylalkanoyl wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, 2tricyclofi3.3.1.1]decanylacetyl, 3-tricyclo[3.3.l.1)decanltlpropionyl, 2-tricyclo[3.3.l.1)decanylpropionyl, 4-tricyclo- [3.3.l.l)decanylbutyryl, 2,2-diinethyl-3-tricyclo[3.3.1.l]decanyipropionyl, 5-tricyclo[3.3.l.1jdecanloeitanoyl, 6tricyclo[3.3.l.l)decanylhexanoyl, 3-methyl-4-tricyclc- [3.3.l.l)decanylbutyryl, and the like.

The "benzoyl wherein the phenyl ring may optionally have a lower alkoxy substituent" includes a benzoyl which may optionally have one to three substituents of a straigiht chain or branched chain alkoxy group having 1 to 6 carbon atoms on the phenyl ring, for example, benzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl, 2-eth'-xybenzoyl, 3-ethoxybenzoyl, 4-butoxybenzoyl, 4-isopropoxybenzoyl, 4-pentyloxybenzoyl, 4-hexyloxybenzo~ 1, 3 ,4dimethoxybenzoy., 3-ethoxy-4-methoxybenzoyl, 2,3-dimethoxybenzoyl, 3,4-diethoxybenzoyl, 2,5-dirmethoxybenzoyl, 2,6dimethoxybenzoyl, 2,4-dimethoxybenzoyl, 2,4,6-trimethoxybenzoyl, 3, 5-dimethoxybenzoyl, 3, 4-dipent yloxybenzoyl, 3,4,5-trimethoxybenzoyl, and the like.

The "phenyl which may optionally have a lower alkoxy substituent" includes a ph,:nyl group which may optionally have one to three substituents of a straight chain or branched .chain alkoxy group having 1 to 6 carbon atoms, for example, phenyl, 2-methoxyphenyl, 3-methoxy-_ inx'r WO 94/01113 IvCr/31P93/00$35 phenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyli 4ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4pentyJloxyphenyl, 4-hexyloxypheny., 3 ,4-dimethoxyphenyl, 3ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, dimethoxyphenyl, 3t4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl, and the like.

The "cycloalkyl" includes a cycloalkyl having 3 to 8 carbon qtomsf for example, cyclopropyl., cyclobutyl, cyclopentyl, cycJlohexyl, cycloheptyl, cyclooctyl, and the like.

The "saturated or unsaturated heterocyclic group which is formed by binding the groups R 11 and R 12 together with the nitrogen atom to which they bond and may be intervened or not with nitrogen, oxygen or sulfur atom" includes, a 5- to lO-membered, saturated or unsaturated, monocyclic or dicyctic heterocyclic group, for example, pyrrolidinyl, piperidinyl, piperazinyl, rnorpholino, thiomorpholino, pyrrolyl, intidazolyl, pyrazolyl, imidazolidinyl, pyrazolinyl, pyrazolid.Liyl, oxazolinyl, oxazolidinyl, isoxazolinyl, isoxazolidinyl, thiazolinyl, thiazolidiny1l, othiazolinyl, isothiazolidinyl, 1#2,3,4tetrahydroquinolyl, 1,2-dihydroquinolyl, indoly.l, isoindolyl, 1,2-dihydroisoquinolyl, 1,2,3t4-tetrahydroisoguinolyl, lH-indazolyl, 1,2-dihyroguinazolyl, 1,2dihydrocinnolyl, 1,2-dihydroquinoxalylt 1,2,3,4-tetrahydroquinazolyl, 1,2,314-tetrahydrocinnolyl, l,2,3,4-tetrahydroquinoxalyl, and the like.

The "phenyl which may optionally have a substituent pa. WO 94/01113 /1 PCMJX/3/0035 selected from a lower alkoxy and a lower alkanoyl" includes a phenyl group which may optionally have one to three substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, phenyl, 2-methoxypnenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-ethoxy- 4-methcxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,6-dimethoxyphenyl, phenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethcxyphenyl, 3methoxy-4-acetylphenyl, 2-acetylphenyl, 3-acetylphenyl, 4acetylphenyl, 2-formylphenyl, 3-propionylphenyl, 4isobutyrylphenyl, 2-pentanoylphenyl, 3-hexanoylphenyl, 3,4diacetylphenyl, 2,5-diacetylphenyl, 3,4,5-triacetylphenyl, and the like.

The "heterocyclic group which is substituted by a member selected from benzoyl, a lower alkanoyl, a phenyl- (lower)alkyl, and a phenyl having optionally a substituent selected from a lower alkoxy and a lower alkanoyl" includes the above heterocyclic groups which have a substituent selected from benzoyl group, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and a phenyl group having optionally one to three substituents selected from a straight chain or branched chain alkoxy WO 94/01113 WO 4/0113i'caPCV11/00835 group having I. to 6 carbon atoms and a straight Chain or branched chain alkanoy. group having 1 to 6 carbon atoms, for example, 3-benzoyl-l-pyrrolidinyl, 4-benzoyl-lpiperidinyl, 4-benzoyl-l-piperazinyl, 4-benzyl-lpiperazinyl, 3-(2-phenylethyl)morpholino, 3-(3-phenylpropyl)thiornorpholino, 3-(4-phenylbutyl)-1-pyrrolyl, 4acetyl-l-piperidinyl, 4-acetyl-l-piperazinyl, 4-formylpiperazinyl, 2-(5-phenylpentyl)-l-imidazo.yl, 3-(6-phenylpentyl)-l-pyrazolyl, 4-(4-methoxyphenyl)-l-piperazinyl, 4- (4-acetylphenyl)-l-piperazinyl, 4-(3-ethoxyphenyl)-1piperazinyl, 4-(3-propionylphenyl)-1-piperazinyl, 1,2,3,4-tet.rahydroquinolin-1-yl, 6-(4-butyrylphenyl)- 1,2,3,4-tetrahydroisoquinolin-2-yl, 4-(2-propoxyphenyll)-lindolyl, 5-(3-pentanoylphenyl)-lH-indazol-l-yl, 6-(3butoxyphenyl)-1,2-dihydroquinazolin-1-yl, 7-(4-hexanoylphenyl)-l,2,-dihydrocinnolin-2-yl, 6-(4-hexyloxyphenyl)- 1,2,3,4-tetrahvdroquinoxalin-1-yl, and the like.

The "alkylene" includes a straight chain or branched chain alkylene group having 2. to 12 carbon atoms, for example, in addition to the above-mentioned lower alkylene groups, heptamethylene, octamethylene, nonamethylene, decamethylene, undecamethylene, dodecamethylene, and the like.

The "lower alkoxycdirbonyl(lower)alkyl wherein the alkyl moiety may optionally be substituted by hydroxy or an amino having optionally a phenyl(lower)alkoxycarbony'.

substituent" includes a straight chain or branched chain alkoxycarbonylalkyl group having I. to 6 carbon atoms in the WO 94/01113 c r/J P93/00835 alkoxy moiety, wherein the alkyl moiety is straight chain or branched chain alkyl group having 1 to 6 carbon atoms and has optionaly a substituent selected from a hydroxy group and an amino group having optionally a substituent of a phenylalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, l-hydroxy-lmethoxycarbonylmethyl, l-methoxycarbonyl-2-hydroxyethyl, 3hydroxy-3-methoxycarbnylpropyl, 2-hydroxy-4-ethoxycarbonylbutyl, 2-hydroxy-6-propoxycarbonylhexyl, 2-hydroxy-2pentyloxycarbonylethyl, l-hydroxy-l-hexyloxycarbonylmethyl, 5-benzyloxycarbonylamino-1-methoxycarbonylpentyl, methoxycarbonylpentyl, 3-(2-phenylethoxycarbonylamno)-lethoxycarbonylpropyl, 4-dmino-l-butyloxycarbonylbutyl, and the like.

The "amino-substituted lower alkanoyl wherein the lower alkanoyl moiety may optionally be substituted by a member selected from a phenyl(lower)alkoxycarbonylamino, hydroxy, a phenyl having optionally a hydroxy substitutent, carbamoyl, imidazolyl and a lower alkyithio, and the amino group may optionally have a substituent selected from a lower alkyl having optionally a hydroxy substitutent, a lower alkenyl, a phenyl(lower)alkyl having optionally a lower alkoxy substituent on the phenyl ring, a lower alkylsulfonyl, a lower alkanoyl, and a phenyl(lower)alkoxycarbonyl" includes an amino-substituted straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, wherein the alkanoyl moiety may optionally be substituted by WO 94/01113 60 PCT/3P93/00835 a member selected from phenylalkoxycarbonylamino wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, a hydroxy group, a phenyl group having optionally one to three hydroxy-substitutents, a carbamoyl group, an imidazolyl group and a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, and the amino group may optionally have a substituent selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and having optionally one to three hydroxy-substitutents, a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and the phenyl ring has optionally one to three substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a straight chain or branched chain alkylsulfonyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, and a phenylalkoxycarbonyl wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, aminoacetyl, 3-formylaminopropionyl, acetylaminoacetyl, 2-propionylaminopropionyl, 4-butyrylaminobutyryl, 2,2-dimethyl-3-isobutyrylaminopropionyl, pentanoylaminopentanoyl, 6-tert-butylcarbonylaminohexanoyl, 3-methyl-4-hexanoylaminobutyryl, 4-methylthio-2-acetylaminobutyryl, 3-(imidazol-4-yl)-2-acetylaminopropionyl, 2acetylaminopropionyl, 3-(4-hydroxyphenyl)-2-benzyloxy- WO 94/01113 1-PCT/J P93/00835 carbonylaminopropionyl, 4-carbamoyl-2-acetylaminobutyryl, 2acetylaminoisopentanoyl, 5-ethylthio-2-acetylaminopentanoyl, 4-(imidazol-2-yl)-2--propionylaminobutyryl, 2-hydroxyphenyl )-2-butyrylaxninohexanoyl, 3-carbamoyl-2-benzyloxycarbonylaminopropionyl, 5-carbamoyl-2-( 2-phenylethoxycarbonylamino)pentanoyl, 3-(2,4-dihydroxyphenyl)-2-(3phenylpropoxycarbonylamino)propionyl, 2 carbonylaminohexanoyl, 3- (4-hydroxyphenyl )-2-aminopropionyl, dime thylaminoacetyl, 3-hydroxy-2-benzyloxycarbonylaminopropionyl, 2-benzyloxycarbonylaminopropionyl, 2-aminopropionyl, 2-aminoisopentanoyl, 2-aminobutyryl, 4-benzyloxycarbonylaminobutyryl, diethylantinoacetyl, 4-acetylaminobutyryl, 4-dimethylaminobutyryl, 2-hydroxyacetyl, ethylaminoacetyl, allylaminoacetyl, berizylaminoacetyl, isopropylaminoacetyl, (N-methyl-N-,benzylamino)acetyl, (N-methyl-N-( 2hydroxyethyl)aminolacetyl, [N-methyl-N-(4-ethoxybenzyl)aminollacetyl, 2-benzyloxycarbonylaminoacety,, methylsulfonylaminoacetyl, (3-methoxybenzyl)aminoacetyl, (N- *nethyl-N-acetylamino)acetyl, pentanoyl, 6-[N-allyl-N-(3,4-dimethoxybenzyl)arnino)hexanoyl, and the like.

The "aiido-substituted lower alkyl wherein the lower alkyl moiety has optionally a substituent selected from a phenyl having optionally a hydroxy substitueit, imidazolyl, carbamoyl and a lower alkylthio, and the amido grout) may optionally have a lower alkyl substituent" includes an amido-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms wherein the WO 94/01113 62 Prri P93/00835 alkyl moiety have optionally a substituent selected from a phenyl having optionally one to three hydroxy-substituents, an imidazolyl group, a carbamoyl group and a straight chain or branched chain alkylthio group having I to 6 carbon atoms, and the amido group may optionally have one or two substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carbamoylmethyl, 2-carbamoylethyl, 1-carbamoylethyl, 3-carbamoylpropyl, 4-carbamoylbutyl, r&-carbamoylpentyl, 6-carbamoylhexyl, 1, l-dimethyl-2-carbamoylethyl, 2-methyl-3-carbamoylpropyl, iethylamidomethyl, 1-ethylamidoethyl, 2-propylamidoethyl, 3-isopropylamidopropyl, 4-butylamidobutyl, amidopentyl, 6-hexylamidohexyl, dimethylamidomethyl, (Nethyl-N-propylamido)methyl, 2-(N-methyl-N-hexylamido)ethyl, 2-(4-hydroxyphenyl)carbamoylethyl, l-carbamoylisobuty., 2- (imidazol-4-yl)-l-carbamoylethyl, l,3-dicarbamoylpropyl, 3methylthio-l-carbamovlpropyl, 2-hydroxyphenyl)-l-methvlamidopropyl, 2,6-dihydroxyphenyl)-l-(N-nethyl-N-hexylamido)butyl, 3-(imidazol-2-yl)-l-propylamidopropy., 1,4dicarbamoylbutyl, 2-ethylthio-l-butylamidobutyl, 4-penty,thio-l--hexylamidobutyl, and the like.

The "carboxy(lower)alkyl" includes a carboxyalkyl group wherein the alkyl moietyl is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carboxymethy., 2-carboxyethyl, l-carboxyethyl, 3carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl, 1,l-dimethyl-2-carboxyethyl, 2-methyl-3-carboxypropyl, and the like.

n -11 63 WO 94/01113 PCT/JP93/00835 The "lower alkoxy(lower)alkyl" includes a straight chain or branched chain alkoxyalkyl group having 1 to 6 carbon atoms in the alkoxy moiety wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methoxymethyl, 2-ethoxyethyl, l-methoxyethyl, 3-methoxypropyl, 4-ethoxybutyl, 6propoxyhexyl, 5-isopropoxypentyl, l,l-dimethyl-2-butoxyethyl, 2-methyl-3-tert-butoxypropyl, 2-pentyloxyethyl, hexyloxymethyl, and the like.

The "amino acid residue which is able to form an amido bond with the amino group to which R 4 and R 5 bind" includes, for example, alanine residue, N2-arginine residue,

N

5 -arginine residue, N 6 -arginine residue, N 4 -asparagine residue, aspartic acid residue, N 5 -glutamine residue, cysteine residue, glutamic acid residue, glycine residue, histidine residue, isoleucine residue, leucine residue, N 2 lysine residue, N6-lysine residue, methionine residue, phenylalanine residue, proline residue, serine residue, threonine residue, tryptophane residue, tyrosine residue, valine residue, and the like.

The "hydroxyimino-substituted lower alkyl" includes a hydroxyimino-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, hydroxyiminomethyl, 1-hydroxyiminoethyl, 2-hydroxyiminoethyl, 3-hydroxyiminopropyl, 4-hydroxyiminobutyl, hydroxyiminopentyl, 6-hydroxyiminohexyl, l,l-dimethyl-2hydroxyiminoethyl, 2-methyl-3-hydroxyiminopropyl, and the like.

64 WO 94/01113 PCT/JP93/00835 The "halogen-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by one to three halogen atoms, for example, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxy, 2-chloroethoxy, 2,2,2trifluoroethoxy, 2,2,2-trichloroethoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy, 3-chloro-2-methylpropoxy, 6-bromohexyloxy, 5,6-dichlorohexyloxy, and the like.

The "phenyl(lower)alkoxycarbonyl" includes a phenylalkoxycarbonyl wherein the alkoxycarbonyl moietyl is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, benzyloxycarbonyl, 2phenylethoxycarbonyl, 1-phenylethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl, carbonyl, 6-phenylhexyloxycarbonyl, l,l-dimethyl-2-phenylethoxycarbonyl, 2-methyl-3-phenylpropoxycarbonyl, and the like.

The "lower alkoxy(lower)alkoxy which is substituted by one or two substituents selected from hydroxy and an amino being optionally substituted by a lower alkyl" includes an alkoxy-alkoxy group wherein both alkoxy moieties are each a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by one or two substituents selected from hydroxy and an amino being optionally substituted by a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, WO94/01113 65PCr/JP93/OO835 hydroxymethoxymethoxy, 2-hydroxyethoxy)propoxy, 4-ilhydroxyethoxy)butoxy, 6-(3-hydroxypropoxy)hexyloxy, 5-(2,3dihydroxypropoxy)pentyloxy, 1,J.-direthyl-2-(4-hydroxybutoxy)ethoxy, 2-methyl-3-(3,4-dihydroxybutoxy)propoxy, 2l-dimethyl--2-hydroxyethoxy)ethoxy, methoxy, (6-hydroxyhexyloxy)methoxy, (2-methyl-3--hydroxypropoxy)methoxy, aminomethoxymethoxy, 2-(l-aminoethoxy)ethoxy, 1-(2-aminoethoxy)ethoxy, 3-(3-aminopropoxy)propoxy, 4-(4-aminobutoxy)butloxy, 5-(5-arninopentyloxy)pentyloxy, 6- (6-arinohexyloxy)hexyloxy, (1,l-dimethyl--2-arninoethoxy)methoxy, (2-methyl-3-aminopropoxy)methoxy, l,l-dimethyl-2- (methylaminomethoxy)ethoxy, 2-methyl-3-(ethylaminoxnethoxy)propoxy, propylaminomethoxymethoxy, isopropylaminomethoxy)ethoxy, 2-(butylaminomethoxy)ethoxy, 3-(tert--butylaminomethoxy)propoxy, 4-(pentylaminornethoxy)butoxy, (hexylaminomethoxy)pentyloxy, 6-(dimethylarninomethoxy)hexyloxy, l,1-dimethyl--2-(diethylaminornethoxy)ethoxy, 2methyl-3-(dipropylaminomethoxy)propoxy, dibutylaniinornethoxyrnethoxy, l-(dipentylaminomethoxy)ethoxy, 2-(dihexylarninomethoxy)ethoxy, 3-(N-methyl-N-ethylaminornethoxy)propoxy, 4- (N-methyl-N-propylarninomethoxy)butoxy, aminornethoxy)pentyloxy, 6-(N-methyl-N-hexylaminomethoxy)hexyloxy, (l-methylaminoethoxy)methoxy, 2-ethylaminoethoxy)ethoxy, 2-(3-propylaminopropoxy)ethoxy, 3-(4-butylaminobutoxy)propoxy, 4-(1,l-dimethyl-2-pentylaminoethoxy)buoy 5 5-hexylaminopentyloxy )pentyloxy, 6- (6-dirnethylaminohexyloxy)hexyloxy, 2-diethylarninoethoxy)propoxy, 4- [2-(N-rethyl-N-hexylamino)ethoxy~butoxy, 5-(3-dihexylamino- Wn QAIM 111 66 WA QAAhlia66 Cri/P93/00835 propoxy)pentyloxy, 6-(4-dibutylaminobutoxy)hexyloxy, 3-12- (N-rnethyl-N-pentylamino) ethoxyipropoxy, 2-hydroxy-3dimethylaminopropoxy)pentyloxy, 2-hydroxy-3-diethylaminoporopoxy)pentyloxy, 2-hydroxy-3-diethylaminopropoxy)propoxy, 4-(3-hydroxy-4-methylaminobutoxy)butoxy, 5-(4methylaminopentyloxy)hexyloxy, and the like.

The "morpholinyl-substituted lower alkoxy which may optionally have a substituent selected from a lower alkyl and oxo" includes a morpholinyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which may optionally have one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atom:, and an oxo group, for example, (2morpholinyl)methoxy, 2-(3-morpholinyl)ethoxy, l-(3morpholinyl)ethoxy, 3-(2-morpholinyl)propoxy, 4-(3morpholinyl)butoxy, 5-(2-morpholinyl)pentyloxy, 6-(3morpholinyl)hexyloxy, 1,1-dimethyl-2-C3-morpholinyl)ethoxy, 2-methyl-3-(2-morpholinyl)propoxy, 6-(l-methyl-5-oxo-3morpholinyl)hexyloxy, (l-ethyl-2-morpholinyl)methoxy, 2-(2oxo-3-morpholinyl)ethoxy, l-(2-propyP-3-morpholinyl)ethoxy, 3- (3-butyl-2-morpholinyl )propoxy, 4- (5-pentyl-3morpholinyl)butoxy, 5-(6-hexyl--2-morpholinyl)pentyloxy, 3- (S-oxo-l-propyl--2-morpholinyl)propoxy, 2-oxo-l-butyl-3morpholinyl)butoxy, 5-(3-oxo-l-pentyl-6-morpholinyl)pentyloxy, 2-oxo-l-hexyl-5-morpholinyl)hexyloxy, and the like.

The "benzimidazolylthio-substituted lower alkoxy" WO 94/01113 67- PCr/JP93/00835 includes a benzimidazolylthio-substituted straight chain or branched chain alkoxy group having 2. to 6 carbon atoms, for example, (benzimidazol-2-yl)thiomethoxy, l-(benzimidazol-4yl)thioethoxy, 2-(benzimidazol-5-yl)thioethoxy, 3- (benzirnidazol-6-yl)thiopropoxy, 4-(benzimidazol--2-yl)thiobutoxy, 5-(benzimidazol-7-yl)thiopentyloxy, 6-(benzimidazol- 2-yl)thiohexyloxy, 1,l-dimethyl-2-(benzimidazol-2-yl)thioethoxy, 2-methyl-3- (benzimidazol-2-yl )thiopropoxy, and the like.

The "benzimidazolylsulfinyl-substituted lower alkoxy" includes a benzimidazolylsulfinyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (benzimidazol-2-yl)sulfinylmethoxy, l-(benzimidazol-4-yl)sulfinylethoxy, 3- (benzimidazol-6--yl)sulfinylpropoxy, 4-(benzimidazol-2-yl)sulfinylbutoxy, 5-(benzimidazol-7-yl)sulfinylpentyloxy, 6- (benzimidazol-2-yl )sulf inylhexyloxy, 1, l-dimethyl-2- (benzimidazol-2-yl)sulfinylethoxy, 2-methyl-3-(benzimidazol- 2-yl)sulfinylpropoxy, and the like.

The "tetrahydropyranyl-substituted lower alkyl" includes a tetrahydropyranyl-substituted straight chain or branched chai,. alkyl group having 1 to 6 carbon atoms, for example, 3- or 4-tetrahydropyranyl)methyl, 3- or 4-tetrahydropyranyl)ethyl, 3- or 4-tetrahydropyranyl)ethyl, 3- or 4-tetrahydropyranyl)propyl, 4- 3- or 4-tetrahydropyranyl)butyl, 3- or 4-tetrahydropyranyl)pentyl, 3- or 4-tetrahydropyranyl)hexyl, 1,1-dimethyl-2-(2-, 3- or 4-tetrahydropyranyl)ethyl, 2- 68 WO 94/01113 PCT/JP93/00835 methyl-3-(2-, 3- or 4-tetrahydropyranyl)propyl, and the like.

The or 6-membered saturated heterocyclic group which is formed by binding R 14 and R 15 together with the nitrogen atom to which they bond with being intervened or not with nitrogen, oxygen or sulfur atom" includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and the like.

The "heterocyclic group having a substituent selected from carbamoyl, a lower alkyl, a phenyl(lower)alkyl, phenyl and a hydroxy-substituted lower alkyl" includes the above-mentioned heterocyclic groups which have one to three substituents selected from a carbamoyl group, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenyl group and a hydroxy-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, 4-phenylpiperazinyl, 2-phenylpyrrolidinyl, 4-phenylpiperidinyl, 3-phenylmorpholino, 3phenylthiomorpholino, 4-benzylpiperazinyl, 3-(2-phenylethyl)pyrrolidinyl, 2-(3-phenylpropyl)pyrrolidinyl, 4-(4phenylbutyl)piperidinyl, 3-(5-phenylpentyl)morpholino, 2-(6phenylhexyl)thiomorpholino, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 2-hexylthiomorpholino, 4ethylpiperazinyl, 3-methyl-4-phenylpiperazinyl, 3-ethyl-4- WO 94/01113 6Ppcr/aP93/0083S benzylpiperidinylt 3-methyl-4-benzylpyrrolidinyll 3-methyl- 3-methyl-5-( morpholino, 4-(2-hydroxyethyl)piperazinyl, 2-(hydroxyiethyl)pyrrolidinyl, 4-(4-hydroxybutyI)piperi6>inyl, hydroxypentyl)thicmorpholino, 3-(6-hydroxyhexyllmocpholino, 2-methyl-4- (2-hydroxyethyl )pyr rolidinyl, 2-carbamoylpyrrolidinyl, 3-carbamoylpyrrolidinyl, 4-carbamoylpiperazinyl, 3-carbamoylpiperazinyl, 2-carbamoylpipera-.inyl, 4-carbamoylpiperidinyl, 3-carbamoylpiperidinyl, 2-carbamoylpiperidinyl, 3-car1tamoylmurpholino, 2-carbamoylthiomorpholino, 2-methyl-3-carbamoylpyrrolidinylI 3-methyl- 4-carbamoylpiperidinyl, 2,6-dimethyl-4-carbamoylpiperazinylI and the like.

The "amino having optionally a phenyl(lower)alkoxycarbonyl substituent" includes an amino group which may optionally have a substituent of a phenylalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, amino, benzyloxycarbonylamino, (2phenylethoxycarbonyl)amino, (l-phenylethoxycarbonyl)amino, (3-phenyjlpropoxycarbonyl)amino, (4-phenylbutoxycarbonyl)amino, (5-phenylpentyloxycarbonyl )aminoI (6-phenyihexyloxycarbonyl)amino, (l11-dimethyl-2-phenylethoxycarbonyl)amino, (2-methyl-3-phenylpropoxycarbonyl)amino, and the like.

The "phenyl having optionally hydro-:y substituent" includes a phenyl group having optionally one~ to three hydroxy-substituents, for example, phenylt 4-hydroxyphenyl, 3-hydroxyphenyl, 2-hydroxyphenyl, 2,4-dihydroxyphenyll 3,4- WO 94/01113 Cr/JP93/0083S dihydroxyphenyl, 213t4-trihydroxyphenyl, arnd the like.

The "phenylsujlfonyl wherein the phenyl ring may optionally have a substituent selected from a lower alkyl, nitro, and an amino having optionally one or two substituents selected from a lower alkanoyl and lower alkvl" includes a phenylsulfonyl group wherein the phenyl ring may optionally have one to three substitutents selected -'rom a straight chain or branched chain altlyl group having 2. to 6 carbon atoms, a nitro group, and an amino group having optionally one or two subztituents selected from a otraight chain or branched chain alkanoyl group ,"aving 1 to 6 carbon atoms and a straight chain or branched chain alkyl group having I to 6 carbon atoms, for example, phenylsulfonyl, 2methyiphenylsulfonyl, 3-methylp~enylaulfonyl, 4-mothylphenylsulfonyl, 2-ethylphenylsulfonyl, 3-ethylphenyls~lfonyl, 4-ethyiphanylsulfonyl, 4-isopropylphenyl.&ulfonylt 4-butylphenylsulfonyl, 2-pentylphenylsulfonyl, 3-hoxvlphenylsulfonyl, 2,4-dimethyiphenylsulfonyl# 3,4-diethylphenylsulfonyl, 3#415-tritrethylphenylsulfonylt 4-ami~nophenylsulfonyl, 3-aminophenylsulfonyl, 2-aminophenylsulfonyl, 3, 4-diaminophenylsulfonyl, 2, sulfonyl. 2,4 ,6-triaminophenylsulfonyl, 4-nitropheny:sulfonyl, 3-nitrophenyisulfonylt 2-nitrophenylsulf4onyl, 2,3dinitrophenylsulfonyl, 2,6-dinitrophenylsulfonyl, 2,4,6trini trophenylsulfonyl, 4-acetylamitnopherylsulfonyl, 4dirnethylaminophenylsultonyl# 3-(N-methyl-N-acetylamino)phenylzulfonyl, 2-methyl-4-aminophenylsulforyl, 3-nitro-4methyl-ohenylsultonyl, 2-ethylaminophenylsul'Oonyl, 2-methyl- -71 WO 94/0 h4 I I~ VISA A)PCIJ P93/0083S 3-diethylaminophenylsulfonyl, and the like.

The "amino-substituted lower alkyl which may optionally have a substituent selected from a lower alkyl and a lower alkanoyl"' includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having I to 6 carbon atoms, for example, aminomethyll 2-aminoethyl, 1-arninoethyll 3-aminoprop 1, 4-aminobutyl, 5-aminopentyll 6-aminohexyl, l1l-dimethyl-2-aminoethylt 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3isopropylaminopropyl, 4-butylaminobutyll pentyl, 6-hexylaminohexyl, dime thylarminomethyl, (N-ethyl-Npropylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl, 2- (acetylamino)ethyl, 3-(acetylamino)propyl, formylaminomethyl, l-(propionylamino)ethyl, 4-(butyrylamino)butyl, (pentanoylamino)pentyll 5-(hexanoylamino)hexyl, 2-(N-methyl- N-acetylamino)ethyl, l-(N-ethyl-N-acetylamino)ethyl, and thie like.

The "piperidinyl having optionally a phenyl(lower)alkyl substituent" IThcludes a piperidinyl which has optionally a substituent of a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atomst for example, 4-piperidinyl, 3-piperidinyl, 2-piperidinyl, l-benzyl-4-piperidinyl, 1- (2-phenylethyl)-3-piperidinyl, 2-(3-phenylpropyl)-S- IUA OA IAI 11-2 72 ~v~J PC/JP93/00835 piperidinyll 3-(4-phenylbutyl)-6-piperidinylI pentyl)-3-piperidinyl, 5-(6-pheaylhexyl)-4-piperidinylI 2benzyl-4-piperidinyl, l-(3-phenylpropyl)-4-piperidinyl, and the like.

The includes an imidazot4,5-c)pyridylcarbonylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (imidazo(4,5-c)pyridin-2-yl)carbonylmethoxy, 2-(imidazot415clpyridin-2-yl)carbonylethoxy, l-(imidazo(4,5-clpyridin-4yJ.)carbonylethoxy, 3-(imidazof4,5-clpyridin-5-yl)carbonylpropoxy, 4-(imidazo(4,5-clpyridin-7-yl)carbonylbutoxy, (imidazof4,5-clpyridin-2-yl)carbonylpentyloxy, 6-(imidazo- 4 i 5 -clpyridin-2-yl)carbonylhexyloxy, l,1-dimethyl-2- (imidazof4,5-clpyridin-2-yl)carbonylethoxy, 2-methyl-3- (imidazo(4,5-clpyridin-2-yl)carbonylpropoxy, and the like.

The "tri(lower alkyl)ammonium" includes an ammnonium group having three of a straight chain or branched chain alkyl. group having 1 to 6 carbon atoms, for examplet trimethylammonium, triethylamxnonium, tripropylamionium, triisopropylammonium, tributylammonium, tri(tert-butyl)ammnonium, tripentylammonium, trihexylamnonium, dimethylethylammonium, diethyipropylamnonium, dimethylbutylamnoniun, diethylmethylamionium, dimethyihexylamionium, dipropylmethylammonium, dibutylethylamnoniun, methylethylpropylamnionium, methylbutylpentylammonium, and the like.

The "pyridyl(lower)alkylI include a pyridylalkyl group wherein the alkyl. moiety is a straight chain or WO 94/01113 73-PCr/JP93/00835 branched chain alkyl. group having 1 to 6 carbon atoms, for example, (2-pyridyl)methyl, (3-pyridyl)methyl, (4-pyridyl)methyl, 2-(2-pyridyl)ethyl, 1-(3-pyridyl)ethyl, 3-(4pyridyl)propyl, 4-(2-pyridyl)butyll S-(3-pyridyl)pentyl, 6- (4-pyridyl)hexyl, 1,1-dimethyl-2'-(2-pyridyl)ethyl, 2-methyl- 3-(3-pyridyl)propyll and the like.

The "lower alkyl which may optionally have a substituent selected from hydroxy and cyano"l includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which may optionally have one to three substituents selected from a hydroxy group and a cyano group, for example, hydroxymethyl, 2-hydroxyethylt l-hydroxyethyl, 3hydroxypropylt 2, 3-dihydroxypropyl, 4-hydroxybutyl, 1,1dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, pentyl, 6-hydroxyhexyll 1-hydroxyisopropyl, 2-methyl-3hydroxypropyl, 2,3-dihydroxyethyl, 3,4-dihydroxybutyl, 5,6dihydroxyhexyl, cyanomethyl, 2-cyanoethyl, 1-cyancethyl, 3cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl, dimethyl-2-cyanoethyl, 2-methyl-3-cyanopropylt and the like.

The "lower alkynyl" includes a straight chain or branched chain alkynyl group having 2 to 6 carbon atoms, for example, ethynylt 2-propynyl, 2-butynyl, 3-butynyl, Imethyl-2-propynyl, 2-pentynyl, 2-hexynyl, and the like.

The "pyrrolidinylcarbonyl which may optionally be substituted by a phenyl(lower)alkoxycarbonyl on the pyrrolidine ring" includes a pyrrolidinylcarbonyl which may optionally be substituted by a phenylalkoxycarbonyl group on the pyrrolidine ring wherein the alkoxy moiety is a straight WO 94/01113 74 PCrJP93/00835 chain or branched chain a).koxy group having 1 to 6 carbon atoms, for example, l-benzyloxycarbonyl-2-pyrroalidinylcarbonyl, 2-pyrrolidinylcarbonyl, 1-pyrrolidinylcarbonyl, 3pyrrolidinylcarbonyl, 1- (2-phenylethoxycarbonyl pyrrolidinylcarbonyl, l-phenylethoxycarbonyl)-lpyrrolidinylcarbonyl, 3- (3-phenylpropoxycarbony pyrrolidinylcarbonyl, 1-(4-phenylbutoxycarbonyl)-2pyrrolidinylcarbonyl, pyrrolidinylcarbonyl, 2-(6-phenylhexyloxycarbonyl)-3pyrrolidinylcarbonyl, and the like.

The "phenyl (lower) alkoxycarbonylamino" includes a phenylalkoxycarbonylamino wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, N-benzyloxycarbonylamino, N-(2-phenylethoxycarbonyl)amino, N-(l-phenylethoxycarbonyl)amino, N-(3-phenylpropoxycarbonyl)amino,

N-

(4-phenylbutoxycarbonyl)amino, carbonyl)amino, N-(6-phenylhexyloxycarbonyl)anino, dimethyl-2-phenylethoxycarbonyl)amino, 2-methyl--3-phenyl-.

propoxycarbonyl)amino, and the like.

The "lower alkyl having optionally a hydroxysubstituent" includes a straight chain or branched chain alkyl group having I to 6 carbon atoms which has optionally one to three hydroxy-substituents, for example, in addition to the above-mentioned lower alkyl groups, hydroxynethyl. 2hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3dihydroxypropyl, 4-hydroxybutyl, 1,l-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxy- WO 94/01113 75- PCr/J P93/00835 hexyl, 1-hydroxyisopropyll 2-methyl-3-hydroxypropyl, 2,3dihydroxybuty., 3 ,4-dihydroxyhexyl, 5, 6-dihydroxyhexyl, 2,3,4-trihydroxybutyl, and the like.

The "hydroxy-substituted lower alkanoyl" indlutes a hydroxy-substituted straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, 2hydroxyacetyl, 3-hydroxypropionyl, 2-hydroxypropionyl, 4hydroxybutyryl, 2, 2-dinethyl-3-hydroxypropionyl, pentanoyl, 6-hydroxyhexanoyl, 3-iethyl-4-hydroxybutyryl, and the like.

The "lower alkanoyloxy(lower)alkanoyl" includes an alkanoyloxy-substituted alkanoyl wherein both alkanoyl moieties are a straight chain or branched chain alkanoy.

group having 2 to 6 carbon atoms, for example, 2-acetyloxyacetyl, 3-propoionyloxypropionyl, 2-butyryloxypropionyl, 4pentanoyloxybutyryl, 2,2-dimethyl-3-hexanoyloxypropionyl, acetyloxypentanoyl, 6-propionyloxyhexanoyl, and the like.

The "phenyl(lower)alkyl wherein the phenyl ring may optionally has a lower alkoxy substituent" includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon~ atoms and the phenyl ring has optionally one to three substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, in addition to the above-mentioned phenyl(lower)alkyl groups, 2-methoxybenzy., 3-methoxybenzyl, 2-(4-methoxyphenyl)ethyl, 2ethoxyphenyl)ethyl, 3-(4-isopropoxyphenyl)propyl, 4-(3pentyloxyphenyl)butyl, 5-(4-hexyloxyphenyl)pentyl, 6-(2- WO 94/01113 6-PCr/J P93/00835 butyloxyphenyl)hexyl, 3 ,4-dimethoxybenzyl, 3-ethoxy-4rnethoxybenzylt 2,3-dimethoxybenzyl, 2,6-dimethoxybenzyl, 3,4,5-trimethoxybenzyl, and the like.

The "cycloalkenylcarbonyl" includes a cycloalkenylcarbonyl group having 3 to 8 carbon atoms, for example, cyclopropenylcarbonyl, cyclobutenylcarbonyl, cyclopentenylcarbonyl, cyclohexenylcarbonyl, cycloheptenylcarbonyl, cyclooctenylcarbonyl, and the like.

The "pyrimidylthio-substituted lower alkoxy" includes a pyrimidylthio-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyrimidyl) thiomethoxy, 2-(4-pyrimidyl)thioethoxy, 1-(5-pyrimidyl)thioethoxy, 3-(6-pyrimidyl)thiopropoxy, 4-(4-pyrimidyl)thiobutoxy, 5-(2-pyrimidyl)thiopentyloxy, 6-(5-pyrirnidyl)thiohexyloxy, l,l-dimethyl-2-(2pyrimidyl)thioethoxy, 2-rnethyl-3-(2-pyririyl)thiopropoxy, and the like.

The "pyrimidylsulfinyl-substituted lower alkoxy" includes a pyrimidylsulfinyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyrimidyl)sulfinylmethoxy, 2-(4-pyrirnidyl)sulfi4nylethoxy, l-(5-pyrimidyl)sulfinylethoxy, 3-(6pyrimidyl)sulfinylpropoxy, 4-(4-pyrimidyl)sulfinylbutoxy, (2-pyrimidyl)sulfinylpentyloxy, hexyloxy, l,l-dimethyl-2-(2-pyrimidyl)sulfinylethoxy, 2methyl-3-(2-pyrimidyl)sulfinylpropoxy, and the like.

The "pyrimidylsulfonyl-substituted lower alkoxy" includes a pyrimidylsulfonyl-substituted straight chain or -77 WO 94/01113 PCT/J P93/00835 branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyrimidyl)sulfonylmethoxy, 2-(4-pyrimidyl)suJlfonylethoxy, 1-(5-pyrimidyl)sulfonylethoxy, 3-(6pyrimidyl)sulfonylpropoxy, 4-(4-pyrimidyl)sulfonylbutoxy, (2-pyrimidyl)sulfonylpentyloxy, hexylo.y, 1,l-dimethyl-2-( 2-pyrimidyl)sulfonylethoxy, 2methyl-3-(2-pyrimidyl)sulfonylpropoxy, and the like.

The "imidazolylthio-substituted lower alkoxy which may optionally have a lower alkyl substituent" includes a imidazolylthio-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which may optionally have a substituent of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms on the imidazolyl group, for example, (2-imidazolyl)thiomethoxy, 2-(4imidazolyl)thioethoxy, 1-(5-imidazolyl)thioathoxy, 3-(2imidazolyl)thiopropoxy, 4-(4-imidazolyl)thiobutoxy, 5-(2imidazolyl)thiopentyloxy, 6-(5-imidazolyI)thiohexvloxy, 1,1dimethyl-2- (2-imidazolyl) thioethoxy, 2-methyl-3- (2-imidazolyl)thiopropoxy, (4-methyl-2-imidazolyl)thiomethoxy, ethyl-4-imidazolyljthioethoxy, thioethoxy, l-butyl-2-imidazoly.) thiopropoxy, 4- (2pentyl-4-imidazolyl)thiobutoxy, 5-(l-methyl-2-imidazolyl)thiopentyloxy, 6- (l-hexyl-5-imidazolyl) thiohexyloxy, 1,1dimethyl-2- Cl-ethyl-2-imidazolyl) thioethoxy, 2-methyl-3-(lpropyl-2-imidazolyl)thiopropoxy, and the like.

The "imidazolylsulfonyl-substitute6 lower alkoxy which may optionally have a lower alkyl substituent" includes a imidazolylsul.fonyl-substituted straight chain or -78 WO 94/01113 PCT/J P93/00835 branched chain alkoxy group having 1 to 6 carbon atoms which may optionally have a substituent of a straight chain or branched chaii 4 alkyl group having 1 to 6 carbon atoms on the imidazolyl group, for example, (2-imidazolyl)sulfonylmethoxy, 2-(4-imidazolyl)sulfonylethoxy, sulfonylethoxy, 3-(2-imidazolyl)sulfonylpropoxy, 4-(4ixidazolyl)sulfonylbutoxy, 5-(2-imidazolyl)sulfonylpentyloxy, 6-(5-imidazolyl)sulfonylhexyloxy, l,1-dimethyl-2-(2imidazolyl)sulfonylethoxy, 2-methyl-3-( 2-imidazolyl)sulfonylpropoxy, (4-methyl-2-imidazolyl)sulfonylmethoxy, 2- (5-ethyl-4-imidazolyl) sulfonylethoxy, 1- imidazolyl)sulfonylethoxy, 3-(l-butyl-2-imidazolyl)sulfonylpropoxy, 4- (2-pentyl-4-imidazolyl )sulfonylbutoxy, 5- (1methyl-2-imidazolyl)sulfonylpentyloxy, imidazolyl)sulfonylhexyloxy, 1,1-dimethyl--2-(1-ethyl-2imidazolyl)sulfonylethoxy, 2-methyl-3-(l--propyl-2imidazolyl)sulfonylpropoxy, and the like.

The "ammonium-substituted lower alkoxy having three substituents selected from a lower alkyl, a lower alkenyl and oxo" includes an ammnonium-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, which have three substituents selected from a straight chain or branched chain alkyl group having I to 6 carbon atoms, a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, and an oxo group, for example, trimethylaminoniummethoxy, 2-(triethylammonium)ethoxy, 1-(tripropylammonium)ethoxy, 3-(tributylammonium)propoxy, 4-(tripentylamxnonium)butoxy, 5-(triethylamxnonium)pentyloxy, 6-(trihexyl- -79- WO 94/01113 rCr/JP93/00835 ammonium)hexyloxy, 1,l-dimethyl-2-(triallylamruonium)ethoxy, 2-rethyl-3-(tributenylanuuonium)propoxy, tri(l-methylallyl)anunonium-methoxyf 2 -[tri(2-pentenyl)ammoniumlethoxy, 1-[tri- (2-hexenyl)amxnoniumlethoxy, 3-(N-allyl-N,N-dimethylamznonium)propoxy, 4-(N,N-diallyl-N-rnethylammonium)butoxy, (N-a!2,!y-N-methylaminc)pentyloxy N-oxide, 6-(N-allyl-Nethylamino)hexyloxy N-oxide, ammonium)pentyloxy, and the Ilke.

The "phenylthio(lower)alkoxy wherein the phenyl.

ring may optionally have a substituent selected from nitro and an amino"' includes a phenylthioalkoxy wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, and the phenyl ring may optionally have one to three substituents selected from a nitro group and an amino group, for example, phenylthiomethoxy, 2-phenylthioethoxy, l-phenylthioethoxy, 3-phenylthiopropoxy, 4-phenyithiobutoxy, 5-pheny2lthiopentyloxy, 6phenyithiohexyloxyt a,l-dimethyl-2-phenylthioethoxy, 2methyl-3-phenylthiopropoxy, (2-nitrophenyl)thiomethoxy, 2- (3-ritrophenyl)thioethoxy, l-(4-nitrophenyl)thioethoxy, 3- (2,3-dinitrophenyl)thiopropoxy, 4-(3,4-dinitrophenyl)thiobutoxy, 5-(4-nitrophenyl)thiopentyloxy, 6-(2,6-dinitrophenyl)thiohexyloxy, l,l-dimethyl-2-(2,4,6-trinitrophenyl)thioethoxy, 2-methyl-3-(4-nitrophenyl)thioporopoxy, (2aminophenyl)thioiethoxy, 2-%3-aminophenyl)thioethoxy, l-(4aminophenyl)thioethoxy, 3-(2,3-diaminophenyl)thiopropoxy, 4- (3,4-diaminophenyl)thiobutoxy, 5-(4-aminophenyl)thiopentyloxy, 6-(2,6-diaminophenyl)thiohexyloxy, 1,1-dimethyl-2- 80 WO 94/01113 PCT/JP93/00835 (2,4,6-triaminophenyl)thioethoxy, 2-methyl-3-(4-aminophenyl)thiopropoxy, and the like.

The "phenylsulfonyl(lower)alkoxy wherein the phenyl ring may optionally have a substituent selected from nitro and an amino having optionally one or two substituents selected from a lower alkanoyl and a lower alkyll" includes a phenylsulfonylalkoxy wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, and the phenyl ring may optionally have one to three substituents selected from a nitro group and an amino group having opitonally one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, phenylsulfonylmethoxy, 2-phenylsulfonylethoxy, 1-phenylsulfonylethoxy, 3-phenylsulfonylpropoxy, 4-phenylsulfonylbutoxy, phenylsulfonylpentyloxy, 6-phenylsulfonylhexyloxy, 1, 1dimethyl-2--phenylsulfonylethoxy, 2-methyl-3-phenylsulfonyapropoxy, (2-aminophenyl)sulfonylmethoxy, 5-(4-aminophenyl)sulfonylpentyloxy, 2-(4-methylaminophenyl)sulfonylethoxy, 1- (3-ethylaminoohenyl )sulfonylethoxy, 3- (N-methyl-N-ethylaiino)phenyl~sulfonylpropoxy, 4-f3-(N-methyl-N-hexylamino)phenylisulfonylbutoxy, 5-(4-dimethylaminophenyl)sulfonylpentyloxy, 4-dipentylaminophenylsulfonylnethoxy, 2isopropylaminophenyl)sulfonylethoxy, l-(3-butylaminbphenyl)sulfonylethoxy, 5- 4-diaminophenyl) sulfonylpentyloxy, 3- [2,3-bis(dimethylamino)phenyllsulfonylpropoxy, 4-[3,4-bis- (methylamino)phenyl~sulfonylbutoxy, 5-(2,4,6-triainino- WO 94/ 01113 PCTIJ P93/00835 phenyl)sulfonylpentyloxy, 6-(3,4,5-tri(methylamino)phenyl)sulfony'ihexyloxy, 5-(4-acetylaminophenyl)sulfonylpentyloxy, 3-[4-(N-methyl-N-acetylamino)phenyllsulfonylpropoxy, 5-14nitrophenyl)sulfonylpentyloxy, 2-(4-nitro-3-methylaminophenyl)sulfonylethoxy, 3-(2,4-dinitrophenyl)sulfonylpropoxy, 4-(2,4,6-trinitrophenyl)sulfonylbutoxy, and the like.

The "pyridylthio-substituted lower alkoxy" includes a pyridyithia-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2pyridyl'jthiomethoxy, 2-(3--pyridyl)thioethoxy, l-(4--pyridyl)thioethoxy, 3-(3-pyridyl)thiopropoxy, 4-(4-pyridyl)thiobutoxy, 5-(2-pyridyl)thiopentyloxy, 5-(4-r.;vridvl)thiopentyloxy, 6-(3-pyridyl)thiohexyloxy, l,1-dime~oyl-2-(2-pyridyl)thioethoxy, 2-methyl-3--(4-pyridyl)thiopropoxy, and the like.

The "1pyridylsulfonyl-substituted lower alkoxy which may optionally have an oxo, subsituent on the pyridine ring" includes a pyridylsulfonyl-substituted straight chain or branched chain alkoxy group having I to 6 carbon atoms which may optionally have an oxo substituent on the pyridine ring, for example, (2-pyridyl)sulfonylmethoxy, 2-(3-pyridyl)sulfonylethoxy, l-(4-pyridyl)sulfonylethoxy, 3-(3-pyridyl)sulfonylpropoxy, 4-(4-pyridyl)sulfonylbutoxy, 5-(2-pyridyl)sulfonylpentyloxy, 5-(4-pyridyl)sulfonylpentyloxy, 6-(3pyridyl)sulfonylhexyloxy, l,1-dimethyl-2-(2-pyridyl)sulfonylethoxy, 2-methyl-3-(4-pyridyl)sulfonylpropoxy, S-(loxido-4-pyridyl)sulfonylpentyloxy, (4-oxo-2-pyridyl)sulfonylmethoxy, 2-(l-oxo-3-pyridyl)sulfonylethoxy, l-(2oxo-4-pyridyl )sulfonylethoxy, 3- (2-oxo-3--pyridyl) sulfonyl- 82 WO 94/01113 PCT/J P93/00835 propoxy, 4 -(3-oxo-4-pyridyl)sulfonylbuto.<y, 5-(l-oxido-2pyridyl)sulfonylpentyloxy, 6-(l-oxido-3-pyridyl)sulfonylhexyloxy, and the like.

The "cycloalkylcarbonyl having optionally one to three substituents selected from hydroxy and a lower alkanoyloxy"l includes a cycloalkylcarbonyl having 3 to 8 carbon atoms which has optionally one to three substituents selected from a hydroxy group and a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, for example, cyclopropylcarbonyl, cyclobutylcar; -,nyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, 2-hydroxycyclopropylcarbonyl, 3-hydroxycyclobutylcarbonyl, 2-hydroxycyclopentylcarbonyl, 3-hydroxyc ,clopentylcarbonyl, 2,4-dihydroxycyclopuentylcarbonyl, 2-hydroxycyclohexylcarbonyl, 3-hydroxycyclohexylcarbonyl, 4-hydroxycyclohexylcarbonyl, 3,4-dihydroxycyclohexylcarbonyl, 2,4-dihydroxycyclohexylcarbonyl, dihydroxycyclohexylcarbonyl, 3, 4, carbonyl, 3-hydroxycycloheptylcarbonyl, 3, 4-dihydroxycycloheptylcarbonyl, 2,3,4-trihydroxycycloheptylcarbonyl, 4hydroxycyclooctylcarbonyl, 4 4, 5,6-trihydroxycyclooctylcarbonyl, 2-acetyloxycvclopropy.carbonyl, 3-propionyloxycyclobutylcarbonyl, 2-butyryloxycyclopentylcarbonyl, 3-pentanoyloxycyclopentylcarbonvl, 2, 4dihexanoyloxycyclopentylcarbonyl, 2-acetyloxycvclohexylcarbonyl, 3-propionyloxycyclohexylcarbonyl, 4-butyryloxvcyc'Lohexylcarbonyl, 3,4-diacetyloxycyclohexylcarbonyl, 2,4diacetyloxycyclohexylcarbonyl, 2, WO 94/01113 PCria P93/00835 carbonyll 3,4,5-triacetyloxycyclohexylcarbonyl, 3,4- 3-pentarioyloxycycloheptylcarbonyl, 3,4-diacetyloxycycloheptylcarbonyl, 2,3,4tripropionyloxycycloheptylcarbonyl, 4-hexanoyloxycyclooctylcarbonyl, 4 ,5-dibutyryloxycyclooctylcarbonyl, 4,5,6triacetyloxycyclooctylcarbonyl, and tne like.

The "tetrahydroypyranyl(lower)alkyl wherein the tetrahyd&roxypyranyl ring may optionally have one to four substituents selected from hydroxy and a lower alkoxy" includes a tetrahydropyranylalkyl wherein the alkyl moiety is a straight chain or branched chain alkyl group having I to 6 carbon atoms, and the tetrahydropyranyl ring may optionally have one to four substituents selected from a hydroxy group and a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-tetrahydropyranyl)methyl, 2-(3-tetrahydrorvranyl)ethyl, tetrahydropyranyl)ethyl, 3-(2--tetrahydropyranyl)propyl, 4- (3-tetrahydropyranyl)butyll 5-(4-tetrahydropyranyl)pentyl, 2-tetrahydropyranyl)hexyl, 1,1-di thyl-2-(3-tetrahydropyranyl)ethyl, 2-methyl-3-(4-tetrah Lropyranyl)propyl, (3hydroxy-2-tetrahydropyranyl)methyl, 2,4-dihydroxy-3tetrahydropyranyl)ethyl, 1-(2,3,5-trihydroxy-4-tetrahydropyranyl)ethyl, 3-(6-methoxy-2-tetrahydropyranyl)propyl, 4- (4-ethoxy-3-tetrahydropyranyl)butyl, 5-(4,6-di~iethoxy-4tetrahydropyranyl)pentyl, 6-(4,5,6-trimethoxy-2-tetrahydropyranyl)hexyl, l,l-dimethyl-2-(2-propoxy-3-tetrahydropyranyl)ethyl, 2-methyl-3-( 6-butoxy-4-tetrahydropyranyl)propyl, (6-pentyloxy-2-tetrahydropyranyl)methyl, 2-(4- WO 94101113 84 CraP93/00835 hexyloxy-3-tetrat opyranyl)ethyl, 2-(3,4,5-trihydroxy-6methoxy-2-tetrahydropyranyl)methylI l-(30,5,6-tetrahydroxy- 2-tetrahydropyranyl)ethyll 3-(3,4,5,6-tetramet.hoxy-2-tetrahydropyranyl)propyl, and the like.

Thie "lower alkanoyl substituted by a 5- or 6memnbered saturated heterocyclic group selected from pyrrolidinyl, piperazinyl, piperidinyl, and morpholinyl" includes a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms which is substituted by a 5- or 6-niembered saturated heterocyclic group selected from piperazinyl, piperidiriyl, and morpholinyl, for example, 2- (l-pyrrolidinyl)acetyll 3-(2-r-yrrolidinyl)propionyl, 2-(3pyrrolidinyl)propionyl, 4-(l-pyrrolidinyl)butyrylt 2,2dimethiyl-3-(2-pyrrolidinyl)propionyl, 5-(3-pyrrolidinyl)pentanoyl, 6-(l-pyrrolidinyl)hexanoyl, 2-(l-pitperazinyl)acetyl, 3-(2-piperazir'yl)propionyl, 2-(3-piperazinyl)propionyl, 4-(l-piperazinyl)butyryl, 2,2-dimethyl-3-(2piperazinyl)propionyl, 5-(3-piperazinyl)pentanoyl, 6-ilpiperazinyl)hexanoyll 2-(l-piperidinyl)acetyl, 3-(2piperidinyl)propionyl, 2-(3-piperidinyl)propionyl, 4-(4piperidinyl)butyryl, 2,2-dimethyl-3-(l-piperidinyl)prcpionyl, 5-(2-piperidinyl)pentanoylt 6-(3-piperidinyl)hexanoyl, 2-(4-morpholinyl)acetyl, 3-(2-morpholinyl)propionylt 2-(3-morpholinyl)propionyl, 4-(4-morpholinyl)butyryl, 2,2-dimethyl-3-(2-morpholinyl)propionylI 5-(3morpholinyl)pentanoyl, 6-(4-morpholiriyl)hexanoyl, and the like.

The above "heterocyclic group-substituted lower- WO 94/01113 PCTIJ P93/00835 alkanoyl which has a substituent selected from a lower alkyl and phenyl" includes the above heterocyclic group-substituted straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, which has one to three substituents, selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and a phenyl group, for example, 2-(2-niethyl-l-pyrrolidinyl)acetyl, 3-(l-ethyl-2-pyrrolidinyl)propionyl, 2-(l-propyl-3-pyrrolidinyl)propionyl, 4-(3butyJ.-l-pyrrolidinyl)butyrylt 2,2-dimethyl-3-(4-pentyl-2pyrrolidinyl)propionyl, 5-(l-hexyl-3-pyrroli-dinyl)pentanoyl, 6-(2,3-diinethyl-1-pyrrolidinyl)hexanoyl, 2-(2,3,4-trimethy.l-pyrrolidinyl)acetyl, 3-(l-phenyl-2-pyrrolidinyl)propionyl, 2-(l-methyl-2-phenyl-3.-pyrrolidinyl)propionyl, 2-(4-methyll-piperazinyl)acetyl, 2-(4-phenyl-l-piperazinyl)acetyl, 3- (4-ethyl--2-piperazinyl)propionyl, 2-(4-propyl-3-piperazinyl)propionyl, 4-(4-butyl-l-piperazinyl)butyryl, 2,2dimethyl-3-(4-pentyl-2-piperazinyl)propionyl, 5-(4-hexyl-3piperazinyl)pentanoyl, 6-(2,4-dimethyl-l-piperazinyl)hexanoyl, 2-(3,4,5-trimethyl-l-piperazinyl)acetyl, 2-(4phenyl-3-methyJ.-l-piperazinyl)acetyl, 2-(4-methyl-l-piperidinyl)acetyl, 3-(J-ethyl-2-piperidinyl)propionyl, 2-(1propyl-3-piperidinyl)propionyl, 4-(l-butyl-4-piperidinyl)butyryl, 2,2-dimethyl-3-(4-pentyl-l-piperidinyl)propionyl, 5-(l-hexyl-2-piperidinyl)pentanoyl, 6-(l-phenyl-3--piperiainyl)hexanoyll 2-(2,5-dimethyl-4-phenyl-l-piperidinyl)dimethyl-4-piperidinyl)acetyl, 2-(3-zethyl-l-morpholinyi)acetyl, 3-(l-ethyl-2-morpholinyl)propionyl, 2-(l-propyl-3- 86 WO 94/01113 PCr/P93/00835 morpholinyl)propionyl, 4-(2-butyl-4-morpholinyl)butyry., 2,2-dimethyl-3-(1-pentyl-2-morpholinyl)propionyl, 5-(2hexyl-3-morpholinyl)pentanoyl, 6-(3,5-dimethy.-4morpholinyl)hexanoyl, 2-(2,3,5-trimethyl-4-morpholinyl)acetyl, 2-(3-phenyl-4-morpholinyljacetyl, 2-methyl-3phenyl-4-morpholinyl)acetyl, and the like.

The "piperidinylcarbony. which may optionally have a lower aikanoyl substituent" includes a piperidinylcarbonyl which may optionally have a substituent of a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, (1-piperidinyl)carbonyl, (2-piperidinyl)carbonyl, (3-piperidinyl)carbonyl, (4-piperidinyl)carbonyl, (l1-acetyl-4-piperidinyl)carbonyl, (4-formyl-l-piperidinyl)carbonyl, (3-propionyl--2-piperidinyl)carbonyl, (1-butyryl-4piperidinyl)carbonyl, (l-pentanoyl-4-piperidinyl)carbonyl, (1-hexanoyl-4-piperidinyl)carbonyl, and the like.

The "lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tertbutoxy, pentyloxy, hexyloxy, and the like.

The "amino having optionally a lower alkyl substituent" includes an amino optionally having one to two straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propyl amino, isopropylamino, butylamino, tert-butylamino, Dentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipenLylamino, dihexylamino, Nmethyl-N--ethylamino, N-ethyl--N-propylamino, N-methyl-N- 87 WO 94/01113 PCr/J P93/00835 butylamino, N-methyl-N-hexylamino, and the like.

The "lower alkyl which has optionally a substituent selected from a halogen atom and hydroxy" includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which may optionally have 1 to 3 substituents selected from a halogen atom and hydroxy, for example, in addition to the above-mentioned lower alkyl qroups, hydroxymethyl, 2-hydroxyethyl, l-hydroxyethyl, 3-hydroxypropyl, 2, 3-dihyroxypropyl, 4-hydroxybutyl, 1 ,l-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichioromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichioroethyl, 3chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4fluorobutyl, 5-chloropentyl, 3-chloro-2--methylpropyl, bromohexyl, 5,6-dichlorohexyl, and the like.

The "amino having optionally a substituent selected from a lower alkyl and a lower alkanoyl" includes an amino having optionally one or two substituents selected frcm a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl- N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexvlamino, 88 WO 94/01113 PrnaP93/00835 N-methyl-N-acetylamino, N-acetylainino, N-fornmylamino, Npropionylamino, N-butyrylamino, N-isobutyrylamino, Npentanoylamino, N-tert-butylcarbonylaninot N-hexanoylaiino, N-ethyl-N-acetylamino, and the like.

The "carbamoyl-substituted lower alkoxy" includes a carbamoyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, carbamoylmethoxy, 2-carbamoylethoxy, 1-carbamoylethoxy, 3carbamoylpropoxy, 4-carbamoylbutoxy, 6-carbamoylhexyloxy, 1,l-dimethyl-2-carbamoylethoxy, 2methyl-3-carbamoylpropoxy, and the like.

The "hydroxy-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and having 1 to 3 hydroxy-substitutents, for example, hydroxymethoxy, 2-hydroxyethoxy, l-hydroxyethoxy, 3-hydroxypropoxy, 2,3-dihydroxypropoxy, 4-hydroxybutoxy, 3,4-dihydroxybutoxy, l,l-dimethyl--2-hydroxyethoxy, hydroxypentyloxy, 6-hydroxyhexyloxy, 2-metnyl-3-hydroxypropoxy, 2,3,4-trihydroxybutoxy, and the like.

The "lower alkoxycarbonyl-substituted lower alkoxy" includes an alkoxycarbonyl-subst4.tuted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, methoxycarbonylmethoxy, 3-methoxycarbonylpropoxy, ethoxycarboxymrethoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, pentyloxy, 6-propoxycarbonylhexy)loxy, l,l-dimethyl-2-butoxy- 89 WO 94/01113 PCT/JP93/00835 carbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2pentyloxycarbonylethoxy, hexyloxycarbonylmethoxy, and the like.

The "carboxy-substituted lower alkoxy" includes a carboxy-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, carboxymethoxy, 2-carboxyethoxy, l-carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy, 1,1dimethyl-2-carboxyethoxy, 2-methyl-3-carboxypropoxy, and the like.

The "phthalimido-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by phthalimido group, for example, phthalimidomethoxy, 2-phthalimidoethoxy, 1phthalimidoethoxy, 3-phthalimidopropoxy, 4-phthalimidobutoxy, 5-phthalimidopentyloxy, 6-phthalimidohexyloxy, 1,1dimethyl-2-phthalimidoethoxy, 2-methyl-3-phthalimidopropoxy, and the like.

The or 6-membered saturated heterocyclic group which is formed by binding the groups R 21 and R 22 together with the nitrogen atom to which they bond with or without being intervened with nitrogen or oxygen atom" includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, and the like.

The above-mentioned "heterocyclic group having a substituent selected from piperidinyl and a lower alkyl" includes the above-mentioned heterocyclic groups having 1 to 3 substituents selected from piperidinyl and a straight 90 WO 94/01113 PCT/JP93/00835 chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-hexylpiperazinyl, 4-(l-piperidinyl)piperidinyl, 3-(l-piperidinyl)pyrrolidinyl, 3-(lpiperidinyl)-4-rnethylpiperazinyl, 3-(l-piperidinyl)morpholino, and the like.

The "phenyl(lower)alkanoyl" includes a phenylalkanoyl wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, phenylacetyl, 3-phenylpropionyl, 2-phenylpropionyl, 4-phenylbutyryl, 2, 2-dimethyl-3-phenylpropionyl, 6-phenylhexanoyl, and the like.

The "cycloalkyl-lower alkanoyl"' includes 38 cycloalkyl-alkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl having 2 to 6 carbon atoms, for example, cyclohexylacetyl, 3-cyclopropylpropionyl, 2-cyclopentylpropionyl, 4-cyclohexylbutyryl, 2, 2dimethyl-3-cycloheptylpropionyl, 5-cyclooctylpentanoyl, 6cyclohexylhexanoyl, and the like.

The "cycloalkylcarbonyl" includes a cycloalkylcarbonyl having 3 to 8 carbon atoms, for example, cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, and the like.

The "phenoxy-lower alkanoyl wherein the phenyl ring has optionally 1 to 3 substituents selected from a lower 91 WO 94/01113 PCr/JP93/00835 alkyl, a lower alkoxy and an amino having optonally a lower alkanoyl substituent" includes a phenoxyalkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl having 2 to 6 carbon atoms and the phenyl.

ring has optionally 1 to 3 substituents selected from a straight chain or branched chain alkyl having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy having 1 to 6 carbon atoms and an amino having optionally a straight chain or branched chain alkanoyl having 1 to 6 carbon atoms, for example, phenoxyacetyl, 3-phenoxypropionyl, 2-phenoxypropionyl, 4-phenoxybutyryl, 2, 2-dimethyl-3-phenoxypropionyl, 5-phenoxypentanoyl, 6-phenoxyhexanoyl, (2-aminophenoxy)acetyl, 3-(4-aminophenoxy)propionyl, (2-methylphenoxy)acetyl, (4-methylphenoxy)acetyl, (3-methylphenoxy)acetyl, (3-methoxyphenoxy)acetyl, (3-acetylaminophenoxy)acetyl, 4-(2-propionylaminophenoxy)butyryl, 2,2-dimethyl-3- 4-butyrylaminophenoxy)propionyl, 2-pentanoylaminophenoxy)pentanoyl, 6-(4-hexanoylaminorhenoxy)hexanoyl, 3-(2ethylphenoxy)propionyl, 2-(4--propylphenoxy)propionyl, 4-(4butylphenoxy)butyryl, 5-(3-pentylphonoxy)pentanoyl, 6-(4hexylphenoxy)hexanoyl, (2,3-dimethylphenoxy)acetyl, dimethylphenoxy)acetyl, (3,4-dimethylphenoxy)acetyl, (3,4,5trimethylphenoxy)acetyl, 3-(4-ethoxyphenoxy)propionyll 2-(2propoxyphenoxy)propionyl, 4-(3-butoxyphenoxy)butyryl, 5-(4pentyloxyphenoxy )pentanoyl, 6- (4-hexyloxyphenoxy )hexanoyl, (3,4-dimethoxyphenoxy)acetyl, (2,4-dimethoxyphenoxy)acetyl, (3,4,5-trimethoxyphenoxy)acetyl, (2-acetylamino-4-methylphenoxy) acetyl, C 4-acetyl- 92 WO 94/01113 PCT/JP93/0083S arnino-3-mrethoxyphenoxy)acetyl, and the like.

The "phthalimido-substituted lower alkanoyl" includes a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms which is substituted by phthalimido group, for example, 2-phthalimi:..acetyl, 3phthalimidoprcpionyl, 2-phthalimidopropionyl, 4-phthalimidobutyryl, 2, 2-dimethyl-3-phthalimidopropionyl, pentanoyl, 6-pohthalimidohexanoyl, 3-methyl-4-phthalimidobutyryl, and the like.

The "lower alkoxycarbonyl-lower alkanoyl" includes an alkoxycarbonyl-alkanoyl group wherein the alkoxy moiety is a straight chain or branched chain alkoxy having 1 to 6 carbon atoms and the alkanoyl moiety is a straight chain or branched chain alkanoyl having 2 to 6 carbon atoms, for example, methoxycarbonylacetyl, 3-nethoxycarbonylpropionyl, ethoxycarbonylacetyl, 3-ethoxycarbonyl-oropionyl, 4-ethoxycarbonylbutyryl, 3-propoxycarbonylpropionyl, 2-methoxycarbonylpropionyl, 6-propoxycarbonylhexanoyl, carbonylpentanoyl, 2,2-dimethyl-3-butoxycarbonylpropionyl, 2-methyl-3-tert-butoxycarbonylp~ipionyl, pentyloxycarbonylacetyl, hexyloxycarbonylacetyl, and the like.

The "carboxy-lower alkanoyl" includes a carboxyalkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl having 2 to 6 carbon atoms, for example, carboxyacetyl, 3-carboxypropionyl, 2-carbo>:ypropionyl, 4-carboxybutyryl, 2, 2-dimethyl-3-carboxypropionyl, 5-carbox~'pentanoyl, 6-carboxyhexanovl, and the like.

WO 94/01113 PCT/JP93/00835 The "naphthyloxy-lower alkanoy)' includes a naphthyloxy-aJlkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl having 2 to 6 carbon atoms, for example, naphtyloxyacetyl, 3-naphtyloxypropionyl, 2-naphtyloxypropionyl, 4-naphthyloxybutyryl, 2, 2dimethyl-3-naphthyloxypropiony., 5-raphthyloxypentanoyl, 6naphthyloxyhexanoyl, and the like.

The I"phenyl-lower alkoxycarbonyl" includes a phenylalkoxycarbonyl wherein the alkoxycarbonyl molety is a straight chain or branched chain alkoxycarbony,,,l group having I to 6 carbon atoms, for example, benzyloxycarbonvl, 2phenylethoxycarbonyl, 1-phenylethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl, carbonyl, 6-phenylhexyloxycarbonyl, l,l-dimethyl-2-phenylethoxycarbonyl, 2-methyl-3-phenylpropoxycarbonyl, and the like.

The '"phenoxy-lower alkyl" includes a phenoxyalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, phenoxymethyl, l-phenoxyethy'l, 2-phenoxyethyl, 3phenoxypro-oyl, 4-phenoxybutyl, 5-phenoxypentyl, 6-phenoxyhexyl, 1,l-dimethyl-2-phenoxyethyl, 2-methyl--3-phenoxypropyl, and the like.

The "phenyl which has optionally 1 to 3 substituents selected from a lower alkyl, a lower alkoxy and a halogen atom" includes a phenyl group which has optionally 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a 94 WO 94/01113 PCT/J P93/00835 straight chain or branched chain alkoxy group having I. toE carbon atoms and a halogen atom, for example, phenyl, 2methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 4-pentyloxyphenyl, 2,4-dimethoxyphenyl, 4-hexyloxyphenyl, 3, 4-dimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, 2,3dimethoxyphenyl, 3, 4-diethoxyphenyl, 2, 2,6-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxynhenyl, 3,4,5-trirnethoxyphenyl, ?-chlorophenyl, 3-chlorophenyl, 4-chiorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-brornophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 3 ,4-dichiorophenyl, 3,5-dichiorophenyl, 2,6-dichiorophenyl, 2,3dichiorophenyl, 2",4-dichJlorophenyl, 3,4-difluorophenyl, dibromopheny., 3,4 ,5-trichiorophenyl, 2-methoxy-3-chlorophenyl, 2-methyiphenyl, 3-methylphenyl, 4-methyiphenyl, 2ethylphenyl, 3-ethyiphenyl, 4-ethylphenyl, 4-isop ropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4dimethylphenyl, 3i4-diethylphenyl, 2,4-dimethyiphenyl, dimethyiphenyl,.2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 3-chloro-4--methylpohenyl, 3-methoxy--4-methyl-5-iodophenyl, 3 ,4-dixnethoxy--5-brornophenyl, 3, 5-diiodo--4-rethoxyphenyl, and the like.

The "amino-lower alkyl having optionally a lower alkyl substituent" includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 subst.-Ltuents of a straight chain or branched chain alkyl 95 WO 94/01113 PCT/J P93/00835 group having 1 to 6 carbon atoms, for example, arninomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, aminopentyl, 6-aminohexyl, l,l-dimethyl--2-aminoethyl, 2methvl-3-aminopropyl, methylaminomethyl, l-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylamino~ropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, (N-ethyl--N-propylamino)rnethyl, 2-(N--nethyl-Nhexylamino)ethyl, and the like.

The or 6-membered saturated heterocyclic group which is formed by binding the groups R 24 and R 25 together with the nitrogen atom to which they bond with or without being intervened wi.th nitrogen or oxygen atom" includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpbholino, and the like.

The above-mentioned "heterocyclic group naving a substitL-uent selecte& from a lower alkyl, a lower a2.ko:c.vcarbonyl and piperidinyl" includes the above-menztionedf heterocyclic groups having 1 to 3 substituents selected f'rom a straight chain or branrched chain alkyl. group having 1 to 6 carbor, atoms, a straight :Thain or branched chain a=lkoxvcarbonyl having 1 to 6 carbon atoms and piperidinvl, for example, in addition to the above-mentioned heterocyclic groups having a substituent selected from a lower alk:1! and piperidinyl, 4-methoxycarbonylpiperazinyl, 4-ethc:cvcarbonylpiperidinyl, 3-propoxvcarbonylpyrrolidinyl, 2-pen.:ylo:.carbonylmoroholino, 4-hexyloxycarbonvlpiperidinyl, 4-c thoxycarbonyl-3-methylpiperi4dinyl, 3-methyl-4-ethoxyc=rbon.-lpiperazinyl, and t-~e like.

96 WO 94/01113 PCT/JP93/00835 The or 6-membered saturated heterocyclic group which is formed by binding the groups R 29 and R 30 together with the nitrogen atom to which they bond with or without being intervened with nitrogen or oxygen atom" includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, and the like.

The above-mentioned "heterocyclic group having a lower alkyl substituent" includes the above-mentioned heterocyclic groups having 1 to 3 substituents of a straight chain or branched chain alkyl gLoup having 1 to 6 carbon atoms, for example, 4-methylpiperazinyl, 3,4-dimeti.ylpiperazinyl, 2-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-hexylpiperazinyl, and the like.

The heterocyclic ring in the formula includes tetrahydroquinolyl, 2,3,4,5-tetrahydro-l'-benzazepinyl, 1,2,3,4,5,6-hexahydrobenzazocinyl, 1,2-dihydroquinolyl, 2,3dihydro-lH-benzazepinyl, 1,2,3,4-tet-ahydrobenzazocinyl, and the like.

The heterocyclic ring in the formula wherein the carbon atom in the group of the formula: -(CH 2 or

-CH=CH-(CH

2 v for W is replaced by oxyqen atom, sulur atom, sulfinyl group, sulfonyl group, or a group of the formula: -NR 28

(R

28 is hydrogen atom or a lower alkyl) includes a heterocylic group wherein the carbon atom in t e group of the formula: -(CH 2 or -CH=CH-(CH 2 v for W is replaced by oxygen atom, sulfur atom, sulfinyl group, sulfonyl group, or a group of the formula: -NR 28

(R

28 is 97- WO 94/01113 P~T/JP93/0083S hydrogen atom or a straight chain or branched chain alkyl having 1 to 6 carbon atc'ma), for example, 3t4-dihydro-2H- 1,4-benzoxazinyl, 1,2,3,5-tetrahydro-4,1-benzoxazepinyl, 1,2,3,4-tetrahydroquinoxalinylt lt2,314,5,6-hexahydro-11Sbenzodiazocinyl, 5-nethyl-1,2,3,4 ,5,6-hexahydro-l, diazocinlt1, 4-methyl-1,2,3,.4-tetrahydroquinoxalin-I., 1,2,3t4-tetrahyiro-.5,l-benzoxazepinyl, 3,4-dihydro-2H4-1,4benzothiazinyl, 2,3,4,5-tetrahydro-1,5-benzothiazepinyl, 1,2,3,5-tetrahydro-4,1-benzothiazepinyl, 4-ethyl-l,2,3,4tetrahydroquinoxalinyl, 4-propyl-1,2,3,4-tetrahydroquinoxalinyl, 4-butyl-l,2,3,4-tetrahydroquinoxalinyl, 4pentyl-1,2,3,4-tetrahydroquinoxalinylI 4-hexyl-2.,2,3,4tetrahydroquinoxalinyl, 2,3,4,5-tetrahydro-lR-l,4-benzodiazepinyl, 4-rethyl-2,3,4,5-tetrahydro-lH-1,4-benzodiazepinyl, 4-ethyl-2,3,4,5-tetrahydro-lH-1,4-beizodiazepinyl, 4-propyl-2,3,4 ,5-1,etrahydro-la-1 ,4-benzodiazepinyl, 4-butyl-2,3t4,5-tetrahydro-lH-1,4-benzodiazepinyl, 4-pentyl-2,3,4,5-tetrahydro-1H-l,4-benzodiazepinyl, 4-hexyl-2,3,4,5-tetrahydro-lH-1,4-benzodiazepinyl, 2,3,4,S-tetrahydro-lH-1,5-benzodiazepinyl, methyl-2, 3,4, 5-tetrahydro-lH-1, 5-benzodiazepinyl, 2,3,4,5-tetrahydro-lH-l,5-benzodiazepinyl, 5=propyl-2,3)4t5tetrahydro-lH-1, 5-benzodiazepinyl, S-butyl-2, 3,4, tetrahydro-lH-l,5-benzodiazepi4nylI 5-pentyl-2,3,4 5-hexyl-213,4 tetrahydro-lH-1, 5-benzodiazepinyl, 3, 4-dihydro-l-oxo-2H4-l,4benzothiazepinyl, 3, 4-dihydro-1 ,1-dioxo-2H-1, 4-benzothiazepinyl, 1-oxo-2,3,4,5-tetrahydro-1, WO 94/01113 JPCM/J 93/fIO835 l,l-dioxo-2,3,4 ,5-tetrahydro-l,5-benzothiazepinyl, 4-oxol,2,3,5-tetrahydro-4,1-benzothiazepinylt 414-dioxo-l,2,3t5tetrahydro-4,l-benzothiazepinyl, and the like.

The "halogen-substitutad lower alkanoyl" includes a straight chain or branched chain alk~noyl group having 1 to 6 carbon atoms which has 1 to 3 substituents of a halogen atom, for example, 2,212-trifluoroacetyl, 2,2,2-trichloroacetylt 2-chloroacetyll 2-bromoacetyl, 2-fluoroacetyll 2iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl, 3,3,3trifluoropropionyl, 3,3#3-trichloropropionyl, 3 -chloropropionyl, 2,3-dichioropropionyl, 4,4,4-trichlorobutyryl, 4fluorobutyryl, 5-chloropentanoylt 3-chloro-2-methylpropionyl, 6-bromohexanoyl, 5,6-dibromohexanoyl, and the like.

The "aminocarbonyl-lower alkoxy having a lower alkyl substituent" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an aminocarbonyl group having I to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methylaminocarbonylmethoxy, 1-ethylaminocarbonylethoxy, 2-propylaminocarbonylethoxy, 3-isopropylaminocarbonylpropoxy, 4-butylaminocarbonylbutoxy, 5-pentylarninocarbonylpentyloxy, 6hexylaminocarbonylhexyloxy, dimethylaminocarbonylmethoxy, 3diethylaminocarbonylptopoxy, diethylaminocarbonylmethoxv, (N-ethyl-N-propylamino)carbonylmethoxy, 2-(N--methyl-N-hexylamino)carbonylethoxy, and the like.

The "carbamoyl-lower alkyl" includes a carbamoyl- WO 94/01113 PCT/JP93/0083S substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carbamoylmethyl, 2carbamoylethyl, 1-carbamoylethyl, 3-carbamoylpropyl, 4carbamoylbutyl, 5-ca rbamoylpentyll 6-ca rbamoylhexyl, 1,1dimethyl-2-carbamoylethyl, 2-methyl-3-carbarnoylpropyl, and the like.

The "amino-lower alkanoyl having optionally a lower alkyl substituent" includes a straight chain or branched chain alkanoyl having 2 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 substituents of a straight chain or branched chain alkyl group having i to 6 carbon atoms, for example, 2-aminoacetyl, 3-aminopropionyl, 2-aminopropionyl, 4-aminobutyryl, 6-aminohexanoyl, 2, 2-dimethyl-3-aminopropionyl, 2-rethyl-3-aminopropionyl, 2-methylaminoacetyl, 2-ethylaminopropionyl, 3-propylaminopropionyl, 3-isopropylaminopropionyl, 4-butylaminobutyryl, 6-hexylaminohexanoyl, 2-dimethylaminoacetyl, 2-diethylaminoacetyl, 2-(N-ethyl-N-propylamino)acetyl, 3-(N-methyl-Nhexylamino)propionylt and the like.

The "amino-lower alkyl having optionally a lower alkanoy. substituent" includes a straight chain or branched chain alkyl having I. to 6 carbon atoms which is substituted by an amino group having optionally a substituent of a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl, 1aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6aminohexyl, 1, l-dimethyl-2-aminoethyl, 2-methyl-3-amino- -100 WO094/01113 PC'/J P93/00835 propyl, acetylaminomethyl, 1-acetylaminoethyl, 2-propionylaminoethyl, 3-isopropionylaminopropyl, 4-butyrylaminobutyl, 6-hexarioylaminohexyl, formylaminomethyl, and the like.

The "anilinocarbony. having optionally a lower alkyl. substituent on the phenyl ring" includes an anilinocarbonyl group having optionally 1 to 3 substituents of a straight chain or branched chain alkyl group having 1 t~o 6 carbon atoms on the phenyl ring, for example, anilinocarbonyl, 2-methylanilinocarbonyl, 3-methylanilinocarbonyl, 4-methylanilinocarbonyl, 2-ethylanilinocarbonyl, 3-ethylanilinocarbonyl, 4-ethylanilinocarbonyl, 4-isopropylanilinocarbonyl, 3-butylanilinocarbonyl, 4-pentylanilinocarbonyl, 4-hexylanilinocarbonyl, 3,4-dimethylanilinocarbonyl, 3,4diethylanilinocarbonyl, 2, 4-dimethylanilinocarbonyl, 2, dimethylanilinocarbonyl, 2,6-dimethylanilinocarbonyl, 3,4,5trimethylanilinocarbonyl, and the like.

The "phenylsulfonyl which has optionally a substituent selected from a halogen and a lower alkyl on the phenyl ring" includes a phenylsulfonyl group which has optionally 1 to 3 substitutents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a halogen atom, for example, phenylsulfonyl, 2chlorophenylsulfonyl, 3-chlorophenylsulfonyl, 4-chlorophenylsulfonyl, 2-fluorophenylsulfonyl, 3-fluorophenylsulfonyl, 4-fluorophenylsulfonyl, 2-bromophenylsulfonyl, 3bromophenylsulfonyl, 4-bromophenylsulfonyl, 2-iodophenylsulfonyl, 3'-iodophenylsulfonyl, 4-iodophenylsulfonyl, 3,4- 101- WO 94/01113 PCTIJ P93/00835 dichiorophenylsulfonyl, 3,5-dichlorophenylsulfonyl, 2, 6-dichlorophenylsulfonyl, 2, 3-dichlorophenylsulfonyl, 2, 4dichiorophenylsulfonyl, 3, 4-difluorophenylsulfonyl, 3, dibromophenylsulfonyl, 3,4, 5-trichiorophenylsulfonyi, 2ethyl-3-chlorophenylsulfonyl, 2-rethyiphenylsulforwi, 3methyiphenylsulfonyl, 4-methyiphenylsulfonyl, 2-ezhylphenylsulfonyl, 3-ethyiphenylsulfonyl, 4-ethylphenyjisulfonyl, 4isopropylphenylsulfonyl, 3-butyiphenylsulfonyl, 4-penzylj'enylsulf'onyl, 4-hexyiphenylsulfonyl, 3 ,4-dime thylphenylsulfonyl, 3, 4-diethylphenylsulfoiyl, 2, 4-dirnethyiphensulfonyl, 2, 5-dimethylphenylsulfonyl, 2, 6-dimethylphenylsulfonyl, 2,4,6-trimethylphenylsulfonyl, 3,4,5-trirnethylphenylsulfonyl, 3-chloro-4-methy.1phenylsu1.fonyl, iodophenylsulfonyl, 3, 4-dimethyl-5-bromophenylsulfonyl, 3, diiodo-4-mxethylphenylsulfonyl, and the like.

The "phthalimido-substituted lower alkyl" includes a straight chain or branched chain alkyl group having I to 6 carbon atoms which is substituted by phthalimido group, for example, phthalimidomethyl, 2-phthalirnidoethyl, 1-phthalimidoethyl, 3-phthalimidopropylt 4-phthalimidobutyC, phthalimidopentyl, 6-phthalimidohexyl, 1,l-dimeth.'l-2phthalimidoethyl, 2-methyl-3-phthalimidopropyl, and the like.

The ''lower alkynyl" includes a straight chain or branched chain alkynyl having 2 to 6 carbon atoms, for example, ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 1 methyl-2-propynyl,. 2-pentynyl, 2-hexynyl, and the like.

The "benzoyl which has optionally a halc~en WO 94/01113 -12-PO'/J P93/00835 substituent on the phenyl ring" includes a benzoyl group which has optionally 1 to 3 substituents of a halogen atom on the phenyl ring, for example, benzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-fluorobenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 3-bromobenzoyl, 4bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 4-iodobenzovl, 3,4-dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,6-dichlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 3,4difluorobenzoyl, 3,5-dibromobenzoyl, 3,4,5-trichlorobenzoyl, and the like.

The "amino-lower alkoxy having optionally a substituent selected from a lower alkyl and a lower alkanoyl"' include a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 substituents selected from a straight chain or branched chain alkyl group) havingI to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy 4-aminobutoxy, 5-aminopent-'loxy, 6-aminohexyloxy, 1,1dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, acety.aminomethoxy, 1-acetylaminoethoxy, 2-propionylaminoethcxy, 3-isopropionylaminopropoxy, 4-butyrylaminobutoxy, pentanoylaminopentyloxy, 6-hexanoylaminohexyloxyt formylaminomethoxy, methylaminomethoxy, l-ethylaminoethoxy, 2propylarninoethoxy, 3-isopropylaminoropoxy, 4-butylamin.obutoxy, 5-pentylaminope.ityloxy, 6-hexylaminohexvloxy, dimethylaminonethoxy, (N-e;:,hyl-N-tpropylamino)methoxy, 2-(N- 0o: WO 94/01113 PCT/J P93/00835 methyl-N-hexylamino)ethoxy, and the like.

The "benzoyloxy which has optionally a halogen substituent on the phenyl ring" includes a benzoyloxy group which has optionally 1 to 3 substituents of a halogen atom on the phenyl ring, for example, benzoyloxy, 2-chlorobenzoyloxy, 3-chlorobenzoyloxy, 4-chlorobenzoyloxy, 2fluorobenzoyloxy, 3-fluorobenzoyloxy, 4-fluorobenzoyloxy, 2bromobenzoyloxy, 3-brornobenzoyloxy, 4-brornobenzoyloxy, 2iodobenzoyloxy, 3-iodobenzoyloxy, 4-iodobenzoyloxy, 3,4dichlorobenzoyloxy, 3, 5-dichlorobenzoyloxy, 2, 6-di;chiorobenzoyloxy, 2, 3-dichlorobenzoyloxy, 2, 4-dichlorobenzoyloxy, 3,4-difluorobenzoyloxy, 3,5-dibrcmobenzoyloxy, 3,41,5trichlorobenzoyloxy, and the like.

The "lower alkanoyloxy-substituted lower alkvJ." includes a straight chain cr branched chain alkyl group) having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkanoyloxy group having g2 to 6 carbon atoms, for example, acetyloxymethyl, 2-1prooionyloxyethyl, l-butyryloxyethyle 3-acetyloxypropyl, 4-acetyloxybutyl, 4-isobutyryloxybutyl, 5-pentanoyloxype.:yl, 6acetyloxyhexyl, 6-tert-butylcarbonyloxyhexyl, 1,1-dimethyl- 2-hexanoyloxyethyl, 2-methyl-3-acetyloxypropyl, and the like.

The "lower alkylsulfonyloxy-lower alkyl"' includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a straight chin or branched chain alkylsulfonyloxy group having 1 to 6 carbon atoms, for example, methylsulfonyloxymethyl, 1-ezhyl- 104 WO 94/01113 PCrIJP93/00835 sulfonyloxyethyl, 2-propylsulfonyloxyethyl, 3-isopropylsulfonyloxypropyl, 4-butylsulfonyloxybutyl, oxypenty., 6-hexylsulfonyloxyhexyl, 1 ,l-dimethyl-2-methylsulfonyloxyethyl, 2-methyl-3-ethylsuilfonyloxypropyl, and the like.

The Ilazido-lower alkyl"' includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an azido group, for example, azidomethyl, 1-azidoethyl, 2-azidoethyl, 3-azidopropyl, 4azidobutyl, 5-azidopentyl, 6-azidohexyl, l,1-dirnethyl-2azidoethyl, 2-methyl-3-azidopropyl, and the like.

The "lower alkanoyloxyimino" includes a straight chain or branched chain alkanoyloxyimino group having 1 to 6 carbon atoms, for example, formyloxyimino, acetyloxyimino, propionyloxyirniino, butyryloxyimino, isobutyryloxyimino, pentanoyloxyimino, tert-butylcarbonyloxyimino, hexanoyloxyimino, and the like.

The "lower alkylidene" includes a straight chain or branched chain alkylidene group having 1 to 6 carbon atoms, for example, methylidene, ethylidene, propyli~ene, isopropylidene, butylidene, pentylidene, hexylidene, and the like.

The 1oxiranyl-substituted lower alkyl"' includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by oxiranyl group, for example, oxiranylmethyl, 1-oxiranylethyl, 2-oxiranylethyl, 3-oxiranyipropyl, 4-oxiranylbutyl, 5-oxiranylpentyl, 6oxiranylhexyl, l,l-dimethyl-2-oxiranylethyl, 2-ii.ethyl-3- WO 94/01113 -15 PCT/JP93/00835 oxiranyipropyl, and the like.

The "lower alkyl having 1 to 2 substituents selected from a lower alkoxy, hydroxy and an amino having optionally a lower alkyl substituent" includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and having 1 to 2 substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, hydroxy and an amino having optionally a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methoxymethyl, 1-ethoxyethyl, 2propoxyethyl, 3-isopropoxypropyl, 4-butoxybutyl, oxypentyl, 6-hexyloxyhexyl, l,l-dimrethyl-2-methoxyethyl, 2methyl-3-ethoxypropyl, 3-methoxy-2-hydroxypropyl, hydroxymethyl, 2-hydroxyethyl, l-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxyethyl, 4-hydroxybutyl, 3,4-dihydroxybutyl, 1,1dimethyl-2-hydroxyethyl, 5, 6-dihydroxyhexyl, pentyl, 6-hydroxyhexyl, hexyl, 2-methyl-3-hydroxypropyl, aminomethyl, 1-aminoethyl, 2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6aminohexyl, l,l-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, ethylaminomethyl, propylaminomethyl, isopropylaminomethyl, butylaminomethyl, tertbutylaminomethyl, pentylaminomethyl, hexylaminomethyl, dimethylaminomethyl, die thylaminomethyl, dipropylaminomethyl, dib,,'tylaminomethyl, dipentylaminomethyl, dihexylaminomethyl, N-methyl-N-ethylaminomethyl, N-methyl-Npropylaminomethyl, N-methyl-N-butylarainomethyl, N-methyl-Nhexylaminomethyl, 1-methylaminoethyl, 2-ethylaminoethyl, 3- 106 WO 94/01113 PCT/J P93/00835 propylaminopropyl, d-butylaminobutyl, l,l-dimethyl-2-pentylaminoethyl, 5-hexylaminopentyl, 6-dirnethylaminohexyl, 4dizuethylaminobutyl, 2-diethylaminoethyl, 1- (N-methyl-Nhexylamino) ethyl, 3-dihexylaminopropyl, 6-die thylaminohexyl, 4-dibutylaminobutyl, 2-(N-methyl-N-pentylamino)ethyl, 2hydroxy-3-diethylaminopropyl, 3-hydroxy-4-rnethylaminobutyl, 5-hydroxy-6-diethylaminohexyl, pentyl, 4-hydroxy-5--methylaminopentyl, aminopentyl, 5-hydroxy-6-ethylaminohexyl, 5-hydroxy-6isopropylaminohexyl, 5-hydroxy-6-aminohexyl, and the like.

The taminocarbonyloxy having optionally a lower alkyl substituent" includes an aminocarbonyloxy group having optionally 1 to 2 substituents of a straight chain or branched chain alkyl qroup having 1 to 6 carbon atoms, for example, antinocarbonyloxy, methylarninocarbonyloxy, ethylaminocarbonyloxy, propylarninocarbonyloxy, isopropylaminocarbonyloxy, butylaminocarbonyloxy, tert-butylaminocarbonyloxy, pentylaminocarboiyloxy, hexylaminocarbonyloxy, dimethylaminocarbonyloxy, diethylaminocarbonyloxy, dipropylaminocarbonyloxy, dibutylaminocarbonyloxy, dipentylaminocarbonyloxy, dihexylaminocarbonyloxy, N-methyl-N-ethylaminocarbonyloxy, N-ethyl-N-propylamiifocarbonyloxy, N-methyl-Nbutylaminocarbonyloxy, N-methyl-N-hexylaminocarbonyloxy, and the like.

The "lower alkanoyloxy having optionally a halogen substituent" includes a straight chain or branched chain alkanoyloxy grout,: having 1 to 6 carbon atoms which has optionally 1 to 3 substituents of a halogen atom, for WO 94/01113 -17-PCTIJP93/00835 example, in addition to the above-mentioned lower alkanoyloxy groups, 2,2,2-trifluoroacetyloxy, 2,2,2-trichloroacetyloxy, 2-chloroacetyloxy, 2-bromoacetyloxy, 2-fluoroacetyloxy, 2-iodoacetyloxy, 2,2-difluoroacetyloxy, 2,2-dibromoacetyloxy, 3,3,3-trifluoropropionyloxy, 3,3,3-trichloropropionyloxy, 3-chloropropionyloxy, 2, 3-dichloropropionyloxy, 4,4,4-trichlorobutyryloxy, 4-fluorobutyryloxy, 3-chloro-2-methylpropionyloxy, 6bromohexanoyloxy, 5,6-dibromohexanoyloxy, and the like.

The "amino-lower alkyl having optionally a substituent selected from a lower alkyl and a lower alkanoyl"' includes a straight chain or branched chain alkyl.

group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoy. group having 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4aminobutyl, 5-aminopentyl, 6-arninohexyl, l,l-dimethyl-2aminoethyl, 2-methyl-3-aminopropyl, acetylaminomethyl, Iacetylaminoethyl, 2-propionylaminoethyl, 3-isopropionylaminopropyl, 4-butyrylaminobutyl, 5-pentanoylaminopentyl, 6hexanoylaminohexyl, formylaminomethyl, methylaminomethyl, 1ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, (N-ethyl-N-propylamino)methyl, 2-(Nmethyl-N-hexylamino)ethyl, and the like.

The "amino-lower alkanoyloxy having optionally a 108 WO 94/01113 0PCT/JP93/00835 lower alkyl substituent" includes a straight chain or branched chain alkanoyloxy having 2 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, 2-aminoacetyloxy, 3-aminopropionyloxy, 2-aminopropionyloxy, 4aminobutyryloxy, 5-aminopentanoyloxy, 6-aminohexanoyloxy, 2,2-dimethyl-3-aminopropionyloxy, 2-methyl-3-aminopropionyloxy, 2-methylaminoacetyloxy, 2-ethylaminopropionyloxy, 3propylaminopropionyloxy, 3-isopropylaminopropionyloxy, 4butylaminobutyryloxy, 5-pentylaminopentanoyloxy, 6-hexylaminohexanoyloxy, 2-dimethylaminoacetyloxy, 2-diethylaminoacetyloxy, 2-(N-ethyl-N-propylamino)acetyloxy, 3-(N-methyl- N-hexylamino)propionyloxy, and the like.

The "pyridyl-lower alkyl" includes a pyridylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (4-pyridyl)methyl, 1-(3-pyridyl)ethyl, 2-(2pyridyl)ethyl, 3-(2-pyridyl)propyl, 4-(3-pyridyl)butyl, (4-pyridyl)pentyl, 6-(2-pyridyl)hexyl, l,l-dimethyl-2-(3pyridyl)ethyl, 2-methyl-3-(4-pyridyl)p.)pyl, and the like.

The or 6-membered saturated heterocyclic group which is formed by binding the groups R 33 and R 34 together with the nitrogen atom to which they bond with or without being intervened with nitrogen, oxygen or sulfur atom" includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and the like.

The above "heterocyclic group which has a 109 WO 94/01113 PCT/J P9310083S substituent selected from oxo, a lower alkyl, a lower alkanoyl and carbamoyl" includes the above heterocyclic groups wnich have 1 to 3 substituents selected from oxo, a straight chain or branche3 chain alkyl group having 1 to 6 carbon atoms, a st iight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, and carbamoyl group, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3ethylpyrrolidinyl, 2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4hexylpiperazinyl, 2-methylthiomorpholino, 4-acetylpiperazinyl, 2-propanoylmorpholino, 3-butyrylthiomorpholino, 3-pentatioylpyrrolidinyi, 4-hexanoylpiperidiny., 3-methyl-4acetylpiperazinyl, 2-carbamoylpyrrolidinyl, 4-carbamoylpiperazinyl, 3-carbamoylthiomorpholino, 2--carbarnoylmorpholino, 3-carbamoylpiperidinyl, 1-oxothiomorpholino, 1,1-dioxothiomorpholino, and the like.

The "aminocarbonyl having optionally a lower alkyl substituent" includes an aminocarbonyl group having optionally 1 to 2 substittents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, tert-butylaminocarbonyl, pentylariinocarbonyl, hexylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl, Nmethyl-N-ethylarninocarbonyl, N-ethyl-N-pDropylaminocarbonyl, N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylamino- -110- WO 94/01113 PCT/JP93/00835 carbonyl, and the like.

The "cyano-substituted lower alkyl"' includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substitu 4 'by cyano group, for example, cyanornethyl, 2-cyanoethyl, 1-cyanoethyl, 3--cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl, 1,1dimethyl-2-cyanoethyl, 2-methyl-3-cyanopropyl, and the like.

The "lower alkoxycarbonyl-substituted lower alkyl" an alkoxycarbony2l-substituted straight chain or branched chain alkyl group having 1 to 6 carbon 4tons wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having I to 6 carbon atoms, for example, methoxycarbonylmethyl, 3-methoxycarbonylpropyl, ethoxycarboxyrnethyl, 3-ethoxycarbonylpropyl, 4-ethoxycarboiiylbutyl, 5-isopropoxycarbonylpentyl, 6propoxycarbonyihexyl, l,1-dimethyl-2-butoxycarb.nylethyl, 2methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxcycarbonylethyl, hexyloxycarbonylmethyl, and the like.

Trhe "carboxy-substituted lower alkyl"' includes a carboxy-substituted alkyl group wherein the alkyl moiety is a straight chains or branched chain alkyl group having 1 to 6 carbon atoms, for example, carboxymethyl, 2-carboxyethyl, 1carboxyethyl, 3-carboxyp.-opyl, 4-carboxybutyl, pentyl, 6-carboxyhexyl, 1,1-dimethyl-2-carboxy thyl, 2methyl-3-carboxypropyl, and the like.

The "letrahydropyranyloxy-substituted lower alkyl" includes a tetrahydropyranyloxy-substicuted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, WO 94/01113 WO 9/0113 vaIC/43/0fiU35 for example, (2-tetrahydropyranyl)oxymethyls 2-(3-tetrahydropyrany1)o:,-yethyl, 1-(4-tetrahydropyranyl)oxyethylI 3- (2-tetrahydropyranyl )oxypropyl, 4- (3-tetrahydropyranyl) oxybutyl, 5-(4-tetrahydropyranyl)oxypentyl, 6-(2-tetrahydropyranyl)oxyhexyl, l,1-dimethyl-2-(3-tetrahydropyranyl)oxyethyl, 2-methyl-3-(4-tetrahydropyranyl)oxypropyl, and the like.

The "piperidiny. having optionally a phenyl-3.ower alkyl substituent" includes a piperidinyl which has optionally a substituent of r- phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, piperidinyl, l-benzyl-4-piperidinyl, l-(2-phenylethyl)-3-piperidinyl, 1- (1-phenylethyl)-2-piperidinyl, l-(3-phenylpropyl)-4piperidinyl, 1-(4-phenylbutyl)-4-L±peridinyl, l-(S-phenylpentyl)-4-piperidinyl, l-(6-phenylhexyl)-4-piperidinyl, 1- (lil-dimethyl-2-phenylethyl)-3-piperidinyl, l-(2-rnethyl-3phenylpropyl)-2-piperidinyl, and the like.

The "imidazolyl-substituted lower alkanoyl" includes an imidazolyl-substituted alkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, (1imidazolyl)acetylt 3-(2-imidazolyl)propionyl, 2-(4imidazolyl)propionylt 4-(l-imidazolyJ~butyryl, 2,2-dimethyl- 3-(2-imidazolyl)propionyl, 5-(4-imidazolyl)pentanoyll 6-(limidazolyl)hexanoylt and the like.

The "amino-lower alkanoyl having optionally a substituent selected from a lower alkyl and a lower alkoxy- 112 WO 94/01113 VCV930l3S carbonyli includes a straight chain or branched chain alkanoyl having 2 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 substituents selected from a straigh. chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, 2-aminoacetyl, 3-aminopropionyl, 2-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyll 6-aminohexanoyl, 2,2dimethyl-3-aminopropionyl, 2-zethyl-3-aminopropionyl, 2methylaminoacetyl, 2-ethylaminopropionyl, 3-propylaminopropionyl, 3-isopropylaminopropionyl, 4-butylaminobutyryl, 6-hexylaminohexanoyl, 2-dimethylaminoacetyl, 2-diethyleminoacetyl, 2-(N-ethyl-N-propylamino)acetyl, 3-(N-methyl-N-hexylamino)propionylI 2-methoxycarbonylaminoacetyl, 2-ethoxycarbonylaminoacetyl, 3-propoxycarbonylaminopropionyl, 4-butoxycarbonylaminobutyryl, 2tert-butoxycarbonylaminoacetyl, pentanoyl, 6-hexyloxycarbonylaminohexanoyl, 2- (N-methyl-Ntert-butoxycarbonylamino)acetyl, and the like.

The "aminocarbonyl-lower alkyl having a lower alkyl substituent" includes a straight chain or branched chain alkyl. group having 1 to 6 carbon atoms which is substituted by an aminocarbonyl group having 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methylaminocarbonylmethyl, 1ethylaminocarbonylethyl, 2-propylaminocarbonylethyl, 3isopropylaminocarbonylpropyl, 4-butylaminocarbonylbutyl, pentylaminocarbonylpentyl, 6-hexylaminocarbonvlhexyll WO 94/01113 Mr/CrI P3/00835 dimethylaminocarbonylmethyl, 3-diethylaminocarbonylpropyl, diethylaminocarbonylmethyl, (N-ethyl-N-propylamino)carbonylmethyl, 2-(N-methyl-N-hexylamino)carbonylethyl, and the like.

The "amino-substituted lower alkoxy having optionally a lower alkyl substituent" includes an aminosubstituted straight chain or branche'. chain alkoxy having 1 to 6 carbon atoms wherein the amino group has optionally 1 to 2 substituents of a straight chain or branched chain alkyl having 1 to 6 carbon atoms, for example, aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 6-aminohexyloxy, l,l-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, methylaminomethoxy, 1ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy, 4-butylaminobutoxy, 5-pentylaminopentyloxy, 6hexylaminohexyloxy, dimethylaminomethoxy, (N-methyl-Npropylamino)methoxy, 2-(N-methyl-N-hexylamino)ethoxy, and the like.

The active ingredients of the present oxytocin antagonists of the present invention can be easily prepared by a conventional method, for example, the carbostyril derivatives of the formula can be prepared, for example, by the method dislcosed in Japanese Patent First Publication (Kokai) No. 173870/1991, and the benzohetrocyclic compounds of the formula can be prepared, for example, by the method disclosed in European Patent No. 450097.

Among the active compounds and of this invention, the compounds having an acidic group can easily -1-1 114 WO 94/01113 PCT/JP93/00835 be converted into salts by treating with a pharmaceutically acceptable basic compound. The basic compound includes, for example, metal hydroxides such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, etc., alkali metal carbonates or hydrogen carbonates such as sodium carbonate, sodium hydrogen carbonate, etc., alkali metal alcoholates such as sodium methylate, potassium ethylate, etc. Besides, among the active compounds and of this invention, the compounds having a basic group can easily be converted into acid addition salts thereof by treating with a pharmaceutically acceptable acid. The acid includes, for example, inorganic acids such as sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, etc., and organic acids such as acetic acid, p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, citric acid, succinic acid, benzoic acid, etc. Among the active compounds and of the invention, the compounds having an ammonium group can be converted into a salt thereof with a pharmaceutically acceptable halogen anion chlorine anion, bromine anion, fluorine anion, or iodine anion). These salts are useful as an active ingredient of the present oxytocin antagonist as like as the compounds and in the free form.

In addition, the active compounds and of this invention include stereoisomers and optical isomers, and these isomers are also useful as the active ingredient in this invention.

The active compounds of the present oxytocin wL5 WO 94/01113 PCT/JP93/00835 antagonst obtained by the method disclosed in European Patent No. 450097 can easily be isolated and purified by a conventional isolation method. The isolation methods are, for example, distillation method, recrystallization method, column chromatography, ion exchange chromatography, gel chromatography, affinity chromtography, preparative thin layer chromatography, extraction with a solvent, and the like.

The compounds of the formulae and their salts are useful as an oxytocin antagonist and are used in the form of a conventional pharmaceutical preparation. The preparation is prepared by using conventional dilutents or carriers such as fillers, thickening agents, binders, wetting agents, disintegrators, surfactants, lubricants, and the like. The pharmaceutical preparations may be selected from various forms in accordance with the desired utilities, and the representative forms are tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections (solutions, suspensions, etc.), and the like. In order to form in tablets, there are used conventional carriers such as vehicles lactose, white sugar, sodium chloride, glucose, urea, starches, calcium carbonate, kaolin, crystalline cellulose, silicic acid, etc.), binders water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrators dry starch, sodium arginate, agar 116 WO 94/01113 PCT/JP93/00835 powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium laurylsulfate, stearic monoglyceride, starches, lactose, etc.), disintegration inhibitors white sugar, stearin, cacao butter, hydrogenated oils, etc.), absorption promoters quaternary ammonium base, sodium laurylsulfate, etc.), wetting agents glycerin, starches, etc.), adsorbents starches, lactose, kaolin, bentonite, colloidal silicates, etc.), lubricants purified talc, stearates, boric acid powder, polyethylene glycol, etc.), and the like. Moreover, the tablets may also be in the form of a conventional coated tablet, such as sugarcoated tablets, gelatin-coated tablets, enteric coated tablets, film coating tablets, or double or multiple layer tablets. In the preparation of pills, the carriers include conventional vehicles glucose, lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin, talc, etc.), binders gum arabic powder, tragacanth powder, gelatin, ethanol, etc.), disintegrators laminaran, agar, etc.), and the like. In the preparation of suppositories, the carriers include conventional vehicles, for example, polyethylene glycol, cacao oils, higher alcohols, higher alcohol esters, gelatin, semi-synthetic glycerides, and the like. Capsules can be prepared by charging a mixture of the active compound of this invention with the above carriers into hard gelatin capsules or soft capsules in a usual manner. In the preparation of injections, the solutions, emulsions or suspendions are steriill- 117 WO 94/01113 PCT/JP93/00835 lized and are preferably made isotonic with the blood. In the preparation of these solutions, emulsions and suspensions, there are used conventional diluents, such as water, ethyl alcohol, macrogol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitan fatty acid esters, and the like. In this case, the pharmaceutical preparations may also be incorporated with sodium chloride, glucose, or glycerin in an amount sufficient to make them isotonic, and may also be incorporated with conventional solubilizers, buffers, anesthetizing agents. Besides, the pharmaceutical preparations may optionally be incorporated with coloring agents, preservatives, perfumes, flavors, sweeting agents, and other medicaments, if required.

The amount of the active compounds of the formulae and of this invention (active ingredient) to be incorporated into the oxytocin antagonist of the present invention is not specified but may be selected from a broad range, but usually, it is preferably in the range of about 1 to 70 by weight, more preferably about 5 to 50 by weight.

The oxytocin antagonist of the present invention may be administered in any method, and suitable method for administration may be determined in accordance with types of the preparations, ages, sexes and other conditions of the patients, the degree of severity of diseases, and the like. For instance, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered orally.

i-1~1 118 WO 94/01113 PCT/JP93/00835 The injections are intraveneously administered alone or together with a conventional auxiliary liquid glucose, amino acid solutions), and further are optionally administered alone in intramuscular, intracutaneous, subcutaneous, or intraperitoneal route, if required. Suppositories are administered in intrarectal route.

The dosage of the oxytocin antagonist of the present invention may be selected in accordance with the sage, ages, sexes and other conditions of the patients, the degree of severity of the diseases, and the like, but is usually in the range of about about 0.6 to 50 mg of the active compound or per 1 kg of body weight of the patient per day. The active compound is preferably contained in an amount of about 10 to 1000 mg per the dosage unit.

Best Mode for Carrying Out the Invention The present invention is illustrated by the following Preparations of oxytocin antagnist, and Experiments of the activities of the active compounds (1) and of the present invention.

Preparation 1 Film coated tablets are prepared from the following components.

Components Amount 1-[1-(4-Dimethylaminobenzoyl)-4piperidinyl]-3,4-dihydrocarbostyril 150 g Avicel (tradename of microcrystalline cellulose, manufactured by Asahi Chemical Industry Co., Ltd., Japan) 40 g 119 WO 94/01113 PCT/JP93/00835 Corn starch 30 g Magnesium stearate 2 g Hydroxypropyl methylcellulose 10 g Polyethylene glycol-6000 3 g Castor oil 40 g Ethanol 40 g The active component of the present invention, Avicel, corn starch and magnesium stearate are mixed and kneaded and the mixture is tabletted using a conventional pounder (R 10 mm) for sugar coating. The tablets thus obtained are coated with a film coating agent consisting of hydroxypropyl methylcellulose, polyethylene glycol-6000, castor oil and ethanol to give film coated tablets.

Preparation 2 Tablets are prepared from the following components.

Components Amount 1-[1-(2-Methoxy-4-ethoxybenzoyl)-4piperidinyl]-3,4-dihydrocarbostyril 150 g Citric acid 1.0 g Lactose 33.5 g Dicalcium phosphate 70.0 g Pullonic F-68 30.0 g Sodium laurylsulfate 15.0 g Polyvinylpyrrolidone 15.0 g Polyethylene glycol (Carbowax 1500) 4.5 g Polyethylene glycol (Carbowax 6000) 45.0 g Corn starch 30.0 g Dry sodium stearate 3.0 g

II

120 WO 94/01113 -PC/JP93/00835 Dry magnesium stearate 3.0 g Ethanol q.s.

The active compound of the present invention, citr.c acid, lactose, dicalcium phosphate, Pullonic F-68 and sodium laurylstearate are mixed. The mixture is screened with No. 60 screen and is granulated with an alcohol solution containing polyvinylpyrrolidone, carbowax 1500 and 6000. If required, an alcohol is added thereto so that the powder mixture is made a paste-like mass. Corn starch is added to the mixture and the mixture is continuously mixed to form uniform particles. The resulting particles are passed through No. 10 screen and entered into a tray and then dried in an oven at 100°C for 12 to 14 hours. The dried particles are screened with No. 16 screen and thereto are added dry sodium laurylsulfate and dry magnesium stearate, and the mixture is tabletted to form the desired shape.

The core tablets thus prepared are vanished and dusted with talc in order to guard from wetting.

Undercoating is applied to the core tablets. In order to administer the tablets orally, the core tablets are vanished several times. In order to give round shape and smooth surface to the tablets, further undercoating and coating with lubricant are applied thereto. The tablets are further coated with a coloring coating material until the desired colored tablets are obtained. After drying, the coated tablets are polished to obtain the desired tablets having uniform gloss.

ICi-l-- I- 121 WO 94/01113 PCT/JP93/00835 Preparation 3 An injection preparation is prepared from the following components.

Components Amount 7-Fluoro-l-[1-(2,4-dimethoxybenzoyl)-4piperidinyl]-3,4-dihydrocarbostyril 5 g Polyethylene glycol (molecular weight: 4000) 0.3 g Sodium chloride 0.9 g Polyoxyethylene sorbitan monooleate 0.4 g Sodium metabisulfite 0.1 g Methyl-paraben 0.18 g Propyl-paraben 0.02 g Distilled water for injection 10.0 ml The above parabens, sodium metabisulfite and sodium chloride are dissolved in distilled water of half volume of the above with stirring at 80°C. The solution thus obtained is cooled to 40 0 C, and the active compound of this invention and further polyethylLne glycol and polyoxyethylene sorbitan monooleate are dissolved in the above solution. To the solution is added distilled water for injection to adjust to the desired volume, and the solution is sterilized by filtering with an appropriate filter paper to give an injection preparation.

Preparation 4 Film coated tablets are prepared from the following components.

Components Amount 4-Methylamino-l-[4-(3,5-dichlorobenzoylamino)benzoyl]-l,2,3,4-tetrahydroquinoline 150 g 122 WO 94/01113 PCT/JP93/00835 Avicel (tradename of microcrystalline cellulose, manufactured by Asahi Chemical Industry Co., Ltd., Japan) 40 g Corn starch 30 g Magnesium stearate 2 g Hydroxypropyl methylcellulose 10 g Polyethylene glycol-6000 3 g Castor oil 40 g Ethanol 40 g The active component of the present invention, Avicel, corn starch and magnesium stearate are mixed and kneaded and the mixture is tabletted using a conventional pounder (R 10 mm) for sugar coating. The tablets thus obtained are coated with a film coating agent consisting of hydroxypropyl methylcellulose, polyethylene glycol-6000, castor oil and ethanol to give film coated tablets.

Preparation Tablets are prepared from the following components.

Components Amount l-[4-(N-Butylanilinoacetylamino)benzoyl]- 2,3,4,5-tetrahydroy-lH-benzazepine 150 g Citric acid 1.0 g Lactose 33.5 g Dicalcium phosphate 70.0 q Pullonic F-68 30.0 g Sodium laurylsulfate 15.0 y Polyvinylpyrrolidone 15.0 g Polyethylene glycol (Carbowax 1500) 4.5 g Polyethylene glycol (Carbowax 6000) 45.0 g

I_

123 WO 94/01113 PCT/JP93/00835 Corn starch 30.0 g Dry sodium stearate 3.0 g Dry magnesium stearate 3.0 g .Ethanol q.s.

The active compound of the present invention, citric acid, lactose, dicalcium phosphate, Pulloni.c -68 and sodium laurylstearate are mixed. The mixture is screened with No. 60 screen and is granulated with an alcohol solution containing polyvinylpyrrolidone, carbowax 1500 and 6000. If required, an alcohol is added thereto so that the powder mixture is made a paste-like mass. Corn starch is added to the mixture and the mixture is continuously mixed to form uniform particles. The resulting particles are passed through No. 10 screen and entered into a tray and then dried in an oven at 100 0 C for 12 to 14 hours. The dried particles are screened with No. 16 screen and thereto are added dry sodium laurylsulfate and dry magnesium stearate, and the mixture is tabletted to form the desired shape.

The core :ablets thus prepared are vanished and dusted with talc in order to guard from wetting.

Undercoating is applied to the core tablets. In order to administer the tablets orally, the core tablets are vanished several times. Yn order to give round shape and smooth surface to the tablets, further undercoating and coating with lubricant are applied thereto. The tablets are further coated with a coloring coating material until the desired 124 WO 94/01113 PCT/JP93/00835 colored tablets are obtained. After drying, the coated tablets are polished to obtain the desired tablets having uniform gloss.

Preparation 6 An injection preparation is prepared from the following components.

ComDonents Amount 4-Methyl-l-[4-(2,3-dimethylbenzoylamino)benzoyl]-2,3,4,b-tetrahydro- 5 g 1H-1,4-benzodiazepine Polyethylene glycol (molecular weight: 4000) 0.3 g Sodium chloride 0.9 g Polyoxyethylene sorbitan monooleate 0.4 g Sodium metabisulfite 0.1 g Methyl-p -aben 0.18 g Propyl-p aben 0 02 g Distilled water for injection 10.0 ml The above parabens, sodium metabisulfite and sodium chloride are dissolved in distilled water of half volume of the above with stirring at 80 0 C. The solution thus obtained is cooled to 40 0 C, and the active compound of this invention and further polyethylene glycol and polyoxyethylene sorbitan monooleate are dissolved in the above solution. To the solution is added distilled water for injection to adjust to the desired volume, and the solution is sterilized by filtering with an appropriate filter paper to give an injection preparation.

Pharmacological Test Oxytocin Receptor Binding Assay WO 94/01113 PCTJP9/3/r Uterin muscle is taken out from a rat which has previously been injected subcutaneously with diethylstilbestrol the day before, and homogenized, which is used as a membrane preparation. The membrane preparation (0.2 mg), 3 H]-oxytocin (100000 dpm, 10-9M), a test compound 9 10-5 M) are inclubated at 250C for one hour in 100 m Tris-HC1 buffer (pH=8.0, 250 pl) containing 5 mM MgC12, 1 mM MEDTA and 0.1 BSA. The mixture is filtered through the glass filter (GF/F) so as to separate the membrane preparation combining with 3 H]-oxytocin, and then, washed twice with the buffer (5 ml). This glass filter is put into a vial and mixted with Aquasole (liquid scintillation cocktail). The amount of 3 H]-oxytocin combining with the membrane is measured by liquid scintillation counter. The rate of the inhibitory effect of the test compound is estimated according to the following equation.

Inhibitory Rate 100 [(C 1 x 100

C

1 The amount of ([3]-oxytocin combining with the membrane in the presence of a test compound (known amount).

CO: The amount of 3 H)-oxytocin combining with the membrane in the absence of a test compound.

B: The amount of t 3 H]-oxytocin combining with the membrane in the presence of the excess amour.: of oxytocin (5 x 10 6

M).

The results are expressed as ICs 5 values, which is WO 94/01113 WO 9/0113 CT/31193/00835 the concentration of the test compound required to achieve the inhibitory effect in the rate of SO The results are shown in the following Tables I and 2.

Test comnounds The compounds of the formula 1-1: l-(l-(4-(6-Azninohexyloxy)benzoyl]-4-piperidinyl)- 3, 4-dihydrocarbostyril J3-2: 1-fl-f 4-(6-Acetylaminohexyloxy)benzoyl] -4piperidinyl)-3, 4-dihydrocarbostyril 1-3: 1-(l-[4-(6-Methylsulfonylaminohexyloxy)benzoyl]-4piper idinyl)-3 ,4-dihydrocarbostyril 1-4: 1-f l-(4-(7-Hydroxy-8-diethylaminooctyloxy)benzoyl]- 4-piper idinyl)-3, 4-dihydrocarbostyril 1-fl-(4-f6-(4-lMethyl-l-piperazinyl)hexyloxy)benzoyl )-4-piperidinyl)-3 ,4-di-hydrocarbostyriI 1-6: 1-f l-(4-(6-fN-Methyl-N-(2-(2-pyridyl)ethyl)amino)hexyloxylbenzoyl )-4-piper idinyl)-3, 4-dihydrocarbostyril 1-7: 1-(l-(4-(6-Dimethylaminohexyloxy)benzoyl)-4piperidinyl)-3, 4-dihydrocarbostyril 1-8: 1-fl-14-(6-(l-Pyrrolidinyl)hexyloxy)benzoyl)-4piperidinyl)-3, 4-dihydrocarbostyril 1-9: 1-(l-(4-(7-(l-Pyrrolidinyl)octyloxy)benzoyl)-4piperidiriyl)-3, 4-dihydrocarbostyril 1-10: 1-fl-f 4-(7-(4-Methyl-l-piperazinyl)octyloxy)benzoyl)-4-piperidinyl)-3, 4-dihydrocarbostyril 1-11: 1-fl-f 4-(4-Acetylaminobutyloxy)benzoyl)-4- WO 94/01113 1'cr, V 93300835 piperidinyl)-3 ,4-dihydrocarbostyril 1-12: 1-(l-t4-(6-Diethylamitno-5-hydroxyhexyloxy)benzoyl)- 4-piperidinyl)-3 ,4-dihydroc-arbostyril 1-13: 4- benzoyl )-4-piperidinyl)-3, 4-dihydrocarbostyril 1-14: 1-(1-(4-(4-(4-Benzyl-l-piperazinyl)butoxy)benzoyl]- 4-piper idinyl)-3 ,4-dihydrocarbostyril 1-15: 1-(1-t4-(4-(1-Piperazinyl)butoxy)benzoyl)-4piperidinyl)-3, 4-dihydrocarbostyriI 1-16: 1-(1-[4-f4-(l-Pipera, inyl)carbonyloxybutoxy1benzoyl )-4-piperidinyl)-3, 4-dihydrocarbostyriI 1-17: 1-(1-14-(5-Hydroxy-6-(4-benzyl-1-piperazinyl)hexyloxy)benzoyll-4-piperidiny1)-3, 4-dihydrocarbostyriI 1-18: 1-(J-[4-(5-Hydroxy-6-[N-methyl-N-(2-hydroxy-2phenylethyl)amino~hexyloxy)benzoyl)-4-piperidinyl)- 3, 4-dihydrocarbostyril 1-19: 1-{1-t4-(6E2(S)-Hydroxymethyl-1--pyrrolidinyl)-5hydroxy)hexyloxy)benzoyl)-4-piperidinyl)-3,4dihydrocarbostyril 1-20: 1-(l-(4-(5-Hydroxy-6-(3,4-dimethoxybenzylamino)hexyloxy)benzoyl)-4-piperidinyl)-3,4-dihydrocarbostyril 1 21: 1-(1-[4-(5-Hydroxy-6-( 4-benzyl-l-piperidino)hexyloxy)benzoylj-4-piperidinyl)-3 ,4-dihydrocarbostyril 1-22: 1-(1-(4-t4-(4-Piperidinylcarbonylamino)butoxy)benzoyl )-4-piperidinyl)-3,4-dihydrocarbostyril 1-23: 1-(1-[4-(5-Methoxy-6-diethylniethylammoniumhexyloxy)benzoyl]-4-piperidinyl)-3,4-dihydrocarbostyril WO 94/01113 PCT/JI*93/00835 iodide 1-24: 1-(1-t4-(Al1ylaminobutoxy)benzoyl)-4-piperidinyl)- 3, 4-dihydrocarbostyri.

1-25: 1-{.-t4-(5-Hydroxy-6-(allylaminohexyloxy)benzoyl)- 4-piper idinyl)-3, 4-dihydrocarbostyril 1-(1-(4-[3-(4-Benzoyl-l-piperazinyl)propoxy)benzoyl 1-4-piperidinyl)-3, 4-dihydrocarbostyril 1-27:, 1-[1-(4-[3-(4-Anilinocarbonyl-1-piperazinyl)propoxylbenzoyl)-4-piperidinyl. 4-dihydrocarbostyril 1-28: 1-(1-(4-(3-Phenysulffonyaminopropoxy)benzoyl..4piperidiriyl)-3, 4-dihydrocarbostyril 1-29: 1-{l-[4-(4-Hydroxy-5-.(1-pyrrolidinyl)pentyloxy)benzoyl ]-4-piperidinyl)-3, 4-dihydrocarbostyril 1-30: 1-(1-[4-(4-Hydroxy-5-(l-piperidinyl)pentyloxy)benzoyll-4-piperidinyl)-3, 4-dihydrocarbostyri.

1-31: 1-fl-(4-(4-Hydroxy-5-(4-mnorpholino)pentyloxy)benzoyl]J-4-piperidinyl)-3, 4-dihydrocarbostyriI 1-32: 1-(I-[4-(3-Diethylaminopropoxy)benzoyl)-4piperidinyl)-3 ,4-dihydrocarbostyril 1-3 3: 1-(1-[4-(3-Hydroxy-4-diethylaminobutoxy)benzoyl)-4piper idinyl}-3 ,4-dihydrocarbostyril 1-3 4: 1-(1-[4-Anilinooxycarbonyl)-4-piperidinyl)-3,4dihydrocarbostyril 1-35: 1-(1-t4-Benzoylaminophenoxycorbonyl1-piperidinyl)- 3, 4-dihydrocarbostyril 1-36: 1-(1-[4-(5-Hydroxypentyloxy)benzoyl)-4piper idinyl)-3, 4-dihydrocarbostyril WO 94/01113 -PCr/JP93/00835 1-37:, (4-Carbamoylmethylaminiocarbonl,'lbutoxy) benzoyl3-4-piperidinyl)-3 ,4-dihydrocarbostyril 1-38: 1-(1-(4-(5-Carbamoyloxypentyloxy)benzoyl]-4piperidinyl]-3, 4-dihydrocarbostyril 1-39: 5,7-Difluoro-l-[l-(2-methoxy-4-ethoxybenzoyl)-4pipe ridiny. 4-dihydrocarbostyril 1-40: (2S)-1,3-Dicarbamoyllpropylarninocarbonylpentyloxy)benzoyl)-4-piperidinyl)-3,4dihydrocarbostyril 1-41: 1-f1-(2-Hydroxy-4-ethoxybenzoyl)-4-piperidilyl)-7fluoro-3, 4-dihydrocarbostyril 1-42: 5-Methyl-l-[l-(2-methoxy-4-ethoxybenzoyl)-4piperidinyl 4-dihydrocarbostyril 1-43: 1-(l1-(4-[5-(l-Iniidazolyl)pentyloxylbenzoyl)-4piper idinyl)-3, 4-dihydrocarbostyri.

1-44: 5-Methyl-l-(1-[4-(3-acetylamiflopropoxy)beflzoyl-4piper idinyl)-3, 4-dihydrocarbo, tyril 1-45: 1-{1-[4-(2-Propionyloxy)benzoyl]-4-piperidinyl)- 3, 4-dihydrocarb'ostyri1 1-46: 1-(l-[4-(4-Carboxybutoxy)benzoyll-4-piperidilyl)- 3, 4-dihydrocarbostyril 1-47: 1-(1-[4-(5-Carbamoylpentyloxy)benzoyll-4piperidinyl)-3, 4-dihydrocarbostyril 1-48: 1-(l-[4-(3-Carbamoylpropylamino)benzoyl)-4piperidinyl)-3, 4-dihydrocarbostyril 1-49: 1-(1-[4-(5-Hydroxypentyloxy)benzoylI-4piperidinyl)-3, 4-dihydrocarbost yril 1-50: 1-{1-t4-(5-Acetylaminopentyloxy)belzoyll-4- 1 WO 94/01113 PCT/J P93/00835 piperidinyl)-3, 4-dihydrocarbostyril 1-51: 1-[1-(4-IMethoxyanilinocarbonyl)-4-piperidinyl)-3,4dihydrocarbostyril 1-52: 1-[l-(4-Ethoxybenzoyl)-4-piperidinyllcarbostyri.

1-53: 6,7-Difluoro-l-[l-(2-methoxy-4-ethoxybenzoyl)-4piper idinyl] 4-dihydrocarbostyril 1-54: 1-(l-(4-(4-(1-Pyrrolyl)butoxylbenzoyl)-4piperidinyl 1-3 ,4-dihydrocarbostyriI 1-55-. 1-[l-f4-t3-(4-llethyl-l-piperazinyl)propoxy]benzoyl)-4-piperidinyl ,4-dihydrocarbostyril dioxalate 1-56: 1-(X-(4-(5-[(S)-l-Carbarnoyl-2-(4-hydroxyphenyl) 1ethylaminocarbonylpentyloxy)benzoyl 1-4piperidinyl)-3 ,4-dihydrocarbostyril 1-57: 7-Fluoro-l-(1-benzoyl-4-piperidinyl)carbostyril 1-58: 7-Fluoro-l-(1-(2,4-dimethoxybenzoyl)-4-piperidinyl 3carbostyril 1-59: 1-(1-[4-(5-[((iS)-l-Carbainoyl-3--(methylthio) Ipropylaminocarbonvlpentyloxy)berzoyl]-4-piperidinyl)-3, 4dihydrocarbostyril 1-60: 1-(1-[4-(5-(2-Hydroxy-3-diethylaminopropoxy)pentyloxy )benzoyl I-4-piperidiriyl)-3 ,4dihydrocarbostyril 1-61: 1-{1-[4-(5-(3-Dimnethylaminopropyl)aminocarbonylpentyloxy )benzoyl I-4-piperidinyl)-3,4dihydrocarbos tyril 1-62: 1-(1-[4-(5-(l-Benzyl-4-piperidinyl)aminocarbonylpentylixy)benzoy1 1-4-piper idinyl)-3 ,4- WO094/01113 11PCr/JP93/00835 dihydrocarbostyril 1-63: 1-(l-i4-(5-Hydroxy-6-(l-pyrrolidinyl)hexyloxy)benzoyl )-4-piperidinyl)-3 ,4-dihydrocarbostyril 1-64: 1-(l-[4-(5-(4-Piperidinyl)aminocarbonylpentyloxy)benzoyl ]-4-piperidinyl)-3, 4-dihydrocarbostyri.

1-65: 1-(l-14-(S-(l-Pyrrolidinyl)pentyloxy)benzoy.)-4piperidinyl)-3, 4-dihydrocarbostyril 1-66: l-(l-(4-(5,6-DihydroxyhexyJloxy)benzoyl)-4piperidinyl)-3, 4-dihydrocarbostyri.

1-67: 1-(l-(4-(5-Hydroxy-6-(3-methoxybenzylamino)hexyloxy ]benzoyl )-4-piperidinyl)-3, 4-dihydrocarbostyril 1-68: (1S)-1-Axinoethylcarbonylamino)propoxy) benzoyl )-4-piperidinyl) 4-dihydrocarbostyril 1-69: 5, 7-Dimethyl-1- (2-methoxy-4-ethoxybenzoyl pipe ridinyl J-3, 4-dihydrocarbostyril 1-70: 1-(l-(4-(5-(2-Irnidazolylsulfonyl)pentyloxy)benzoyl)-4-piperidinyl)-3, 4-dihydrocarbostyril 1-71: 1-(l-(4-(5-Hydroxy-6-tN-methyl-N-(2-(2-pyridyl)ethyl)amino)hexyloxylbenzoyl )-4-piperidinyl)-3 ,4dihydrocarbostyri.

1-72: 1-f 1-(4-(5-(2-(4-Methyl-l-piperazinyl)acetylamino)pentyloxy Ibenzoy -4-piperidinyl)-3, 4-dihydrocarbostyril 1-73: 1-(1-(4-tS-(l-Oxo-4-pyridylsulfonyl)pentyloxy)benzoyl-4-piperidinyl)-3, 4-dihydrocarbostyril 1-74: 1-(1-(4-f[5-(3-Hydroxy-l-piperidino)pentyloxy)benzoyl)-4-piperidinyl)-3 ,4-dihydrocarbostyril 1 332- WO 94/01113 PC/JP93/00835 1-75: 1-(l-(4-[15-(4-Diethylaminophenylsulfonyl)pentyloxylbenzoyl)-4-piperidinyl)-3, 4-dihydrocarbostyril 1-76: 1-(l-t4-(5-(4-Dimethylaminobenzoyamino)penityloxy)benzoyl 1-4-piperidinyl.)-3, 4-dihydrocarbostyril 1-77: 1-{1-(4-[5-(2-(2-Hydroxyethyl)-1-piperazinyl)pentyloxy Ibenzoyl )-4-piperidinyl)-3, 4-dihydrocarbostyri.

1-78: 1-{1-(4-[5-(N,N-(2-Hydroxyethyl)arninolpentyloxy)benzoyl-4-piperidinyl)-3 ,4-dihydrocarbostyriI 1-79: 1-(1-t4-(5-Hydroxy-6-(l-piperidinyl)hexyloxy)benzoyl)3-4-piperidinyl}-3, 4-dihydrocarbostyri.

1-80: 5-Hydroxy-l-(1-[4-(3-acetylaminopropoxy)benzoyl)-4piperidinyl)-3, 4-dihydrocarbostyril 1-81: 1-fl(t2-Methoxy-4- (4-carbamoylbutoxy )benzoyl piper idinyl)-3 ,4-dihydrocarbostyril 1-82: 1-(1-t4-(5-(2-Methyl-l-piperidinyl)pentyloxylbenzoyl 1-4-piper idinyl}-3, 4-dihydrocarbostyril 1-83: 5-Acetoxy-1-( 1-(2-rethoxy-4-ethoxybenzoyl)-4piperidinyl. 4-dihydrocarbostyril 1-84: (5-Isopropylamnino)pentyloxylbenzoyll-4piper idinyl}-3 ,4-dihydrocarbostyri.

1-85: 1-(1-(4-(2,4-Di-(5-(1-pyrrolidinyl)pentyloxy)1benzoyl)-4-piperidinyl)-3, 4-dihydrocarbostyril 1-86: 1-(l-t4-(5-Dimethylaminopentyloxy)benzoyl]-4piperidinyl)-3 ,4-dihydrocarbostyril 1-87: 1-{1-[2-Methoxy-4-(4-thiomorpholinocarbonylbutyloxy)benzoyll-4-piperidinyl)-3 ,4-dihydrocarbostyriI 1-88: 1-{1-(2-Methoxy-4-[4-(l-oxo-4-thiomorpholino)- 133 WO 94/01113 PCT/JP93/0083S carbonyjlbutyloxybenzoyl)-4-piperidinyl}-3, 4dihydrocarbostyril 1-89: 1-(1-(2-Methoxy-4-(1,1-dioxo-4-thiomorpholino)carbonylbutyloxybeizoyl )-4-piperidinyl)-3, 4dihydrocarbostyri.

1-90: 1-(l-[4-(5-tert-Butylaminopentyloxy)benzoyl]-4piperidinyl)-3, 4-dihydrocarbostyril 1-91: 1-(l-[4-(5-(2-Propynylamino)pentyloxy)benzoyll-4piperidinyl)-3 ,4-dihydrocarbostyril 1-92: i-f 1-(4-(6-Hydroxy-7-diethylarnino)heptyloxy)benzoyl I-4-piperidinyl}-3 ,4-dihydrocarbostyril 1-93: 1-(l-[4-(5-Cyclopropylaminopentyloxy)benzoyl)-4piperidinyl)-3 ,4-dihydrocarbostyril 1-94: 1-(l-(4-(5-Tricyclo[3.3.1.1]decanylmethylaminopentyloxy)benzoyl ]-4-piperidinyl)-3,4dihydrocarbostyril 1-95: '1-(l-[5-[3-(3-Azaspiro(5,_5)undecanyl) spiro-4- -piperidinyl )pentyloxy) benzoyl 1-4pipe ridinyl}-3 ,4-dihydrocarbostyril 1-96: 1-(l-[4-(5-Butylaminopentyloxy)benzoyl)-4piperidinyl}-3, 4-dihydrocarbostyril 1-97: -(5-Cyclohexylaminopentyloxy)benzoyl]-4piper idinyl)-3, 4-dihydrocarbostyril 1-98: 1-(l-(4-(5-Tricyclo[3.3.1.1)decanylamilopeltyl oxy)benzoyl ]-4-piperidinyl}-3, 4-dihydrocarbostyril 1-99 1-(l-[4-(3-Acetylaminopropoxy)benzoyl)-4piperidinyl)-3, 4-dihiydrocarbostyril -134 WO 94/01113 PC/JP93/ 00835 The compounds of the formula 2-1: 3- Methyl-i-f 4- (2-methylbenzoylamino) benzoyl 1- 1,2,3, 4-tetrahydroquinoline 2-2: 5-Methyl-i-f 2-methylbenzoyiamino)benzoyll- 2,3, 4, 2-3: 5-Hydroxymethyi-7-chioro-l- f4- (2-rethylbenzoyiamino) benzoyl 1-2, 3,4, 5-tetrahydro-1E-benzazepine 2-4: 4 -Hydroxy-l-f4-(2-methylbenzoylamino)benzoyl)- 1,2,3, 4-tetrahydroqu incline 4-Hydroxy-1- f4- (2-methylbenzoylami no) benzoyi I- 2,3,4, 2-6: 5-Hydroxy-l-[2-methox-y-4-(2-methylbenzoylamino)benzoyi 1-2,3,4, 2-7: 5-Hydroxy-6-methyl-i-[f2-chloro-4- methyibenzoylamino)benzoyll-2,3,4,5-tetrahydro-lH-benzazepine 2-8: 4 -Methyl-5-hydroxy-l-4-(2..methylbenzoylamino)-.

benzoyi 1-2,3,4, 2-9: 5-Hydroxy-7-chloro-l-[f2-methoxy-4-(2-methylbenzoylaminio) benzoylj-2 2-10: 5-Hydroxy-7-chloro-l- f2-methyl-4- (2-methylbenzoyiamino) benzoyl 2-11: 5-Hydroxy-7-chloro-i- f3-methoxy-4- (2-methylbenzoyiamino) benzoyl 1-2,3,4, 2-12: 5-Hydroxy-7-chloro-l-(4-[2-(2-methylphenyl)acetylamino lbenzoyl}-2 2--13: 5-Hydroxy-7i-chloro-l-f3-methoxy-4-(2-chlorobenzoylamino) benzoyl 1-2,3,4, 2-14: 5-Hydroxy-l- f2-chloro-4- 4-dichlorobenzoylamino) 135 WO 94/01113 PCr/JP93/00835 benzo 11-2,3,4 ,5-tetrahydro-1'H-benzazepine 2-15: 5-Oxo-J-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5tetrahydro-1E-benzazepine 2-16: 4-Oxo-l-[4-(2-methylbenzoylamino)benzoyl)-2,3,4,5tetrahydro-lH-benzazepine 2-17: 5-Oxo-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl ,5-tetrahydro-1H-benzazepine 2-18: 5-Oxo-1- [2-methyl-4- (2-methylbenzoylami no) benzoyl I- 2,3,4, 2-19: 5-Hydroxy-6-methyl-1- [2-chloro-4- (2-methylbenzoylamino)benzoyll-2,3,4, 5-tetrahydro--1H-benzazepine 2-20: 5-Acetyloxy-l-114-(2-methylbenzoylamino)benzoyl]- 2,3,4 ,5-tetrahyio-1H-benzazepine 2-21: 4-Dimethylaminomn' thy--4-(2-methylbenzoylamino)benzoyll1-1,2,3 ,4-tetrahydroquinoline 2-22: 5-Aminomethyl-l-[4-(2-methylbenzoylamino)benzoyl)- 2,3,4 ,5-tet rahydro-1H-benzazepine 2-23: 5-B ormylaminomethyl-1- (2-methylbenzoylamino) benzoyll-2 5-tetrahydro-1H-benzazepine 2-24: 5-Acetyloxymethyl-1- (2-rnethylbenzoylanino) benzoyl 1-2,3,4, 5-tetrahydro-1H-benzazepine 2-25: 5-Methylsulfonyloxymethyl-l-[4-(2-methylbenzoylamino) benzoyl 1-2, 3,4, 5-tetrahydro-1H-benzazepine 2-26: 1-[2-Chloro-4-(2-methylbenzoylamino)benzoyl]- 2,3,4, oxirane 2-27: 5-Methylaminocarbonyloxy-1- (2-methylbenzoylamino)benzoyll-2, 3,4,5-tetrahydro-lH-benzazepine WO 94/01113 -16-PCTIJP93OO83S 2-28: 5-Carbamoyloxy-l- (2-methylbenzoylamino) benzoy. 2,3,4, 2-29: 5-Dimethylarninocarboriyloxy-l-r 4-C 2-methylbenzoyl,amino)benzoyl 3-2,3,4, 2-30: 5-Carboxymethoxy-l-[4-(2-methylbenzoylamino)benzoyl 3-2,3,4, 2-31: 5- (4-Dimethylaminobutoxy 2-rethylbenzoylamino) benzoyl 3-2,3,4, 5-tetrahydro-1H-benzazepine 2-32: 5-( 3 -Aminopro-ooxy)-l-[4-(2-methylbenzoylamino)benzoyl 1-2,3,4, 2-33: 5-( 2 -Dimethylaminoethoxy)-7-fuoro--[3-methoxy4- (2-methylbenzoylamino )benzoyl 3-2,3 ,4 1H-benzazepine hydrochloride 2-34: 3-Phthalimidlopropoxy )-l-l4-C 2-methylbenzoylamino) benzoyl 1-2,3,4, 2-35: 5-Hydroxyimino-l-[4-(2-methylbenzoylamino)benzoyl).

2,3, 4 2-36: 5-Acetyloxyimino-1-[ 2-methylbenzoylamino)benzoyl. 2-37: 5-Methylidene-1- [2-chloro-4-(C2-methylbenzoylamino) benzoyl 3-2,3, 4, 2-38: 5-Methylidene-l-[4-(2-methylbenzoylamino)benzoyl]- 2,3, 4 2-39: Potassium {1-12-chloro-4-(2-methylbenzoylamino)benzoyl]-2, 3,4, imino-O-sulfonat e 2-40: 5-(2-Dimethylaminoacetyloxy)-l-[4-(2-methylbenzoylamino) benzoyl. WO 94/01113 17- PCT/JP93/00835 2-41: 5-(2-Direthylaminoacetyloxy)-7-fluoro-l-(2-methoxy- 2-methylbenzoylani no) benzoyl 3, tetrahydro-lH-benzazepine 2-'42: 5- (2-Dirnethylaminoacetyloxy) -7-chloro-l- (2cbhlorobenzoylamino) -2-methoxybenzoyl 1-2,3,4,5tetrahydro-lH-benzazepine hydrochloride 2-43: 5- (2-Dimethylaminoacetyloxy )-7-chloro-l- f3-rnethoxy- 4- (2-methylbenzoylamino )benzoyl tetrahydro-lH-benzazepine hydrochloride 2-44: 2-Dimethylaminoacetyloxy)-7-chloro-l-[ 3-chioro- 2-rethylbenzoylamino)benzoyl ,3,4,5tetrahydro-lH-benzazepine 2-45: 5-(2-Dimethylaminoacetyloxy)-7-chloro-l-{2-methoxy- 4-f (2-methylphenyl)acetylamino) ]benzoyl)-2,3,4,5tetrahydro-lH-benzazepine hydrochloride 2-46: 5-(4-Dimethylaminobutyryloxy)-7-chloro-l-[2methoxy-4- (2-rethylbenzoylamino) benzoyl)]-2,3, tetrahydro-lH-benzazepine hydrochloride 2-47: 5- (2-Dimethylarninoacetyloxy luoro-l- [2-chioro- 4- (2-rethylbenzoylamino) benzoyl 1-2,3,4 tetrahydro-lH-benzazepine 2-48: 5-(2--Dimethylaxinoacetyloxy)-7-chloro-l-[2-methyl- 2-chlorobenzoylamino) benzoyl 1-2,3 ,4 tetrahydro-lH-benzazepine hydrochloride 2-49: 5-(2-Aminoacetyloxy)-*7-chloro-l-[3-methoxy-4-(2chlorobenzoylamino)benzoyl]-2,3,4,s-tetrahydr. iRbenzazepine hydrochloride 2-50: 5-(2-Aminoacetyloxy)-7-chloro-l-[3-chloro-4-(2- -138 WO 94/01113 PCT/JP93/00835 methylbenzoylamino) benzoyl 1-2,3, 4, benzazepine hydrochloride 2-51: 5- (2-Arninoacetyloxy) -7-f luoro-l- (2-chloro-4- (2methylbenzoylamino) benzoyl)]-2,3, 4 benzazepine hydrochloride 2-52: 5-(2-Aminoacetyloxy)-7-chloro-l-[2-methyl-4-(2chlorobenzoylaimino)benzoyll-2,3,4, benzazepine hydrochloride 2-53: 5-Carbarnoylmethoxy-l-[4-(2-methylbenizoylanino\1benzoyl 1-2,3,4, 2-54: 5-Dimethylaminocarbonylrnethoxy-l- (2-methylbenzoylamino )benzoyl 3,4, benzazepine 2-55: 5-Carbamoylmethylaminocarbonylmethoxy-7-chlorc-l- [4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5t e tra hy dr o -lH- benz a 'ep in e 2-56: 5-(4-Methyl-l-piperazinylcarbonylnethoxy)-l-[4-(2methylbenzoyldmino) benzoyl.] 3, 4 benzazepine 2-57: 5-Ama io-l-(4-(2-methylbenzoylamino)benzoyl)- 2,3,4, 2-58: 3-Dimethylamino-l-[4-(3,5-dichlorobenzoylamino)benzoyl 4-tetrahydroguinoline 2-59: 4-Methiylamino-l-[4-(2-methylbenzoylamino)benzoyl)- 1, 2,3,4-tetrahydroquinoline 2-60: 4-Dimethylamino-l- [3-methoxy-4- (2-rnethylbenzoylamino) benzoyl 4-tetrahydroguinoline 2-61: 3-Dimethylamino-l-[ 3-methoxy-4-( 2-methylbenzoyl- WO N/01113 19M/9/03 amino) benzoyl -tetrahydro-lH-benzazepint- 2-62: 5-(N-Methyl-N--ethylamino)-l-t4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-c'etrahydro-1H-benzazepine 2-63: 5-Dime thylamino-l- (2-methylbenzoyJlamino benzoyl 1-2,3,4, 5-tetrahydro-1H-benzazepine 2-64: 5-Dimethylarnino-l-[(2-chloro-4- (2-methy3.benzoylamino) benzoyl 1-2, 3,4 ,5-tetrahydro-1H-bernzazepine 2-65: 5-Dimethy3.amino-1-[ 3-ethoxy-4-( 2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-Ii-benzazepine 2-66: 5-Dimethylamino-1-t3-hydroxy-4-( 2-nethylbenzoylamino)benzoyl 3,4, 2-67: 5-Dimethylamino-l-[3-berzyloxy-4-(2-methylbenzcylamino)benzoyl)-2,3,4,5-tetrahydro-lH-benzazepine 2-68: 5-DimethyJlamino-l- [2-ethoxy-4- (2-methylbenzoylamino) benzoyl 1-2,3,4, 2-69: 5-Dimethylamino-l-(3-methyl-4-(2-methylbenzoyl- &mino)benzoylj-2,3,4,5-tetrahydro-1H-benzazepine 2-70: 5-Dimethylamino-l- f2-f luoro-4- (2-methylbenzoylamino)benzoyll-2,3,4,5-tetrahydro-lH-benzazepiie 2-71: 5-Dimethylaminc-l-[3-fluoro-4-(2-methylbenzoylamino)benzoyl]-2t3,4,5-tetrahydro-1Hi-benzazepine 2-72: 5-Dimethylamino-l-[3-methoxy-4-(2,3-dimethylbenzoylami no) benzoyl 1-2, 3,4, benzazepine 2-73: S-Dimethylamino-1-( 4-(,"-methylanilinocarbonyl)benzoyl 1-2,3,4, 5-tetrahydro-1H-benzazepine 2-74: 5-Dimethylamino-l-(3-hydroxy-4-(2-chlorobenzoylamino)benzoyl)-2,3,4, S-tetrahydro-1E-benzazepine 140 WO 94/91113 PCY/J P93100835 2-75: 3-Hydroxy-4-dimethyJlamino-l- (2-methylben2oylaminio)berizoyl]-1,2,3,4-tetrahydroquinoline 2-76: 4-Methyl-S-dime thylamino-l-(4- (2-methylbenzoylamino)benzoyl]-2, 3,4, 2-77: 5-Methylamino-l-f4-(2-methylbenzoylamino)benzoyl)- -tetrahydro-lH-benzazepine 2-78- 5-Methylamino-l-(2-rnethyl-4-(2-methylbenzoylamino)benzoyl 1-2,3,4 2-79: 5-Methylamino-l-(2-chloro-4-(2-mnethylbenzoylamino)benzoyl 1-2,3,4 2-80: 5-Propylamino-l-[4-(2-metzhylbenzoylamino)benzoyl]- 2,3,4 2-81: 5-Ethylamino-l-(4-(2-methylbenzoylamino)benzoyl)- 2, 3, 4, -tetrahydro-lH-benzazepine 2-82: 5-Allylamino-l-t2-chloro-4-(2-methylbenzoylanino)benzoylj.-2,3,4, 2-83: 5-Acetylamino-l-(4-(2-rnethylbenzoylamino)benzoyl)- 2,3,4, 2-84: 5-(N-Acetyl-N-methylamino)-l-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-lH-benzazepine 2-85: 5-CycJlopropylamino-l- [2-chloro-4- (2-methylbenzoylamino) benzoyl 1-2,3,4, 5-tetrahydro-1H--benzazepine 2-86: 5-(2-Dimethylaminoethylaniino)-l-i2-chloro-4-(2methylbenzoylamino)benzoyl)-2,34,5-tetrahydro-1benzazepine 2-87-. 5- (3-Dimethy2.-2-hydroxypropylamino) -1-f4- (2-chiorobenzoylamino) berizoyl benzazepine WO 94/01113 -ci 14P9PJx3/00835 2-88: 5-(2,3-Dihydroxypropylamino)-l-(4-(2-methylbenzovlamino) benzoyl 1-2,3,4, 2-89:. 5-[N-(3-Hydroxypropyl)-N-methylamino)-l-(4-(2methylbenzoylamino)benzoyil-2 benzazepine 2-90: 5-Benzoylamino-l-(4-(2-methylbenzoylamino)benzoylj- 2,3,4, 5-tetrahydto-1H-benzazepine 2-91: 5-(N-Cyanornethyl-N-methylamino)-l-t4-(2-methylbenzoylamino )benzoyi 1-2,3,4 benzazepine 2-92: 5-(N-Carbamoylmethyl-N-methylamino)-I-t4-(2-methylbenzoylamino)benzoyi benzazepine 2-93: 5-fN-(3-ti-Tetrahydropyranyloxylpropyl)-N-methyl)amino-i-[(4- (2-methyibenzoylanino) benzoyl 1-2,3,4 tetrahydro-iH-benzazepine 2-94: 5-,N-(3-Acetyloxypropyl)-N-methyllamino-l-(4-(2methyibenzoyiamino)benzoyl)-2, 1,4,5-tetrahydro-lEbenzazepine 2-95: 5-(l-Benzyl-4-piperidinyi)amino-i-[4-(2-methyibenzoyiamino)benzoylj-2, 3,4, benzazepine 2-96: 3-(4-Methyi-l-piperazinyl)-l-t4-(2,3-dimet"hylbenzoylainino)benzoyll-1, 2,3, 4-tetrahydroquinoline 2-97: 3-(l-Pyrroiidinyl)-1-(4-(2,3-dimethylbenzoylamino)benzoyi 1-1,2,3, 4-tetrahydroquinoline 2-98B: 5-Hydroxy-5-hydroxymethyl-l- t2-chloro-4- C2-me thybenzoy2.amino) benzoyl) 1- 42- WO 94/01113 PCr/J93/00835 benzazepine 2-99: 5-Hydroxy-5-hydroxymethyl-1-f 4- (2-me thylbenzoylamino)benzoyll-2,3,4,5-tetrahydro-Z -benzazepine 2-100: 5-Hydroxyrnethyl-5-N-methyJ~amino-l-(4-( 2-methylbenzoylamitno)benzoyl]-2 13,4 benzazepine 2-101: 5-Hydroxy-5-(N-methylamino)rnethyl-l-f4-(2-methylbenzoylaiino) benzoyl 3-2,3,4, ben za zepin e 2-102: 5-Hydroxy-5-Inethyl-1-f4-(2-methylbenzoylamino)benzoyl]-2,3,4 ,5-tetrahydro-1H-benzazepine 2-103: 5-(N-Ethoxycarbonylmethyl-N-methylarnino)-1-(4-(2niethylbenzoylamino) benzoyl] berizazepine 2-104: 1-f4-(2-methylbenzoylarnino)benzoylj-l,2,3,5tetrahydro-4 ,1-benzoxazepine 2-105: 1-t4-(2-Methylbenzoylamino)benzoylI-1,2,3,4- 1-benzoxazepine 2-106: 4-Methyl-1-f4-(2-methylbenzoylaxnino)benzoyll- 1,2,3, 4-tetrahydroquinoxaline 2-107: 4-Methyl-1-114-(3,5-dichlorobenzoylamino)benzoyl)- 2,3,4, 5-tetr=ahydro-1H-1, 4-benzodiazepine 2-108- 5-Methyl-1-(4-benzoylaminobenzoyl)-2,3,4,5tetrahydro-1E-1, 2-109: 5-Isopropyl-1-( 4-(2,3-dimethylbenzoylamino)benzoyll-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine 2-110: 1-[4-(2-methvlbenzoylamino)benzoyl]-1,2-dihydroquinoline -143 WO 94/01113 PC-ri3P93/00835 2-111: 5-[2-(4-Morpholino)acetyloxy-7-choro--[2.

methoxy-4-( 2-methylbenzoylarino)benzoyl)-2,3,4,5tetrahydro-11i-benzazepine hydrochloride 2-112: 5-(2-Isopropylaminoacetyloxy)-7-chloro-l-(2methoxy-4-(2-methylbenzoylamino)benzoyl)-2,3,4,5tetrahydro-lH-benzazepine hydrochloride 2-1123: 5-(l,5-Diaminopentylcarbony2.oxy)-7-chloro-l-t 2methoxy-4- (2-methylben~ioylamino )benzoyl. -2,3,4 tetrahydro-lH-benzazepine hydrochloride 2-114: 5-( 3 -Amrinopropionyloxy)-7-chloro-l-[2-methoxy-4-( 2methylbenzoylamino)benzoyl 1-2,3,4, benzazepine hydrochloride 2-115: 5-(4-Dinlethylaminobutyryloxy)-7-chloro-1-t3methoxy-4- (2-methylbenzoylanino) benzoyl 1-2, 3,4 tetrahydro-lH-benzazepine hydrochloride 2-116: 5-(1,5-Diaminopentylcarbonyloxy)-7-chloro-l-[3methoxy-4- (2-methylbenzoylamino) benzoyl 1-2,3,4 tetrahydro-lH-benzazepine hydrochloride 2-117: 5-(3-Aminopropionyloxy)-7-fluoro-1-f 2-chloro-4-( 2methylbenzoylanino) benzoyl 1-2,3, 4, benzazepine hydrochloride 2-118: 5-Formyloxy-7-chloro-l-[4-(2-methylbenzoylamino)berizoyl 1-2,3,4 2-119:- 5-Dimethylaminocarbonylmethyl-7-chloro-l-[(4- (2methylbenzoylamino) benzoyl 1-2,3,4, 5-tetrahydro-1Hbenzazepine 2-120: 1-14-[3-Methylphenylsulfonylamino)benzoyl)-2,3,4 tetrahydro-lH-benzazepine -144 WO 94/01113 PCr/J 93/0083 2-121: 1-[4-(2-Methylbenzoylamino)benzoyl]-2,3,4,stetrahydro-lH-oenzazepine 2-122: 1-(4-(4-Methylbenzoylamino)benzoyl]-2,3,4,5tetrahydro-lH-benzazepine 2-123:, 1-[4-(2,3-DimethylAbenzoylarnino)benzoyl)-2-,3,4,5tetrahydro-lH-benzazepine 2-124: 1-t4-(2-Chlorobenzoylamino)benzoyll-2,3,4,5tetrahydro-lH-benzazepine 2-125: 1-[4-(2-Bromobenzoylamino)benzoyl]-2,3,4,5tetrahydro-lH-benzazepine 2-126: 1-(4-(2-Methoxybenz-oylamino)benzoyl]-2,3,415tetrahydro-lH-benzazepine 2-127: 1-(4-Cyclohexylcarbonylaminobenzoyl)-2,3.A tetrahydro-1H-benzazepine 2-128: 1-(4-(2-Carbamoylmethoxybenzoylamino)benzoyl)- 2,3 ,4 2-129: 1-{4-[2-(6-Isopropylaninohexyloxy)beizoylanino)benzoyl)-2, 3,4, 5-tetrahydro-1H-benzazepine 2-130-. 1-[4-(2-(N-Phenyl-l' -ethynylarino)acetylamino)benzoyl 5-tetrahydro-1H-benzazepine 2-131: 1-[4-(2-(N-Phenyl-N-methylamino)acetylamino)benzoyll-2, 3,4, 2-132: 1-f (2-(4-Phenylamino)acetylamino)benzoyl.l-2,3,4,5tetrahydro-1H-benzazepine 2-133t 1-t(4-(2-[N-Phenyl-N-(2-acetyloxy)ethoxylamino)acetylainino)benzoyl 5-tetrahydro-1Hbenzazepine 2-134- 1-U[4-(2-(2-Acetylaminophenoxy)acetylamino)l- 145 WO 94/01113 PMTJP93/00835 benzoyl)-2, 3,4 ,5-tetrahydro-1H-benzazepine 2-135: 1-t4-(3-Fluorobenzoylarnino)benzoyl]-1,2,3,4tetrahydroquinoline 2-136: 1-t4-Tricyclo[3.3.1.l]decanylcarbonylaminobenzoyl)- 1,2,3, 4-tetrahydroquinoline 2-137: 1-(4-Benzylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoline 2-138: 1-[4-(2-Furoylamino)benzoyl]-l,2,3,4-tetrahydroquinoJline 2-139: 1-[4-(3-Thenoylarnino)benzoyl)-2.,2,3,4-tetrahydroquinoline 2-140: )-(4-(3-Ethoxybenzoylamino)benzoyl]-1,2,3,4tetrahydroquinoline 2-141: 7-Chloro-1-(4-(3-hyaLoxybenzoylamino)benzoyl)- 2,3,4, 2-142:. 7-Chloro-l-[4-(3-acetyloxybenzoylamino)benzoyl]- 2,3,4 ,5-tetrahydro-1H-benzazepine 2-143: 7-Chloro-l-[4-(2-carbanoylrethoxybenzoylamino)benzoyl S-tetrahydro-1H-benzazepine 2-144: 7-Chloro-1-f3-f2-(2-dimethylaminoethoxy)benzoylaminolbenzoyl)-2,3,4, 5-teL rahydro-lH-benzazepine hydrochloride 2-145: 7-Chloro-1-(4-[ 2-f 4-isopropylarninobutoxy)benzoylamino] benzoyl}-2 5-tetrahydro-1H-benzazepine 2-146: 1-[4-(2-Methylbenzoylamino)benzoyl)-1,2,3k4,*5,6hexahydrobenzazocine 2-147: 1-[4-(2-Methoxybenzoylamino)benzoyl]-1,2,3,4,5,6hexahydrobenzoazocine -146 WO 94/01113 PCr/JP93/00835 2-148: 6-Methyl-l-[4-(3,4-dichlorobenzoylamirio)benzoyl]- 1,2,3, 4-tetrahydroquinoline 2-149: 1-t4-(3-Methylbenzoylamino)benzoyllperhydroquinoline 2-150: 1-f 4-(2-Methylbenzoylandno)benzoyll-1,2,3,4tetrahydroquinoline 2-151: 1-[4-(4-Methoxycarbonylbenzoylanino)benzoyl)- 1,2,31 4-tetrahydroquinoline 2-152: 1-14-(2-Nitrobenzoylamino)benzoyl)-1,2,3,4tetrahydroquinoline 2-153: 1-(4-Isobutyrylaminobenzoyl)-1,2,3,4-tetrahydroguinoline 2-154: 1-[4-(2,3-Dimethylbenzoylamino)benzoyl)-2,3,4,5tetrahydro-lH-benzazepine 2-155: 4-Methyl---F4-cyclohexylcarbonylaminobenzoyl 2,3 5-tetrahydro-1H-benzazepine 2-156: 3-Methyl-l-f4-(2-methylbenzoylamino)benzoyll- 1, 2,3, 4-tetrahydroquinoline 2-157: 2-Methyl-l-(4-benzoylarninobenzoyl)-1,2,3,4tetrahydroquinoline 2-158: 1-{4-114-(6-(l-Piperidyljhexyloxy)benzoylamino]benzoyl)i-2 2-159: 1-f 4- (2-Chloro-4-aminobenzoylaiino) benzoyl I- 2,3,4, 5-tetrahydrQ-1H-benzazepine 2-160: 3-Dimethylaminocarbonyl-1-[4-(3, amino) benzoyl 1-1,2,3 ,4-tetrahydroquinoline 2-161: 1-(4-[2-(4-Methoxyanilino)acetylaminolbenzoyl}- 2,3,4, 5-tetrahydro-1H-benzazepine 147 WO 94/01113 PCri/ P93/00835 2-162: 1-{4-[2-(2-(4-Morpholino)ethoxy)benzoylaminolbenzoyl)-2 ,3 5-tetrahydro-1H-benzazepine 2-163: 1-(4-172-(4-Hydroxybutoxy)benzoylaminolbenzoyl}- 2,3,4 ,5-tetrahydro-1H-benzazepine 2'-164: 1-{4-(2-Diethylarninocarbonylmethoxybenzoylamino)benzoyl)-2 5-tetrahydro-1H-benzazepiie 2-165: N-(phenyl)aminolacetylarnino)benzoyl)-2, 3,4,5-tetrahydro-1H-benzazepine 2-166: 4-Isopropyl-1-{4-(2,3-dinethylbenzoylarnino)benzoyl}-2,3,4, 5-tetrahydro-1H-1, 4-benzodiazepine 2-167: 1-(4-[4-(2-Diethylaminoacetyl-1-piperidinyl)carbonylamino ]benzoyl)-2 5-Let rahydro-iBbenzazepine hydrochloride 2-168: 5-Methoxy-l-[4-(2-methylbenzoylamino)benzoyl]- 2,3, 4, 5-tetrahydro-1H-benzazepine 2-169: 5-Ethoxycarbonylmethoxy-1- 14- (2-methylbenzoylamino) benzoyl 1-2,3, 4,5-tetrahydro-1R-benzazepine 2-170: 5-Hydroxymethyl-l-[ 4-(2-methylbenzoylamino)benzoyl 3-2,3,4, 5-teL rahydro-1H-benzazepine 2-171: 1-[4-(2-Methylberizoylamino)benzoylj-2,3,4,5tetrahydro-1H-benzazepine-5-spiro-2 '-oxirane 2-172:- 5-[N-Methyl,N-(2-hydroxy-3-diethylaminopropyl) amino-l-[4-(2-rnethylbenzoylamino)benzoyll-2,3,4,5tetrahydro-lH-benzazepine 2-173: 5-[N-eth 1,N-n-propyl)amino-1-[4-(2-methylbenzoylamino)benzoyll-2,3 2-174: 5-(4-Morpholiriocarbonylmethoxy)-1-(4-(2-methylbenzoylamino)benzoyl)-2,3,4,5-tetrahydro-lH- WO 94/01113 148 PCr/JP93/00S35 benzazepine 2-175: 5-(4-Thiornorpholinocarbonylmethoxy)---4-(2-methylbenzoylamino )benzoy. benzazepine 2-176: 5-(Anilinocarbonylamino)-1-[4-(2-nethylbenzoylamino) benzoylj-2,3,4, 2-177: S-Isobutylamino-1-[ 2-methylbenzoylami no)benzoyl 2-178: 5-Formylamino-1-[ 2-methylbenzoylamino)benzoyll- 2,3,4 2-179: 5-(l-Oxothiomorpholinocarbonylmethoxy)-l-[4-(2rethylbenzoylamino )benzoyl)]-2,3,4 benzazepine 2-180: 5-Methylaminocarbonylamino-1-[ 4- (2-methylbenzoylamino) benzoyl]-2 5-tetrahydro-1H-benzazepine 2-181: 5-(1-Pyrrol)-1-114-(2-rethylbenzoylamino)benzoyl]- 2, 3,4, 5-tetrahydro-1H-benzazepine 2-182: 5-[(2S)-2-Carbamoyl-(l-pyrrolidinyl) Icarbonylmethoxy-l- 14- (2-methylbenzoylamino) benzoyl 1- 2,3,4 2-183: 5-Carbamoylmethylaminocarbonylmethoxy-l- Ij4-( 2methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1Hbenzazepine 2-184: 5-f (1,1-Dioxothiomorpholino)carbonylmethoxyl-1-(4- (2-methylbenzoylanino) benzoyl 1-2,3,4, 1H-benzazepine 2-185: 5-1 (4-Acetyl1-1-piperazinyl)carbonylmethoxy])-1-[A- (2-methylbenzoylamino)benzoyl 149- WO 94/01113 PCTF/J P93/00835 1H-benzazepine 2-186: 7-Chloro-5-dimethylamino-l-[4-( 2-methylbenzoylamino) benzoyl 3-2,3,4, 2-187: 5-Ethoxycarbonylamino-l-[4-(2-methylbenzoylamino)benzoyl]-2,3,4 ,2-188: 5-(2-Methylamino)acetylamino-l-[4-(2-methylbenzoylamino) benzoyl 3-2,3, 4, 5-tetrahydro-1H-benzazepine 2-189: 5-[N-Methyl,N-(2-hydroxyethyl)aminocarbonylmethoxyl-l-[ 2-methylbenzoylamino)benzoyl]- 2,3,4 ,5-tetrahydro-1H-benzazepine 2-190: 5-Dimethylamino-l- (2-methylbenzoyloxy )benzoyl 3- 2,3,4, 5-tetrahydro-1H-benzazepine 2-191: 2-[N-Methyl-N-{1-[4-(2-methylbenzoylamino)benzoyll- 2,3,4,5-tetrahydrc-1H-benzazepin-5-yl)aminoiacetic acid potassium salt 2-192: 5-(2-[N--Methyl,N-(l-imidazol) ]acetylamino)-1-[4-(2methylaminobenzoylamino )benzoyl 3-2,3,4 tetrahydro-lH-benzazepine 2-193: 5-Dimethylamino-l-[4-(2-dimethylaninobenzoylanino)benzoyl 5-tetrahydro-1E-benzazepine 2-194: 5-(2-Axninoacetylamino)-1-[4-(2-methylarninobenzoylamino) benzoyl 3-2,3, 4 ,5-tetrahydro-1H-benzazepine 2-195: 5-[2-(1-Imidazol)acetylamino]-1-[4-(2-methylaminobenzoylamino)benzoyl)-2,3,4,5-tetrahydro-1Hbenzazepine 2-196: 8-Chloro-5-dimethylamino-l-( 2-me thylbenzoylamino) benzoyl 3-2,3, 4, 5-tetrahydro-1H-benzazepine 2-197: 8-Chloro-5-methylamino-l- (2-methylbenzoylamino U WO 94/01113 -150 PCT/JP93/00835 benzoyl'-2,3,4, 2-198: 5-( 2 -tert-Butoxycarbonylamino)acetylamino)-l-[4-(2nmethylbenzoylamino) benzoyl 1-2,3,4, benzazepine 2-199: 6-Chloro-5-hydroxy-1- 2-methylbenzoylamino) berizoyl 1-2,3,4, 5-tetrahydro-1H-benzazepine 2-200: 6-Chloro-5-dimethylamino-l- (2-methylbenzoylamino)benzoyl]-2, 3,4,5-tetrahydro-lH-benzazepine 2-201: 7-Chloro-5-cyclopropylamino-l- (2-methylbenzoylamino) benzoyl 1-2,3,4 ,5-tetrahydro-1H-benzazepine 2-202-. 9 -Chloro-5-methylamino-l-[4-(2-methylbenzoylamino)benzoyl 1-2,3,4, 2-203: 9-Chloro-5-dimethylamino-l- (2-methylbenzoylamino) benzoyl 1-2,3,4, 5-tetrahydro-lH-benza7 epine 2-204: 5-Dimethlamino-l-[ 2-methylbenzylcarbonylamino)benzoyl 1-2,3,4 2-205: 6-Methylamino-1-[4- (2-methylbenzoylamnino)benzoyl)- 1, 2,3,4,5, 6-hexahydrobenzazocine 2-206: 7-Chloro-5-methylamino-l- [3-methoxy-4-(C2-methylbenzoylamino )benzoyl 1-2,3,4, benzazepine 2- 207: 7-Chloro-5-dimethylamino-l- [3-methoxy-4- (2-methylbenzoylamino )benzoyl 1-2,3,4, benzazepine 2-'208: 7-Chloro-5-cyclopropylamino-l-[ 3-methoxy-4-( 2methylbenzoylamino) benzoyl 1-2, 3,4, benzazepine 2-209: 7-Methoxy-5-oxo-l-[4-(2-methylbenzoylamino)- WO 94/0~1113 PCT/JP93/00835 benzoyl 1-2, 4, 2-210: 7-Methyl-5-methylamino-1- 2-methylbenzoylaminrx) benzoyl 1-2,3,4, 5-tetrahydro-1H-benzazepine 2-211: 7-Methyl-5-cyclopropylani-.o-1- (2-methylbenzcoylamino) benzoyl 1-2,3,4, 5-tet:cahydro-1H-benzazepine 2-212: 7-Methyl-5-dimethylamino-1-[ 4- (2-methylbenzoylamino) benzoyl] 3,4, 5-tetrahydro-1H-benzazepiie 2-213: 7-M4ethoxy-5-oxo-l- [3-methoxy-4-(C2-methylbenzoylamino) benzoyl 1-2,3,4, 5-tetrahydro-1H-benzazepine 2-214: 7-Methoxy-5-mnethylamino-l- [2-chloro-4- (2-methylbenzoylamino)benzoyl 1-2,3,4, 5-tetrahydro-1Hbenzazepine 2-215: 7-Bromo-5-methylamino-1-[ 2-methylbenzoylamino)benzoyl 1-2,3,4, 5-tetrahydro-1H-benzazepine 2-216: 7-Chloro-5-methylamino-1-[ 2-chloro-4-( 2-methylbenzoylamino)benzoyl 1-2,3,4, 5-tetrahydro-1Hbenzazepine 2-217: 7-Chloro-5-cyclopropylamino-l- II2-chloro-4- (2mnethylbenzoylamino) benzoyl 1-2, 3,4, benzazepine 2-218: 7-Chloro-5-dimethylamino-1- I2-chloro-4- (2-rathylbenzoylamino)benzoyl 5-tetrahydro-1Hbenzazepine 2-219: 7-Methyl-5-(N-methyl,N-ethyl)amino-1-[4-(2-methylbenzoylamino) benzoyl 1-2 benzazepine 2-220: 7-]Bromu-5-dimethylaminoT1lt 2-met..ylbenzoylamino)benzoyll-2,3,4,5-tetrahydro-1lH-benzazepine WO 94/01113 152 P3/OOM/0035 2-221-. 7-Methoxy-5-methylamino-1-[ 2-methylbenzoylamino)benzoyl]-2 2-222: 7-Methoxy-5-methylamino-l-( 3-mnethoxy-4-( 2-methylbenzoylam.no)benzoyll-2,3,4,5-tetrahydro-1Hbenzazepine 2-223: 7-Methoxy-5-dimethylamino-l-12-chloro-4-(2-methylbenzoyJlamino)benzoylj-2, 3,4,5-tetrahydro-1Hbenzazepine 2-224: 7-Methyl-5-methylamino-l-f2-chloro-4-(2-methylbenzoylamino) benzoyl 3-2,3,4, S-tetrehydro-lHbenzazepine 2-225: 7-Methoxy-5-dimethylamino-1-f4-( 2-methylbenzoylamino) benzoyi 3-2,3,4, 5-tetrahydro-1H-benzazepine 2-226: 7-Methyl-5-cyclopropylamino-!.-( 2-chloro-4-( 2methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1Hbenzazepine 2-227: 7-Chloro-S-allylamino-1-f 2-chloro-4- (2-met"hylbenzoylamino) benzoyl 3-2,3,4, benzazepine 2-228: 7-Chloro-5-dimethylamino-l-[2-methyl-4-(2-methylbenzoylamino)benzoyl)-2, 3,4, benzazepine 2-229: 6-Methylamino-l-(2-chloro-4-(2-methylbenzoylamino)benzoy. 3-1,2,3, 4 6-hexahydrobenzazocine 2-230: 7-Methoxy-5-dimethylamino-1- t3-methoxy-4- (2-methylbenzoylamino)benzoyl)-2,3,4,5-tetrahydro-lHbenzazepine 2-231: 7-Methoxy-5-cyclopropylamino-l- t2-chloro-4- (2- L 3 WO 94/01113 VC/JP93/00835 methylbenzoylarnino)benzoyl]-2,3,4,5-totrahydro-1flben2azepine 2-232:. 7-Chloro-5-ethylamino-1-( 2-chloro-4- (2-methylbenzoyla~iino) benzoyl 1-2,3,4, benzazepine 2-233: 7-Methoxy-5-cyclopropyl-l-f 3-methoxy-4-(2-methylbenzoylamino)benzoyl)-2,3,4 benzazepine 2-234: 7-Dime thylamino-5-oxo-l-( 2-chloro-4-( 2-methylbenzoylamino)benzoyl)-2,3,4,5-tetrahydro-lHbenzazepine 2-235: 8-Chloro-6-methylamino-l-( 2-chloro-4-( 2-methylbenzoylamino) benzoyl 3-1, 2,3,4 6-hexahiydrobenzazoci ne 2-236: 7-Methoxy-5-cycl.opropy3lamino-l- (2-mo thylbenzoylamino)berizoyl)-2,3,4 2-237: 7-Methoxy-5-hydroxy-l-f 2-chloru-4- (2-me thylbenzoylamino)benzoylj-2 2-238:- 6-Chloro-4 -me thylami no-l- 2-me thy lbenzo-larriino) benzoyl]-l, 2,3, 4-tetrahydroquinoline 2-239: 7-Dimethylamino-5-methylamino-l-[ 2-chloro-4-( 2methylbenzoylamino)benzoyl 3-2,3,4, S-tetrahydro-1Hbenza~epine 2-240: 7-Methyl-5-dimethylamino-1-( 2-chloro-4- (2-methylbenzoylamino) benzoy. -2,3,4 ,5-tetrahydro-1HRbenzazepine 2-241: 7-Dimethylamino-5-hydroxy-1-( 2-chloro-4-( 2-methylbenzoylamino )benzoyl 3-2,3,4k 5-tetrahydro-1H- -154- WO 94/01113 PrriaP93/00835 benzazepine 2-242: 6-Chloro-4-methylamino-l-(2-chloro-4-(2-mothylbenzoylamino)benzoyl]-l, 2,3,4-tetrahydroquinoline 2-243: 7-Chloro-5-niethylamino-l- (2-methoxy-4- (2-methylbenzoylamino)benzoyl 1-2,3t4 benzazopine 2-244: 7-Chloro-5-climethylamino-l-(2-methoxy-4-( 2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-lnbenzazepine 2-245: (+)-5-Dimethylamino-l-(4-(2-methylbenzoylamino)benzoyl 3-2,3,4, 5-tetrahydre -lH-benzazepine hydrochloride 2-246: (-)-5-Oiniethylanino-l-4-(2-methylbenzoylamino)benzoyl 1-2, 3,4 hydrochloride 2-247: 7-Chloro-5-cyclopropylamino-l-t 2-methyl-4-(2methylbenzoylamino) benzoyl 3-2, 3, 4 benzazepine 2-248: 7-Methyl-5-methy2.amino-l-f2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-lHbenzazepine 2-249: 8-Methoxy-6-methylamino-l-t2-chloro-4-(2-methylbenzoylamirio)benzoyll-1, 2,3,4 ,5,6-1,'exahydroberizazocine 2-250: 7-Methoxy-5-rnethylamino-l-[ 2-methylbenzoylamino)benzoyl]-l,2,3,4-tetrahydroquinoline 2-251: 6-Methoxy-4-methylamino-l-t2-chloro-4-(2-methylbenzoylamino)benzoylj-1,2,3,4-tetrahydroquinoliie WO 94/01113 PCr/JP93I00835 2-2S2: 7-Fluoro-5-eyelopropylamino--(4-( 2-nethylbenzoyl= amino) benzoyl 1-2,3,4, 2-253: 7-Fluoro-5-cyclopropylamino-l- (2-chloro-4- (2methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1nbenzazepine 2-254: 7-Fluoro-5-cyclopropyl-1-( 3-me thoxy-4- (2-methylbenzoylamino) benzoyl 1-2 3,4 ,5-tetrahydro-1Hbenzazepine 2-255: 6-Methoxy-4-dimethylamino-l- (2-methylbenzoylamino)benzoylj-1, 2,3,4-tetrahydroquinoline 2-256: 7-Methoxy-4-dimethylamino-1-12-chloro-4-( 2-methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline 2-257: 7-Methyl-5-methylamino-l-(3-methoxy-4-(2-mrethylbenzoylamino)benzoyl)-2,3,4, benzazepine 2-258: 7-Methyl-5-dimethylamino-l-[3-methoxy-4-(2-methylbenzoylamino)benzoyl 1-2,3,4, benzazepine 2-259: 6-Chloro-4-methylamino-l- (2-methyl-4- (2-methylbenzoylamino)benzoyl']-l,2,3,4-tetrahydroquinoline 2-260: 7-Chloro-5-dimnethylamino-l-(2-methyl-4-f2-methylbenzoylamino) benzoyl 1-1, 2,3, 4-tetrahydroguinoline 2-261: 7-Fluoro-5-methylamino--[ 3-methoxy-4- (2-methylbenzoylamino) benzoyl benzazepine 2-262: 7-Fluoro-5-dimethylamino-l-t 4- (2-methy'lbenzoylamino)benzoyl 1-2,3,4, 2-263: 7-Fluoro-5-dimethylamino-1- 2-chloro-4- (2-methyl- WO 94/01113 -1 PCr/JP93/00835 benzoylanino)benzoyl. benzazepine 2-264: 7-Chloro-5-allylamino-1-(4-( 2-methylbenzoylamino)benzoyl 1-2,3,4, 2-265: 7-Chloro-5-(N-methyl,N-allyl)amnino-1-(4-(2-methylbenzoylarnino)benzoyl 3-2,3,4 ,S-tetrahydro-lHbenzazepine 2-266: 7-Fluoro-5-dimethylamino-1-[3-rnethoxy-4-(2-methylbenzoylaniino) benzoyl 1-2,3,4, 5-tetrahydro-1Hbenzazepine 2-267: 7-Methoxy-5-methylamino-l-[(2-inethyl-4- (2-methylberzoylamino)benzoyl)-2,3,4,5-tetrahydro-1Hbenzazepine 2-268: 7-Methoxy-5-dimethylamino-l-(2-methyl-4-(2-methylbenzoylamino) benzoyl 1-2,3,4, benzazepine 2-269: 6-Methyj.-4-methylamino-1-( 4-(2-methylbenzoylamino)benzoyl 1-1,2,3, 4-tetrahydroquinoline 2-270: 6-Chloro-4-methylamino-3-methyl-1-[ 2-methylbenzoylamino) benzoyl 1-1,2,3, 4-tetrahydroquinoline 2-271: 4-Methylamino-3-methyl-1-[4-(2-methylbenzovlamino)benzoyl 1-1,2,3, 4-tetrahydroquinoline 2-272: 6-Chloro-4-methylamino-l-( 2-chloro-4-( 2-methylbenzoylamino) benzoyl 1-1,2,3, 4-tetrahydroquinoline 2-273: 6-Chloro-4-dimethylamino-1-t4-(2-methylbenzoylamino) benzoyl 3-1, 2,3, 4-tetrahydroquinoline 2-274: 6-Chloro-4-dimethylamino-1-( 2-chloro-4-( 2-methylbenzoylamino)benzoyl)-1, 2,3,4-tetrahydroquinoline 157 WO 94/01113 PrriaP9310083S 2-275: -6-Methyl-4-dlimethylamino-l-f 2-methylbenzoylamino) benzoyl 2,3, 4-tetrahydroquinoline 2-276: 6-Methyl-4-dimethylamino--2-chloro-4-(2-methYlbenzoylamino)benzoyl-12,34-tetrahydroquiolile 2-277: 6-Chloro-4-dimethylamino-3-methyl-1-[2-chloro-4- (2methylbenzoylamino) benzoyl 3-1,2,3, 4-tetrahydroquinoline 2-278: 4-Dimethylainino-3-methyl-1-t 2-ch2.oro-4- (2-methylbenzoylamino) benzoyl 3-1,2,3, 4-tetrahydroguinoline 2-279: 8-Chloro-6-methylamino--4-(2-methylbelzoylamilo)benzoyl 3-1,2, 3,4, 5, 6-hexahydrobenzazocine 2-280: 7-Chloro-5-al1ylamino--3-methoxy-4-(2-methylbenzoylamino)benzoyll-2, 3,4, 5-tetrahydro-1Hbenzazepine 2-281: 7-Chloro-5-(N-methyl,N-ethyl)amnfl-(3-methoxy-4- (2-methylbenzoylamino)benzoyl 3-2,3,4, 1H-benzazepine 2-282: 7-Chloro-5-(N-methyl,N-ally1)amiflo-l-[3-metho~y- 4 (2-chlorobenzoylamino) benzoyl 3-2, 3,4 1H-benzazepine 2-283: 7-Fluoro-5-hydroxy--4-(2-methylbelzoylamiflo)benzoy.. 4, 2-284: 7-Fluoro-5-hydroxy-l-[2-chloro-4-(2-ethylbelzoylamino) benzoyl. 2-285: 7-Fluoro-5-hydroxy-l-t3-methoxy4(2methylbelzoylamino) benzoyl 3-2,3,4, 2-286: 5-Dimethy-lamifol-4(2ethylbelzoylamilo)benzoyl 3-2,3,4, 5-tetrahydro-1H-benzazepine WO 94/01113 -PUT/i P93/00835 2-287: S-Chloro-f 4-(2-mnethylbenzoylamino)benzoy11i- 2, 3, 4 ,5-tetrahydro-1fl-benzazepine 2-288:, 7-Methoxy-5-methylidene-1-f2-chloro-4-(2-methylbenzoylamino)benzoyl 3-2,3,4, beozazepine 2-289: 7-Chloro-4-methyl-l-[ 2-rnethylbern'oylama no)benzoyl 3-2,3,4,5-terrahydro-1H-1 ,4-benzodiazepine 2-290: 4-Methyl-1-[ 2-chloro-4-(2-methylbenzoylamino)benzoyl 1-2,3,4 ,5-tetrahydro-lH-1, 4-benzodiazepine 2-291.: 7-Methoxy-S-hydroxymethyl-5-hydroxy-l-( 2-chloro-1- (2-methylbenzoylamino)benzoyl)-2,3,4,5-tetrahydro- 1H-benzazepi ne 2-292: 7-Methoxy--niethy3.amino-1-( 2-me thoxy-4-( 2-rnehy2.benzoylamino)benzoyll-2,3,4,5-tetrahydro-1Hbenzazepine 2-293: 7-M4etho,-y-5-hydroxy-l-[ 2-methoxy-4-( 2-methylbenzoylarnino)benzoyl]-2,3,4,5-tetrahyd"c-1benzazepine 2-294: 7-Fluoro-5-t2-(4-nethyl--l-piperazinyl)etho.\y]-l-t2methoxy,-4-(2-methylbenzoylamino)benzoyl)-2,3,4,tetrahydro-lI'-benzazepine 2-295: 7-Ch2.oro-l-(2-methoxy-4-t2-(4-t4-ntethyl-lpiperazinvllbutoxy,)benzoylamino~benzoyl)-2,3,4,5tetrahvdro-1H-benzazepine 2-296: 7-Chloro-5-(2--(isopropylamino)ethoxy)-l-(2-methyl- 2-methl benzoy-lamino) benzoyl 1-2 ,3,4 tetrahvdro-lH-benzazepine hydrochloride 2-297-. 7-Chloro-5- (4-methyl-l-piperazinyl )carbonylmethyl- WO 94/01113 159 PCr/3P93/00835 2-chloro-4- (2-methylbenzoylamino)benzoyl)I- 2,3,4, 5-tetrahydro-1H-benzazepine hydrochloride 2-298: 7-Chloro-l-(3-methoxy-4-f 2-(2-dimethylarninoethoxy)benzoylaminolbenzoyl)-2 benzazepine 2-299: 7-Chloro-5-(4-mrethyl-l-piperidinyl)carbonylmethyl- 1- (2-methylberizoylamino)benzoyl 1-2, 3,4,5tetrahydro-lH-benzazepine hydrochloride 2-300: 7-Clhloro-S-(2-dimethylaminoethyl)-l-( 2-methoxy-4- (2-methylbenzoyJlamino)benzoyl lH-benzazepine hydrochloride 2-301: 7-Chloro-4-hydroxy-l- (2-methoxy-4- (2-nethylbenzoylamino)benzoyll-2 2-302: 7-Chloro-l-[2-chloro-4-(2-acetyloxybenzoylamino)benzoyl 1-2,3,4 2-303: 7-Chloro-l-t 2-chloro-4-( 2-hydroxybenzoyJlamino)benzoyl 1-2,3,4 2-304: 7-Chloro-l-( 2-rnethyl-4-( 2-hydroxybenzoylainino)benzoyl 1-2,3,4 2-305: 7-Fluoro-5-( (4-dimethylamino-1-piperidino)carbonylmethyl 1-1- [2-methoxy-4- (2-nethylbenzoylamino) benzoyl 1-2,3,4 2-306: 7-Fluoro-5-(l-piperidinocarbonylmethyl)-l-E 2methoxy-4- (2-methylbenzoylamino )benzoyl. -2,3,4,5tetrahydro-lH-benzazepine 2-307: 7-Chloro-5-[ (l-methyl-4-piperidinyl)aminocarbonylmethoxyl-l-( 2-methyl-4-( 2-inethylberzoylamino)benzoyi 1-2,3,4 ,5-tetrahydro-1I-benzazepine 160- WO 94/01113 PCf/J P93/00835 hydrochloride 2-308: 7-Chloro-5-(2-acetylaminoethyl)-1-j2-methoxy-4-(2methylberizoylamino )benzoyl) -2,3 ,4 benzazepine 2-309: 7-Chloro-5-dimethylaminocarbonylnethyl-l-[ 4- (2methylberizoylamino) benzoyl. 3,4, benzazepine 2-310: 7-Chloro-5-carbamoylmethyl-l- (2-me thylbenzoylamino)benzoyl)-2,3,4,5-tetrahydro-lI-benzazepine 2-311: 7-Chloro-5-[ (4-rethyl-l-piperazinyl)carbonylmethoxy 3-1-f4- (2-me thylbenzoylanino) benzoyl 1- 2,3,4, 2-312: 7-Fluoro-5-[ (4-acetylamino-l-pip~eridino)carbonylmethyl] -1-C4-(2-methylbenzoylamnino)benzoylj- 2,3,4, 2-313: 7-Chloro-5-[ (4-acetylamino-1-piperidino)carbonylmethyl 3-1-f2-methoxy-4-( 2-rethylbenzoylamino)benzoy. 5-tetrahydro-1H-benzazepine 2-314: 5-[(4-Acetylamino-1-piperidino)carbonylmethyl)-7fluoro-l- II2-rnethoxy-4- (2-bromomethylbenzoylanino) benzoyl 1-2,3,4, 2-315: 7-Chloro-1- [2-chloro-4- (2-carbamoylrnethoxybenzoylamino)benzoyll-2,3, 4,5-tetrahydro-1H-benzazeDine 2-316: 7-Chloro-1-{2-chloro-4-f2-(2-dimethylaminoethoxy)benzoylamino)benzoyl}-2,3,4, 5-tetrahydro-1Hbenzazepine 2-317: 7-Chloro-l-(2-chloro-4-[ 2-(4-dimethylaminobutoxy)benzoylaminoljbenzoyl)-2,3,4, 161 WO 94/01113 PCr/JP93/00835 benzazepine 2-318: 7-Chloro-1-(2-chloro-4-( 4-isopropylaminobutoxy)benzoylaminolbenzoyl)-2 benzazepine 2-319: 7-Chloro-l-(2-methyl-4-(2-c~.rbamoylmethoxy)benzoylamino~benzoyl)-2 2-320: 7-Chloro-5-(2-hydroxyethyl)-1-[4-(2-methylbenzoylamino) benzoyl 1-2, 3,4, 5-tetrahydro-1H-benzazepine 2-321: 7-Chloro-5- (2-hydroxyethyl 2-chlorobenzoylamino) benzoyl 1-2,3,4, 2-322: 7-Chloro-5- (2-hydroxyethoxy [4-C 2-methylbenzoylamino) benzoyl 1-2,3,4 ,5-tetrahydro-1H-benzazepine 2-323: 7-Chloro-5-(2-hydroxyethoxy)-1-j14-(2-chlorobenzoylamino) benzoyl 1-2,3,4, 5-tetrahydro-1H-benzazepine 2-324: 7-Chloro-5-(2-dimnethylaminoethyl)-l-[4-(2-chlorobenzoylamino)beizoyl 1-2,3,4, benzazepine 2-325: 7-Chloro-5-(2-chloroethyl)-l-[4-(2-chlorobenzoylamino)benzoyl]-2, 3,4, 5-tetrahydro-1H-benzazepine 2-326: 7-Chloro-5-(2-dimethylaminoethyl)-1-[4-(2-methylbenzoylamino) benzoyl 1-2,3,4 benzazepine 2-327: 7-Chloro-5-(2-isopropylaminoethyl)-1-[4-(2-chlorobenzoylamino )benzoyl 1-2,3,4 ,5-tetrahydro-1Hbenzazepine 2-328: 7-Chloro-5-(2-isopropylaminoethyl)-l-t4-(2-methylbenzoylarnino)benzoyll-2,3,4,5-tetrahydro-lHbenzazepine -162 WO 94/01113 PCrIJP93OOB35 2-329: 7-Chloro-5--(2-tert-butylaminoethyl)-l-(4-(2-chlorobenzoyjlamino)benzoylj-2,3,4 benzazepine 2-330: 7-Chloro-5-(2-tert-butylaminoethyl)-l-[4-(2-methylbenzoylaniino)benzoyll-2,3,4,5-tetrahydro-lHbenzazepine 2-331: 7-Chloro-5-( 2-isopropylaminoethoxy)-l-( 4-(2-chlorobenzoylainino)benzoyl 1-2,3,4, benzazepine 2-332: 7-hoo5(-spoyaiotoy--4(-ehl benzoylamino)benzoyl 1-2,3,4, benzazepine 2-333: 7-Chloro-5-(2-tert-butylaminoethoxy)-I-[4-(2methylbenzoylamino)benzoyl 1-2,3,4, benzazepine 2-334: 7-Chloro-4-methylamino-1-[ 2-rethoxy-4-( 2-methylbenzoylamino)benzoyl 1-2,3,4, benzazepine 2-335: 7-Chloro-4-dimethylamino-1- [2-methoxy-4- (2-methylbenzoylamiio) benzoyl. 3, 4, -tetrahydro-lHbenzazepine 2-336: 7-Chloro-5-*(2-direthylaminoethyl)-1-fj2-methyl-4-(2chlorobenzoyl'amino)benzoyl 1-2,3,4, 5-tetrahydro-1Hberizazepine 2-337: 7-Chloro-5- (2-diethylaminoethyl [2-methyl-4- (2chlorobenzoylamino) benzoyl. 5-tetrahydro-1Hbenzazepine 2-338: 7-Chloro-5- (2-isopropylaininoethyl) [2-methyl-4- WO 94/01113 -13PCT/JP93/00835 (2-chlorobenzoylaniino)benzoyl]-2,3,4,5-tetrahydro- JH-benzazepine 2-339: 7-Chloro-5- (2-tert-butylaminoethy))-1- (2-mnethyl-4- (2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro- 1H-benzazepine 2-340: 7-Chloro-5-(2-dimethylaminoethoxy)-J.-[3-methoxy-4- (2-chlorobenzoylamino) benzoyl 3-2,3,4, JH-benzazepine 2-341: 7-Chloro-S-(2-diethylaniinoethoxy)-l-(3-methoxy-4- (2-chlorobenzoylarnino)benzoylI-2,3,4,5-tetrahydro- 1H-benzazepine 2-342: 7-Chloro-5-:2-isopropylaminoethoxy)-1-[3-methoxy-4- (2-chlorobenzoylamino)benzoylj-2,3,4,5-tetrahydro- 1H-benzazepine 2-343: 7-Chloro-5-( 2-diethylaminoethoxy)-l-[ 3-methoxy-4- (2-methylbenzoylami no) benzoyl 3-2 1H-benzazepine 2-344: 7-Chloro-5-(C2-isopropylaminoethoxy) (3-methoxy-4- (2-methylbenzoylamino)benzoyl)-2,3,4,5-tetrahydro- 1H--benzazepine 2-345: 7-Chloro-5-(2-tert-butylethoxy)--3-methoxy-4-(2methylbenzoylamino) benzoyl 3-2,3,4, benzazepine 2-346: 7-Chloro-5-(2-diethylaminoethyl)1l[2ifeth0xy4(2methylbenzoylamino) benzoyl 1-2, 3,4 benzazepine 2-347: 7-Chloro-5- (2-isopropylaminoethyl -1-2-methoxy-4- (2-methyJlbenzoylamino) benzoyl 3-2,3, 4, -164 WO %/01113 PCT/JP93/00835 1H-benzazepine 2-348: 7-Chloro-5-(2-tert-butylamiioethyl)-l-[2-rnethoxy-4- (2-methylbenzoylamino)benzoy1 1-2,3,4, IH-berizazepine 2-349: 7-Chloro-5-(2-diethylaminoethyl)-1-[2-rnethoxy-4-(2chlorobenzoylamino)benzoyl 1-2,3,4, benzazepine 2-350: 7-Chloro-5-(2-isopropylaminoethyl)-l-[2-rnethoxy-4- (2-chlorobenzoylarnino)benzoyl 1-2,3,4 1H-berizazepine 2-351: ?-Chloro-5-(2-tert-butylaminoethyl)-l-f12-methoxy-4- (2-chlorobenzoylamino )benzoyl 1-2, 3,4 1H-benzazepine 2-352: 7-Chloro-l-[ 2-methoxy-4-( 3-hydroxybenzoylamino)benzoyl 1-2,3,4, 2-353: 7-Chloro-l-[3-methoxy-4-(2-hydroxybenzoylamino)benzoyl 1-2,3,4 2-354: 7-Chloro-l-[3-methoxy-4-(2-carbanioylmethoxybenzoylamino )benzoyl 1-2,3,4, 2-355: 7-Chloro-l-{3-methoxy-4-[2-(2-dimethylarninoethoxy)benzoylarninolbenzoyl)-2 benzazepine 2-356: 7-Chloro-l-(3-methoxy-4-[2-(2-isopropylaminoethoxy)Vinzoylaminolbenzoyl}-2,3,4, 5-tetrahydro-1Hbenzazepine 2-357: 7-Chloro-1-(3-methoxy-4-t 2-(4-dimethylaminobutoxy)benzoylarnino 1benzoyl}-2,3,4, benzazepine WO 94/01113 15- PL-T/JP93/00835 2-358: 7-Chloro-l-(3-methoxy-4-[2-(4-isopropylaiinobutoxy) benzoylamino Ibenzoyl}-2, 3, 4 ,5-tet rahydro-lHbenzazepiie 2-359: 7-Chloro-4-hydroxv?-1-[2-rnethoxy-4- (2-methvlbenzoylamino)benzoyl]-2,3,4,5-tetiahydro-lH-benzazepine 2-360: 7-Chloro-5-(2-aminoethyl)-l-[2-methoxy-4-(2mnethylbenzoylamino) benzoyl 1-2, 3, 4,5-tetrahydro-l1Hbenzazepine hydrochloride 2-361: 7-Chloro-4-hydroxy-l-[2-methyl-4-(2-methylbenzovlamino) benzoyl 3-2,3,4, 2-362: 7-Chloro---[ 2-methyl-4-( 2-acetyloxybenzovlamino)benzoyl]-2,3,4,.5-tetrahydro-1H-benzazepine 2-363: 7-Chloro-5-carbamovlmethoxy-l-[2-methyl-4-(2chlorobenzoylaiino)benzoy. ]-2,3,4,5-tetrahivdro-lHbenz azepine 2-364: 7-Fluoro-5-(2-diethylaminoethyl)-l-[2-methyl-4-(2chlorobenzoylarnino)benzoyl}-2,3,4, benzazepine 2-365: 7-Fluoro-5-(2-isopropyaminoethy)--2-r~ethvl-4- (2-chlorobenzoylamino) benzovl)-2,3,4, 1H-benzazepine 2-366: 7-Fluoro-5-(2-tert-butylaminoethyl)-1-[2-methyl-4- (2-chlorobenzoylanino) benzoyl 3-2,3,4, 5-tee -rahydro- 1H-benzazepine 2-367: 7-Chloro-5-(2-ethylaminoethoxy)---2-methoxy-4- (2chlorobenzoylamino) benzoyl 3-2, 3 benzazepine 2-368: 7-Chloro-5-(2-acetylaminoethoxy)-l-[2-nethoxv-4-(2- I r6 WO 94/01113 PCr/JP93/00835 chlorobenzoylamino)benzoyl]-2,3,4 1 5-tetrahydro-1Hlbenzazepine 2-369: 7-Chloro -5-(2-isopropylaminoethoxy)-l12-methoxy-4- (2-bromobenzoylamino)benzoyl)-2,3,4 1}-benzazepine 2-370: 7-Chloro-5-methoxy-1-f2-methoxy-4-(2-niethylbenzoylamino) benzoyl 1-2, 3, 4 5-tetrahydro-1A1-benzazepine 2-371: 7-Chloro-5-(N-niethyl,N-f2-(2-pyridyl)ethyl)aminocarbonylmethoxy-l- (2-trifluorornethyl-4-( 2-methyl- *benzoylamino)benzoyl)-2,3,4,5-tetrahydro-lHbenzazepine 2-372: 7-Chloro-S-(2-(N-ethylN-butylamino)ethoxy]-1-[2methoxy-4-(2-chlorobenzoylamino)benzoy.,,-2,3,4,5tetrahydro-1H-benzazepine 167 WO 94/01113 PCri/ P93/00835 a~t 105 m4 Table 1 Inhibitory Rate Test IC 50 Test IC 50 Comp.Comp.

No. (U'

M

No. (U'

M

1-1 1-3 1-7 1-9 1-11 1-13 1-15 1-17 1-19 1-21 1-23 1-25 1-27 1-29 1-31 1-33 1-35 1-37 1-39 1-41 1-43 1-45 1-47 1-49 1-51 1-53 7.60 4.37 8.38 7.66 4.89 5.05 4.75 U. 18 4.32 5.10 5.10 4.99 7.14 13 .6 7.*24 33.8 14.6 32.4 1.91 0.85 7.70 4.14 9.24 3.28 7.85 40.1 72.7 1-2 1-4 1-6 1-8 1-10 1-12 1-14 1-16 1-18 1-20 1-22 1-24 1-26 1-28 1-30 1-32 1-34 1-36 1-38 1-40 1-42 1-44 1-46 1-48 1-50 1-52 1-54 5.63 3.96 4.57 8.23 4 .09 3.55 43.8 6.03 23.3 7.13 4.32 22.7 24.2 5.55 24.6 28.7 10.8 4.45 4.38 2.92 4.54 8.28 40.1 24.5 8.59 6.85 47.4 1,68 WO 94/01113 PCr/JP93/00835 Test

IC

50 Test

ICS

0 Cornp. Comp.

No. (PM) No. zM 1-55 1-57 1-59 1-61 1-63 1-65 1-67 1-69 1-71 1-73 1-75 1-77 1-79 1-81 1-83 1-85 1-87 1-89 1-91 1-93 1-95 1-97 1-99 45.7 30.3 3.19 5.08 5.73 6.86 6.80 41.4 3.42 2.85 44.10 3.29 8.74 1.89 1.91 15.7 9.85 6.73 7.05 5.13 4.02 3.87 4.6 1-56 1-58 1-60 1-62 1-64 1-66 1-68 1-70 1-72 1-74 1-76 1-78 1-80 1-82 1-84 1-86 1-88 1-90 1-92 1-94 1-96 1-98 2.92 43.8 4.29 5.13 4.55 45.8 49.7 2.93 5.82 7.39 43.3 5.16 6.62 4 .69 5.'54 8.21 2.45 5.75 2.32 7.44 3.10 7.13 169 WO 94/01113 PCr/JP93/00835 Table 2 (*;Inhibitory Rate ()at 10- 5 14 **:Inhibitory Rate %)at 10-6 1 Test IC 50 Test IC 50 Conip. Comp.

No. (U

TM

No. (IM) 2-1.

2-3 2-7 2-9 2-11 2-13 2-15 2-17 2-19 2-21 2-23 2-25 2-27 2-29 2-31 2-33 2-35 2-37 2-41 2-43 2-45 2-47 2-49 2-51 2-53 4.01 0.22 1.57 25.0 0.23 0.34 0.23 15.3 43.2 14.8 27.2 0.72 2.82 7.25 37.1 1.83 1 .12 41.1 6.604 27.9 0.48 0.55 0.23 8.35 0.55 4.79 5.81 2-2 2-4 2-6 2-8 2-10 2-12 2-14 2-16 2-18 2-20 2-22 2-24 2-26 2-28 2-30 2-32 2-34 2-36 2-38 2-40 2-42 2-44 2-46 2-48 2-50 2-52 2-54 1.55 21.3 1.26 0.52 3.07 0.60 42.0 5.30 37.8 5.20 3.89 2.49 8.89 7.61 8.10 2.55 4.04 35.9 1.50 1.38 0.07 4 .29 0 .07 3.64 2.93 2.70 2.92 170 WO 94/01113 PCr/JP93/00835 Test IC 50 Test IC 50 Comp. Comnp.

No. (aiM) No.(tM 2-55 2-57 2-59 2-61 2-63 2-65 2-67 2-69 2-71 2-73 2-75 2-77 2-79 2-81 2-83 2-85 2-87 2-89 2-91 2-93 2-95 2-97 2-99 2-101 2-1.03 2-105 2-107 2-10 9 0.38 8.79 22.8 22.7 5.30 33.9 28.5 31 07 8.93 32.0 6.10 19.6 22.4 30.1 40.3 5.55 2.58 8.62 5.38 5.56 3.81 44.2 14.6 3.03 33.7 3.57 8.75 2-56 2-58 2-60 2-62 2-64 2-66 2-68 2-70 2-72 2-74 2-76 2-78 2-80 2-82 2-84 2-86 2-88 2-90 2-92 2-94 2-96 2-98 2-10 0 2-10 2 2-10 4 2-106 2-10 8 2-110 1.83 3.82 5.01 37.9 12.0 16 .8 16.9 5.19 26.3 22.9 1.55 10.3 8.39 27.5 7.92 37.3 2.37 26.5 2.47 3.19 9 .19 16.6 21.8 3.48 7 .61 32.4 5.84 36.9 *171 WO 94/01113 PMTJ P93/00835 Test IC 5 0 Test IC 5 0 Conip. Comp.

No. (PiM) No.(j) 2-111 2-113 2-115 2-117 2-119 2-121 2-1 23 2-125 2-127 2-129 2-131 2-133 2-135 2-137 2-139 2-141 2-143 2-145 2-147 14 9 2-151 2-153 2-155 2-157 2-159 2-161 2-163 2-165 2-167 0.05 0.11 0.46 6.02 0.62 1.18 1.24 0.88 1.02 45.0 2.05 4.16 19 .0 11. 4 8.97 2.41 5.76 8.54 13. 2 4 .83 10.9 8.96 2.54 13.8 6.73 6.32 22.2 8.42 25. 2 2-112 2-114 2-116 2-118 2-120 2-122 2-124 2-126 2-12 8 2-130 2-132 2-134 2-13 6 2-13 8 2-14 0 2-142 2-144 2-14 6 2-14 8 2-150 2-15 2 2-15 4 2-15 6 2-15 8 2-16 0 2-16 2 2-16 4 2-166 2-168 0.05 0.03 1 .26 0.55 3.33 9 .6 1 1.29 7 .34 46.4 8.42 8.29 46.9 10.0 16.2 19.0 3 .29 8.26 3.15 7.02 3.33 21.7 7 .93" 4.01 23.7 49.3 30.7 23.3 8.75 1.60 172 WO 94/01113 PCrIJP93/00835 Test IC 50 Test IC 50 Cornp. Cornp.

No. (PM) No. (Ijm) 2-169 2-171 2-173 2-175 2-177 2-179 2-181 2-183 2-18 5 2-187 2-189 2-191 2-193 2-19 5 2-197 2-199 2-201 2-203 2-205 2-207 2-209 2-211 2-213 2-215 2-217 2-219 2-221 2-223 1.76 1.90 43.4 1.24 24.1 2.63 14.2 2.09 1.47 10.1 2.36 15.6 7.60 53.4 44.1 31.1 1.17 6.00 38.2 3.07 17.8 3.49 36.1 0.49 48.8 3.78 2.32 4.53 2-170 2-172 2-17 4 2-17 6 2-17 8 2-18 0 2-182 2-184 2-18 6 2-18 8 2-190 2-19 2 2-19 4 2-196 2-19 8 2-20 0 2-20 2 2-20 4 2-20 6 2-208 2-210 2-212 2-214 2-216 2-218 2-220 2-222 2-22 4 0.96 5.34 1.78 21.1 9.26 28.*6 1.34 2.40 1.44 41.7 34.2 7.71 26.7 8.93 46.0 38.1 4.45 47.4 1.58 3.19 2.71 1.44 5.06 4.76 8.58 1.35 3.37 45.6 -173 WO 94/01113 PCrIJP93/OP" Test IC 50 Test ICS 0 Comp. Comp.

2-225 1.76 2-226 9.19 2-227 47.4 ()2-228 40.4 2-229 34.4 ()2-230 4.17 2-231 5.39 2-232 42.8 2-233 5.27 2-234 22.2 2-235 2.86 2-236 3.05 2-237 2.40 2-238 2.47 2-239 15.8 ()2-240 7.83 2-241 18.1 ()2-242 44.5 2-243 3.19 2-244 16.4 ?-245 20.2 *)2-246 2.60 2-247 9.78 2-248 43.1 2-249 1.76 2-250 41.1 2-251 11.6 ()2-252 5.56 2-253 33.7 ()2-254 6.09 2-255 3.21 2-256 29.5 z.-257 5.82 2-258 5.80' 2-259 25.0 ()2-260 26.8 2-261 8.34 2-262 5.68 2-263 49.8 ()2-264 0.83 2-265 7.32 2-266 6.68 2-267 9.46 2-268 35.0 2-269 45.1 ()2-270 0.26 2-271 2.17 2-272 9.46 2-273 3.20 2-274 10.5 2-275 4.47 2-276 32.8 2-277 26.0 ()2-278 18.8 2-279 1.1.8 2-280 3.92 174 WO 94/01113 PCr/J P93/00835 Test IC 50 Test IC 50 Comp. Comp.

No. (i)No. (jm) 2-281 2-283 2-285 2-287 2-289 2-291 2-293 2-295 2-297 2-299 2-301 2-303 2-305 2-307 2-309 2-311 2-313 2-315 2-317 2-319 2-321 2-323 2-3 25 2-327 2-3 29 2-331 2-333 2-335 36.9 1.18 0.94 1.17 2.41 33.8 89.7 3.69 1.85 0.36 0.12 14.4 0.22 1.94 0.25 0.10 0.13 4.44 6.75 3.58 0.30 0.25 27.6 0.37 0.45 0.30 0.52 0.14 2-28 2 2-284 2-286 2-288 2-29 0 2-29 2 2-29 4 2-29G6 2-29 8 2-30 0 2-302 2-304 2-306 2-308 2-310 2-312 2-314 2-316 2-318 2-320 2-3 22 2-324 2-3 26 2-3 28 2-330 2-33 2 2-334 2-33 6 35.9 3.43 1.81 3.62 7.58 46.0 1.64 2.18 47.3 0.97 29.6 17.7 0 .09 0 .09 0.28 1.22 0.10 3.52 8.01 0.22 0.23 1.76 0 .61 0.35 0.33 0.38 0.35 7.54 175 WO 94/01113 PCr/JP93/00835 Test

IC

50 Test

IC

50 Comp. comnp.

No. (uim) 2-337 4.23 2-338 7.55 2-339 5.41 2-340 0.57 2-341 0.49 2-342 0.62 2-343 0.60 2-344 1.87 2-345 2.50 2-346 0.33 2-347 0.64 2-348 0.66 2-349 0.51. 2-350 0.43 2-351 0.86 2-352 0.72 2-353 31.6 2 -354 4.52 2-355 9.50 2-356 9.23 2-357 0.57 2-158 5.18 2-359 0.08 2-360 0.45 2-361 1.37 362 24.2(* 2-363 4.00 2-364 4.49 2-365 4.40 2-366 9.29 2-367 0.10 2--368 0.21 2-369 88.8 (*)2-370 0.78 2-371 1.93 2-372 0.88 175a Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

*S

S. 94t222,p:noper\dab,43569.spe,175

Claims (4)

1. A method for the protection or treatment of premature delivery, dysmenorrhoea, endometritis, or for stopping labour preparatory to Caearian delivery, which comprises administering an oxytocin antagonist which is a carbostyril derivative of the formula (Rl)q- (l) R wherein R 1 is hydrogen atom; nitro; a lower alkoxy; a lower alkoxycarbonyl; a lower alkyl; a halogen atom; an amino having optionally one or two substituents selected from a lower alkanoyl, a lower alkyl, benzoyl and a phenyl(lower)- alkoxycarbonyl; hydroxy; cyano; carboxy; a lower alkanoyloxy; or hydrazinocarbonyl, q is an integer of 1 to 3, and 20 R is a group of the formula: Cn -R2 o ox (R 3 )m wherein R 2 is hydrogen atom; a lower alkoxycarbonyl; a phenoxycarbonyl wherein the phenyl ring may optionally be substituted by one to three substituents selected from nitro and an amino having optionally one or two substituents 30 selected from a lower alkanoyl, a lower alkyl and benzoyl; a I phenyl (lower) alkenylcarbonyl; a phenyl (lower) alkanoyl wherein the lower alkanoyl moiety may optionally be substituted by an amino having optionally a lower alkoxycarbonyl substituent; an alkanoyl; an alkenylcarbonyl; 941222,pAopc\dab,4350 spc, 176 177 WO 94/01113 PCT/JP93/00835 a phenylsulfonyl wherein the phenyl ring may optionally be substituted by a lower alkoxy; a group of the formula: -CONR 8 R 9 (wherein R 8 and R 9 are the same or different and are each hydrogen atom or a phenyl which may optionally have one to three substituents selected from a lower alkoxy, a lower alkyl, a halogen atom, an amino having optionally one or two substituents selected from a lower alkyl and a lower alkanoyl, and nitro); a heterocyclic group-substituted carbonyl wherein the heterocyclic group may optionally have one to three substituents selected from a phenyl(lower)- alkoxycarbonyl, a phenyl(lower)ulkoxy, oxo, a lower alkyl, and a lower alkylenedioxy; a group of the formula: -CO CH 3 "CH 3 CH CH 3 '1H3 naphthylcarbonyl; a thienyl(lower)alkanoyl; a tricyclo- [3.3.1.l]decanyl(lower)alkanoyl; tricyclo[3.3.1.1]- decanylcarbonyl; or a group of the formula: /R1 3 )p (R (wherein p is 0 or an integer of 1 to 3, and R 13 is hydroxy; an alkoxy; an alkoxy which has one or two substituents selected from hydroxy, a lower alkanoyloxy, a tri(lower)alkylammonium, a lower alkoxy, and a group of the formula: -NR 14 R 15 [wherein R 14 and R 15 are the same or different and are each hydrogen atom, a lower alkyl, a hydroxy-substituted lower alkyl, a lower alkanoyl, a P78 WO 94/01113 PCT/JP93/00835 tetrahydropyranyl(lower)alkyl, phenyl, a phenyl(lower)alkyl (wherein the alkyl moiety may optionally be substituted by hydroxy and the phenyl ring may optionally be substituted by a lowei alkoxy), or a pyridyl(lower)alkyl; or R 14 and R 1 may bind with the nitrogen atom to which they bond to form a or 6-membered, saturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom (wherein the heterocyclic group may optionally be iubstituted by a member selected from carbamoyl, a lower alkyl, a phenyl(lower)alkyl, phenyl and a hydroxy- substituted lower alkyl)]; a carboxy-substituted alkoxy; a halogen-substituted lower alkoxy; a lower alkoxycarbonyl- substituted alkoxy; a lower alkanoyloxy-substituted lower alkoxy; a lower alkenyloxy-substituted lower alkoxy; a lower alkoxy(lower)alkoxy; a lower alkylsulfonyloxy-substituted lower alkoxy; a benzoyloxy-substituted lower alkoxy; tricycloli33...l]decanyl-substituted lower alkoxy; a lower alkoxy(lower)alkoxy which is substituted by one or two subs~tuents selected from hydroxy and an amino being optionally substituted by a lower alkyl; a morpholinyl- substituted lower alkoxy which may optionally be substituted by a lower alkyl or oxo; a benzimidazolylthio-substituted lower alkoxy; a benzimidazolylsulfinyl-substituted lower alkoxy; a group of the formula: -NR 4 R 5 (wherein A is an alkylene, is an integer of 0 or 1, E is a group of the formula: -CO- or -OCO-, R and R 5 are the same or different and are each hydrogen atom; a lower alkyl which may optionally be substituted by hydroxy or cyano; a lower WO 94/01113 PCT/JP93/00835 alkenyl; a lower alkynyl; a phenyl(lower)alkyl; a lower alkanoyl which may optionally have one to three substituents of a halogen atom; a benzoyl wherein the phenyl ring may optionally be substituted by a member selected from nizro and an amino having optionally cne or two substituents selected from a lower alkyl, a Thwer alkanoyl and a phenyl(lower)alkoxycarbonyl; phenyl; a lower alkoxycarbonyl; a lower alkoxycarbonyl(lower)alkyl wherein the lower alkyl moiety may optionally be substituted by hydroxy or an amino having optionally a phenyl(lower)alkoxycarbonyl substituent; an amido having optionally a lower alkyl substituent"c; a pyrrolidinyl-substituted carbonyl wherein the pyrrolidinyl ring may optionally be substituted by a phenyl(lower)alkoxy- carbonyly an amino-substituted lower alkanoy wherein the lower alkanoyl moiety may optionally be substituted by a member selected from phenyl(lower)alkoxycarbonylamino, hydroxy, a phenyl having optionally a hydroxy substitutent, carbamoyl, imidazolyl and a lower alkylthio, and the amino group may optionally have a substituent selected from a lower alkyl having optionally a hydroxy substitutent, a lower alkenyl, phenyl(lower)alkyl having optionally a lower alkoxy substituent on the phenyl ring, a lower alkylsulfonyl, a lower alkanoyl, and a phenyl(lower)alkoxy- carbonyl; a hydroxy-substituted lower alkanoyl; a lower alkanoyloxy(lower)alkanoyl; a lower alkylsulfonyl; a phenylsulfonyl wherein the phenyl ring may optionally be substituted by a lower alkyl, nitro or an amino having optionally one or two substituents selected from a lower WO94/01113 180 PCT/JP93/00835 alkyl and a lower alkanoyl; an amido-substituted lower alkyl wherein the lower alkyl moiety have optionally a substituent selected from a phenyl having optionally a hydroxy substi- tuent, imidazolyl, carbamoyl and a lower alkylthio, and the amido group may optionally have a lower alkyl substituent; an amino-substituted lower alkyl which may optionally substituted by a lower alkyl or a lower alkanoyl; anilino- carbonyl; a piperidinyl which may optionally be substituted by a phenyl(lower)alkyl; a cycloalkyl, a cycloalkenyl- carbonyl; a cycloalkylcarbonyl which may optionally have one to three substituents selected from hydroxy and a lower alkanoyloxy; a tetrahydropyranyl-substituted lower alkyl wherein the tetrahydropyranyl ring may optionally have one to four substituents selected from hydroxy and a lower alkoxy; a lower alkanoyl which is substituted by a 5- or 6- membered saturated heterocyclic group selected from pyrrolidinyl, piperazinyl, piperidinyl and morpholinyl wherein the heterocyclic group have optionally a substituent selected from a lower alkyl and phenyl; a piperidinyl- substituted carbonyl which may optionally be substituted by a lower alkanoyl; a lower alkanoyloxy(lower)alkyl; a pyridyl-substituted lower alkyl; or an amino acid residue which can form an amido group with its amino group, or R 4 and R 5 may bind together with the nitrogen atom to which they bond to form a 5- or 6-membered, saturated or unsaturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom, wherein the heterocyclic group may optionally be substituted by a member 18L WO 94/01113 Cr/ JP93/00835 selected from a phenyl having optionally a subsituent selected from a lower alkoxy and a halogen atom, oxo, hydroxy, a lower alkenyl, carboxy, a phenyl(lower)alkyl having optionally a hydroxy substituent on the lower alkyl moiety, a lower alkanoyl, a lower alkyl having optionally a hydroxy substituent, benzoyl, an amido having optionally a lower alkyl substituent, anilinocarbonyl, a benzoyl(lower)- alkyl, a lower alkylsulfonyl, piperidinyl, pyrimidinyl, pyridyl, and a lower alkoxycarbonyl); a carbamoyloxy- substituted lower alkoxy; a lower alkylthio-substituted lower alkoxy; a lower alkylsulfonyl-substituted lower alkoxy; a lower alkylsulfinyl-substituted lower alkoxy; an alkenyloxy; phenoxy; a lower alkanoyloxy; a lower alkyl- sulfonyloxy; a lower alkynyloxy; a phenyl(lower)alkoxy; a cycloalkyl; a cycloalkyloxyt a cycloalkenyloxy; imidazo- a group of the formula: NR 6 R 7 (wherein a is as defined above, B is a lower alkylene or a group of and R6 and R 7 are the same or different and are each hydrogen atom, a lower alkyl, a lower alkanoyl having optionally one to three halogen substituents, a carboxy(lower)alkyl, a lower alkoxycarbonyl, a lower alkoxycarbonyl(lower)alkyl, a lower alkenyl, an amido-substituted lower alkyl having optionally a lower alkyl substituent, or a phenyl(lower)alkoxycarbonyl, or R 6 and R7 may bind together with nitrogen atom to which they bond to form a 5- or 6-membered, saturated or unsaturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom, wherein the heterocyclic WO 94/01113 182 PCT/JP93/00835 group may optionally have a substituent selected from a lower alkoxycarbonyl, a lower alkyl, a lower alkylthio, and oxo); nitro; a halogen atom; a lower alkylsulfonyl; a lower alkyl which may optionally have one to three substituents selected from a halogen atom, hydroxy, phenyl and a lower alkoxy; a cyano-substituted lower alkoxy; an oxiranyl- substituted lower alkoxy; a phthalimido-substituted alkoxy; an amidino-substituted lower alkoxy, a pyrrolyl-substituted lower alkoxy; cyano; a lower alkoxycarbonyl; amidino; carbamoyl; carboxy; a lower alkanoyl; benzoyl; a lower alkoxycarbonyl(lower)alkyl; a carboxy(lower)alkyl; a lower alkoxy(lower)alkyl; a lower alkanoyloxy(lower)alkyl; hydroxyimino-substituted lower alkyl; phenyl; a lower alkylthio; a lower alkylsulfinyl; a lower alkenyl having optionally a hydroxy substituent; a lower alkylenedioxy, a lower alkylsilyl; a pyrimidylthio-substituted lower alkoxy; a pyrimidylsulfinyl-substituted lower alkoxy; a pyrmidyl- sufonyl-substituted lower alkoxy; an imidazolylthio- substituted lower alkoxy which may optionally have a lower alkyl substituent; an imidazolylsulfonyl-substituted lower alkoxy which may optionally have a lower alkyl substituent; an ammonium-lower alkoxy having three substituents selected from lower alkyl, lower alkenyl and oxo; a phenylthio- substituted lower alkoxy wherein the phenyl ring may optionally have a substituent selected from nitro and amino; a phenylsulfonyl-substituted lower alkoxy wherein the phenyl ring may optionally have a substituent selected from nitro and an amino having optionally one or two substituents 183 selected from a lower alkanoyl and lower alkyl; a pyridylthio-substituted lower alkoxy; or a pyridylsuflonyl- substituted lower alkoxy wherein the pyridyl ring may optionally be substituted by oxo), n is an integer of 1 or 2, m is 0 or an integer of 1 to 3, R 3 is a lower alkyl, R 10 is a group of the formula: -NR 1 R 12 (wherein 9 is as defined above and R 11 and R 12 are the same or different and are each hydrogen atom, a lower alkyl, a phenyl(lower)alkyl, a lower alkenyl, a benzoyl whic} -ay optionally have a lower alkoxy substituent, tricyclo[3.3.1.1]decanyl, a phenyl which may optionally have a lower alkoxy substituent, or a cycloalkyl, or R 11 and R 12 may bind together with the nitrogen atom to which they bond to form a saturated or unsaturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom, wherein the heterocyclic group may optionally have a substituent selected from a benzoyl, a lower alkanoyl, a phenyl(lower)- "alkyl and a phenyl which may optionally be substituted by a lower alkoxy or a lower alkanoyl), the bond between 3- and

4-positions of the carbostyril ring is single bond or double bond, provided that when R 1 is hydrogen atom and the 9 in the formula: -NR 1 1R 12 is 0, R 11 and R 12 are not simultaneously hydrogen atom, or a pharmaceutically acceptable salt thereof, or a benzoheterocyclic compound of the formula __II_ WO 94/01113 184 -PCT/JP93/00835 R 16 (2) N R 17 R wherein R 1 6 is hydrogen atom, a halogen atom, a lower alkyl, an amino having optionally a lower alkyl substituent, or a lower alkoxy, R 17 is hydrogen atom, a halogen atom, a lower alkoxy, a phenyl(lower)alkoxy, hydroxy, a lower alkyl, an amino having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkoxy, an amino-substituted lower alkoxy having optionally a lower alkyl substituent, or a benzoyloxy which has optionally a halogen substituent on the phenyl ring, R 1 8 is a group of the formula: -NR 1 9 R 2 0 or a group of the formula: -CONR 26 R 27 R 1 9 is hydrogen atom, a benzoyl which has optionally a halogen substituent on the phenyl ring, or a lower alkyl, (R 31 R 2 0 is a group of the formula: [wherein R 31 is a halogen atom; a lower alkyl which has optionally a substituent selected from a halogen atom and hydroxy; hydroxy; a lower alkoxy; a lower alkanoyloxy; a lower alkylthio; a lower alkanoyl; carboxy; a lower alkoxycarbonyl; cyano; nitro; an amino which has optionally 185 WO 94/01113 PCT/JP93/00835 a substituent selected from a lower alkyl and a lower alkanoyl; phenyl; a cycloalkyl; a lower alkanoyloxy- substituted lower alkoxy; a carboxy-substituted lower alkoxy; a halogen-substituted lower alkoxy; a carbamoyl- substituted lower alkoxy; a hydroxy-substituted lower alkoxy; a lower alkoxycarbonyl-substituted lower alkoxy; a phthalimido-substituted lower alkoxy; an aminocarbonyl-lower alkoxy having a lower alkyl substituent; or a group of the formula: -O-F-N 21 R 22 (F is a lower alkylene, and R 21 and R 22 are the same or different and are each hydrogen atom, a lower alkyl having optionally a hydroxy substituent, a lower alkanoyl, or benzoyl, or R 21 and R 22 may bind together with the nitrogen atom Qo which they bond to form a 5- or 6- membered saturated heterocyclic group with or without being intervened with nitrogen or oxygen atom wherein the hetero- cyclic group has optionally a substituent selected from piperidinyl and a lower alkyl); and r is an integer of 0 to a phenyl-lower alkoxycarbonyl, a lower alkanoyl, a phenyl-lower alkanoyl, a cycloalkyl-lower alkanoyl, a cycloalkylcarbonyl, tricyclo[3.3.l.1)decanylcarbonyl, naphthylcarbonyl, pyridylcarbonyl, furoyl, thenoyl, a phenoxy-lower alkanoyl wherein the phenyl ring has optionally 1 to 3 substituents selected from a lower alkyl, a lower alkoxy and an amino having optionally a lower alkanoyl substituent, a phthalimido-substituted lower alkanoyl, a lower alkoxycarbonyl-lower alkanoyl, a carboxy- lower alkanoyl, a haphthyloxy-lower alkanoyl, a halogen- substituted lower alkanoyl, a group of the formula: 186 WO 94/01113 PCT/JP93/00835 -COC N-R 23 (wherein R 23 is hydrogen atom, a lower alkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, an amino-lower alkanoyl having optionally a lower alkyl substituent, or a lower alkanoyl), an anilinocarbonyl which has optionally a lower alkyl substituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonyl which has optionally a substituent selected from a halogen atom and a lower alkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula: -CO-G-(CO)s-NR 2 4 R 2 5 (wherein G is a lower alkylene, s is an integer of 0 or 1, and R 24 and R 2 5 are the same or different and are each hydrogen atom, a lower alkyl having optionally a hydroxy substituent, a cycloalkyl, a phenyl- lower alkyl, a lower alkanoyl, a lower alkenyl, a phenoxy- lower alkyl, a phenyl which has optionally 1 to 3 substituents selected from an amino-lower alkyl having optionally a lower alkanoyl substituent, a lower alkyl, a lower alkoxy and a halogen atom, a phthalimido-substituted lower alkyl, an amino-lower alkyl having optionally a lower alkanoyl substituent, a lower alkynyl, or an amino-lower alkyl having optionally a lower alkyl substituent, or R 24 and R 2 5 may bind together with the nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with nitrogen or oxygen atom wherein the heterocylic group has optionally a substituent selected from a lower alkyl, a lower alkoxycarbonyl and piperidinyl), R 2 6 is hydrogen atom or a lower alkyl, R 27 is a cycloalkyl, or a phenyl which has 187 WO 94/01113 PCT/JP93/00835 optionally 1 to 3 substituents selected from a lower alkoxy, a lower alkyl and a halogen atom, W is a group of the formula: -(CH 2 (t is an integer of 3 to or a group of the formula: -CH=CH-(CH 2 v (v is an integer of 1 to the carbon atom of these groups: -(CH 2 and -CH=CH-(CH 2 v being optionally replaced by oxygen atom, sulfur atom, sulfinyl, sulfonyl, or a group of the formula: -NR 28 (R 28 is hydrogen atom, a cycloalkyl, or a lower alkyl), and further said -(CH2) t and -CH=CH-(CH 2 v groups having optionally 1 to 3 substituents selected from a lower alkyl having optionally a hydroxy subatituent, a lower alkoxycarbonyl, carboxy, hydroxy, oxo, a lower alkanoyloxy having optionally a halogen substituent, an amino-lower alkyl having optionally a substituent selected from a lower alkyl and a lower alkanoyl, a lower alkanoyloxy-substituted lower alkyl, a lower alkyl sulfonyloxy-lower alkyl, an azido-lower. alkyl, a group of the formula: -OCH 2 an aminocarbonyloxy having optionally a lower alkyl substituent, a lower alkoxy, a lower alkoxycarbonyl-substituted lower alkoxy, a carboxy- substituted lower alkoxy, an aminocarbonyl-lower alkoxy having optionally a lower alkyl substituent, an amino-lower alkoxy having optionally a substituent selected from a lower alkyl and a lower alkanoyl, a phthalimido-substituted lower alkoxy, hydroxyimino, a lower alkanoyloxy-imino, a lower alkylidene, a halogen atom, azido, sulfoxyimino, a group of the formula: (R 32 is hydrogen atom or a lower /O WO 94/01113 188 PCT/JP93/00835 alkyl), hydrazino, pyrrolyl, an amino-lower alkanoyloxy having optionally a lower alkyl substituent, a group of the formula: -O-F-CO-NR 33 R 34 (F is as defined above, and R 33 and R 34 are the same or different and are each hydrogen atom, a lower alkyl, a carbamoyl-substituted lower alkyl, a hydroxy- substituted lower alkyl, or a pyridyl-lower alkyl, or R 3 and R 34 may bind together with nitrogen atom to which they bond to form a 5- or 6-membered saturated heterocyclic group with or without being intervened with nitrogen, oxygen or sulfur atom wherein the heterocyclic group has optionally a substituent selected from oxo, a lower alkyl, a lower alkanoyl, and carbamoyl), or a group of the formula: -(CO)s- NR29N 30 (wherein s is as defined above, and R 29 and R 30 are the same or different and are each hydrogen atom, a lower alkyl, a lower alkenyl, a lower alkanoyl, a cycloalkyl, an oxiranyl-substituted lower alkyl, a lower alkyl having optionally 1 to 2 substituents selected from a lower alkoxy, hydroxy and an amino having optionally a lower alkyl substituent, a phenyl-lower alkyl, a pyridyl-lower alkyl, a lower alkylsulfonyl, benzoyl, a lower alkoxycarbonyl, anilinocarbonyl, an aminocarbonyl having optionally a lower alkyl substituent, a cyano-substituted lower alkyl, a lower alkoxycarbonyl-substituted lower alkyl, a carbamoyl- substituted lower alkyl, a carboxy-substituted lower alkyl, a tetrahydropyranyloxy-substituted lower alkyl, a lower alkanoyloxy-substituted lower alkyl, a piperidinyl having optionally a phenyl-lower alkyl substituent on the piperidinyl ring, a halogen-substituted lower alkanoyl, an

189- imidazolyl-substituted lower alkanoyl, an amino-lower alkanoyl having optionally a substituent selected from a lower alkyl and a lower alkoxycarbonyl, an aminocarbonyl- lower alkyl having optionally a lower alkyl substituent, or a phenyl-lower alkoxycarbonyl, or R 29 and R 30 may bind together with nitrogen atom to which they bond to form a or 6-membered saturated heterocyclic group with or without being intervened with nitrogen or oxygen, wherein the heterocyclic group may optionally have a substituent selected from a lower alkyl, a phenyl-lower alkyl and a lower alkanoyl, or a pharmaceutical acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier or diluent to a warm-blooded animal including a human being. 2. The method according to claim 1, wherein the oxytocin antagonist is a carbostyril derivative of the formula as set forth in claim 1, or a pharmaceutically acceptable salt thereof. 3. The method according to claim 1, wherein the oxytocin antagonist is a benzoheterocyclic compound of the 20 formula as set forth in claim 1 or a pharmaceutically acceptable salt thereof. i 4. The method according to claim 2, wherein R is a group of the formula: 25 C N-R 2 in which R 2 R 3 m and n are the same as defined above. 5. The method according to claim 2, S o 94222,pAopr\dnb,40569,spc, 189 I 190 WO 94/01113 PCT/JP93/00835 wherein R is a group of the formula: in which R 10 is the same as defined above. 6. The ayto-cin-c ta according to claim 4, wherein R 2 is a group of the formula: -CO(R")p in which R 13 and p are the same as defined above. 7. The -i according to claim 4, wherein R2 is hydrogen atom; a lower alkoxycarbonyl; a phenoxycarbonyl wherein the phenyl ring may optionally be substituted by one to three substituents selected from nitro and an amino having optionally one or two substituents selected from a lower alkanoyl, a lower alkyl and benzoyl; a phenyl(lower)alkenylcarbonyl; a phenyl(lower)alkanoyl wherein the lower alkanoyl moiety may optionally be substituted by an amino having optionally a lower alkoxy- carbonyl substituent; an alkanoyl; an alkenylcarbonyl; a phenylsulfonyl wherein the phenyl ring may optionally be substituted by a lower alkoxy; a group of the formula: -CONR8R 9 (wherein R 8 and R 9 are the same or different and are each hydrogen atom or a phenyl which may optionally have one to three substituents selected from a lower alkoxy, a lower alkyl, a halogen atom, an amino having optionally one or two substituents selected from a lower alkyl and a lower WO 94/01113 -11-PCT/JP93/00835 alkanoyl, and nitro); a heterocyclic group-substituted carbonyl wherein the heterocyclic group may optionally have one to three substituents selected from a phenyl(lower)- alkoxycarbonyl, a phenyl(lower)alkoxy, oxo, a lower alkyl, and a lower alkyltenedioxy); a group of the formula: -CO OH 3 COH "'CH3 OH 3 3 naphthylcarbonyl; a thienyl(lower)alkanoyl; a tricyclo- [3.3.l.lldecanyl(lower)alkanoyl, or tricyclo[3.3.l.lI- decanylcarbonyl. 8. The erryteeln eert-ajna.st~according to claim 6, wherein R 13 is a group of the formula: -_NR 4 R 5 (in which A, E, R 4 and R 5 are the same as defined above), and p is an integer of 1 to 3. 9. The zytzi.2rty4e.\ccording to claim 6, wherein R 13 is an alkoxy which has one or two substituents selEcted from hydroxy, a lower alkanoyloxy, a tri(lower)- alkylammonium, a lower alkoxy, and a group of the formula: -I1R 14 R 15 [whe rein R 14 and R5are the same oL different and are each hydrogen atom, a lower alkyl, a hydroxy-substituted lower alkyl, a lower alkanoyl, a tetrahydropyranyl(lower)- alkyl, phenyl, a phenyl(lower)alkyl (wherein the alkyl moiety may optionally be substituted by hydroxy and the pheny, ring may optionally be substituted by a lower 14j> alkoxy), or a pyridyl~lower)alkyl; or R 1 and R 1 may bind 192 WO 94/01113 PCr/JP93/00835 together with the nitrogen atom to which they bond to form a or 6-membered, saturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom (wherein the heterocyclic group may optionally be substituted by a member selected from carbamoyl, a lower alkyl, a phenyl(lower)alkyl, phenyl and a hydroxy- substituted lower alkyl)), and p is an integer of 1 to 3. The r'nn-" \according to claim 6, wherein R13 is hydroxy; an alkoxy; a carboxy-substitated alkoxy; a halogen-substituted lower alkoxy; a lower alkoxy- carbonyl-substituted alkoxy; a lower alkanoyloxy-substituted lower alkoxy; a lower alkenyloxy-substituted lower alkoxy; a lower alkoxy(lower)alkoxy; a lower alkylsulfonyloxy- substituted lower alkoxy; a benzoyloxy-substituted Xower alkoxy; tricyclo[3.3.1.1]decanyl-sub;tituted .ower alkoxy; a lower alkoxy(lower)alkoxy which is substituted by one or two substituents selected from hydroxy and an amino being optionally substituted by a lower alkyl; a morpholinyl- substituted lower alkoxy which may optionally be substituted by a lower alkyl or oxo; a benzimidazolylthio-substituted lower alkoxy; a benzimidazolylsulfinyl-substituted lower alkoxy; a carbamoyloxy-substituted lower alkoxy; a lower alkylthio-substituted lower alkoxy; a lower alkylsulfonyl- substituted lower alkoxy; a lower alkylsulfinyl-substituted lower alkoxy; an alkenyloxy; phenoxy; a lower alkanoyloxy; a lower alkylsulfonyloxy; a lower alkynyloxy; a phenyl(lower)- alkoxy; a cycloalkyl; a cycloalkyloxy; a cycloalkenyloxy; S imidazo-[4,5-c]pyridyl-carbonyl(lower)alkoxy; a group of the WO 94/01113 19 PICT/JP93/00835 formula: 9 ,NR 6 R 7 (Ahprein i is as defined above, B is a lower alkyl~ne or a group of -CO-o and R 6 and R 7 are the same or diffe ertc and are each hydrogen atom, a lower alkyl, a lower alkanoyl having optionally one to three halogen substituents, a -,rboxy(lower)alkyl, a lower el)oxycarbonyl, a lower alkox, x~y(lower) alkyl, a lower alkenyl, an amido-substituted lower alkyl having optionally a lower alkyl substituent, or a phenyl(lower)alkoxycarbonyl, or R 6 and R 7 may bind together with nitrogen atom to which they bond to form a 5- or 6-membered, saturated or unsaturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom, wherein the heterocyclic group may optionally have a substituont selected from a lower alkoxycarbonyl, a lower alkyl, a lower alkylthio, or oxo); nitro; a halogen atom; a lower alkylsulfonyl; a lower alkyl which may optionally have one to three substituents selected from a halogen atom, hydroxy, phenyl and a lower alkoxy; a cyano-substituted lower alkoxyr- an oxiranyl- substituted lower alkoxy; a phthalimido-substituted alkoxy; an amidino-substituted lower alkoxy, a pyrrolyl-substituted lower alkoxy; cyano; a lower aihoxycarbonyl; amidino; carbamoyl; carboxy; a lower alkanoyl; benzoyl; a lowaL alkoxycarbonyl(lower)alkyl; a carboxy(lower)alkyl; a lower alkoxy(lower)alkyl; a lower alkanoyloxy(lower)alkyl; hydroxyimino-substituted lower alkyl; phenyl; a lovier alkylthio; a lower alkylsulfinyl; a lower alkenyl having optionally a hydroxy substituent; a lower alkylenedioxy, a lower alkylsilyl; a pyrimidylthio-substituted lower alkoxy; S194 WO94/01113 PCT/JP93/00835 a pyrimidylsulfinyl-substituted lower alkoxy; a pyrmidyl- sufonyl-substituted lower alkoxy; an imidazolylthio- substituted lower alkoxy which may optionally have a lower alkyl substituent; an imidazolylsulfonyl-substituted lower alkoxy which may optionally have a lower alkyl substituent; an ammonium-lower alkoxy having three substituents selected from lower alkyl, lower alkenyl and oxo; a phenylthio- sbstituted lower alkoxy wherein the phenyl ring may optionally have a substituent selected from nitro and amino; a phenylsulfonyl-substituted lower alkoxy wherein the phenyl ring may optionally have a substituent selected from nitro and an amino having optionally one or two substituents selected from a lower alkanoyl and lower alkyl; a pyridylthio-substituted lower alkoxy; or a pyridylsuflonyl- substituted lower alkoxy wherein the pyridyl ring may optionally be substituted by oxo. 11. The-ey~oi.-e n odin according to claim 8, wherein r is 0. 12. The ybokea~~aie9 according to claim 11, wherein R 4 and R 5 are the same or different and each hydrogen atom, a lower alkanoyl which may optionally have one to three substituents of a halogen atom. 13. The .o nan-ta- oneatje according to claim 11, wherein R 4 and R 5 may bind together with the nitrogen atom to which they bend to form a 5- or 6-membered, saturated or unsaturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom, in which the heterocyclic group may optionally be substituted by a member WO 94/01113 PCr/JP93/00835 selected from a phenyl having optionally a subsituent selected from a lower alkoxy and a halogen atom, oxot hydroxy, a lower alkenyl, carboxy, a phenyl(lower)alkyl having optionally a hydroxy substituent on the lower alkyl moiety, a lower alkanoyl, a lower alkyl having optionally a hydroxy substituent, benzoyl, an amido having optionally a lower alkyl substituent, anilinocarbonyl, a benzoyl(lower)- alkyl, a lower alkylsulfonyl, piperidinyl, pyrimidinyl, pyridyl, and a lower alkoxycarbonyl. 14. The rn-y't-e-in anlagonict'a ccording to claim 13, wherein the 5- or 6-membered, saturated or unsaturated heterocyclic group which is formed by binding the groups R 4 and R 5 together with the nitrogen atom to which they bond and may be intervened or not with nitrogen, oxygen or sulfur atom is pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyrrolyl, pyrazoly, imidazolyl, imidazolidinyl, 1,2,4-triazolyl, 1,2,3,4-tetrazolyl, pyrrolinyl, imidazolinyl, pyrazo2.inyl, pyrazolidinyl, oxazolinyl, oxazolidinyl, isoxazolinyll isoxazolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl or isothiazolidinyl. The Uooin a;4agonirt4according to any one of claim 12 and 14, wherein RI is hydrogen atom or a halogen atom, and the bond between 3-position and 4-position is single riond. 16. Te o~rtocin2nt.gnir according to claim 2, wherein the activ6 ingredient is a compound selected from 1- ALq,(l-[4-(3-acetylaminopropoxy)benzoyl)-4-piperidinyl)>3 4.- WO 94/01113 PCT/JP93/00835 dihydrocarbostyril, l-(l-(4-(4-acetylaminobutoxy)benzoyl]-4- piperidinyl)-3,4-dihydrocarbostyril: pentyloxy)benzoyl)-4-piperidinyl)-3,4-dihydrocarbostyril, 1- (l-t4-(3-carbamoyloxypropoxy)benzoyl)-4-piperidinyl)-3,4- dihydrocarbostyril, 7-fluoro-l-(l-14-(3-acetylaninopropoxy)- benzoyll-4-piperidinyl)-3..4-dihydrocarbostyril, (l-pyrrolidiriyl )penty2.oxy benzoyl )-4-piperidinyl)-3,4- dihydrocarbostyril, l-(J-4-(6-diethylamino-5-hydroxyhexyl- oxy)benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril, [5-hydroxy-6-( 1-pyrrolidinyl )hexyloxy Ibenzoyl 1-4- piperidinyl)-3,4-dihydrocarbostyril, l-(l-(4-[5-hydroxy-6- dimethylanzinohexyloxy)benzoyl 1-4-piper idinyl)-3, 4-dihydro- carbostyril, 4-(4-hydroxy-5-dirnethylaminopentyloxy)- benzoyl)-4-piperidinyl)-3,4-dihydrocarbostyril, hydroxy-8-diethylaminooctyloxy)benzoyl)-4-piperidinyl)-3,4- dihydrocarbostyril, 1-(l-t benzoyll-4--piperidinyl)-3,4-dihydrocarbostyril and a pharmaceutically acceptable salt thereof. 17. The D__5kacodn to claim 3, wherein R 16 is hydrogen atom, arnd R 17 is hydrogen atom, a halogen atom, a lower alkoxy or a lower alkyl. 18. The e~y-teein 1. -5 -4n-JAaccording to claim 3, wherein R 16 is a halogen atom, and p 17 is hydrogen atom, a halogen atom, a lower alkoxy or a lower alkyl. 19. The o9cyteen an codn to claim 3, wherein R1 6 is a lower alkyl, an amino having optionally a lower alkyl substituent, or a lower alkoxy, and R 17 is hydrogen atom, a halogen atom, a lower alkoxy ov a lower 197 WO 94/01113 PCT/JP93/00835 alkyl. The Qxela hwatt4ng ikaccording to claim 3, wherein R 17 is a phenyl(lower)alkoxy, hydroxy, an amino having optionally a lower alkyl substituent, a carbamoyl- substituted lower alkoxy, an amino-substituted lower alkoxy having optionally a lower alkyl substituent, or a benzoyloxy which has optionally a halogen substituent on the phenyl ring. 21. The omYemt-e 2ap A- according to claim 17, wherein P 18 is a group of the formula: -NR 1 9 R 20 in which R 19 is hydrogen atom and R20 is a group of the formula: (R 3 1 )r -CO (wherein R 31 and r are the same as defined above). 22. The O.toa1 eirP -nrding to claim 3, wherein R18 is a group of the formula: -NR 19 NR 20 in which R 19 is hydrogen atom, and R 2 0 is a phenyl-lower alkoxy- carbonyl, a lower alkanoyl, a phenyl-lower alkanoyl, a cycloalkyl-lower alkanoyl, a cycloalkylcarbonyl, tricyclo- [3.3.l.l]decanylcarbonyl, naphthylcarbonyl, pyridylcarbonyl, furoyl, thenoyl, a phenoxy-lower alkanoyl wherein the phenyl ring has optionally 1 to 3 substituents selected from a lower alkyl, a lower alkoxy and an amino having optionally a lower alkanoyl substituent, a phthalimido-substituted lower alkanoyl, a lower alkoxycarbonyl-lower alkanoyl, a carboxy- lower alkanoyl, a naphthyloxy-lower alkanoyl, a halogen- substituted lower alkanoyl, a group of the formula: !9 WO94/01113 PCT/JP93/00835 -COC N-R23 (wherein R 23 is hydrogen atom, a lower alkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, an amino-lower alkanoyl having optionally a lower alkyl substituent, or a lower alkanoyl), an anilinocarbonyl which has optionally a lower alkyl substituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonyl which has optionally a substituent selected from a halogen atom and a lower alkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula: -CO-G-(CO)s-NR 24 R 25 (wherein G is a lower alkylene, s is 0 or an ingeger of 1, and R 2 4 and R 25 are the sa=e or different and -each hydrogen atom, a lower alkyl having optionally a hydroxy substituent, a cycloalkyl, a phenyl- lower alkyl, a lower alkanoyl, a lower alkenyl, a pheroxy- lower alkyl, a phenyl which has optionally 1 to 3 substituents selected from an amino-lower alkyl having optionally a lower alkanoyl substituent, a lower alkyl, a lower alkoxy and a halogen atom, a phthalimido-substizuted lower alkyl, an amino-lower alkyl having optionally a lower alkanoyl substituent, a lower alkynyl, or an amino-lower alkyl having optionally a lower alkyl substituent, or R 24 and R 25 may bind together with the nitrogen atom to which they bond to form a 5- or 6-membered saturated heterccyclic group with or without being intervened with nitrogen or oxygen atom wherein the heterocylic group has optionally a substituent selected from a lower alkyl, a lower alkcxy- carbonyl and piperidinyl. 23. The o:yr ooeen antagona.#e\according to claim 3, Swherein R 18 is a group of the formula: -CONR 26 R 27 in which

199- R 26 and R 27 are the s&t.e as defined above. 24. The method according to claim 3, wherein R 18 is a group of the formula: -NR 19 R 20 in which R 1 9 is a lower alkyl, and R 20 is the same as defined above. The method according to claim 18, wherein R 18 is a group of the formula: -NR 19 R 20 in which R 1 9 is hydrogen atom, and R 20 is a group of the formula: (R3)r -Co (R 31 and r are the same as defined above). 26. The method according to claim 19, wherein R 18 is a group of the formula: -NR 19 R 20 in which R 19 is hydrogen atom, and R 20 is a group of the formula: (R 3 1 )r -CO (R 3 1 and r are the same as defined .f above). 27. The method according to any one of claims 21, and 26, wherein R 3 1 is a halogen atom or a lower alkyl which has optionally a substituent selected from a halogen atom and hydroxy. 28. The method according to claim 3, wherein W is a group of the formula: -(CH 2 in which t is 4, and the 30 carbon atom thereof is not replaced by any oxygen atom, "sulfur atom, sulfinyl, sulfonyl, or a group of the formula: -NR 28 (R 28 is the same as defined above), and the group of the formula: -(CH 2 has no substituent. 941222,p.\operdab,43569,spc, 199 -200- 29. The method according to claim 3, wherein W is a group of the formula: -(CH 2 in which t is 4, and the carbon atom thereof is not replaced by any oxygen atom, sulfur atom, sulfinyl, sulfonyl, or a group of the formula: -NR 28 (R 28 is the same as defined above), and the group of the formula: -(CH 2 has a substituent of the formula: -(CO)-NR 29 R 30 (R 29 and R 30 are the same as defined above). The method according to claim 29, wherein s is 0, R 29 and R 30 are the same or different and each hydrogen atom, a lower alkyl or a cycloalkyl. 31. The method according to claim 3, wherein W is a group of the formula: -(CH 2 in which t is 3. 32. The method according to claim 3, wherein W is a group of the formula: -(CH 2 in which t is 4. 33. The method according to claim 3, wherein W is a group of the formula: -(CH 2 in which t is 34. The method according to claim 3, wherein W is a group of the formula; -CH=CH-(CH 2 v in which v is 1. The method according to claim 3, wherein W is a 20 group of the formula: -CH=CH-(CH 2 v in which v is 2. 36. The method according to claim 3, wherein W is a group of the formula -CH=CH-(CH 2 v in which v is 3. 37. The method according to claim 3, 941222,p:\opcr\dab,43569,spc,200 _L-r 201 WO 94/01113 PCT/JP93/00835 wherein W is a group of the formula: -(CH 2 in which t is 4, and the carbon atom thereof is not replaced by any oxygen atom, sulfur atom, sulfinyl, sulfonyl, or a group of the formula:-NR 28 (R 28 is the same as defined above), and the group of the formula:-(CH 2 has 1 to 3 substituents selected from a lower alkyl having optionally a hydroxy substituent, hydroxy, an amino-lower alkyl having optionally a substituent selected from a lower alkyl and a lower alkanoyl, an amino-lower ilkanoyloxy having optionally a lower alkyl substituent, a group of the formula: -O-F-CO-NR 33 R 34 R 33 and R 34 are the same as defined above). 38. The -t i =atgntaccording to claim 3, wherein W is a group of the formula: -(CH 2 in which t is 4, and the cargon atom thereof is not replaced by any oxygen atom, sulfur atom, sulfinyl, sulfonyl, or a group of the formula:-NR 28 (R 28 is the same as defined above), and the group of the formula:-(CH 2 has 1 to 3 substituents selected from a lower alkyl having optionally a hydroxy- substituent, and hydroxy. 39. The 9:Eytein anttagon-izt according to claim 32, wherein the heterocyclic group of the formula: W N) is 2,3,4,5-tetrahydro-H-benzazepine. The ir:t:i according to claim 3, wherein the active ingredient is a compound selected from dimethylamino-l-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5- tetrahydro-1H-benzazepine, 7-chloro-5-hydroxy-l- [2-methyl-4- 202 (2-methylbenzoylamino)benzoyl I -2,3,4,5-tetrahydro-LH- benzoazepine, 7-chloro-5-hydroxy-l- [2-methoxy-4- (2-methyl- benzoylamino) benzoyl] 3,4, 5-tetrahydro-1H-benzazepine, 7- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-lH-benzazepine, and a pharmaceutically acceptable aalt thereof. 41. A method for antagonizing oxytocin participating in uterin smooth muscle constriction, which comprises administering an oxytocin antagonist as defined in any one of claims 1 to 40 to a warm-blooded animal including a human being. 42. A method for the protectic-1' or treatment of premature delivery, dysmenorrhoea, endometritis, or for stopping labour preparatory to Caearian delivery or a method for antagonizing oxytocin participating in uterin smooth muscle constriction, substantially as hereinbef ore described with reference to the Pharmacological Test. DATED this 22nd day of December, 1994 Otsuka Pharmaceutical Company, Limited 25 By Its Patent Attorneys DAVIES COLLISON CAVE *9 S .5 S S S 5.5. S. S S S S S. 5* 0 S a S -5 S S S. *5 S. 5* S S 55 S S S 5* 0 5* *5 S SS S 55 S '?AL~z U 94 I222,p\,cpe Mab,43569.spc,202 INTERNATIONAL SEARCH REPORT International Application No PCT/JP 93/00835 -I I. CLASSIFICATION OF SUBJECT MATTER (if several classification symbols apply, Indicate all)* According to International Patent Classification (IPC) or to both National Cassification and IPC Int.C1. 5 A61K31/47; A61K31/44; A61K31/495; A61K31/535 A61K31/55 U. FIELDS SEARCHED Minimum Documentation Scarched 7 Classification System Classification Symbols Int.Cl. 5 A61K Documentation Searched other than Minimum Documentation to the Extent that such Documents are Included in the Fields Searched 8 I. DOCUMENTS CONSIDERED TO BE RELEVANT' Category Citation of Document, it with Indication, where appropriate, of the relevant passages 1 Relevant to CI!m No. 3 X EP,A,0 382 185 (OTSUKA PHARMACEUTICAL CO., 1-2,4-16 LTD) 16 August 1990 cited in the application Y see abstract 41-42, 44,46 see page 317, line 31 line 57; claims X WO,A,9 105 549 (OTSUKA PHARMACEUTICAL 1,3, COMPANY, LIMITED) 17-40 2 May 1991 cited in the application Y see abstract; claims 41,43, 45-46 o Special categories of dted documents :10 later document published after the internstional filing date or priority date and not in conflict with the application but document defining the general state of the art which Is not cited to understand the principle or theory underlying the considered to be of particular relevance invention earlier document but published on or after the International X document of particular relevance; the claimed .ventlon filing date cannot be considered novel or cannot be considered to 'L document which may throw doubts on priority claim(s) or involve an inventive step which is cited to establish the publication date of another document of particular relevance; the claimed invention citation or other special reason (as specified) cannot be considered to Involve an inventive step when the document referring to an oral disclosure, use, exhibition or document is combined with one or more other such docu- other means ments, such combination being obvious to a person skilled r document published prior to the international filing date but in the art. later than the priority date claimed document member of the same patent family IV. CERTIFICATION Date of the Actual Completion of the International Se.'ch Date of Mailing of this International Search Report 17 SEPTEMBER i993 g 0s 9 International Searching Authority Signature of Authorized Officer EUROPEAN PATENT OFFICE HOFF P.J. Frm PCTIISA21O (tocwd set) (Jmamy W1 PCT/JP 93/00835 Internadonal Application No m. DOCUMnENTS CONSIDERED TO BE RELEVANT (CONTINUED FROM THE SECOND SHEET, Category Citation of Document, with indication, where appropriate, of the relevant passages Relevant to Clam No. Y EP,A,0 421 802 (MERCK CO. INC.) 41,43, April 1991 45-46 cited in the application see abstract see page 8, line 50 line 56; claims Y THE JOURNAL OF LABORATORY AND CLINICAL 41-46 MEDICINE vol. 114, no. 6, 1989, pages 617 632 M. MANNING ET AL. 'DISCOVERY, DEVELOPMENT, AND SOME USES OF VASOPRESSIN AND OXYTOCIN ANTAGONISTS' see the whole document, in particular pages 618 and 619 Y THIRD INTERNATIONAL VASOPRESSIN CONFERENCE 41-45 August 1990, pages 339 347 M. AKERLJND 'MECHANISMS BY WHICH VASOPRESSIN INDUCES PAIN OF PRIMARY DYSMENORRHOEA AND THE USE OF VASOPRESSIN AND OXYTOCIN ANTAGONISTS IN THE MANAGEMENT OF PRIMARY DYSMENORRHOEA AND PRETERM LABOUR' see the whole document Y AMERICAN JOURNAL OF OBSTETRICS AND 41-46 GYNECOLOGY vol. 161, 1989, pages 1637 1643 M. IVANISEVIC ET AL. 'VASOPRESSIN RECEPTORS IN HUMAN PREGNANT MYOMETRIUM AND DECIDUA: INTERACTIONS WITH OXYTOCIN AND VASOPRESSIN AGONISTS AND ANTAGONISTS' see the whole document, in particular pages 1637and 1642 X LIFE SCIENCES 1-2,4,6, vol. 50, no. 25, June 1992, 8,11,12, pages 1953 1958 15-16, D.J. PETTIBONE ET AL. 'RADIOLIGAND BINDING 41-42,44 STUDIES REVEAL MARKED SPECIES DIFFERENCES IN THE VASOPRESSIN V1 RECEPTOR OF RAT, RHESUS AND HUMAN TISSUES' see the whole document Form PCTIISA/2IO (eodn Skd) (Jmnsay 19M) ANNEX TO THE INTERNATIONAL SEARCH REPORT ON INTERNATIO1NAL PATENT APPLICATION NO. 9300835 75314 This annex fists the patent family members relating to the rPitent documents cited in the above-wentioncd international mearch report. The members are as contained in the European Patent Offce EDP file on The Europeun Patent Office is in no way liable for theme porticu!ars vhich ame merely given for iChe purpose of information. 17/09/93 PatntdoumntPublication Patent fanmily Publication cited in search report -daem bes)date EP-A-0382185 16-08-90 JP-A- US-A- 1046529 4173870 5225402 31-10-90 29-07-91 06-07-93 tWO1-A-9 105549 02-05-91 AU-B- 630284 22-10-92 AU-A- 7291791 19-12-91 EP-A- 0450097 09-10-91 CN-A- 1051038 01-05-91 JP-A- 4154765 27-05-92 EP-A-0421802 10-04-91 CA-A- 2026856 06-04-9 1 JP-A- 3204866 06-09-91 US-A- 5175159 29-12-92 0- 01 ,6 For more details about this annex :see Official Journal of the European Patent Mwil, No. 12/82