WO1994001113A1 - Antagoniste de l'oxytocine - Google Patents

Antagoniste de l'oxytocine Download PDF

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Publication number
WO1994001113A1
WO1994001113A1 PCT/JP1993/000835 JP9300835W WO9401113A1 WO 1994001113 A1 WO1994001113 A1 WO 1994001113A1 JP 9300835 W JP9300835 W JP 9300835W WO 9401113 A1 WO9401113 A1 WO 9401113A1
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Prior art keywords
optionally
substituted
alkyl
alkoxy
group
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PCT/JP1993/000835
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English (en)
Inventor
Hidenori Ogawa
Hisashi Miyamoto
Kazumi Kondo
Hiroshi Yamashita
Kenji Nakaya
Michinori Tanaka
Kazuyoshi Kitano
Keizo Kan
Michiaki Tominaga
Yoichi Yabuuchi
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Otsuka Pharmaceutical Company, Limited
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Application filed by Otsuka Pharmaceutical Company, Limited filed Critical Otsuka Pharmaceutical Company, Limited
Priority to EP93913553A priority Critical patent/EP0602209A1/fr
Priority to AU43569/93A priority patent/AU657424B2/en
Priority to KR1019940700707A priority patent/KR100210977B1/ko
Publication of WO1994001113A1 publication Critical patent/WO1994001113A1/fr
Priority to KR1019997000408A priority patent/KR100248605B1/ko

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole

Definitions

  • 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,
  • prostaglandin, and vasodilation activity are useful in the protection or treatment of oxytocin relating diseases, e.g. premature delivery, dysmenorrhea,
  • endometr itis , or in stopping labour preparatory to Caesarian delivery.
  • the carboxytril derivatives of the following formula (1) and the benzohetrocyclic compounds of the following formula (2), 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).
  • EP-0421802-A2 discloses that 3-substituted-1,4-benzodiazepines of the following formula are antagonists of oxytocin and are useful in the treatment of preterm labour and dysmenorrhea and for stoppage of labour preparatory to Caesarian delivery:
  • R 1 is H, C 1 -C 6 alkyl, lower alkenyl, lower alkynyl, -X 12 COOR 6 , -X 11 -cyclo(lower)alkyl, -X 12 NR 4 R 5 , -X 12 CONR 4 R 5 , -X 12 CN or -X 11 CX 10 ;
  • R 2 is H, lower alkyl, substituted or unsubstituted phenyl, etc,;
  • R 3 is H, -X 11 NR 18 X 11 R 7 , etc.;
  • R 9 and R 10 are each H, OH or CH 3 ;
  • R 13 is H, lower alkyl, acyl, O, cyclo(lower)alkyl, -X 11 COX 9 X 11 R 7 or -X 11 COX 11 R 7 ;
  • X 1 is H, NO 2 , CF 3 , CN, OH, lower alkyl, halo, etc.;
  • These compounds have a 1,4-benzodiazepine nucleus which is inclusive within the active compounds of the formula (2) of the present invention, but are different in the subs t i tuen t at 1-position.
  • the present inventors have intensively studied the carbostyril derivatives of the formula (1) and the benzohetrocyclic compounds of the formula (2), and have found that these compounds and pharmaceutically acceptable salts thereof have excellent oxytocin antagonistic activity and have accomplished the present invention.
  • carbostyril derivatives which are one of active ingredients of the oxytocin antagonist of the present invention, have the following formula (1):
  • 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
  • R is a group of the formula:
  • R 2 is hydrogen atom; a lower alkoxycarbonyl; a phenoxycarbonyl wherein the phenyl r ing 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
  • alkoxycarbonyl substituent an alkanoyl; an alkenylcarbonyl; a phenylsulfonyl wherein the phenyl ring may optionally be substituted by a lower alkoxy; a group of the formula:
  • 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)alkoxy, oxo, a lower alkyl, and a lower alkylenedioxy; a group of the formula:
  • R 13 is hydroxy; an alkoxy; an alkoxy which has one or two substituents selected from hydroxy, a lower alkanoyloxy, a tri(lower)alkylarnmonium, 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
  • 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
  • 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-substituted lower alkanoyl wherein the lower alkanoyl moiety may optionally be subst i tuted by a member selected from phenyl(lower)alkoxycarbonylamino, hydroxy, a phenyl having optionally a hydroxy substitutent, carbamoyl, imidazolyl and a lower alky
  • 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 optionally one or two substituents selected from a lower 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 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 substituted 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 cycloalkylcarbon
  • 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
  • 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
  • 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 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 carbamoyloxysubstituted lower alkoxy;
  • 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 nitrogen, oxygen or sulfur atom, wherein the heterocyclic group may optionally have a substituent selected from a lower alk
  • hydroxyimino-substituted lower alkyl phenyl; a lower alkylthio; a lower alkylsulfinyl; a lower alkenyl having optionally a hydroxy substituent; a lower alkylenedioxy, a lower alkylsilyy; a pyrimidylthio-substituted lower alkoxy; a pyrimidylsulfinyl-substituted lower alkoxy; a pyrmidylsufonyl-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 phen
  • a substituent selected from nitro and amino 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
  • 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: -(CO) l -NR 11 R 1 2 (wherein a is as defined above and R and R 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[3.3.1.1]decanyl, a phenyl which may optionally have a lower alkoxy substituent, or a
  • R 1 1 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 wi th nitrogen , oxygen or sulfur atom , wherein the heterocyclic group may optionally have a substituent
  • 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 l in the formula: -(CO) l -NR 11 R 12 is 0 and R 11 , R 12 are not simultaneously hydrogen atom.
  • benzoheterocyclic compounds which are also one of the active ingredient of the present oxytocin antagonist, have the following formula (2):
  • 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
  • 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 20 is a group of the formula:
  • 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 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
  • 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:
  • 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 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
  • 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, a lower alkyl and a halogen atom,
  • W is a group of the formula: -(CH 2 ) t - (t is an integer of 3 to 5), or a group of the formula:
  • R 28 is hydrogen atom, a cycloalkyl, or a lower alkyl
  • 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:
  • 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
  • a lower alkyl substituent 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 piperidine ring, a halogen-substituted lower alkanoyl, an 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 al
  • the carbostyril derivatives of the formula (1) and their salts, and the benzoheterocyclic compounds of the formula (2) and their salts have excellent inhibitory effect on uterin smooth muscle constriction, inhibitory effect on milk secretion, inhibitory effect on synthesis and
  • Each group in the above formulae (1) and (2) includes specifically the following groups.
  • 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,
  • the "lower alkyl” includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, tertbutyl, pentyl, hexyl, and the like.
  • halogen atom includes fluorine atom, chlorine atom, bromine atom and iodine atome.
  • 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, 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-hexylamino, N-methyl-
  • 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 example, amino, methylamino, ethylamino, propylamino,
  • phenyl(lower)alkyl includes a phenylalkyl group wherein the alkyl moiety is a straight chain or
  • branched chain alkyl group having 1 to 6 carbon atoms for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 1,1-dimethyl-2-phenylethyl, 2-methyl-3-phenylpropyl, and the like.
  • substituents 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 phenylalkyl 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, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-prop
  • 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 " 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 15 [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
  • 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
  • substituents selected from carbamoyl, 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, 1-hydroxyethoxy, 3-hydroxypropoxy, 2,3-dihydroxyethoxy, 4-hydroxybutoxy, 3,4-dihydroxybutoxy, 1,1-dimethyl2-hydroxyethoxy, 5,6-dihydroxyhexyloxy, 5-hydroxypentyloxy, 6-hydroxyhexyloxy, 7-hydroxyheptyloxy, 8-hydroxyoctyloxy, 9-hydroxynonyloxy, 10-hydroxyde
  • dihexylaminomethoxy N-methyl-N-ethylaminomethoxy, N-methylN-propylaminomethoxy, N-methyl-N-butylaminomethoxy, N-methyl-N-hexylaminomethoxy, 1-methylaminoethoxy, 2-ethylaminoethoxy, 3-propylaminopropoxy, 4-butylaminobutoxy, 1,1-dimethyl-2-pentylaminoethoxy, 5-hexylaminopentyloxy, 6-dimethylaminohexyloxy, 7-methylaminoheptyloxy, 8-dimethylaminooctyloxy, 4-dimethylaminobutoxy, 2-diethylaminoethoxy, 1-(N-methyl-N-hexylamino)ethoxy, 3-dihexylaminopropoxy, 6-diethylaminohexyloxy, 4-dibutylaminobutoxy, 9-(N
  • the "carboxy-substituted alkoxy” includes a carboxy-substituted alkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 12 carbon atoms, for example, carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy, 1,1-dimethyl-2- carboxyethoxy, 2-methyl-3-carboxypropoxy, 7-carboxyheptyloxy, 8-carboxyoctyloxy, 9-carboxynonyloxy, 10-carboxydecyloxy, 11-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, methoxycarbonylmethoxy, 3-methoxycarbonylpropoxy, ethoxycarbonylmethoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy, 6-propoxycarbonylhexyloxy, 1,1-d-methyl-2-butoxycarbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, hexyloxycarbonylmethoxy, 7-methoxycarbonylheptyloxy, 8-ethoxycarbonyloctyloxy, 9
  • 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, 2-propionyloxyethoxy, 1-butyryloxyethoxy, 4-acetyloxybutoxy, 3-acetyloxypropoxy, 4-isobutyryloxybutoxy, 5-pentanoyloxypentyloxy, 6-acetyloxyhexyloxy, 6-tert-butylcarbonyloxyhexyloxy, 1,1-di-ethyl-2-hexanoyloxyethoxy, 2-methyl-3- acetyloxypropoxy, and the like.
  • lower alkenyloxy-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 group having 2 to 6 carbon atoms for example, vinyloxymethoxy, 2-allyloxyethoxy, 1-(2-butenyloxy)ethoxy, 3-allyloxypropoxy, 4-(3-butenyloxy)butoxy, 5-(1-methylallyloxy)pentyloxy, 6-(2-pentenyloxy)hexyloxy, 1,1-dimethyl-2-(2-hexenyloxy)ethoxy, 2-methyl-3-allyloxypropoxy, and the like.
  • the "lower alkoxy(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 alkoxy group having 1 to 6 carbon atoms, for example, methoxymethoxy, 3-methoxypropoxy, 4-ethoxybutoxy, 6-propoxyhexyloxy, 5-isopropoxypentyloxy, 1,1-dimethyl-2-butoxyethoxy, 2-methyl-3-tert-butoxypropoxy, 2-pentyloxyethoxy, hexyloxymethoxy, and the like.
  • lower alkylsulfonyloxy-substi tuted 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 alkylsulfonyloxy group having 1 to 6 carbon atoms, for example, methylsulfonyloxymethoxy, 3-methylsulfonyloxypropoxy, 4-ethylsulfonyloxybutoxy, 2-methylsulfoyloxyethoxy, 6-propylsulfonyloxyhexyloxy, 5-isopropylsulfonyloxypentyloxy, 1,1-dimethyl-2-butylsulfonyloxyethoxy, 2-methyl-3-methlsulfonyloxypropoxy, and the like.
  • the "benzoyloxy-substituted lower alkoxy” includes a benzoyloxyalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, benzoyloxymethoxy, 2-benzoyloxyethoxy, 1-benzoyloxyethoxy, 3-benzoyloxypropoxy, 4-benzoyloxybutoxy, 6-benzoyloxyhexyloxy, 5-benzoyloxypentyloxy, 1,1-dimethyl-2-benzoyloxyethoxy, 2-methyl-3-benzoyloxypropoxy, and the like.
  • tricyclo[3.3.1.1]decanyl-substituted lower alkoxy includes a tricyclo[3.3.1.1]decanyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, tricyclo[3.3.1.1]decanylmethoxy, 2-tricyclo[3.3.1.1]decanylethoxy, 1-tricyclo[3.3.1.1]decanylethoxy, 3-tricyclo[3.3.1.1]decanylpropoxy, 4-tricyclo[3.3.1.1]decanylbutoxy, 5-tricyclo[3.3.1.1] decanylpentyloxy, 6-tricyclo[3.3.1.1]decanylhexyloxy, 1,1-dimethyl2-tricyclo[3.3.1.1]decanylethoxy, 2-methyl-3-tricyclo[3.3.1.1]decanylpropoxy, and the like.
  • the "lower alkylene” includes a straight chain or branched chain alkylene group having 1 to 6 carbon atoms, for example, methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, 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.
  • amino having optionally one or two substituents selected from a lower alkyl, a lower alkanoyl and a phenyl(lower)alkoxycarbonyl 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 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, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexy
  • the "benzoyl wherein the phenyl ring may optionally has a substituent 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” includes a benzoyl group wherein the phenyl ring may
  • the "lower alkoxycarbonyl” includes a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxy- carbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, and the like.
  • the "lower alkoxycarbonyl(lower)alkyl” includes a straight chain or branched 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, methoxycarbonylmethyl, 3-methoxycarbonylpropyl, 3-ethoxycarbonylpropyl, ethoxycarbonylmethyl, 4-ethoxycarbonylbutyl, 1-ethoxycarbonylethyl, 1-methoxycarbonylethyl, 6-propoxycarbonylhexyl, 5-isopropoxycarbonylpentyl, 1,1-dimethyl-2-butoxycarbonylethyl, 2-methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl, hexyloxycarbonylmethyl, and the like.
  • the "amido having optionally a lower alkyl substituent” includes an amido having optionally one or two substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carbamoyl, methylamido, ethylamido, propylamido, isopropylamido, butylamido, tert-butylamido, pentylamido, hexylamido, dimethylamido, diethylamido, dipropylamido, dibutylamido, dipentylamido, dihexylamido, N-methyl-N-ethylamido, N-ethyl-N-propylamido, N-methyl-N-butylamido, N-methyl-N-hexylarnido, and the like.
  • lower alkylsulfonyl includes a straight chain or branched chain alkylsulfonyl group having 1 to 6 carbon atoms, for example, methylsulfonyl, ethylsulfonyl, propyl sulfonyl, isopropylsulfonyl, butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl, and the like.
  • 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” 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.
  • 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 1 to 6 carbon atoms and a halogen atom for example, phenyl, 2-methoxyphenyl, 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, 2,3-dimethoxyphenyl, 3 , 4-diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,5dimethoxyphenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl
  • heterocyclic group which is substituted by a member selected from a phenyl having optionally a
  • 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 phenylalkyl group 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 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, 1-hydroxy-1-phenylmethyl, 1-phenyl-2-hydroxyethyl, 2-phenyl-2-hydroxyethyl, 3-hydroxy-3-phenylpropyl, 2-hydroxy-4-phenylbutyl, 6-hydroxy6-phenylhexyl, 3,4-dimethoxybenzyl, 3-methoxybenzyl, 1-(2-methoxyphenyl)ethyl, 2-(4-methoxyphenyl)ethyl
  • 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, 1-benzoylethyl, 2-benzoylethyl, 3- benzoylpropyl, 4-benzoylbutyl, 5-benzoylpentyl, 6-benzoylhexyl, 1,1-dimethyl-2-benzoylethyl, 2-methyl-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 1 to 6 carbon atoms, for example, carbamoyloxymethoxy, 2-carbamoyloxyethoxy, 1-carbamoyloxyethoxy, 3carbamoyloxypropoxy, 4-carbamoyloxybutoxy, 5-carbamoyloxypentyloxy, 6-carbamoyloxyhexyloxy, 1,1-dimethyl-2-carbamoyloxyethoxy, 2-methyl-3-carbamoyloxypropoxy, and the like.
  • lower alkylthio-substituted alkoxy includes a alkylthio-substituted straight chain or branched chain alkoxy 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, 5-isopropylthiopentylsxy, 1,1-dimethyl-2-butylthioethoxy, 2-methyl-3-methylthiopropoxy, and the like.
  • 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 1 to 6 carbon atoms for example, methylsulfonylmethoxy, 3-ethylsulfonylpropoxy, 4-methylsulfonylbutoxy, 2-methylsulfonylethoxy, 6-propylsulfonylhexyloxy, 5-isopropylsulfonylpentyloxy, 1,1-dimethyl-2-butylsulfonylethoxy, 2-methyl-3-methylsulfonylpropoxy, and the like.
  • lower alkylsulfinyl-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 alkylsulfinyl group having 1 to 6 carbon atoms for example, methylsulfinylmethoxy, 3-ethylsulfinylpropoxy, 4-methylsulfinylbutoxy, 2-methylsulfinylethoxy, 6-propylsulfinylhexyloxy, 5-isopropylsulfinylpentyloxy, 1,1-dimethyl-2-butylsulfinylethoxy, 2-methyl-3-methylsulfinylpropoxy, and the like.
  • alkenyloxy includes a straight chain or branched chain alkenyl group having 2 to 12 carbon atoms and containing one to three double bonds, for example, 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-methyl4-heptenyloxy, 2-methyl-5-heptenyloxy, 4-methyl-2-heptenyloxy, 3-methyl-1-heptenyloxy, 1,3-heptadienyloxy, 1,4-heptadienyloxy, 1,5-heptadienyloxy, 1,6-heptadienyloxy, 2,
  • lower alkanoyloxy includes a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, for example, formyloxy, acetyloxy, propionyloxy,
  • butyryloxy isobutyryloxy, pentanoyloxy, tert-butylcarbonyloxy, hexanoyloxy, and the like.
  • lower alkylsulfonyloxy includes a straight chain or branched chain alkylsulfonyloxy group having 1 to 6 carbon atoms, for example, methylsulfonyloxy, ethylsulfonyloxy, isopropylsulfonyloxy, butylsulfonyloxy, tert-butylsulfonyloxy, pentylsulfonyloxy, hexylsulfonyloxy, and the like.
  • lower alkynyloxy includes a straight chain or branched chain alkynyloxy group having 2 to 6 carbon atoms, for example, ethynyloxy, 2-propynyloxy, 2-butynyloxy, 3-butynyloxy, 1-methyl-2-propynyloxy, 2-pentynyloxy, 2-hexynyloxy, and the like.
  • phenyl (lower )alkoxy includes a phenylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy, 6-phenylhexyloxy, 1,1-dimethyl-2-phenylethoxy, 2-methyl-3- phenylpropoxy, and the like.
  • cycloalkyloxy includes a cycloalkyloxy group having 3 to 8 carbon atoms, for example, cyclopropyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, and the like.
  • cycloalkenyloxy includes a cycloalkenyloxy group having 3 to 8 carbon atoms, 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, 2-fluoroacetyl, 2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl, 3,3,3-trifluoropropionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl, 2,3-dichlopropionyl, 4,4,4-trichloro butyryl, 4-fluorobutyryl, 5-chloropentanoyl,
  • lower alkenyl includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, for example, vinyl, allyl, 2-butenyl, 3-butenyl, 1-methylallyl, 2-pentenyl, 2-hexenyl, and the like.
  • lower alkylthio includes a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio, hexylthio, and the like.
  • the "5- or 6-membered, saturated or unsaturated heterocyclic group which is formed by binding R 6 and R 7 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, pyrrolyl, imidazolinyl, pyrazolinyl,
  • 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 from a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having 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-butoxycarbonylpiperazinyl, 4methylpiperazinyl, 2-ethylthioimidazolyl, 2-oxopyrrolidinyl, 2-oxo-oxazolidinyl, 3-oxopiperazinyl, 4-methoxycarbonylpiperazinyl, 3-ethoxycarbonylpiperidinyl, 2-propoxycarbonylpyrrolidinyl, 3-pentyloxycarbon
  • the "lower alkyl which may optionally have one to three substituents selected from a halogen atom, hydroxy, phenyl and a lower alkoxy” 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 halogen atom, hydroxy, phenyl and a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, in addition to the above-mentioned lower alkyl groups, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihyroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5 ,5,4-tri'hydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3- hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl
  • the "cyano-substituted lower alkoxy” includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by cyano group, for example, cyanomethoxy, 2-cyanoethoxy, 1-cyanoethoxy, 3-cyanopropoxy, 4-cyanobutoxy, 5-cyanopentyloxy, 6-cyanohexyloxy, 1,1-dimethyl-2-cyanoethoxy, 2-methyl-3-cyanopropoxy, and the like.
  • the "oxiranyl-substituted lower alkoxy” includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by oxiranyl group, for example, glycidoxy, 2-oxiranylethoxy, 1-oxiranylethoxy, 3- oxiranylpropoxy, 4-oxiranylbutoxy, 5-oxiranylpentyloxy, 6-oxiranylhexyloxy, 1,1-dimethyl-2-oxiranylethoxy, 2-methyl-3- oxiranylpropoxy, and the like.
  • phthalimido-substituted alkoxy includes a straight chain or branched chain alkoxy group having 1 to 12 carbon atoms which is substituted by phthalimido group, for example, phthalimidomethoxy, 2-phthalimidoethoxy, 1-phthalimidoethoxy, 3-phthalimidopropoxy, 4-phthalimidobutoxy, 5phthalimidopentyloxy, 6-phthalimidohexyloxy, 1,1-dimethyl-2-phthalimidoethoxy, 2-methyl-3-phthalimidopropoxy, 7-phthalimidoheptyloxy, 8-phthalimidooctyloxy, 9-phthalimidononyloxy, 10-phthalimidodecyloxy, 11-phthalimidoundecyloxy, 12- phthalimidododecyloxy, 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, (1-pyrrolyl)methoxy, 2-(2-pyrrolyl)ethoxy, 1-(3-pyrrolyl)ethoxy, 3-(1-pyrrolyl)propoxy, 4-(1-pyrrolyl)butoxy, 5-(2-pyrrolyl)pentyloxy, 6-(3-pyrrolyl)hexyloxy, 1,1-dimethyl-2-(1-pyrrolyl)ethoxy, 2-methyl-3-(1-pyrrolyl)propoxy, and the like.
  • the "amidino-substituted lower alkoxy” 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, 1-amidinoethoxy, 3-amidinopropoxy, 2-amidinobutoxy, 5-amidinopentyloxy, 6-amidinohexyloxy, 1,1-dimethyl-2-amidinoethoxy, 2-methyl-3- amidinopropoxy, and the like.
  • lower alkanoyloxy ( lower)alkyl includes a straight chain or branched chain alkyl 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, acetyloxymethyl, 2-propionyloxyethyl, 1-butyryloxyethyl, 3-acetyloxypropyl, 4-isobutyryloxybutyl, 5-pentanoyloxypentyl, 6-tert-butylcarbonyloxyhexyl, 1,1-dimethyl-2-hexanoyloxyethyl, 2-methyl-3-acetyloxypropyl, and the like.
  • lower alkylsulfinyl includes a straight chain or branched chain alkylsulfinyl group having 1 to 6 carbon atoms, for example, methylsulfinyl, ethylsulfinyl,
  • lower alkenyl having optionally a hydroxysubstituent include a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms and having
  • hydroxy-substituent for example, in addition to the above-mentioned lower alkenyl groups, 1-hydroxyallyl, 4-hydroxy-1-butenyl, 4-hydroxy-2-butenyl, 2-hydroxy-3-butenyl, 5-hydroxy-2-pentenyl, 6-hydroxy-2-hexenyl, and the like.
  • lower alkylenedioxy includes a straight chain or branched chain alkylenedioxy group having 1 to 4 carbon atoms, for example, methylenedioxy, ethylenedioxy,
  • trimethylenedioxy 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,
  • 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, butyrylamino, isobutyrylamino, pentanoylamino, tert-butylcarbonylamino, hexanoylamino, and the like.
  • 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
  • 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
  • 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-dini-rophenoxycarbonyl, 3,4,5-trinitrophenoxycarbonyl, 2-aminophenoxycarbonyl, 3-aminophenoxycarbonyl, 4-aminophenoxycarbonyl, 3-acetylaminophenoxycarbonyl, 4-formylaminophenoxycarbonyl, 4-isobutyrylaminophenoxycarbonyl, 2-pentanoylaminophenoxycarbon
  • phenyl(lower)alkenylcarbonyl 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, cinnamoyl, 4-phenyl-3-butenoyl, 4-phenyl-2-butenoyl, 5-phenyl-4-pentenoyl, 5-phenyl-3-pentenoyl, 5-phenyl-2-pentenoyl, 6-phenyl-5-hexenoyl, 6-phenyl-4-hexenoyl, 6-phenyl-3-hexenoyl, 6-phenyl-2-hexenoyl, 2-methyl-4-phenyl-3-butenoyl, and the like.
  • amino having optionally a lower alkoxycarbonyl substituent includes an amino being optionally substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, amino, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, tert-butoxycarbonylamino, pentyloxycarbonylamino, hexyloxycarbonylamino, and the like.
  • 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 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-phenylpropionyl, 2-phenylpropionyl, 4-phenylbutyryl, 2 , 2-dimethyl-3-phenylpropionyl, 5-phenylpentanoyl, 6-phenylhexanoyl, 3-methyl-4-phenylbutyryl, 2-amino-4-phenylacetyl, 2-tert-butoxycarbonylamino-2-phenylace
  • 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.
  • 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, 2-butenylcarbonyl, 1-methylallylcarbonyl, 2-pentenylcarbonyl, 2-hexenylcarbonyl, 1-heptenylcarbonyl, 1-octenylcarbonyl, 1-nonenylcarbonyl, 1-decenylcarbonyl, 1-undecenylcarbonyl, 1-dodecenylcarbonyl, 2-heptenylcarbonyl, 3-heptenylcarbonyl, 2-methyl-4-heptenylcarbonyl, 2-methyl-5-heptenylcarbonyl, 4-methyl-2-heptenylcarbonyl, 3-methyl-1-heptenylcarbonyl, 1,3-heptadienylcarbonyl,
  • phenylsulfonyl wherein the phenyl ring may 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, 4-isopropoxyphenylsulfonyl, 4-pentyloxyphenylsulfonyl, 4-hexyloxyphenylsulfonyl, 3,4-dimethoxyphenylsulfonyl, 3-ethoxy
  • 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
  • alkanoyl, and nitro 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, 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- methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-e
  • heterocyclic group-substituted carbonyl includes a carbonyl group which is substituted by a 5- to 10-membered, monocyclic or dicyclic heterocyclic groups containing one or two hetero atoms selected from nitrogen atom, oxygen atom and/or sulfur atom, for example, 2-pyrrolidinylcarbonyl, 3-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl, 1-piperazinylcarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl, 2-tetrahydrofurylcarbonyl, 2-thienylcarbonyl, 3-thienylcarbonyl, 2-pyrrolylcarbonyl, 3-pyrrolylcarbonyl, 2-furoyl, 3-furoyl, 2-pyridylcarbonyl, 3-pyridylcarbonyl, 4-pyridylcarbonyl, 3-pyridazylcarbonyl, 2-thiazolylcarbonyl, 2-oxazolylcarbonyl, 2-
  • heterocyclic group-substituted carbonyl which has one to three substitutents selected from a phenyl (lower)alkoxycarbonyl, a phenyl(lower)alkoxy, oxo, a lower alkyl and a lower alkylenedioxy
  • heterocyclic group-substituted carbonyl groups which have one to three substituents selected from a phenylalkoxycarbonyl group wherein the alkoxycarbonyl 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
  • the "thienyl(lower)alkanoyl” includes a thienylalkanoyl wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 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.
  • tricyclo[3.3.1.1]decanyl(lower)adkanoyl includes a tricyclo[3.3.1.1]decanylalkanoyl wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, 2- tricyclo[3.3.1.1]decanylacetyl, 3-tricyclo[3.3.1.1]decanylpropionyl, 2-tricyclo[3.3.1.1]decanylpropionyl, 4-tricyclo[3.3.1.1]decanylbutyryl, 2,2-dimethyl-3-tricyclo[3.3.1.1]decanylpropionyl, 5-tricyclo[3.3.1.l]decanylpentanoyl, 6-tricyclo[3.3.1.1]decanylhexanoyl, 3-methyl-4-tricyclo[ 3.3.1.1]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 straight 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-ethoxybenzoyl, 3-ethoxybenzoyl, 4-butoxybenzoyl, 4-isopropoxybenzoyl, 4-pentyloxybenzoyl, 4-hexyloxybenzoyl, 3,4dimethoxybenzoyl, 3-ethoxy-4-methoxybenzoyl, 2,3-dimethoxybenzoyl, 3,4-diethoxybenzoyl, 2 ,5-dimethoxybenzoyl, 2,6dimethoxybenzoyl, 2,4-dimethoxybenzoyl
  • phenyl which may optionally have a lower alkoxy substituent includes a phenyl 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 phenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,5dimethoxyphenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl,
  • cycloalkyl includes a cycloalkyl having 3 to 8 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like.
  • intervened or not with nitrogen, oxygen or sulfur atom includes, a 5- to 10-membered, saturated or unsaturated, monocyclic or dicyclic heterocyclic group, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino,
  • phenyl which may optionally have a substituent 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-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-ethoxy4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphen
  • 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 group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, 3-benzoyl-1-pyrrolidinyl, 4-benzoyl-1-piperid
  • alkylene includes a straight chain or branched chain alkylene group having 1 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 alkoxycarbonyl(lower)alkyl wherein the alkyl moiety may optionally be substituted by hydroxy or an amino having optionally a phenyl(lower)alkoxycarbonyl substituent” includes a straight chain or branched chain alkoxycarbonylalkyl group having 1 to 6 carbon atoms in the 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, 1-hydroxy-1-methoxycarbonylmethyl, 1-methoxycarbonyl-2-hydroxyethyl, 3-hydroxy-3-methoxycarbonylpropyl, 2-hydroxy-4-ethoxycarbonyl
  • 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 alkylthio, 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 optional
  • 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
  • amido-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms wherein the 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 1 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, 5-carbamoylpentyl, 6-carbamoylhexyl, 1,1-dimethyl-2-carbamoylethyl, 2-methyl-3-carbamoylpropy
  • 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, carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl, 1,1-dimethyl-2-carboxyethyl, 2-methyl-3-carboxypropyl, and the like.
  • the "lower alkoxy(lowe )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, 1-methoxyethyl, 3-methoxypropyl, 4-ethoxybutyl, 6propoxyhexyl, 5-isopropoxypentyl, 1,1-dimethyl-2-butoxyethyl, 2-methyl-3-tert-butoxypropyl, 2-pentyloxyethyl, hexyloxymethyl, and the like.
  • 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, N 2 -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, N 6 -lysine residue, methionine residue, phenylalanine residue, proline residue, serine residue, threonine residue, tryptophane residue, tyrosine residue, valine residue, and the like.
  • 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, 5-hydroxyiminopentyl, 6-hydroxyiminohexyl, 1,1-dimethyl-2-hydroxyiminoethyl, 2-methyl-3-hydroxyiminopropyl, and the like.
  • 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, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy, 5-chloropentyloxy, 3-chloro-2-methylpropoxy, 6-bromohexyloxy, 5,6-dichlorohexyloxy, and the like.
  • 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, 2-phenylethoxycarbonyl, 1-phenylethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl, 5-phenylpentyloxycarbonyl, 6-phenylhexyloxycarbonyl, 1,1-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, hydroxymethoxymethoxy, 3-(2-hydroxyethoxy)propoxy, 4-(1-hydroxyethoxy)butoxy, 6-(3-hydroxypropoxy)hexyloxy, 5-(2,3-dihydroxypropoxy)pentyloxy, 1,1-dimethyl-2-(4-hydroxybutoxy)ethoxy, 2-methyl-3-(3,4-dihydroxybutoxy)propoxy, 2-(1,1-dimethyl-2-hydroxyethoxy)ethoxy,
  • 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 atoms, and an oxo group, for example, (2-morpholinyl)methoxy, 2-(3-morpholinyl)ethoxy, 1-(3-morpholinyl)ethoxy, 3-(2-morpholinyl)propoxy, 4-(3-morpholinyl)butoxy, 5-(2-morpholinyl)pentyloxy, 6-(3-morpholinyl)hexyloxy, 1,1-dimethyl-2-(3-morpholinyl)ethoxy, 2-methyl-3-(2-morpholinyl)propoxy, 6-(1-methyl-5-oxo-3-morph
  • the "benzimidazolylthio-substituted lower alkoxy” includes a benzimidazolylthio-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (benzimidazol-2-yl)thiomethoxy, 1-(benzimidazol-4-yl)thioethoxy, 2-(benzimidazol-5-yl)thioethoxy, 3-(benzimidazol-6-yl)thiopropoxy, 4-(benzimidazol-2-yl) thiobutoxy, 5-(benzimidazol-7-yl)thiopentyloxy, 6-(benzimidazol2-yl)thiohexyloxy, 1,1-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, 1-(benzimidazol-4-yl)sulfinylethoxy, 3-(benzimidazol-6-yl)sulfinylpropoxy, 4-(benzimidazol-2-yl)sulfinylbutoxy, 5-(benzimidazol-7-yl)sulfinylpentyloxy, 6-(benzimidazol-2-yl)sulfinylhexyloxy, 1,1-dimethyl-2-(benzimidazol-2-yl)sulfinylethoxy, 2-methyl-3-(benzimidazol2-yl)sulfinylpropoxy, and
  • tetrahydropyranyl-substituted lower alkyl includes a tetrahydropyranyl-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (2-, 3- or 4-tetrahydropyranyl)methyl, 2-(2-, 3- or 4-tetrahydropyranyl)ethyl, 1-(2-, 3- or 4-tetrahydropyranyl)ethyl, 3-(2-, 3- or 4-tetrahydropyranyl)propyl, 4-(2-, 3- or 4-tetrahydropyranyl)butyl, 5-(2-, 3- or 4-tetrahydropyranyl)pentyl, 6-(2-, 3- or 4-tetrahydropyranyl)hexyl, 1,1-dimethyl-2-(2-, 3- or 4-tetrahydropyranyl)ethyl, 2- methyl-3-(2-, 3- or 4-tetrahydropyranyl)propyl,
  • the "5- 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.
  • heterocyclic group having a substituent selected from carbamoyl, a lower alkyl, a phenyl(lower)alkyl, phenyl and a hydroxy-substituted lower alkyl is selected from carbamoyl, a lower alkyl, a phenyl(lower)alkyl, phenyl and a hydroxy-substituted lower alkyl
  • 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, 3-phenylthiomorpholino, 4-benzylpiperazinyl, 3-(2-phenylethyl)pyrrolidinyl, 2-(3-phenylpropyl)pyrrolidinyl, 4-(4-phenylbutyl)piperidinyl, 3-(5-phenylpent
  • 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, ( 2-phenylethoxycarbonyl)amino, (1-phenylethoxycarbonyl)amino, (3-phenylpropoxycarbonyl)amino, (4-phenylbutoxycarbonyl)amino, (5-phenylpentyloxycarbonyl)amino, (6-phenylhexyloxycarbonyl)amino, (1,1-dimethyl-2-phenylethoxycarbonyl)amino, ( 2-methyl-3-phenylpropoxycarbonyl)amino, and the like.
  • phenyl having optionally hydroxy substituent includes a phenyl group having optionally one to three hydroxy-substituents, for example, phenyl, 4-hydroxyphenyl, 3-hydroxyphenyl, 2-hydroxyphenyl, 2,4-dihydroxyphenyl, 3,4- dihydroxyphenyl, 2,3,4-trihydroxyphenyl, and the like.
  • phenylsulfonyl 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 alkyl includes a phenylsulfonyl group wherein the phenyl ring may optionally have one to three substitutents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a 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 and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, phenylsulfonyl, 2-methylphenylsulfonyl, 3-methylphenylsulfonyl, 4-methylphenylsulfonyl, 2-ethylphenylsulfon
  • amino-substituted lower alkyl which may optionally have a substituent selected from a lower alkyl and a lower alkanoyl
  • the "piperidinyl having optionally a phenyl(lower)alkyl substituent" includes a piperidinyl which has
  • a substituent of a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms for example, 4-piperidinyl, 3-piperidinyl, 2-piperidinyl, 1-benzyl-4-piperidinyl, 1-(2-phenylethyl)-3-piperidinyl, 2-(3-phenylpropyl)-5- piperidinyl, 3-(4-phenylbutyl)-6-piperidinyl, 4-(5-phenylpentyl)-3-piperidinyl, 5-(6-phenylhexyl)-4-piperidinyl, 2-benzyl-4-piperidinyl, 1-(3-phenylpropyl)-4-piperidinyl, and the like.
  • the "imidazo[4,5-c]pyridylcarbonyl(lower)alkoxy” includes an imidazo[4,5-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-(imidazo[4,5-c]pyridin-2-yl)carbonylethoxy, 1-(imidazo[4,5-c]pyridin-4- yl)carbonylethoxy, 3-(imidazo[4,5-c]pyridin-5-yl)carbonylpropoxy, 4-(imidazo[4,5-c]pyridin-7-yl)carbonylbutoxy, 5-(imidazo[4,5-c]pyridin-2-yl)carbonylpentyloxy, 6-(imidazo[4,5-c]pyridin-2-yl)carbonylhexy
  • tri(lower alkyl)ammonium includes an ammonium group having three of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example,
  • the "pyridyl(lower)alkyl” include a pyridylalkyl group wherein the alkyl moiety is a straight chain or 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-(4-pyridyl)propyl, 4-(2-pyridyl)butyl, 5-(3-pyridyl)pentyl, 6-(4-pyridyl)hexyl, 1,1-dimethyl-2-(2-pyridyl)ethyl, 2-methyl-3-(3-pyridyl)propyl, and the like.
  • the "lower alkyl which may optionally have a substituent selected from hydroxy and cyano" 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-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, 2,3-dihydroxyethyl, 3,4-dihydroxybutyl, 5,6-dihydroxyhexyl, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl,
  • lower alkynyl includes a straight chain or branched chain alkynyl group 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.
  • pyrrolidine ring includes a pyrrolidmylcarbonyl which may optionally be substituted by a phenylalkoxycarbonyl group on the pyrrolidine ring wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, 1-benzyloxycarbonyl-2-pyrrolidinylcarbonyl, 2-pyrrolidinylcarbonyl, 1-pyrrolidinylcarbonyl, 3-pyrrolidinylearbonyl, 1-(2-phenylethoxycarbonyl)-2-pyrrolidinylcarbonyl, 2-(1-phenylethoxycarbonyl)-1-pyrrolidinylcarbonyl, 3-(3-phenylpropoxycarbonyl)-2-pyrrolidinylcarbonyl, 1-(4-phenylbutoxycarbonyl)-2-pyrrolidinylcarbonyl, 2-(5-phenylpentyloxycarbonyl)-1-pyr
  • phenyl(lower)alkoxycarbonylamino includes a phenylalkoxycarbonylammo 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-(1-phenylethoxycarbonyl)amino, N-(3-phenylpropoxycarbonyl)amino, N-(4-phenylbutoxycarbonyl)amino, N-(5-phenylpentyloxycarbonyl)amino, N-(6-phenylhexyloxycarbonyl)amino, N-(1,1-dimethyl-2-phenylethoxycarbonyl)amino, N-(2-methyl-3-phenylpropoxycarbonyl)amino, and the like.
  • the "lower alkyl having optionally a hydroxysubstituent” includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which has optionally one to three hydroxy-substituents, for example, in addition to the above-mentioned lower alkyl groups, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxy hexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, 2,3-dihydroxybutyl, 3,4-dihydroxyhexyl, 5,6-dihydroxyhexyl, 2,3,4-trihydroxybutyl, and the like.
  • hydroxy-substituted lower alkanoyl includes a hydroxy-substituted straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, 2-hydroxyacetyl, 3-hydroxypropionyl, 2-hydroxypropionyl, 4-hydroxybutyryl, 2,2-dimethyl-3-hydroxypropionyl, 5-hydroxypentanoyl, 6-hydroxyhexanoyl, 3-methyl-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 alkanoyl group having 2 to 6 carbon atoms, for example, 2-acetyloxyacetyl, 3-propionyloxypropionyl, 2-butyryloxypropionyl, 4-pentanoyloxybutyryl, 2,2-dimethyl-3-hexanoyloxypropionyl, 5-acetyloxypentanoyl, 6-propionyloxyhexanoyl, and the like.
  • 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-methoxybenzyl, 3-methoxybenzyl, 2-(4-methoxyphenyl)ethyl, 1-(2-ethoxyphenyl)ethyl, 3-(4-isopropoxyphenyl)propyl, 4-(3-pentyloxyphenyl)butyl, 5-(4-hexyloxyphenyl)pentyl, 6-(2- butyloxyphenyl)hexyl,
  • 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-pyrimidyl)thiohexyloxy, 1,1-dimethyl-2-(2-pyrimidyl)thioethoxy, 2-methyl-3-(2-pyrimidyl)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-pyrimidyl)sulfinylethoxy, 1-(5-pyrimidyl)sulfinylethoxy, 3-(6-pyrimidyl)sulfinylpropoxy, 4-(4-pyrimidyl)sulfinylbutoxy, 5- (2-pyrimidyl)sulfinylpentyloxy, 6-(5-pyrimidyl)sulfinylhexyloxy, 1,1-dimethyl-2-(2-pyrimidyl)sulfinylethoxy, 2-methyl-3-(2-pyrimidyl)sulfinylpropoxy, and the like
  • the "pyrimidylsulfonyl-substituted lower alkoxy” includes a pyrimidylsulfonyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyrimidyl)sulfonylmethoxy, 2-(4-pyrimidyl)sulfonylethoxy, 1-(5-pyrimidyl)sulfonylethoxy, 3-(6-pyrimidyl)sulfonylpropoxy, 4-(4-pyrimidyl)sulfonylbutoxy, 5-(2-pyrimidyl)sulfonylpentyloxy, 6-(5-pyrimidyl)sulfonylhexyloxy, 1,1-dimethyl-2-(2-pyrimidyl)sulfonylethoxy, 2-methyl-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-(4-imidazolyl)thioethoxy, 1-(5-imidazolyl)thioethoxy, 3-(2- imidazolyl) thiopropoxy, 4-(4-imidazolyl)thiobutoxy, 5-(2-imidazolyl)thiopentyloxy, 6-(5-imidazolyl)thiohexyloxy, 1,1-dimethyl-2-(2-imidazolyl)thioethoxy, 2-methyl-3-(2-imidazolyl)
  • the "imidazolylsulfonyl-substituted lower alkoxy which may optionally have a lower alkyl substituent” includes a imidazolylsulfonyl-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)sulfonylmethoxy, 2-(4-imidazolyl)sulfonylethoxy, 1-(5-imidazolyl)sulfonylethoxy, 3-(2-imidazolyl)sulfonylpropoxy, 4-(4-imidazolyl)sulfonylbutoxy, 5-(2-imidazolyl)sulfonylpentyloxy, 6-(5-imidazolyl)sulfonylhexyloxy
  • the "ammonium-substituted lower alkoxy having three substituents selected from a lower alkyl, a lower alkenyl and oxo" includes an ammonium-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 1 to 6 carbon atoms, a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, and an oxo group, for example, trimethylammoniummethoxy, 2-(triethylammonium)ethoxy, 1-(tripropylammonium)ethoxy, 3-(tributylammonium)propoxy, 4-(tripentylammonium)butoxy, 5-(triethylammonium)pentyloxy, 6-(trihexyl ammonium)hexyloxy, 1,1-dimethyl-2-(triallylammonium)ethoxy
  • 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
  • substituents selected from a nitro group and an amino group for example, phenylthiomethoxy, 2-phenylthioethoxy, 1-phenylthioethoxy, 3-phenylthiopropoxy, 4-phenylthiobutoxy, 5-phenylthiopentyloxy, 6-phenylthiohexyloxy, 1,1-dimethyl-2-phenylthioethoxy, 2-methyl-3-phenylthiopropoxy, (2-nitrophenyl)thiomethoxy, 2-(3-nitrophenyl)thioethoxy, 1-(4-nitrophenyl)thioethoxy, 3-(2,3-dinitrophenyl)thiopropoxy, 4-(3,4-dinitrophenyl)thiobutoxy, 5-(4-nitrophenyl)thiopentyloxy, 6-(2,6-dinitrophenyl)thiohexyloxy, 1,1-dimethyl-2-(2,4,6-trinitrophenyl)thi
  • 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 alkyl 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-phenylsulf
  • the "pyridylthio-substituted lower alkoxy” includes a pyridylthio-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyridyl)thiomethoxy, 2-(3-pyridyl)thioethoxy, 1-(4-pyridyl)thioethoxy, 3-(3-pyridyl)thiopropoxy, 4-(4-pyridyl)thiobutoxy, 5-(2-pyridyl)thiopentyloxy, 5-(4-pyridyl)thiopentyloxy, 6-(3-pyridyl)thiohexyloxy, 1,1-dimethyl-2-(2-pyridyl)thioethoxy, 2-methyl-3-(4-pyridyl)thiopropoxy, and the like.
  • the "pyridylsulfonyl-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 1 to 6 carbon atoms which may optionally have an oxo substituent on the pyridine ring, for example, (2-pyridyl)sulfonylmethoxy, 2-(3-pyridyl)sulfonylethoxy, 1-(4-pyridyl)sulfonylethoxy, 3-(3-pyridyl)sulfonylpropoxy, 4-(4-pyridyl)sulfonylbutoxy, 5-(2-pyridyl)sulfonylpentyloxy, 5-(4-pyridyl)sulfonylpentyloxy, 6- ( 3-pyr idy
  • cycloalkylcarbonyl having optionally one to three substituents selected from hydroxy and a lower
  • alkanoyloxy 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, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, 2-hydroxycyclopropylcarbonyl, 3-hydroxycyclobutylcarbonyl, 2-hydroxycyclopentylcarbonyl, 3-hydroxycyclopentylcarbonyl, 2,4-dihydroxycyclopentylcarbonyl, 2-hydroxycyclohexylcarbonyl, 3-hydroxycyclohexylcarbonyl, 4-hydroxycyclohexylcarbonyl, 3,4-dihydroxycyclohexylcarbonyl, 2,4-dihydroxycycl
  • tetrahydroypyranyl(lower)alkyl wherein the tetrahydroxypyranyl 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 1 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-tetrahydropyranyl)ethyl, 1-(4-tetrahydropyranyl)ethyl, 3-(2-tetrahydropyranyl)propyl, 4-(3-tetrahydropyranyl)butyl, 5-(4-tetrahydropyranyl)pentyl,
  • the "lower alkanoyl substituted by a 5- or 6-membered 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-membered saturated heterocyclic group selected from pyrrolidinyl, piperazinyl, piperidinyl, and morpholinyl, for example, 2-(1-pyrrolidinyl)acetyl, 3- ( 2-pyr rol idinyl ) propionyl , 2- ( 3-pyr rolidinyl ) propionyl , 4-(1-pyrrolidinyl)butyryl, 2,2-dimethyl-3-(2-pyrrolidinyl)propionyl, 5-(3-pyrrolidinyl)pentanoyl, 6-(1-pyrrolidinyl)hexanoyl, 2-
  • heterocyclic group-substituted lower alkanoyl which has a substituent selected from a lower alkyl and phenyl
  • the "piperidinylcarbonyl which may optionally have a lower alkanoyl 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, (1-acetyl-4-piperidinyl)carbonyl, (4-formyl-1-piperidinyl)carbonyl, ( 3-propionyl-2-piperidinyl)carbonyl, ( 1-butyryl-4-piperidinyl)carbonyl, (1-pentanoyl-4-piperidinyl)carbonyl, (1-hexanoyl-4-piperidinyl)carbonyl, and the like.
  • 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.
  • 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, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N- 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
  • amino having optionally a substituent selected from a lower alkyl and a lower alkanoyl 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 st raight 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-ethylN-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N
  • 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, 3-carbamoylpropoxy, 4-carbamoylbutoxy, 5-carbamoylpentyloxy, 6-carbamoylhexyloxy, 1,1-dimethyl-2-carbamoylethoxy, 2-methyl-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, 1-hydroxyethoxy, 3-hydroxypropoxy, 2,3-dihydroxypropoxy, 4-hydroxybutoxy, 3,4-dihydroxybutoxy, 1,1-dimethyl-2-hydroxyethoxy, 5-hydroxypentyloxy, 6-hydroxyhexyloxy, 2-metnyl-3-hydroxypropoxy, 2,3,4-trihydroxybutoxy, and the like.
  • lower alkoxycarbonyl-substituted lower alkoxy includes an alkoxycarbonyl-substituted 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, ethoxycarboxymethoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy, 6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxy carbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, 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, 1-carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy, 1,1-dimethyl-2-carboxyethoxy, 2-methyl-3-carboxypropoxy, and the like.
  • 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, 1-phthalimidoethoxy, 3-phthalimidopropoxy, 4-phthalimidobutoxy, 5-phthalimidopentyloxy, 6-phthalimidohexyloxy, 1,1-dimethyl-2-phthalimidoethoxy, 2-methyl-3-phthalimidopropoxy, and the like.
  • the "5- 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.
  • 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 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-(1-piperidinyl)piperidinyl, 3-(1-piperidinyl)pyrrolidinyl, 3-(1-piperidinyl)-4-methylpiperazinyl, 3-(1-piperidinyl)morpholino, and the like.
  • 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, 5-phenylpentanoyl, 6-phenylhexanoyl, and the like.
  • cycloalkyl-lower alkanoyl includes C 3 -C 8 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, 2,2-dimethyl-3-cycloheptylpropionyl, 5-cyclooctylpentanoyl, 6-cyclohexylhexanoyl, and the like.
  • cycloalkylcarbonyl includes a cycloalkylcarbonyl having 3 to 8 carbon atoms, for example,
  • 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 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,
  • 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-phthalimidoacetyl, 3-phthalimidopropionyl, 2-phthalimidopropionyl, 4-phthalimidobutyryl, 2,2-dimethyl-3-phthalimidopropionyl, 5-phthalimidopentanoyl, 6-phthalimidohexanoyl, 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-methoxycarbonylpropionyl, ethoxycarbonylacetyl, 3-ethoxycarbonylpropionyl, 4-ethoxycarbonylbutyryl, 3-propoxycarbonylpropionyl, 2-methoxycarbonylpropionyl, 6-propoxycarbonylhexanoyl, 5-isopropoxycarbonylpentanoyl, 2,2-dimethyl-3-butoxycarbonylpropionyl, 2-methyl-3-tert-butoxycarbonylpropionyl, pentyloxycarbonylacetyl, he
  • 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-carboxypropionyl, 4-carboxybutyryl, 2,2-dimethyl-3-carboxypropionyl, 5-carboxypentanoyl, 6-carboxyhexanoyl, and the like.
  • the "naphthyloxy-lower alkanoyl” includes a
  • naphthyloxy-alkanoyl 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, 2,2-dimethyl-3-naphthyloxypropionyl, 5-naphthyloxypentanoyl, 6-naphthyloxyhexanoyl, and the like.
  • the "phenyl-lower alkoxycarbonyl” includes a phenylalkoxycarbonyl wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, benzyloxycarbonyl, 2-phenylethoxycarbonyl, 1-phenylethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl, 5-phenylpentyloxycarbonyl, 6-phenylhexyloxycarbonyl, 1,1-dimethyl-2-phenylethoxycarbonyl, 2-methyl-3-phenylpropoxycarbonyl, and the like.
  • 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, 1-phenoxyethyl, 2-phenoxyethyl, 3-phenoxypropyl, 4-phenoxybutyl, 5-phenoxypentyl, 6-phenoxyhexyl, 1,1-dimethyl-2-phenoxyethyl, 2-methyl-3-phenoxypropyl, and the like.
  • 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 straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and a halogen atom, for example, phenyl, 2-methoxyphenyl, 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, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-d
  • 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 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, (N-e
  • the "5- 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 with nitrogen or oxygen atom” includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, and the like.
  • heterocyclic group navir.g a substituent selected from a lower alkyl, a lower alkoxycarbonyl and piperidinyl includes the above-mentioned heterocyclic groups having 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxycarbonyl having 1 to 6 carbon atoms and piperidinyl, for example, in addition to the above-mentioned heterocyclic groups having a substituent selected from a lower alkyl and piperidinyl, 4-methoxycarbonylpiperazinyl, 4-ethcxycarbonylpiperidinyl, 3-propoxycarbonylpyrrolidinyl, 2-pentyloxycarbonylmorpholino, 4-hexyloxycarbonylpiperidinyl, 4-ethoxycarbonyl-3-methylpiperidinyl, 3-methyl-4-ethoxycarbonylpipe
  • the "5- 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.
  • 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 group having 1 to 6 carbon atoms, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 2-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-hexylpiperazinyl, and the like.
  • the heterocyclic ring in the formula (2) includes tetrahydroquinolyl, 2,3,4,5-tetrahydro-1H-benzazepinyl, 1,2,3,4,5,6-hexahydrobenzazocinyl, 1,2-dihydroquinolyl, 2,3-dihydro-1H-benzazepinyl, 1,2,3,4-tetrahydrobenzazocinyl, and the like.
  • halogen-substituted lower alkanoyl includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms which has 1 to 3 substituents of a halogen atom, for example, 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl, 2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl, 3,3,3-trifluoropropionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl, 2,3-dichloropropionyl, 4,4,4-trichlorobutyryl, 4-fluorobutyryl, 5-chloropentanoyl, 3-chloro-2-methylpropionyl, 6-bromohexanoyl, 5,6-dibromohe
  • 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 1 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-isopropyIaminocarbonyIpropoxy, 4-butyIaminocarbonylbutoxy, 5-pentylaminocarbonylpentyloxy, 6-hexylaminocarbonylhexyloxy, dimethylammocarbonylmethoxy, 3-diethylaminocarbonylpropoxy, diethylaminocarbonyImethoxy, (N-ethyl-N-propylamino)carbonylmethoxy, 2- (N-methyl-N-hexylamino) carbonylethoxy, and the like.
  • the "carbamoyl-lower alkyl” includes a carbamoyl- substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carbamoylmethyl, 2-carbamoylethyl, 1-carbamoylethyl, 3-carbamoylpropyl, 4-carbamoylbutyl, 5-carbamoylpentyl, 6-carbamoylhexyl, 1,1-dimethyl-2-carbamoylethyl, 2-methyl-3-carbamoylpropyl, and the like.
  • 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
  • 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-aminoacetyl, 3-aminopropionyl, 2-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl, 6-aminohexanoyl, 2,2-dimethyl-3-aminopropionyl, 2-methyl-3-aminopropionyl, 2-methylaminoacetyl, 2-ethylaminopropionyl, 3-propylaminopropionyl, 3-isopropylaminopropionyl, 4-butylaminobutyryl, 5-pentylaminopentanoyl, 6-hexylaminohexanoyl, 2-dimethylaminoacetyl, 2-diethylaminoacetyl, 2-(N-ethyl-N-propylamino)acetyl, 3-(
  • amino-lower alkyl having optionally a lower alkanoyl substituent includes a straight chain or branched chain alkyl having 1 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, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-amino- propyl, acetylaminomethyl, 1-acetylaminoethyl, 2-propionylaminoethyl, 3-isopropionylaminopropyl, 4-butyrylaminobutyl, 5-pentanoylaminopentyl, 6-hexanoylaminohexyl,
  • anilinocarbonyl 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 to 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, 3,4-diethylanilinocarbonyl, 2,4-dimethylanilinocarbonyl, 2,5-dimethylanilinocarbonyl, 2,6-dimethylanilinocarbonyl, 3,4,5-trimethylanilinocarbonyl
  • phenylsulfonyl which has optionally a substituent selected from a halogen and a lower alkyl on the phenyl ring
  • 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, 2-chlorophenylsulfonyl, 3-chlorophenylsulfonyl, 4-chlorophenylsulfonyl, 2-fluorophenylsulfonyl, 3-fluorophenylsulfonyl, 4-fluorophenylsulfonyl, 2-bromophenylsulfonyl, 3-bromophenylsulfonyl, 4-bromophenylsulfonyl, 2-iodophenylsulfonyl, 3-
  • phthalimido-substituted lower alkyl includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by phthalimido croup, for example, phthalimidomethyl, 2-phthalimidoethyl, 1-phthalimidoethyl, 3-phthalimidopropyl, 4-phthalimidobutyl, 5-phthalimidopentyl, 6-phthalimidohexyl, 1,1-dimethyl-2-phthalimidoethyl, 2-methyl-3-phthalimidopropyl, and the like.
  • the "lower alkynyl” includes a straight chair, 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 halogen 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, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl , 4-iodobenzoyl , 3 , 4-dichlorobenzoyl , 3 , 5-dichlorobenzoyl, 2 , 6-dichlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 3,4-difluorobenzoyl
  • 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 having 1 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-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, acetylaminomethoxy, 1-acetylaminoethoxy, 2-propionylaminoethcxy, 3-isopropionylaminopropoxy, 4-butyrylaminobutoxy, 5-pentanoylaminopentyloxy, 6-hexanoylaminohe
  • 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, 2-fluorobenzoyloxy, 3-fluorobenzoyloxy, 4-fluorobenzoyloxy, 2-bromobenzoyloxy, 3-bromobenzoyloxy, 4-bromobenzoyioxy, 2-iodobenzoyloxy, 3-iodobenzoyloxy, 4-iodobenzoyloxy, 3,4-dichlorobenzoyloxy, 3,5-dichlorobenzoyloxy, 2,6-dichlorobenzoyloxy, 2 ,3-dichlorobenzoyloxy, 2,4-dichlorobenzo
  • lower alkanoyloxy-substituted lower alkyl includes a straight chain or branched chain alkyl 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, acetyloxymethyl, 2-propionyloxyethyl, 1-butyryloxyethyl, 3-acetyloxypropyl, 4-acetyloxybutyl, 4-isobutyryloxybutyl, 5-pentanoyloxypentyl, 6acetyloxyhexyl, 6-tert-butylcarbonyloxyhexyl, 1,1-dimethyl2-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 chain or branched chain alkylsulfonyloxy group having 1 to 6 carbon atoms, for example, methylsulfonyloxymethyl, 1-ethyl- sulfonyloxyethyl, 2-propylsulfonyloxyethyl, 3-isopropylsulfonyloxypropyl, 4-butylsulfonyloxybutyl, 5-pentylsulfoyloxypentyl, 6-hexylsulfonyloxyhexyl, 1,1-dimethyl-2-methylsulfonyloxyethyl, 2-methyl-3-ethylsulfonyloxypropyl, and the like.
  • the "azido-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, 4-azidobutyl, 5-azidopentyl, 6-azidohexyl, 1,1-dimethyl-2-azidoethyl, 2-methyl-3-azidopropyl, and the like.
  • an azido group for example, azidomethyl, 1-azidoethyl, 2-azidoethyl, 3-azidopropyl, 4-azidobutyl, 5-azidopentyl, 6-azidohexyl, 1,1-dimethyl-2-azidoethyl, 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, propionyloxyimino, butyryloxyimino, isobutyryloxyimino, pentanoyloxyimino, tert-butylcarbonyloxyimino, hexanoyloxyimino , and the like .
  • lower alkylidene includes a straight chain or branched chain alkylidene group having 1 to 6 carbon atoms, for example, methylidene, ethylidene, propylidene,
  • oxiranyl-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-oxiranylpropyl, 4-oxiranylbutyl, 5-oxiranylpentyl, 6-oxiranylhexyl, 1,1-dimethyl-2-oxiranylethyl, 2-methyl-3- oxiranylpropyl, and the like.
  • 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, 2-propoxyethyl, 3-isopropoxypropyl, 4-butoxybutyl, 5-pentyloxypentyl, 6-hexyloxyhexyl, 1,1-dimethyl-2-methoxyethyl, 2-methyl-3-ethoxypropyl, 3-methoxy-2-hydroxypropyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxy
  • aminocarbonyloxy having optionally a lower alkyl substituent includes an aminocarbonyloxy group having optionally 1 to 2 substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminocarbonyloxy, methylaminocarbonyloxy, ethylaminocarbonyloxy, propylaminocarbonyloxy, isopropylaminocarbonyloxy, butylammocarbonyloxy, tert-butylaminocarbonyloxy, pentylaminocarbonyloxy, hexylaminocarbonyloxy,
  • dimethylaminocarbonyloxy diethylaminocarbonyloxy, dipropylaminocarbonyloxy, dibutylaminocarbonyloxy, dipentylaminocarbonyloxy, dihexylaminocarbonyloxy, N-methyl-N-ethylaminocarbonyloxy, N-ethyl-N-propylaminocarbonyloxy, N-methyl-N-butylaminocarbonyloxy, N-methyl-N-hexylaminocarbonyloxy, and the like.
  • the "lower alkanoyloxy having optionally a halogen substituent” includes a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms which has optionally 1 to 3 substituents of a halogen atom, for ⁇ xample, 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-fluorobuty
  • 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 alkanoyl group having 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, acetylaminomethyl, 1-acetylaminoethyl, 2-propionylaminoethyl, 3-isopropionylaminopropyl, 4-butyrylaminobutyl, 5-pentanoylaminopentyl, 6-hexanoylamin
  • amino-lower alkanoyloxy having optionally a 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, 3-propylaminopropionyloxy, 3-isopropylaminopropionyloxy, 4butylaminobutyryloxy, 5-pentylaminopentano
  • 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-(2-pyridyl)ethyl, 3-(2-pyridyl)propyl, 4-(3-pyridyl)butyl, 5-(4-pyridyl)pentyl, 6-(2-pyridyl)hexyl, 1,1-dimethyl-2-(3-pyridyl)ethyl, 2-methyl-3-(4-pyridyl)propyl, and the like.
  • the "5- 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,
  • heterocyclic group which has a substituent selected from oxo, a lower alkyl, a lower alkanoyl and carbamoyl includes the above heterocyclic groups which have 1 to 3 substituents selected from oxo, 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 carbamoyl group, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-hexylpiperazinyl, 2-methylthiomorpholino, 4-acetylpiperazinyl, 2-propanoylmorpholino, 3-butyrylthiomorpholino, 3-pentanoylpyrrol
  • aminocarbonyl having optionally a lower alkyl substituent includes an aminocarbonyl group having
  • substituents 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, pentylaminocarbonyl, hexylaminocarbonyl, dimethylaminocarbonyl,
  • diethylaminocarbonyl dipropylaminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylaminocarbonyl, N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylamino c1rbonyl, 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 substituted by cyano group, for example, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl, 1,1-dimethyl-2-cyanoethyl, 2-methyl-3-cyanopropyl, and the like.
  • the "lower alkoxycarbonyl-substituted lower alkyl” includes an alkoxycarbonyl-substituted straight chain or branched chain alkyl 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, methoxycarbonylmethyl, 3-methoxycarbonylpropyl, ethoxycarboxymethyl, 3-ethoxycarbonylpropyl, 4-ethoxycarbonylbutyl, 5-isopropoxycarbonylpentyl, 6-propoxycarbonylhexyl, 1,1-dimethyl-2-butoxycarbonylethyl, 2-methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl, hexyloxycarbonylmethyl, and the like.
  • the "carboxy-substituted lower alkyl” includes a carboxy-substituted alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl, 1,1-dimethyl-2-carboxyethyl, 2-methyl-3-carboxypropyl, and the like.
  • the "tetrahydropyranyloxy-substituted lower alkyl” includes a tetrahydropyranyloxy-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (2-tetrahydropyranyl)oxymethyl, 2-(3-tetrahydropyranyl)oxyethyl, 1-(4-tetrahydropyranyl)oxyethyl, 3-(2-tetrahydropyranyl)oxypropyl, 4-(3-tetrahydropyranyl)oxybutyl, 5-(4-tetrahydropyranyl)oxypentyl, 6-(2-tetrahydro ⁇ pyranyl)oxyhexyl, 1,1-dimethyl-2-(3-tetrahydropyranyl)oxyethyl, 2-methyl-3-(4-tetrahydropyranyl)oxypropyl, and the like.
  • the "piperidinyl having optionally a phenyl-lower alkyl substituent" includes a piperidinyl which has
  • a substituent of a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms for example, piperidinyl, 1-benzyl-4-piperidinyl, 1-(2-phenylethyl)-3-piperidinyl, 1-(1-phenylethyl)-2-piperidinyl, 1-(3-phenylpropyl)-4-piperidinyl, 1-(4-phenylbutyl)-4-piperidinyl, 1-(5-phenylpentyl)-4-piperidinyl, 1-(6-phenylhexyl)-4-piperidinyl, 1- (1,1-dimethyl-2-phenylethyl)-3-piperidinyl, 1-(2-methyl-3-phenylpropyl)-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, (1- imidazolyl)acetyl, 3-(2-imidazolyl)propionyl, 2-(4-imidazolyl)propionyl, 4-(1-imidazolyl)butyryl, 2,2-dimethyl-3-(2-imidazolyl)propionyl, 5-(4-imidazolyl)pentanoyl, 6-(1-imidazolyl)hexanoyl, and the like.
  • amino-lower alkanoyl having optionally a substituent selected from a lower alkyl and a lower alkoxy carbonyl 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
  • a straight 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-aminopentanoyl, 6-aminohexanoyl, 2,2-dimethyl-3-aminopropionyl, 2-methyl-3-aminopropionyl, 2-methylaminoacetyl, 2-ethylaminopropionyl, 3-propylaminopropionyl, 3-isopropylaminopropionyl, 4-butylaminobutyryl, 5-pentylaminopentanoyl, 6-hexylaminohexanoyl, 2-dimethylaminoacetyl, 2-diethylaminoacetyl, 2-(N-ethyl-N-propy
  • 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, 1-ethylaminocarbonylethyl, 2-propylaminocarbonylethyl, 3-isopropylaminocarbonylpropyl, 4-butylaminocarbonylbutyl, 5-pentylaminocarbonylpentyl, 6-hexylaminocarbonylhexyl, dimethylaminocarbonylmethyl, 3-diethylaminocarbonylpropyl, diethylaminocarbonylmethyl, (N-ethyl-N-propylamino)carbonylmethyl, 2-(N-methyl-N-hexylamino)carbonyl
  • amino-substituted lower alkoxy having optionally a lower alkyl substituent includes an aminosubstituted straight chain or branched 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, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy, 4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, (N
  • 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 (1) 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 (2) can be prepared, for example, by the method disclosed in European Patent No. 450097.
  • the carbostyril derivatives of the formula (1) can be prepared, for example, by the method dislcosed in Japanese Patent First Publication (Kokai) No. 173870/1991
  • the benzohetrocyclic compounds of the formula (2) can be prepared, for example, by the method disclosed in European Patent No. 450097.
  • the compounds having an acidic group can easily be converted into salts by treating with a pharmaceutically acceptable basic compound.
  • the basic compound includes, for example, metal hydroxides such as sodium hydroxide,
  • 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.
  • the compounds having an ammonium group can be converted into a salt thereof with a pharmaceutically acceptable halogen anion (e.g. chlorine anion, bromine anion, fluorine anion, or iodine anion).
  • halogen anion e.g. chlorine anion, bromine anion, fluorine anion, or iodine anion.
  • active compounds (1) and (2) of this invention include stereoisomers and optical isomers, and these isomers are also useful as the active ingredient in this invention.
  • 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 (1), (2) 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.
  • conventional carriers such as vehicles (e.g.
  • lactose white sugar, sodium chloride, glucose, urea, starches, calcium carbonate, kaolin, crystalline cellulose, silicic acid, etc.
  • binders e.g. water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution,
  • disintegrators e.g. dry starch, sodium arginate, agar powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium laurylsulfate, stearic monoglyceride, starches, lactose, etc.
  • disintegration inhibitors e.g. white sugar, stearin, cacao butter, hydrogenated oils, etc.
  • absorption promoters e.g. quaternary ammonium base, sodium laurylsulfate, etc.
  • wetting agents e.g. glycerin, starches, etc.
  • adsorbents e.g.
  • 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.
  • the carriers include conventional vehicles (e.g. glucose, lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin, talc, etc.), binders (e.g. gum arable powder, tragacanth powder, gelatin, ethanol, etc.), disintegrators (e.g. laminaran, agar, etc.), and the like.
  • the carriers include conventional vehicles, for example, polyethylene glycol, cacao oils, higher
  • 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.
  • the solutions, emulsions or suspendions are steri lized and are preferably made isotonic with the blood.
  • 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.
  • 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 (1) and (2) 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.
  • the injections are intraveneously administered alone or together with a conventional auxiliary liquid (e.g. 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.
  • a conventional auxiliary liquid e.g. glucose, amino acid solutions
  • the dosage of the oxytocin antagonist of the present invention may be selected in accordance with the usage, 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 (1) or (2) per 1 kg of body weight of the patient per day.
  • the active compound is preferably
  • the present invention is illustrated by the following Preparations of oxytocin antagnist, and
  • Film coated tablets are prepared from the following components.
  • 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.
  • Tablets are prepared from the following components
  • Citric acid 1.0 g
  • the active compound of the present invention citric 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
  • the core tablets thus prepared are vanished and dusted with talc in order to guard from wetting.
  • Undercoating is applied to the core tablets.
  • the core tablets are vanished several times.
  • 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.
  • An injection preparation is prepared from the following components.
  • Polyethylene glycol (molecular weight: 4000) 0 . 3 9
  • 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°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.
  • Film coated tablets are prepared from the following components.
  • 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.
  • Tablets are prepared from the following components.
  • Citric acid 1.0 g
  • Polyethylene glycol (Carbowax 6000) 45.0 g Corn starch 30.0 g
  • the active compound of the present invention citric 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
  • the core tablets thus prepared are vanished and dusted with talc in order to guard from wetting.
  • Undercoating is applied to the core tablets.
  • the core tablets are vanished several times.
  • 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.
  • An injection preparation is prepared from the following components.
  • Polyethylene glycol (molecular weight: 4000) 0.3 g
  • 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°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.
  • Oxytocin Receptor Binding Assay 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 mixture is filtered through the glass filter (GF/F) so as to separate the membrane
  • Inhibitory Rate (%) 100 - [ ( C ⁇ B ) / ( C Q -3 ) ] x 100
  • IC 50 values which is the concentration of the test compound required to achieve the inhibitory effect in the rate of 50 %.
  • 2-53 5-Carbamoylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine
  • 2-54 5-Dimethylaminocarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H- benzazepine
  • 2-84 5-(N-Acetyl-N-methylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine
  • 2-85 5-Cyclopropylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine
  • 2-86 5-(2-Dimethylaminoethylamino)-1-[2-chloro-4-(2- methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H- benzazepine
  • 2-102 5-Hydroxy-5-methyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine
  • 2-103 5-(N-Ethoxycarbonylmethyl-N-methylamino)-1-[4-(2- methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H- benzazepine
  • 2-107 4-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]- 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine
  • 2-108 5-Methyl-1-(4-benzoylaminobenzoyl]-2,3,4,5- tetrahydro-1H-1,5-benzodiazepine
  • 2-109 5-Isopropyl-1-[4-(2,3-dimethylbenzoylarnino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine
  • 2-110 1-[4-(2-methylbenzoylamino)benzoyl]-1,2-dihydroquinoline
  • 2-111 5- [ 2- ( 4-Morpholino)acetyloxy ] -7-chloro-1- [ 2- methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5- tetrahydro-1H-benzazepine hydrochloride
  • 2-120 1-[4-[3-Methylphenylsulfonylamino)benzoyl]-2,3,4,5- tetrahydro-1H-benzazepine
  • 2-121 1-[4-(2-Methylbenzoylamino)benzoyl]-2,3,4,5- tetrahydro-1H-benzazepine
  • 2-129 1- ⁇ 4-[2-(6-Isopropylaminohexyloxy)benzoylamino]benzoyl ⁇ -2,3,4,5-tetrahydro-1H-benzazepine
  • 2-130 1-[4-(2-(N-Phenyl-N-ethynylamino)acetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine
  • 2-131 1-[4-(2-(N-Phenyl-N-methylamino)acetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine
  • 2-132 1-[(2-(4-Phenylamino)acetylamino)benzoyl]-2,3,4,5- tetrahydro-1H-benzazepine
  • 2-145 7-Chloro-1- ⁇ 4-[2-[4-isopropylaminobutoxy)benzoylamino]benzoyl ⁇ -2,3,4,5-tetrahydro-1H-benzazepine
  • 2-146 1-[4-(2-Methylbenzoylamino)benzoyl]-1,2,3,4,5,6- hexahydrobenzazocine
  • 2-158 1- ⁇ 4-[4-(6-(1-Piperidyl)hexyloxy)benzoylamino]benzoyl ⁇ -2,3,4,5-tetrahydro-1H-benzazepine
  • 2-159 1-[4-(2-Chloro-4-aminobenzoylamino)benzoyl]- 2,3,4,5-tetrahydro-1H-benzazepine
  • 2-160 3-Dimethylaminocarbonyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline 2-161: 1- ⁇ 4-[2-(4-Methoxyanilino)acetylamino]benzoyl ⁇ - 2,3,4,5-tetrahydro-1H-benzazepine 2-162: 1- ⁇ 4-[2-(2-(4-Morpholino)ethoxy)benzoylamino]benzoyl ⁇ -2,3,4,5-tetrahydro-1H-benzazepine 2-163: 1- ⁇ 4-[2-(4-Hydroxybutoxy)benzoylamino]benzoyl ⁇ - 2,3,4,5-tetrahydro-1H-benzazepine
  • 2-164 1- ⁇ 4-(2-Diethylaminocarbonylmethoxybenzoylamino)benzoyl ⁇ -2,3,4,5-tetrahydro-1H-benzazepine
  • 2-165 1- ⁇ 4-(2-[N-(1-(2-Propyl)), N-(phenyl)amino]acetylamino)benzoyl ⁇ -2,3,4,5-tetrahydro-1H-benzazepine
  • 2-166 4-Isopropyl-1- ⁇ 4-(2,3-dimethylbenzoylamino)benzoyl ⁇ -2,3,4,5-tetrahydro-1H-1,4-benzodiazepine
  • 2-167 1- ⁇ 4-[4-(2-Diethylaminoacetyl-1-piperidinyl)carbonylamino]benzoyl ⁇ -2,3,4,5-tetrahydro-1H- benzazepine hydrochloride
  • 2-176 5-(Anilinocarbonylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine
  • 2-177 5-Isobutylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine
  • 2-178 5-Formylamino-1-[4-(2-methylbenzoylamino)benzoyl]- 2,3,4,5-tetrahydro-1H-benzazepine
  • Test IC 50 Test IC 50
  • Test IC 50 Test IC 50
  • Test IC 50 Test IC 50
  • Test IC 50 Test IC 50
  • Test IC 50 Test IC 50

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Abstract

L'invention concerne un antagoniste de l'oxytocine qui comprend, comme ingrédient actif, le dérivé carbostyrile répondant à la formule (1) ou bien le composé benzohétérocyclique répondant à la formule (2), ou bien un sel pharmaceutiquement acceptable dudit dérivé ou dudit composé. L'antagoniste selon l'invention présente une excellente activité dirigée contre l'oxytocine et peut, par conséquent, être utilisé dans la prévention ou le traitement de maladies associées à l'oxytocine, notamment pour prévenir un accouchement prématuré, pour traiter les dysménorrhées et les endométrites, ou bien pour stopper le travail afin de pouvoir pratiquer une césarienne.
PCT/JP1993/000835 1992-07-02 1993-06-22 Antagoniste de l'oxytocine WO1994001113A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP93913553A EP0602209A1 (fr) 1992-07-02 1993-06-22 Antagoniste de l'oxytocine
AU43569/93A AU657424B2 (en) 1992-07-02 1993-06-22 Oxytocin antagonist
KR1019940700707A KR100210977B1 (ko) 1992-07-02 1993-06-22 옥시토신 길항제
KR1019997000408A KR100248605B1 (en) 1992-07-02 1999-01-20 Oxytocin antagonist

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP17556692 1992-07-02
JP4/175563 1992-07-02
JP4/175566 1992-07-02
JP17556392 1992-07-02

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Publication Number Publication Date
WO1994001113A1 true WO1994001113A1 (fr) 1994-01-20

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EP (1) EP0602209A1 (fr)
CN (1) CN1091288A (fr)
AU (1) AU657424B2 (fr)
CA (1) CA2116334A1 (fr)
ID (1) ID15999A (fr)
MX (1) MX9304015A (fr)
TW (1) TW249201B (fr)
WO (1) WO1994001113A1 (fr)

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US5356904A (en) * 1992-10-07 1994-10-18 Merck & Co., Inc. Carbostyril oxytocin receptor antagonists
WO1995002405A1 (fr) * 1993-07-16 1995-01-26 Merck & Co., Inc. Benzoxasinone et benzopyrimidinone piperidinyle utiles comme antagonistes tocolytiques du recepteur de l'oxytocine
WO1997022591A1 (fr) * 1995-12-15 1997-06-26 Otsuka Pharmaceutical Company, Limited Derives de la benzazepine agonistes de la vasopressine
EP0805681A1 (fr) * 1995-01-24 1997-11-12 Merck & Co., Inc. Antagonistes tocolytiques des recepteurs de l'oxytocine
US5726172A (en) * 1996-01-16 1998-03-10 Merck & Co., Inc. Tocolytic oxytocin receptor antagonists
US6340678B1 (en) 1997-03-06 2002-01-22 Yamanouchi Pharmaceutical Co., Ltd. 4,4-difluoro-2,3,4,5-tetrahydro-1H-1-benzoazepine derivatives and drug compositions containing them
WO2003016316A1 (fr) * 2001-08-16 2003-02-27 Ferring B.V. Diazacycloalkanes utilises comme agonistes de l'ocytocine
WO2003105849A1 (fr) * 2002-06-13 2003-12-24 Rheogene, Inc. Tetrahydroquinolines destinees a moduler l'expression de genes exogenes par le biais d'un complexe de recepteurs de l'ecdysone
WO2004065351A1 (fr) * 2003-01-24 2004-08-05 Novartis Ag Derives amido et leur utilisation comme inhibiteurs de la 11-beta-hydroxysteroide deshydrogenase de type 1
US6900200B2 (en) 2001-04-12 2005-05-31 Wyeth Tricyclic hydroxy carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
US6977254B2 (en) 2001-04-12 2005-12-20 Wyeth Hydroxy cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists
US7022699B2 (en) 2001-04-12 2006-04-04 Wyeth Cyclohexenyl phenyl diazepines vasopressin and oxytocin receptor modulators
JP2006512404A (ja) * 2002-10-22 2006-04-13 グラクソ　グループ　リミテッド Ｈ３受容体リガンドとしてのアリールオキシアルキルアミン誘導体
US7064120B2 (en) 2001-04-12 2006-06-20 Wyeth Tricyclic pyridyl carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
US7109193B2 (en) 2001-04-12 2006-09-19 Wyeth Tricyclic diazepines tocolytic oxytocin receptor antagonists
US7202239B2 (en) 2001-04-12 2007-04-10 Wyeth Cyclohexylphenyl carboxamides tocolytic oxytocin receptor antagonists
US7211672B2 (en) 2002-10-04 2007-05-01 Millennium Pharmaceuticals, Inc. PGD2 receptor antagonists for the treatment of inflammatory diseases
US7326700B2 (en) 2001-04-12 2008-02-05 Wyeth Cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists
US7423032B2 (en) 2003-02-24 2008-09-09 Otsuka Pharmaceutical Co., Ltd. Method for treating severe heart failure and medicament therefor
US7504508B2 (en) 2002-10-04 2009-03-17 Millennium Pharmaceuticals, Inc. PGD2 receptor antagonists for the treatment of inflammatory diseases
US7547804B2 (en) 2002-07-15 2009-06-16 Myriad Genetics, Inc. Compounds, compositions, and methods employing same
US7671058B2 (en) 2006-06-21 2010-03-02 Institute Of Medicinal Molecular Design, Inc. N-(3,4-disubstituted phenyl) salicylamide derivatives
US7951950B2 (en) 2005-02-24 2011-05-31 Millennium Pharmaceuticals, Inc. PGD2 receptor antagonists for the treatment of inflammatory diseases
US9073868B2 (en) 2007-06-26 2015-07-07 Otsuka Pharmaceutical Co., Ltd. Benzazepine derivatives useful as vasopressin antagonists
US9096546B2 (en) 2007-05-10 2015-08-04 Albany Molecular Research, Inc. Aryl- and heteroaryl-substituted tetrahydrobenzo-1,4-diazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
US9102669B2 (en) 2011-12-06 2015-08-11 Janssen Pharmaceutica Nv Substituted piperidinyl-pyridazinyl derivatives useful as SCD 1 inhibitors
US9238658B2 (en) 2011-12-06 2016-01-19 Janssen Pharmaceutica Nv Substituted piperidinyl-carboxamide derivatives useful as SCD 1 inhibitors
WO2019004421A1 (fr) 2017-06-30 2019-01-03 Otsuka Pharmaceutical Co., Ltd. Dérivés de benzazépine
WO2022156449A1 (fr) * 2021-01-19 2022-07-28 徐州医科大学 Nouveau composé de benzoazépine, composition et utilisation associées
EP3813819A4 (fr) * 2018-06-29 2022-08-17 Kinnate Biopharma Inc. Inhibiteurs de kinases dépendantes des cyclines
US11690825B2 (en) 2016-03-09 2023-07-04 Board Of Regents, The University Of Texas System 20-HETE receptor (GPR75) antagonists and methods of use
EP4253367A4 (fr) * 2020-11-26 2024-10-23 Shanghai Jemincare Pharmaceuticals Co Ltd Nouveau dérivé spiro de benzazépine

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US5356904A (en) * 1992-10-07 1994-10-18 Merck & Co., Inc. Carbostyril oxytocin receptor antagonists
WO1995002405A1 (fr) * 1993-07-16 1995-01-26 Merck & Co., Inc. Benzoxasinone et benzopyrimidinone piperidinyle utiles comme antagonistes tocolytiques du recepteur de l'oxytocine
US5665719A (en) * 1993-07-16 1997-09-09 Merck & Co., Inc. Benzoxazinone and benzopyrimidinone piperidinyl tocolytic oxytocin receptor antagonists
EP0805681A1 (fr) * 1995-01-24 1997-11-12 Merck & Co., Inc. Antagonistes tocolytiques des recepteurs de l'oxytocine
EP0805681A4 (fr) * 1995-01-24 1998-05-06 Merck & Co Inc Antagonistes tocolytiques des recepteurs de l'oxytocine
WO1997022591A1 (fr) * 1995-12-15 1997-06-26 Otsuka Pharmaceutical Company, Limited Derives de la benzazepine agonistes de la vasopressine
US6096736A (en) * 1995-12-15 2000-08-01 Otsuka Pharmaceutical Company, Limited Benzazepine derivatives with vasopressin agonistic activity
US5726172A (en) * 1996-01-16 1998-03-10 Merck & Co., Inc. Tocolytic oxytocin receptor antagonists
US6340678B1 (en) 1997-03-06 2002-01-22 Yamanouchi Pharmaceutical Co., Ltd. 4,4-difluoro-2,3,4,5-tetrahydro-1H-1-benzoazepine derivatives and drug compositions containing them
US7109193B2 (en) 2001-04-12 2006-09-19 Wyeth Tricyclic diazepines tocolytic oxytocin receptor antagonists
US7326700B2 (en) 2001-04-12 2008-02-05 Wyeth Cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists
US6900200B2 (en) 2001-04-12 2005-05-31 Wyeth Tricyclic hydroxy carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
US6977254B2 (en) 2001-04-12 2005-12-20 Wyeth Hydroxy cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists
US7022699B2 (en) 2001-04-12 2006-04-04 Wyeth Cyclohexenyl phenyl diazepines vasopressin and oxytocin receptor modulators
US7202239B2 (en) 2001-04-12 2007-04-10 Wyeth Cyclohexylphenyl carboxamides tocolytic oxytocin receptor antagonists
US7064120B2 (en) 2001-04-12 2006-06-20 Wyeth Tricyclic pyridyl carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
WO2003016316A1 (fr) * 2001-08-16 2003-02-27 Ferring B.V. Diazacycloalkanes utilises comme agonistes de l'ocytocine
WO2003105849A1 (fr) * 2002-06-13 2003-12-24 Rheogene, Inc. Tetrahydroquinolines destinees a moduler l'expression de genes exogenes par le biais d'un complexe de recepteurs de l'ecdysone
US7547804B2 (en) 2002-07-15 2009-06-16 Myriad Genetics, Inc. Compounds, compositions, and methods employing same
US7211672B2 (en) 2002-10-04 2007-05-01 Millennium Pharmaceuticals, Inc. PGD2 receptor antagonists for the treatment of inflammatory diseases
US7504508B2 (en) 2002-10-04 2009-03-17 Millennium Pharmaceuticals, Inc. PGD2 receptor antagonists for the treatment of inflammatory diseases
JP2006512404A (ja) * 2002-10-22 2006-04-13 グラクソ　グループ　リミテッド Ｈ３受容体リガンドとしてのアリールオキシアルキルアミン誘導体
WO2004065351A1 (fr) * 2003-01-24 2004-08-05 Novartis Ag Derives amido et leur utilisation comme inhibiteurs de la 11-beta-hydroxysteroide deshydrogenase de type 1
US7423032B2 (en) 2003-02-24 2008-09-09 Otsuka Pharmaceutical Co., Ltd. Method for treating severe heart failure and medicament therefor
EP2000142A1 (fr) 2003-02-24 2008-12-10 Otsuka Pharmaceutical Co., Ltd. Procédé pour traiter une insuffisance cardiaque grave et médicament associé
US7749993B2 (en) 2003-02-24 2010-07-06 Otsuka Pharmaceutical Co., Ltd. Method for treating severe heart failure and medicament therefor
US7951950B2 (en) 2005-02-24 2011-05-31 Millennium Pharmaceuticals, Inc. PGD2 receptor antagonists for the treatment of inflammatory diseases
US7671058B2 (en) 2006-06-21 2010-03-02 Institute Of Medicinal Molecular Design, Inc. N-(3,4-disubstituted phenyl) salicylamide derivatives
US9096546B2 (en) 2007-05-10 2015-08-04 Albany Molecular Research, Inc. Aryl- and heteroaryl-substituted tetrahydrobenzo-1,4-diazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
US9073868B2 (en) 2007-06-26 2015-07-07 Otsuka Pharmaceutical Co., Ltd. Benzazepine derivatives useful as vasopressin antagonists
US9102669B2 (en) 2011-12-06 2015-08-11 Janssen Pharmaceutica Nv Substituted piperidinyl-pyridazinyl derivatives useful as SCD 1 inhibitors
US9238658B2 (en) 2011-12-06 2016-01-19 Janssen Pharmaceutica Nv Substituted piperidinyl-carboxamide derivatives useful as SCD 1 inhibitors
US11690825B2 (en) 2016-03-09 2023-07-04 Board Of Regents, The University Of Texas System 20-HETE receptor (GPR75) antagonists and methods of use
WO2019004421A1 (fr) 2017-06-30 2019-01-03 Otsuka Pharmaceutical Co., Ltd. Dérivés de benzazépine
KR20200020910A (ko) 2017-06-30 2020-02-26 오츠카 세이야쿠 가부시키가이샤 벤즈아제핀 유도체
US10889570B2 (en) 2017-06-30 2021-01-12 Otsuka Pharmaceutical Co., Ltd. Benzazepine derivatives
US11673878B2 (en) 2017-06-30 2023-06-13 Otsuka Pharmaceutical Co., Ltd. Benzazepine derivatives
EP3813819A4 (fr) * 2018-06-29 2022-08-17 Kinnate Biopharma Inc. Inhibiteurs de kinases dépendantes des cyclines
EP4253367A4 (fr) * 2020-11-26 2024-10-23 Shanghai Jemincare Pharmaceuticals Co Ltd Nouveau dérivé spiro de benzazépine
WO2022156449A1 (fr) * 2021-01-19 2022-07-28 徐州医科大学 Nouveau composé de benzoazépine, composition et utilisation associées

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CA2116334A1 (fr) 1994-01-20
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AU4356993A (en) 1994-01-31
MX9304015A (es) 1994-02-28
CN1091288A (zh) 1994-08-31
TW249201B (fr) 1995-06-11
AU657424B2 (en) 1995-03-09

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