Novel benzoheterocyclic compounds of the formula: ##STR1## which have excellent vasopressin antagonistic activities and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor, and a vasopressin antagonistic composition containing the compound as the active ingredient.

TECHNICAL FIELD 
This invention relates to novel benzoheterocyclic compounds which have 
excellent vasopressin antagonistic activities and are useful as 
vasodilator, hypotensive agent, water diuretics, platelet aggregation 
inhibitor. 
DISCLOSURE OF THE INVENTION 
The benzoheterocyclic compounds of this invention have the following 
formula: 
##STR2## 
wherein R.sup.1 is hydrogen atom, a halogen atom, a lower alkyl, an amino 
having optionally a lower alkyl substituent, or a lower alkoxy, 
R.sup.2 is hydrogen atom, a halogen atom, a lower alkoxy, a 
phenyl(lower)alkoxy, hydroxy, a lower alkyl, an amino having optionally a 
lower alkyl substituent, a carbamoyl-substituted lower alkoxy, an 
amino-substituted lower alkoxy having optionally a lower alkyl 
substituent, or a benzoyloxy which has optionally a halogen substituent on 
the phenyl ring, 
R.sup.3 is a group of the formula: 
##STR3## 
or a group of the formula: 
##STR4## 
R.sup.4 is hydrogen atom, a benzoyl which has optionally a halogen 
substituent on the phenyl ring, or a lower alkyl, 
R.sup.5 is a group of the formula: 
##STR5## 
wherein R.sup.16 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: 
##STR6## 
(A is a lower alkylene, and R.sup.6 and R.sup.7 are the same or different 
and are each hydrogen atom, a lower alkyl having optionally a hydroxy 
substituent, a lower alkanoyl, or benzoyl, or R.sup.6 and R.sup.7 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 or oxygen atom wherein the heterocyclic group has optionally a 
substituent selected from piperidinyl and a lower alkyl); and m is an 
integer of 0 to 3!, a phenyl-lower alkoxycarbonyl, a lower alkanoyl, a 
phenyl-lower alkanoyl, a cycloalkyl-lower alkanoyl, a cycloalkylcarbonyl, 
tricyclo3.3.1.1!-decanylcarbonyl, naphthylcarbonyl, pyridylcarbonyl, 
furoyl, thenoyl, a phenoxy-lower alkanoyl which phenyl ring has optionally 
1 to 3 substituents selected from a lower alkyl, a lower alkoxy and an 
amino having optionally a lower alkanoyl substituent, a 
phthalimido-substituted lower alkanoyl, a lower alkoxycarbonyl-lower 
alkanoyl, a carboxy-lower alkanoyl, a naphthyloxy-lower alkanoyl, a 
halogen-substituted lower alkanoyl, a group of the formula: 
##STR7## 
(wherein R.sup.8 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: 
##STR8## 
(wherein B is a lower alkylene, n is an integer of 0 or 1, and R.sup.9 
and R.sup.10 are the same or different and are each hydrogen atom, a lower 
alkyl having optionally a hydroxy substituent, a cycloalkyl, a 
phenyl-lower alkyl, a lower alkanoyl, a lower alkenyl, a phenoxy-lower 
alkyl, a phenyl which has optionally 1 to 3 substituents selected from an 
amino-lower alkyl having optionally a lower alkanoyl substituent, a lower 
alkyl, a lower alkoxy and a halogen atom, a phthalimido-substituted lower 
alkyl, an amino-lower alkyl having optionally a lower alkanoyl 
substituent, a lower alkynyl, or an amino-lower alkyl having optionally a 
lower alkyl substituent, or R.sup.9 and R.sup.10 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 or 
oxygen atom wherein the heterocylic group has optionally a substituent 
selected from a lower alkyl, a lower alkoxycarboyl and piperidinyl), 
R.sup.11 is hydrogen atom or a lower alkyl, 
R.sup.12 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.sub.2).sub.p -- (p is an integer of 3 to 
5), or a group of the formula: --CH.dbd.CH--(CH.sub.2).sub.q -- (q is an 
integer of 1 to 3), the carbon atom of these groups: --(CH.sub.2).sub.p -- 
and --CH.dbd.CH--(CH.sub.2).sub.q -- being optionally replaced by oxygen 
atom, sulfur atom, sulfinyl, sulfonyl, or a group of the formula: 
##STR9## 
(R.sup.13 is hydrogen atom, a cycloalkyl, or a lower alkyl), and further 
said --(CH.sub.2).sub.p -- and --CH.dbd.CH--(CH.sub.2).sub.q -- groups 
having optionally 1 to 3 substituents selected from a lower alkyl having 
optionally a hydroxy substituent, a lower alkoxycarbonyl, carboxy, 
hydroxy, oxo, a lower alkanoyloxy having optionally a halogen substituent, 
an amino-lower alkyl having optionally a substituent selected from a lower 
alkyl and a lower alkanoyl, a lower alkanoyloxy-substituted lower alkyl, a 
lower alkyl sulfonyloxy-lower alkyl, an azido-lower alkyl, a group of the 
formula: 
##STR10## 
an aminocarbonyloxy having optionally a lower alkyl substituent, a lower 
alkoxy, a lower alkoxycarbonyl-substituted lower alkoxy, a 
carboxy-substituted lower alkoxy, an aminocarbonyl-lower alkoxy having 
optionally a lower alkyl substituent, an amino-lower alkoxy having 
optionally a substituent selected from a lower alkyl and a lower alkanoyl, 
a phthalimido-substituted lower alkoxy, hydroxyimino, a lower 
alkanoyloxy-imino, a lower alkylidene, a halogen atom, azido, 
sulfoxyimino, a group of the formula: 
##STR11## 
(R.sup.81 is hydrogen atom or a lower alkyl), hydrazino, pyrrolyl, an 
amino-lower alkanoyloxy having optionally a lower alkyl substituent, a 
group of the formula: 
##STR12## 
(A is as defined above, and R.sup.82 and R.sup.83 are the same or 
different and are each hydrogen atom, a lower alkyl, a 
carbamoyl-substituted lower alkyl, a hydroxy-substituted lower alkyl, or a 
pyridyl-lower alkyl, or R.sup.82 and R.sup.83 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), and a 
group of the formula: 
##STR13## 
(wherein n is as defined above, and R.sup.14 and R.sup.15 are the same or 
different and are each hydrogen atom, a lower alkyl, a lower alkenyl, a 
lower alkanoyl, a cycloalkyl, an oxiranyl-substituted lower alkyl, a lower 
alkyl having optionally 1 to 2 substituents selected from a lower alkoxy, 
hydroxy and an amino having optionally a lower alkyl substituent, a 
phenyl-lower alkyl, a pyridyl-lower alkyl, a lower alkylsulfonyl, benzoyl, 
a lower alkoxycarbonyl, anilinocarbonyl, an aminocarbonyl having 
optionally a lower alkyl substituent, a cyano-substituted lower alkyl, a 
lower alkoxycarbonyl-substituted lower alkyl, a carbamoyl-substituted 
lower alkyl, a carboxy-substituted lower alkyl, a 
tetrahydropyranyloxy-substituted lower alkyl, a lower 
alkanoyloxy-substituted lower alkyl, a piperidinyl having optionally a 
phenyl-lower alkyl substituent on the piperidinyl ring, a 
halogen-substituted lower alkanoyl, an imidazolyl-substituted lower 
alkanoyl, an amino-lower alkanoyl having optionally a substituent selected 
from a lower alkyl and a lower alkoxycarbonyl, an aminocarbonyl-lower 
alkyl having optionally a lower alkyl substituent, or a phenyl-lower 
alkoxycarbonyl, or R.sup.14 and R.sup.15 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 or oxygen, wherein 
the heterocyclic group may optionally have a substituent selected from a 
lower alkyl, a phenyl-lower alkyl or a lower alkanoyl). 
The benzoheterocyclic compounds of the formula (1) and their salts have 
excellent vasopressin antagonistic activities and vasodilating activity, 
hypotensive activity, activity for inhibiting saccharide release in liver, 
activity for inhibiting growth of mesangium cells, water diuretic 
activity, platelet agglutination inhibitory activity and are useful as 
vasodilator, hypotensive agent, water diuretics, platelet agglutination 
inhibitor and are used for the prophylaxis and treatment of hypertension, 
edema, ascites, heart failure, renal function disorder, vasopressin 
parasecretion syndrome (SIADH), hepatocirrhosis, hyponatremia, 
hypokaliemia, diabetic, circulation disorder, and the like. 
Each group in the above formula (1) includes specifically the following 
groups. 
The "lower alkoxy" includes a straight chain or branched chain alkoxy group 
having 1 to 6 carbon atoms, for example, methoxy, ethoxy, propoxy, 
isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, and the like. 
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, tert-butyl, pentyl, hexyl, and the like. 
The "halogen atom" includes fluorine atom, chlorine atom, bromine atom and 
iodine atome. 
The "amino having optionally a lower alkyl substituent" 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, 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, and the like. 
The "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. 
The "lower alkyl which has optionally a substituent selected from a halogen 
atom and hydroxy" includes a straight chain or branched chain alkyl group 
having 1 to 6 carbon atoms which may optionally have 1 to 3 substituents 
selected from a halogen atom and hydroxy, for example, in addition to the 
above-mentioned lower alkyl groups, 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, 
trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, 
iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 
2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 
2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 
3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dichlorohexyl, 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 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. 
The "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 "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. 
The "lower alkoxycarbonyl" includes a straight chain or branched chain 
alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for 
example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, 
isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, 
pentyloxycarbonyl, hexyloxycarbonyl, and the like. 
The "amino having optionally a substituent selected from a lower alkyl and 
a lower alkanoyl" includes an amino having optionally one or two 
substituents selected 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, 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-N-acetylamino, N-acetylamino, N-formylamino, N-propionylamino, 
N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, 
N-tert-butylcarbonylamino, N-hexanoylamino, N-ethyl-N-acetylamino, and the 
like. 
The "cycloalkyl" includes a cycloalkyl having 3 to 8 carbon atoms, for 
example, cyclopentyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 
cyclooctyl, and the like. 
The "lower alkanoyloxy-substituted lower alkoxy" includes a straight chain 
or branched chain alkoxy group having 1 to 6 carbon atoms which is 
substituted by a straight chain or branched chain alkanoyloxy group having 
2 to 6 carbon atoms, for example, acetyloxymethoxy, 2-propionyloxyethoxy, 
1-butyryloxyethoxy, 3-acetyloxypropoxy, 4-acetyloxybutoxy, 
4-isobutyryloxybutoxy, 5-pentanoyloxypentyloxy, 6-acetyloxyhexyloxy, 
6-tert-butylcarbonyloxyhexyloxy, 1,1-dimethyl-2-hexanoyloxyethoxy, 
2-methyl-3-acetyloxypropoxy, and the like. 
The "carbamoyl-substituted lower alkoxy" includes a carbamoyl-substituted 
alkoxy group wherein the alkoxy moiety is a 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-methyl-3-hydroxypropoxy, 2,3,4-trihydroxybutoxy, and 
the like. 
The "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-butoxycarbonylethoxy, 
2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, 
hexyloxycarbonylmethoxy, and the like. 
The "carboxy-substituted lower alkoxy" includes a carboxy-substituted 
alkoxy group wherein the alkoxy moiety is a 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. 
The "phthalimido-substituted lower alkoxy" includes a straight chain or 
branched chain alkoxy group having 1 to 6 carbon atoms which is 
substituted by phthalimido group, for example, phthalimidomethoxy, 
2-phthalimidoethoxy, 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.sup.6 and R.sup.7 together with the nitrogen atom to 
which they bond with or without being intervened with nitrogen or oxygen 
atom" includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, 
morpholino, and the like. 
The "heterocyclic group having a substituent selected from piperidinyl and 
a lower alkyl" includes a heterocyclic group 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-methylpiperiazinyl, 
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. 
The "phenyl(lower)alkanoyl" includes a phenylalkanoyl wherein the alkanoyl 
moiety is a straight chain or branched chain alkanoyl group having 2 to 6 
carbon atoms, for example, phenylacetyl, 3-phenylpropionyl, 
2-phenylpropionyl, 4-phenylbutyryl, 2,2-dimethyl-3-phenylpropionyl, 
5-phenylpentanoyl, 6-phenylhexanoyl, and the like. 
The "cycloalkyl-lower alkanoyl" includes C.sub.3 -C.sub.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. 
The "cycloalkylcarbonyl" includes a cycloalkylcarbonyl having 3 to 8 carbon 
atoms, for example, cyclopropylcarbonyl, cyclobutylcarbonyl, 
cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, 
cyclooctylcarbonyl, and the like. 
The "amino having optionally a lower alkanoyl substituent" includes an 
amino having optionally 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. 
The "phenoxy-lower alkanoyl which phenyl ring has optionally 1 to 3 
substituents selected from a lower alkyl, a lower alkoxy and an amino 
having optionally a lower alkanoyl substituent" includes a phenoxyalkanoyl 
group wherein the alkanoyl moiety is a straight chain or branched chain 
alkanoyl having 2 to 6 carbon atoms and the phenyl ring has optionally 1 
to 3 substituents selected from a straight chain or branched chain alkyl 
having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy 
having 1 to 6 carbon atoms and an amino having optionally a straight chain 
or branched chain alkanoyl having 1 to 6 carbon atoms, for example, 
phenoxyacetyl, 3-phenoxypropionyl, 2-phenoxypropionyl, 4-phenoxybutyryl, 
2,2-dimethyl-3-phenoxypropionyl, 5-phenoxypentanoyl, 6-phenoxyhexanoyl, 
(2-aminophenoxy)acetyl, 3-(4-aminophenoxy)propionyl, 
(2-methylphenoxy)acetyl, (4-methylphenoxy)acetyl, (3-methylphenoxy)acetyl, 
(3-methoxyphenoxy)acetyl, (3-acetylaminophenoxy)acetyl, 
4-(2-propionylaminophenoxy)butyryl, 
2,2-dimethyl-3-(4-butyrylaminophenoxy)propionyl, 
5-(2-pentanoylaminophenoxy)pentanoyl, 6-(4-hexanoylaminophenoxy)hexanoyl, 
3-(2-ethylphenoxy)propionyl, 2-(4-propylphenoxy)propionyl, 
4-(4-butylphenoxy)butyryl, 5-(3-pentylphenoxy)pentanoyl, 
6-(4-hexylphenoxy)hexanoyl, (2,3-dimethylphenoxy)acetyl, 
(2,5-dimethylphenoxy)acetyl, (3,4-dimethylphenoxy)acetyl, 
(3,4,5-trimethylphenoxy)acetyl, 3-(4-ethoxyphenoxy)propionyl, 
2-(2-propoxyphenoxy)propionyl, 4-(3-butoxyphenoxy)butyryl, 
5-(4-pentyloxyphenoxy)pentanoyl, 6-(4-hexyloxyphenoxy)hexanoyl, 
(3,4-dimethoxyphenoxy)acetyl, (3,5-dimethoxyphenoxy)acetyl, 
(2,4-dimethoxyphenoxy)acetyl, (3,4,5-trimethoxyphenoxy)acetyl, 
(2-acetylamino-4-methylphenoxy)acetyl, 
(4-acetylamino-3-methoxyphenoxy)acetyl, and the like. 
The "phthalimido-substituted lower alkanoyl" includes a straight chain or 
branched chain alkanoyl group having 2 to 6 carbon atoms which is 
substituted by phthalimido group, for example, 2-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, 
hexyloxycarbonylacetyl, and the like. 
The "carboxy-lower alkanoyl" includes a carboxyalkanoyl group wherein the 
alkanoyl moiety is a straight chain or branched chain alkanoyl having 2 to 
6 carbon atoms, for example, carboxyacetyl, 3-carboxypropionyl, 
2-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. 
The "lower alkyl having optionally a hydroxy substituent" includes a 
straight chain or branched chain alkyl having 1 to 6 carbon atoms and 
having optionally 1 to 3 hydroxy substituents, for example, hydroxymethyl, 
2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxyethyl, 
4-hydroxybutyl, 3,4-dihydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 
5-hydroxypentyl, 6-hydroxyhexyl, 2-methyl-3-hydroxypropyl, 
2,3,4-trihydroxybutyl, and the like. 
The "phenyl-lower alkyl" includes a phenylalkyl group wherein the alkyl 
moiety is a straight chain or branched chain alkyl group having 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. 
The "phenoxy-lower alkyl" includes a phenoxyalkyl group wherein the alkyl 
moiety is a straight chain or branched chain alkyl group having 1 to 6 
carbon atoms, for example, phenoxymethyl, 1-phenoxyethyl, 2-phenoxyethyl, 
3-phenoxypropyl, 4-phenoxybutyl, 5-phenoxypentyl, 6-phenoxyhexyl, 
1,1-dimethyl-2-phenoxyethyl, 2-methyl-3-phenoxypropyl, and the like. 
The "phenyl which has optionally 1 to 3 substituents selected from a lower 
alkyl, a lower alkoxy and a halogen atom" includes a phenyl group which 
has optionally 1 to 3 substituents selected from a straight chain or 
branched chain alkyl group having 1 to 6 carbon atoms, a 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, 
3,5-dimethoxyphenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl, 
2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 
3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 
4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 
3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 
2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-difluorophenyl, 
3,5-dibromophenyl, 3,4,5-trichlorophenyl, 2-methoxy-3-chlorophenyl, 
2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 
3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 
4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 
2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 
3,4,5-trimethylphenyl, 3-chloro-4-methylphenyl, 
3-methoxy-4-methyl-5-iodophenyl, 3,4-dimethoxy-5-bromophenyl, 
3,5-diiodo-4-methoxyphenyl, and the like. 
The "amino-lower alkyl having optionally a lower alkyl substituent" 
includes a straight chain or branched chain alkyl group having 1 to 6 
carbon atoms which is substituted by an amino group having optionally 1 to 
2 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-ethyl-N-propylamino)methyl, 
2-(N-methyl-N-hexylamino)ethyl, and the like. 
The "5- or 6-membered saturated heterocyclic group which is formed by 
binding the groups R.sup.9 and R.sup.10 together with the nitrogen atom to 
which they bond with or without being intervened with nitrogen or oxygen 
atom" includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, 
morpholino, and the like. 
The "heterocyclic group having a substituent selected from a lower alkyl, a 
lower alkoxycarbonyl and piperidinyl" includes a heterocyclic group 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 
of a lower alkyl and piperidinyl, 4-methoxycarbonylpiperazinyl, 
4-ethoxycarbonylpiperidinyl, 3-propoxycarbonylpyrrolidinyl, 
2-pentyloxycarbonylmorpholino, 4-hexyloxycarbonylpiperidinyl, 
4-ethoxycarbonyl-3-methylpiperidinyl, 
3-methyl-4-ethoxycarbonylpiperazinyl, and the like. 
The "5- or 6-membered saturated heterocyclic group which is formed by 
binding the groups R.sup.14 and R.sup.15 together with the nitrogen atom 
to which they bond with or without being intervened with nitrogen or 
oxygen atom" includes, for example, pyrrolidinyl, piperidinyl, 
piperazinyl, morpholino, and the like. 
The "heterocyclic group having a lower alkyl substituent" includes a 
heterocyclic group 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, 3-ethylpyrrolidinyl, 
2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 
3-pentylmorpholino, 4-hexylpiperazinyl, and the like. 
The heterocyclic ring in the formula (1) 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. 
The heterocyclic ring in the formula (1) wherein the carbon atom in the 
group of the formula: --(CH.sub.2).sub.p -- or 
--CH.dbd.CH--(CH.sub.2).sub.q -- for W is replaced by oxygen atom, sulfur 
atom, sulfinyl, sulfonyl, or a group of the formula: 
##STR14## 
(R.sup.13 is hydrogen atom or a lower alkyl) includes a heterocylic group 
wherein the carbon atom in the group of the formula: --(CH.sub.2).sub.p -- 
or --CH.dbd.CH--(CH.sub.2).sub.q -- for W is replaced by oxygen atom, 
sulfur atom, sulfinyl, sulfonyl, or a group of the formula: 
##STR15## 
(R.sup.13 is hydrogen atom or a straight chain or branched chain alkyl 
having 1 to 6 carbon atoms), for example, 3,4-dihydro-2H-1,4-benzoxazinyl, 
1,2,3,5-tetrahydro-4,1-benzoxazepinyl, 1,2,3,4-tetrahydroquinoxalinyl, 
1,2,3,4,5,6-hexahydro-1,5-benzodiazocinyl, 
5-methyl-1,2,3,4,5,6-hexahydro-1,5-benzodiazocinyl, 
4-methyl-1,2,3,4-tetrahydroquinoxalinyl, 
1,2,3,4-tetrahydro-5,1-benzoxazepinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 
2,3,4,5-tetrahydro-1,5-benzothiazepinyl, 
1,2,3,5-tetrahydro-4,1-benzothiazepinyl, 
4-ethyl-1,2,3,4-tetrahydroquinoxalinyl, 
4-propyl-1,2,3,4-tetrahydroquinoxalinyl, 
4-butyl-1,2,3,4-tetrahydroquinoxalinyl, 
4-pentyl-1,2,3,4-tetrahydroquinoxalinyl, 
4-hexyl-1,2,3,4-tetrahydroquinoxalinyl, 
2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 
4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 
4-ethyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 
4-propyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 
4-butyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 
4-pentyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 
4-hexyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 
2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 
5-methyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 
5-ethyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 
5-propyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 
5-butyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 
5-pentyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 
5-hexyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 
3,4-dihydro-1-oxo-2H-1,4-benzothiazepinyl, 
3,4-dihydro-1,1-dioxo-2H-1,4-benzothiazepinyl, 
1-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepinyl, 
1,1-dioxo-2,3,4,5-tetrahydro-1,5-benzothiazepinyl, 
4-oxo-1,2,3,5-tetrahydro-4,1-benzothiazepinyl, 
4,4-dioxo-1,2,3,5-tetrahydro-4,1-benzothiazepinyl, and the like. 
The "halogen-substituted lower alkoxy" includes a straight chain or 
branched chain alkoxy group having 1 to 6 carbon atoms which has 1 to 3 
substituents of a halogen atom, 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. 
The "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-dibromohexanoyl, and the like. 
The "aminocarbonyl-lower alkoxy having a lower alkyl substituent" includes 
a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms 
which is substituted by an aminocarbonyl group having 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-isopropylaminocarbonylpropoxy, 4-butylaminocarbonylbutoxy, 
5-pentylaminocarbonylpentyloxy, 6-hexylaminocarbonylhexyloxy, 
dimethylaminocarbonylmethoxy, 3-diethylaminocarbonylpropoxy, 
diethylaminocarbonylmethoxy, (N-ethyl-N-propylamino)carbonylmethoxy, 
2-(N-methyl-N-hexylamino)carbonylethoxy, and the like. 
The "carbamoyl-lower alkyl" includes a carbamoyl-substituted alkyl group 
wherein the alkyl moiety is 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-carbamoylpropyl, and the like. 
The "amino-lower alkanoyl having optionally a lower alkyl substituent" 
includes a straight chain or branched chain alkanoyl having 2 to 6 carbon 
atoms which is substituted by an amino group having optionally 1 to 2 
substituents of a straight chain or branched chain alkyl group having 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-(N-methyl-N-hexylamino)propionyl, and 
the like. 
The "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-aminopropyl, acetylaminomethyl, 
1-acetylaminoethyl, 2-propionylaminoethyl, 3-isopropionylaminopropyl, 
4-butyrylaminobutyl, 5-pentanoylaminopentyl, 6-hexanoylaminohexyl, 
formylaminomethyl, and the like. 
The "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, and the like. 
The "phenylsulfonyl which has optionally a substituent selected from a 
halogen and a lower alkyl on the phenyl ring" includes a phenylsulfonyl 
group which has optionally 1 to 3 substitutents selected from a straight 
chain or branched chain alkyl group having 1 to 6 carbon atoms and a 
halogen atom, for example, phenylsulfonyl, 2-chlorophenylsulfonyl, 
3-chlorophenylsulfonyl, 4-chlorophenylsulfonyl, 2-fluorophenylsulfonyl, 
3-fluorophenylsulfonyl, 4-fluorophenylsulfonyl, 2-bromophenylsulfonyl, 
3-bromophenylsulfonyl, 4-bromophenylsulfonyl, 2-iodophenylsulfonyl, 
3-iodophenylsulfonyl, 4-iodophenylsulfonyl, 3,4-dichlorophenylsulfonyl, 
3,5-dichlorophenylsulfonyl, 2,6-dichlorophenylsulfonyl, 
2,3-dichlorophenylsulfonyl, 2,4-dichlorophenylsulfonyl, 
3,4-difluorophenylsulfonyl, 3,5-dibromophenylsulfonyl, 
3,4,5-trichlorophenylsulfonyl, 2-ethyl-3-chlorophenylsulfonyl, 
2-methylphenylsulfonyl, 3-methylphenylsulfonyl, 4-methylphenylsulfonyl, 
2-ethylphenylsulfonyl, 3-ethylphenylsulfonyl, 4-ethylphenylsulfonyl, 
4-isopropylphenylsulfonyl, 3-butylphenylsulfonyl, 4-pentylphenylsulfonyl, 
4-hexylphenylsulfonyl, 3,4-dimethylphenylsulfonyl, 
3,4-diethylphenylsulfonyl, 2,4-dimethylphenylsulfonyl, 
2,5-dimethylphenylsulfonyl, 2,6-dimethylphenylsulfonyl, 
3,4,6-trimethylphenylsulfonyl, 3,4,5-trimethylphenylsulfonyl, 
3-chloro-4-methylphenylsulfonyl, 4-methyl-5-iodophenylsulfonyl, 
3,4-dimethyl-5-bromophenylsulfonyl, 3,5-diiodo-4-methylphenylsulfonyl, and 
the like. 
The "phthalimido-substituted lower alkyl" includes a straight chain or 
branched chain alkyl group having 1 to 6 carbon atoms which is substituted 
by phthalimido group, 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 chain or branched chain alkynyl 
having 2 to 6 carbon atoms, for example, ethynyl, 2-propynyl, 2-butynyl, 
3-butynyl, 1-methyl-2-propynyl, 2-pentynyl, 2-hexynyl, and the like. 
The "benzoyl which has optionally a 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, 3,5-dibromobenzoyl, 
3,4,5-trichlorobenzoyl, and the like. 
The "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. 
The "amino-lower alkoxy having optionally a substituent selected from a 
lower alkyl and a lower alkanoyl" include a straight chain or branched 
chain alkoxy group having 1 to 6 carbon atoms which is substituted by an 
amino group having optionally 1 to 2 substituents selected from a straight 
chain or branched chain alkyl group 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-propionylaminoethoxy, 3-isopropionylaminopropoxy, 
4-butyrylaminobutoxy, 5-pentanoylaminopentyloxy, 6-hexanoylaminohexyloxy, 
formylaminomethoxy, methylaminomethoxy, 1-ethylaminoethoxy, 
2-propylaminoethoxy, 3-isopropylaminopropoxy, 4-butylaminobutoxy, 
5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, 
(N-ethyl-N-propylamino)methoxy, 2-(N-methyl-N-hexylamino)ethoxy, and the 
like. 
The "benzoyloxy which has optionally a halogen substituent on the phenyl 
ring" includes a benzoyloxy group which has optionally 1 to 3 substituents 
of a halogen atom on the phenyl ring, for example, benzoyloxy, 
2-chlorobenzoyloxy, 3-chlorobenzoyloxy, 4-chlorobenzoyloxy, 
2-fluorobenzoyloxy, 3-fluorobenzoyloxy, 4-fluorobenzoyloxy, 
2-bromobenzoyloxy, 3-bromobenzoyloxy, 4-bromobenzoyloxy, 2-iodobenzoyloxy, 
3-iodobenzoyloxy, 4-iodobenzoyloxy, 3,4-dichlorobenzoyloxy, 
3,5-dichlorobenzoyloxy, 2,6-dichlorobenzoyloxy, 2,3-dichlorobenzoyloxy, 
2,4-dichlorobenzoyloxy, 3,4-difluorobenzoyloxy, 3,5-dibromobenzoyloxy, 
3,4,5-trichlorobenzoyloxy, and the like. 
The "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, 6-acetyloxyhexyl, 
6-tert-butylcarbonyloxyhexyl, 1,1-dimethyl-2-hexanoyloxyethyl, 
2-methyl-3-acetyloxypropyl, and the like. 
The "lower alkylsulfonyloxy-lower alkyl" includes a straight chain or 
branched chain alkyl group having 1 to 6 carbon atoms which is substituted 
by a straight chain or branched chain alkylsulfonyloxy group having 1 to 6 
carbon atoms, for example, methylsulfonyloxymethyl, 
1-ethylsulfonyloxyethyl, 2-propylsulfonyloxyethyl, 
3-isopropylsulfonyloxypropyl, 4-butylsulfonyloxybutyl, 
5-pentylsulfoyloxypentyl, 6-hexylsulfonyloxyhexyl, 
1,1-dimethyl-2-methylsulfoyloxyethyl, 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. 
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. 
The "lower alkylidene" includes a straight chain or branched chain 
alkylidene group having 1 to 6 carbon atoms, for example, methylidene, 
ethylidene, propylidene, isopropylidene, butylidene, pentylidene, 
hexylidene, and the like. 
The "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. 
The "lower alkyl having 1 to 2 substituents selected from a lower alkoxy, 
hydroxy and an amino having optionally a lower alkyl substituent" includes 
a straight chain or branched chain alkyl group having 1 to 6 carbon atoms 
and having 1 to 2 substituents selected from a straight chain or branched 
chain alkoxy group having 1 to 6 carbon atoms, hydroxy and an amino having 
optionally a straight chain or branched chain alkyl group having 1 to 6 
carbon atoms, for example, methoxymethyl, 1-ethoxyethyl, 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-dihydroxyethyl, 4-hydroxybutyl, 3,4-dihydroxybutyl, 
1,1-dimethyl-2-hydroxyethyl, 5,6-dihydroxyhexyl, 5-hydroxypentyl, 
6-hydroxyhexyl, 6-(N-ethyl-N-methylamino)-5-methoxyhexyl, 
2-methyl-3-hydroxypropyl, aminomethyl, 1-aminoethyl, 2-aminoethyl, 
3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 
1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 
ethylaminomethy, propylaminomethyl, isopropylaminomethyl, 
butylaminomethyl, tert-butylaminomethyl, pentylaminomethyl, 
hexylaminomethyl, dimethylaminomethyl, diethylaminomethyl, 
dipropylaminomethyl, dibutylaminomethyl, dipentylaminomethyl, 
dihexylaminomethyl, N-methyl-N-ethylaminomethyl, 
N-methyl-N-propylaminomethyl, N-methyl-N-butylaminomethyl, 
N-methyl-N-hexylaminomethyl, 1-methylaminoethyl, 2-ethylaminoethyl, 
3-propylaminopropyl, 4-butylaminobutyl, 1,1-dimethyl-2-pentylaminoethyl, 
5-hexylaminopentyl, 6-dimethylaminohexyl, 4-dimethylaminobutyl, 
2-diethylaminoethyl, 1-(N-methyl-N-hexylamino)ethyl, 3-dihexylaminopropyl, 
6-diethylaminohexyl, 4-dibutylaminobutyl, 2-(N-methyl-N-pentylamino)ethyl, 
2-hydroxy-3-diethylaminopropyl, 3-hydroxy-4-methylaminobutyl, 
5-hydroxy-6-diethylaminohexyl, 4-hydroxy-5-dimethylaminopentyl, 
4-hydroxy-5-methylaminopentyl, 4-hydroxy-5-diethylaminopentyl, 
5-hydroxy-6-ethylaminohexyl, 5-hydroxy-6-isopropylaminohexyl, 
5-hydroxy-6-aminohexyl, and the like. 
The "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, 
butylaminocarbonyloxy, 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 
example, in addition to the above lower alkanoyl group, 
2,2,2-trifluoroacetyloxy, 2,2,2-trichloroacetyloxy, 2-chloroacetyloxy, 
2-bromoacetyloxy, 2-fluoroacetyloxy, 2-iodoacetyloxy, 
2,2-difluoroacetyloxy, 2,2-dibromoacetyloxy, 3,3,3-trifluoropropionyloxy, 
3,3,3-trichloropropionyloxy, 3-chloropropionyloxy, 
2,3-dichloropropionyloxy, 4,4,4-trichlorobutyryloxy, 4-fluorobutyryloxy, 
5-chloropentanoyloxy, 3-chloro-2-methylpropionyloxy, 6-bromohexanoyloxy, 
5,6-dibromohexanoyloxy, and the like. 
The "amino-lower alkyl having optionally a substituent selected from a 
lower alkyl and a lower alkanoyl" include 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-hexanoylaminohexyl, 
formylaminomethyl, methylaminomethyl, 1-ethylaminoethyl, 
2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 
5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 
(N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl, and the 
like. 
The "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, 4-aminobutyryloxy, 5-aminopentanoyloxy, 
6-aminohexanoyloxy, 2,2-dimethyl-3-aminopropionyloxy, 
2-methyl-3-aminopropionyloxy, 2-methylaminoacetyloxy, 
2-ethylaminopropionyloxy, 3-propylaminopropionyloxy, 
3-isopropylaminopropionyloxy, 4-butylaminobutyryloxy, 
5-pentylaminopentanoyloxy, 6-hexylaminohexanoyloxy, 
2-dimethylaminoacetyloxy, 2-diethylaminoacetyloxy, 
2-(N-ethyl-N-propylamino)acetyloxy, 3-(N-methyl-N-hexylamino)propionyloxy, 
and the like. 
The "pyridyl-lower alkyl" 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, (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.sup.82 and R.sup.83 together with the nitrogen atom 
to which they bond with or without being intervened with nitrogen, oxygen 
or sulfur atom" includes, for example, pyrrolidinyl, piperidinyl, 
piperazinyl, morpholino, thiomorpholino, and the like. 
The above heterocyclic group which has a 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-propionylmorpholino, 3-butyrylthiomorpholino, 3-pentanoylpyrrolidinyl, 
4-hexanoylpiperidinyl, 3-methyl-4-acetylpiperazinyl, 
2-carbamoylpyrrolidinyl, 4-carbamoylpiperazinyl, 
3-carbamoylthiomorpholino, 2-carbamoylmorpholino, 3-carbamoylpiperidinyl, 
1-oxo-thiomorpholino, 1,1-dioxothiomorpholino, and the like. 
The "lower alkylsulfonyl" includes a straight chain or branched chain 
alkylsulfonyl group having 1 to 6 carbon atoms, for example, 
methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, 
butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl, and the 
like. 
The "aminocarbonyl having optionally a lower alkyl substituent" includes an 
aminocarbonyl group having optionally 1 to 2 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-hexylaminocarbonyl, 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-caynoethyl, 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-tetrahydropyranyloxy)methyl, 2-(3-tetrahydropyranyloxy)ethyl, 
1-(4-tetrahydropyranyloxy)ethyl, 3-(2-tetrahydropyranyloxy)propyl, 
4-(3-tetrahydropyranyloxy)butyl, 5-(4-tetrahydropyranyloxy)pentyl, 
6-(2-tetrahydropyranyloxy)hexyl, 
1,1-dimethyl-2-(3-tetrahydropyranyloxy)ethyl, 
2-methyl-3-(4-tetrahydropyranyloxy)propyl, and the like. 
The "piperidinyl having optionally a phenyl-lower alkyl substituent" 
includes a piperidinyl which has optionally a substituent of a phenylalkyl 
group wherein the alkyl moiety is a straight chain or branched chain alkyl 
group having 1 to 6 carbon 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. 
The "amino-lower alkanoyl having optionally a substituent selected from a 
lower alkyl and a lower alkoxycarbonyl" includes a straight chain or 
branched chain alkanoyl having 2 to 6 carbon atoms which is substituted by 
an amino group having optionally 1 to 2 substituents selected from a 
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-propylamino)acetyl, 3-(N-methyl-N-hexylamino)propionyl, 
2-methoxycarbonylaminoacetyl, 2-ethoxycarbonylaminoacetyl, 
3-propoxycarbonylaminopropionyl, 4-butoxycarbonylaminobutyryl, 
2-tert-butoxycarbonylaminoacetyl, 5-pentyloxycarbonylaminopentanoyl, 
6-hexyloxycarbonylaminohexanoyl, 
2-(N-methyl-N-tert-butoxycarbonylamino)acetyl, and the like. 
The "aminocarbonyl-lower alkyl having a lower alkyl substituent" includes a 
straight chain or branched chain alkyl group having 1 to 6 carbon atoms 
which is substituted by an aminocarbonyl group having 1 to 2 substituents 
of a straight chain or branched chain alkyl group having 1 to 6 carbon 
atoms, for example, methylaminocarbonylmethyl, 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)carbonylethyl, and the like. 
The "amino-substituted lower alkoxy having optionally a lower alkyl 
substituent" includes an amino-substituted straight chain or branched 
chain alkoxy having 1 to 6 carbon atoms which has optionally 1 to 2 
substituents of a straight chain or branched chain alkyl having 1 to 6 
carbon atoms, such as 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-ethyl-N-propylamino)methoxy, 
2-(N-methyl-N-hexylamino)ethoxy, and the like. 
The compounds of the present invention can be prepared by various 
processes, for example, by the processes shown in the following reaction 
schemes. 
##STR16## 
wherein R.sup.1, R.sup.2, R.sup.3, and W are the same as defined above. 
The process of Reaction Scheme-1 is carried out by reacting a 
benzoheterocyclic compound of the formula (2) and a carboxylic acid 
compound of the formula (3) by a conventional amido bond forming reaction. 
The amido bond forming reaction can be carried out under the conditions 
for the conventional amido bond forming reaction, for example, 
(a) a mixed acid anhydride process, i.e. a process of reacting the 
carboxylic acid compound (3) with an alkylhalocarboxylic acid to form a 
mixed acid anhydride and reacting the resultant with the amine compound 
(2), 
(b) an activated ester process, i.e. a process of converting the carboxylic 
acid compound (3) into an activated ester, such as p-nitrophenyl ester, 
N-hydroxysuccinimide ester, 1-hydroxybenzotriazole ester, etc., and 
reacting the resultant with the amine compound (2), 
(c) a carbodiimide process, i.e. a process of condensing the carboxylic 
acid compound (3) and the amine compound (2) in the presence of an 
activating agent such as dicyclohexylcarbodiimide, carbonyldiimidazole, 
etc., 
(d) other processes, i.e. a process of converting the carboxylic acid 
compound (3) into a carboxylic anhydride by treatment with a dehydrating 
agent such as acetic anhydride, and reacting the resultant with the amine 
compound (2); a process of reacting an ester of the carboxylic acid 
compound (3) with a lower alcohol and the amine compound (2) at a high 
temperature under high pressure; a process of reacting an acid halide 
compound of the carboxylic acid compound (3), i.e. a carboxylic acid 
halide, with the amine compound (2), and the like. 
The mixed acid anhydride used in the above mixed acid anhydride process (a) 
is obtained by the known Schotten-Baumann reaction, and the reaction 
product is used without isolation from the reaction mixture for the 
reaction with the amine compound (2) to give the desired compound of the 
formula (1). The Schotten-Baumann reaction is usually carried out in the 
presence of a basic compound. The basic compound is any conventional 
compounds used for the Schotten-Baumann reaction and includes, for 
example, organic basic compounds such as triethylamine, trimethylamine, 
pyridine, dimethylaniline, N-methylmorpholine, 
1,5-diazabicyclo4.3.0!nonene-5 (DBN), 1,8-diazabicyclo5.4.0!undecene-7 
(DBU), 1,4-diazabicyclo2.2.2!octane (DABCO), etc., and inorganic basic 
compounds such as potassium carbonate, sodium carbonate, potassium 
hydrogen carbonate, sodium hydrogen carbonate, etc. The reaction is 
usually carried out at a temperature of from about -20.degree. C. to about 
100.degree. C., preferably from about 0.degree. C. to about 50.degree. C., 
for about 5 minutes to about 10 hours, preferably about 5 minutes to about 
2 hours. 
The reaction of the thus obtained mixed acid anhydride with the amine 
compound (2) is usually carried out at a temperature of from about 
-20.degree. C. to about 150.degree. C., preferably about 10.degree. C. to 
about 50.degree. C., for about 5 minutes to about 10 hours, preferably 
about 5 minutes to about 5 hours. The mixed acid anhydride process is 
usually carried out in an appropriate solvent. The solvent is any 
conventional solvents which are usually used in the mixed acid anhydride 
process and includes, for example, halogenated hydrocarbons (e.g. 
chloroform, dichloromethane dichloroethane, etc.), aromatic hydrocarbons 
(e.g. benzene, toluene, xylene, etc.), ethers (e.g. diethyl ether, 
diisopropyl ether, tetrahydrofuran, dimethoxyethane, etc.), esters (e.g. 
methyl acetate, ethyl acetate, etc.), aprotic polar solvents (e.g. 
N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, 
etc.), or a mixture of these solvents. The alkylhalocarboxylic acid used 
in the mixed acid anhydride process includes, for example, methyl 
chloroformate, methyl bromoformate, ethyl chloroformate, ethyl 
bromoformate, isobutyl chloroformate, and the like. In said process, the 
carboxylic acid compound (3), the alkylhalocarboxylic acid and the amine 
(2) are usually used in each equimolar amount, but preferably, the 
alkylhalocarboxylic acid and the carboxylic acid compound (3) are used 
each in an amount of about 1 to 1.5 mole to 1 mole of the amine (2). 
Among the above other processes (d), in case of the process of reacting the 
carboxylic acid halide with the amine compound (2), the reaction is 
usually carried out in the presence of a basic compound in an appropriate 
solvent. The basic compound is any conventional compounds and includes, in 
addition to the basic compounds used for the above-mentioned 
Schotten-Baumann reaction, sodium hydroxide, potassium hydroxide, sodium 
hydride, potassium hydride. etc. The solvent includes, in addition to the 
solvents used for the above-mentioned mixed acid anhydride process, 
alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, 
ethylcellosolve, methylcellosolve, etc.), acetonitrile, pyridine, acetone, 
water, and the like. The amount of the amine compound (2) and the 
carboxylic acid halide is not critical, but the carboxylic acid halide is 
usually used at least in equimolar amount, preferably about 1 to 5 moles 
to 1 mole of the amine compound (2). The reaction is usually carried out 
at a temperature of from about -20.degree. C. to about 180.degree. C., 
preferably from about 0.degree. C. to about 150.degree. C., for about 5 
minutes to about 30 hours. 
The amido bond forming reaction in the above Reaction Scheme-1 may also be 
carried out by reacting the carboxylic acid compound (3) and the amine (2) 
in the presence of a condensation agent, i.e. phosphoric compounds such as 
triphenylphosphine, diphenylphosphinyl chloride, 
phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate, diethyl 
phosphorocyanidate, diphenylphosphoric azide, 
bis(2-oxo-3-oxazolidinyl)phosphinic chloride, etc. The reaction is usually 
carried out in the presence of the solvent and basic compound as used in 
the above reaction of the carboxylic acid halide and the amine (2) at a 
temperature of from about -20.degree. C. to about 150.degree. C., 
preferably about 0.degree. C. to about 100.degree. C., for about 5 minutes 
to about 30 hours. The condensation agent and the carboxylic acid compound 
(3) are used at least in equimolar amount, preferably about 1 to 2 moles, 
to 1 mole of the amine (2). 
##STR17## 
wherein R.sup.1, R.sup.2, R.sup.4 and W are as defined above, R.sup.5a is 
the same as R.sup.5 as defined above except excluding an anilinocarbonyl 
having optionally a lower alkyl substituent on the phenyl ring, a 
phenylsulfonyl having optionally a substituent selected from a halogen 
atom and a lower alkyl on the phenyl ring and quinolylsulfonyl. 
The reaction of the compound (2b) and the compound (4) is carried out in 
the same manner as in the reaction of the compound (2) and the compound 
(3) in the above Reaction Scheme-1. 
##STR18## 
wherein R.sup.1, R.sup.2, R.sup.11, R.sup.12 and W are as defined above. 
The reaction of the compound (5) and the compound (6) is carried out under 
the same conditions as used in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
##STR19## 
wherein R.sup.1, R.sup.2, R.sup.5 and W are as defined above, and R.sup.4a 
is a lower alkyl, R.sup.17 and R.sup.18 are each hydrogen atom or a lower 
alkyl, and X is a halogen atom. 
The reaction of the compound (7) and the compound (8) is usually carried 
out in an inert solvent in the presence or absence of a basic compound. 
The inert solvent includes, for example, aromatic hydrocarbons (e.g. 
benzene, toluene, xylene, etc.), ethers (e.g. tetrahydrofuran, dioxane, 
diethylene glycol dimethyl ether, etc.), halogenated hydrocarbons (e.g. 
dichloromethane, chloroform, carbon tetrachloride, etc.), lower alcohols 
(e.g. methanol, ethanol, isopropanol, butanol, tert-butanol, etc.), acetic 
acid, ethyl acetate, acetone, acetonitrile, pyridine, dimethylsulfoxide, 
dimethylformamide, hexamethylphosphoric triamide, etc., or a mixture of 
these solvents. The basic compound includes, for example, carbonates (e.g. 
sodium carbonate, potassium carbonate, sodium hydrogen carbonate, 
potassium hydrogen carbonate, etc.), metal hydroxides (e.g. sodium 
hydroxide, potassium hydroxide, etc.), sodium hydride, potassium, sodium, 
sodium amide, metal alcoholates (e.g. sodium methoxide, sodium ethoxide, 
etc.), and organic basic compounds (e.g. pyridine, 
N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine, 
1,5-diazabicyclo4.3.0!nonene-(5) (DBN), 1,8-diazabicyclo5.4.0!undecene-7 
(DBU), 1,4-diazabicyclo2.2.2!octane (DABCO), etc.). The amount of the 
compound (7) and the compound (8) is not critical, but the compound (8) is 
usually used at least in equivalent amount, preferably 1 to 10 moles, to 1 
mole of the compound (7). The reaction is usually carried out at a 
temperature of from about 0.degree. C. to about 200.degree. C., preferably 
from about 0.degree. C. to about 170.degree. C., for about 30 minutes to 
about 30 hours. In the reaction, an alkali metal halide (e.g. sodium 
iodide, potassium iodide, etc.) may be added to the reaction system. 
The reaction of the compound (7) and the compound (9) is carried out in an 
appropriate solvent or without solvent in the presence of a reducing 
agent. The solvent includes, for example, water, alcohols (e.g. methanol, 
ethanol, isopropanol, etc.), acetonitrile, formic acid, acetic acid, 
ethers (e.g. dioxane, diethyl ether, diglyme, tetrahydrofuran, etc.), 
aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or a mixture 
of these solvents. The reducing agent includes, for example, formic acid, 
fatty acid alkali metal salts (e.g. sodium formate, etc.), hydrogenating 
reducing agents (e.g. sodium boro hydride, sodium cyanoboro hydride, 
lithium aluminum hydride, etc.), catalystic reducing agents (e.g. 
palladium black, palladium-carbon, platinum oxide, platinum black, Raney 
nickel, etc.). 
When formic acid is used as the reducing agent, the reaction is usually 
carried out at a temperature of from room temperature to about 200.degree. 
C., preferably about 50.degree. C. to about 150.degree. C., for about 1 to 
10 hours. The formic acid is usually used in a large excess amount to the 
compound (7). 
When a hydrogenating reducing agent is used, the reaction is usually 
carried out at a temperature of about -30.degree. C. to about 100.degree. 
C., preferably about 0.degree. C. to about 70.degree. C., for about 30 
minutes to about 12 hours. The reducing agent is usually used in an amount 
of 1 to 20 moles, preferably 1 to 6 moles, to 1 mole of the compound (7). 
When lithium aluminum hydride is used as the reducing agent, it is 
preferable to use a solvent selected from ethers (e.g. diethyl ether, 
dioxane, tetrahydrofuran, diglyme, etc.) and aromatic hydrocarbons (e.g. 
benzene, toluene, xylene, etc.). 
When a catalytic reducing agent is used, the reaction is usually carried 
out under atmospheric pressure to about 20 atm., preferably atmospheric 
pressure to about 10 atm. under hydrogen atmosphere or in the presence of 
a hydrogen donor (e.g. formic acid, ammonium formate, cyclohexene, 
hydrazine hydrate, etc.) at a temperature of about -30.degree. C. to about 
100.degree. C., preferably about 0.degree. C. to about 60.degree. C., for 
about 1 to 12 hours. The catalytic reducing agent is usually used in an 
amount of about 0.1 to 40% by weight, preferably about 1 to 20% by weight, 
of the amount of the compound (7). The compound (9) is usually used at 
least in equivalent amount, preferably equivalent to a large excess 
amount, to the compound (7). 
##STR20## 
wherein R.sup.1, R.sup.2, R.sup.12, R.sup.17, R.sup.18, X and W are as 
defined above, and R.sup.11a is a lower alkyl. 
##STR21## 
wherein R.sup.1, R.sup.2, R.sup.11, X and W are as defined above, and 
R.sup.12a is a cycloalkyl. 
The reaction of the compound (10) and the compound (11) in the Reaction 
Scheme-5A and the reaction of the compound (12) and the compound (13) in 
the Reaction Scheme-5B are carried out in the same manner as in the 
reaction of the compound (7) and the compound (8) in the above Reaction 
Scheme-4. 
Besides, the reaction of the compound (10) and the compound (9) in the 
Reaction Scheme-5A is carried out in the same manner as in the reaction of 
the compound (7) and the compound (9) in the above Reaction Scheme-4. 
##STR22## 
wherein R.sup.1, R.sup.2, R.sup.4, R.sup.16, R.sup.6, R.sup.7, X, W, and A 
are as defined above, l is 0 or an integer of 1 to 3, l' and l" are each 
an integer of 1 to 3, provided that l+l' and l+l" are each an integer not 
more than 3. 
##STR23## 
wherein R.sup.1, R.sup.2, R.sup.4, R.sup.16, X, W, A, l, l', and l" are as 
defined above, and R.sup.19 is a lower alkanoyloxy, R.sup.20 is a lower 
alkanoyloxy, hydroxy or phthalimido, R.sup.21 is the same as R.sup.19 and 
R.sup.20, and M is an alkali metal (e.g. potassium, sodium, etc.). 
The reaction of the compound (1g) and the compound (14) in the Reaction 
Scheme-6A and the reaction of the compound (1g) and the compound (15) or 
(16) in the Reaction Scheme-6B can be carried out under the same 
conditions as in the reaction of the compound (7) and the compound (8) in 
the above Reaction Scheme-4. In the reaction, an alkali metal halide (e.g. 
sodium iodide, potassium iodide, etc.) may be added to the reaction 
system. 
##STR24## 
wherein R.sup.1, R.sup.2, R.sup.4, R.sup.16, W, l, l', l" and A are as 
defined above. 
The reaction of converting the compound (1j) into the compound (1k) can be 
carried out by reacting the compound (1j) with hydrazine in an appropriate 
solvent or by hydrolyzing the compound (1j). The solvent used in the 
reaction with hydrazine includes water and further the same solvent as 
used in the reaction of the compound (2b) and the compound (4) in the 
above Reaction Scheme-2. The reaction is usually carried out at a 
temperature of from room temperature to about 120.degree. C., preferably 
about 0.degree. C. to about 100.degree. C., for about 0.5 to 5 hours. 
Hydrazine is usually used in an amount of at least 1 mole, preferably 
about 1 to 5 moles, to 1 mole of the compound (1j). 
The hydrolysis can be carried out in an appropriate solvent or without 
solvent in the presence of an acid or a basic compound. The solvent 
includes, for example, water, lower alcohols (e.g. methanol, ethanol, 
isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), 
ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, 
etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixture of 
these solvents. The acid includes, for example, mineral acids (e.g. 
hydrochloric acid, sulfuric acid, hydrobromic acid, etc.) and organic 
acids (e.g. formic acid, acetic acid, aromatic sulfonic acids, etc.). The 
basic compound includes, for example, metal carbonates (e.g. sodium 
carbonate, potassium carbonate, etc.), metal hydroxides (e.g. sodium 
hydroxide, potassium hydroxide, calcium hydroxide, etc.), and the like. 
The reaction is usually carried out at a temperature of from room 
temperature to about 200.degree. C., preferably from room temperature to 
about 150.degree. C., for about 10 minutes to 25 hours. 
##STR25## 
wherein R.sup.1, R.sup.2, R.sup.4, W, R.sup.16, l, l', l", X, and A are as 
defined above, and R.sup.22 is a lower alkanoyl. 
The reaction of the compound (1l) and the compound (17) is carried out 
under the same conditions as in the reaction of the compound (7) and the 
compound (8) in the Reaction Scheme-4. In the reaction, an alkali metal 
halide (e.g. sodium iodide, potassium iodide, etc.) may be added to the 
reaction system. 
The reaction of converting the compound (1m) into the compound (1l) can be 
carried out under the same condition as in the hydrolysis of the compound 
(1j) in the Reaction Scheme-7. 
##STR26## 
wherein R.sup.1, R.sup.2, R.sup.4, W, R.sup.16, l, l', l", and X are as 
defined above, and R.sup.23 is a lower alkyl, a lower 
alkanoyloxy-substituted lower alkyl, a halogen-substituted lower alkyl, a 
carboxy-substituted lower alkyl, a carbamoyl-substituted lower alkyl, a 
hydroxy-substituted lower alkyl, a lower alkoxycarbonyl-substituted lower 
alkyl, a phthalimido-substituted lower alkyl, an aminocarbonyl-lower alkyl 
having optionally a lower alkyl substituent, or a group of the formula: 
##STR27## 
(A, R.sup.6 and R.sup.7 are as defined above). 
The reaction of the compound (1n) and the compound (18) can be carried out 
under the same conditions as in the reaction of the compound (7) and the 
compound (8) in the above Reaction Scheme-4. In the reaction, an alkali 
metal halide (e.g. sodium iodide, potassium iodide, etc.) may be added to 
the reaction system. 
##STR28## 
wherein R.sup.1, R.sup.2, R.sup.4, W, R.sup.16, R.sup.17, R.sup.18, l, X, 
and A are as defined above, and R.sup.6' is hydrogen atom, a lower alkyl 
having optionally a hydroxy substituent, a lower alkanoyl, or benzoyl, 
R.sup.7a is a lower alkyl having optionally a hydroxy substituent, and 
R.sup.7b is a lower alkanoyl or benzoyl. 
The reaction of the compound (1p) and the compound (19) or the compound (9) 
can be carried out under the same conditions as in the reaction of the 
compound (7) and the compound (8) or the compound (9) in the above 
Reaction Scheme-4. 
The reaction of the compound (1p) and the compound (20) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the Reaction Scheme-1. 
Besides, the compound (1r) can also be obtained by reacting the compound 
(1p) with a compound of the formula: (R.sup.7b).sub.2 O(R.sup.7b is as 
defined above). The reaction can be carried out in an appropriate solvent 
or without solvent in the presence or absence, preferably presence, of a 
basic compound. The solvent includes, for example, the above-mentioned 
aromatic hydrocarbons, lower alcohols (e.g. methanol, ethanol, propanol, 
etc.), dimethylformamide, dimethylsulfoxide, and further halogenated 
hydrocarbons (e.g. chloroform, methylene chloride, etc.), acetone, 
pyridine, etc. The basic compound includes, for example, tertiary amines 
(e.g. triethylamine, pyridine, etc.), sodium hydroxide, potassium 
hydroxide, sodium hydride, and the like. The above reaction can also be 
carried out in a solvent such as acetic acid or benzoic acid in the 
presence of a mineral acid (e.g. sulfuric acid, etc.). The acid anhydride 
is usually used in an equimolar amount or more, preferably 1 to 10 moles, 
to 1 mole of the starting compound, and the reaction is usually carried 
out at a temperature of about 0.degree. C. to about 200.degree. C., 
preferably from about 0.degree. C. to about 150.degree. C., for about 0.5 
to 15 hours. 
##STR29## 
wherein R.sup.1, R.sup.2, R.sup.4, R.sup.9, R.sup.10, W, and B are as 
defined above. 
The reaction of the compound (1s) and the compound (21) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
##STR30## 
wherein R.sup.1, R.sup.2, R.sup.4, W, R.sup.9, R.sup.10, X, and B are as 
defined above. 
The reaction of the compound (1u) and the compound (21) can be carried out 
under the same conditions as in the reaction of the compound (7) and the 
compound (8) in the above Reaction Scheme-4. In the reaction, an alkali 
metal halide (e.g. sodium iodide, potassium iodide, etc.) may be added to 
the reaction system. 
##STR31## 
wherein R.sup.1, R.sup.2, R.sup.4, W, and B are as defined above, and 
R.sup.24 is a lower alkyl. 
The reaction of the compound (2b) and the compound (22) can be carried out 
in an appropriate inert solvent. The inert solvent includes, for example, 
aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. 
tetrahydrofuran, dioxane, diethylene glycol dimethyl ether, etc.), lower 
alcohols (e.g. methanol, ethanol, isopropanol, butanol, etc.), halogenated 
hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, 
etc.), acetic acid, ethyl acetate, acetonitrile, dimethylsulfoxide, 
dimethylformamide, hexamethylphosphoric triamide, and the like. The amount 
of the compound (2b) and the compound (22) is not critical, but the 
compound (22) is usually used in an amount of at least one mole, 
preferably 1 to 2 moles, to 1 mole of the compound (2b). The reaction is 
usually carried out at a temperature of from about 0.degree. C. to about 
150.degree. C., preferably from about 0.degree. C. to about 100.degree. 
C., for about 30 minutes to about 10 hours. 
The esterification of the compound (1w) is usually carried out by reacting 
the starting compound with an alcohol (e.g. methanol, ethanol, 
isopropanol, etc.) in the presence of a mineral acid (e.g. hydrochloric 
acid, sulfuric acid, etc.) and a halogenating agent (e.g. thionyl 
chloride, phosphorus oxychloride, phosphorus pentachloride, phosphorus 
trichloride, etc.) at a temperature of 0.degree. C. to 150.degree. C., 
preferably 50.degree. C. to 100.degree. C., for about 1 to 10 hours. 
The hydrolysis of the compound (1x) can be carried out under the same 
conditions as in the hydrolysis of the compound (1j) in the Reaction 
Scheme-7. 
##STR32## 
wherein R.sup.1, R.sup.2, R.sup.4, W, B, M, and X are as defined above, 
and R.sup.25 is a phenyl which has optionally 1 to 3 substituents selected 
from a lower alkyl, a lower alkoxy and an amino having optionally a lower 
alkanoyl substituent, or naphthyl, and R.sup.25' is a phenoxy which has 
optionally 1 to 3 substituents selected from a lower alkyl, a lower alkoxy 
and an amino having optionally a lower alkanoyl substituent, naphthyloxy 
or phthalimido. 
The reaction of the compound (1u) and the compound (23) or (23a) can be 
carried out under the same conditions as in the reaction of the compound 
(7) and the compound (8) in the above Reaction Scheme-4. 
The compound (1y) wherein R.sup.25' is phthalimido can be converted into 
the compound (1y) wherein R.sup.25' is amino under the same conditions as 
in the reaction of converting the compound (1j) into the compound (1k) in 
the above Reaction Scheme-7. 
##STR33## 
wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above, and R.sup.26 is 
oxo, R.sup.27 is hydroxy, and W' is the same as W, provided that the 
substituents on the group --(CH.sub.2).sub.p -- or 
--CH.dbd.CH--(CH.sub.2).sub.q -- are 0 to 2, and R.sup.28 and R.sup.29 are 
the same or different and are each hydrogen atom, a lower alkenyl, a 
cycloalkyl, an oxiranyl-substituted lower alkyl, a lower alkyl having 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 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 which has optionally a 
phenyl-lower alkyl substituent, an aminocarbonyl-lower alkyl having 
optionally a lower alkyl substituent, or a lower alkyl, or R.sup.28 and 
R.sup.29 may bind together with the nitrogen atom to which they bond to 
form a 5- or 6-membered saturated heterocyclic group with or without being 
intervened with nitrogen or oxygen atom, which heterocyclic ring may 
optionally have a substituent selected from a lower alkyl, a phenyl-lower 
alkyl, or a lower alkanoyl. 
The conversion of the compound (1A) into the compound (1B) is carried out 
by reduction thereof. The reducing reaction is preferably carried out by 
using a hydrogenating reducing agent (e.g. lithium aluminum hydride, 
sodium boro hydride, diborane, etc.). The reducing agent is usually used 
in an amount of at least one mole, preferably 1 to 15 moles, to 1 mole of 
the starting compound. The reducing reaction is usually carried out in an 
appropriate solvent, for example, water, alcohols (e.g. methanol, ethanol, 
isopropanol, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, 
diisopropyl ether, diglyme, etc.), or a mixture of these solvents, at a 
temperature of from about -60.degree. C. to about 150.degree. C., 
preferably about -30.degree. C. to about 100.degree. C., for about 10 
minutes to 15 hours. When lithium aluminum hydride or diborane is used as 
the reducing agent, it is preferable to use an anhydrous solvent such as 
tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc. 
The reaction of converting the compound (1A) into the compound (1C) is 
usually carried out in an appropriate solvent or without solvent in the 
presence or absence of a dehydrating agent. The solvent includes, for 
example, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), 
aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated 
hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon 
tetrachloride, etc.), aprotic polar solvents (e.g. dimethylformamide, 
dimethylacetamide, N-methylpyrrolidone, etc.), or a mixture of these 
solvents. The dehydrating agent includes, for example, conventional drying 
agent used for dehydrating solvents (e.g. molecular sieves, etc.), mineral 
acids (e.g. hydrochloric acid, sulfuric acid, borone trifluoride, etc.), 
organic acids (e.g. p-toluenesulfonic acid, etc.), and the like. The 
reaction is usually carried out at a temperature of from room temperature 
to about 250.degree. C., preferably from about 50.degree. C. to about 
200.degree. C., for about 1 to 48 hours. The amount of the compound (24) 
is not critical, but it is usually used at least in an equivalent amount, 
preferably equimolar to largely excess to the amount of the compound (1A). 
The dehydrating agent is preferably used in a largely excess amount in 
case of the drying agent and in a catalytic amount in case of the acid. 
The subsequent reducing reaction can be carried out by various methods, for 
example by catalytically hydrogenating the compound in an appropriate 
solvent in the presence of a catalyst. The solvent includes, for example, 
water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), 
hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. diethylene 
glycol dimethyl ether, dioxane, tetrahydrofuran, diethyl ether, etc.), 
esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents 
(e.g. dimethylformamide, etc.), or a mixture of these solvents. The 
catalyst includes, for example, palladium, palladium black, 
palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, 
and the like. The catalyst is usually used in an amount of 0.02 to 1 part 
by weight to 1 part by weight of the starting compound. The reaction is 
usually carried out at a temperature of from about -20.degree. C. to about 
100.degree. C., preferably about 0.degree. C. to about 70.degree. C., 
under a hydrogen atmospheric pressure of 1 to 10 atm. for about 0.5 to 20 
hours. 
Although the reducting reaction can be carried out under the above 
conditions, it is preferably carried out by using a hydrogenating reducing 
agent. The hydrogenating reducing agent includes, for example, lithium 
aluminum hydride, sodium borohydride, diborane, etc., and it is usually 
used in an amount of at least one mole, preferably 1 to 10 moles, to 1 
mole of the compound (1A). The reaction is usually carried out in an 
appropriate solvent, such as water, lower alcohols (e.g. methanol, 
ethanol, isopropanol, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, 
diglyme, etc.), dimethylformamide, or a mixture of these solvents, at a 
temperature of about -60.degree. C. to about 50.degree. C., preferably 
about -30.degree. C. to room temperature, for about 10 minutes to about 5 
hours. When lithium aluminum hydride or diborane is used as the reducing 
agent, it is preferable to use an anhydrous solvent such as diethyl ether, 
tetrahydrofuran, diglyme, etc. 
The compound (1C) wherein at least one of R.sup.28 and R.sup.29 is hydrogen 
atom can be converted into the compound (1C) wherein at least one of 
R.sup.28 and R.sup.29 is a lower alkyl by reacting the compound (1C) with 
the compound (8) or the compound (9) under the same conditions as in the 
reaction of the compound (7) and the compound (8) or (9) in the above 
Reaction Scheme-4. 
##STR34## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.14, R.sup.15, W', and M are as 
defined above, and R.sup.31 is a phenyl-lower alkyl, and R.sup.30 is a 
lower alkoxycarbonyl. 
The reaction of converting the compound (1D) into the compound (1E) can be 
carried out under the same conditions as in the reaction of converting the 
compound (1A) into the compound (1B) in the above Reaction Scheme-15. 
The reaction of converting the compound (1D) into the compound (1F) can be 
carried out under the same conditions as in the hydrolysis reaction of the 
compound (1j) in the above Reaction Scheme-7. 
The reaction of the compound (1F) and the compound (25) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
The halogenation of the compound (1F) can be carried out under a 
conventional condition for halogenation of a carboxylic acid. The reaction 
of the thus-obtained carboxylic acid halide of the compound (1F) with the 
compound (26) is carried out in an appropriate solvent in the presence or 
absence of a basic compound. The solvent includes, for example, 
halogenated hydrocarbons (e.g. methylene chloride, chloroform, etc.), 
aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. 
diethyl ether, tetrahydrofuran, dimethoxyethane, etc.), esters (e.g. 
methyl acetate, ethyl acetate, etc.), aprotic polar solvents (e.g. 
N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, 
etc.), alcohols (e.g. methanol, ethanol, propanol, butanol, 
3-methoxy-1-butanol, ethyl cellosolve, methyl cellosolve, etc.), pyridine, 
acetone, acetonitrile, water, or a mixture of these solvents. The basic 
compound includes, for example, organic bases such as triethylamine, 
trimethylamine, pyridine, dimethylaniline, N-methylmorpholine, DBN, DBU, 
DABCO, etc., inorganic bases such as potassium carbonate, sodium 
carbonate, potassium hydroxide, sodium hydroxide, potassium hydride, 
sodium hydride, silver carbonate, alcoholates (e.g. sodium methylate, 
sodium ethylate, etc.), and the like. The compound (26) is usually used in 
an amount of at least 1 mole, preferably 1 to 1.5 mole, to 1 mole of the 
carboxylic acid halide of the compound (1F). The reaction is usually 
carried out at a temperature of from -30.degree. C. to about 180.degree. 
C., preferably from about 0.degree. C. to about 150.degree. C., for about 
5 minutes to 30 hours. 
The reaction of the compound (1H) and the compound (27) is carried out in 
an appropriate solvent or without solvent at a temperature of from about 
0.degree. C. to about 200.degree. C., preferably from room temperature to 
about 150.degree. C. The solvent includes the same solvents as used in the 
above reaction of the carboxylic acid halide of the compound (1F) and the 
compound (26). The compound (27) is preferably used in an amount largely 
excess to the compound (1H). The reaction is usually completed in a 
reaction time of about 1 to 5 hours. 
The reaction of converting the compound (1I) into the compound (1J) can be 
carried out by reducing the compound. The reducing reaction is usually 
carried out by catalytically hydrogenating the compound in an appropriate 
solvent in the presence of a catalyst. The solvent includes, for example, 
water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), 
hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, 
tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, etc.), 
esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents 
(e.g. N,N-dimethylformamide, etc.), acetic acid, or a mixture of these 
solvents. The catalyst includes, for example, palladium, palladium black, 
palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, 
and the like. The catalyst is usually used in an amount of 0.02 to 1 part 
by weight to 1 part by weight of the starting compound. The reaction is 
usually carried out at a temperature of from about -20.degree. C. to about 
100.degree. C., preferably about 0.degree. C. to about 80.degree. C., 
under a hydrogen atmospheric pressure of 1 to 10 atm. for about 0.5 to 20 
hours. 
##STR35## 
wherein R.sup.1, R.sup.2, R.sup.3, W', l, R.sup.17, R.sup.18, and X are as 
defined above, and R.sup.14a is hydrogen atom, a lower alkyl, a lower 
alkanoyl, a lower alkenyl, a cycloalkyl, an oxiranyl-substituted lower 
alkyl, a lower alkyl having 1 to 2 substituents selected from a lower 
alkoxy, hydroxy and an amino having optionally a lower alkyl substituent, 
a phenyl-lower alkyl, a pyridyl-lower alkyl, a lower alkylsulfonyl, 
benzoyl, a lower alkoxycarbonyl, anilinocarbonyl, an aminocarbonyl having 
optionally a lower alkyl substituent, a cyano-substituted lower alkyl, a 
lower alkoxycarbonyl-substituted lower alkyl, a carbamoyl-substituted 
lower alkyl, a carboxy-substituted lower alkyl, a 
tetrahydropyranyloxy-substituted lower alkyl, a lower 
alkanoyloxy-substituted lower alkyl, a piperidinyl having optionally a 
phenyl-lower alkyl substituent, a halogen-substituted lower alkanoyl, an 
imiazolyl-substituted lower alkanoyl, an amino-lower alkanoyl having 
optionally a substituent selected from a lower alkyl and a lower 
alkoxycarbonyl, an aminocarbonyl-lower alkyl having optionally a lower 
alkyl substituent, or a phenyl-lower alkoxycarbonyl, R.sup.15a is a lower 
alkyl, a cycloalkyl, an oxiranyl-substituted lower alkyl, a lower alkyl 
having 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, 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, an aminocarbonyl-lower alkyl having 
optionally a lower alkyl substituent, or a lower alkenyl, and R.sup.15b is 
a lower alkanoyl, a phenyl-lower alkoxycarbonyl, benzoyl, a lower 
alkoxycarbonyl, a halogen-substituted lower alkanoyl, an 
imidazolyl-substituted lower alkanoyl, or an amino-lower alkanoyl having 
optionally a substituent selected from a lower alkyl and a lower 
alkoxycarbonyl. 
The reaction of the compound (1K) and the compound (28) or the compound (9) 
can be carried out under the same conditions as in the reaction of the 
compound (7) and the compound (8) or the compound (9) in the above 
Reaction Scheme-4. 
The reaction of the compound (1K) and th e compound (29) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. The compound (1M) can also be 
obtained by reacting the compound (1K) with a compound of the formula 
(R.sup.15b).sub.2 O (wherein R.sup.15b is as defined above). The reaction 
can be carried out under the same conditions as in the reaction of the 
compound (1p) and the compound of the formula: (R.sup.7b).sub.2 O as 
described hereinbefore. 
The compound (1M) wherein R.sup.15b is formyl can also be prepared by 
reacting the compound (1K) with a formate of the formula: HCOCR.sup.82 
(R.sup.82 is a lower alkyl). The reaction is usually carried out in the 
solvent as used in the reaction of the compound (7) and the compound (8) 
in the above Reaction Scheme-4 or without solvent, at a temperature of 
about 0.degree. C. to about 200.degree. C., preferably about 0.degree. C. 
to about 170.degree. C., for about 30 minutes to about 30 hours. The 
formate is preferably used in a largely excess amount to the compound 
(1K). 
##STR36## 
wherein R.sup.1, R.sup.2, R.sup.4, R.sup.16, W, l, l' and l" are as 
defined above, and R.sup.32 is a lower alkoxycarbonyl-substituted lower 
alkoxy, R.sup.33 is a carbamoyl-substituted lower alkoxy, R.sup.34 is a 
carboxy-substituted lower alkoxy, R.sup.44 is an amino having optionally a 
lower alkyl substituent, and R.sup.45 is an aminocarbonyl-lower alkoxy 
having optionally a lower alkyl substituent. 
The conversion of the compound (1N) into the compound (10) can be carried 
out by reacting the compound with aqueous ammonia in an appropriate 
solvent in an autoclave. The solvent includes the same solvents as used in 
the reaction of the carboxylic acid halide and the amine (2) in the above 
Reaction Scheme-1. The aqueous ammonia is used in a largely excess amount 
to the compound (1N). The reaction proceeds advantageously by adding an 
ammonium halide (e.g. ammonium chloride, etc.) to the reaction system. The 
reaction is usually carried out at a temperature of from room temperature 
to about 200.degree. C., preferably from room temperature to about 
150.degree. C., for about 1 to 10 hours. 
The reaction of converting the compound (1N) into the compound (1P) can be 
carried out under the same conditions as in the hydrolysis of the compound 
(1j) in the above Reaction Scheme-7. 
The reaction of the compound (1P) and the compound (30) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
##STR37## 
wherein R.sup.1, R.sup.2, R.sup.4, R.sup.16, W, l, l' and l" are as 
defined above. 
The reducing reaction in the above reaction scheme is usually carried out, 
for example, (i) with a reducing catalyst in an appropriate solvent or 
(ii) with a reducing agent such as a mixture of a metal or metal salt with 
an acid, or a mixture of a metal or metal salt with an alkali metal 
hydroxide, a sulfide or an ammonium salt in an appropriate inert solvent. 
In case of using a reducing catalyst, the solvent includes, for example, 
water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), 
hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, 
tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, etc.), 
esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents 
(e.g. N,N-dimethylformamide, etc.), or a mixture of these solvents. The 
catalyst includes, for example, palladium, palladium black, 
palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, 
and the like. The catalyst is usually used in an amount of 0.02 to 1 part 
by weight to 1 part by weight of the starting compound. The reaction is 
usually carried out at a temperature of from about -20.degree. C. to about 
150.degree. C., preferably about 0.degree. C. to about 100.degree. C., 
under a hydrogen pressure of 1 to 10 atm. for about 0.5 to 10 hours. In 
the reaction, an acid such as hydrochloric acid may optionally added to 
the reaction system. 
In case of the above method (ii), the reducting agent includes a mixture of 
iron, zinc, tin or stannous chloride and a mineral acid (e.g. hydrochloric 
acid, sulfuric acid, etc.), or a mixture of iron, ferrous sulfate, zinc or 
tin and an alkali metal hydroxide (e.g. sodium hydroxide, etc.), a sulfide 
(e.g. ammonium sulfide, etc.), aqueous ammonia, or an ammonium salt (e.g. 
ammonium chloride, etc.). The inert solvent includes, for example water, 
acetic acid, methanol, ethanol, dioxane, and the like. The reducing 
reaction conditions are determined depending on the kinds of the reducting 
agent, but in case of using a reducing agent comprising stannous chloride 
and hydrochloric acid, for example, it is preferably carried out at a 
temperature of about 0.degree. C. to room temperature for about 0.5 to 10 
hours. The reducing agent is usually used in an amount of at least one 
mole, preferably 1 to 5 moles, to 1 mole of the starting compound. 
##STR38## 
wherein R.sup.1, R.sup.2, R.sup.4, R.sup.16, R.sup.17, R.sup.18, l, l', l" 
and W are as defined above, and R.sup.36 is a lower alkyl, R.sup.37 is a 
lower alkanoyl, and R.sup.35 is hydrogen atom, a lower alkyl or a lower 
alkanoyl. 
The reaction of the compound (1S) and the compound (31) or the compound (9) 
can be carried out under the same conditions as in the reaction of the 
compound (7) and the compound (8) or the compound (9) in the above 
Reaction Scheme-4. 
The reaction of the compound (1S) and the compound (32) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. Besides, the compound (1U) 
can also be obtained by reacting the compound (1S) with a compound of the 
formula: (R.sup.37).sub.2 O (R.sup.37 is as defined above). The reaction 
is carried out under the same conditions as in the above reaction of the 
compound (1p) and a compound of the formula: (R.sup.7b).sub.2 O. 
The compound (1) wherein R.sup.8 is a phenyl-lower alkoxycarbonyl can be 
converted into the compound (1) wherein R.sup.8 is hydrogen atom in the 
same manner as in the reaction of converting the compound (1I) into the 
compound (1J) in the above Reaction Scheme-16. 
Other derivatives of the starting compound (2) can be prepared, for 
example, by the process as shown in the following reaction scheme. 
##STR39## 
wherein R.sup.1, R.sup.2, and W are as defined above. 
The reaction of the compound (2) and the compound (33) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
The reaction of converting the compound (34) into the compound (2a) can be 
carried out under the same conditions as in the reducing reaction in the 
above Reaction Scheme-19. 
The starting compound (5) can be prepared, for example, by the process of 
the following reaction scheme. 
##STR40## 
wherein R.sup.1, R.sup.2, and W are as defined above, and R.sup.38 is a 
lower alkyl. 
The reaction of the compound (2) and the compound (35) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
The reaction of converting the compound (36) into the compound (5) can be 
carried out under the same conditions as in the hydrolysis reaction in the 
above Reaction Scheme-7. 
##STR41## 
wherein R.sup.1, R.sup.2, R.sup.4, R.sup.16, l, l', l", X, and W are as 
defined above, and R.sup.39 is a lower alkanoyl. 
The reaction of the compound (1W) and the compound (37) can be carried out 
under the same conditions as in the reaction of the compound (1n) and the 
compound (18) in the above Reaction Scheme-9. 
The hydrolysis reaction of the compound (1X) can be carried out under the 
same conditions as in the hydrolysis of the compound (1j) in the above 
Reaction Scheme-7. 
##STR42## 
wherein R.sup.1, R.sup.2, R.sup.4, R.sup.16, l, l', l", and W are as 
defined above, R.sup.40 is a lower alkanoyl, and R.sup.41 is a 
hydroxy-substituted lower alkyl. 
The reaction of converting the compound (1Y) into the compound (1Z) can be 
carried out under the same conditions as in the reaction of converting the 
compound (1A) into the compound (1B) in the above Reaction Scheme-15. 
##STR43## 
wherein R.sup.1, R.sup.2, R.sup.4, R.sup.16, l, l', l", and W are as 
defined above, R.sup.42 is a lower alkoxycarbonyl and R.sup.43 is 
carboxyl. 
The reaction of converting the compound (1aa) into the compound (1bb) can 
be carried out under the same conditions as in the hydrolysis of the 
compound (1j) in the above Reaction Scheme-7. 
The esterification reaction of the compound (1bb) can be carried out under 
the same conditions as in the esterification of the compound (1w) in the 
above Reaction Scheme-13. 
##STR44## 
wherein R.sup.1, R.sup.2, R.sup.4, and W are as defined above, and 
R.sup.46 is a phenyl having optionally a lower alkyl substituent. 
The reaction of the compound (2b) and the compound (38) is usually carried 
out in an appropriate solvent or without solvent in the presence or 
absence, preferably in the absence, of a basic compound. The solvent and 
basic compound are the same as those used in the reaction of the 
carboxylic acid halide and the amine (2) in the above Reaction Scheme-1. 
The compound (38) is usually used in an amount of about 1 to 5 moles, 
preferably about 1 to 3 moles, to 1 mole of the compound (2b). The 
reaction is usually carried out at a temperature of from about 0.degree. 
C. to about 200.degree. C., preferably from room temperature to about 
150.degree. C., for about 5 minutes to about 30 hours. In the reaction, a 
boron compound (e.g. boron trifluoride etherate, etc.) may be added to the 
reaction system. 
##STR45## 
wherein R.sup.1, R.sup.2, R.sup.4, W, and X are as defined above, and 
R.sup.47 is a phenylsulfonyl which has optionally a substituent selected 
from a halogen atom and a lower alkyl on the phenyl ring, or 
quinolylsulfonyl. 
The reaction of the compound (2b) and the compound (39) can be carried out 
under the same conditions as in the reaction of the compound (7) and the 
compound (8) in the above Reaction Scheme-4. 
##STR46## 
wherein R.sup.1, R.sup.2, R.sup.4, W, R.sup.17, R.sup.18, and X are as 
defined above, R.sup.48 is a phenyl-lower alkoxycarbonyl, a lower 
alkanoyl, an amino-lower alkanoyl having optionally a lower alkyl 
substituent, and R.sup.49 is a lower alkyl or a carbamoyl-lower alkyl. 
The reaction of the compound (1ee) and the compound (40) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
The reaction of the compound (1ee) and the compound (41) or the compound 
(9) can be carried out under the same conditions as in the reaction of the 
compound (7) and the compound (8) or the compound (9) in the above 
Reaction Scheme-4, provided that in the reaction product (1ff) produced by 
the reaction of the compound (1ee) and the compound (9), the group 
R.sup.49 is a lower alkyl. 
##STR47## 
wherein R.sup.1, R.sup.2, R.sup.5, and W are as defined above, and 
R.sup.50 is a benzoyl having optionally a halogen substituent on the 
phenyl ring. 
The reaction of the compound (7) and the compound (42) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
##STR48## 
wherein R.sup.1, W', R.sup.26, R.sup.2, and R.sup.3 are as defined above, 
R.sup.103 is hydroxy or sulfoxy, and R.sup.51 is hydroxyimino or 
sulfoxyimino. 
The reaction of the compound (1A) and the compound (43) is usually carried 
out in an appropriate inert solvent in the presence or absence of a basic 
compound. The basic compound includes, for example, inorganic basic 
compounds such as sodium hydroxide, potassium hydroxide, sodium carbonate, 
potassium carbonate, etc., and organic basic compounds such as piperidine, 
pyridine, triethylamine, 1,5-diazabicyclo4.3.0!nonene-5 (DBN), 
1,8-diazabicyclo5.4.0!undecene-7 (DBU), 1,4-diazabicyclo2.2.2!octane 
(DABCO), etc. The inert solvent includes, for example, lower alcohols 
(e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. dioxane, 
tetrahydrofuran, diethyl ether, ethylene glycol monomethyl ether, etc.), 
aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated 
hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon 
tetrachloride, etc.), pyridine, dimethylformamide, dimethylsulfoxide, 
hexamethylphosphoric triamide, etc., or a mixture of these solvents. The 
compound (43) is usually used at least in equivalent amount, preferably 1 
to 5 moles, to 1 mole of the compound (1A). The reaction is usually 
carried out at a temperature of from room temperature to about 200.degree. 
C., preferably from about 50.degree. C. to 150.degree. C., for about 1 to 
10 hours. 
##STR49## 
wherein R.sup.1, W', R.sup.27, R.sup.2, M, and R.sup.3 are as defined 
above, and R.sup.52 is a halogen atom. 
The halogenation of the compound (1B) is usually carried out in an 
appropriate solvent or without solvent by reacting the compound (1B) with 
a halogenating agent. 
The halogenating agent includes mineral acids (e.g. hydrochloric acid, 
hydrobromic acid, etc.), N,N-diethyl-1,2,2-trichlorovinylamide, phosphorus 
pentachloride, phosphorus pentabromide, phosphorus oxychloride, thionyl 
chloride, methanesulfonyl chloride, or a combination of a phenyl-lower 
alkyl halide (e.g. p-toluenesulfonyl chloride, etc.) and a basic compound. 
The basic compound includes the same compounds as used in the reaction of 
the compound (1A) and the compound (43) in the above Reaction Scheme-30. 
The solvent includes, for example, ethers (e.g. dioxane, tetrahydrofuran, 
etc.), halogenated hydrocarbons (e.g. chloroform, methylene chloride, 
carbon tetrachloride, etc.), and the like. The amount of the halogenating 
agent may vary depending on the kinds of the halogenating agents, and in 
case of a combination of a phenyl-lower alkyl halide (e.g. 
p-toluenesulfonyl chloride, etc.) and a basic compound, it is used in an 
amount of at least 1 mole, preferably 1 to 2 moles, to 1 mole of the 
compound (1B), and in case of other halogenating agents, it is used at 
least in an equimolar amount, usually in a largely excess amount, to the 
compound (1B). The reaction is usually carried out at a temperature of 
from room temperature to about 150.degree. C., preferably from room 
temperature to about 80.degree. C., for about 1 to 80 hours. 
The reaction of the compound (1jj) and the compound (44) can be carried out 
under the same conditions as in the reaction of the compound (7) and the 
compound (8) in the above Reaction Scheme-4. 
The reducing reaction of the compound (1kk) can be carried out under the 
same conditions as in the reducing reaction using a reducing catalyst for 
converting the compound (1A) into the compound (1C) in the above Reaction 
Scheme-15. 
##STR50## 
wherein R.sup.1, W', R.sup.2, R.sup.3, R.sup.27, X, and A are as defined 
above, R.sup.53 is a lower alkanoyloxy having optionally a halogen 
substituent, R.sup.54 is a lower alkoxy, an amino-lower alkanoyloxy having 
optionally a lower alkyl substituent, or a group of the formula: 
##STR51## 
(A, R.sup.82 and R.sup.83 are as defined above), R.sup.55 is a lower 
alkoxycarbonyl-substituted lower alkoxy, R.sup.56 is a carboxy-substituted 
lower alkoxy, R.sup.57 is an aminocarbonyl-lower alkoxy having optionally 
a lower alkyl substituent, R.sup.54a is a lower alkyl, an amino-lower 
alkanoyl having optionally a lower alkyl substituent, or a group of the 
formula: 
##STR52## 
(A, R.sup.82 and R.sup.83 are as defined above), R.sup.55a is a lower 
alkoxycarbonyl-substituted lower alkyl, R.sup.58 and R.sup.59 are the same 
or different and are each hydrogen atom or a lower alkyl, and R.sup.22a is 
a lower alkanoyl having optionally a halogen substituent. 
##STR53## 
wherein R.sup.1, W', R.sup.2, R.sup.3, X, R.sup.27, and A are as defined 
above, and R.sup.61 and R.sup.62 are the same or different and are each 
hydrogen atom, a lower alkyl or a lower alkanoyl. 
The reaction of the compound (1B) and the compound (45) or the compound 
(46) in the Reaction Scheme-32A can be carried out under the same 
conditions as in the reaction of the compound (1n) and the compound (18) 
in the above Reaction Scheme-9. 
The reaction of the compound (1B) and the compound (47) and the reaction of 
the compound (1B) and the compound (48) can be carried out under the same 
conditions as in the reaction of the compound (1n) and the compound (18) 
in the above Reaction Scheme-9. 
The reaction of converting the compound (1oo) into the compound (1pp) can 
be carried out under the same conditions as in the hydrolysis reaction of 
the compound (1j) in the above Reaction Scheme-7. 
The reaction of the compound (1oo) and the compound (49) and the reaction 
of the compound (1pp) and the compound (49) can be carried out under the 
same conditions as in the reaction of the compound (2) and the compound 
(3) in the above Reaction Scheme-1. 
The reaction of the compound (1B) and the compound (49a) in the Reaction 
Scheme-32B can be carried out under the same conditions as in the reaction 
of the compound (1n) and the compound (18) in the above Reaction Scheme-9. 
##STR54## 
wherein R.sup.1, W', R.sup.2, R.sup.3, R.sup.27, R.sup.61, R.sup.62, M, 
and X are as defined above, R.sup.60 is a halogen-substituted lower alkyl, 
R.sup.64 is a phthalimido-substituted lower alkyl, R.sup.63 is an 
amino-lower alkoxy having optionally a substituent selected from a lower 
alkyl and a lower alkanoyl, or a phthalimido-substituted lower alkoxy, and 
R.sup.65 is an amino-substituted lower alkyl. 
The reaction of the compound (1B) and the compound (50) and the reaction of 
the compound (1B) and the compound (52) can be carried out under the same 
conditions as in the reaction of the compound (1n) and the compound (18) 
in the above Reaction Scheme-9. 
The reaction of the compound (1rr) and the compound (51) or the compound 
(23a) can be carried out under the same conditions as in the reaction of 
the compound (19) and the compound (14) in the above Reaction Scheme-6. 
The reaction of converting the compound (1tt) into the compound (1uu) can 
be carried out under the same conditions as in the reaction of converting 
the compound (1j) into the compound (1k) in the above Reaction Scheme-7. 
##STR55## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.61, W', A, R.sup.17, R.sup.18, 
and X are as defined above, R.sup.62a is a lower alkyl, and R.sup.62b is a 
lower alkanoyl. 
The reaction of the compound (1vv) and the compound (53) or the compound 
(9) can be carried out under the same conditions as in the reaction of the 
compound (7) and the compound (8) or the compound (9) in the above 
Reaction Scheme-4. 
The reaction of the compound (1vv) and the compound (54) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
The reaction of the compound (1vv) and the compound (55) can be carried out 
under the same conditions as in the reaction of the compound (1p) and the 
compound of the formula: (R.sup.7b).sub.2 O in the above Reaction 
Scheme-10. 
##STR56## 
wherein R.sup.1, R.sup.2, R.sup.3, and W' are as defined above, R.sup.58' 
and R.sup.59' are the same or different and are each hydrogen atom, a 
lower alkyl, or a lower alkanoyl. 
The reaction of converting the compound (1yy) into the compound (1zz) is 
usually carried out by reducing the compound (1yy). 
The reducting reaction is preferably carried out by using a hydrogenating 
reducing agent. The hydrogenating reducing agent includes, for example, 
lithium aluminum hydride, sodium boro hydride, diborane, etc. The reducing 
agent is usually used in an amount of at least one mole, preferably 1 to 
15 moles, to 1 mole of the starting compound. The reducing reaction is 
usually carried out in an appropriate solvent, such as water, lower 
alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. 
tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.), or a 
mixture of these solvents, at a temperature of about -60.degree. C. to 
about 150.degree. C., preferably about -30.degree. C. to 100.degree. C., 
for about 10 minutes to about 5 hours. When lithium aluminum hydride or 
diborane is used as the reducing agent, it is preferable to use an 
anhydrous solvent such as diethyl ether, tetrahydrofuran, diglyme, etc. 
##STR57## 
wherein R.sup.1, W', R.sup.2, R.sup.3, R.sup.62a, R.sup.62b, X, R.sup.17, 
R.sup.18, and A are as defined above, R.sup.58a is hydrogen atom, a lower 
alkyl or a lower alkanoyl. 
The reaction of the compound (1AA) and the compound (53) or the compound 
(9) can be carried out under the same conditions as in the reaction of the 
compound (7) and the compound (8) or the compound (9) in the above 
Reaction Scheme-4. 
The reaction of the compound (1AA) and the compound (54) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
The reaction of the compound (1AA) and the compound (55) can be carried out 
under the same conditions as in the reaction of the compound (1p) and the 
compound of the formula: (R.sup.7b).sub.2 O in the above Reaction 
Scheme-10. 
The compound (1BB) wherein R.sup.62b is formyl can also be prepared by 
reacting the compound (1AA) with a formate of the formula: HCOOR.sup.82 
under the same conditions as in the reaction of the compound (1K) and the 
compound of the formula: HCOOR.sup.82 as described hereinbefore. 
The compounds of the formula (1) wherein W is sulfur atom or sulfinyl, or 
R.sup.82 and R.sup.83 bind together with the nitrogen atom to which they 
bond to form thiomorpholino or 1-oxo-thiomorpholino can be converted into 
the corresponding compounds of the formula (1) wherein W is sulfinyl or 
sulfonyl, or R.sup.82 and R.sup.83 bind together with the nitrogen atom to 
which they bond to form 1-oxo-thiomorpholino or 1,1-dioxo-thiomorpholino, 
respectively, by oxidation thereof. 
The oxidation reaction is carried out in an appropriate solvent in the 
presence of an oxidizing agent. The solvent includes, for example, water, 
organic acids (e.g. formic acid, acetic acid, trifluoroacetic acid, etc.), 
alcohols (e.g. methanol, ethanol, etc.), halogenated hydrocarbons (e.g. 
chloroform, dichloromethane, etc.), or a mixture of these solvents. The 
oxidizing agent includes, for example, peracids (e.g. performic acid, 
peracetic acid, trifluoro-peracetic acid, perbenzoic acid, 
m-chloroperbenzoic acid, o-carboxy-perbenzoic acid, etc.), hydrogen 
peroxide, sodium metaperiodate, dichromic acid, dichromates (e.g. sodium 
dichromate, potassium dichromate, etc.), permanganic acid, permanganates 
(e.g. potassium permanganate, sodium permanganate, etc.), lead salts (e.g. 
lead tetraacetate, etc.), and the like. The oxidizing agent is usually 
used in an amount of at least 1 mole, preferably 1 to 2 moles, to 1 mole 
of the starting compound. Besides, in cases of the oxidation of converting 
the sulfur atom into sulfonyl group, the oxidizing agent is usually used 
at least 2 moles, preferably 2 to 4 moles, to 1 mole of the starting 
compound. The above reaction is usually carried out at a temperature of 
about -10.degree. C. to about 40.degree. C., preferably from about 
-10.degree. C. to room temperature, for about 1 to 100 hours. 
The compound (1) wherein R.sup.16 or R.sup.2 is a lower alkoxy can be 
converted into the correspond compound (1) wherein R.sup.16 or R.sup.2 is 
hydroxy by heating the compound in a mixture of an acid (e.g. hydrobromic 
acid, hydrochloric acid, etc.) and a solvent (e.g. water, methanol, 
ethanol, isopropyl alcohol, etc.) at 30.degree. to 150.degree. C., 
preferably at 50.degree. to 120.degree. C. 
Besides, the compound (1) wherein R.sup.16 or R.sup.2 is hydroxy can also 
be prepared by hydrolysis of the above compound (1) wherein R.sup.16 or 
R.sup.2 is a lower alkoxy. The hydrolysis can be carried out in an 
appropriate solvent in the presence of an acid. The solvent includes, for 
example, water, lower alcohols (e.g. methanol, ethanol, isopropyl alcohol, 
etc.), ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated 
hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, 
etc.), polar solvents (e.g. acetonitrile, etc.), or a mixture of these 
solvents. The acid includes, for example, mineral acids (e.g. hydrochloric 
acid, hydrobromic acid, etc.), Lewis acids (e.g. boron trifluoride, 
aluminum chloride, boron tribromide, etc.), iodides (e.g. sodium iodide, 
potassium iodide, etc.), or a mixture of the above Lewis acid and iodide. 
The reaction is usually carried out at a temperature of from room 
temperature to about 150.degree. C., preferably from room temperature to 
about 100 C., for about 0.5 to 30 hours. 
##STR58## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.62b, and W' are as defined above, 
R.sup.51a is hydroxyimino, and R.sup.66 is a lower alkanoyloxyimino. 
The reaction of the compound (1ii') and the compound (54) can be carried 
out under the same conditions as in the reaction of the compound (2) and 
the compound (3) in the above Reaction Scheme-1. 
The reaction of the compound (1ii') and the compound (55) can be carried 
out under the same conditions as in the reaction of the compound (1p) and 
the compound of the formula: (R.sup.7b).sub.2 O in the above Reaction 
Scheme-10. 
##STR59## 
wherein R.sup.1, R.sup.2, R.sup.3, W', R.sup.26, R.sup.14, R.sup.15, 
R.sup.62b, X and M are as defined above, R.sup.67 is methylidene, R.sup.68 
is a group of the formula: 
##STR60## 
and R.sup.69 is a group of the formula: 
##STR61## 
(R.sup.14 and R.sup.15 are as defined above), or 
##STR62## 
(R.sup.7D is an amino having optionally a substituent selected from a 
lower alkyl and a lower alkanoyl, R.sup.70 is a lower alkylsulfonyl, and 
W" is the same as the above W, provided that the number of the substituent 
in the groups --(CH.sub.2).sub.p -- and --CH.dbd.CH--(CH.sub.2).sub.q -- 
is 0 or 1. 
The reaction of converting the compound (1A) into the compound (1EE) is 
carried out in an appropriate solvent in the presence of a Wittig reagent 
and a basic compound. The Wittig reagent includes, for example, a 
phosphoric compound of the formula: 
EQU (R.sup.71).sub.3 P.sup.+ --CH.sub.2 --R.sup.72 !X.sup.- (A) 
wherein R.sup.71 is phenyl, R.sup.72 is hydrogen atom or a lower alkyl, and 
X is a halogen atom. The basic compound includes inorganic bases (e.g. 
metallic sodium, metallic potassium, sodium hydride, sodium amide, sodium 
hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, 
sodium hydrogen carbonate, etc.), metal alcoholates (e.g. sodium 
methylate, sodium ethylate, potassium t-butoxide, etc.), alkyl or aryl 
lithiums or lithium amides (e.g. methyl lithium, n-butyl lithium, phenyl 
lithium, lithium diisopropylamide, etc.), organic bases (e.g. pyridine, 
piperidine, quinoline, triethylamine, N,N-dimethylaniline, etc.). The 
solvent includes any solvent which does not affect on the reaction, for 
example, ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, monoglyme, 
diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, 
etc.), aliphatic hydrocarbons (e.g. n-hexane, heptane, cyclohexane, etc.), 
amines (e.g. pyridine, N,N-dimethylaniline, etc.), aprotic polar solvents 
(e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric 
triamide, etc.), alcohols (e.g. methanol, ethanol, isopropanol, etc.), and 
the like. The reaction is usually carried out at a temperature of about 
-80.degree. C. to about 150.degree. C., preferably about -80.degree. C. to 
about 120.degree. C., for about 0.5 to 15 hours. 
The reaction of converting the compound (1EE) into the compound (1LL) can 
be carried out under the same conditions as in the catalytically 
hydrogenation reaction for converting the compound (1A) into the compound 
(1C) in the above Reaction Scheme-15. 
The reaction of converting the compound (1EE) into the compound (1FF) is 
carried out under the same conditions as in the reaction of converting the 
compound (1) wherein W is sulfur atom or sulfinyl into the corresponding 
compound (1) wherein W is sulfinyl or sulfonyl respectively as described 
herebefore. 
The reaction of the compound (1FF) and the compound (25) can be carried out 
under the same conditions as in the reaction of the compound (7) and the 
compound (8) in the above Reaction Scheme-4. 
The reaction of converting the compound (1EE) into the compound (1E) can be 
carried out by firstly subjecting it to hydroboration reaction and then to 
oxidation. 
The hydroboration reaction is carried out in a solvent such as ethers (e.g. 
diethyl ether, tetrahydrofuran, dioxane, etc.) in the presence of a 
hydroborating agent at a temperature of from about 0.degree. C. to about 
50.degree. C., preferably about 0.degree. C. to room temperature, for 
about 1 to 10 hours. The hydroborating agent includes boron hydride 
compounds, for example, BH.sub.3.tetrahydrofuran, 
BH.sub.3.S(CH.sub.3).sub.2, BH.sub.2 Cl, (CH.sub.3).sub.2 
CHC(CH.sub.3).sub.2 BH.sub.2, (CH.sub.3).sub.2 CHCH(CH.sub.3)BH, 
##STR63## 
and the like. 
The subsequent oxidation is carried out in water in the presence of an 
oxidizing agent. The oxidizing agent includes, for example, alkaline 
hydrogen peroxides (e.g. hydrogen peroxide--sodium hydroxide, etc.), and 
air oxidation is also used. The reaction is usually carried out at a 
temperature of from room temperature to about 150.degree. C., preferably 
from room temperature to about 100.degree. C., for 0.5 to 7 hours. 
The hydroborating agent and the oxidizing agent are each used in an amount 
of at least 1 mole, preferably 1 to 2 mole, to 1 mole of the compound 
(1EE). 
The reaction of the compound (1E) and the compound (54) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
The reaction of the compound (1E) and the compound (55) can be carried out 
under the same conditions as in the reaction of the compound (1p) and the 
compound of the formula: (R.sup.7b).sub.2 O in the above Reaction 
Scheme-10. 
The reaction of the compound (1E) and the compound (56) can be carried out 
under the same conditions as in the reaction of the compound (7) and the 
compound (8) in the above Reaction Scheme-4. 
The reaction of the compound (1HH) and the compound (44) can be carried out 
under the same conditions as in the reaction of the compound (7) and the 
compound (8) in the above Reaction Scheme-4. 
The reducing reaction of the compound (1JJ) can be carried out under the 
same conditions as in the catalytic hydrogenation reaction for converting 
the compound (1A) into the compound (1C) in the above Reaction Scheme-15. 
The reaction of converting the compound (1EE) into the compound (1MM) can 
be carried out by reacting with an oxidizing agent in an appropriate 
solvent in the presence of a co-oxidizing agent. 
The solvent used for the reaction with an oxidizing agent includes, for 
example, pyridine, ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, 
etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), 
halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, 
chloroform, carbon tetrachloride, etc.), esters (e.g. ethyl acetate, 
etc.), water, alcohols (e.g. methanol, ethanol, isopropanol, t-butanole, 
etc.), or a mixture of these solvents. The co-oxidizing agent includes, 
for example, organic amine N-oxides (e.g. pyridine N-oxide, 
N-ethyldiisopropylamine N-oxide, N-methylmorpholine N-oxide, 
trimethylamine N-oxide, triethylamine N-oxide, etc.). The oxidizing agent 
includes, for example, osmium tetraoxide, and the like. The oxidizing 
agent is usually used in an amount of at least 1 mole, preferably 1 to 5 
moles, to 1 mole of the starting compound. The reaction is usually carried 
out at a temperature of from -20.degree. C. to 150.degree. C., preferably 
from room temperature to 100.degree. C., for about 1 to 10 hours. 
##STR64## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.27, W', M, and X are as defined 
above, R.sup.73 is an aminocarbonyl having optionally a lower alkyl 
substituent, R.sup.74 is an aminocarbonyloxy having optionally a lower 
alkyl substituent, R.sup.74' is a lower alkyl. 
The reaction of the compound (1A) and the compound (57) can be carried out 
under the same conditions as in the reaction of the compound (7) and the 
compound (8) in the above Reaction Scheme-4. 
The reaction of the compound (1A) and the compound (59) is carried out in 
an appropriate solvent in the presence of an acid. The solvent includes 
the same solvent as used in the reaction of the compound (7) and the 
compound (8) in the above Reaction Scheme-4. The acid includes, for 
example, mineral acids (e.g. hydrochloride acid, sulfuric acid, etc.), 
sulfonic acids (e.g. methanesulfonic acid, p-toluenesulfonic acid, etc.), 
alkanoic acids (e.g. trifluoroacetic acid, etc.), and the like. The 
compound (59) is used in an amount of at least 1 mole, preferably 1 to 5 
moles, to 1 mole of the compound (1A). The reaction is usually carried out 
at a temperature of from room temperature to about 150.degree. C., 
preferably from room temperature to about 100.degree. C., for about 1 to 7 
hours. 
The reaction of the compound (1A) and the compound (58) can be carried out 
under the same conditions as in the reaction of the compound (2b) and the 
compound (38) in the above Reaction Scheme-26. 
##STR65## 
wherein R.sup.1, R.sup.2, R.sup.3, X, and q are as defined above, and 
R.sup.75, R.sup.76 and R.sup.77 are each a lower alkyl, and the carbon 
atom in the formula: --(CH.sub.2).sub.q -- may be substituted by oxygen 
atom, sulfur atom, sulfinyl, sulfonyl, or a group of the formula: 
##STR66## 
(R.sup.13 is as defined above), and further the group: --(CH.sub.2).sub.q 
-- may optionally have 1 to 3 substituents selected from a lower alkyl 
having optionally a hydroxy substituent, a lower alkoxycarbonyl, carboxyl, 
hydroxy, oxo, a lower alkanoyloxy having optionally a halogen substituent, 
an amino-lower alkyl having optionally a substituent selected from a lower 
alkyl and a lower alkanoyl, a lower alkanoyloxy-substituted lower alkyl, a 
lower alkylsulfonyloxy-lower alkyl, an azido-lower alkyl, a group of the 
formula: 
##STR67## 
an aminocarbonyloxy having optionally a lower alkyl substituent, a lower 
alkoxy, a lower alkoxycarbonyl-substituted lower alkoxy, a 
carboxy-substituted lower alkoxy, an aminocarbonyl-lower alkoxy having 
optionally a lower alkyl substituent, an amino-lower-alkoxy having 
optionally a substituent selected from a lower alkyl and a lower alkanoyl, 
a phthalimido-substituted lower alkoxy, hydroxyimino, a lower 
alkanoyloxyimino, a lower alkylidene, a halogen atom, azido, sulfoxyimino, 
a group of the formula: 
##STR68## 
(R.sup.81 is hydrogen atom or a lower alkyl), hydrazino, pyrrolyl, an 
amino-lower alkanoyloxy having optionally a lower alkyl substituent, a 
group of the formula: 
##STR69## 
(A is as defined above, and R.sup.82 and R.sup.83 are the same or 
different and are each hydrogen atom, a lower alkyl, a 
carbamoyl-substituted lower alkyl, a hydroxy-substituted lower alkyl, or a 
pyridyl-lower alkyl, or R.sup.82 and R.sup.83 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), and a 
group of the formula: 
##STR70## 
(n is as defined above, and R.sup.14 and R.sup.15 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 1 to 2 substituents selected from a lower alkoxy, hydroxy and 
an amino having optionally a lower alkyl substituent, a phenyl-lower 
alkyl, a pyridyl-lower alkyl, a lower alkylsulfonyl, benzoyl, a lower 
alkoxycarbonyl, anilinocarbonyl, an aminocarbonyl having optionally a 
lower alkyl substituent, a cyano-substituted lower alkyl, a lower 
alkoxycarbonyl-substituted lower alkyl, a carbamoyl-substituted lower 
alkyl, a carboxy-substituted lower alkyl, a 
tetrahydropyranyloxy-substituted lower alkyl, a lower 
alkanoyloxy-substituted lower alkyl, a piperidinyl having optionally a 
phenyl-lower alkyl substituent on the piperidinyl ring, a 
halogen-substituted lower alkanoyl, an imidazolyl-substituted lower 
alkanoyl, an amino-lower alkanoyl having optionally a substituent selected 
from a lower alkyl and a lower alkoxycarbonyl, an aminocarbonyl-lower 
alkyl having optionally a lower alkyl substituent, or a phenyl-lower 
alkoxycarbonyl, or R.sup.14 and R.sup.15 may bind together with the 
nitrogen atom to which they bond to form a 5- or 6-membered saturated 
heterocyclic group with or without being intervened with nitrogen or 
oxygen atom, which heterocyclic group may optionally have a substituent 
selected from a lower alkyl, a phenyl-lower alkyl and a lower alkanoyl. 
The reaction of the compound (100) and the compound (60) is carried out in 
an appropriate solvent in an autoclave. The solvent includes any solvent 
as used in the reaction of the compound (7) and the compound (8) in the 
above Reaction Scheme-4. The reaction is usually carried out at a 
temperature of from room temperature to about 200.degree. C., preferably 
from room temperature to about 150.degree. C., for about 1 to 7 hours. 
The subsequent deamination reaction is carried out in an appropriate 
solvent in the presence of a basic compound. The solvent includes the same 
solvent as used in the above reaction of the compound (100) and the 
compound (60). The basic compound includes any basic compound as used in 
the reaction of converting the compound (1A) into the compound (1EE) in 
the above Reaction Scheme-38. The reaction is usually carried out at a 
temperature of from room temperature to about 150.degree. C., preferably 
from room temperature to about 100.degree. C., for about 1 to 10 hours. 
##STR71## 
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.14, M, and W' are as defined 
above, R.sup.78 is an oxiranyl-substituted lower alkyl, R.sup.79 is a 
lower alkoxy, or an amino having optionally a lower alkyl substituent, and 
R.sup.80 is a lower alkyl having 2 substituents selected from hydroxy, a 
lower alkoxy, and an amino having optionally a lower alkyl substituent. 
The reaction of the compound (1QQ) and the compound (61) can be carried out 
under the same conditions as in the reaction of the compound (7) and the 
compound (8) in the above Reaction Scheme-4. 
The reaction of the compound (1QQ) and the compound (62) can be carried out 
by firstly reacting them in trifluoroacetic acid at a temperature of about 
0.degree. C. to about 100.degree. C., preferably about 0.degree. C. to 
about 50.degree. C., for about 1 to 7 hours, followed by hydrolysis of the 
resultant. 
The hydrolysis is carried out in an appropriate solvent or without solvent 
in the presence of an acid or a basic compound. The solvent includes, for 
example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, 
etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. 
dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty 
acids (e.g. acetic acid, formic acid, etc.), or a mixture of these 
solvents. The acid includes, for example, mineral acids (e.g. hydrochloric 
acid, sulfuric acid, hydrobromic acid, etc.), organic acids (e.g. formic 
acid, acetic acid, aromatic sulfonic acid, etc.), and the like. The basic 
compound includes, for example, metal carbonates (e.g. sodium carbonate, 
potassium carbonate, etc.), metal hydroxides (e.g. sodium hydroxide, 
potassium hydroxide, calcium hydroxide, etc.). The reaction is usually 
carried out at a temperature of from room temperature to about 200.degree. 
C., preferably from room temperature to about 150.degree. C., for about 
0.5 to 25 hours. 
##STR72## 
wherein R.sup.1, R.sup.2, R.sup.3, and W' are as defined above, and 
R.sup.81 is hydroxyimino or a lower alkanoyloxyimino. 
The reaction of converting the compound (1SS) into the compound (1ll) is 
carried out by catalytically hydrogenating the compound (1SS) in an 
appropriate solvent in the presence of a catalyst. The solvent includes, 
for example, water, acetic acid, alcohols (e.g. methanol, ethanol, 
isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.,), ethers 
(e.g. diethylene glycol dimethyl ether, dioxane, tetrahydrofuran, diethyl 
ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic 
polar solvents (e.g. dimethylformamide, etc.), or a mixture of these 
solvents. The catalyst includes, for example, palladium, palladium black, 
palladium-carbon, platinum, platinum oxide, copper chromate, Raney nickel, 
and the like. The catalyst is usually used in an amount of 0.02 to 1 part 
by weight to 1 part by weight of the compound (1SS). The reaction is 
usually carried out at a temperature of from about -20.degree. C. to about 
100.degree. C., preferably about 0.degree. C. to about 70.degree. C., 
under a hydrogen atmospheric pressure of 1 to 10 atm. for about 0.5 to 20 
hours. 
Alternatively, the reducing reaction can also be carried out by using a 
hydrogenating reducing agent. The hydrogenating reducing agent includes, 
for example, lithium aluminum hydride, sodium boro hydride, diborane, etc. 
The reducing agent is usually used in an amount of at least one mole, 
preferably 1 to 10 moles, to 1 mole of the compound (1SS). The reaction is 
usually carried out in an appropriate solvent, such as water, lower 
alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. 
tetrahydrofuran, diethyl ether, diglyme, etc.), acetic acid, and the like, 
at a temperature of about 0.degree. C. to about 200.degree. C., preferably 
about 0.degree. C. to 170.degree. C., for about 10 minutes to about 10 
hours. When lithium aluminum hydride or diborane is used as the reducing 
agent, it is preferable to use an anhydrous solvent such as diethyl ether, 
tetrahydrofuran, diglyme, etc. 
##STR73## 
wherein R.sup.1, R.sup.2, R.sup.3, W', l, R.sup.14a are as defined above, 
and R.sup.83 is phenyl or a lower alkyl. 
The reaction of the compound (1K) and the compound (63) can be carried out 
under the same conditions as in the reaction of the compound (2b) and the 
compound (38) in the above Reaction Scheme-26. 
##STR74## 
wherein R.sup.1, R.sup.2, R.sup.3, W', l, R.sup.14a are as defined above. 
The reaction of the compound (1K) and the glyconitrile (64) can be carried 
out in an appropriate solvent. The solvent includes the same solvent as 
used in the reaction of the compound (7) and the compound (8) in the above 
Reaction Scheme-4. The reaction is usually carried out at a temperature of 
from about 0.degree. C. to about 150.degree. C., preferably about 
0.degree. C. to about 100.degree. C., for about 1 to 10 hours. The 
glyconitrile (64) is used in an amount of at least 1 mole, preferably 1 to 
2 moles, to 1 mole of the compound (1K). 
##STR75## 
wherein R.sup.1, R.sup.2, R.sup.3, W', l, R.sup.14a are as defined above, 
R.sup.84 is a lower alkoxycarbonyl-substituted lower alkyl, R.sup.85 is an 
amino having optionally a lower alkyl substituent, R.sup.86 is an 
aminocarbonyl-lower alkyl having optionally a lower alkyl substituent, and 
R.sup.87 is a carboxy-substituted lower alkyl. 
The reaction of the compound (1VV) and the compound (65) can be carried out 
under the same conditions as in the reaction of the compound (2) and the 
compound (3) in the above Reaction Scheme-1. 
The hydrolysis reaction of the compound (1VV) can be carried out under the 
same conditions as in the hydrolysis reaction of the compound (1QQ) and 
the compound (62) in the above Reaction Scheme-41. 
##STR76## 
wherein R.sup.1, R.sup.2, R.sup.3, W', l, X, and R.sup.14a are as defined 
above, R.sup.88 is a tetrahydropyranyloxy-substituted lower alkyl, 
R.sup.89 is a lower alkanoyloxy-substituted lower alkyl, R.sup.90 is a 
hydroxy-substituted lower alkyl, and R.sup.91 is a lower alkanoyl. 
The reaction of the compound (1YY) and the compound (66) can be carried out 
in a solvent such as acetic acid at a temperature of about 0.degree. C. to 
about 200.degree. C., preferably about 0.degree. C. to about 150.degree. 
C., for about 0.5 to 15 hours. 
The hydrolysis reaction of the compound (1YY) can be carried out under the 
same conditions as in the hydrolysis reaction of the compound (1QQ) and 
the compound (62) in the above Reaction Scheme-41, wherein a pyridinium 
salt (e.g. pyridinium p-toluenesulfonate, etc.) may be used as the acid. 
##STR77## 
wherein R.sup.1, R.sup.2, R.sup.3, W', and R.sup.26 are as defined above. 
The reaction of converting the compound (1A) into the compound (1bbb) can 
be carried out under the same conditions as in the reaction of converting 
the compound (1A) into the compound (1C) in the above Reaction Scheme-15. 
##STR78## 
wherein R.sup.1, R.sup.2, R.sup.3 and W' are as defined above, R.sup.92 
and R.sup.93 are each a lower alkoxy. 
The reaction of the compound (1ll) and the compound (68) is carried out in 
an appropriate solvent in the presence of an acid. The solvent includes, 
for example, water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), 
ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, 
tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty acids (e.g. 
acetic acid, formic acid, etc.), or a mixture of these solvents. The acid 
includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric 
acid, hydrobromic acid, etc.), organic acids (e.g. formic acid, acetic 
acid, aromatic sulfonic acids, etc.). The reaction is usually carried out 
at a temperature of from room temperature to about 200.degree. C., 
preferably from room temperature to about 150.degree. C., for about 0.5 to 
5 hours. The compound (68) is usually used in an amount of at least 1 
mole, preferably 1 to 2 moles, to 1 mole of the compound (1ll). 
##STR79## 
wherein R.sup.1, R.sup.2, R.sup.3, W', and R.sup.14a are as defined above, 
R.sup.94 is a halogen-substituted lower alkanoyl, R.sup.95 is an 
imidazolyl-substituted lower alkanoyl or an amino-lower alkanoyl having 
optionally a substituent selected from a lower alkyl and a lower 
alkoxycarbonyl, and R.sup.96 is imidazolyl, or an amino having optionally 
a substituent selected from a lower alkyl and a lower alkoxycarbonyl. 
The reaction of the compound (1ddd) and the compound (69) can be carried 
out under the same conditions as in the reaction of the compound (7) and 
the compound (8) in the above Reaction Scheme-4. 
##STR80## 
wherein R.sup.1, R.sup.2, R.sup.3, and W' are as defined above, R.sup.97 
is a lower alkanoyloxy having a halogen substituent, R.sup.98 is an amino 
having optionally a lower alkyl substituent, and R.sup.99 is an 
amino-lower alkanoyloxy having optionally a lower alkyl substituent. 
The reaction of the compound (1fff) and the compound (70) can be carried 
out under the same conditions as in the reaction of the compound (7) and 
the compound (8) in the above Reaction Scheme-4. 
##STR81## 
wherein R.sup.1, R.sup.2, R.sup.3, W', R.sup.82, and R.sup.83 are as 
defined above, R.sup.100 is a carboxy-substituted lower alkoxy, and 
R.sup.101 is a group of the formula: 
##STR82## 
(A, R.sup.82 and R.sup.83 are as defined above). 
The reaction of the compound (1hhh) and the compound (71) can be carried 
out under the same conditions as in the reaction of the compound (2) and 
the compound (3) in the above Reaction Scheme-1. 
##STR83## 
wherein R.sup.1, R.sup.2, R.sup.3, W", X, and R.sup.82 are as defined 
above, and R.sup.102 is hydrogen atom or a lower alkyl, provided that in 
the compound (1jjj), the groups of the formulae: --NH--R.sup.102 and --OH 
are substituted at the positions adjacent each other. 
The reaction of the compound (1jjj) and the compound (72) can be carried 
out under the same conditions as in the reaction of the compound (7) and 
the compound (8) in the above Reaction Scheme-4. 
##STR84## 
wherein R.sup.1, R.sup.2, R.sup.3, W', R.sup.26 and X are as defined 
above, and R.sup.104 is a lower alkyl. 
The reaction of the compound (1A) and the compound (73) can be carried out 
in an appropriate solvent. The solvent includes, for example, ethers 
(diethyl ether, dioxane, tetrahydrofuran, etc.), aromatic hydrocarbons 
(e.g. benzene, toluene, xylene, etc.), saturated hydrocarbons (e.g. 
pentane, hexane, heptane, cyclohexane, etc.), or a mixture of these 
solvents. The reaction is usually carried out at a temperature of from 
about -70.degree. C. to about 50.degree. C., preferably from about 
-30.degree. C. to room temperature, for about 1 to 6 hours. The compound 
(73) is used in an amount of at least 1 mole, preferably 1 to 5 moles, to 
1 mole of the compound (1A). 
##STR85## 
wherein R.sup.1, R.sup.2, R.sup.3, W', R.sup.58', R.sup.59', and A are as 
defined above, and R.sup.105 is a lower alkylsulfonyloxy. 
The reaction of the compound (1mmm) and the compound (74) can be carried 
out under the same conditions as in the reaction of the compound (7) and 
the compound (8) in the above Reaction Scheme-4. 
Among the active compounds (1) of this invention, 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, potassium 
hydroxide, lithium hydroxide, calcium hydroxide, etc., alkali metal 
carbonates or hydrogen carbonates such as sodium carbonate, sodium 
hydrogen carbonate, etc., alkali metal alcoholates such as sodium 
methylate, potassium ethylate, etc. Besides, among the active compounds 
(1) of this invention, the compounds having a basic group can easily be 
converted into acid addition salts thereof by treating with a 
pharmaceutically acceptable acid. The acid includes, for example, 
inorganic acids such as sulfuric acid, nitric acid, hydrochloric acid, 
hydrobromic acid, etc., and organic acids such as acetic acid, 
p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, 
fumaric acid, citric acid, succinic acid, benzoic acid, etc. These salts 
are useful as an active ingredient as like as the compounds (1) in the 
free form. 
In addition, the compounds (1) of this invention include stereoisomers and 
optical isomers, and these isomers are also useful as the active 
ingredient in this invention. 
The compounds of this invention thus obtained can easily be isolated and 
purified by conventional isolation methods. 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 and their salts of this invention are useful as a vasopressin 
antagonist and are used in the form of a conventional pharmaceutical 
preparation. The preparation is prepared by using conventional dilutents 
or carriers such as fillers, thickening agents, binders, wetting agents, 
disintegrators, surfactants, lubricants, and the like. The pharmaceutical 
preparations may be selected from various forms in accordance with the 
desired utilities, and the representative forms are tablets, pills, 
powders, solutions, suspensions, emulsions, granules, capsules, 
suppositories, injections (solutions, suspensions, etc.), and the like. In 
order to form in tablets, there are used 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, carboxymethyl cellulose, shellac, methyl 
cellulose, potassium phosphate, polyvinylpyrrolidone, etc.), 
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. starches, 
lactose, kaolin, bentonite, colloidal silicates, etc.), lubricants (e.g. 
purified talc, stearates, boric acid powder, polyethylene glycol, etc.), 
and the like. Moreover, the tablets may also be in the form of a 
conventional coated tablet, such as sugar-coated tablets, gelatin-coated 
tablets, enteric coated tablets, film coating tablets, or double or 
multiple layer tablets. In the preparation of pills, the carriers include 
vehicles (e.g. glucose, lactose, starches, cacao butter, hydrogenated 
vegetable oils, kaolin, talc, etc.), binders (e.g. gum arabic powder, 
tragacanth powder, gelatin, ethanol, etc.), disintegrators (e.g. 
laminaran, agar, etc.), and the like. In the preparation of suppositories, 
the carriers include, for example, polyethylene glycol, cacao butter, 
higher alcohols, higher alcohol esters, gelatin, semi-synthetic 
glycerides, and the like. Capsules can be prepared by charging a mixture 
of the compound of this invention with the above carriers into hard 
gelatin capsules or soft capsules in a usual manner. In the preparation of 
injections, the solutions, emulsions or suspensions are sterilized and are 
preferably made isotonic with the blood. In the preparation of these 
solutions, emulsions and suspensions, there are used conventional 
diluents, such as water, ethyl alcohol, macrogol (propylene glycol), 
ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, 
polyoxyethylene sorbitan fatty acid esters, and the like. In this case, 
the pharmaceutical preparations may also be incorporated with sodium 
chloride, glucose, or glycerin in an amount sufficient to make them 
isotonic, and may also be incorporated with conventional solubilizers, 
buffers, anesthetizing agents. Besides, the pharmaceutical preparations 
may optionally be incorporated with coloring agents, preservatives, 
perfumes, flavors, sweeting agents, and other medicaments, if required. 
The amount of the active compound of this invention (active ingredient) to 
be incorporated into the anti-vasopressin preparations is not specified 
but may be selected from a broad range, but usually, it is preferably in 
the range of 1 to 70% by weight, more preferably 5 to 50% by weight. 
The anti-vasopressin preparation of this invention may be administered in 
any method, and suitable method for administration may be determined in 
accordance with various forms of preparation, 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. 
The dosage of the anti-vasopressin agent of this 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 0.6 to 50 mg of the active compound of this 
invention per 1 kg of body weight of the patient per day. The active 
compound is preferably contained in an amount of 10 to 1000 mg per the 
dosage unit.