JPH11193276A - Substituted condensed heterocyclic compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound having excellent improving actions on insulin resistance, lowering actions on blood sugar, antiinflammatory actions, etc., slight adverse effects and high fat solubility, useful as a preventive and/or a therapeutic agent for diabetic, hyperlipemia, etc. SOLUTION: This compound is shown by formula I [R<1> is a group of formula II (R<4> is a phenyl substituted with 1-4 groups selected from a halogen, etc.; R<5> is H or the like; R<6> is H, a 1-6C alkyl or the like; D is an oxygen atom or the like; E is a nitrogen atom or the like) or the like; R<2> is H or the like; R<3> is a group of formula III or the like; A is a 1-6C alkylene; B is an oxygen atom or a sulfur atom; or the like] or its pharmacologically acceptable salt such as 4- 4-[5-(4-hydroxy-2,3,5-trimethylphenoxy)-3-methyl-3H-imidazo[4,5- b]pyridin-2-ylmethoxy]benzyl} benzyl}thiazolidine-2,4-dione. The compound of formula I is obtained by from a compound of formula IV (R<1a> is the same as R<1> ) and a compound of formula V [R<2a> is the same as R<2> and R<3a> is a group of formula VI (R<8> is triphenylmethyl) of the like].

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an excellent insulin resistance improving effect, a blood glucose lowering effect, an anti-inflammatory effect, an immunoregulatory effect, an aldose reductase inhibitory effect, a 5-lipoxygenase inhibitory effect, and a lipid peroxide production inhibitory effect. , PPAR activating action, anti-osteoporosis action, leukotriene antagonism,
The present invention relates to a substituted fused heterocyclic compound having a fat cell formation promoting action, a cancer cell growth suppressing action, and a calcium antagonistic action, or a pharmacologically acceptable salt thereof.

Furthermore, the present invention provides a disease improved by the above-mentioned effects, such as diabetes, which contains the above-mentioned substituted condensed heterocyclic compound or a pharmaceutically acceptable salt thereof as an active ingredient.
Hyperlipidemia, obesity, impaired glucose tolerance, hypertension, fatty liver, diabetic complications (eg, retinopathy, nephropathy, neurosis, cataract,
Coronary artery disease and the like. ), Arteriosclerosis, gestational diabetes, polycystic ovary syndrome, cardiovascular disease (eg, ischemic heart disease, etc.), cell damage caused by atherosclerosis or ischemic heart disease (eg, Gout, inflammatory diseases (eg, osteoarthritis, pain, fever, rheumatoid arthritis, inflammatory bowel disease, acne, sunburn, psoriasis, eczema, allergic disease, asthma, etc.). GI ulcer, cachexia, autoimmune disease, pancreatitis, etc.), cancer, osteoporosis, cataract and the like.

[0003] The present invention further provides a substituted condensed heterocyclic compound or a pharmaceutically acceptable salt thereof, an α-glucosidase inhibitor, an aldose reductase inhibitor, a biguanide agent, a statin compound, a squalene synthesis inhibitor, and a fibrate. The present invention relates to a pharmaceutical composition (particularly preferably a preventive and / or therapeutic agent for diabetes or diabetic complications) comprising a combination of at least one of a system compound, an LDL catabolism promoter and an angiotensin converting enzyme inhibitor.

[0004]

2. Description of the Related Art At present, it has been reported that thiazolidine compounds, oxazolidine compounds and the like are useful as preventive or therapeutic agents for various diseases such as diabetes and hyperlipidemia. For example, a number of thiazolidine compounds having a hypoglycemic effect have been reported in Chem. Pharm. Bull., 30, 3580-3.
600 (1982), Prog. Clin. Biol. Res., 265, 177-192 (1
988), Diabetes, 37 (11), 1549-1558 (1988), Arzneim.
-Forsch., 40 (1), 37-42 (1990), EP04441605
No. A and the like.

The effect of thiazolidine compounds on hyperlipidemia is described in Diabetes, 40 (12), 1669-1674 (1991), Am.
hysiol., 267 (1 Pt 1), E95-E101 (1994), Diabetes, 4
3 (10), 1203-1210 (1994), etc.

[0006] The effects of thiazolidine compounds on glucose intolerance and insulin resistance are described in Arzneim.-Forsch., 40 (2).
Pt 1), 156-162 (1990), Metabolism, 40 (10), 1025-
1230 (1991), Diabetes, 43 (2), 204-211 (1994).

[0007] In recent years, a normal human having insulin resistance develops diabetes without impaired glucose tolerance and a drug for improving insulin resistance has been used as a preventive agent for the onset of diabetes in normal humans as described above. N.En also be useful
gl.J.Med., 331 (18), 1226-1227 (1994).

The effect of thiazolidine compounds on hypertension is described in Metabolism, 42 (1), 75-80 (1993), Am. J. Physi.
ol., 265 (4 Pt 2), R726-R732 (1993), Diabetes, 43
(2), 204-211 (1994).

The effect of thiazolidine compounds on coronary artery disease has been reported by Am. J. Physiol., 265 (4 Pt 2), R726-R732 (1
993), Hypertension, 24 (2), 170-175 (1994).

The effect of thiazolidine compounds on arteriosclerosis has been reported by Am. J. Physiol., 265 (4Pt 2), R726-R732 (19).
93).

The action of thiazolidine compounds on cachexia is described in Endocrinology, 135 (5), 2279-2282 (1994), Endr.
ocrinology, 136 (4), 1474-1481 (1995) and the like.

Further, among the thiazolidine compounds having a hypoglycemic effect, compounds having a heterocyclic group are described in WO9.
2 / 07839A, WO92 / 07850A, EP
No. 0745600A discloses an oxazolidine-2,4-dione compound having a hypoglycemic effect, which is described in WO92 / 025.
No. 20A and the like.

A compound having a blood sugar lowering effect and having a 3,5-dioxooxadiazolidine-2-ylmethylphenyl group or a compound having an N-hydroxyureido group is disclosed in WO 92 / 03425A.

[0014] EP 0067398 A discloses that
-{4- [5- (3,5-Di-tert-butyl-4-hydroxyphenylthio) -3-methyl-3H-imidazo [4,5-b] pyridin-2-ylmethoxy] benzyl} thiazolidine-2 , 4-dione are disclosed only as exemplary compounds.

[0015]

SUMMARY OF THE INVENTION The present inventors have studied the synthesis of a series of substituted condensed heterocyclic compounds and their pharmacological activities over many years, and as a result, have found that substituted condensed heterocyclic compounds having a novel structure can be obtained. Excellent, insulin resistance improving action, blood glucose lowering action, anti-inflammatory action, immunomodulatory action, aldose reductase inhibitory action, 5-lipoxygenase inhibitory action, lipid peroxide production inhibitory action, PPAR activating action,
It has anti-osteoporosis action, leukotriene antagonism, adipocyte-promoting action, cancer cell growth inhibitory action, calcium antagonism, fewer side effects, and furthermore, it is found that it has a characteristic of high fat solubility. The present invention has been completed.

[0016] Another object of the present invention is to provide a disease improved by the above-mentioned effects, for example, diabetes, hyperlipidemia, obesity, which contains the above-mentioned substituted condensed heterocyclic compound or a pharmaceutically acceptable salt thereof as an active ingredient. Disease, impaired glucose tolerance, hypertension, fatty liver, diabetic complications (eg, retinopathy, nephropathy, neuropathy, cataract, coronary artery disease, etc.), arteriosclerosis, gestational diabetes mellitus, polycystic ovary syndrome, heart Vascular disease (eg, ischemic heart disease, etc.), cell damage caused by atherosclerosis or ischemic heart disease (eg, brain damage caused by stroke, etc.), gout, Inflammatory diseases (eg, osteoarthritis, pain, fever, rheumatoid arthritis,
Inflammatory enteritis, acne, sunburn, psoriasis, eczema, allergic diseases, asthma, GI ulcer, cachexia, autoimmune diseases, pancreatitis and the like. ), Cancer, osteoporosis, cataract and the like.

Still another object of the present invention is to provide the above-mentioned substituted fused heterocyclic compound or a pharmaceutically acceptable salt thereof, and α-
Pharmaceutical compositions comprising a combination of at least one of a glucosidase inhibitor, an aldose reductase inhibitor, a biguanide, a statin compound, a squalene synthesis inhibitor, a fibrate compound, an LDL catabolism promoter and an angiotensin converting enzyme inhibitor (particularly preferred) Is a prophylactic and / or therapeutic agent for diabetes or diabetic complications).

[0018]

The substituted fused heterocyclic compound of the present invention has the general formula (I).

[0019]

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In the above formula, R ¹ is a general formula

[0021]

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Or the general formula

[0023]

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Wherein R ⁴ is a phenyl group substituted with 1 to 5 groups selected from a substituent group α or a substituent group α
Represents a pyridyl group which may be substituted by 1 to 4 groups selected from: R ⁵ represents a hydrogen atom or a group selected from the substituent group α; R ⁶ represents a hydrogen atom, C ₁ -C 1 to 3 C ₆ -C ₁₀ aryl groups which may be substituted with ₆ alkyl groups, groups selected from substituent group β or 1 to 3 groups which may be substituted with groups selected from substituent group β shows the C ₇ -C ₁₆ aralkyl group, D is represents an oxygen atom or a sulfur atom, E is, a group or a nitrogen atom having a CH. R ² represents a hydrogen atom or a group selected from substituent group α, and R ³ represents a group represented by the formula

[0025]

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Wherein A is a C ₁ -C ₆ alkylene group, and B is an oxygen atom or a sulfur atom.
However, 5- {4- [5- (3,5-di-t-butyl-4)
-Hydroxyphenylthio) -3-methyl-3H-imidazo [4,5-b] pyridin-2-ylmethoxy] benzyl {thiazolidine-2,4-dione is excluded. <Substituent group α> Halogen atom; hydroxy group; C ₁ -C
₆ alkyl groups; halogeno C ₁ -C ₆ alkyl groups; C _1-
A C ₆ alkoxy group; a C ₁ -C ₆ alkylthio group; an amino group which may be substituted with a group selected from the substituent group γ; 1 to 3 substituents which may be substituted with a group selected from the substituent group β , C ₃ -C ₁₀ cycloalkyl, C ₆ -C ₁₀ aryl,
C ₇ -C ₁₆ aralkyl, C ₆ -C ₁₀ aryloxy, C
₇ -C ₁₆ aralkyloxy and C ₆ -C ₁₀ arylthio group; 5 or 6-membered aromatic heterocyclic containing nitrogen atom; C ₁ -C ₇ aliphatic acyloxy group; a nitrogen atom 4 to 7-membered saturated heterocyclic group containing A ring group; a nitro group; and a cyano group. <Substituent group β> halogen atom, hydroxy group, C ₁ -C
₆ alkyl group, halogeno C ₁ -C ₆ alkyl group, C _1-
A C ₆ alkoxy group, an amino group optionally substituted with a group selected from the substituent group γ, a C ₆ -C ₁₀ aryl group, and a nitro group. <Substituent group γ> C ₁ -C ₁₀ alkyl group, optionally substituted C ₆ -C ₁₀ aryl and C ₇ -C ₁₆ aralkyl group, and acyl group (the acyl group is a C ₁ -C ₇ aliphatic Aromatic acyl group and optionally substituted C ₇ -C ₁₁ aromatic acyl, C ₈ -C ₁₂ araliphatic acyl, C ₄ -C ₁₁ cycloalkylcarbonyl and 5- to 6-membered aromatic heterocycle containing nitrogen atom Represents a carbonyl group.).

In the above, the "halogen atom" in the definition of the substituent groups α and β is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and is preferably a fluorine atom or a chlorine atom.

In the above, the term "C ₁ -C ₆ alkyl group" in the definition of R ^{6 and the} substituent groups α and β represents a straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms. , Ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl,
Isopentyl, 2-methylbutyl, neopentyl, 1-
Ethylpropyl, hexyl, 4-methylpentyl, 3-
Methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2, 3-dimethylbutyl, 2-ethylbutyl group wherein the R ^6, preferably a C ₁ -C ₄ alkyl group, more preferably C ₁ -C
_{It is a 2-} alkyl group, particularly preferably a methyl group. In the substituent group α, a methyl or t-butyl group is preferable, and in the substituent group β, a methyl, ethyl or t-butyl group is preferable.

In the above, the “halogeno C ₁ -C ₆ alkyl group” in the definition of the substituent groups α and β is the above-mentioned C ₁ -C ₆ alkyl group.
Represents a group in which 1 to 3 of the above halogen atoms are bonded to a -C ₆ alkyl group;
2,2-trichloroethyl, 2,2,2-trifluoroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2-iodoethyl, 3-chloropropyl, 4-fluorobutyl, 6-iodohexyl, , 2
-Dibromoethyl, preferably halogeno C ₁ -C
_{It is a 2-} alkyl group, particularly preferably a trifluoromethyl group.

In the above, the “C ₁ -C ₆ alkoxy group” in the definition of the substituent groups α and β is the above-mentioned C ₁ -C ₆
An alkyl group represents a group bonded to an oxygen atom, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, pentoxy, isopentoxy, 2-methylbutoxy, neopentoxy, 1-ethylpropoxy , Hexyloxy,
4-methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 3,3-dimethylbutoxy, 2,2-
Dimethylbutoxy, 1,1-dimethylbutoxy, 1,2
-Dimethylbutoxy, 1,3-dimethylbutoxy, 2,
3-dimethylbutoxy, 2-ethylbutoxy group,
Preferably a C ₁ -C ₂ alkoxy group, particularly preferably a methoxy group.

In the above, the "C ₁ -C ₆ alkylthio group" in the definition of the substituent group α indicates a group in which the above C ₁ -C ₆ alkyl group is bonded to a sulfur atom, for example, methylthio, ethylthio, propylthio, Isopropylthio,
Butylthio, isobutylthio, s-butylthio, t-butylthio, pentylthio, isopentylthio, 2-methylbutylthio, neopentylthio, 1-ethylpropylthio, hexylthio, 4-methylpentylthio, 3-methylpentylthio, -Methylpentylthio, 1-methylpentylthio, 3,3-dimethylbutylthio, 2,2
-Dimethylbutylthio, 1,1-dimethylbutylthio,
1,2-dimethylbutylthio, 1,3-dimethylbutylthio, 2,3-dimethylbutylthio, 2-ethylbutylthio, preferably C ₁ -C ₂ alkylthio, and particularly preferably It is a methylthio group.

In the above, the “amino group optionally substituted by a group selected from the substituent group γ” in the definition of the substituent groups α and β is a C ₁ -C ₁₀ alkyl group, which may be substituted. C ₆ -C ₁₀ aryl and C ₇ -C ₁₆ aralkyl groups
(The substituent is one to three selected from the group consisting of halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy and C ₁ -C ₆ alkylthio. And an acyl group (C ₁
A C ₇ aliphatic acyl group, and halogen, hydroxy,
C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C
₁ -C ₆ alkoxy and C ₁ -C ₆ with a group selected from the group consisting of alkylthio 1 to may be three substituents,
C ₇ -C ₁₁ aromatic acyl, showing a C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ cycloalkylcarbonyl and 5 to 6 membered aromatic heterocyclic carbonyl group containing a nitrogen atom. ) Represents an amino group which may be substituted with one or two identical or different groups selected from the substituent group γ.

[0033] In the above, "C ₁ -C ₁₀ alkyl group" in the definition of Substituent group γ represents a linear or branched chain alkyl group having 1 to 10 carbon atoms, for example, the C ₁ -C
₆ alkyl, heptyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1-propylbutyl, 4,4
-Dimethylpentyl, octyl, 1-methylheptyl,
2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl, 6-methylheptyl,
1-propylpentyl, 2-ethylhexyl, 5,5-
Dimethylhexyl, nonyl, 3-methyloctyl, 4-
Methyloctyl, 5-methyloctyl, 6-methyloctyl, 1-propylhexyl, 2-ethylheptyl,
6,6-dimethylheptyl, decyl, 1-methylnonyl, 3-methylnonyl, 8-methylnonyl, 3-ethyloctyl, 3,7-dimethyloctyl, 7,7-dimethyloctyl, preferably C ₁ -C _{It is an 8} alkyl group, particularly preferably a methyl, butyl, isobutyl, pentyl, hexyl, heptyl or octyl group.

[0034] In the above, C ₆ -C ₁₀ in the "optionally substituted C ₆ -C ₁₀ aryl" in the definition of Substituent group γ
The aryl moiety represents an aromatic hydrocarbon group having 6 to 10 carbon atoms, and is, for example, a phenyl, indenyl or naphthyl group, preferably a phenyl group.

[0035] In the above, C ₇ -C of the "optionally substituted C ₇ -C ₁₆ aralkyl" in the definition of Substituent group γ
_{The 16} aralkyl moiety represents a group in which the C ₆ -C ₁₀ aryl group is bonded to the C ₁ -C ₆ alkyl group, for example, benzyl, naphthylmethyl, indenylmethyl, diphenylmethyl, 1-phenethyl, 2-phenethyl , 1-naphthylethyl, 2-naphthylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl,
-Naphthylpropyl, 2-naphthylpropyl, 3-naphthylpropyl, 1-phenylbutyl, 2-phenylbutyl, 3-phenylbutyl, 4-phenylbutyl, 1-naphthylbutyl, 2-naphthylbutyl, 3-naphthylbutyl, 4 -Naphthylbutyl, 5-phenylpentyl, 5-
A naphthylpentyl, 6-phenylhexyl, 6-naphthylhexyl group, preferably a benzyl group.

In the above, the “C ₁ -C ₇ aliphatic acyl group” in the definition of the substituent group γ means that a hydrogen atom or a saturated or unsaturated C ₁ -C ₆ chain hydrocarbon group is bonded to a carbonyl group. Represents a group, for example, formyl, acetyl,
Propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, acryloyl, methacryloyl, crotonoyl group, preferably acetyl, propionyl or pivaloyl group,
Particularly preferred is an acetyl group.

[0037] In the above, C ₇ of the "optionally substituted C ₇ -C ₁₁ aromatic acyl" in the definition of Substituent group gamma -
The C ₁₁ aromatic acyl moiety represents a group in which a C ₆ -C ₁₀ aryl group is bonded to a carbonyl group.
-Indanecarbonyl, 2-indanecarbonyl, 1-
Or a 2-naphthoyl group, preferably a benzoyl or naphthoyl group.

In the above, the C ₈ -C ₁₂ araliphatic acyl which may be substituted in the definition of the substituent group γ
₈ -C ₁₂ aromatic aliphatic acyl moiety, a phenyl group C ₂ -
And a group bonded to a C ₆ aliphatic acyl group, such as phenylacetyl, 3-phenylpropionyl, 4-phenylbutyryl, 5-phenylpentanoyl, or 6-phenylhexanoyl, Group.

[0039] In the above, C ₄ -C ₁₁ cycloalkylcarbonyl part of the "optionally substituted C ₄ -C ₁₁ cycloalkylcarbonyl" in the definition of Substituent group γ is, C
₃ -C indicates ₁₀ cycloalkyl group (condensed have 3 to 10-membered may be saturated cyclic hydrocarbon groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, and adamantyl group, suitably is C ₃ -C ₆ cycloalkyl group.)
Shows a group bonded to a carbonyl group, for example, cyclopropanoyl, cyclobutyryl, cyclopentanoyl, cyclohexanoyl, cycloheptylcarbonyl, norbornylcarbonyl, adamantylcarbonyl group,
It is preferably a C ₄ -C ₇ cycloalkylcarbonyl group, particularly preferably a cyclopentanoyl or cyclohexanoyl group.

In the above, the 5- or 6-membered aromatic heterocyclic carbonyl moiety containing a nitrogen atom of the “5- to 6-membered aromatic heterocyclic carbonyl containing an optionally substituted nitrogen atom” in the definition of the substituent group γ is A 5- or 6-membered aromatic heterocycle containing at least one nitrogen atom and optionally containing a heteroatom selected from the group of heteroatoms consisting of a nitrogen atom, an oxygen atom and a sulfur atom (for example, pyrrolyl, imidazolyl, pyrazolyl, Triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazolyl, oxazolyl, oxadiazolyl, and thiadiazolyl groups) to which a carbonyl group is bonded.
Pyrazolylcarbonyl, triazolylcarbonyl, tetrazolylcarbonyl, nicotinoyl, isonicotinoyl, pyrazinylcarbonyl, pyrimidinylcarbonyl,
Pyridazinylcarbonyl, thiazolylcarbonyl, oxazolylcarbonyl, oxadiazolylcarbonyl, thiadiazolylcarbonyl group, preferably pyridylcarbonyl group, particularly preferably nicotinoyl or isonicotinoyl group .

The “amino group optionally substituted with a group selected from the substituent group γ” in the definition of the substituent groups α and β is, for example, amino; methylamino, ethylamino, propylamino, isopropyl Amino, butylamino, s-butylamino, t-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, N-ethyl-N-methylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, phenylamino , 2-, 3- or 4-fluorophenylamino, 2-, 3- or 4-chlorophenylamino, 2-, 3- or 4-bromophenylamino, 2,3-difluorophenylamino, 2,4-difluorophenyl Amino, 2,4-dichlorophenylamino, 1- or - indenyl amino, 1- or 2-naphthylamino, diphenylamino, benzylamino, 2-, 3- or 4-fluorobenzylamino, 2-, 3- or 4-chlorobenzyl-amino, 2
-, 3- or 4-bromobenzylamino, 2,3-
Difluorobenzylamino, 2,4-difluorobenzylamino, 2,4-dichlorobenzylamino, 1- or 2-naphthylmethylamino, 1-indenylmethylamino, 1- or 2-phenethylamino, 1-2
-Or 3-phenylpropylamino, 4-phenylbutylamino, 1-phenylbutylamino, 5-phenylpentylamino, 6-phenylhexylamino, dibenzylamino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyryl Amino, valerylamino, isovalerylamino, pivaloylamino, hexanoylamino, acryloylamino, methacryloylamino, crotoylamino, benzoylamino, 1-indanecarbonylamino, 1- or 2
-Naphthoylamino, 2-, 3- or 4-fluorobenzoylamino, 2-, 3- or 4-chlorobenzoylamino, 2-, 3- or 4-bromobenzoylamino, 2,3-difluorobenzoylamino, ,
4-difluorobenzoylamino, 2,4-dichlorobenzoylamino, 2,6-diisopropylbenzoylamino, 4-trifluoromethylbenzoylamino, 4-
Hydroxy-3,5-dimethylbenzoylamino, 4-
Hydroxy-3,5-di-t-butylbenzoylamino, 1-indanecarbonylamino, 1- or 2-
Naphthoylamino, phenylacetylamino, 3-phenylpropionylamino, 4-phenylbutyrylamino, 5-phenylpentanoylamino, 6-phenylhexanoylamino, 2-, 3- or 4-fluorophenylacetylamino, 2- 2,3- or 4-chlorophenylacetylamino, 2-, 3- or 4-bromophenylacetylamino, 2,3-difluorophenylacetylamino, 2,4-difluorophenylacetylamino, 2,4-dichlorophenylacetylamino,
Cyclopropionylamino, cyclobutyrylamino, cyclopentanoylamino, cyclohexanoylamino,
Pyrrolylcarbonylamino, imidazolylcarbonylamino, pyrazolylcarbonylamino, triazolylcarbonylamino, tetrazolylcarbonylamino, nicotinoylamino, isonicotinoylamino, pyrazinylcarbonylamino, pyrimidinylcarbonylamino, pyridazinylcarbonylamino , Thiazolylcarbonylamino, oxazolylcarbonylamino, oxadiazolylcarbonylamino, thiadiazolylcarbonylamino,
N, N-diacetylamino, N-formyl-N-hexylamino, N-acetyl-N-methylamino, N-acetyl-N-ethylamino, N-acetyl-N-propylamino, N-acetyl-N-butyl Amino, N-acetyl-N-pentylamino, N-acetyl-N-hexylamino, N-benzoyl-N-methylamino, N-benzoyl-N-ethylamino, N-benzoyl-N-propylamino, N-benzoyl -N-butylamino, N-
Benzoyl-N-pentylamino, N-benzoyl-N
-Hexylamino, N-benzoyl-N-phenylamino, N-benzyl-N-benzoylamino, N-4-trifluoromethylbenzyl-N-2,4-difluorobenzoylamino, N-2,4-difluorobenzyl- N
-Nicotinoylamino, N-3-chlorobenzoyl-N
-Methylamino, N-3-chlorobenzoyl-N-hexylamino, N-3-chlorobenzyl-N-acetylamino, N-2,4-difluorobenzoyl-N-hexylamino, N-2,4-difluorobenzoyl -N-phenylamino, N-2,4-difluorobenzoyl-N
-Phenylamino, N-4-trifluoromethylbenzoyl-N-butylamino, N-3,5-di-t-butyl-4-hydroxybenzoyl-N-hexylamino, N
-Hexyl-N-1-naphthoylamino, N-hexyl-N-2-naphthoylamino, N-hexyl-N-phenylacetylamino, N-isobutyl-N-cycloheptanoylamino, N-butyl-N- Nicotinoylamino, N-hexyl-N-nicotinoylamino, N-isonicotinoyl-N-hexylamino group, preferably an amino group, an amino group substituted by one or two groups (the substituent is Or the same or different and is a group selected from the group consisting of a C ₁ -C ₁₀ alkyl group and an optionally substituted C ₆ -C ₁₀ aryl and C ₇ -C ₁₆ aralkyl group.) An acylamino group which may be substituted with a group selected from group γ (the acylamino group indicates an amino group substituted with the above-mentioned acyl group), more preferably an amino group, Roh or di -C ₁ -C ₁₀ alkyl amino group or a C ₁ -C ₁₀ alkyl or optionally substituted C ₇ -C be ₁₆ aralkyl which may be substituted with an acylamino group, further preferably more, amino A group, a mono- or di-C ₁ -C ₁₀ alkylamino group or an optionally substituted C ₇ -C ₁₁ aromatic acylamino, C ₄
—C ₁₁ cycloalkylcarbonylamino or a 5- to 6-membered aromatic heterocyclic carbonylamino group containing a nitrogen atom, particularly preferably amino, dimethylamino, hexylamino, acetylamino, benzoylamino, 3-chlorobenzoylamino , 2,4-difluorobenzoylamino, 4-hydroxy-3,5-di-t-butylbenzoylamino, naphthoylamino, cyclopentanoylamino, cyclohexanoylamino, nicotinoylamino, isonicotinoylamino, N- An acetyl-N-hexylamino or adamantylcarbonylamino group.

In the above, the C ₃ -C ₁₀ cycloalkyl of the “C ₃ -C ₁₀ cycloalkyl group optionally substituted by 1 to 3 groups selected from the substituent group β” in the definition of the substituent group α. The moiety has the same meaning as described above, and is preferably a C ₃ -C ₁₀ cycloalkyl group optionally substituted with one group selected from the substituent group β, more preferably,
A group selected from the group consisting of halogen, hydroxy, C ₁ -C ₆ alkyl and halogeno C ₁ -C ₆ alkyl;
An optionally substituted C ₃ -C ₁₀ cycloalkyl group, more preferably fluorine, chlorine, hydroxy, methyl,
Ethyl, t-butyl, trifluoromethyl, methoxy,
It is an adamantyl group which may be substituted with one amino, methylamino or dimethylamino, and particularly preferably an adamantyl group.

In the above, “C ₆ -C ₁₀ aryl group which may be substituted by 1 to 3 groups selected from substituent group β” and substituent group β in the definition of R ⁶ and substituent group α
C ₆ -C ₁₀ of the "C ₆ -C ₁₀ aryl group" in the definition of
The aryl moiety has the same meaning as described above, and R ⁶ is preferably a group selected from the group consisting of halogen, hydroxy, C ₁ -C ₆ alkyl and halogeno C ₁ -C ₆ alkyl by 1 to 3 An optionally substituted phenyl group, particularly preferably an optionally substituted phenyl group selected from the group consisting of fluorine, chlorine, hydroxy, methyl, ethyl and trifluoromethyl groups. .
In the substituent group α, it is preferably a C ₆ -C ₁₀ aryl group optionally substituted by one group selected from the substituent group β, more preferably halogen, hydroxy, C ₁ -C
₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆
A C ₆ -C ₁₀ aryl group optionally substituted with one or more aminos which may be substituted with an alkoxy or a group selected from a substituent group γ, more preferably fluorine, chlorine, hydroxy, methyl, ethyl , T-butyl, trifluoromethyl, methoxy, amino, methylamino or dimethylamino, and is particularly preferably a phenyl group, particularly preferably a phenyl or 4-hydroxyphenyl group.
In the substituent group β, a phenyl group is preferable.

[0044] In the above, C ₇ -C ₁₆ of the "optionally be 1 to 3 substituted with a group selected from the substituent group beta C ₇ -C ₁₆ aralkyl group" in the definition of R ⁶ and Substituent group α
The aralkyl moiety has the same meaning as described above, and R ⁶ is preferably halogen, hydroxy, C ₁ -C ₆
A benzyl group which may be substituted by 1 to 3 groups selected from the group consisting of alkyl and halogeno C ₁ -C ₆ alkyl, particularly preferably fluorine, chlorine, hydroxy, methyl, ethyl and trifluoromethyl. A benzyl group which may be substituted with a group selected from the group consisting of: In substituent group α, it is preferably a C ₇ -C ₁₆ aralkyl group which may be substituted by one group selected from substituent group β, more preferably halogen, hydroxy, C ₁ -C
₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆
A benzyl group which may be substituted with one amino which may be substituted with an alkoxy or a group selected from a substituent group γ, more preferably fluorine, chlorine, hydroxy, methyl,
Ethyl, t-butyl, trifluoromethyl, methoxy,
A benzyl group which may be substituted by one amino, methylamino or dimethylamino group, particularly preferably a benzyl group.

In the above, the C ₆ -C ₁₀ aryloxy of the “C ₆ -C ₁₀ aryloxy group optionally substituted by 1 to 3 groups selected from the substituent group β” in the definition of the substituent group α. The moiety represents a group in which the C ₆ -C ₁₀ aryl is bonded to an oxygen atom, for example, phenoxy, 1-indenyloxy, 2-indenyloxy, 3-indenyloxy, 1-naphthyloxy, 2-naphthyl An oxy group, preferably a phenoxy group.

In the above, the C ₇ -C ₁₆ aralkyloxy of the “C ₇ -C ₁₆ aralkyloxy group which may be substituted by 1 to 3 groups selected from the substituent group β” in the definition of the substituent group α. moiety refers to the group which the C ₇ -C ₁₆ aralkyl groups linked to an oxygen atom, for example, benzyloxy, naphthylmethoxy, indenyl methoxy, diphenylmethoxy, 1-phenethyloxy, 2-phenethyloxy, 1-Nafuchiruetokishi , 2-naphthylethoxy,
1-phenylpropoxy, 2-phenylpropoxy, 3
-Phenylpropoxy, 1-naphthylpropoxy, 2-
Naphthylpropoxy, 3-naphthylpropoxy, 1-phenylbutoxy, 2-phenylbutoxy, 3-phenylbutoxy, 4-phenylbutoxy, 1-naphthylbutoxy, 2-naphthylbutoxy, 3-naphthylbutoxy, 4
-Naphthylbutoxy, 5-phenylpentyloxy, 5
-Naphthylpentyloxy, 6-phenylhexyloxy, 6-naphthylhexyloxy, preferably benzyloxy.

[0047] In the above, C ₆ -C ₁₀ arylthio moiety of the "optionally substituted 1 to 3 groups selected from substituent group β C ₆ -C ₁₀ arylthio group" in the definition of Substituent group α is A group in which the C ₆ -C ₁₀ aryl group is bonded to a sulfur atom, for example, phenylthio, 1-indenylthio, 2-indenylthio, 3-indenylthio,
It is a 1-naphthylthio or 2-naphthylthio group, preferably a phenylthio group.

In the above, the “C ₁ -C ₇ aliphatic acyloxy group” in the definition of the substituent group α is the above-mentioned C ₁ -C 7
7 represents a group in which an oxygen atom is bonded to an aliphatic acyl group. , A crotoyloxy group, preferably an acetoxy group.

In the above, the “4- to 7-membered saturated heterocyclic group containing a nitrogen atom” in the definition of the substituent group α includes a heteroatom containing at least one nitrogen atom and further comprising a nitrogen atom, an oxygen atom and a sulfur atom. Represents a 4- to 7-membered saturated heterocyclic group which may contain a hetero atom selected from the group of atoms, for example, azetidinyl, pyrrolidinyl, imidazolidinyl, thiazolidinyl, pyrazolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl,
A homopiperazinyl group, preferably, pyrrolidinyl,
It is a piperidinyl or morpholinyl group, particularly preferably a pyrrolidin-1-yl, piperidin-1-yl or morpholin-4-yl group.

In the above, the “5- to 6-membered aromatic heterocyclic group containing a nitrogen atom” in the definition of the substituent group α has the same meaning as described above, and is preferably imidazolyl,
A tetrazolyl or pyridinyl group, particularly preferably,
A pyridin-2-yl or pyridin-3-yl group.

In the above, in the definition of R ⁴ , “a phenyl group substituted by 1 to 5 groups selected from the substituent group α” is a halogen atom; a hydroxy group; a C ₁ -C ₆
Alkyl group; halogeno C ₁ -C ₆ alkyl group; C ₁ -C
_{A 6-} alkoxy group; a C ₁ -C ₆ alkylthio group; an amino group which may be substituted with a group selected from substituent group γ; and 1 to 3 groups which may be substituted with a group selected from substituent group β. C ₃ -C ₁₀ cycloalkyl, C ₆ -C ₁₀ aryl,
C ₇ -C ₁₆ aralkyl, C ₆ -C ₁₀ aryloxy, C
₇ -C ₁₆ aralkyloxy and C ₆ -C ₁₀ arylthio group; 5 or 6-membered aromatic heterocyclic containing nitrogen atom; C ₁ -C ₇ aliphatic acyloxy group; a nitrogen atom 4 to 7-membered saturated heterocyclic group containing A phenyl group substituted by 1 to 5 groups selected from the group consisting of a ring group; a nitro group; and a cyano group, for example, 2-, 3- or 4-fluorophenyl, 2-, 3- or 4 -Chlorophenyl, 2
-, 3- or 4-bromophenyl, 2-, 3- or 4-iodophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, pentafluorophenyl, 3,5-dichlorophenyl, 2-, 3- Or 4-hydroxyphenyl, 3,5-dihydroxyphenyl, 2-, 3- or 4-methylphenyl, 2-, 3
-Or 4-ethylphenyl, 2-, 3- or 4
-Propylphenyl, 2-, 3- or 4-isopropylphenyl, 2-, 3- or 4-butylphenyl, 2-, 3- or 4-s-butylphenyl, 2
-, 3- or 4-t-butylphenyl, 2-, 3-
Or 4-trifluoromethylphenyl, 2-, 3-
Or 4-methoxyphenyl, 2-, 3- or 4
-Ethoxyphenyl, 2-, 3- or 4-propoxyphenyl, 2-, 3- or 4-isopropoxyphenyl, 2-, 3- or 4-butoxyphenyl, 2
-, 3- or 4-s-butoxyphenyl, 2-, 3
-Or 4-t-butoxyphenyl, 2-, 3- or 4-methylthiophenyl, 2-, 3- or 4-
Ethylthiophenyl, 2-, 3- or 4-isopropylthiophenyl, 2-, 3- or 4-aminophenyl, 3,5-diaminophenyl, 2-, 3- or 4-methylaminophenyl, 2-, 3 -Or 4-dimethylaminophenyl, 2-, 3- or 4- (N-
Ethyl-N-methylamino) phenyl, 2-, 3- or 4-diethylaminophenyl, 2-, 3- or 4- (n-pentylamino) phenyl, 2-, 3- or 4- (n-hexylamino) Phenyl, 2-, 3-
Or 4-phenylaminophenyl, 2-, 3- or 4-benzylaminophenyl, 2-, 3- or 4-formylaminophenyl, 2-, 3- or 4-
Acetylaminophenyl, 2-, 3- or 4-propionylaminophenyl, 2-, 3- or 4-benzoylaminophenyl, 2-, 3- or 4- (2
-, 3- or 4-fluorobenzoylamino) phenyl, 2-, 3- or 4- (2-, 3- or 4
-Chlorobenzoylamino) phenyl, 2-, 3- or 4- (2,4-difluorobenzoylamino) phenyl, 2-, 3- or 4- (4-hydroxy-3,
5-dimethylbenzoylamino) phenyl, 2-, 3-
Or 4- (4-hydroxy-3,5-di-t-butylbenzoylamino) phenyl, 2-, 3- or 4
-(1- or 2-naphthoylamino) phenyl, 2
-, 3- or 4-phenylacetylaminophenyl, 2-, 3- or 4- (2-, 3- or 4-
Fluorophenylacetylamino) phenyl, 2-, 3
-Or 4- (2-, 3- or 4-chlorophenylacetylamino) phenyl, 2-, 3- or 4-
(3-phenylpropionylamino) phenyl, 2-,
3- or 4-cyclopentanoylaminophenyl,
2-, 3- or 4-cyclohexanoylaminophenyl, 2-, 3- or 4-nicotinoylaminophenyl, 2-, 3- or 4-isonicotinoylaminophenyl, 2-, 3- or 4- ( N-acetyl-N
-Methylamino) phenyl, 2-, 3- or 4-
(N-acetyl-N-pentylamino) phenyl, 2
-, 3- or 4- (N-acetyl-N-hexylamino) phenyl, 2-, 3- or 4- (N-benzoyl-N-hexylamino) phenyl, 2-, 3- or 4- (N- 3-chlorobenzoyl-N-methylamino) phenyl, 2-, 3- or 4- (N-3-chlorobenzoyl-N-hexylamino) phenyl, 2-,
3- or 4- (N-2,4-difluorobenzoyl-N-hexylamino) phenyl, 2-, 3- or 4- [N- (1- or 2-naphthoyl) -N-hexylamino] phenyl, -, 3- or 4- (N-
Hexyl-N-phenylacetylamino) phenyl, 2
-, 3- or 4- (N-isobutyl-N-cycloheptanoylamino) phenyl, 2-, 3- or 4-
(N-butyl-N-nicotinoylamino) phenyl, 2
-, 3- or 4-cyclopentylphenylyl, 2
-, 3- or 4-cyclohexylphenylyl, 2
-, 3- or 4- (1-adamantyl) phenyl,
2-, 3- or 4-biphenylyl, 2-, 3- or 4- (2'-, 3'- or 4'-hydroxy)
Biphenylyl, 2-, 3- or 4- (4-hydroxy-3,5-dimethylphenyl) phenyl, 2-, 3-
Or 4- (4-hydroxy-3,5-diisopropylphenyl) phenyl, 2-, 3- or 4- (3,
5-di-t-butyl-4-hydroxyphenyl) phenyl, 2-, 3- or 4-benzylphenyl, 2-,
3- or 4- (4-hydroxybenzyl) phenyl, 2-, 3- or 4- (4-hydroxy-3,5
-Dimethylbenzyl) phenyl, 2-, 3- or 4
-(3,5-di-tert-butyl-4-hydroxybenzyl) phenyl, 2-, 3- or 4-phenoxyphenyl, 2-, 3- or 4- (4-hydroxyphenoxy) phenyl, 2-, 3 -Or 4- (4-hydroxy-3,5-dimethylphenoxy) phenyl, 2-,
3- or 4- (3,5-di-tert-butyl-4-hydroxyphenoxy) phenyl, 2-, 3- or 4-
Benzyloxyphenyl, 2-, 3- or 4- (4
-Hydroxybenzyloxy) phenyl, 2-, 3- or 4- (4-hydroxy-3,5-dimethylbenzyloxy) phenyl, 2-, 3- or 4- (3,5
-Di-t-butyl-4-hydroxybenzyloxy) phenyl, 2-, 3- or 4-phenylthiophenyl, 2-, 3- or 4- (4-hydroxyphenylthio) phenyl, 2-, 3- or 4- (3,5-dimethyl-4-hydroxyphenylthio) phenyl, 2
-, 3- or 4- (3,5-di-t-butyl-4-
(Hydroxyphenylthio) phenyl, 2-, 3- or 4-formyloxyphenyl, 2-, 3- or 4
-Acetoxyphenyl, 2-, 3- or 4-propionyloxyphenyl, 2-, 3- or 4- (1-
Azetidinyl) phenyl, 2-, 3- or 4- (1
-, 2- or 3-pyrrolidinyl) phenyl, 2-,
3- or 4- (1-, 2-, 3- or 4-piperidinyl) phenyl, 2-, 3- or 4- (2-,
3- or 4-morpholinyl) phenyl, 2-, 3-
Or 4- (2-, 3- or 4-thiomorpholinyl) phenyl, 2-, 3- or 4- (1- or 2-piperazinyl) phenyl, 2-, 3- or 4-
(1-, 2- or 4-imidazolyl) phenyl, 2
-, 3- or 4- (tetrazol-5-yl) phenyl, 2-, 3- or 4- (2-, 3- or 4
-Pyridyl) phenyl, 2-, 3- or 4-nitrophenyl, 2-, 3- or 4-cyanophenyl, 2
-Or 3-chloro-4-hydroxyphenyl, 4-
Chloro-3,5-dihydroxyphenyl, 3,5-dichloro-4-hydroxyphenyl, 2-fluoro-4-hydroxy-3,5-dimethylphenyl, 3-fluoro-
5-hydroxy-2,6-dimethylphenyl, 4-fluoro-3-hydroxy-2,5-dimethylphenyl, 2
-Chloro-4-hydroxy-3,5-dimethylphenyl, 3-chloro-5-hydroxy-2,6-dimethylphenyl, 4-chloro-3-hydroxy-2,5-dimethylphenyl, 2- or 3-amino -4-chlorophenyl, 2,3-dichloro-4-aminophenyl, 2- or 3-chloro-4-methylaminophenyl, 2-hydroxy-3- or 4-methylphenyl, 2-hydroxy-3,4-dimethyl Phenyl, 3-hydroxy-
4- or 5-methylphenyl, 3-hydroxy-
2,4-dimethylphenyl, 4-hydroxy-2- or 3-methylphenyl, 2- or 3-ethyl-4
-Hydroxyphenyl, 4-hydroxy-2- or 3-propylphenyl, 4-hydroxy-2- or 3-isopropylphenyl, 2- or 3-t-butyl-4-hydroxyphenyl, 4-hydroxy-2,3
-Dimethylphenyl, 4-hydroxy-2,5-dimethylphenyl, 4-hydroxy-3,5-dimethylphenyl, 3,5-diethyl-4-hydroxyphenyl, 3-
t-butyl-4-hydroxy-5-methylphenyl, 4
-Hydroxy-3,5-dipropylphenyl, 4-hydroxy-3,5-diisopropylphenyl, 2,5-di-tert-butyl-4-hydroxyphenyl, 3,5-di-
t-butyl-4-hydroxyphenyl, 4-hydroxy-2,3,5-trimethylphenyl, 4-hydroxy-
2,3,6-trimethylphenyl, 4-hydroxy-
2,3,5,6-tetramethylphenyl, 4-hydroxy-3,5-dimethoxyphenyl, 2- or 3-hydroxy-4-dimethylaminophenyl, 4-benzyl- (2- or 3-hydroxy) phenyl, 3-, 5
-Or 6-benzyl-2-hydroxyphenyl, 3
-Hydroxy-4-nitrophenyl, 3-amino-4-
Methylphenyl, 4-amino-2,3-dimethylphenyl, 4-amino-2,6-dimethylphenyl, 4-amino-3,5-dimethylphenyl, 4-amino-3,5-
Diethylphenyl, 4-amino-3,5-dipropylphenyl, 4-amino-3,5-diisopropylphenyl, 4-amino-3,5-di-t-butylphenyl,
-Methylamino-3,5-dimethylphenyl, 4- (N
-Ethyl-N-methylamino) -3,5-dimethylphenyl, 4-acetylamino-3,5-dimethylphenyl, 4-acetylamino-3,5-di-t-butylphenyl, 4-benzoylamino-3 , 5-dimethylphenyl, 4-acetoxy-3,5-dimethylphenyl, 4-
Acetoxy-2,3,5-trimethylphenyl, 3,5
-Dimethyl-4-nitrophenyl group.

[0052] In the above, "1 to 4 which may be substituted pyridyl group with a group selected from Substituent group α" in the definition of R ⁴ is halogen atom; hydroxy group; C ₁ -
C ₆ alkyl group; halogeno C ₁ -C ₆ alkyl group; C ₁
-C ₆ alkoxy group; C ₁ -C ₆ alkylthio group which can be substituted by a group selected from substituent group γ amino group;
C ₃ -C ₁₀ cycloalkyl, C ₆ -C ₁₀ aryl, C ₇ -C ₁₆ aralkyl, C ₆ -C ₁₀ aryloxy, which may be substituted by 1 to 3 groups selected from the substituent group β. C ₇ -C ₁₆ aralkyloxy and C ₆ -C ₁₀ arylthio groups; C ₁ -C ₇ aliphatic acyloxy group; 4- to 7-membered saturated heterocyclic group containing a nitrogen atom; 5- or 6-membered aromatic containing a nitrogen atom A heterocyclic group; a nitro group; and a pyridyl group which may be substituted by 1 to 4 groups selected from the group consisting of a cyano group, for example, 2-, 3- or 4
-Pyridyl, 3-, 4-, 5- or 6-fluoro-
2-pyridyl, 2-, 4-, 5- or 6-fluoro-3-pyridyl, 2- or 3-fluoro-4-pyridyl, 3-, 4-, 5- or 6-chloro-2-pyridyl, 2 -, 4-, 5- or 6-chloro-3-pyridyl, 2- or 3-chloro-4-pyridyl, 3-,
4-, 5- or 6-bromo-2-pyridyl, 2-,
4-, 5- or 6-bromo-3-pyridyl, 2- or 3-bromo-4-pyridyl, 3-, 4-, 5- or 6-iodo-2-pyridyl, 2-, 4-, 5- Or 6-iodo-3-pyridyl, 2- or 3-iodo-4-pyridyl, 3-, 4-, 5- or 6-hydroxy-2-pyridyl, 2-, 4-, 5- or 6
-Hydroxy-3-pyridyl, 2- or 3-hydroxy-4-pyridyl, 3-, 4-, 5- or 6-methyl-2-pyridyl, 2-, 4-, 5- or 6-methyl-3- Pyridyl, 2- or 3-methyl-4-pyridyl, 3,5-dimethyl-4-pyridyl, 3-, 4
-, 5- or 6-ethyl-2-pyridyl, 2-, 4
-, 5- or 6-ethyl-3-pyridyl, 2- or 3-ethyl-4-pyridyl, 3,5-diethyl-4
-Pyridyl, 3-, 4-, 5- or 6-propyl-
2-pyridyl, 2-, 4-, 5- or 6-propyl-3-pyridyl, 2- or 3-propyl-4-pyridyl, 3,5-dipropyl-4-pyridyl, 3-, 4
-, 5- or 6-isopropyl-2-pyridyl, 2
-, 4-, 5- or 6-isopropyl-3-pyridyl, 2- or 3-isopropyl-4-pyridyl,
3,5-diisopropyl-4-pyridyl, 3-, 4-,
5- or 6-tert-butyl-2-pyridyl, 2,4
-, 5- or 6-tert-butyl-3-pyridyl, 2-
Or 3-t-butyl-4-pyridyl, 3,5-di-
t-butyl-4-pyridyl, 3-, 4-, 5- or 6-trifluoromethyl-2-pyridyl, 2-, 4-,
5- or 6-trifluoromethyl-3-pyridyl,
2- or 3-trifluoromethyl-4-pyridyl,
3-, 4-, 5- or 6-methoxy-2-pyridyl, 2-, 4-, 5- or 6-methoxy-3-pyridyl, 2- or 3-methoxy-4-pyridyl, 3
-, 4-, 5- or 6-ethoxy-2-pyridyl,
2-, 4-, 5- or 6-ethoxy-3-pyridyl, 2- or 3-ethoxy-4-pyridyl, 3-,
4-, 5- or 6-propoxy-2-pyridyl, 2
-, 4-, 5- or 6-propoxy-3-pyridyl, 2- or 3-propoxy-4-pyridyl, 3
-, 4-, 5- or 6-isopropoxy-2-pyridyl, 2-, 4-, 5- or 6-isopropoxy-
3-pyridyl, 2- or 3-isopropoxy-4-
Pyridyl, 3-, 4-, 5- or 6-t-butoxy-2-pyridyl, 2-, 4-, 5- or 6-t-butoxy-3-pyridyl, 2- or 3-t-butoxy-4 -Pyridyl, 4-methylthio-2-pyridyl, 6-
Isopropylthio-3-pyridyl, 6-t-butylthio-2-pyridyl, 3-, 4-, 5- or 6-amino-2-pyridyl, 2-, 4-, 5- or 6-amino-3-pyridyl , 2- or 3-amino-4-pyridyl, 3-, 4-, 5- or 6-methylamino-2-
Pyridyl, 2-, 4-, 5- or 6-methylamino-3-pyridyl, 2- or 3-methylamino-4-
Pyridyl, 5-phenylamino-2-pyridyl, 5-benzylamino-2-pyridyl, 5-acetylamino-2
-Pyridyl, 5-benzoylamino-2-pyridyl, 5
-Phenylacetylamino-2-pyridyl, 6-phenyl-2-pyridyl, 6- (4-hydroxyphenyl)-
2-pyridyl, 6- (4-hydroxy-3,5-dimethylphenyl) -2-pyridyl, 6- (3,5-di-t-
Butyl-4-hydroxyphenyl) -2-pyridyl, 6
-Benzyl-2-pyridyl, 6- (4-hydroxybenzyl) -2-pyridyl, 6- (4-hydroxy-3,5
-Dimethylbenzyl) -2-pyridyl, 6- (3,5-
Di-tert-butyl-4-hydroxybenzyl) -2-pyridyl, 6-phenoxy-2-pyridyl, 6- (4-hydroxyphenoxy) -2-pyridyl, 6- (4-hydroxy-3,5-dimethylphenoxy) ) -2-pyridyl,
6- (3,5-di-t-butyl-4-hydroxyphenoxy) -2-pyridyl, 6-benzyloxy-2-pyridyl, 6- (4-hydroxybenzyloxy) -2-pyridyl, 6- (4 -Hydroxy-3,5-dimethylbenzyloxy) -2-pyridyl, 6- (3,5-di-t-)
Butyl-4-hydroxybenzyloxy) -2-pyridyl, 6-phenylthio-2-pyridyl, 6- (4-hydroxyphenylthio) -2-pyridyl, 6- (4-hydroxy-3,5-dimethylphenylthio) -2-pyridyl, 6- (3,5-di-tert-butyl-4-hydroxyphenylthio) -2-pyridyl, 3-, 4-, 5- or 6-formyloxy-2-pyridyl, 2-, 4-, 5
-Or 6-formyloxy-3-pyridyl, 2- or 3-formyloxy-4-pyridyl, 3-, 4
-, 5- or 6-acetoxy-2-pyridyl, 2
-, 4-, 5- or 6-acetoxy-3-pyridyl, 2- or 3-acetoxy-4-pyridyl, 6-
(1-pyrrolidinyl) -2-pyridyl, 6- (1-piperidinyl) -2-pyridyl, 6- (4-morpholinyl)
-2-pyridyl, 3-, 4-, 5- or 6-nitro-2-pyridyl, 2-, 4-, 5- or 6-nitro-3-pyridyl, 2- or 3-nitro-4-pyridyl, 5-amino-6-fluoro-2-pyridyl, 5-amino-6-chloro-2-pyridyl, 6-chloro-3-nitro-2-pyridyl, 6-methoxy-5-methyl-3-
Pyridyl, 6-methyl-2-nitro-3-pyridyl, 6
-Chloro-3-nitro-2-pyridyl, 6-methoxy-
3-nitro-2-pyridyl, 6-isopropoxy-3-
Examples include nitro-2-pyridyl, 6-t-butoxy-3-nitro-2-pyridyl, and 6- (4-hydroxy-3,5-dimethylphenoxy) -5-nitro-2-pyridyl group.

Examples of the “pyridyl group which may be substituted by 1 to 4 groups selected from the substituent group α” include:
Preferably, a pyridyl group optionally substituted by one of the following substituents (the substituent is halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkoxy, _1- C ₆ alkylthio, amino or nitro which may be substituted with a group selected from substituent group γ), and more preferably a pyridyl group which may be substituted with one of the following substituents ( The substituent is fluorine, chlorine, hydroxy, methyl, ethyl, t-butyl, trifluoromethyl, methoxy, amino, methylamino, dimethylamino or nitro.), And particularly preferably a pyridyl group. .

In the above, “C _1-
"C ₆ alkylene group" represents a linear or branched alkylene group having 1 to 6 carbon atoms, for example, methylene, methylmethylene, ethylene, propylene, trimethylene, methylethylene, ethylethylene, tetramethylene, 1-methyl Trimethylene, 2-methyltrimethylene, 3-methyltrimethylene, 1,1-dimethylethylene, pentamethylene, 1-methyltetramethylene, 2-methyltetramethylene, 3-methyltetramethylene, 4-methyltetramethylene, propyl Ethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, hexamethylene, 1-methylpentamethylene, 2-methylpentamethylene, 3-methylpentamethylene, 4-methyl Pentamethylene, 5-methylpentamethylene, , 1-dimethyl tetramethylene,
2,2-dimethyltetramethylene, 3,3-dimethyltetramethylene, 4,4-dimethyltetramethylene, butylethylene and isobutylethylene;
_A C ₁ -C ₄ alkylene group, more preferably C ₁ -C ₂
An alkylene group, particularly preferably a methylene group.

The compound (I) of the present invention can be converted into a salt according to a conventional method. Such salts include, for example,
Metal salts such as alkali metal salts such as sodium salt, potassium salt and lithium salt, alkaline earth metal salts such as calcium salt and magnesium salt, aluminum salt, iron salt, zinc salt, copper salt, nickel salt and cobalt salt Inorganic salts such as ammonium salts, t-octylamine salts, dibenzylamine salts, morpholine salts, glucosamine salts, phenylglycine alkyl ester salts, ethylenediamine salts, N-
Methylglucamine salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt,
N, N'-dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-
Amine salts such as organic salts such as benzyl-N-phenethylamine salt, piperazine salt, tetramethylammonium salt, tris (hydroxymethyl) aminomethane salt; hydrofluoride, hydrochloride, hydrobromide, iodide Hydrohalides such as hydrochlorides; nitrates, perchlorates, sulfates,
Inorganic salts such as phosphates; lower alkane sulfonates such as methanesulfonate, trifluoromethanesulfonate and ethanesulfonate; arylsulfonates such as benzenesulfonate and p-toluenesulfonate Organic salts such as salts, acetic acid, malic acid, fumarate, succinate, citrate, tartrate, oxalate, and maleate; and, such as ornithate, glutamate, and aspartate Amino acid salts, and preferably,
It is a hydrohalide or an organic acid salt.

The compound (I) of the present invention may be left in the air or recrystallized to absorb water, adsorb water, or form a hydrate. When forming such a solvate, all of them are included in the present invention. Furthermore, the compound (I) of the present invention may absorb some other solvent to form a solvate, and such a compound is also included in the present invention. Further, the present invention also includes all compounds which are metabolized in vivo and converted into the compound (I) of the present invention or a pharmaceutically acceptable salt thereof, so-called prodrugs.

The compound (I) of the present invention has various isomers. That is, R ³ is a 2,4-dioxothiazolidine-5-ylmethyl group (IV-2) or a 2,4-dioxooxazolidine-5-ylmethyl group (IV-3)
In the case of, the 5-position of the thiazolidine ring or oxazolidine ring has an asymmetric carbon atom, and there are stereoisomers having R-coordination and S-coordination. Each of them, or any proportion thereof, is encompassed by the present invention. Such a stereoisomer may be obtained by synthesizing compound (I) using the optically resolved raw material compound, or subjecting the synthesized compound (I) to optical resolution using an ordinary optical resolution method or separation method as desired. Can be. In the compound (I) of the present invention, R ³ represents a 2,4-dioxothiazolidine-5-ylmethyl group (IV-2) or a 2,4-dioxooxazolidin-5-ylmethyl group (IV-3) Or a 3,5-dioxooxadiazolidine-2-ylmethyl group (IV-4)
In this case, the existence of various tautomers is conceivable, and each of the compounds or each of the compounds in any proportion thereof is included in the present invention. Such isomers are, for example, as shown below.

[0058]

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[0059]

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[0060]

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[0061]

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[0062] In addition, the drug which forms a pharmaceutical composition in combination with the compound (I) of the present invention or a pharmacologically acceptable salt thereof includes α-glucosidase inhibitors, aldose reductase inhibitors, biguanides, statin compounds Squalene synthesis inhibitors, fibrate compounds, LDL catabolism promoters and angiotensin converting enzyme inhibitors.

In the above, the α-glucosidase inhibitor is a drug which has an action of inhibiting digestion enzymes such as amylase, maltase, α-dextrinase and sucrase to delay the digestion of starch and sucrose. ,
Acarbose, N- (1,3-dihydroxy-2-propyl) valiolamine (generic name: voglibose), miglitol and the like can be mentioned.

In the above, aldose reductase inhibitors are agents that prevent diabetic complications by inhibiting the rate-limiting enzyme in the first step of the polyol pathway, such as tolrestat, epalrestat, 2,
7-difluoro-spiro (9H-fluorene-9,4 '
-Imidazolidine) -2 ', 5'-dione (generic name: imirestat), 3-[(4-bromo-2-fluorophenyl) methyl] -7-chloro-3,4-dihydro-2,
4-dioxo-1 (2H) -quinazolineacetic acid (generic name:
Zenarestat), 6-fluoro-2,3-dihydro-
2 ', 5'-dioxo-spiro [4H-1-benzopyran-4,4'-imidazolidine] -2-carboxamide
(SNK-860), Zopolrestat, Sorvinyl,
1-[(3-bromo-2-benzofuranyl) sulfonyl] -2,4-imidazolidinedione (M-1620
9) and the like.

In the above description, the biguanide is a drug having an anaerobic glycolysis-promoting action, an insulin action enhancement at the peripheral, glucose absorption from the intestinal tract, hepatic gluconeogenesis, fatty acid oxidation inhibition, and the like. For example, phenformin, metformin, buformin and the like can be mentioned.

In the above description, the statin compound is a drug which lowers blood cholesterol by inhibiting hydroxymethylglutaryl-CoA (HMG-CoA) reductase, for example, pravastatin and its sodium salt, simvastatin, lovastatin ,
Atorvastatin, fluvastatin and the like can be mentioned.

In the above description, the squalene synthesis inhibitor is a drug that lowers blood cholesterol by inhibiting squalene synthesis, for example, (S) -α
-[Bis (2,2-dimethyl-1-oxopropoxy)
Methoxy] phosphinyl-3-phenoxybenzenebutanesulfonic acid monopotassium salt (BMS-188494)
And the like.

In the above, a fibrate compound is used to inhibit triglyceride synthesis and secretion in the liver,
A drug that lowers blood triglycerides by activating lipoprotein lipase. Nicofibrate, pyrifibrate, ronifibrate, simfibrate, theofibrate and the like can be mentioned.

In the above, the LDL catabolic promoter is L
It is a drug that lowers blood cholesterol by increasing the DL (low density lipoprotein) receptor. 4-bis (4-fluorophenyl) methyl-1-piperazinyl] ethyl]-
7,7-diphenyl-2,4,6-heptatrienoic acid amide and the like can be mentioned.

The above-mentioned statins, squalene synthesis inhibitors, fibrate compounds and LDL catabolism promoters may be replaced with other drugs having an effect of lowering blood cholesterol and triglycerides. Examples of such agents include nicotinic acid derivative preparations such as nicomol and niceritrol; antioxidants such as probucol; and ion exchange resin preparations such as cholestyramine.

In the above, an angiotensin converting enzyme inhibitor is a drug which lowers blood pressure and partially lowers blood glucose in diabetic patients by inhibiting angiotensin converting enzyme, and includes, for example, captopril, enalapril, alacepril , Delapril, ramipril, lisinopril, imidapril, benazepril, selonapril, cilazapril, enalaprilate,
Fosinopril, mobertopril, perindopril, quinapril, spirapril, temocapril, trandolapril and the like can be mentioned.

In the compound (I) of the present invention, preferred compounds are (1) a compound in which R ¹ is a group having the general formula (II), and (2) R ² and R ⁵ are the same or different. And a hydrogen atom, a halogen atom, a hydroxy group, C _1-
C ₆ alkyl group, halogeno C ₁ -C ₆ alkyl group, C ₁
-C ₆ alkoxy group, C ₁ -C ₆ alkylthio group or a compound which is an amino group which may be substituted with a group selected from substituent group γ, (3) R ² and R ⁵ are the same or different, A compound which is a hydrogen atom, a fluorine atom, a chlorine atom, a hydroxy group, a methyl group, an ethyl group, a trifluoromethyl group, a methoxy group, a methylthio group or an amino group, (4) R
^A compound wherein ² and R ⁵ are hydrogen atoms, (5) R ³ is
Compound is a group having the formula (IV-1) to (IV-3), (6 ) R 3 is a compound which is a group having the formula (IV-2) or (IV-3), (7 ) R 3 Has the formula (IV-2)
(8) R ⁴ is a compound having the following substituent:
A pyridyl group which may be substituted by 1 (the substituent is halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C _1-
C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkylthio, amino or nitro which may be substituted with a group selected from substituent group γ. (9)
R ⁴ is a pyridyl group optionally substituted by one of the following substituents (the substituent is fluorine, chlorine, hydroxy, methyl, ethyl, t-butyl, trifluoromethyl, methoxy, methylthio, amino, methylamino, Dimethylamino or nitro), (10) a compound wherein R ⁴ is a pyridyl group, and (11) a phenyl group wherein R ⁴ is at least one substituted with a group selected from the following substituent groups. (The substituent group may be a C ₃ -C ₁₀ cycloalkyl, C ₁ -C ₁₀ cycloalkyl, which may be substituted with 1 to 3 groups selected from the substituent group β.
₆ -C consisting ₁₀ aryl and C ₇ -C ₁₆ aralkyl, 5- or 6-membered aromatic heterocyclic ring containing 4 to 7-membered saturated heterocyclic ring and the nitrogen atom containing a nitrogen atom. ) Is a compound
(12) R ⁴ is a phenyl group substituted by one of the following substituents (the substituent group is a C ₃ -C ₁₀ cycloalkyl which may be substituted by one group selected from a substituent group β. , C ₆ −
C ₁₀ aryl or C ₇ -C ₁₆ aralkyl, a 4- to 7-membered saturated heterocycle containing a nitrogen atom or a 5- or 6-membered aromatic heterocycle containing a nitrogen atom. ), (1)
3) R ⁴ is a phenyl group substituted by one of the following substituents (the substituent may be halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy or substituted A C ₃ -C ₁₀ cycloalkyl, C ₆ -C ₁₀ aryl or C ₇ -C ₁₆ aralkyl, containing a nitrogen atom, which may be substituted by one amino which may be substituted by a group selected from group γ (14) a phenyl group in which R ⁴ is substituted by one of the following substituents (a 4- to 7-membered saturated heterocyclic ring or a 5- or 6-membered aromatic heterocyclic ring containing a nitrogen atom): The groups are halogen, hydroxy, C
₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁
A phenyl or benzyl, adamantyl, pyrrolidinyl, morpholinyl, piperidinyl, imidazolyl, tetrazolyl or pyridinyl group, which may be substituted with one amino group which may be substituted with -C ₆ alkoxy or a group selected from substituent group γ. . ) Is a compound
(15) R ⁴ is a phenyl group substituted by one of the following substituents (the substituent is fluorine, chlorine, hydroxy, methyl, ethyl, t-butyl, trifluoromethyl, methoxy, amino, methylamino or dimethyl Phenyl or benzyl, adamantyl, pyrrolidinyl, morpholinyl, piperidinyl, imidazolyl, tetrazolyl or pyridinyl group which may be substituted by one amino), (16) wherein R ⁴ is 4-biphenylyl,
Benzylphenyl, 4'-hydroxybiphenylyl,
(Pyrrolidin-1-yl) phenyl, (morpholine-4
-Yl) phenyl, (piperidin-1-yl) phenyl, (pyridin-2-yl) phenyl, (pyridine-3
(17) a compound in which R ⁴ is substituted by one acylamino which may be substituted with a group selected from the substituent group γ, and A group selected from the group of substituents 1 to 3
Optionally substituted phenyl groups (the substituents include halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C _1-
C ₆ alkyl, consisting C ₁ -C ₆ alkoxy and C ₁ -C ₆ alkylthio. (18) R ⁴
Is substituted with one acylamino which may be substituted with a group selected from the group of substituents γ, and further substituted with one to three phenyl groups which may be substituted with one to three groups selected from the following group of substituents. Motogun consists halogen and C ₁ -C ₆ alkyl.), compound, (19) R ⁴ is substituted by C ₁ -C ₁₀ alkyl or optionally substituted C ₇ -C ₁₂ aralkyl One substituted with a good acylamino,
A compound which is a phenyl group optionally substituted with 1 to 3 C ₁ -C ₆ alkyl, (20) R ⁴ is 1
A monosubstituted phenyl group (the substituent may be a C ₇ -C ₁₁ aromatic acylamino, a C ₄ -C ₁₁ cycloalkylcarbonylamino or a 5- to 6-membered aromatic heterocyclic carbonyl containing a nitrogen atom, Wherein R ⁴ is benzoylamino, 3-chlorobenzoylamino, 2,4-difluorobenzoylamino, 4-hydroxy-3,5-di-t-butylbenzoylamino, naphtho Ilamino, cyclopentanoylamino, cyclohexanoylamino, nicotinoylamino,
Isonicotinoyl amino compound is a phenyl group substituted with N- acetyl -N- hexylamino or adamantyl carbonyl amino, is (22) R ^4, amino, 1
Amino substituted with from 2 to 2 groups, wherein said substituents are the same or different and are selected from C ₁ -C ₁₀ alkyl and optionally substituted C ₆ -C ₁₀ aryl and C ₇ -C ₁₆ aralkyl Is substituted with one or more nitro or cyano groups, and is further substituted with one to one of the following substituent groups.
3 phenyl groups which may be substituted (the substituent groups include halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁
-C ₆ alkyl, C ₁ -C ₆ alkoxy and C ₁ -C ₆
Consists of alkylthio. (23) R ⁴
Is a phenyl group substituted with one amino, mono- or di-C ₁ -C ₁₀ alkylamino or cyano, and further optionally substituted with one or two C ₁ -C ₆ alkyl, (24 ) R ⁴ is 4-aminophenyl, 4-amino-3,5-dimethylphenyl, 4-amino-3,5-
A compound which is di-t-butylphenyl, 3- or 4-dimethylaminophenyl or 4-cyanophenyl group,
(25) R ^4, it may be 1 to 3 substituted with a group selected from the substituent group beta, C ₆ -C ₁₀ aryloxy, C
₇ -C ₁₆ is one substituted with aralkyloxy or C ₆ -C ₁₀ arylthio, further, 1 to 3 optionally substituted phenyl group (the substituent group with a group selected from the following substituent group is halogen , Hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy and C
Consisting of ₁ -C ₆ alkylthio. ), (2)
6) R ⁴ is substituted with C ₆ -C ₁₀ aryloxy which may be substituted with 1 to 3 groups selected from a substituent group β, and further substituted with 1 to 2 C ₁ -C ₆ alkyl. A compound which is a phenyl group which may be substituted, and (27) C ₆ − in which one R ⁴ may be substituted with a group selected from substituent group β.
C ₁₀ compounds aryloxy-substituted phenyl group, (28) R ⁴ is 4-phenoxyphenyl compound, (29) R ⁴ is one to five groups selected from the following substituent group A substituted phenyl group (the substituents include halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C
₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆
Alkylthio and C ₁ -C ₇ aliphatic acyloxy. ), Compound, (30) R ⁴ is halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkylthio or C ₁ -C ₇ A phenyl group substituted with one aliphatic acyloxy and further optionally substituted with one to four groups selected from the following substituent groups (the substituent groups are halogen, C ₁
-C consisting ₆ alkyl and halogeno C ₁ -C ₆ alkyl. And (31) a phenyl group or a phenyl group in which R ⁴ is substituted with one C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkylthio. (32) R ⁴ is a compound represented by halogeno C _1-
C ₂ alkyl, C ₁ -C ₂ alkoxy or C ₁ -C
One substituted phenyl group, or 1 to ₂ alkylthio
(33) a compound wherein R ⁴ is a 4-trifluoromethylphenyl, 4-methylthiophenyl, 4-methoxyphenyl or pentafluorophenyl group; (33) a compound which is a phenyl group substituted with 5 fluorine atoms or chlorine atoms;
(34) a phenyl group in which R ⁴ is substituted by _one hydroxy or C ₁ -C ₇ aliphatic acyloxy, and further optionally substituted by 1 to 3 groups selected from the following substituent group (the substituent The group consisting of halogen and C ₁ -C ₆ alkyl), wherein (35) R ⁴ is hydroxy
1 group is substituted, and further, a group selected from the following substituent group
A compound which is a phenyl group which may be substituted with 1 to 3 substituents (the substituent group is composed of halogen and C ₁ -C ₆ alkyl); (36) R ⁴ is substituted with 1 hydroxy group; A compound which is a phenyl group which may be substituted with 1 to 3 groups selected from the following substituent groups (the substituent group is composed of fluorine, chlorine, methyl and t-butyl);
(37) R ⁴ is 4-hydroxyphenyl, 4-hydroxy-3,5-dimethylphenyl, 4-hydroxy-
3,5-di-t-butylphenyl, 4-hydroxy-
A compound which is a 2,3,5-trimethylphenyl, 2-chloro-4-hydroxy-3,5-dimethylphenyl group,
(38) R ⁶ is a hydrogen atom, a C ₁ -C ₆ alkyl group, or a phenyl or benzyl group which may be substituted by 1 to 3 substituent (s) selected from the following substituent groups; Substituent groups include halogen, hydroxy, C ₁ -C ₆
Alkyl and halogeno C ₁ -C ₆ alkyl. )
(39) R ⁶ is a hydrogen atom, C ₁ -C ₄
An alkyl group, or one which may be substituted with the following substituents,
A compound which is a phenyl or benzyl group (the substituent is fluorine, chlorine, hydroxy, methyl or ethyl); (40) a compound wherein R ⁶ is a hydrogen atom or a C ₁ -C ₄ alkyl group; A) a compound wherein R ⁶ is a C ₁ -C ₂ alkyl group; (42) a compound wherein R ⁶ is a methyl group; (43) a compound wherein A is a C ₁ -C ₄ alkylene group; Is a C ₁ -C ₂ alkylene group, (45) A is a methylene group, (4
6) a compound wherein B is an oxygen atom, (47) a compound wherein D is an oxygen atom, (48) a compound wherein D is a sulfur atom, (49) a compound wherein E is a group having CH, 5
0) Compounds in which E is a nitrogen atom can be mentioned.

Further, (1), (2)-(4), (5)-
(7), (8)-(37), (38)-(42), (4
3)-(45), (46), (47)-(48) and (49)-(50) are also preferably selected from 2 to 9 and arbitrarily combined.

The compounds of the present invention include, for example, the compounds described in Tables 1 to 10, but the present invention is not limited to these compounds. The compounds shown in Tables 1 to 10 correspond to the compounds represented by the formulas (I-1)-(I-
It has the structural formula of 10). However, the abbreviations in the table are as follows.

Ac: acetyl group Ada (1): 1-adamantyl group Bu: butyl group sBu: s-butyl group tBu: t-butyl group Bz: benzyl group Et: ethyl group Hx: hexyl group cHx: cyclohexyl group Imid ( 1): 1-imidazolyl group Me: methyl group Mor (4): 4-morpholinyl group Np (1): 1-naphthyl group Np (2): 2-naphthyl group Ph: phenyl group Pip (1): 1-piperidinyl Group Pipra (1): 1-piperazinyl group Pn: pentyl group cPn: cyclopentyl group Pr: propyl group iPr: isopropyl group Pyr (2): 2-pyridyl group Pyr (3): 3-pyridyl group Pyr (4): 4 -Pyridyl group Pyrd (1): 1-pyrrolidinyl group TioMor (4): 4-thiomorpholinyl group Tz: tetrazol-5-yl group.

[0076]

[Table 1]

[0077]

Embedded image

[0078]  Cpd.No. R^Two R^Four R^Five R⁶ -A- B D E  1-1 H 2-F-Ph H Me -CH_Two-O O CH 1-2 H 3-F-Ph H Me -CH_Two-O O CH 1-3 H 4-F-Ph H Me -CH_Two-O O CH 1-4 H 4-F-Ph H Me -CH_Two-O S CH 1-5 H 2-Cl-Ph H Me -CH_Two-O O CH 1-6 H 3-Cl-Ph H Me -CH_Two-O O CH 1-7 H 4-Cl-Ph H Me -CH_Two-O O CH 1-8 H 4-Cl-Ph H Me -CH_Two-O S CH 1-9 H 4-Br-Ph H Me -CH_Two-O O CH 1-10 H 2-OH-Ph H H -CH_Two-O O CH 1-11 H 2-OH-Ph H Me -CH_Two-O O CH 1-12 H 2-OH-Ph H Me -CH_Two-O O N 1-13 H 2-OH-Ph H Me -CH_Two-O S CH 1-14 H 2-OH-Ph H Me -CH_Two-O S N 1-15 H 2-OH-Ph H Me -CH_Two-S O CH 1-16 H 2-OH-Ph H Me-(CH_Two)_Two-O O CH 1-17 H 2-OH-Ph H Me-(CH_Two)_Two-O ON 1-18 H 2-OH-Ph H Me-(CH_Two)_Two-O S CH 1-19 H 2-OH-Ph H Me -CH (Me)-O O CH 1-20 H 2-OH-Ph H Me-(CH_Two)_Three-O O CH 1-21 H 2-OH-Ph H Me-(CH_Two)_Three-O S CH 1-22 H 2-OH-Ph H Me-(CH_Two)_Three-S O CH 1-23 H 2-OH-Ph H Et -CH_Two-O O CH 1-24 H 2-OH-Ph H Et -CH_Two-O ON 1-25 H 2-OH-Ph H Et -CH_Two-O S CH 1-26 H 2-OH-Ph H Et-(CH_Two)_Two-O O CH 1-27 H 2-OH-Ph H tBu -CH_Two-O O CH 1-28 H 2-OH-Ph H tBu -CH_Two-O S CH 1-29 H 2-OH-Ph H Ph -CH_Two-O O CH 1-30 H 2-OH-Ph H Bz -CH_Two-O O CH 1-31 H 2-OH-Ph 5-Cl Me -CH_Two-O O CH 1-32 H 2-OH-Ph 5-Me Me -CH_Two-O O CH 1-33 H 2-OH-Ph 5-MeO Me -CH_Two-O O CH 1-34 2-Cl 2-OH-Ph H Me -CH_Two-O O CH 1-35 3-Cl 2-OH-Ph H Me -CH_Two-O O CH 1-36 2-Me 2-OH-Ph H Me -CH_Two-O O CH 1-37 3-Me 2-OH-Ph H Me -CH_Two-O O CH 1-38 2-MeO 2-OH-Ph H Me -CH_Two-O O CH 1-39 3-MeO 2-OH-Ph H Me -CH_Two-O O CH 1-40 H 3-OH-Ph H H -CH_Two-O O CH 1-41 H 3-OH-Ph H Me -CH_Two-O O CH 1-42 H 3-OH-Ph H Me -CH_Two-O O N 1-43 H 3-OH-Ph H Me -CH_Two-O S CH 1-44 H 3-OH-Ph H Me -CH_Two-O S N 1-45 H 3-OH-Ph H Me -CH_Two-S O CH 1-46 H 3-OH-Ph H Me-(CH_Two)_Two-O O CH 1-47 H 3-OH-Ph H Me-(CH_Two)_Two-O O N 1-48 H 3-OH-Ph H Me-(CH_Two)_Two-O S CH 1-49 H 3-OH-Ph H Me -CH (Me)-O O CH 1-50 H 3-OH-Ph H Me-(CH_Two)_Three-O O CH 1-51 H 3-OH-Ph H Et -CH_Two-O O CH 1-52 H 3-OH-Ph H Et -CH_Two-O ON 1-53 H 3-OH-Ph H Et -CH_Two-O S CH 1-54 H 3-OH-Ph H Et-(CH_Two)_Two-O O CH 1-55 H 3-OH-Ph H tBu -CH_Two-O O CH 1-56 H 3-OH-Ph H tBu -CH_Two-O S CH 1-57 H 3-OH-Ph H Ph -CH_Two-O O CH 1-58 H 3-OH-Ph H Bz -CH_Two-O O CH 1-59 H 3-OH-Ph 5-Cl Me -CH_Two-O O CH 1-60 H 3-OH-Ph 5-Me Me -CH_Two-O O CH 1-61 H 3-OH-Ph 5-MeO Me -CH_Two-O O CH 1-62 2-Cl 3-OH-Ph H Me -CH_Two-O O CH 1-63 3-Cl 3-OH-Ph H Me -CH_Two-O O CH 1-64 2-Me 3-OH-Ph H Me -CH_Two-O O CH 1-65 3-Me 3-OH-Ph H Me -CH_Two-O O CH 1-66 2-MeO 3-OH-Ph H Me -CH_Two-O O CH 1-67 3-MeO 3-OH-Ph H Me -CH_Two-O O CH 1-68 H 4-OH-Ph H H -CH_Two-O O CH 1-69 H 4-OH-Ph H H -CH_Two-O S CH 1-70 H 4-OH-Ph H Me -CH_Two-O O CH 1-71 H 4-OH-Ph H Me -CH_Two-O ON 1-72 H 4-OH-Ph H Me -CH_Two-O S CH 1-73 H 4-OH-Ph H Me -CH_Two-O S N 1-74 H 4-OH-Ph H Me -CH_Two-S O CH 1-75 H 4-OH-Ph H Me -CH_Two-S ON 1-76 H 4-OH-Ph H Me -CH_Two-S S CH 1-77 H 4-OH-Ph H Me -CH_Two-S SN 1-78 H 4-OH-Ph H Me-(CH_Two)_Two-O O CH 1-79 H 4-OH-Ph H Me-(CH_Two)_Two-O ON 1-80 H 4-OH-Ph H Me-(CH_Two)_Two-O S CH 1-81 H 4-OH-Ph H Me-(CH_Two)_Two-O S N 1-82 H 4-OH-Ph H Me-(CH_Two)_Two-SO CH 1-83 H 4-OH-Ph H Me -CH (Me)-OO CH 1-84 H 4-OH-Ph H Me -CH (Me)-OS CH 1-85 H 4-OH-Ph H Me-(CH_Two)_Three-O O CH 1-86 H 4-OH-Ph H Me-(CH_Two)_Three-O S CH 1-87 H 4-OH-Ph H Me-(CH_Two)_Four-O O CH 1-88 H 4-OH-Ph H Et -CH_Two-O O CH 1-89 H 4-OH-Ph H Et -CH_Two-O ON 1-90 H 4-OH-Ph H Et -CH_Two-O S CH 1-91 H 4-OH-Ph H Et -CH_Two-O S N 1-92 H 4-OH-Ph H Et -CH_Two-S O CH 1-93 H 4-OH-Ph H Et-(CH_Two)_Two-O O CH 1-94 H 4-OH-Ph H Et-(CH_Two)_Two-O S CH 1-95 H 4-OH-Ph H Pr -CH_Two-O O CH 1-96 H 4-OH-Ph H iPr -CH_Two-O O CH 1-97 H 4-OH-Ph H Bu -CH_Two-O O CH 1-98 H 4-OH-Ph H sBu -CH_Two-O O CH 1-99 H 4-OH-Ph H sBu-(CH_Two)_Three-O O CH 1-100 H 4-OH-Ph H tBu -CH_Two-O O CH 1-101 H 4-OH-Ph H tBu -CH_Two-O S CH 1-102 H 4-OH-Ph H Ph -CH_Two-O O CH 1-103 H 4-OH-Ph H Ph -CH_Two-O O N 1-104 H 4-OH-Ph H Ph -CH_Two-O S CH 1-105 H 4-OH-Ph H Ph-(CH_Two)_Two-O O CH 1-106 H 4-OH-Ph H Bz -CH_Two-O O CH 1-107 H 4-OH-Ph H Bz -CH_Two-O O N 1-108 H 4-OH-Ph H Bz -CH_Two-O S CH 1-109 H 4-OH-Ph H Bz-(CH_Two)_Two-O O CH 1-110 H 4-OH-Ph 5-F Me -CH_Two-O O CH 1-111 H 4-OH-Ph 4-Cl Me -CH_Two-O O CH 1-112 H 4-OH-Ph 5-Cl Me -CH_Two-O O CH 1-113 H 4-OH-Ph 4-Me Me -CH_Two-O O CH 1-114 H 4-OH-Ph 5-Me Me -CH_Two-O O CH 1-115 H 4-OH-Ph 4-MeO Me -CH_Two-O O CH 1-116 H 4-OH-Ph 5-MeO Me -CH_Two-O O CH 1-117 H 4-OH-Ph 5-MeO Me -CH_Two-O S CH 1-118 H 4-OH-Ph 5-MeS Me -CH_Two-O O CH 1-119 3-F 4-OH-Ph H Me -CH_Two-O O CH 1-120 2-Cl 4-OH-Ph H Me -CH_Two-O O CH 1-121 3-Cl 4-OH-Ph H Me -CH_Two-O O CH 1-122 2-Me 4-OH-Ph H Me -CH_Two-O O CH 1-123 3-Me 4-OH-Ph H Me -CH_Two-O O CH 1-124 3-CF_Three 4-OH-Ph H Me -CH_Two-O O CH 1-125 2-MeO 4-OH-Ph H Me -CH_Two-O O CH 1-126 3-MeO 4-OH-Ph H Me -CH_Two-O O CH 1-127 H 2-Me-Ph H Me -CH_Two-O O CH 1-128 H 3-Me-Ph H Me -CH_Two-O O CH 1-129 H 4-Me-Ph H Me -CH_Two-O O CH 1-130 H 3-CF_Three-Ph H Me -CH_Two-O O CH 1-131 H 4-CF_Three-Ph H Me -CH_Two-O O CH 1-132 H 4-MeO-Ph H Me -CH_Two-O O CH 1-133 H 4-EtO-Ph H Me -CH_Two-O O CH 1-134 H 4-iPrO-Ph H Me -CH_Two-O O CH 1-135 H 4-iPrO-Ph H Me -CH_Two-O S CH 1-136 H 4-MeS-Ph H Me -CH_Two-O O CH 1-137 H 4-MeS-Ph H Me -CH_Two-O S CH 1-138 H 2-NH_Two-Ph H Me -CH_Two-O O CH 1-139 H 2-NH_Two-Ph H Me -CH_Two-O S CH 1-140 H 3-NH_Two-Ph H Me -CH_Two-O O CH 1-141 H 3-NH_Two-Ph H Me -CH_Two-O S CH 1-142 H 4-NH_Two-Ph H Me -CH_Two-O O CH 1-143 H 4-NH_Two-Ph H Me -CH_Two-O O N 1-144 H 4-NH_Two-Ph H Me -CH_Two-O S CH 1-145 H 4-NH_Two-Ph H Et -CH_Two-O O CH 1-146 H 4-NH_Two-Ph H Et -CH_Two-O S CH 1-147 H 2-NHMe-Ph H Me -CH_Two-O O CH 1-148 H 3-NHMe-Ph H Me -CH_Two-O O CH 1-149 H 4-NHMe-Ph H Me -CH_Two-O O CH 1-150 H 4-NHMe-Ph H Me -CH_Two-O S CH 1-151 H 2-N (Me)_Two-Ph H Me -CH_Two-O O CH 1-152 H 2-N (Me)_Two-Ph H Me -CH_Two-O S CH 1-153 H 3-N (Me)_Two-Ph H Me -CH_Two-O O CH 1-154 H 3-N (Me)_Two-Ph H Me -CH_Two-O S CH 1-155 H 4-N (Me)_Two-Ph H Me -CH_Two-O O CH 1-156 H 4-N (Me)_Two-Ph H Me -CH_Two-O O N 1-157 H 4-N (Me)_Two-Ph H Me -CH_Two-O S CH 1-158 H 4-N (Me)_Two-Ph H Et -CH_Two-O O CH 1-159 H 4-N (Me)_Two-Ph H Et -CH_Two-O S CH 1-160 H 4-NHEt-Ph H Me -CH_Two-O O CH 1-161 H 4-NMeEt-Ph H Me -CH_Two-O O CH 1-162 H 4-NHPh-Ph H Me -CH_Two-O O CH 1-163 H 4-NHBz-Ph H Me -CH_Two-O O CH 1-164 H 4-NHAc-Ph H Me -CH_Two-O O CH 1-165 H 4-NHAc-Ph H Me -CH_Two-O S CH 1-166 H 4-N (Me) Ac-Ph H Me -CH_Two-O O CH 1-167 H 4-N (Me) Ac-Ph H Me -CH_Two-O S CH 1-168 H 3-Ph-Ph H Me -CH_Two-O O CH 1-169 H 4-Ph-Ph H Me -CH_Two-O O CH 1-170 H 4-Ph-Ph H Me -CH_Two-O S CH 1-171 H 4- (4-OH-Ph) Ph H Me -CH_Two-O O CH 1-172 H 4- (4-OH-Ph) Ph H Me -CH_Two-O S CH 1-173 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH_Two-O O CH 1-174 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH_Two-O O N 1-175 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH_Two-O S CH 1-176 H 4- (4-OH-3,5-diMe-Ph) Ph H Et -CH_Two-O O CH 1-177 H 4- (4-OH-3,5-diMe-Ph) Ph H Et -CH_Two-O S CH 1-178 H 4- (4-OH-3,5-ditBu-Ph) Ph H Me -CH_Two-O O CH 1-179 H 4- (4-OH-3,5-ditBu-Ph) Ph H Me -CH_Two-O O N 1-180 H 4- (4-OH-3,5-ditBu-Ph) Ph H Me -CH_Two-O S CH 1-181 H 4- (4-OH-3,5-ditBu-Ph) Ph H Et -CH_Two-O O CH 1-182 H 4- (4-OH-3,5-ditBu-Ph) Ph H Et -CH_Two-O S CH 1-183 H 3-Bz-Ph H Me -CH_Two-O O CH 1-184 H 4-Bz-Ph H Me -CH_Two-O O CH 1-185 H 4-Bz-Ph H Me -CH_Two-O S CH 1-186 H 4- (4-OH-Bz) Ph H Me -CH_Two-O O CH 1-187 H 4- (4-OH-Bz) Ph H Me -CH_Two-O S CH 1-188 H 4- (4-OH-3,5-diMe-Bz) Ph H Me -CH_Two-O O CH 1-189 H 4- (4-OH-3,5-diMe-Bz) Ph H Me -CH_Two-O S CH 1-190 H 4- (4-OH-3,5-ditBu-Bz) Ph H Me -CH_Two-O O CH 1-191 H 4- (4-OH-3,5-ditBu-Bz) Ph H Me -CH_Two-O S CH 1-192 H 3-PhO-Ph H Me -CH_Two-O O CH 1-193 H 4-PhO-Ph H Me -CH_Two-O O CH 1-194 H 4-PhO-Ph H Me -CH_Two-O S CH 1-195 H 3-PhS-Ph H Me -CH_Two-O O CH 1-196 H 4-PhS-Ph H Me -CH_Two-O O CH 1-197 H 4-PhS-Ph H Me -CH_Two-O S CH 1-198 H 4-AcO-Ph H Me -CH_Two-O O CH 1-199 H 2-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-200 H 2-Pyrd (1) -Ph H Me -CH_Two-O O N 1-201 H 2-Pyrd (1) -Ph H Me -CH_Two-O S CH 1-202 H 2-Pyrd (1) -Ph H Me-(CH_Two)_Two-O O CH 1-203 H 2-Pyrd (1) -Ph H Et -CH_Two-O O CH 1-204 H 2-Pyrd (1) -Ph H Et -CH_Two-O S CH 1-205 H 2-Pyrd (1) -Ph H tBu -CH_Two-O O CH 1-206 H 3-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-207 H 3-Pyrd (1) -Ph H Me -CH_Two-O O N 1-208 H 3-Pyrd (1) -Ph H Me -CH_Two-O S CH 1-209 H 3-Pyrd (1) -Ph H Me-(CH_Two)_Two-O O CH 1-210 H 3-Pyrd (1) -Ph H Et -CH_Two-O O CH 1-211 H 3-Pyrd (1) -Ph H Et -CH_Two-O S CH 1-212 H 3-Pyrd (1) -Ph H tBu -CH_Two-O O CH 1-213 H 4-Pyrd (1) -Ph H H -CH_Two-O O CH 1-214 H 4-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-215 H 4-Pyrd (1) -Ph H Me -CH_Two-O O N 1-216 H 4-Pyrd (1) -Ph H Me -CH_Two-O S CH 1-217 H 4-Pyrd (1) -Ph H Me -CH_Two-O S N 1-218 H 4-Pyrd (1) -Ph H Me -CH_Two-S O CH 1-219 H 4-Pyrd (1) -Ph H Me-(CH_Two)_Two-O O CH 1-220 H 4-Pyrd (1) -Ph H Me-(CH_Two)_Two-O O N 1-221 H 4-Pyrd (1) -Ph H Me-(CH_Two)_Two-O S CH 1-222 H 4-Pyrd (1) -Ph H Me -CH (Me)-O O CH 1-223 H 4-Pyrd (1) -Ph H Me-(CH_Two)_Three-O O CH 1-224 H 4-Pyrd (1) -Ph H Et -CH_Two-O O CH 1-225 H 4-Pyrd (1) -Ph H Et -CH_Two-O O N 1-226 H 4-Pyrd (1) -Ph H Et -CH_Two-O S CH 1-227 H 4-Pyrd (1) -Ph H Et-(CH_Two)_Two-O O CH 1-228 H 4-Pyrd (1) -Ph H tBu -CH_Two-O O CH 1-229 H 4-Pyrd (1) -Ph H tBu -CH_Two-O S CH 1-230 H 4-Pyrd (1) -Ph H Ph -CH_Two-O O CH 1-231 H 4-Pyrd (1) -Ph H Bz -CH_Two-O O CH 1-232 H 4-Pyrd (1) -Ph 5-Cl Me -CH_Two-O O CH 1-233 H 4-Pyrd (1) -Ph 5-Me Me -CH_Two-O O CH 1-234 H 4-Pyrd (1) -Ph 5-MeO Me -CH_Two-O O CH 1-235 2-Cl 4-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-236 3-Cl 4-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-237 2-Me 4-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-238 3-Me 4-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-239 2-MeO 4-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-240 3-MeO 4-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-241 H 2-Pip (1) -Ph H Me -CH_Two-O O CH 1-242 H 2-Pip (1) -Ph H Me -CH_Two-O O N 1-243 H 2-Pip (1) -Ph H Me -CH_Two-O S CH 1-244 H 2-Pip (1) -Ph H Me-(CH_Two)_Two-O O CH 1-245 H 2-Pip (1) -Ph H Et -CH_Two-O O CH 1-246 H 2-Pip (1) -Ph H Et -CH_Two-O S CH 1-247 H 2-Pip (1) -Ph H tBu -CH_Two-O O CH 1-248 H 3-Pip (1) -Ph H Me -CH_Two-O O CH 1-249 H 3-Pip (1) -Ph H Me -CH_Two-O O N 1-250 H 3-Pip (1) -Ph H Me -CH_Two-O S CH 1-251 H 3-Pip (1) -Ph H Me-(CH_Two)_Two-O O CH 1-252 H 3-Pip (1) -Ph H Et -CH_Two-O O CH 1-253 H 3-Pip (1) -Ph H Et -CH_Two-O S CH 1-254 H 3-Pip (1) -Ph H Et-(CH_Two)_Three-S O CH 1-255 H 3-Pip (1) -Ph H tBu -CH_Two-O O CH 1-256 H 4-Pip (1) -Ph H H -CH_Two-O O CH 1-257 H 4-Pip (1) -Ph H Me -CH_Two-O O CH 1-258 H 4-Pip (1) -Ph H Me -CH_Two-O O N 1-259 H 4-Pip (1) -Ph H Me -CH_Two-O S CH 1-260 H 4-Pip (1) -Ph H Me -CH_Two-O S N 1-261 H 4-Pip (1) -Ph H Me -CH_Two-S O CH 1-262 H 4-Pip (1) -Ph H Me-(CH_Two)_Two-O O CH 1-263 H 4-Pip (1) -Ph H Me-(CH_Two)_Two-O O N 1-264 H 4-Pip (1) -Ph H Me-(CH_Two)_Two-O S CH 1-265 H 4-Pip (1) -Ph H Me -CH (Me)-O O CH 1-266 H 4-Pip (1) -Ph H Me-(CH_Two)_Three-O O CH 1-267 H 4-Pip (1) -Ph H Et -CH_Two-O O CH 1-268 H 4-Pip (1) -Ph H Et -CH_Two-O O N 1-269 H 4-Pip (1) -Ph H Et -CH_Two-O S CH 1-270 H 4-Pip (1) -Ph H Et-(CH_Two)_Two-O O CH 1-271 H 4-Pip (1) -Ph H tBu -CH_Two-O O CH 1-272 H 4-Pip (1) -Ph H tBu -CH_Two-O S CH 1-273 H 4-Pip (1) -Ph H Ph -CH_Two-O O CH 1-274 H 4-Pip (1) -Ph H Bz -CH_Two-O O CH 1-275 H 4-Pip (1) -Ph 4-Cl Me -CH_Two-O O CH 1-276 H 4-Pip (1) -Ph 5-Me Me -CH_Two-O O CH 1-277 H 4-Pip (1) -Ph 5-MeO Me -CH_Two-O O CH 1-278 2-Cl 4-Pip (1) -Ph H Me -CH_Two-O O CH 1-279 3-Cl 4-Pip (1) -Ph H Me -CH_Two-O O CH 1-280 2-Me 4-Pip (1) -Ph H Me -CH_Two-O O CH 1-281 3-Me 4-Pip (1) -Ph H Me -CH_Two-O O CH 1-282 2-MeO 4-Pip (1) -Ph H Me -CH_Two-O O CH 1-283 3-MeO 4-Pip (1) -Ph H Me -CH_Two-O O CH 1-284 H 2-Mor (4) -Ph H Me -CH_Two-O O CH 1-285 H 2-Mor (4) -Ph H Me -CH_Two-O O N 1-286 H 2-Mor (4) -Ph H Me -CH_Two-O S CH 1-287 H 2-Mor (4) -Ph H Me-(CH_Two)_Two-O O CH 1-288 H 2-Mor (4) -Ph H Me-(CH_Two)_Three-O O CH 1-289 H 2-Mor (4) -Ph H Et -CH_Two-O O CH 1-290 H 2-Mor (4) -Ph H Et -CH_Two-O S CH 1-291 H 2-Mor (4) -Ph H tBu -CH_Two-O O CH 1-292 H 3-Mor (4) -Ph H Me -CH_Two-O O CH 1-293 H 3-Mor (4) -Ph H Me -CH_Two-O O N 1-294 H 3-Mor (4) -Ph H Me -CH_Two-O S CH 1-295 H 3-Mor (4) -Ph H Me-(CH_Two)_Two-O O CH 1-296 H 3-Mor (4) -Ph H Me-(CH_Two)_Three-O O CH 1-297 H 3-Mor (4) -Ph H Et -CH_Two-O O CH 1-298 H 3-Mor (4) -Ph H Et -CH_Two-O S CH 1-299 H 3-Mor (4) -Ph H tBu -CH_Two-O O CH 1-300 3-MeO 3-Mor (4) -Ph 4-Me Pr-(CH_Two)_Three-S S CH 1-301 H 4-Mor (4) -Ph H H -CH_Two-O O CH 1-302 H 4-Mor (4) -Ph H Me -CH_Two-O O CH 1-303 H 4-Mor (4) -Ph H Me -CH_Two-O O N 1-304 H 4-Mor (4) -Ph H Me -CH_Two-O S CH 1-305 H 4-Mor (4) -Ph H Me -CH_Two-O S N 1-306 H 4-Mor (4) -Ph H Me -CH_Two-S O CH 1-307 H 4-Mor (4) -Ph H Me-(CH_Two)_Two-O O CH 1-308 H 4-Mor (4) -Ph H Me-(CH_Two)_Two-O O N 1-309 H 4-Mor (4) -Ph H Me-(CH_Two)_Two-O S CH 1-310 H 4-Mor (4) -Ph H Me -CH (Me)-O O CH 1-311 H 4-Mor (4) -Ph H Me-(CH_Two)_Three-O O CH 1-312 H 4-Mor (4) -Ph H Et -CH_Two-O O CH 1-313 H 4-Mor (4) -Ph H Et -CH_Two-O O N 1-314 H 4-Mor (4) -Ph H Et -CH_Two-O S CH 1-315 H 4-Mor (4) -Ph H Et-(CH_Two)_Two-O O CH 1-316 H 4-Mor (4) -Ph H tBu -CH_Two-O O CH 1-317 H 4-Mor (4) -Ph H tBu -CH_Two-O S CH 1-318 H 4-Mor (4) -Ph H Ph -CH_Two-O O CH 1-319 H 4-Mor (4) -Ph H Bz -CH_Two-O O CH 1-320 H 4-Mor (4) -Ph 5-Cl Me -CH_Two-O O CH 1-321 H 4-Mor (4) -Ph 5-Me Me -CH_Two-O O CH 1-322 H 4-Mor (4) -Ph 5-MeO Me -CH_Two-O O CH 1-323 2-Cl 4-Mor (4) -Ph H Me -CH_Two-O O CH 1-324 3-Cl 4-Mor (4) -Ph H Me -CH_Two-O O CH 1-325 2-Me 4-Mor (4) -Ph H Me -CH_Two-O O CH 1-326 3-Me 4-Mor (4) -Ph H Me -CH_Two-O O CH 1-327 2-MeO 4-Mor (4) -Ph H Me -CH_Two-O O CH 1-328 3-MeO 4-Mor (4) -Ph H Me -CH_Two-O O CH 1-329 H 2-TioMor (4) -Ph H Me -CH_Two-O O CH 1-330 H 2-TioMor (4) -Ph H Me -CH_Two-O S CH 1-331 H 3-TioMor (4) -Ph H Me -CH_Two-O O CH 1-332 H 3-TioMor (4) -Ph H Me -CH_Two-O S CH 1-333 H 4-TioMor (4) -Ph H Me -CH_Two-O O CH 1-334 H 4-TioMor (4) -Ph H Me -CH_Two-O O N 1-335 H 4-TioMor (4) -Ph H Me -CH_Two-O S CH 1-336 H 4-TioMor (4) -Ph H Et -CH_Two-O O CH 1-337 H 4-TioMor (4) -Ph H Et -CH_Two-O S CH 1-338 H 2-Pipra (1) -Ph H Me -CH_Two-O O CH 1-339 H 2-Pipra (1) -Ph H Me -CH_Two-O S CH 1-340 H 3-Pipra (1) -Ph H Me -CH_Two-O O CH 1-341 H 3-Pipra (1) -Ph H Me -CH_Two-O S CH 1-342 H 4-Pipra (1) -Ph H Me -CH_Two-O O CH 1-343 H 4-Pipra (1) -Ph H Me -CH_Two-O O N 1-344 H 4-Pipra (1) -Ph H Me -CH_Two-O S CH 1-345 H 4-Pipra (1) -Ph H Me-(CH_Two)_Two-O O CH 1-346 H 4-Pipra (1) -Ph H Me-(CH_Two)_Three-O O CH 1-347 H 4-Pipra (1) -Ph H Et -CH_Two-O O CH 1-348 H 4-Pipra (1) -Ph H Et -CH_Two-O S CH 1-349 H 4-Pipra (1) -Ph H tBu -CH_Two-O O CH 1-350 H 2-NO_Two-Ph H Me -CH_Two-O O CH 1-351 H 3-NO_Two-Ph H Me -CH_Two-O O CH 1-352 H 4-NO_Two-Ph H Me -CH_Two-O O CH 1-353 H 4-NO_Two-Ph H Me -CH_Two-O S CH 1-354 H 3-F-4-OH-Ph H Me -CH_Two-O O CH 1-355 H 2-Cl-4-OH-Ph H Me -CH_Two-O O CH 1-356 H 2-Cl-4-OH-Ph H Me -CH_Two-O S CH 1-357 H 3-Cl-4-OH-Ph H Me -CH_Two-O O CH 1-358 H 3-Cl-4-OH-Ph H Me -CH_Two-O O N 1-359 H 3-Cl-4-OH-Ph H Me -CH_Two-O S CH 1-360 H 3-Cl-4-OH-Ph H Et -CH_Two-O O CH 1-361 H 3-Cl-4-OH-Ph H Et -CH_Two-O S CH 1-362 H 2-F-4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-363 H 2-F-4-OH-3,5-diMe-Ph H Me -CH_Two-O S CH 1-364 H 4-F-3-OH-2,5-diEt-Ph H Me -CH_Two-O O CH 1-365 H 4-F-3-OH-2,5-diEt-Ph H Me -CH_Two-O S CH 1-366 H 2-Cl-4-OH-3,5-diMe-Ph H H -CH_Two-O O CH 1-367 H 2-Cl-4-OH-3,5-diMe-Ph H H -CH_Two-O S CH 1-368 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-369 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O O N 1-370 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O S CH 1-371 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O S N 1-372 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-S O CH 1-373 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-S O N 1-374 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-S S CH 1-375 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-S SN 1-376 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH_Two)_Two-O O CH 1-377 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH_Two)_Two-O O N 1-378 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH_Two)_Two-O S CH 1-379 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH_Two)_Two-O S N 1-380 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH_Two)_Two-SO CH 1-381 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH (Me)-OO CH 1-382 H 2-Cl-4-OH-3,5-diMe- Ph H Me -CH (Me)-OS CH 1-383 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH_Two)_Three-O O CH 1-384 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH_Two)_Three-O S CH 1-385 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH_Two)_Four-O O CH 1-386 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH_Two-O O CH 1-387 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH_Two-O O N 1-388 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH_Two-O S CH 1-389 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH_Two-O S N 1-390 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH_Two-S O CH 1-391 H 2-Cl-4-OH-3,5-diMe-Ph H Et-(CH_Two)_Two-O O CH 1-392 H 2-Cl-4-OH-3,5-diMe-Ph H Et-(CH_Two)_Two-O S CH 1-393 H 2-Cl-4-OH-3,5-diMe-Ph H Pr -CH_Two-O O CH 1-394 H 2-Cl-4-OH-3,5-diMe-Ph H iPr -CH_Two-O O CH 1-395 H 2-Cl-4-OH-3,5-diMe-Ph H Bu -CH_Two-O O CH 1-396 H 2-Cl-4-OH-3,5-diMe-Ph H sBu -CH_Two-O O CH 1-397 H 2-Cl-4-OH-3,5-diMe-Ph H sBu-(CH_Two)_Three-O O CH 1-398 H 2-Cl-4-OH-3,5-diMe-Ph H tBu -CH_Two-O O CH 1-399 H 2-Cl-4-OH-3,5-diMe-Ph H tBu -CH_Two-O S CH 1-400 H 2-Cl-4-OH-3,5-diMe-Ph H Ph -CH_Two-O O CH 1-401 H 2-Cl-4-OH-3,5-diMe-Ph H Ph -CH_Two-O O N 1-402 H 2-Cl-4-OH-3,5-diMe-Ph H Ph -CH_Two-O S CH 1-403 H 2-Cl-4-OH-3,5-diMe-Ph H Ph-(CH_Two)_Two-O O CH 1-404 H 2-Cl-4-OH-3,5-diMe-Ph H Bz -CH_Two-O O CH 1-405 H 2-Cl-4-OH-3,5-diMe-Ph H Bz -CH_Two-O O N 1-406 H 2-Cl-4-OH-3,5-diMe-Ph H Bz -CH_Two-O S CH 1-407 H 2-Cl-4-OH-3,5-diMe-Ph H Bz-(CH_Two)_Two-O O CH 1-408 H 2-Cl-4-OH-3,5-diMe-Ph 5-F Me -CH_Two-O O CH 1-409 H 2-Cl-4-OH-3,5-diMe-Ph 4-Cl Me -CH_Two-O O CH 1-410 H 2-Cl-4-OH-3,5-diMe-Ph 5-Cl Me -CH_Two-O O CH 1-411 H 2-Cl-4-OH-3,5-diMe-Ph 4-Me Me -CH_Two-O O CH 1-412 H 2-Cl-4-OH-3,5-diMe-Ph 5-Me Me -CH_Two-O O CH 1-413 H 2-Cl-4-OH-3,5-diMe-Ph 4-MeO Me -CH_Two-O O CH 1-414 H 2-Cl-4-OH-3,5-diMe-Ph 5-MeO Me -CH_Two-O O CH 1-415 H 2-Cl-4-OH-3,5-diMe-Ph 5-MeS Me -CH_Two-O O CH 1-416 3-F 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-417 2-Cl 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-418 3-Cl 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-419 2-Me 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-420 3-Me 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-421 3-CF_Three 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-422 2-MeO 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-423 3-MeO 2-Cl-4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-424 H 2-Cl-4-OH-3,5-diEt-Ph H Me -CH_Two-O O CH 1-425 H 2-Cl-4-OH-3,5-diEt-Ph H Me -CH_Two-O S CH 1-426 H 2-Cl-4-OH-3,5-ditBu-Ph H Me -CH_Two-O O CH 1-427 H 2-Cl-4-OH-3,5-ditBu-Ph H Me -CH_Two-O S CH 1-428 H 3-Cl-5-OH-2,6-diMe-Ph H Me -CH_Two-O O CH 1-429 H 3-Cl-5-OH-2,6-diMe-Ph H Me -CH_Two-O O N 1-430 H 3-Cl-5-OH-2,6-diMe-Ph H Me -CH_Two-O S CH 1-431 H 3-Cl-5-OH-2,6-diMe-Ph H Et -CH_Two-O O CH 1-432 H 3-Cl-5-OH-2,6-diMe-Ph H Et -CH_Two-O S CH 1-433 H 4-Cl-3-OH-2,5-diMe-Ph H Me -CH_Two-O O CH 1-434 H 4-Cl-3-OH-2,5-diMe-Ph H Me -CH_Two-O O N 1-435 H 4-Cl-3-OH-2,5-diMe-Ph H Me -CH_Two-O S CH 1-436 H 4-Cl-3-OH-2,5-diMe-Ph H Et -CH_Two-O O CH 1-437 H 4-Cl-3-OH-2,5-diMe-Ph H Et -CH_Two-O S CH 1-438 H 3-Cl-4-NH_Two-Ph H Me -CH_Two-O O CH 1-439 H 3-Cl-4-NH_Two-Ph H Me -CH_Two-O S CH 1-440 H 3,5-diCl-4-NH_Two-Ph H Me -CH_Two-O O CH 1-441 H 3,5-diCl-4-NH_Two-Ph H Me -CH_Two-O O N 1-442 H 3,5-diCl-4-NH_Two-Ph H Me -CH_Two-O S CH 1-443 H 3,5-diCl-4-NH_Two-Ph H Et -CH_Two-O O CH 1-444 H 3,5-diCl-4-NH_Two-Ph H Et -CH_Two-O S CH 1-445 H 3,5-diF-4-NH_Two-Ph H Me -CH_Two-O O CH 1-446 H 3,5-diF-4-NH_Two-Ph H Me -CH_Two-O S CH 1-447 H 4-NHMe-3-Cl-Ph H Me -CH_Two-O O CH 1-448 H 4-NHMe-3-Cl-Ph H Me -CH_Two-O S CH 1-449 H 3-Cl-4-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-450 H 3-Cl-4-Pyrd (1) -Ph H Me -CH_Two-O S CH 1-451 H 3-OH-4-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-452 H 3-OH-4-Pyrd (1) -Ph H Me -CH_Two-O S CH 1-453 H 3-Cl-6-Me-4-Pyrd (1) -Ph H Me -CH_Two-O O CH 1-454 H 3-Cl-6-Me-4-Pyrd (1) -Ph H Me -CH_Two-O S CH 1-455 H 2-Me-4-Pip (1) -Ph H Me -CH_Two-O O CH 1-456 H 2-Me-4-Pip (1) -Ph H Me -CH_Two-O S CH 1-457 H 2-Me-4-Mor (4) -Ph H Me -CH_Two-O O CH 1-458 H 2-Me-4-Mor (4) -Ph H Me -CH_Two-O S CH 1-459 H 2-OH-3-Me-Ph H Me -CH_Two-O O CH 1-460 H 2-OH-3-Me-Ph H Me -CH_Two-O S CH 1-461 H 2-OH-4-Me-Ph H Me -CH_Two-O O CH 1-462 H 2-OH-4-Me-Ph H Me -CH_Two-O S CH 1-463 H 2-OH-3,4-diMe-Ph H Me -CH_Two-O O CH 1-464 H 2-OH-3,4-diMe-Ph H Me -CH_Two-O O N 1-465 H 2-OH-3,4-diMe-Ph H Me -CH_Two-O S CH 1-466 H 2-OH-3,4-diMe-Ph H Et -CH_Two-O O CH 1-467 H 2-OH-3,4-diMe-Ph H Et -CH_Two-O S CH 1-468 H 3-OH-2-Me-Ph H Me -CH_Two-O O CH 1-469 H 3-OH-2-Me-Ph H Me -CH_Two-O S CH 1-470 H 3-OH-4-Me-Ph H Me -CH_Two-O O CH 1-471 H 3-OH-4-Me-Ph H Me -CH_Two-O S CH 1-472 H 3-OH-5-Me-Ph H Me -CH_Two-O O CH 1-473 H 3-OH-5-Me-Ph H Me -CH_Two-O S CH 1-474 H 3-OH-6-Me-Ph H Me -CH_Two-O O CH 1-475 H 3-OH-6-Me-Ph H Me -CH_Two-O S CH 1-476 H 3-OH-2,4-diMe-Ph H Me -CH_Two-O O CH 1-477 H 3-OH-2,4-diMe-Ph H Me -CH_Two-O O N 1-478 H 3-OH-2,4-diMe-Ph H Me -CH_Two-O S CH 1-479 H 3-OH-2,4-diMe-Ph H Et -CH_Two-O O CH 1-480 H 3-OH-2,4-diMe-Ph H Et -CH_Two-O S CH 1-481 H 4-OH-2-Me-Ph H Me -CH_Two-O O CH 1-482 H 4-OH-2-Me-Ph H Me -CH_Two-O O N 1-483 H 4-OH-2-Me-Ph H Me -CH_Two-O S CH 1-484 H 4-OH-2-Me-Ph H Et -CH_Two-O O CH 1-485 H 4-OH-2-Me-Ph H Et -CH_Two-O S CH 1-486 H 4-OH-3-Me-Ph H Me -CH_Two-O O CH 1-487 H 4-OH-3-Me-Ph H Me -CH_Two-O O N 1-488 H 4-OH-3-Me-Ph H Me -CH_Two-O S CH 1-489 H 4-OH-3-Me-Ph H Me-(CH_Two)_Two-O O CH 1-490 H 4-OH-3-Me-Ph H Et -CH_Two-O O CH 1-491 H 4-OH-3-Me-Ph H Et -CH_Two-O S CH 1-492 H 4-OH-3-Me-Ph H tBu -CH_Two-O O CH 1-493 H 4-OH-3-Me-Ph 5-Cl Me -CH_Two-O O CH 1-494 H 4-OH-2-Et-Ph H Me -CH_Two-O O CH 1-495 H 4-OH-2-Et-Ph H Me -CH_Two-O S CH 1-496 H 4-OH-3-Et-Ph H Me -CH_Two-O O CH 1-497 H 4-OH-3-Et-Ph H Me -CH_Two-O S CH 1-498 H 4-OH-3-Pr-Ph H Me -CH_Two-O O CH 1-499 H 4-OH-2-tBu-Ph H Me -CH_Two-O O CH 1-500 H 4-OH-2-tBu-Ph H Me -CH_Two-O S CH 1-501 H 4-OH-3-tBu-Ph H Me -CH_Two-O O CH 1-502 H 4-OH-3-tBu-Ph H Me -CH_Two-O ON 1-503 H 4-OH-3-tBu-Ph H Me -CH_Two-O S CH 1-504 H 4-OH-3-tBu-Ph H Et -CH_Two-O O CH 1-505 H 4-OH-3-tBu-Ph H Et -CH_Two-O S CH 1-506 H 4-OH-2,3-diMe-Ph H Me -CH_Two-O O CH 1-507 H 4-OH-2,3-diMe-Ph H Me -CH_Two-O ON 1-508 H 4-OH-2,3-diMe-Ph H Me -CH_Two-O S CH 1-509 H 4-OH-2,3-diMe-Ph H Me-(CH_Two)_Three-S O CH 1-510 H 4-OH-2,3-diMe-Ph H Et -CH_Two-O O CH 1-511 H 4-OH-2,3-diMe-Ph H Et -CH_Two-O S CH 1-512 H 4-OH-2,3-diMe-Ph H tBu -CH_Two-O O CH 1-513 H 4-OH-2,5-diMe-Ph H Me -CH_Two-O O CH 1-514 H 4-OH-2,5-diMe-Ph H Me -CH_Two-O ON 1-515 H 4-OH-2,5-diMe-Ph H Me -CH_Two-O S CH 1-516 H 4-OH-2,5-diMe-Ph H Et -CH_Two-O O CH 1-517 H 4-OH-2,5-diMe-Ph H Et -CH_Two-O S CH 1-518 H 4-OH-3,5-diMe-Ph H H -CH_Two-O O CH 1-519 H 4-OH-3,5-diMe-Ph H H -CH_Two-O S CH 1-520 H 4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-521 H 4-OH-3,5-diMe-Ph H Me -CH_Two-O ON 1-522 H 4-OH-3,5-diMe-Ph H Me -CH_Two-O S CH 1-523 H 4-OH-3,5-diMe-Ph H Me -CH_Two-O S N 1-524 H 4-OH-3,5-diMe-Ph H Me -CH_Two-S O CH 1-525 H 4-OH-3,5-diMe-Ph H Me -CH_Two-S ON 1-526 H 4-OH-3,5-diMe-Ph H Me -CH_Two-S S CH 1-527 H 4-OH-3,5-diMe-Ph H Me -CH_Two-S SN 1-528 H 4-OH-3,5-diMe-Ph H Me-(CH_Two)_Two-O O CH 1-529 H 4-OH-3,5-diMe-Ph H Me-(CH_Two)_Two-O ON 1-530 H 4-OH-3,5-diMe-Ph H Me-(CH_Two)_Two-O S CH 1-531 H 4-OH-3,5-diMe-Ph H Me-(CH_Two)_Two-O S N 1-532 H 4-OH-3,5-diMe-Ph H Me-(CH_Two)_Two-SO CH 1-533 H 4-OH-3,5-diMe-Ph H Me -CH (Me)-OO CH 1-534 H 4-OH-3,5-diMe-Ph H Me -CH (Me) -OS CH 1-535 H 4-OH-3,5-diMe-Ph H Me-(CH_Two)_Three-O O CH 1-536 H 4-OH-3,5-diMe-Ph H Me-(CH_Two)_Three-O S CH 1-537 H 4-OH-3,5-diMe-Ph H Me-(CH_Two)_Four-O O CH 1-538 H 4-OH-3,5-diMe-Ph H Et -CH_Two-O O CH 1-539 H 4-OH-3,5-diMe-Ph H Et -CH_Two-O ON 1-540 H 4-OH-3,5-diMe-Ph H Et -CH_Two-O S CH 1-541 H 4-OH-3,5-diMe-Ph H Et -CH_Two-O S N 1-542 H 4-OH-3,5-diMe-Ph H Et -CH_Two-S O CH 1-543 H 4-OH-3,5-diMe-Ph H Et-(CH_Two)_Two-O O CH 1-544 H 4-OH-3,5-diMe-Ph H Et-(CH_Two)_Two-O S CH 1-545 H 4-OH-3,5-diMe-Ph H Pr -CH_Two-O O CH 1-546 H 4-OH-3,5-diMe-Ph H iPr -CH_Two-O O CH 1-547 H 4-OH-3,5-diMe-Ph H Bu -CH_Two-O O CH 1-548 H 4-OH-3,5-diMe-Ph H sBu -CH_Two-O O CH 1-549 H 4-OH-3,5-diMe-Ph H sBu-(CH_Two)_Three-O O CH 1-550 H 4-OH-3,5-diMe-Ph H tBu -CH_Two-O O CH 1-551 H 4-OH-3,5-diMe-Ph H tBu -CH_Two-O S CH 1-552 H 4-OH-3,5-diMe-Ph H Ph -CH_Two-O O CH 1-554 H 4-OH-3,5-diMe-Ph H Ph -CH_Two-O S CH 1-555 H 4-OH-3,5-diMe-Ph H Ph-(CH_Two)_Two-O O CH 1-556 H 4-OH-3,5-diMe-Ph H Bz -CH_Two-O O CH 1-557 H 4-OH-3,5-diMe-Ph H Bz -CH_Two-O ON 1-558 H 4-OH-3,5-diMe-Ph H Bz -CH_Two-O S CH 1-559 H 4-OH-3,5-diMe-Ph H Bz-(CH_Two)_Two-O O CH 1-560 H 4-OH-3,5-diMe-Ph 5-F Me -CH_Two-O O CH 1-561 H 4-OH-3,5-diMe-Ph 4-Cl Me -CH_Two-O O CH 1-562 H 4-OH-3,5-diMe-Ph 5-Cl Me -CH_Two-O O CH 1-563 H 4-OH-3,5-diMe-Ph 4-Me Me -CH_Two-O O CH 1-564 H 4-OH-3,5-diMe-Ph 5-Me Me -CH_Two-O O CH 1-565 H 4-OH-3,5-diMe-Ph 4-MeO Me -CH_Two-O O CH 1-566 H 4-OH-3,5-diMe-Ph 5-MeO Me -CH_Two-O O CH 1-567 H 4-OH-3,5-diMe-Ph 5-MeS Me -CH_Two-O O CH 1-568 3-F 4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-569 2-Cl 4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-570 3-Cl 4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-571 2-Me 4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-572 3-Me 4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-573 3-CF_Three 4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-574 2-MeO 4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-575 2-MeO 4-OH-3,5-diMe-Ph H Me -CH_Two-O S CH 1-576 3-MeO 4-OH-3,5-diMe-Ph H Me -CH_Two-O O CH 1-577 H 3,5-diEt-4-OH-Ph H Me -CH_Two-O O CH 1-578 H 3,5-diEt-4-OH-Ph H Me -CH_Two-O ON 1-579 H 3,5-diEt-4-OH-Ph H Me -CH_Two-O S CH 1-580 H 3,5-diEt-4-OH-Ph H Et -CH_Two-O O CH 1-581 H 3,5-diEt-4-OH-Ph H Et -CH_Two-O S CH 1-582 H 3-tBu-4-OH-5-Me-Ph H Me -CH_Two-O O CH 1-583 H 3-tBu-4-OH-5-Me-Ph H Me -CH_Two-O ON 1-584 H 3-tBu-4-OH-5-Me-Ph H Me -CH_Two-O S CH 1-585 H 3-tBu-4-OH-5-Me-Ph H Et -CH_Two-O O CH 1-586 H 3-tBu-4-OH-5-Me-Ph H Et -CH_Two-O S CH 1-587 H 4-OH-3,5-diPr-Ph H Me -CH_Two-O O CH 1-588 H 4-OH-3,5-diPr-Ph H Me -CH_Two-O S CH 1-589 H 4-OH-3,5-diiPr-Ph H Me -CH_Two-O O CH 1-590 H 4-OH-3,5-diiPr-Ph H Me -CH_Two-O S CH 1-591 H 3,5-ditBu-4-OH-Ph H H -CH_Two-O O CH 1-592 H 3,5-ditBu-4-OH-Ph H H -CH_Two-O S CH 1-593 H 3,5-ditBu-4-OH-Ph H Me -CH_Two-O O CH 1-594 H 3,5-ditBu-4-OH-Ph H Me -CH_Two-O ON 1-595 H 3,5-ditBu-4-OH-Ph H Me -CH_Two-O S CH 1-596 H 3,5-ditBu-4-OH-Ph H Me -CH_Two-O S N 1-597 H 3,5-ditBu-4-OH-Ph H Me -CH_Two-S O CH 1-598 H 3,5-ditBu-4-OH-Ph H Me -CH_Two-S ON 1-599 H 3,5-ditBu-4-OH-Ph H Me -CH_Two-S S CH 1-600 H 3,5-ditBu-4-OH-Ph H Me -CH_Two-S SN 1-601 H 3,5-ditBu-4-OH-Ph H Me-(CH_Two)_Two-O O CH 1-602 H 3,5-ditBu-4-OH-Ph H Me-(CH_Two)_Two-O ON 1-603 H 3,5-ditBu-4-OH-Ph H Me-(CH_Two)_Two-O S CH 1-604 H 3,5-ditBu-4-OH-Ph H Me-(CH_Two)_Two-OSN 1-605 H 3,5-ditBu-4-OH-Ph H Me-(CH_Two)_Two-SO CH 1-606 H 3,5-ditBu-4-OH-Ph H Me -CH (Me)-OO CH 1-607 H 3,5-ditBu-4-OH-Ph H Me -CH (Me) -OS CH 1-608 H 3,5-ditBu-4-OH-Ph H Me-(CH_Two)_Three-O O CH 1-609 H 3,5-ditBu-4-OH-Ph H Me-(CH_Two)_Three-O S CH 1-610 H 3,5-ditBu-4-OH-Ph H Me-(CH_Two)_Four-O O CH 1-611 H 3,5-ditBu-4-OH-Ph H Et -CH_Two-O O CH 1-612 H 3,5-ditBu-4-OH-Ph H Et -CH_Two-O ON 1-613 H 3,5-ditBu-4-OH-Ph H Et -CH_Two-O S CH 1-614 H 3,5-ditBu-4-OH-Ph H Et -CH_Two-O S N 1-615 H 3,5-ditBu-4-OH-Ph H Et -CH_Two-S O CH 1-616 H 3,5-ditBu-4-OH-Ph H Et-(CH_Two)_Two-O O CH 1-617 H 3,5-ditBu-4-OH-Ph H Et-(CH_Two)_Two-O S CH 1-618 H 3,5-ditBu-4-OH-Ph H Pr -CH_Two-O O CH 1-619 H 3,5-ditBu-4-OH-Ph H iPr -CH_Two-O O CH 1-620 H 3,5-ditBu-4-OH-Ph H Bu -CH_Two-O O CH 1-621 H 3,5-ditBu-4-OH-Ph H sBu -CH_Two-O O CH 1-622 H 3,5-ditBu-4-OH-Ph H sBu-(CH_Two)_Three-O O CH 1-623 H 3,5-ditBu-4-OH-Ph H tBu -CH_Two-O O CH 1-624 H 3,5-ditBu-4-OH-Ph H tBu -CH_Two-O S CH 1-625 H 3,5-ditBu-4-OH-Ph H Ph -CH_Two-O O CH 1-626 H 3,5-ditBu-4-OH-Ph H Ph -CH_Two-O ON 1-627 H 3,5-ditBu-4-OH-Ph H Ph -CH_Two-O S CH 1-628 H 3,5-ditBu-4-OH-Ph H Ph-(CH_Two)_Two-O O CH 1-629 H 3,5-ditBu-4-OH-Ph H Bz -CH_Two-O O CH 1-630 H 3,5-ditBu-4-OH-Ph H Bz -CH_Two-O ON 1-631 H 3,5-ditBu-4-OH-Ph H Bz -CH_Two-O S CH 1-632 H 3,5-ditBu-4-OH-Ph H Bz-(CH_Two)_Two-O O CH 1-633 H 3,5-ditBu-4-OH-Ph 5-F Me -CH_Two-O O CH 1-634 H 3,5-ditBu-4-OH-Ph 5-Cl Me -CH_Two-O S CH 1-635 H 3,5-ditBu-4-OH-Ph 5-Cl Me -CH_Two-O O CH 1-636 H 3,5-ditBu-4-OH-Ph 4-Me Me -CH_Two-O O CH 1-637 H 3,5-ditBu-4-OH-Ph 5-Me Me -CH_Two-O O CH 1-638 H 3,5-ditBu-4-OH-Ph 4-MeO Me -CH_Two-O O CH 1-639 H 3,5-ditBu-4-OH-Ph 5-MeO Me -CH_Two-O O CH 1-640 3-F 3,5-ditBu-4-OH-Ph H Me -CH_Two-O O CH 1-641 2-Cl 3,5-ditBu-4-OH-Ph H Me -CH_Two-O O CH 1-642 3-Cl 3,5-ditBu-4-OH-Ph H Me -CH_Two-O O CH 1-643 2-Me 3,5-ditBu-4-OH-Ph H Me -CH_Two-O O CH 1-644 3-Me 3,5-ditBu-4-OH-Ph H Me -CH_Two-O O CH 1-645 3-CF_Three 3,5-ditBu-4-OH-Ph H Me -CH_Two-O O CH 1-646 2-MeO 3,5-ditBu-4-OH-Ph H Me -CH_Two-O O CH 1-647 3-MeO 3,5-ditBu-4-OH-Ph H Me -CH_Two-O O CH 1-648 H 4-OH-2,3,5-triMe-Ph H H -CH_Two-O O CH 1-649 H 4-OH-2,3,5-triMe-Ph H H -CH_Two-O S CH 1-650 H 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O O CH 1-651 H 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O ON 1-652 H 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O S CH 1-653 H 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O S N 1-654 H 4-OH-2,3,5-triMe-Ph H Me -CH_Two-S O CH 1-655 H 4-OH-2,3,5-triMe-Ph H Me -CH_Two-S ON 1-656 H 4-OH-2,3,5-triMe-Ph H Me -CH_Two-S S CH 1-657 H 4-OH-2,3,5-triMe-Ph H Me -CH_Two-S SN 1-658 H 4-OH-2,3,5-triMe-Ph H Me-(CH_Two)_Two-O O CH 1-659 H 4-OH-2,3,5-triMe-Ph H Me-(CH_Two)_Two-O ON 1-660 H 4-OH-2,3,5-triMe-Ph H Me-(CH_Two)_Two-O S CH 1-661 H 4-OH-2,3,5-triMe-Ph H Me-(CH_Two)_Two-O S N 1-662 H 4-OH-2,3,5-triMe-Ph H Me-(CH_Two)_Two-SO CH 1-663 H 4-OH-2,3,5-triMe-Ph H Me -CH (Me)-OO CH 1-664 H 4-OH-2,3,5-triMe-Ph H Me- CH (Me)-OS CH 1-665 H 4-OH-2,3,5-triMe-Ph H Me-(CH_Two)_Three-O O CH 1-666 H 4-OH-2,3,5-triMe-Ph H Me-(CH_Two)_Three-O S CH 1-667 H 4-OH-2,3,5-triMe-Ph H Me-(CH_Two)_Four-O O CH 1-668 H 4-OH-2,3,5-triMe-Ph H Et -CH_Two-O O CH 1-669 H 4-OH-2,3,5-triMe-Ph H Et -CH_Two-O ON 1-670 H 4-OH-2,3,5-triMe-Ph H Et -CH_Two-O S CH 1-671 H 4-OH-2,3,5-triMe-Ph H Et -CH_Two-O S N 1-672 H 4-OH-2,3,5-triMe-Ph H Et -CH_Two-S O CH 1-673 H 4-OH-2,3,5-triMe-Ph H Et-(CH_Two)_Two-O O CH 1-674 H 4-OH-2,3,5-triMe-Ph H Et-(CH_Two)_Two-O S CH 1-675 H 4-OH-2,3,5-triMe-Ph H Pr -CH_Two-O O CH 1-676 H 4-OH-2,3,5-triMe-Ph H iPr -CH_Two-O O CH 1-677 H 4-OH-2,3,5-triMe-Ph H Bu -CH_Two-O O CH 1-678 H 4-OH-2,3,5-triMe-Ph H sBu -CH_Two-O O CH 1-679 H 4-OH-2,3,5-triMe-Ph H sBu-(CH_Two)_Three-O O CH 1-680 H 4-OH-2,3,5-triMe-Ph H tBu -CH_Two-O O CH 1-681 H 4-OH-2,3,5-triMe-Ph H tBu -CH_Two-O S CH 1-682 H 4-OH-2,3,5-triMe-Ph H Ph -CH_Two-O O CH 1-683 H 4-OH-2,3,5-triMe-Ph H Ph -CH_Two-O ON 1-684 H 4-OH-2,3,5-triMe-Ph H Ph -CH_Two-O S CH 1-685 H 4-OH-2,3,5-triMe-Ph H Ph-(CH_Two)_Two-O O CH 1-686 H 4-OH-2,3,5-triMe-Ph H Bz -CH_Two-O O CH 1-687 H 4-OH-2,3,5-triMe-Ph H Bz -CH_Two-O ON 1-688 H 4-OH-2,3,5-triMe-Ph H Bz -CH_Two-O S CH 1-689 H 4-OH-2,3,5-triMe-Ph H Bz-(CH_Two)_Two-O O CH 1-690 H 4-OH-2,3,5-triMe-Ph 5-F Me -CH_Two-O O CH 1-691 H 4-OH-2,3,5-triMe-Ph 4-Cl Me -CH_Two-O O CH 1-692 H 4-OH-2,3,5-triMe-Ph 5-Cl Me -CH_Two-O O CH 1-693 H 4-OH-2,3,5-triMe-Ph 4-Me Me -CH_Two-O O CH 1-694 H 4-OH-2,3,5-triMe-Ph 5-Me Me -CH_Two-O O CH 1-695 H 4-OH-2,3,5-triMe-Ph 4-MeO Me -CH_Two-O O CH 1-696 H 4-OH-2,3,5-triMe-Ph 5-MeO Me -CH_Two-O O CH 1-697 H 4-OH-2,3,5-triMe-Ph 5-MeS Me -CH_Two-O O CH 1-698 3-F 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O O CH 1-699 2-Cl 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O O CH 1-700 3-Cl 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O O CH 1-701 2-Me 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O O CH 1-702 3-Me 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O O CH 1-703 3-CF_Three 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O O CH 1-704 2-MeO 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O O CH 1-705 3-MeO 4-OH-2,3,5-triMe-Ph H Me -CH_Two-O O CH 1-706 H 4-OH-2,3,6-triMe-Ph H Me -CH_Two-O O CH 1-707 H 4-OH-2,3,6-triMe-Ph H Me -CH_Two-O ON 1-708 H 4-OH-2,3,6-triMe-Ph H Me -CH_Two-O S CH 1-709 H 4-OH-2,3,6-triMe-Ph H Et -CH_Two-O O CH 1-710 H 4-OH-2,3,6-triMe-Ph H Et -CH_Two-O S CH 1-711 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH_Two-O O CH 1-712 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH_Two-O ON 1-713 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH_Two-O S CH 1-714 H 4-OH-2,3,5,6-tetraMe-Ph H Et -CH_Two-O O CH 1-715 H 4-OH-2,3,5,6-tetraMe-Ph H Et -CH_Two-O S CH 1-716 H 4-OH-3,5-diCF_Three-Ph H Me -CH_Two-O O CH 1-717 H 4-OH-3,5-diCF_Three-Ph H Me -CH_Two-O S CH 1-718 H 4-OH-3,5-diMeO-Ph H Me -CH_Two-O O CH 1-719 H 4-OH-3,5-diMeO-Ph H Me -CH_Two-O S CH 1-720 H 4-OH-3,5-ditBuO-Ph H Me -CH_Two-O O CH 1-721 H 4-OH-3,5-ditBuO-Ph H Me -CH_Two-O S CH 1-722 H 3-NH_Two-4-Me-Ph H Me -CH_Two-O O CH 1-723 H 3-NH_Two-4-Me-Ph H Me -CH_Two-O O N 1-724 H 3-NH_Two-4-Me-Ph H Me -CH_Two-O S CH 1-725 H 3-NH_Two-4-Me-Ph H Et -CH_Two-O O CH 1-726 H 3-NH_Two-4-Me-Ph H Et -CH_Two-O S CH 1-727 H 4-NH_Two-2,3-diMe-Ph H Me -CH_Two-O O CH 1-728 H 4-NH_Two-2,3-diMe-Ph H Me -CH_Two-O O N 1-729 H 4-NH_Two-2,3-diMe-Ph H Me -CH_Two-O S CH 1-730 H 4-NH_Two-2,3-diMe-Ph H Et -CH_Two-O O CH 1-731 H 4-NH_Two-2,3-diMe-Ph H Et -CH_Two-O S CH 1-732 H 4-NH_Two-2,6-diMe-Ph H Me -CH_Two-O O CH 1-733 H 4-NH_Two-2,6-diMe-Ph H Me -CH_Two-O O N 1-734 H 4-NH_Two-2,6-diMe-Ph H Me -CH_Two-O S CH 1-735 H 4-NH_Two-2,6-diMe-Ph H Et -CH_Two-O O CH 1-736 H 4-NH_Two-2,6-diMe-Ph H Et -CH_Two-O S CH 1-737 H 4-NH_Two-3,5-diMe-Ph H H -CH_Two-O O CH 1-738 H 4-NH_Two-3,5-diMe-Ph H H -CH_Two-O S CH 1-739 H 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O O CH 1-740 H 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O O N 1-741 H 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O S CH 1-742 H 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O S N 1-743 H 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-S O CH 1-744 H 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-S ON 1-745 H 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-S S CH 1-746 H 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-S SN 1-747 H 4-NH_Two-3,5-diMe-Ph H Me-(CH_Two)_Two-O O CH 1-748 H 4-NH_Two-3,5-diMe-Ph H Me-(CH_Two)_Two-O ON 1-749 H 4-NH_Two-3,5-diMe-Ph H Me-(CH_Two)_Two-O S CH 1-750 H 4-NH_Two-3,5-diMe-Ph H Me-(CH_Two)_Two-O S N 1-751 H 4-NH_Two-3,5-diMe-Ph H Me-(CH_Two)_Two-S O CH 1-752 H 4-NH_Two-3,5-diMe-Ph H Me -CH (Me)-O O CH 1-753 H 4-NH_Two-3,5-diMe-Ph H Me -CH (Me)-O S CH 1-754 H 4-NH_Two-3,5-diMe-Ph H Me-(CH_Two)_Three-O O CH 1-755 H 4-NH_Two-3,5-diMe-Ph H Me-(CH_Two)_Three-O S CH 1-756 H 4-NH_Two-3,5-diMe-Ph H Me-(CH_Two)_Four-O O CH 1-757 H 4-NH_Two-3,5-diMe-Ph H Et -CH_Two-O O CH 1-758 H 4-NH_Two-3,5-diMe-Ph H Et -CH_Two-O ON 1-759 H 4-NH_Two-3,5-diMe-Ph H Et -CH_Two-O S CH 1-760 H 4-NH_Two-3,5-diMe-Ph H Et -CH_Two-O S N 1-761 H 4-NH_Two-3,5-diMe-Ph H Et -CH_Two-S O CH 1-762 H 4-NH_Two-3,5-diMe-Ph H Et-(CH_Two)_Two-O O CH 1-763 H 4-NH_Two-3,5-diMe-Ph H Et-(CH_Two)_Two-O S CH 1-764 H 4-NH_Two-3,5-diMe-Ph H Pr -CH_Two-O O CH 1-765 H 4-NH_Two-3,5-diMe-Ph H iPr -CH_Two-O O CH 1-766 H 4-NH_Two-3,5-diMe-Ph H Bu -CH_Two-O O CH 1-767 H 4-NH_Two-3,5-diMe-Ph H sBu -CH_Two-O O CH 1-768 H 4-NH_Two-3,5-diMe-Ph H sBu-(CH_Two)_Three-O O CH 1-769 H 4-NH_Two-3,5-diMe-Ph H tBu -CH_Two-O O CH 1-770 H 4-NH_Two-3,5-diMe-Ph H tBu -CH_Two-O S CH 1-771 H 4-NH_Two-3,5-diMe-Ph H Ph -CH_Two-O O CH 1-772 H 4-NH_Two-3,5-diMe-Ph H Ph -CH_Two-O ON 1-773 H 4-NH_Two-3,5-diMe-Ph H Ph -CH_Two-O S CH 1-774 H 4-NH_Two-3,5-diMe-Ph H Ph-(CH_Two)_Two-O O CH 1-775 H 4-NH_Two-3,5-diMe-Ph H Bz -CH_Two-O O CH 1-776 H 4-NH_Two-3,5-diMe-Ph H Bz -CH_Two-O O N 1-777 H 4-NH_Two-3,5-diMe-Ph H Bz -CH_Two-O S CH 1-778 H 4-NH_Two-3,5-diMe-Ph H Bz-(CH_Two)_Two-O O CH 1-779 H 4-NH_Two-3,5-diMe-Ph 5-F Me -CH_Two-O O CH 1-780 H 4-NH_Two-3,5-diMe-Ph 4-Cl Me -CH_Two-O O CH 1-781 H 4-NH_Two-3,5-diMe-Ph 5-Cl Me -CH_Two-O O CH 1-782 H 4-NH_Two-3,5-diMe-Ph 4-Me Me -CH_Two-O O CH 1-783 H 4-NH_Two-3,5-diMe-Ph 5-Me Me -CH_Two-O O CH 1-784 H 4-NH_Two-3,5-diMe-Ph 4-MeO Me -CH_Two-O O CH 1-785 H 4-NH_Two-3,5-diMe-Ph 5-MeO Me -CH_Two-O O CH 1-786 3-F 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O O CH 1-787 2-Cl 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O O CH 1-788 3-Cl 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O O CH 1-789 2-Me 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O O CH 1-790 3-Me 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O O CH 1-791 3-CF_Three 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O O CH 1-792 2-MeO 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O O CH 1-793 3-MeO 4-NH_Two-3,5-diMe-Ph H Me -CH_Two-O O CH 1-794 H 4-NH_Two-3,5-diEt-Ph H Me -CH_Two-O O CH 1-795 H 4-NH_Two-3,5-diEt-Ph H Me -CH_Two-O O N 1-796 H 4-NH_Two-3,5-diEt-Ph H Me -CH_Two-O S CH 1-797 H 4-NH_Two-3,5-diEt-Ph H Et -CH_Two-O O CH 1-798 H 4-NH_Two-3,5-diEt-Ph H Et -CH_Two-O S CH 1-799 H 4-NH_Two-3,5-ditBu-Ph H Me -CH_Two-O O CH 1-800 H 4-NH_Two-3,5-ditBu-Ph H Me -CH_Two-O S CH 1-801 H 4-NHMe-3,5-diMe-Ph H Me -CH_Two-O O CH 1-802 H 4-NHMe-3,5-diMe-Ph H Me -CH_Two-O ON 1-803 H 4-NHMe-3,5-diMe-Ph H Me -CH_Two-O S CH 1-804 H 4-NHMe-3,5-diMe-Ph H Et -CH_Two-O O CH 1-805 H 4-NHMe-3,5-dime-Ph H Et -CH_Two-O S CH 1-806 H 4-NHEt-3,5-diMe-Ph H Me -CH_Two-O O CH 1-807 H 4-NHEt-3,5-diMe-Ph H Me -CH_Two-O S CH 1-808 H 4-NHAc-3,5-diMe-Ph H Me -CH_Two-O O CH 1-809 H 4-NHAc-3,5-diMe-Ph H Me -CH_Two-O S CH 1-810 H 4-NO_Two-2,6-diMe-Ph H Me -CH_Two-O O CH 1-811 H 4-NO_Two-2,6-diMe-Ph H Me -CH_Two-O S CH 1-812 H 4-NO_Two-3,5-diMe-Ph H Me -CH_Two-O O CH 1-813 H 4-NO_Two-3,5-diMe-Ph H Me -CH_Two-O O N 1-814 H 4-NO_Two-3,5-diMe-Ph H Me -CH_Two-O S CH 1-815 H 4-NO_Two-3,5-diMe-Ph H Et -CH_Two-O O CH 1-816 H 4-NO_Two-3,5-diMe-Ph H Et -CH_Two-O S CH 1-817 H 4-NO_Two-3,5-ditBu-Ph H Me -CH_Two-O O CH 1-818 H 4-NO_Two-3,5-ditBu-Ph H Me -CH_Two-O S CH 1-819 H Pyr (2) H H -CH_Two-O O CH 1-820 H Pyr (2) H H -CH_Two-O S CH 1-821 H Pyr (2) H Me -CH_Two-O O CH 1-822 H Pyr (2) H Me -CH_Two-O ON 1-823 H Pyr (2) H Me -CH_Two-O S CH 1-824 H Pyr (2) H Me -CH_Two-O S N 1-825 H Pyr (2) H Me -CH_Two-S O CH 1-826 H Pyr (2) H Me -CH_Two-S ON 1-827 H Pyr (2) H Me -CH_Two-S S CH 1-828 H Pyr (2) H Me -CH_Two-S SN 1-829 H Pyr (2) H Me-(CH_Two)_Two-O O CH 1-830 H Pyr (2) H Me-(CH_Two)_Two-O ON 1-831 H Pyr (2) H Me-(CH_Two)_Two-O S CH 1-832 H Pyr (2) H Me-(CH_Two)_Two-OSN 1-833 H Pyr (2) H Me-(CH_Two)_Two-SO CH 1-834 H Pyr (2) H Me -CH (Me)-OO CH 1-835 H Pyr (2) H Me -CH (Me)-OS CH 1-836 H Pyr (2) H Me- (CH_Two)_Three-O O CH 1-837 H Pyr (2) H Me-(CH_Two)_Three-O S CH 1-838 H Pyr (2) H Me-(CH_Two)_Four-O O CH 1-839 H Pyr (2) H Et -CH_Two-O O CH 1-840 H Pyr (2) H Et -CH_Two-O ON 1-841 H Pyr (2) H Et -CH_Two-O S CH 1-842 H Pyr (2) H Et -CH_Two-O S N 1-843 H Pyr (2) H Et -CH_Two-S O CH 1-844 H Pyr (2) H Et-(CH_Two)_Two-O O CH 1-845 H Pyr (2) H Et-(CH_Two)_Two-O S CH 1-846 H Pyr (2) H Pr -CH_Two-O O CH 1-847 H Pyr (2) H iPr -CH_Two-O O CH 1-848 H Pyr (2) H Bu -CH_Two-O O CH 1-849 H Pyr (2) H sBu -CH_Two-O O CH 1-850 H Pyr (2) H sBu-(CH_Two)_Three-O O CH 1-851 H Pyr (2) H tBu -CH_Two-O O CH 1-852 H Pyr (2) H tBu -CH_Two-O S CH 1-853 H Pyr (2) H Ph -CH_Two-O O CH 1-854 H Pyr (2) H Ph -CH_Two-O ON 1-855 H Pyr (2) H Ph -CH_Two-O S CH 1-856 H Pyr (2) H Ph-(CH_Two)_Two-O O CH 1-857 H Pyr (2) H Bz -CH_Two-O O CH 1-858 H Pyr (2) H Bz -CH_Two-O ON 1-859 H Pyr (2) H Bz -CH_Two-O S CH 1-860 H Pyr (2) H Bz-(CH_Two)_Two-O O CH 1-861 H Pyr (2) 5-F Me -CH_Two-O O CH 1-862 H Pyr (2) 4-Cl Me -CH_Two-O O CH 1-863 H Pyr (2) 5-Cl Me -CH_Two-O O CH 1-864 H Pyr (2) 4-Me Me -CH_Two-O O CH 1-865 H Pyr (2) 5-Me Me -CH_Two-O O CH 1-866 H Pyr (2) 4-MeO Me -CH_Two-O O CH 1-867 H Pyr (2) 5-MeO Me -CH_Two-O O CH 1-868 H Pyr (2) 5-MeS Me -CH_Two-O O CH 1-869 3-F Pyr (2) H Me -CH_Two-O O CH 1-870 2-Cl Pyr (2) H Me -CH_Two-O O CH 1-871 3-Cl Pyr (2) H Me -CH_Two-O O CH 1-872 2-Me Pyr (2) H Me -CH_Two-O O CH 1-873 3-Me Pyr (2) H Me -CH_Two-O O CH 1-874 3-CF_Three Pyr (2) H Me -CH_Two-O O CH 1-875 2-MeO Pyr (2) H Me -CH_Two-O O CH 1-876 3-MeO Pyr (2) H Me -CH_Two-O O CH 1-877 H 5-F-Pyr (2) H Me -CH_Two-O O CH 1-878 H 5-F-Pyr (2) H Me -CH_Two-O S CH 1-879 H 6-F-Pyr (2) H Me -CH_Two-O O CH 1-880 H 6-F-Pyr (2) H Me -CH_Two-O S CH 1-881 H 5-Cl-Pyr (2) H Me -CH_Two-O O CH 1-882 H 5-Cl-Pyr (2) H Me -CH_Two-O ON 1-883 H 5-Cl-Pyr (2) H Me -CH_Two-O S CH 1-884 H 5-Cl-Pyr (2) H Et -CH_Two-O O CH 1-885 H 5-Cl-Pyr (2) H Et -CH_Two-O S CH 1-886 H 6-Cl-Pyr (2) H Me -CH_Two-O O CH 1-887 H 6-Cl-Pyr (2) H Me -CH_Two-O ON 1-888 H 6-Cl-Pyr (2) H Me -CH_Two-O S CH 1-889 H 6-Cl-Pyr (2) H Et -CH_Two-O O CH 1-890 H 6-Cl-Pyr (2) H Et -CH_Two-O S CH 1-891 H 6-Me-Pyr (2) H Me -CH_Two-O O CH 1-892 H 6-Me-Pyr (2) H Me -CH_Two-O S CH 1-893 H 6-Et-Pyr (2) H Me -CH_Two-O O CH 1-894 H 6-CF_Three-Pyr (2) H Me -CH_Two-O O CH 1-895 H 6-MeO-Pyr (2) H Me -CH_Two-O O CH 1-896 H 6-MeO-Pyr (2) H Me -CH_Two-O ON 1-897 H 6-MeO-Pyr (2) H Me -CH_Two-O S CH 1-898 H 6-MeO-Pyr (2) H Et -CH_Two-O O CH 1-899 H 6-MeO-Pyr (2) H Et -CH_Two-O S CH 1-900 H 6-EtO-Pyr (2) H Me -CH_Two-O O CH 1-901 H 6-EtO-Pyr (2) H Me -CH_Two-O S CH 1-902 H 6-iPrO-Pyr (2) H Me -CH_Two-O O CH 1-903 H 6-MeS-Pyr (2) H Me -CH_Two-O O CH 1-904 H 3-NH_Two-Pyr (2) H Me -CH_Two-O O CH 1-905 H 3-NH_Two-Pyr (2) H Me -CH_Two-O ON 1-906 H 3-NH_Two-Pyr (2) H Me -CH_Two-O S CH 1-907 H 3-NH_Two-Pyr (2) H Et -CH_Two-O O CH 1-908 H 3-NH_Two-Pyr (2) H Et -CH_Two-O S CH 1-909 H 5-NH_Two-Pyr (2) H Me -CH_Two-O O CH 1-910 H 5-NH_Two-Pyr (2) H Me -CH_Two-O ON 1-911 H 5-NH_Two-Pyr (2) H Me -CH_Two-O S CH 1-912 H 5-NH_Two-Pyr (2) H Et -CH_Two-O O CH 1-913 H 5-NH_Two-Pyr (2) H Et -CH_Two-O S CH 1-914 H 3-NHMe-Pyr (2) H Me -CH_Two-O O CH 1-915 H 3-NHMe-Pyr (2) H Me -CH_Two-O S CH 1-916 H 5-NHMe-Pyr (2) H Me -CH_Two-O O CH 1-917 H 5-NHMe-Pyr (2) H Me -CH_Two-O S CH 1-918 H 3-N (Me)_Two-Pyr (2) H Me -CH_Two-O O CH 1-919 H 5-N (Me)_Two-Pyr (2) H Me -CH_Two-O O CH 1-920 H 3-NO_Two-Pyr (2) H Me -CH_Two-O O CH 1-921 H 3-NO_Two-Pyr (2) H Me -CH_Two-O ON 1-922 H 3-NO_Two-Pyr (2) H Me -CH_Two-O S CH 1-923 H 3-NO_Two-Pyr (2) H Et -CH_Two-O O CH 1-924 H 3-NO_Two-Pyr (2) H Et -CH_Two-O S CH 1-925 H 5-NO_Two-Pyr (2) H Me -CH_Two-O O CH 1-926 H 5-NO_Two-Pyr (2) H Me -CH_Two-O ON 1-927 H 5-NO_Two-Pyr (2) H Me -CH_Two-O S CH 1-928 H 5-NO_Two-Pyr (2) H Et -CH_Two-O O CH 1-929 H 5-NO_Two-Pyr (2) H Et -CH_Two-O S CH 1-930 H 5-NH_Two-6-Cl-Pyr (2) H Me -CH_Two-O O CH 1-931 H 5-NH_Two-6-Cl-Pyr (2) H Me -CH_Two-O ON 1-932 H 5-NH_Two-6-Cl-Pyr (2) H Me -CH_Two-O S CH 1-933 H 5-NH_Two-6-Cl-Pyr (2) H Et -CH_Two-O O CH 1-934 H 5-NH_Two-6-Cl-Pyr (2) H Et -CH_Two-O S CH 1-935 3-MeO 5-NH_Two-6-Cl-Pyr (2) 5-MeO Et-(CH_Two)_Four-S S CH 1-936 H Pyr (3) H H -CH_Two-O O CH 1-937 H Pyr (3) H H -CH_Two-O S CH 1-938 H Pyr (3) H Me -CH_Two-O O CH 1-939 H Pyr (3) H Me -CH_Two-O ON 1-940 H Pyr (3) H Me -CH_Two-O S CH 1-941 H Pyr (3) H Me -CH_Two-O S N 1-942 H Pyr (3) H Me -CH_Two-S O CH 1-943 H Pyr (3) H Me -CH_Two-S ON 1-944 H Pyr (3) H Me -CH_Two-S S CH 1-945 H Pyr (3) H Me -CH_Two-S SN 1-946 H Pyr (3) H Me-(CH_Two)_Two-O O CH 1-947 H Pyr (3) H Me-(CH_Two)_Two-O ON 1-948 H Pyr (3) H Me-(CH_Two)_Two-O S CH 1-949 H Pyr (3) H Me-(CH_Two)_Two-O S N 1-950 H Pyr (3) H Me-(CH_Two)_Two-SO CH 1-951 H Pyr (3) H Me -CH (Me)-OO CH 1-952 H Pyr (3) H Me -CH (Me)-OS CH 1-953 H Pyr (3) H Me- (CH_Two)_Three-O O CH 1-954 H Pyr (3) H Me-(CH_Two)_Three-O S CH 1-955 H Pyr (3) H Me-(CH_Two)_Four-O O CH 1-956 H Pyr (3) H Et -CH_Two-O O CH 1-957 H Pyr (3) H Et -CH_Two-O ON 1-958 H Pyr (3) H Et -CH_Two-O S CH 1-959 H Pyr (3) H Et -CH_Two-O S N 1-960 H Pyr (3) H Et -CH_Two-S O CH 1-961 H Pyr (3) H Et-(CH_Two)_Two-O O CH 1-962 H Pyr (3) H Et-(CH_Two)_Two-O S CH 1-963 H Pyr (3) H Pr -CH_Two-O O CH 1-964 H Pyr (3) H iPr -CH_Two-O O CH 1-965 H Pyr (3) H Bu -CH_Two-O O CH 1-966 H Pyr (3) H sBu -CH_Two-O O CH 1-967 H Pyr (3) H sBu-(CH_Two)_Three-O O CH 1-968 H Pyr (3) H tBu -CH_Two-O O CH 1-969 H Pyr (3) H tBu -CH_Two-O S CH 1-970 H Pyr (3) H Pn-(CH_Two)_Three-O O CH 1-971 H Pyr (3) H Ph -CH_Two-O O CH 1-972 H Pyr (3) H Ph -CH_Two-O ON 1-973 H Pyr (3) H Ph -CH_Two-O S CH 1-974 H Pyr (3) H Ph-(CH_Two)_Two-O O CH 1-975 H Pyr (3) H Bz -CH_Two-O O CH 1-976 H Pyr (3) H Bz -CH_Two-O ON 1-977 H Pyr (3) H Bz -CH_Two-O S CH 1-978 H Pyr (3) H Bz-(CH_Two)_Two-O O CH 1-979 H Pyr (3) 5-F Me -CH_Two-O O CH 1-980 H Pyr (3) 4-Cl Me -CH_Two-O O CH 1-981 H Pyr (3) 5-Cl Me -CH_Two-O O CH 1-982 H Pyr (3) 4-Me Me -CH_Two-O O CH 1-983 H Pyr (3) 5-Me Me -CH_Two-O O CH 1-984 H Pyr (3) 4-MeO Me -CH_Two-O O CH 1-985 H Pyr (3) 5-MeO Me -CH_Two-O O CH 1-986 H Pyr (3) 5-MeS Me -CH_Two-O O CH 1-987 3-F Pyr (3) H Me -CH_Two-O O CH 1-988 2-Cl Pyr (3) H Me -CH_Two-O O CH 1-989 3-Cl Pyr (3) H Me -CH_Two-O O CH 1-990 2-Me Pyr (3) H Me -CH_Two-O O CH 1-991 3-Me Pyr (3) H Me -CH_Two-O O CH 1-992 3-CF_Three Pyr (3) H Me -CH_Two-O O CH 1-993 2-MeO Pyr (3) H Me -CH_Two-O O CH 1-994 3-MeO Pyr (3) H Me -CH_Two-O O CH 1-995 H 6-Cl-Pyr (3) H Me -CH_Two-O O CH 1-996 H 6-Cl-Pyr (3) H Me -CH_Two-O S CH 1-997 H 6-Me-Pyr (3) H Me -CH_Two-O O CH 1-998 H 6-Me-Pyr (3) H Me -CH_Two-O S CH 1-999 H 5-MeO-Pyr (3) H Me -CH_Two-O O CH 1-1000 H 5-MeO-Pyr (3) H Me -CH_Two-O ON 1-11-1 H 5-MeO-Pyr (3) H Me -CH_Two-O S CH 1-1002 H 5-MeO-Pyr (3) H Et -CH_Two-O O CH 1-1003 H 5-MeO-Pyr (3) H Et -CH_Two-O S CH 1-1004 H 6-MeO-Pyr (3) H Me -CH_Two-O O CH 1-1005 H 6-MeO-Pyr (3) H Me -CH_Two-O O N 1-1006 H 6-MeO-Pyr (3) H Me -CH_Two-O S CH 1-1007 H 6-MeO-Pyr (3) H Me-(CH_Two)_Two-O O CH 1-1008 H 6-MeO-Pyr (3) H Me-(CH_Two)_Three-O O CH 1-1009 H 6-MeO-Pyr (3) H Et -CH_Two-O O CH 1-1010 H 6-MeO-Pyr (3) H Et -CH_Two-O S CH 1-1011 H 6-MeO-Pyr (3) H tBu -CH_Two-O O CH 1-1012 H 6-EtO-Pyr (3) H Me -CH_Two-O O CH 1-1013 H 6-EtO-Pyr (3) H Me -CH_Two-O S CH 1-1014 H 6-iPrO-Pyr (3) H Me -CH_Two-O O CH 1-1015 H 6-iPrO-Pyr (3) H Me -CH_Two-O O N 1-1016 H 6-iPrO-Pyr (3) H Me -CH_Two-O S CH 1-1017 H 6-iPrO-Pyr (3) H Et -CH_Two-O O CH 1-1018 H 6-iPrO-Pyr (3) H Et -CH_Two-O S CH 1-1019 H 6-MeO-5-Me-Pyr (3) H Me -CH_Two-O O CH 1-1020 H 6-MeO-5-Me-Pyr (3) H Me -CH_Two-O ON 1-1021 H 6-MeO-5-Me-Pyr (3) H Me -CH_Two-O S CH 1-1022 H 6-MeO-5-Me-Pyr (3) H Et -CH_Two-O O CH 1-1023 H 6-MeO-5-Me-Pyr (3) H Et -CH_Two-O S CH 1-1024 H 2-NO_Two-6-Me-Pyr (3) H Me -CH_Two-O O CH 1-1025 H 2-NO_Two-6-Me-Pyr (3) H Me -CH_Two-O ON 1-1026 H 2-NO_Two-6-Me-Pyr (3) H Me -CH_Two-O S CH 1-1027 H 2-NO_Two-6-Me-Pyr (3) H Et -CH_Two-O O CH 1-1028 H 2-NO_Two-6-Me-Pyr (3) H Et -CH_Two-O S CH 1-1029 H Pyr (4) H H -CH_Two-O O CH 1-1030 H Pyr (4) H H -CH_Two-O S CH 1-1031 H Pyr (4) H Me -CH_Two-O O CH 1-1032 H Pyr (4) H Me -CH_Two-O ON 1-1033 H Pyr (4) H Me -CH_Two-O S CH 1-1034 H Pyr (4) H Me -CH_Two-O S N 1-1035 H Pyr (4) H Me -CH_Two-S O CH 1-1036 H Pyr (4) H Me -CH_Two-S ON 1-1037 H Pyr (4) H Me -CH_Two-S S CH 1-1038 H Pyr (4) H Me -CH_Two-S S N 1-1039 H Pyr (4) H Me-(CH_Two)_Two-O O CH 1-1040 H Pyr (4) H Me-(CH_Two)_Two-O ON 1-1041 H Pyr (4) H Me-(CH_Two)_Two-O S CH 1-1042 H Pyr (4) H Me-(CH_Two)_Two-OSN 1-1043 H Pyr (4) H Me-(CH_Two)_Two-SO CH 1-1044 H Pyr (4) H Me -CH (Me)-OO CH 1-1045 H Pyr (4) H Me -CH (Me)-OS CH 1-1046 H Pyr (4) H Me- (CH_Two)_Three-O O CH 1-1047 H Pyr (4) H Me-(CH_Two)_Three-O S CH 1-1048 H Pyr (4) H Me-(CH_Two)_Four-O O CH 1-1049 H Pyr (4) H Et -CH_Two-O O CH 1-1050 H Pyr (4) H Et -CH_Two-O ON 1-1051 H Pyr (4) H Et -CH_Two-O S CH 1-1052 H Pyr (4) H Et -CH_Two-OSN 1-1053 H Pyr (4) H Et -CH_Two-S O CH 1-1054 H Pyr (4) H Et-(CH_Two)_Two-O O CH 1-1055 H Pyr (4) H Et-(CH_Two)_Two-O S CH 1-1056 H Pyr (4) H Pr -CH_Two-O O CH 1-1057 H Pyr (4) H iPr -CH_Two-O O CH 1-1058 H Pyr (4) H Bu -CH_Two-O O CH 1-1059 H Pyr (4) H sBu -CH_Two-O O CH 1-1060 H Pyr (4) H sBu-(CH_Two)_Three-O O CH 1-1061 H Pyr (4) H tBu -CH_Two-O O CH 1-1062 H Pyr (4) H tBu -CH_Two-O S CH 1-1063 H Pyr (4) H Ph -CH_Two-O O CH 1-1064 H Pyr (4) H Ph -CH_Two-O ON 1-1065 H Pyr (4) H Ph -CH_Two-O S CH 1-1066 H Pyr (4) H Ph-(CH_Two)_Two-O O CH 1-1067 H Pyr (4) H Bz -CH_Two-O O CH 1-1068 H Pyr (4) H Bz -CH_Two-O ON 1-1069 H Pyr (4) H Bz -CH_Two-O S CH 1-1070 H Pyr (4) H Bz-(CH_Two)_Two-O O CH 1-1071 H Pyr (4) 5-F Me -CH_Two-O O CH 1-1072 H Pyr (4) 4-Cl Me -CH_Two-O O CH 1-1073 H Pyr (4) 5-Cl Me -CH_Two-O O CH 1-1074 H Pyr (4) 4-Me Me -CH_Two-O O CH 1-1075 H Pyr (4) 5-Me Me -CH_Two-O O CH 1-1076 H Pyr (4) 4-MeO Me -CH_Two-O O
CH 1-1077 H Pyr (4) 5-MeO Me -CH_Two-O O CH 1-1078 H Pyr (4) 5-MeS Me -CH_Two-O O CH 1-1079 3-F Pyr (4) H Me -CH_Two-O O CH 1-1080 2-Cl Pyr (4) H Me -CH_Two-O O CH 1-1081 3-Cl Pyr (4) H Me -CH_Two-O O CH 1-1082 2-Me Pyr (4) H Me -CH_Two-O O CH 1-1083 3-Me Pyr (4) H Me -CH_Two-O O CH 1-1084 3-CF_Three Pyr (4) H Me -CH_Two-O O CH 1-1085 2-MeO Pyr (4) H Me -CH_Two-O O CH 1-1086 3-MeO Pyr (4) H Me -CH_Two-O O CH 1-1087 H 2-F-Pyr (4) H Me -CH_Two-O O CH 1-1088 H 2-F-Pyr (4) H Me -CH_Two-O S CH 1-1089 H 2-Cl-Pyr (4) H Me -CH_Two-O O CH 1-1090 H 2-Cl-Pyr (4) H Me -CH_Two-O S CH 1-1091 H 2-Me-Pyr (4) H Me -CH_Two-O O CH 1-1092 H 2-Me-Pyr (4) H Me -CH_Two-O ON 1-1093 H 2-Me-Pyr (4) H Me -CH_Two-O S CH 1-1094 H 2-Me-Pyr (4) H Et -CH_Two-O O CH 1-1095 H 2-Me-Pyr (4) H Et -CH_Two-O S CH 1-1096 H 2-Et-Pyr (4) H Me -CH_Two-O O CH 1-1097 H 2-Et-Pyr (4) H Me -CH_Two-O S CH 1-1098 H 2,6-diMe-Pyr (4) H Me -CH_Two-O O CH 1-1099 H 2,6-diMe-Pyr (4) H Me -CH_Two-O O N 1-1100 H 2,6-diMe-Pyr (4) H Me -CH_Two-O S CH 1-1101 H 2,6-diMe-Pyr (4) H Me-(CH_Two)_Two-O O CH 1-1102 H 2,6-diMe-Pyr (4) H Et -CH_Two-O O CH 1-1103 H 2,6-diMe-Pyr (4) H Et -CH_Two-O S CH 1-1104 H 2,6-diMe-Pyr (4) H tBu -CH_Two-O O CH 1-1105 H 3,6-diMe-Pyr (4) H Me -CH_Two-O O CH 1-1106 H 3,6-diMe-Pyr (4) H Me -CH_Two-O O N 1-1107 H 3,6-diMe-Pyr (4) H Me -CH_Two-O S CH 1-1108 H 3,6-diMe-Pyr (4) H Et -CH_Two-O O CH 1-1109 H 3,6-diMe-Pyr (4) H Et -CH_Two-O S CH 1-1110 H 2-MeO-Pyr (4) H Me -CH_Two-O O CH 1-1111 H 2-MeO-Pyr (4) H Me -CH_Two-O ON 1-11-1 H 2-MeO-Pyr (4) H Me -CH_Two-O S CH 1-1113 H 2-MeO-Pyr (4) H Et -CH_Two-O O CH 1-1114 H 2-MeO-Pyr (4) H Et -CH_Two-O S CH 1-1115 H 2-EtO-Pyr (4) H Me -CH_Two-O O CH 1-1116 H 2-Imid (1) -Ph H Me -CH_Two-O O N 1-1117 H 2-Imid (1) -Ph H Me -CH_Two-O O CH 1-1118 H 2-Imid (1) -Ph H Me -CH_Two-O S CH 1-1119 H 2-Imid (1) -Ph H Me -CH_Two-O S N 1-1120 H 3-Imid (1) -Ph H Me -CH_Two-O ON 1-11-1 H 3-Imid (1) -Ph H Me -CH_Two-O O CH 1-1122 H 3-Imid (1) -Ph H Me -CH_Two-O S CH 1-1123 H 3-Imid (1) -Ph H Me -CH_Two-O S N 1-1124 H 4-Imid (1) -Ph H H -CH_Two-O O CH 1-1125 H 4-Imid (1) -Ph H H -CH_Two-O S CH 1-1126 H 4-Imid (1) -Ph H Me -CH_Two-O O CH 1-1127 H 4-Imid (1) -Ph H Me -CH_Two-O O N 1-1128 H 4-Imid (1) -Ph H Me -CH_Two-O S CH 1-1129 H 4-Imid (1) -Ph H Me -CH_Two-O S N 1-1130 H 4-Imid (1) -Ph H Me -CH_Two-S O CH 1-1131 H 4-Imid (1) -Ph H Me -CH_Two-S O N 1-1132 H 4-Imid (1) -Ph H Me -CH_Two-S S CH 1-1133 H 4-Imid (1) -Ph H Me -CH_Two-S S N 1-1134 H 4-Imid (1) -Ph H Me-(CH_Two)_Two-O O CH 1-1135 H 4-Imid (1) -Ph H Me-(CH_Two)_Two-O O N 1-1136 H 4-Imid (1) -Ph H Me-(CH_Two)_Two-O S CH 1-1137 H 4-Imid (1) -Ph H Me-(CH_Two)_Two-O S N 1-1138 H 4-Imid (1) -Ph H Et -CH_Two-O O CH 1-1139 H 4-Imid (1) -Ph H Et -CH_Two-O O N 1-1140 H 4-Imid (1) -Ph H Et -CH_Two-O S CH 1-1141 H 4-Imid (1) -Ph H Et -CH_Two-O S N 1-1142 H 4-Imid (1) -Ph H Ph -CH_Two-O O CH 1-1143 H 4-Imid (1) -Ph H Bz -CH_Two-O O CH 1-1144 H 2-Tz-Ph H Me -CH_Two-O O N 1-1145 H 2-Tz-Ph H Me -CH_Two-O O CH 1-1146 H 2-Tz-Ph H Me -CH_Two-O S CH 1-1147 H 2-Tz-Ph H Me -CH_Two-O S N 1-1148 H 3-Tz-Ph H Me -CH_Two-O O N 1-1149 H 3-Tz-Ph H Me -CH_Two-O O CH 1-1150 H 3-Tz-Ph H Me -CH_Two-O S CH 1-1151 H 3-Tz-Ph H Me -CH_Two-O S N 1-1152 H 4-Tz-Ph H H -CH_Two-O O CH 1-1153 H 4-Tz-Ph H H -CH_Two-O S CH 1-1154 H 4-Tz-Ph H Me -CH_Two-O O CH 1-1155 H 4-Tz-Ph H Me -CH_Two-O O N 1-1156 H 4-Tz-Ph H Me -CH_Two-O S CH 1-1157 H 4-Tz-Ph H Me -CH_Two-O S N 1-1158 H 4-Tz-Ph H Me -CH_Two-S O CH 1-1159 H 4-Tz-Ph H Me -CH_Two-S ON 1-1160 H 4-Tz-Ph H Me -CH_Two-S S CH 1-1161 H 4-Tz-Ph H Me -CH_Two-S S N 1-1162 H 4-Tz-Ph H Me-(CH_Two)_Two-O O CH 1-1163 H 4-Tz-Ph H Me-(CH_Two)_Two-O O N 1-1164 H 4-Tz-Ph H Me-(CH_Two)_Two-O S CH 1-1165 H 4-Tz-Ph H Me-(CH_Two)_Two-O S N 1-1166 H 4-Tz-Ph H Et -CH_Two-O O CH 1-1167 H 4-Tz-Ph H Et -CH_Two-O O N 1-1168 H 4-Tz-Ph H Et -CH_Two-O S CH 1-1169 H 4-Tz-Ph H Et -CH_Two-O S N 1-1170 H 4-Tz-Ph H Ph -CH_Two-O O CH 1-1171 H 4-Tz-Ph H Bz -CH_Two-O O CH 1-1172 H 2-Ada (1) -Ph H Me -CH_Two-O O N 1-1173 H 2-Ada (1) -Ph H Me -CH_Two-O O CH 1-1174 H 2-Ada (1) -Ph H Me -CH_Two-O S CH 1-1175 H 2-Ada (1) -Ph H Me -CH_Two-O S N 1-1176 H 3-Ada (1) -Ph H Me -CH_Two-O O CH 1-1177 H 3-Ada (1) -Ph H Me -CH_Two-O O N 1-1178 H 3-Ada (1) -Ph H Me -CH_Two-O S CH 1-1179 H 3-Ada (1) -Ph H Me -CH_Two-O S N 1-1180 H 4-Ada (1) -Ph H H -CH_Two-O O CH 1-1181 H 4-Ada (1) -Ph H H -CH_Two-O S CH 1-1182 H 4-Ada (1) -Ph H Me -CH_Two-O O CH 1-1183 H 4-Ada (1) -Ph H Me -CH_Two-O O N 1-1184 H 4-Ada (1) -Ph H Me -CH_Two-O S CH 1-1185 H 4-Ada (1) -Ph H Me -CH_Two-O S N 1-1186 H 4-Ada (1) -Ph H Me -CH_Two-S O CH 1-1187 H 4-Ada (1) -Ph H Me -CH_Two-S ON 1-1188 H 4-Ada (1) -Ph H Me -CH_Two-S S CH 1-1189 H 4-Ada (1) -Ph H Me -CH_Two-S S N 1-1190 H 4-Ada (1) -Ph H Me-(CH_Two)_Two-O O CH 1-1191 H 4-Ada (1) -Ph H Me-(CH_Two)_Two-O O N 1-1192 H 4-Ada (1) -Ph H Me-(CH_Two)_Two-O S CH 1-1193 H 4-Ada (1) -Ph H Me-(CH_Two)_Two-O S N 1-1194 H 4-Ada (1) -Ph H Et -CH_Two-O O CH 1-1195 H 4-Ada (1) -Ph H Et -CH_Two-O O N 1-1196 H 4-Ada (1) -Ph H Et -CH_Two-O S CH 1-1197 H 4-Ada (1) -Ph H Et -CH_Two-O S N 1-1198 H 4-Ada (1) -Ph H Ph -CH_Two-O O CH 1-1199 H 4-Ada (1) -Ph H Bz -CH_Two-O O CH 1-1200 H 2-CN-Ph H Me -CH_Two-O O N 1-1201 H 2-CN-Ph H Me -CH_Two-O O CH 1-1202 H 2-CN-Ph H Me -CH_Two-O S CH 1-1203 H 2-CN-Ph H Me -CH_Two-O S N 1-1204 H 3-CN-Ph H Me -CH_Two-O O CH 1-1205 H 3-CN-Ph H Me -CH_Two-O O N 1-1206 H 3-CN-Ph H Me -CH_Two-O S CH 1-1207 H 3-CN-Ph H Me -CH_Two-O S N 1-1208 H 4-CN-Ph H H -CH_Two-O O CH 1-1209 H 4-CN-Ph H H -CH_Two-O S CH 1-1210 H 4-CN-Ph H Me -CH_Two-O O CH 1-1211 H 4-CN-Ph H Me -CH_Two-O O N 1-1212 H 4-CN-Ph H Me -CH_Two-O S CH 1-1213 H 4-CN-Ph H Me -CH_Two-O S N 1-1214 H 4-CN-Ph H Me -CH_Two-S O CH 1-1215 H 4-CN-Ph H Me -CH_Two-S ON 1-1216 H 4-CN-Ph H Me -CH_Two-S S CH 1-1217 H 4-CN-Ph H Me -CH_Two-S S N 1-1218 H 4-CN-Ph H Me-(CH_Two)_Two-O O CH 1-1219 H 4-CN-Ph H Me-(CH_Two)_Two-O O N 1-1220 H 4-CN-Ph H Me-(CH_Two)_Two-O S CH 1-1221 H 4-CN-Ph H Me-(CH_Two)_Two-O S N 1-1222 H 4-CN-Ph H Et -CH_Two-O O CH 1-1223 H 4-CN-Ph H Et -CH_Two-O O N 1-1224 H 4-CN-Ph H Et -CH_Two-O S CH 1-1225 H 4-CN-Ph H Et -CH_Two-O S N 1-1226 H 4-CN-Ph H Ph -CH_Two-O O CH 1-1227 H 4-CN-Ph H Bz -CH_Two-O O CH 1-1228 H 4-Bz-2-OH-Ph H Me -CH_Two-O O CH 1-1229 H 4-Bz-2-OH-Ph H Me -CH_Two-O O N 1-1230 H 4-Bz-3-OH-Ph H Me -CH_Two-O O CH 1-1231 H 4-Bz-3-OH-Ph H Me -CH_Two-O O N 1-1232 H 4-Bz-3-OH-Ph H Me -CH_Two-O S CH 1-1233 H 4-Bz-3-OH-Ph H Me -CH_Two-O S N 1-1234 H 4-OH-2,5-ditBu-Ph H Me -CH_Two-O O CH 1-1235 H pentaF-Ph H Me -CH_Two-O O CH 1-1236 H pentaF-Ph H Me -CH_Two-O O N 1-1237 H pentaF-Ph H Me -CH_Two-O S CH 1-1238 H pentaF-Ph H Me -CH_Two-O S N 1-1239 H 4-NHPn-Ph H Me -CH_Two-O O CH 1-1240 H 2-NHHx-Ph H Me -CH_Two-O O CH 1-1241 H 3-NHHx-Ph H Me -CH_Two-O O CH 1-1242 H 4-NHHx-Ph H Me -CH_Two-O O CH 1-1243 H 4-NHHx-Ph H Me -CH_Two-O O N 1-1244 H 4-NHHx-Ph H Me -CH_Two-O S CH 1-1245 H 4-NHHx-Ph H Me -CH_Two-O S N 1-1246 H 2-NHCOPh-Ph H Me -CH_Two-O O CH 1-1247 H 3-NHCOPh-Ph H Me -CH_Two-O O CH 1-1248 H 4-NHCOPh-Ph H Me -CH_Two-O O CH 1-1249 H 4-NHCOPh-Ph H Me -CH_Two-O O N 1-1250 H 4-NHCOPh-Ph H Me -CH_Two-O S CH 1-1251 H 4-NHCOPh-Ph H Me -CH_Two-O S N 1-1252 H 4-NHCO (3-F-Ph) -Ph H Me -CH_Two-O O CH 1-1253 H 4-NHCO (2-Cl-Ph) -Ph H Me -CH_Two-O O CH 1-1254 H 2-NHCO (3-Cl-Ph) -Ph H Me -CH_Two-O O CH 1-1255 H 3-NHCO (3-Cl-Ph) -Ph H Me -CH_Two-O O CH 1-1256 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH_Two-O O CH 1-1257 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH_Two-O O N 1-1258 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH_Two-O S CH 1-1259 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH_Two-O S N 1-1260 H 4-NHCO (4-Cl-Ph) -Ph H Me -CH_Two-O O CH 1-1261 H 2-NHCO (2,4-diF-Ph) -Ph H Me -CH_Two-O O CH 1-1262 H 3-NHCO (2,4-diF-Ph) -Ph H Me -CH_Two-O O CH 1-1263 H 4-NHCO (2,4-diF-Ph) -Ph H Me -CH_Two-O O CH 1-1264 H 4-NHCO (2,4-diF-Ph) -Ph H Me -CH_Two-O O N 1-1265 H 4-NHCO (2,4-diF-Ph) -Ph H Me -CH_Two-O S CH 1-1266 H 4-NHCO (2,4-diF-Ph) -Ph H Me -CH_Two-O S N 1-1267 H 2-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH_Two-O O CH 1-1268 H 3-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH_Two-O O CH 1-1269 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH_Two-O O CH 1-1270 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH_Two-O O N 1-1271 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH_Two-O S CH 1-1272 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH_Two-O S N 1-1273 H 4-NHCONp (1) -Ph H Me -CH_Two-O O CH 1-1274 H 4-NHCONp (1) -Ph H Me -CH_Two-O O N 1-1275 H 4-NHCONp (1) -Ph H Me -CH_Two-O S CH 1-1276 H 4-NHCONp (1) -Ph H Me -CH_Two-O S N 1-1277 H 4-NHCONp (2) -Ph H Me -CH_Two-O O CH 1-1279 H 4-NHCONp (2) -Ph H Me -CH_Two-O S CH 1-1280 H 4-NHCONp (2) -Ph H Me -CH_Two-O S N 1-1281 H 4-NHCOBz-Ph H Me -CH_Two-O O CH 1-1282 H 4-NHCO (2-Cl-Bz) -Ph H Me -CH_Two-O O CH 1-1283 H 2-NHCO (3-Cl-Bz) -Ph H Me -CH_Two-O O CH 1-1284 H 3-NHCO (3-Cl-Bz) -Ph H Me -CH_Two-O O CH 1-1285 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH_Two-O O CH 1-1286 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH_Two-O O N 1-1287 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH_Two-O S CH 1-1288 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH_Two-O S N 1-1289 H 4-NHCO (4-Cl-Bz) -Ph H Me -CH_Two-O O CH 1-1290 H 2-NHCOcPn-Ph H Me -CH_Two-O O CH 1-1291 H 3-NHCOcPn-Ph H Me -CH_Two-O O CH 1-1292 H 4-NHCOcPn-Ph H Me -CH_Two-O O CH 1-1293 H 4-NHCOcPn-Ph H Me -CH_Two-O O N 1-1294 H 4-NHCOcPn-Ph H Me -CH_Two-O S CH 1-1295 H 4-NHCOcPn-Ph H Me -CH_Two-O S N 1-1296 H 2-NHCOcHx-Ph H Me -CH_Two-O O CH 1-1297 H 3-NHCOcHx-Ph H Me -CH_Two-O O CH 1-1298 H 4-NHCOcHx-Ph H Me -CH_Two-O O CH 1-1299 H 4-NHCOcHx-Ph H Me -CH_Two-O O N 1-1300 H 4-NHCOcHx-Ph H Me -CH_Two-O S CH 1-1301 H 4-NHCOcHx-Ph H Me -CH_Two-O S N 1-1302 H 4-NHCOPyr (2) -Ph H Me -CH_Two-O O CH 1-1303 H 2-NHCOPyr (3) -Ph H Me -CH_Two-O O CH 1-1304 H 3-NHCOPyr (3) -Ph H Me -CH_Two-O O CH 1-1305 H 4-NHCOPyr (3) -Ph H Me -CH_Two-O O CH 1-1306 H 4-NHCOPyr (3) -Ph H Me -CH_Two-O O N 1-1307 H 4-NHCOPyr (3) -Ph H Me -CH_Two-O S CH 1-1308 H 4-NHCOPyr (3) -Ph H Me -CH_Two-O S N 1-1309 H 2-NHCOPyr (4) -Ph H Me -CH_Two-O O CH 1-1310 H 3-NHCOPyr (4) -Ph H Me -CH_Two-O O CH 1-1311 H 4-NHCOPyr (4) -Ph H Me -CH_Two-O O CH 1-1312 H 4-NHCOPyr (4) -Ph H Me -CH_Two-O O N 1-1313 H 4-NHCOPyr (4) -Ph H Me -CH_Two-O S CH 1-1314 H 4-NHCOPyr (4) -Ph H Me -CH_Two-O S N 1-1315 H 4-N (Ac) Pn-Ph H Me -CH_Two-O O CH 1-1316 H 2-N (Ac) Hx-Ph H Me -CH_Two-O O CH 1-1317 H 3-N (Ac) Hx-Ph H Me -CH_Two-O O CH 1-1318 H 4-N (Ac) Hx-Ph H Me -CH_Two-O O CH 1-1319 H 4-N (Ac) Hx-Ph H Me -CH_Two-O O N 1-1320 H 4-N (Ac) Hx-Ph H Me -CH_Two-O S CH 1-1321 H 4-N (Ac) Hx-Ph H Me -CH_Two-O S N 1-1322 H 4-N (COPh) Hx-Ph H Me -CH_Two-O O CH 1-1323 H 4-N [CO (3-Cl-Ph)] Hx-Ph H Me -CH_Two-O O CH 1-1324 H 4-N [CO (2,4-diF-Ph)] Hx-Ph H Me -CH_Two-O O CH 1-1325 H 4-N [CONp (1)] Hx-Ph H Me -CH_Two-O O CH 1-1326 H 4-N (COBz) Hx-Ph H Me -CH_Two-O O CH 1-1327 H 2-Ph-Ph H Me -CH_Two-O O CH  .

[0079]

[Table 2]

[0080]

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[0081] Cpd.No.R ² R ⁴ R ⁵ R ⁶ -A- BDE 2-1 H 4-F-Ph H Me -CH ₂ -OO CH 2-2 H 4-Cl-Ph H Me -CH ₂ -OO CH 2-3 H 2-OH-Ph H Me -CH ₂ -OO CH 2-4 H 2-OH-Ph H Me -CH ₂ -OS CH 2-5 H 2-OH-Ph H Me -CH ₂ -SO CH 2-6 H 2-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 2-7 H 2-OH-Ph H Et -CH ₂ -OO CH 2-8 H 2-OH-Ph H Et -CH ₂ -OS CH 2-9 H 2-OH-Ph H tBu -CH ₂ -OO CH 2-10 H 3-OH-Ph H Me -CH ₂ -OO CH 2-11 H 3-OH-Ph H Me -CH ₂ -OS CH 2-12 H 3-OH-Ph H Me -CH ₂ -SO CH 2-13 H 3-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 2-14 H 3-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 2-15 H 3-OH-Ph H Et -CH ₂ -OO CH 2-16 H 3-OH-Ph H Et -CH ₂ -OS CH 2-17 H 3-OH-Ph H tBu -CH ₂ -OO CH 2- 18 H 4-OH-Ph HH -CH ₂ -OO CH 2-19 H 4-OH-Ph H Me -CH ₂ -OO CH 2-20 H 4-OH-Ph H Me -CH ₂ -OON 2-21 H 4-OH-Ph H Me -CH ₂ -OS CH 2-22 H 4-OH-Ph H Me -CH ₂ -OSN 2-23 H 4-OH-Ph H Me -CH ₂ -SO CH 2-24 H 4-OH-Ph H Me -CH ₂ -SON 2-25 H 4-OH-Ph H Me -CH ₂ -SS CH 2-26 H 4-OH-Ph H Me -CH ₂ -SSN 2-27 H 4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 2-28 H 4-OH-Ph H Me-(CH ₂ ) ₂ -OON 2-29 H 4-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 2-30 H 4-OH-Ph H Me -CH (Me)-OO CH 2-31 H 4-OH-Ph H Me-(CH ₂ ) ₃ -OO CH 2-32 H 4-OH-Ph H Et -CH ₂ -OO CH 2-33 H 4-OH-Ph H Et -CH ₂ -OON 2-34 H 4-OH-Ph H Et -CH ₂ -OS CH 2-35 H 4-OH-Ph H Et-(CH ₂ ) ₂ -OO CH 2-36 H 4-OH-Ph H tBu -CH ₂ -OO CH 2-37 H 4-OH-Ph H tBu -CH ₂ -OS CH 2-38 H 4-OH-Ph H Ph -CH ₂ -OO CH 2-39 H 4-OH-Ph H Bz -CH ₂ -OO CH 2-40 H 4-OH-Ph 6-Cl Me -CH ₂ -OO CH 2-41 H 4-OH -Ph 6-Me Me -CH ₂ -OO CH 2-42 H 4-OH-Ph 6-MeO Me -CH ₂ -OO CH 2-43 2-Cl 4-OH-Ph H Me -CH ₂ -OO CH 2-44 3-Cl 4-OH-Ph H Me -CH ₂ -OO CH 2-45 2-Me 4-OH-Ph H Me -CH ₂ -OO CH 2-46 3-Me 4-OH-Ph H Me -CH ₂ -OO CH 2-47 2-MeO 4-OH-Ph H Me -CH ₂ -OO CH 2-48 3-MeO 4-OH-Ph H Me -CH ₂ -OO CH 2-49 H 3 -CF ₃ -Ph H Me -CH ₂ -OO CH 2-50 H 4-iPrO-Ph H Me -CH ₂ -OO CH 2-51 H 4-MeS-Ph H Me -CH ₂ -OO CH 2-52 H 2-NH ₂ -Ph H Me -CH ₂ -OO CH 2-53 H 3-NH ₂ -Ph H Me -CH ₂ -OO CH 2-54 H 4-NH ₂ -Ph H Me -CH ₂ -OO CH 2-55 H 4-NH ₂ -Ph H Me -CH ₂ -OS CH 2-56 H 4-NHMe-Ph H Me -CH ₂ -OO CH 2-57 H 2-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 2-58 H 3-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 2-59 H 4-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 2- 60 H 4-N (Me) ₂ -Ph H Me -CH ₂ -OS CH 2-61 H 4-N (Me) ₂ -Ph H Et -CH ₂ -OO CH 2-62 H 4-NHAc-Ph H Me -CH ₂ -OO CH 2-63 H 4-N (Me) Ac-Ph H Me -CH ₂ -OO CH 2-64 H 4-Ph-Ph H Me -CH ₂ -OO CH 2-65 H 4 -(4-OH-Ph) Ph H Me -CH ₂ -OO CH 2-66 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH ₂ -OO CH 2-67 H 4 -(4-OH-3,5-diMe-Ph) Ph H Me -CH ₂ -OS CH 2-68 H 4- (4-OH-3,5-ditBu-Ph) Ph H Me -CH ₂ -OO CH 2-69 H 4- (4-OH-3,5-ditBu-Ph) Ph H Me -CH ₂ -OS CH 2-70 H 4-Bz-Ph H Me -CH ₂ -OO CH 2-71 H 4- (4-OH-Bz) Ph H Me -CH ₂ -OO CH 2-72 H 4- (4-OH-3,5-diMe-Bz) Ph H Me -CH ₂ -OO CH 2-73 H 4- (4-OH-3,5-ditBu-Bz) Ph H Me -CH ₂ -OO CH 2-74 H 4-PhO-Ph H Me -CH ₂ -OO CH 2-75 H 4-PhS-Ph H Me -CH ₂ -OO CH 2-76 H 2-Pyrd (1) -Ph H Me -CH ₂ -OO CH 2-77 H 2-Pyrd (1) -Ph H Me -CH ₂ -OON 2-78 H 2-Pyrd (1) -Ph H Me -CH ₂ -OS CH 2-79 H 2-Pyrd (1) -Ph H Et -CH ₂ -OO CH 2-80 H 2-Pyrd (1) -Ph H Et -CH ₂ -OS CH 2-81 H 3-Pyrd (1) -Ph H Me -CH ₂ -OO CH 2-8 2 H 3-Pyrd (1) -Ph H Me -CH ₂ -OON 2-83 H 3-Pyrd (1) -Ph H Me -CH ₂ -OS CH 2-84 H 3-Pyrd (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 2-85 H 3-Pyrd (1) -Ph H Et -CH ₂ -OO CH 2-86 H 4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 2-87 H 4-Pyrd (1) -Ph H Me -CH ₂ -OON 2-88 H 4-Pyrd (1) -Ph H Me -CH ₂ -OS CH 2-89 H 4-Pyrd (1)- Ph H Me-(CH ₂ ) ₂ -OO CH 2-90 H 4-Pyrd (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 2-91 H 4-Pyrd (1) -Ph H Et- CH ₂ -OO CH 2-92 H 4-Pyrd (1) -Ph H Et -CH ₂ -OS CH 2-93 H 4-Pyrd (1) -Ph H tBu -CH ₂ -OO CH 2-94 H 2 -Pip (1) -Ph H Me -CH ₂ -OO CH 2-95 H 2-Pip (1) -Ph H Me -CH ₂ -OON 2-96 H 2-Pip (1) -Ph H Me -CH ₂ -OS CH 2-97 H 2-Pip (1) -Ph H Et -CH ₂ -OO CH 2-98 H 2-Pip (1) -Ph H Et -CH ₂ -OS CH 2-99 H 3- Pip (1) -Ph H Me -CH ₂ -OO CH 2-100 H 3-Pip (1) -Ph H Me -CH ₂ -OON 2-101 H 3-Pip (1) -Ph H Me -CH ₂ - OS CH 2-102 H 3-Pip (1) -Ph H Et -CH 2 - OO CH 2-103 H 3-Pip (1) -Ph H Et -CH 2 - OS CH 2-104 H 3-Pip (1) -Ph H Et-(CH ₂ ) ₃ -SO CH 2-105 H 4-Pip (1) -Ph H Me -CH ₂ -OO CH 2-106 H 4-Pip (1) -Ph H Me -CH ₂ -OON 2-107 H 4-Pip (1) -Ph H M e -CH ₂ -OS CH 2-108 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 2-109 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 2-110 H 4-Pip (1) -Ph H Et -CH ₂ -OO CH 2-112 H 4-Pip (1) -Ph H Et -CH ₂ -OS CH 2-112 H 4-Pip (1) -Ph H tBu -CH ₂ -OO CH 2-113 H 4-Pip (1) -Ph 4-Cl Me -CH ₂ -OO CH 2-114 2-MeO 4-Pip (1) -Ph H Me -CH ₂ -OO CH 2-115 H 2-Mor (4) -Ph H Me -CH ₂ -OO CH 2-116 H 2-Mor (4) -Ph H Me -CH ₂ -OON 2-117 H 2-Mor (4) -Ph H Me -CH ₂ -OS CH 2-118 H 2-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 2-119 H 2-Mor (4)- Ph H Et -CH ₂ -OO CH 2-120 H 2-Mor (4) -Ph H Et -CH ₂ -OS CH 2-121 H 3-Mor (4) -Ph H Me -CH ₂ -OO CH 2 -122 H 3-Mor (4) -Ph H Me -CH ₂ -OON 2-123 H 3-Mor (4) -Ph H Me -CH ₂ -OS CH 2-124 H 3-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 2-125 H 3-Mor (4) -Ph H Et -CH ₂ -OO CH 2-126 H 3-Mor (4) -Ph H Et -CH ₂ -OS CH 2-127 H 4-Mor (4) -Ph H Me -CH ₂ -OO CH 2-128 H 4-Mor (4) -Ph H Me -CH ₂ -OON 2-129 H 4-Mor (4) -Ph H Me -CH ₂ -OS CH 2-130 H 4-Mor (4) -Ph H Me-(CH ₂ ) ₂ -OO CH 2-131 H 4-Mor (4) -Ph H Et -CH ₂ -OO CH 2-132 H 4-Mor (4) -Ph H Et -CH ₂ -OS CH 2-133 H 4-Mor (4) -Ph H tBu -CH ₂ -OO CH 2-134 H 2-TioMor (4) -Ph H Me -CH ₂ -OO CH 2-135 H 3-TioMor (4) -Ph H Me -CH ₂ -OO CH 2-136 H 4-TioMor (4) -Ph H Me -CH ₂ -OO CH 2-137 H 4-TioMor (4) -Ph H Me -CH ₂ -OS CH 2-138 H 2-Pipra (1) -Ph H Me -CH ₂ -OO CH 2-139 H 3-Pipra (1) -Ph H Me -CH ₂ -OO CH 2-140 H 4-Pipra (1) -Ph H Me -CH ₂ -OO CH 2-141 H 4-Pipra (1) -Ph H Me -CH ₂ -OON 2-142 H 4-Pipra (1) -Ph H Me -CH ₂ -OS CH 2-143 H 4-Pipra (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 2-144 H 4-Pipra (1) -Ph H Et -CH ₂ -OO CH 2 -145 H 4-Pipra (1) -Ph H Et -CH ₂ -OS CH 2-146 H 4-NO ₂ -Ph H Me -CH ₂ -OO CH 2-147 H 2-Cl-4-OH-Ph H Me -CH ₂ -OO CH 2-148 H 3-Cl-4-OH-Ph H Me -CH ₂ -OO CH 2-149 H 3-Cl-4-OH-Ph H Me -CH ₂ -OS CH 2-150 H 2-F-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 2-151 H 4-F-3-OH-2,5-diEt-Ph H Me -CH ₂ -OO CH 2-152 H 2-Cl-4-OH-3,5-diMe-Ph HH -CH ₂ -OO CH 2-153 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 2-154 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 2-155 H 2-Cl-4-OH-3,5-diMe -Ph H Me -CH ₂ -OS CH 2-156 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OSN 2-157 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -SO CH 2-158 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -SS CH 2-159 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 2-160 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OON 2-161 H 2-Cl-4- OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OS CH 2-162 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH (Me)-OO CH 2 -163 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₃ -OO CH 2-164 H 2-Cl-4-OH-3,5-diMe-Ph H Me -(CH ₂ ) ₄ -OO CH 2-165 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 2-166 H 2-Cl-4-OH-3, 5-diMe-Ph H Et -CH ₂ -OON 2-167 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OS CH 2-168 H 2-Cl-4-OH -3,5-diMe-Ph H Et-(CH ₂ ) ₂ -OO CH 2-169 H 2-Cl-4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 2-170 H 2-Cl-4-OH-3,5-diMe-Ph H tBu -CH ₂ -OS CH 2-171 H 2-Cl-4-OH-3,5-diMe-Ph H Ph -CH ₂ -OO CH 2-172 H 2-Cl-4-OH-3,5-diMe-Ph H Bz -CH ₂ -OO CH 2-173 H 2-Cl-4-OH-3,5-diMe-Ph 6-Cl Me -CH ₂ -OO CH 2-174 H 2-Cl-4-OH-3,5-diMe-Ph 6-Me Me -CH ₂ -OO CH 2-175 H 2-Cl-4-OH-3,5 -diMe-Ph 6-M eO Me -CH ₂ -OO CH 2-176 2-Cl 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 2-177 3-Cl 2-Cl-4-OH -3,5-diMe-Ph H Me -CH ₂ -OO CH 2-178 2-Me 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 2-179 3- Me 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 2-180 2-MeO 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 2-181 H 2-Cl-4-OH-3,5-diEt-Ph H Me -CH ₂ -OO CH 2-182 H 2-Cl-4-OH-3,5-ditBu-Ph H Me -CH ₂ -OO CH 2-183 H 3-Cl-5-OH-2,6-diMe-Ph H Me -CH ₂ -OO CH 2-184 H 3-Cl-5-OH-2,6- diMe-Ph H Me -CH ₂ -OS CH 2-185 H 4-Cl-3-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 2-186 H 4-Cl-3-OH- 2,5-diMe-Ph H Me -CH ₂ -OS CH 2-187 H 3-Cl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 2-188 H 3,5-diCl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 2-189 H 3,5-diCl-4-NH ₂ -Ph H Me -CH ₂ -OS CH 2-190 H 3,5-diF-4-NH _2- Ph H Me -CH ₂ -OO CH 2-191 H 4-NHMe-3-Cl-Ph H Me -CH ₂ -OO CH 2-192 H 3-Cl-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 2-193 H 3-OH-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 2-194 H 3-Cl-6-Me-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 2-195 H 2-Me-4-Pip (1) -Ph H Me -CH ₂ -OO CH 2-196 H 2-Me-4- Mor (4) -Ph H Me -CH ₂ -OO CH 2-197 H 2-OH-3-Me-Ph H Me -CH ₂ -OO CH 2-198 H 2-OH-4-Me-Ph H Me -CH ₂ -OO CH 2-199 H 2-OH-3,4-diMe-Ph H Me -CH ₂ -OO CH 2-200 H 2-OH-3,4-diMe-Ph H Me -CH _2- OS CH 2-201 H 3-OH-2-Me-Ph H Me -CH ₂ -OO CH 2-202 H 3-OH-4-Me-Ph H Me -CH ₂ -OO CH 2-203 H 3- OH-5-Me-Ph H Me -CH ₂ -OO CH 2-204 H 3-OH-6-Me-Ph H Me -CH ₂ -OO CH 2-205 H 3-OH-2,4-diMe- Ph H Me -CH ₂ -OO CH 2-206 H 3-OH-2,4-diMe-Ph H Me -CH ₂ -OS CH 2-207 H 4-OH-2-Me-Ph H Me -CH ₂ -OO CH 2-208 H 4-OH-2-Me-Ph H Me -CH ₂ -OS CH 2-209 H 4-OH-3-Me-Ph H Me -CH ₂ -OO CH 2-210 H 4 -OH-3-Me-Ph H Me -CH ₂ -OON 2-211 H 4-OH-3-Me-Ph H Me -CH ₂ -OS CH 2-212 H 4-OH-3-Me-Ph H Et -CH ₂ -OO CH 2-213 H 4-OH-3-Me-Ph H Et -CH ₂ -OS CH 2-214 H 4-OH-3-Me-Ph 6-Cl Me -CH ₂ -OO CH 2-215 H 4-OH-2-Et-Ph H Me -CH ₂ -OO CH 2-216 H 4-OH-3-Et-Ph H Me -CH ₂ -OO CH 2-217 H 4-OH -2-tBu-Ph H Me -CH ₂ -OO CH 2-218 H 4-OH-3-tBu-Ph H Me -CH ₂ -OO CH 2-219 H 4-OH-3-tBu-Ph H Me -CH ₂ -OS CH 2-220 H 4-OH-2,3-diMe-Ph H Me- CH ₂ -OO CH 2-221 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OON 2-222 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OS CH 2-223 H 4-OH-2,3-diMe-Ph H Me-(CH ₂ ) ₃ -SO CH 2-224 H 4-OH-2,3-diMe-Ph H Et -CH ₂ -OO CH 2 -225 H 4-OH-2,3-diMe-Ph H Et -CH ₂ -OS CH 2-226 H 4-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 2-227 H 4 -OH-2,5-diMe-Ph H Me -CH ₂ -OS CH 2-228 H 4-OH-3,5-diMe-Ph HH -CH ₂ -OO CH 2-229 H 4-OH-3, 5-diMe-Ph H Me -CH ₂ -OO CH 2-230 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 2-231 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 2-232 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OSN 2-233 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -SO CH 2-234 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 2-235 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OON 2-236 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OS CH 2-237 H 4-OH-3,5-diMe-Ph H Me -CH ( Me)-OO CH 2-238 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₃ -OO CH 2-239 H 4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 2-240 H 4-OH-3,5-diMe-Ph H Et -CH ₂ -OON 2-241 H 4-OH-3,5-diMe-Ph H Et -CH ₂ -OS CH 2 -242 H 4-OH-3,5-diMe-Ph H Et-(CH ₂ ) ₂ -OO CH 2-243 H 4-OH-3,5-diMe-Ph H sBu -CH ₂ -OO CH 2-244 H 4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 2-245 H 4-OH-3,5-diMe-Ph H tBu -CH ₂ -OS CH 2-246 H 4-OH-3,5-diMe-Ph H Ph -CH ₂ -OO CH 2-247 H 4-OH- 3,5-diMe-Ph H Bz -CH ₂ -OO CH 2-248 H 4-OH-3,5-diMe-Ph 6-Cl Me -CH ₂ -OO CH 2-249 H 4-OH-3, 5-diMe-Ph 6-Me Me -CH ₂ -OO CH 2-250 H 4-OH-3,5-diMe-Ph 6-MeO Me -CH ₂ -OO CH 2-251 2-Cl 4-OH- 3,5-diMe-Ph H Me -CH ₂ -OO CH 2-252 3-Cl 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 2-253 2-Me 4-OH- 3,5-diMe-Ph H Me -CH ₂ -OO CH 2-254 3-Me 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 2-255 2-MeO 4-OH- 3,5-diMe-Ph H Me -CH ₂ -OO CH 2-256 3-MeO 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 2-257 H 3,5-diEt- 4-OH-Ph H Me -CH ₂ -OO CH 2-258 H 3,5-diEt-4-OH-Ph H Me -CH ₂ -OS CH 2-259 H 3-tBu-4-OH-5- Me-Ph H Me -CH ₂ -OO CH 2-260 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OS CH 2-261 H 4-OH-3,5-diPr- Ph H Me -CH ₂ -OO CH 2-262 H 4-OH-3,5-diiPr-Ph H Me -CH ₂ -OO CH 2-263 H 3,5-ditBu-4-OH-Ph HH -CH ₂ -OO CH 2-264 H 3,5-ditBu-4-OH-Ph H Me -CH _2- OO CH 2-265 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OON 2-266 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OS CH 2-267 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OSN 2-268 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -SO CH 2-269 H 3,5- ditBu-4-OH-Ph H Me -CH ₂ -SS CH 2-270 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 2-271 H 3,5-ditBu -4-OH-Ph H Me-(CH ₂ ) ₂ -OON 2-272 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 2-273 H 3,5- ditBu-4-OH-Ph H Me -CH (Me)-OO CH 2-274 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₃ -OO CH 2-275 H 3,5 -ditBu-4-OH-Ph H Me-(CH ₂ ) ₃ -OS CH 2-276 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OO CH 2-277 H 3,5- ditBu-4-OH-Ph H Et -CH ₂ -OON 2-278 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OS CH 2-279 H 3,5-ditBu-4-OH -Ph H Et-(CH ₂ ) ₂ -OO CH 2-280 H 3,5-ditBu-4-OH-Ph H tBu -CH ₂ -OO CH 2-281 H 3,5-ditBu-4-OH- Ph H tBu -CH ₂ -OS CH 2-282 H 3,5-ditBu-4-OH-Ph H Ph -CH ₂ -OO CH 2-283 H 3,5-ditBu-4-OH-Ph H Bz- CH ₂ -OO CH 2-284 H 3,5-ditBu-4-OH-Ph 6-Cl Me -CH ₂ -OS CH 2-285 H 3,5-ditBu-4-OH-Ph 6-Cl Me- CH ₂ -OO CH 2-286 H 3,5-ditBu- 4-OH-Ph 6-Me Me -CH ₂ -OO CH 2-287 H 3,5-ditBu-4-OH-Ph 6-MeO Me -CH ₂ -OO CH 2-288 2-Cl 3,5- ditBu-4-OH-Ph H Me -CH ₂ -OO CH 2-289 3-Cl 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 2-290 2-Me 3,5- ditBu-4-OH-Ph H Me -CH ₂ -OO CH 2-291 3-Me 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 2-292 2-MeO 3,5- ditBu-4-OH-Ph H Me -CH ₂ -OO CH 2-293 3-MeO 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 2-294 H 4-OH-2, 3,5-triMe-Ph HH -CH ₂ -OO CH 2-295 H 4-OH-2,3,5-triMe-Ph HH -CH ₂ -OS CH 2-296 H 4-OH-2,3, 5-triMe-Ph H Me -CH ₂ -OO CH 2-297 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OON 2-298 H 4-OH-2,3,5 -triMe-Ph H Me -CH ₂ -OS CH 2-299 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OSN 2-300 H 4-OH-2,3,5- triMe-Ph H Me -CH ₂ -SO CH 2-301 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₂ -OO CH 2-302 H 4-OH-2,3 , 5-triMe-Ph H Me-(CH ₂ ) ₂ -OON 2-303 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₂ -OS CH 2-304 H 4- OH-2,3,5-triMe-Ph H Me -CH (Me)-OO CH 2-305 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₃ -OO CH 2 -306 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OO CH 2-307 H 4 -OH-2,3,5-triMe-Ph H Et -CH ₂ -OON 2-308 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OS CH 2-309 H 4- OH-2,3,5-triMe-Ph H Et -CH ₂ -OSN 2-310 H 4-OH-2,3,5-triMe-Ph H Et-(CH ₂ ) ₂ -OO CH 2-311 H 4-OH-2,3,5-triMe-Ph H iPr -CH ₂ -OO CH 2-312 H 4-OH-2,3,5-triMe-Ph H tBu -CH ₂ -OO CH 2-313 H 4-OH-2,3,5-triMe-Ph H tBu -CH ₂ -OS CH 2-314 H 4-OH-2,3,5-triMe-Ph H Ph -CH ₂ -OO CH 2-315 H 4-OH-2,3,5-triMe-Ph H Bz -CH ₂ -OO CH 2-316 H 4-OH-2,3,5-triMe-Ph 6-Cl Me -CH ₂ -OO CH 2- 317 H 4-OH-2,3,5-triMe-Ph 6-Me Me -CH ₂ -OO CH 2-318 H 4-OH-2,3,5-triMe-Ph 6-MeO Me -CH _2- OO CH 2-319 2-Cl 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 2-320 3-Cl 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 2-321 2-Me 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 2-322 3-Me 4-OH-2,3,5-triMe -Ph H Me -CH ₂ -OO CH 2-323 2-MeO 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 2-324 2-MeO 4-OH-2,3 , 5-triMe-Ph H Me -CH ₂ -OO CH 2-325 H 4-OH-2,3,6-triMe-Ph H Me -CH ₂ -OO CH 2-326 H 4-OH-2,3 , 6-triMe-Ph H Me -CH ₂ -OS CH 2-327 H 4-OH-2,3,5,6-tetraMe-Ph H M e -CH ₂ -OO CH 2-328 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH ₂ -OS CH 2-329 H 4-OH-3,5-diCF ₃ -Ph H Me -CH ₂ -OO CH 2-330 H 4-OH-3,5-diMeO-Ph H Me -CH ₂ -OO CH 2-331 H 4-OH-3,5-ditBuO-Ph H Me -CH ₂ -OO CH 2-332 H 3-NH ₂ -4-Me-Ph H Me -CH ₂ -OO CH 2-333 H 3-NH ₂ -4-Me-Ph H Me -CH ₂ -OS CH 2- 334 H 4-NH ₂ -2,3-diMe-Ph H Me -CH ₂ -OO CH 2-335 H 4-NH ₂ -2,3-diMe-Ph H Me -CH ₂ -OS CH 2-336 H 4-NH ₂ -2,6-diMe-Ph H Me -CH ₂ -OO CH 2-337 H 4-NH ₂ -2,6-diMe-Ph H Me -CH ₂ -OS CH 2-338 H 4- NH ₂ -3,5-diMe-Ph HH -CH ₂ -OO CH 2-339 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 2-340 H 4-NH _2- 3,5-diMe-Ph H Me -CH ₂ -OON 2-341 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 2-342 H 4-NH ₂ -3,5 -diMe-Ph H Me -CH ₂ -OSN 2-343 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -SO CH 2-344 H 4-NH ₂ -3,5-diMe- Ph H Me-(CH ₂ ) ₂ -OO CH 2-345 H 4-NH ₂ -3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OON 2-346 H 4-NH ₂ -3,5 -diMe-Ph H Me-(CH ₂ ) ₂ -OS CH 2-347 H 4-NH ₂ -3,5-diMe-Ph H Me -CH (Me)-OO CH 2-348 H 4-NH _2- 3,5-diMe-Ph H Me-(CH ₂ ) ₃ -OO CH 2-349 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OO CH 2-350 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OON 2-351 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OS CH 2-352 H 4-NH ₂ -3,5-diMe-Ph H Et-(CH ₂ ) ₂ -OO CH 2-353 H 4-NH ₂ -3,5-diMe-Ph H tBu -CH ₂ -OO CH 2-354 H 4-NH ₂ -3,5-diMe-Ph H tBu -CH ₂ -OS CH 2 -355 H 4-NH ₂ -3,5-diMe-Ph H Ph -CH ₂ -OO CH 2-356 H 4-NH ₂ -3,5-diMe-Ph H Bz -CH ₂ -OO CH 2-357 H 4-NH ₂ -3,5-diMe-Ph 6-Cl Me -CH ₂ -OO CH 2-358 H 4-NH ₂ -3,5-diMe-Ph 6-Me Me -CH ₂ -OO CH 2 -359 H 4-NH ₂ -3,5-diMe-Ph 6-MeO Me -CH ₂ -OO CH 2-360 2-Cl 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 2-361 3-Cl 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 2-362 2-Me 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 2-363 3-Me 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 2-364 2-MeO 4-NH ₂ -3,5-diMe-Ph H Me- CH ₂ -OO CH 2-365 3-MeO 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 2-366 H 4-NH ₂ -3,5-diEt-Ph H Me- CH ₂ -OO CH 2-367 H 4-NH ₂ -3,5-diEt-Ph H Me -CH ₂ -OS CH 2-368 H 4-NH ₂ -3,5-ditBu-Ph H Me -CH ₂ -OO CH 2-369 H 4-NHMe- 3,5-diMe-Ph H Me -CH ₂ -OO CH 2-370 H 4-NHMe-3,5-diMe-Ph H Me -CH ₂ -OS CH 2-371 H 4-NHEt-3,5- diMe-Ph H Me -CH ₂ -OO CH 2-372 H 4-NHAc-3,5-diMe-Ph H Me -CH ₂ -OO CH 2-373 H 4-NO ₂ -2,6-diMe-Ph H Me -CH ₂ -OO CH 2-374 H 4-NO ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 2-375 H 4-NO ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 2-376 H 4-NO ₂ -3,5-ditBu-Ph H Me -CH ₂ -OO CH 2-377 H Pyr (2) HH -CH ₂ -OO CH 2-378 H Pyr (2) H Me -CH ₂ -OO CH 2-379 H Pyr (2) H Me -CH ₂ -OON 2-380 H Pyr (2) H Me -CH ₂ -OS CH 2-381 H Pyr (2) H Me -CH ₂ -OSN 2-382 H Pyr (2) H Me -CH ₂ -SO CH 2-383 H Pyr (2) H Me-(CH ₂ ) ₂ -OO CH 2-384 H Pyr (2) H Me-(CH ₂ ) ₂ -OON 2-385 H Pyr (2) H Me-(CH ₂ ) ₂ -OS CH 2-386 H Pyr (2) H Me -CH (Me)-OO CH 2-387 H Pyr (2) H Me-(CH ₂ ) ₃ -OO CH 2-388 H Pyr (2) H Et -CH ₂ -OO CH 2-389 H Pyr (2) H Et -CH ₂ -OON 2-390 H Pyr (2) H Et -CH ₂ -OS CH 2-391 H Pyr (2) H Et-(CH ₂ ) ₂ -OO CH 2-392 H Pyr (2) H tBu -CH ₂ -OO CH 2- 393 H Pyr (2) H tBu -CH ₂ -OS CH 2-394 H Pyr (2) H Ph -CH ₂ -OO CH 2-395 H Pyr ( 2) H Bz -CH ₂ -OO CH 2-396 H Pyr (2) 4-Cl Me -CH ₂ -OO CH 2-397 H Pyr (2) 6-Cl Me -CH ₂ -OO CH 2-398 H Pyr (2) 6-Me Me -CH ₂ -OO CH 2-399 H Pyr (2) 6-MeO Me -CH ₂ -OO CH 2-400 2-Cl Pyr (2) H Me -CH ₂ -OO CH 2-401 3-Cl Pyr (2) H Me -CH ₂ -OO CH 2-402 2-Me Pyr (2) H Me -CH ₂ -OO CH 2-403 3-Me Pyr (2) H Me -CH ₂ -OO CH 2-404 2-MeO Pyr (2) H Me -CH ₂ -OO CH 2-405 3-MeO Pyr (2) H Me -CH ₂ -OO CH 2-406 H 5-F-Pyr ( 2) H Me -CH ₂ -OO CH 2-407 H 6-F-Pyr (2) H Me -CH ₂ -OO CH 2-408 H 5-Cl-Pyr (2) H Me -CH ₂ -OO CH 2-409 H 5-Cl-Pyr (2) H Me -CH ₂ -OS CH 2-410 H 6-Cl-Pyr (2) H Me -CH ₂ -OO CH 2-411 H 6-Cl-Pyr ( 2) H Me -CH ₂ -OS CH 2-412 H 6-Me-Pyr (2) H Me -CH ₂ -OO CH 2-413 H 6-MeO-Pyr (2) H Me -CH ₂ -OO CH 2-414 H 6-MeO-Pyr (2) H Me -CH ₂ -OS CH 2-415 H 6-EtO-Pyr (2) H Me -CH ₂ -OO CH 2-416 H 3-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 2-417 H 3-NH ₂ -Pyr (2) H Me -CH ₂ -OS CH 2-418 H 5-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 2-419 H 5-NH ₂ -Pyr (2) H Me -CH ₂ -OS CH 2-420 H 3-NHMe-Pyr (2) H Me -CH ₂ -OO CH 2-421 H 5-NHMe-Pyr (2) H Me -CH ₂ -OO CH 2-422 H 3-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 2-423 H 3-NO ₂ -Pyr (2 ) H Me -CH ₂ -OS CH 2-424 H 5-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 2-425 H 5-NO ₂ -Pyr (2) H Me -CH ₂ -OS CH 2-426 H 5-NH ₂ -6-Cl-Pyr (2) H Me -CH ₂ -OO CH 2-427 H 5-NH ₂ -6-Cl-Pyr (2) H Me -CH ₂ -OS CH 2-428 3-MeO 5-NH ₂ -6-Cl-Pyr (2) 6-MeO Et-(CH ₂ ) ₄ -SS CH 2-429 H Pyr (3) HH -CH ₂ -OO CH 2- 430 H Pyr (3) H Me -CH ₂ -OO CH 2-431 H Pyr (3) H Me -CH ₂ -OON 2-432 H Pyr (3) H Me -CH ₂ -OS CH 2-433 H Pyr (3) H Me -CH ₂ -OSN 2-434 H Pyr (3) H Me -CH ₂ -SO CH 2-435 H Pyr (3) H Me-(CH ₂ ) ₂ -OO CH 2-436 H Pyr (3) H Me-(CH ₂ ) ₂ -OON 2-437 H Pyr (3) H Me-(CH ₂ ) ₂ -OS CH 2-438 H Pyr (3) H Me -CH (Me)-OO CH 2-439 H Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 2-440 H Pyr (3) H Et -CH ₂ -OO CH 2-441 H Pyr (3) H Et -CH ₂ -OON 2-442 H Pyr (3) H Et -CH ₂ -OS CH 2-443 H Pyr (3) H Et -CH ₂ -OSN 2-444 H Pyr (3) H Et-(CH ₂ ) ₂ -OO CH 2-445 H Pyr (3) H tBu -CH ₂ -OO CH 2-446 H Pyr (3) H tBu -CH ₂ -OS CH 2-447 H Pyr (3) H Pn-(CH ₂ ) ₃ -OO CH 2-448 H Pyr (3) H Ph -CH ₂ -OO CH 2-449 H Pyr (3) H Ph -CH ₂ -OON 2-450 H Pyr (3) H Ph -CH ₂ -OS CH 2-451 H Pyr (3) H Bz -CH ₂ -OO CH 2-452 H Pyr (3) 6-Cl Me -CH ₂ -OO CH 2-453 H Pyr (3) 6-Me Me -CH ₂ -OO CH 2-454 H Pyr (3) 6-MeO Me -CH ₂ -OO CH 2-455 2-Cl Pyr (3) H Me -CH ₂ -OO CH 2-456 3 -Cl Pyr (3) H Me -CH ₂ -OO CH 2-457 2-Me Pyr (3) H Me -CH ₂ -OO CH 2-458 3-Me Pyr (3) H Me -CH ₂ -OO CH 2-459 2-MeO Pyr (3) H Me -CH ₂ -OO CH 2-460 3-MeO Pyr (3) H Me -CH ₂ -OO CH 2-461 H 6-Cl-Pyr (3) H Me -CH ₂ -OO CH 2-462 H 6-Me-Pyr (3) H Me -CH ₂ -OO CH 2-463 H 5-MeO-Pyr (3) H Me -CH ₂ -OO CH 2-464 H 5-MeO-Pyr (3) H Me -CH ₂ -OS CH 2-465 H 6-MeO-Pyr (3) H Me -CH ₂ -OO CH 2-466 H 6-MeO-Pyr (3) H Me -CH ₂ -OON 2-467 H 6-MeO-Pyr (3) H Me -CH ₂ -OS CH 2-468 H 6-MeO-Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 2- 469 H 6-MeO-Pyr (3) H Et -CH ₂ -OO CH 2-470 H 6-MeO-Pyr (3) H Et -CH ₂ -OS CH 2-471 H 6-EtO-Pyr (3) H Me -CH ₂ -OO CH 2-472 H 6-iPrO-Pyr (3) H Me -CH ₂ -OO CH 2-473 H 6-iPrO-Pyr (3) H Me -CH ₂ -OS CH 2-474 H 6-MeO-5-Me-Pyr (3) H Me -CH ₂ -OO CH 2-475 H 6-MeO-5-Me-Pyr (3) H Me- CH ₂ -OS CH 2-476 H 2-NO ₂ -6-Me-Pyr (3) H Me -CH ₂ -OO CH 2-477 H 2-NO ₂ -6-Me-Pyr (3) H Me- CH ₂ -OS CH 2-478 H Pyr (4) HH -CH ₂ -OO CH 2-479 H Pyr (4) H Me -CH ₂ -OO CH 2-480 H Pyr (4) H Me -CH _2- OON 2-481 H Pyr (4) H Me -CH ₂ -OS CH 2-482 H Pyr (4) H Me -CH ₂ -OSN 2-483 H Pyr (4) H Me -CH ₂ -SO CH 2- 484 H Pyr (4) H Me -CH ₂ -SS CH 2-485 H Pyr (4) H Me-(CH ₂ ) ₂ -OO CH 2-486 H Pyr (4) H Me-(CH ₂ ) _2- OON 2-487 H Pyr (4) H Me-(CH ₂ ) ₂ -OS CH 2-488 H Pyr (4) H Me -CH (Me)-OO CH 2-489 H Pyr (4) H Me-( CH ₂ ) ₃ -OO CH 2-490 H Pyr (4) H Et -CH ₂ -OO CH 2-491 H Pyr (4) H Et -CH ₂ -OON 2-492 H Pyr (4) H Et -CH ₂ -OS CH 2-493 H Pyr (4) H Et-(CH ₂ ) ₂ -OO CH 2-494 H Pyr (4) H tBu -CH ₂ -OO CH 2-495 H Pyr (4) H tBu- CH ₂ -OS CH 2-496 H Pyr (4) H Ph -CH ₂ -OO CH 2-497 H Pyr (4) H Bz -CH ₂ -OO CH 2-498 H Pyr (4) H Bz -CH ₂ -OS CH 2-499 H Pyr (4) 6-Cl Me -CH ₂ -OO CH 2-500 H Pyr (4) 6-Me Me -CH ₂ -OO CH 2-501 H Pyr (4) 6-MeO Me -CH ₂ -OO CH 2-502 2-Cl Pyr (4) H Me -CH ₂ -OO CH 2-503 3-Cl Pyr (4) H Me -CH ₂ -OO CH 2-504 2-Me Pyr (4) H Me -CH ₂ -OO CH 2-505 3-Me Pyr (4) H Me -CH ₂ -OO CH 2-506 2-MeO Pyr (4) H Me -CH ₂ -OO CH 2-507 3-MeO Pyr (4) H Me -CH ₂ -OO CH 2-508 H 2-F-Pyr (4) H Me -CH ₂ -OO CH 2 -509 H 2-Cl-Pyr (4) H Me -CH ₂ -OO CH 2-510 H 2-Me-Pyr (4) H Me -CH ₂ -OO CH 2-511 H 2-Me-Pyr (4 ) H Me -CH ₂ -OS CH 2-512 H 2-Et-Pyr (4) H Me -CH ₂ -OO CH 2-513 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 2-514 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OON 2-515 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OS CH 2-516 H 2, 6-diMe-Pyr (4) H Et -CH ₂ -OO CH 2-517 H 2,6-diMe-Pyr (4) H Et -CH ₂ -OS CH 2-518 H 3,6-diMe-Pyr ( 4) H Me -CH ₂ -OO CH 2-519 H 3,6-diMe-Pyr (4) H Me -CH ₂ -OS CH 2-520 H 2-MeO-Pyr (4) H Me -CH _2- OO CH 2-521 H 2-MeO-Pyr (4) H Me -CH ₂ -OS CH 2-522 H 4-Imid (1) -Ph H Me -CH ₂ -OO CH 2-523 H 4-Imid ( 1) -Ph H Me -CH ₂ -OON 2-524 H 4-Imid (1) -Ph H Me -CH ₂ -OS CH 2-525 H 4-Imid (1) -Ph H Me -CH ₂ -OSN Two -526 H 4-Tz-Ph H Me -CH ₂ -OO CH 2-527 H 4-Tz-Ph H Me -CH ₂ -OON 2-528 H 4-Tz-Ph H Me -CH ₂ -OS CH 2 -529 H 4-Tz-Ph H Me -CH ₂ -OSN 2-530 H 4-Ada (1) -Ph H Me -CH ₂ -OO CH 2-531 H 4-Ada (1) -Ph H Me- CH ₂ -OON 2-532 H 4-Ada (1) -Ph H Me -CH ₂ -OS CH 2-533 H 4-Ada (1) -Ph H Me -CH ₂ -OSN 2-534 H 4-CN -Ph H Me -CH ₂ -OO CH 2-535 H 4-CN-Ph H Me -CH ₂ -OON 2-536 H 4-CN-Ph H Me -CH ₂ -OS CH 2-537 H 4-CN -Ph H Me -CH ₂ -OSN 2-538 H 4-Bz-3-OH-Ph H Me -CH ₂ -OO CH 2-539 H 4-Bz-3-OH-Ph H Me -CH ₂ -OON 2-540 H 4-OH-2,5-ditBu-Ph H Me -CH ₂ -OO CH 2-541 H pentaF-Ph H Me -CH ₂ -OO CH 2-542 H 4-NHCOPh-Ph H Me- CH ₂ -OO CH 2-543 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH ₂ -OO CH 2-544 H 4-NHCO (2,4-diF-Ph) -Ph H Me- CH ₂ -OO CH 2-545 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH ₂ -OO CH 2-546 H 4-NHCONp (1) -Ph H Me- CH ₂ -OO CH 2-547 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH ₂ -OO CH 2-548 H 4-NHCOcPn-Ph H Me -CH ₂ -OO CH 2-549 H 4-NHCOcHx-Ph H Me -CH ₂ -OO CH 2-550 H 4-NHCOPyr (3) -Ph H Me -CH ₂ -OO CH 2-551 H 4-NHCOPy r (4) -Ph H Me -CH ₂ -OO CH 2-552 H 4-NHHx-Ph H Me -CH ₂ -OO CH 2-553 H 4-NH (Ac) Hx-Ph H Me -CH _2- OO CH .

[0082]

[Table 3]

[0083]

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[0084] Cpd.No.R ² R ⁴ R ⁵ R ⁶ -A- BDE 3-1 H 4-F-Ph H Me -CH ₂ -OO CH 3-2 H 4-Cl-Ph H Me -CH ₂ -OO CH 3-3 H 2-OH-Ph H Me -CH ₂ -OO CH 3-4 H 2-OH-Ph H Me -CH ₂ -OS CH 3-5 H 2-OH-Ph H Me -CH ₂ -SO CH 3-6 H 2-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 3-7 H 2-OH-Ph H Et -CH ₂ -OO CH 3-8 H 2-OH-Ph H Et -CH ₂ -OS CH 3-9 H 2-OH-Ph H tBu -CH ₂ -OO CH 3-10 H 3-OH-Ph H Me -CH ₂ -OO CH 3-11 H 3-OH-Ph H Me -CH ₂ -OS CH 3-12 H 3-OH-Ph H Me -CH ₂ -SO CH 3-13 H 3-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 3-14 H 3-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 3-15 H 3-OH-Ph H Et -CH ₂ -OO CH 3-16 H 3-OH-Ph H Et -CH ₂ -OS CH 3-17 H 3-OH-Ph H tBu -CH ₂ -OO CH 3- 18 H 4-OH-Ph HH -CH ₂ -OO CH 3-19 H 4-OH-Ph H Me -CH ₂ -OO CH 3-20 H 4-OH-Ph H Me -CH ₂ -OON 3-21 H 4-OH-Ph H Me -CH ₂ -OS CH 3-22 H 4-OH-Ph H Me -CH ₂ -OSN 3-23 H 4-OH-Ph H Me -CH ₂ -SO CH 3-24 H 4-OH-Ph H Me -CH ₂ -SON 3-25 H 4-OH-Ph H Me -CH ₂ -SS CH 3-26 H 4-OH-Ph H Me -CH ₂ -SSN 3-27 H 4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 3-28 H 4-OH-Ph H Me-(CH ₂ ) ₂ -OON 3-29 H 4-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 3-30 H 4-OH-Ph H Me -CH (Me)-OO CH 3-31 H 4-OH-Ph H Me-(CH ₂ ) ₃ -OO CH 3-32 H 4-OH-Ph H Et -CH ₂ -OO CH 3-33 H 4-OH-Ph H Et -CH ₂ -OON 3-34 H 4-OH-Ph H Et -CH ₂ -OS CH 3-35 H 4-OH-Ph H Et-(CH ₂ ) ₂ -OO CH 3-36 H 4-OH-Ph H tBu -CH ₂ -OO CH 3-37 H 4-OH-Ph H tBu -CH ₂ -OS CH 3-38 H 4-OH-Ph H Ph -CH ₂ -OO CH 3-39 H 4-OH-Ph H Bz -CH ₂ -OO CH 3-40 H 4-OH-Ph 5-Cl Me -CH ₂ -OO CH 3-41 H 4-OH -Ph 5-Me Me -CH ₂ -OO CH 3-42 H 4-OH-Ph 5-MeO Me -CH ₂ -OO CH 3-43 2-Cl 4-OH-Ph H Me -CH ₂ -OO CH 3-44 3-Cl 4-OH-Ph H Me -CH ₂ -OO CH 3-45 2-Me 4-OH-Ph H Me -CH ₂ -OO CH 3-46 3-Me 4-OH-Ph H Me -CH ₂ -OO CH 3-47 2-MeO 4-OH-Ph H Me -CH ₂ -OO CH 3-48 3-MeO 4-OH-Ph H Me -CH ₂ -OO CH 3-49 H 3 -CF ₃ -Ph H Me -CH ₂ -OO CH 3-50 H 4-iPrO-Ph H Me -CH ₂ -OO CH 3-51 H 4-MeS-Ph H Me -CH ₂ -OO CH 3-52 H 2-NH ₂ -Ph H Me -CH ₂ -OO CH 3-53 H 3-NH ₂ -Ph H Me -CH ₂ -OO CH 3-54 H 4-NH ₂ -Ph H Me -CH ₂ -OO CH 3-55 H 4-NH ₂ -Ph H Me -CH ₂ -OS CH 3-56 H 4-NHMe-Ph H Me -CH ₂ -OO CH 3-57 H 2-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 3-58 H 3-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 3-59 H 4-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 3- 60 H 4-N (Me) ₂ -Ph H Me -CH ₂ -OS CH 3-61 H 4-N (Me) ₂ -Ph H Et -CH ₂ -OO CH 3-62 H 4-NHAc-Ph H Me -CH ₂ -OO CH 3-63 H 4-N (Me) Ac-Ph H Me -CH ₂ -OO CH 3-64 H 4-Ph-Ph H Me -CH ₂ -OO CH 3-65 H 4 -(4-OH-Ph) Ph H Me -CH ₂ -OO CH 3-66 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH ₂ -OO CH 3-67 H 4 -(4-OH-3,5-diMe-Ph) Ph H Me -CH ₂ -OS CH 3-68 H 4- (4-OH-3,5-ditBu-Ph) Ph H Me -CH ₂ -OO CH 3-69 H 4- (4-OH-3,5-ditBu-Ph) Ph H Me -CH ₂ -OS CH 3-70 H 4-Bz-Ph H Me -CH ₂ -OO CH 3-71 H 4- (4-OH-Bz) Ph H Me -CH ₂ -OO CH 3-72 H 4- (4-OH-3,5-diMe-Bz) Ph H Me -CH ₂ -OO CH 3-73 H 4- (4-OH-3,5-ditBu-Bz) Ph H Me -CH ₂ -OO CH 3-74 H 4-PhO-Ph H Me -CH ₂ -OO CH 3-75 H 4-PhS-Ph H Me -CH ₂ -OO CH 3-76 H 2-Pyrd (1) -Ph H Me -CH ₂ -OO CH 3-77 H 2-Pyrd (1) -Ph H Me -CH ₂ -OON 3-78 H 2-Pyrd (1) -Ph H Me -CH ₂ -OS CH 3-79 H 2-Pyrd (1) -Ph H Et -CH ₂ -OO CH 3-80 H 2-Pyrd (1) -Ph H Et -CH ₂ -OS CH 3-81 H 3-Pyrd (1) -Ph H Me -CH ₂ -OO CH 3-8 2 H 3-Pyrd (1) -Ph H Me -CH ₂ -OON 3-83 H 3-Pyrd (1) -Ph H Me -CH ₂ -OS CH 3-84 H 3-Pyrd (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 3-85 H 3-Pyrd (1) -Ph H Et -CH ₂ -OO CH 3-86 H 4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 3-87 H 4-Pyrd (1) -Ph H Me -CH ₂ -OON 3-88 H 4-Pyrd (1) -Ph H Me -CH ₂ -OS CH 3-89 H 4-Pyrd (1)- Ph H Me-(CH ₂ ) ₂ -OO CH 3-90 H 4-Pyrd (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 3-91 H 4-Pyrd (1) -Ph H Et- CH ₂ -OO CH 3-92 H 4-Pyrd (1) -Ph H Et -CH ₂ -OS CH 3-93 H 4-Pyrd (1) -Ph H tBu -CH ₂ -OO CH 3-94 H 2 -Pip (1) -Ph H Me -CH ₂ -OO CH 3-95 H 2-Pip (1) -Ph H Me -CH ₂ -OON 3-96 H 2-Pip (1) -Ph H Me -CH ₂ -OS CH 3-97 H 2-Pip (1) -Ph H Et -CH ₂ -OO CH 3-98 H 2-Pip (1) -Ph H Et -CH ₂ -OS CH 3-99 H 3- Pip (1) -Ph H Me -CH ₂ -OO CH 3-100 H 3-Pip (1) -Ph H Me -CH ₂ -OON 3-101 H 3-Pip (1) -Ph H Me -CH ₂ - OS CH 3-102 H 3-Pip (1) -Ph H Et -CH 2 - OO CH 3-103 H 3-Pip (1) -Ph H Et -CH 2 - OS CH 3-104 H 3-Pip (1) -Ph H Et-(CH ₂ ) ₃ -SO CH 3-105 H 4-Pip (1) -Ph H Me -CH ₂ -OO CH 3-106 H 4-Pip (1) -Ph H Me -CH ₂ -OON 3-107 H 4-Pip (1) -Ph H M e -CH ₂ -OS CH 3-108 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 3-109 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 3-110 H 4-Pip (1) -Ph H Et -CH ₂ -OO CH 3-111 H 4-Pip (1) -Ph H Et -CH ₂ -OS CH 3-112 H 4-Pip (1) -Ph H tBu -CH ₂ -OO CH 3-113 H 4-Pip (1) -Ph 4-Cl Me -CH ₂ -OO CH 3-114 2-MeO 4-Pip (1) -Ph H Me -CH ₂ -OO CH 3-115 H 2-Mor (4) -Ph H Me -CH ₂ -OO CH 3-116 H 2-Mor (4) -Ph H Me -CH ₂ -OON 3-117 H 2-Mor (4) -Ph H Me -CH ₂ -OS CH 3-118 H 2-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 3-119 H 2-Mor (4)- Ph H Et -CH ₂ -OO CH 3-120 H 2-Mor (4) -Ph H Et -CH ₂ -OS CH 3-121 H 3-Mor (4) -Ph H Me -CH ₂ -OO CH 3 -122 H 3-Mor (4) -Ph H Me -CH ₂ -OON 3-123 H 3-Mor (4) -Ph H Me -CH ₂ -OS CH 3-124 H 3-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 3-125 H 3-Mor (4) -Ph H Et -CH ₂ -OO CH 3-126 H 3-Mor (4) -Ph H Et -CH ₂ -OS CH 3-127 H 4-Mor (4) -Ph H Me -CH ₂ -OO CH 3-128 H 4-Mor (4) -Ph H Me -CH ₂ -OON 3-129 H 4-Mor (4) -Ph H Me -CH ₂ -OS CH 3-130 H 4-Mor (4) -Ph H Me-(CH ₂ ) ₂ -OO CH 3-131 H 4-Mor (4) -Ph H Et -CH ₂ -OO CH 3-132 H 4-Mor (4) -Ph H Et -CH ₂ -OS CH 3-133 H 4-Mor (4) -Ph H tBu -CH ₂ -OO CH 3-134 H 2-TioMor (4) -Ph H Me -CH ₂ -OO CH 3-135 H 3-TioMor (4) -Ph H Me -CH ₂ -OO CH 3-136 H 4-TioMor (4) -Ph H Me -CH ₂ -OO CH 3-137 H 4-TioMor (4) -Ph H Me -CH ₂ -OS CH 3-138 H 2-Pipra (1) -Ph H Me -CH ₂ -OO CH 3-139 H 3-Pipra (1) -Ph H Me -CH ₂ -OO CH 3-140 H 4-Pipra (1) -Ph H Me -CH ₂ -OO CH 3-141 H 4-Pipra (1) -Ph H Me -CH ₂ -OON 3-142 H 4-Pipra (1) -Ph H Me -CH ₂ -OS CH 3-143 H 4-Pipra (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 3-144 H 4-Pipra (1) -Ph H Et -CH ₂ -OO CH 3 -145 H 4-Pipra (1) -Ph H Et -CH ₂ -OS CH 3-146 H 4-NO ₂ -Ph H Me -CH ₂ -OO CH 3-147 H 2-Cl-4-OH-Ph H Me -CH ₂ -OO CH 3-148 H 3-Cl-4-OH-Ph H Me -CH ₂ -OO CH 3-149 H 3-Cl-4-OH-Ph H Me -CH ₂ -OS CH 3-150 H 2-F-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 3-151 H 4-F-3-OH-2,5-diEt-Ph H Me -CH ₂ -OO CH 3-152 H 2-Cl-4-OH-3,5-diMe-Ph HH -CH ₂ -OO CH 3-153 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 3-154 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 3-155 H 2-Cl-4-OH-3,5-diMe -Ph H Me -CH ₂ -OS CH 3-156 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OSN 3-157 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -SO CH 3-158 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -SS CH 3-159 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 3-160 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OON 3-161 H 2-Cl-4- OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OS CH 3-162 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH (Me)-OO CH 3 -163 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₃ -OO CH 3-164 H 2-Cl-4-OH-3,5-diMe-Ph H Me -(CH ₂ ) ₄ -OO CH 3-165 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 3-166 H 2-Cl-4-OH-3, 5-diMe-Ph H Et -CH ₂ -OON 3-167 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OS CH 3-168 H 2-Cl-4-OH -3,5-diMe-Ph H Et-(CH ₂ ) ₂ -OO CH 3-169 H 2-Cl-4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 3-170 H 2-Cl-4-OH-3,5-diMe-Ph H tBu -CH ₂ -OS CH 3-171 H 2-Cl-4-OH-3,5-diMe-Ph H Ph -CH ₂ -OO CH 3-172 H 2-Cl-4-OH-3,5-diMe-Ph H Bz -CH ₂ -OO CH 3-173 H 2-Cl-4-OH-3,5-diMe-Ph 5-Cl Me -CH ₂ -OO CH 3-174 H 2-Cl-4-OH-3,5-diMe-Ph 5-Me Me -CH ₂ -OO CH 3-175 H 2-Cl-4-OH-3,5 -diMe-Ph 5-M eO Me -CH ₂ -OO CH 3-176 2-Cl 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 3-177 3-Cl 2-Cl-4-OH -3,5-diMe-Ph H Me -CH ₂ -OO CH 3-178 2-Me 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 3-179 3- Me 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 3-180 2-MeO 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 3-181 H 2-Cl-4-OH-3,5-diEt-Ph H Me -CH ₂ -OO CH 3-182 H 2-Cl-4-OH-3,5-ditBu-Ph H Me -CH ₂ -OO CH 3-183 H 3-Cl-5-OH-2,6-diMe-Ph H Me -CH ₂ -OO CH 3-184 H 3-Cl-5-OH-2,6- diMe-Ph H Me -CH ₂ -OS CH 3-185 H 4-Cl-3-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 3-186 H 4-Cl-3-OH- 2,5-diMe-Ph H Me -CH ₂ -OS CH 3-187 H 3-Cl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 3-188 H 3,5-diCl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 3-189 H 3,5-diCl-4-NH ₂ -Ph H Me -CH ₂ -OS CH 3-190 H 3,5-diF-4-NH _2- Ph H Me -CH ₂ -OO CH 3-191 H 4-NHMe-3-Cl-Ph H Me -CH ₂ -OO CH 3-192 H 3-Cl-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 3-193 H 3-OH-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 3-194 H 3-Cl-6-Me-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 3-195 H 2-Me-4-Pip (1) -Ph H Me -CH ₂ -OO CH 3-196 H 2-Me-4- Mor (4) -Ph H Me -CH ₂ -OO CH 3-197 H 2-OH-3-Me-Ph H Me -CH ₂ -OO CH 3-198 H 2-OH-4-Me-Ph H Me -CH ₂ -OO CH 3-199 H 2-OH-3,4-diMe-Ph H Me -CH ₂ -OO CH 3-200 H 2-OH-3,4-diMe-Ph H Me -CH _2- OS CH 3-201 H 3-OH-2-Me-Ph H Me -CH ₂ -OO CH 3-202 H 3-OH-4-Me-Ph H Me -CH ₂ -OO CH 3-203 H 3- OH-5-Me-Ph H Me -CH ₂ -OO CH 3-204 H 3-OH-6-Me-Ph H Me -CH ₂ -OO CH 3-205 H 3-OH-2,4-diMe- Ph H Me -CH ₂ -OO CH 3-206 H 3-OH-2,4-diMe-Ph H Me -CH ₂ -OS CH 3-207 H 4-OH-2-Me-Ph H Me -CH ₂ -OO CH 3-208 H 4-OH-2-Me-Ph H Me -CH ₂ -OS CH 3-209 H 4-OH-3-Me-Ph H Me -CH ₂ -OO CH 3-210 H 4 -OH-3-Me-Ph H Me -CH ₂ -OON 3-211 H 4-OH-3-Me-Ph H Me -CH ₂ -OS CH 3-212 H 4-OH-3-Me-Ph H Et -CH ₂ -OO CH 3-213 H 4-OH-3-Me-Ph H Et -CH ₂ -OS CH 3-214 H 4-OH-3-Me-Ph 5-Cl Me -CH ₂ -OO CH 3-215 H 4-OH-2-Et-Ph H Me -CH ₂ -OO CH 3-216 H 4-OH-3-Et-Ph H Me -CH ₂ -OO CH 3-217 H 4-OH -2-tBu-Ph H Me -CH ₂ -OO CH 3-218 H 4-OH-3-tBu-Ph H Me -CH ₂ -OO CH 3-219 H 4-OH-3-tBu-Ph H Me -CH ₂ -OS CH 3-220 H 4-OH-2,3-diMe-Ph H Me- CH ₂ -OO CH 3-221 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OON 3-222 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OS CH 3-223 H 4-OH-2,3-diMe-Ph H Me-(CH ₂ ) ₃ -SO CH 3-224 H 4-OH-2,3-diMe-Ph H Et -CH ₂ -OO CH 3 -225 H 4-OH-2,3-diMe-Ph H Et -CH ₂ -OS CH 3-226 H 4-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 3-227 H 4 -OH-2,5-diMe-Ph H Me -CH ₂ -OS CH 3-228 H 4-OH-3,5-diMe-Ph HH -CH ₂ -OO CH 3-229 H 4-OH-3, 5-diMe-Ph H Me -CH ₂ -OO CH 3-230 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 3-231 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 3-232 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OSN 3-233 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -SO CH 3-234 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 3-235 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OON 3-236 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OS CH 3-237 H 4-OH-3,5-diMe-Ph H Me -CH ( Me)-OO CH 3-238 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₃ -OO CH 3-239 H 4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 3-240 H 4-OH-3,5-diMe-Ph H Et -CH ₂ -OON 3-241 H 4-OH-3,5-diMe-Ph H Et -CH ₂ -OS CH 3 -242 H 4-OH-3,5-diMe-Ph H Et-(CH ₂ ) ₂ -OO CH 3-243 H 4-OH-3,5-diMe-Ph H sBu -CH ₂ -OO CH 3-244 H 4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 3-245 H 4-OH-3,5-diMe-Ph H tBu -CH ₂ -OS CH 3-246 H 4-OH-3,5-diMe-Ph H Ph -CH ₂ -OO CH 3-247 H 4-OH- 3,5-diMe-Ph H Bz -CH ₂ -OO CH 3-248 H 4-OH-3,5-diMe-Ph 5-Cl Me -CH ₂ -OO CH 3-249 H 4-OH-3, 5-diMe-Ph 5-Me Me -CH ₂ -OO CH 3-250 H 4-OH-3,5-diMe-Ph 5-MeO Me -CH ₂ -OO CH 3-251 2-Cl 4-OH- 3,5-diMe-Ph H Me -CH ₂ -OO CH 3-252 3-Cl 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 3-253 2-Me 4-OH- 3,5-diMe-Ph H Me -CH ₂ -OO CH 3-254 3-Me 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 3-255 2-MeO 4-OH- 3,5-diMe-Ph H Me -CH ₂ -OO CH 3-256 3-MeO 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 3-257 H 3,5-diEt- 4-OH-Ph H Me -CH ₂ -OO CH 3-258 H 3,5-diEt-4-OH-Ph H Me -CH ₂ -OS CH 3-259 H 3-tBu-4-OH-5- Me-Ph H Me -CH ₂ -OO CH 3-260 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OS CH 3-261 H 4-OH-3,5-diPr- Ph H Me -CH ₂ -OO CH 3-262 H 4-OH-3,5-diiPr-Ph H Me -CH ₂ -OO CH 3-263 H 3,5-ditBu-4-OH-Ph HH -CH ₂ -OO CH 3-264 H 3,5-ditBu-4-OH-Ph H Me -CH _2- OO CH 3-265 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OON 3-266 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OS CH 3-267 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OSN 3-268 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -SO CH 3-269 H 3,5- ditBu-4-OH-Ph H Me -CH ₂ -SS CH 3-270 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 3-271 H 3,5-ditBu -4-OH-Ph H Me-(CH ₂ ) ₂ -OON 3-272 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 3-273 H 3,5- ditBu-4-OH-Ph H Me -CH (Me)-OO CH 3-274 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₃ -OO CH 3-275 H 3,5 -ditBu-4-OH-Ph H Me-(CH ₂ ) ₃ -OS CH 3-276 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OO CH 3-277 H 3,5- ditBu-4-OH-Ph H Et -CH ₂ -OON 3-278 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OS CH 3-279 H 3,5-ditBu-4-OH -Ph H Et-(CH ₂ ) ₂ -OO CH 3-280 H 3,5-ditBu-4-OH-Ph H tBu -CH ₂ -OO CH 3-281 H 3,5-ditBu-4-OH- Ph H tBu -CH ₂ -OS CH 3-282 H 3,5-ditBu-4-OH-Ph H Ph -CH ₂ -OO CH 3-283 H 3,5-ditBu-4-OH-Ph H Bz- CH ₂ -OO CH 3-284 H 3,5-ditBu-4-OH-Ph 5-Cl Me -CH ₂ -OS CH 3-285 H 3,5-ditBu-4-OH-Ph 5-Cl Me- CH ₂ -OO CH 3-286 H 3,5-ditBu- 4-OH-Ph 5-Me Me -CH ₂ -OO CH 3-287 H 3,5-ditBu-4-OH-Ph 5-MeO Me -CH ₂ -OO CH 3-288 2-Cl 3,5- ditBu-4-OH-Ph H Me -CH ₂ -OO CH 3-289 3-Cl 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 3-290 2-Me 3,5- ditBu-4-OH-Ph H Me -CH ₂ -OO CH 3-291 3-Me 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 3-292 2-MeO 3,5- ditBu-4-OH-Ph H Me -CH ₂ -OO CH 3-293 3-MeO 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 3-294 H 4-OH-2, 3,5-triMe-Ph HH -CH ₂ -OO CH 3-295 H 4-OH-2,3,5-triMe-Ph HH -CH ₂ -OS CH 3-296 H 4-OH-2,3, 5-triMe-Ph H Me -CH ₂ -OO CH 3-297 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OON 3-298 H 4-OH-2,3,5 -triMe-Ph H Me -CH ₂ -OS CH 3-299 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OSN 3-300 H 4-OH-2,3,5- triMe-Ph H Me -CH ₂ -SO CH 3-301 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₂ -OO CH 3-302 H 4-OH-2,3 , 5-triMe-Ph H Me-(CH ₂ ) ₂ -OON 3-303 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₂ -OS CH 3-304 H 4- OH-2,3,5-triMe-Ph H Me -CH (Me)-OO CH 3-305 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₃ -OO CH 3 -306 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OO CH 3-307 H 4 -OH-2,3,5-triMe-Ph H Et -CH ₂ -OON 3-308 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OS CH 3-309 H 4- OH-2,3,5-triMe-Ph H Et -CH ₂ -OSN 3-310 H 4-OH-2,3,5-triMe-Ph H Et-(CH ₂ ) ₂ -OO CH 3-311 H 4-OH-2,3,5-triMe-Ph H iPr -CH ₂ -OO CH 3-312 H 4-OH-2,3,5-triMe-Ph H tBu -CH ₂ -OO CH 3-313 H 4-OH-2,3,5-triMe-Ph H tBu -CH ₂ -OS CH 3-314 H 4-OH-2,3,5-triMe-Ph H Ph -CH ₂ -OO CH 3-315 H 4-OH-2,3,5-triMe-Ph H Bz -CH ₂ -OO CH 3-316 H 4-OH-2,3,5-triMe-Ph 5-Cl Me -CH ₂ -OO CH 3- 317 H 4-OH-2,3,5-triMe-Ph 5-Me Me -CH ₂ -OO CH 3-318 H 4-OH-2,3,5-triMe-Ph 5-MeO Me -CH _2- OO CH 3-319 2-Cl 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 3-320 3-Cl 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 3-321 2-Me 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 3-322 3-Me 4-OH-2,3,5-triMe -Ph H Me -CH ₂ -OO CH 3-323 2-MeO 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 3-324 2-MeO 4-OH-2,3 , 5-triMe-Ph H Me -CH ₂ -OO CH 3-325 H 4-OH-2,3,6-triMe-Ph H Me -CH ₂ -OO CH 3-326 H 4-OH-2,3 , 6-triMe-Ph H Me -CH ₂ -OS CH 3-327 H 4-OH-2,3,5,6-tetraMe-Ph H M e -CH ₂ -OO CH 3-328 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH ₂ -OS CH 3-329 H 4-OH-3,5-diCF ₃ -Ph H Me -CH ₂ -OO CH 3-330 H 4-OH-3,5-diMeO-Ph H Me -CH ₂ -OO CH 3-331 H 4-OH-3,5-ditBuO-Ph H Me -CH ₂ -OO CH 3-332 H 3-NH ₂ -4-Me-Ph H Me -CH ₂ -OO CH 3-333 H 3-NH ₂ -4-Me-Ph H Me -CH ₂ -OS CH 3- 334 H 4-NH ₂ -2,3-diMe-Ph H Me -CH ₂ -OO CH 3-335 H 4-NH ₂ -2,3-diMe-Ph H Me -CH ₂ -OS CH 3-336 H 4-NH ₂ -2,6-diMe-Ph H Me -CH ₂ -OO CH 3-337 H 4-NH ₂ -2,6-diMe-Ph H Me -CH ₂ -OS CH 3-338 H 4- NH ₂ -3,5-diMe-Ph HH -CH ₂ -OO CH 3-339 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 3-340 H 4-NH _2- 3,5-diMe-Ph H Me -CH ₂ -OON 3-341 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 3-342 H 4-NH ₂ -3,5 -diMe-Ph H Me -CH ₂ -OSN 3-343 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -SO CH 3-344 H 4-NH ₂ -3,5-diMe- Ph H Me-(CH ₂ ) ₂ -OO CH 3-345 H 4-NH ₂ -3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OON 3-346 H 4-NH ₂ -3,5 -diMe-Ph H Me-(CH ₂ ) ₂ -OS CH 3-347 H 4-NH ₂ -3,5-diMe-Ph H Me -CH (Me)-OO CH 3-348 H 4-NH _2- 3,5-diMe-Ph H Me-(CH ₂ ) ₃ -OO CH 3-349 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OO CH 3-350 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OON 3-351 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OS CH 3-352 H 4-NH ₂ -3,5-diMe-Ph H Et-(CH ₂ ) ₂ -OO CH 3-353 H 4-NH ₂ -3,5-diMe-Ph H tBu -CH ₂ -OO CH 3-354 H 4-NH ₂ -3,5-diMe-Ph H tBu -CH ₂ -OS CH 3 -355 H 4-NH ₂ -3,5-diMe-Ph H Ph -CH ₂ -OO CH 3-356 H 4-NH ₂ -3,5-diMe-Ph H Bz -CH ₂ -OO CH 3-357 H 4-NH ₂ -3,5-diMe-Ph 5-Cl Me -CH ₂ -OO CH 3-358 H 4-NH ₂ -3,5-diMe-Ph 5-Me Me -CH ₂ -OO CH 3 -359 H 4-NH ₂ -3,5-diMe-Ph 5-MeO Me -CH ₂ -OO CH 3-360 2-Cl 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 3-361 3-Cl 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 3-362 2-Me 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 3-363 3-Me 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 3-364 2-MeO 4-NH ₂ -3,5-diMe-Ph H Me- CH ₂ -OO CH 3-365 3-MeO 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 3-366 H 4-NH ₂ -3,5-diEt-Ph H Me- CH ₂ -OO CH 3-367 H 4-NH ₂ -3,5-diEt-Ph H Me -CH ₂ -OS CH 3-368 H 4-NH ₂ -3,5-ditBu-Ph H Me -CH ₂ -OO CH 3-369 H 4-NHMe- 3,5-diMe-Ph H Me -CH ₂ -OO CH 3-370 H 4-NHMe-3,5-diMe-Ph H Me -CH ₂ -OS CH 3-371 H 4-NHEt-3,5- diMe-Ph H Me -CH ₂ -OO CH 3-372 H 4-NHAc-3,5-diMe-Ph H Me -CH ₂ -OO CH 3-373 H 4-NO ₂ -2,6-diMe-Ph H Me -CH ₂ -OO CH 3-374 H 4-NO ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 3-375 H 4-NO ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 3-376 H 4-NO ₂ -3,5-ditBu-Ph H Me -CH ₂ -OO CH 3-377 H Pyr (2) HH -CH ₂ -OO CH 3-378 H Pyr (2) H Me -CH ₂ -OO CH 3-379 H Pyr (2) H Me -CH ₂ -OON 3-380 H Pyr (2) H Me -CH ₂ -OS CH 3-381 H Pyr (2) H Me -CH ₂ -OSN 3-382 H Pyr (2) H Me -CH ₂ -SO CH 3-383 H Pyr (2) H Me-(CH ₂ ) ₂ -OO CH 3-384 H Pyr (2) H Me-(CH ₂ ) ₂ -OON 3-385 H Pyr (2) H Me-(CH ₂ ) ₂ -OS CH 3-386 H Pyr (2) H Me -CH (Me)-OO CH 3-387 H Pyr (2) H Me-(CH ₂ ) ₃ -OO CH 3-388 H Pyr (2) H Et -CH ₂ -OO CH 3-389 H Pyr (2) H Et -CH ₂ -OON 3-390 H Pyr (2) H Et -CH ₂ -OS CH 3-391 H Pyr (2) H Et-(CH ₂ ) ₂ -OO CH 3-392 H Pyr (2) H tBu -CH ₂ -OO CH 3- 393 H Pyr (2) H tBu -CH ₂ -OS CH 3-394 H Pyr (2) H Ph -CH ₂ -OO CH 3-395 H Pyr ( 2) H Bz -CH ₂ -OO CH 3-396 H Pyr (2) 4-Cl Me -CH ₂ -OO CH 3-397 H Pyr (2) 5-Cl Me -CH ₂ -OO CH 3-398 H Pyr (2) 5-Me Me -CH ₂ -OO CH 3-399 H Pyr (2) 5-MeO Me -CH ₂ -OO CH 3-400 2-Cl Pyr (2) H Me -CH ₂ -OO CH 3-401 3-Cl Pyr (2) H Me -CH ₂ -OO CH 3-402 2-Me Pyr (2) H Me -CH ₂ -OO CH 3-403 3-Me Pyr (2) H Me -CH ₂ -OO CH 3-404 2-MeO Pyr (2) H Me -CH ₂ -OO CH 3-405 3-MeO Pyr (2) H Me -CH ₂ -OO CH 3-406 H 5-F-Pyr ( 2) H Me -CH ₂ -OO CH 3-407 H 6-F-Pyr (2) H Me -CH ₂ -OO CH 3-408 H 5-Cl-Pyr (2) H Me -CH ₂ -OO CH 3-409 H 5-Cl-Pyr (2) H Me -CH ₂ -OS CH 3-410 H 6-Cl-Pyr (2) H Me -CH ₂ -OO CH 3-411 H 6-Cl-Pyr ( 2) H Me -CH ₂ -OS CH 3-412 H 6-Me-Pyr (2) H Me -CH ₂ -OO CH 3-413 H 6-MeO-Pyr (2) H Me -CH ₂ -OO CH 3-414 H 6-MeO-Pyr (2) H Me -CH ₂ -OS CH 3-415 H 6-EtO-Pyr (2) H Me -CH ₂ -OO CH 3-416 H 3-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 3-417 H 3-NH ₂ -Pyr (2) H Me -CH ₂ -OS CH 3-418 H 5-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 3-419 H 5-NH ₂ -Pyr (2) H Me -CH ₂ -OS CH 3-420 H 3-NHMe-Pyr (2) H Me -CH ₂ -OO CH 3-421 H 5-NHMe-Pyr (2) H Me -CH ₂ -OO CH 3-422 H 3-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 3-423 H 3-NO ₂ -Pyr (2 ) H Me -CH ₂ -OS CH 3-424 H 5-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 3-425 H 5-NO ₂ -Pyr (2) H Me -CH ₂ -OS CH 3-426 H 5-NH ₂ -6-Cl-Pyr (2) H Me -CH ₂ -OO CH 3-427 H 5-NH ₂ -6-Cl-Pyr (2) H Me -CH ₂ -OS CH 3-428 3-MeO 5-NH ₂ -6-Cl-Pyr (2) 5-MeO Et-(CH ₂ ) ₄ -SS CH 3-429 H Pyr (3) HH -CH ₂ -OO CH 3- 430 H Pyr (3) H Me -CH ₂ -OO CH 3-431 H Pyr (3) H Me -CH ₂ -OON 3-432 H Pyr (3) H Me -CH ₂ -OS CH 3-433 H Pyr (3) H Me -CH ₂ -OSN 3-434 H Pyr (3) H Me -CH ₂ -SO CH 3-435 H Pyr (3) H Me-(CH ₂ ) ₂ -OO CH 3-436 H Pyr (3) H Me-(CH ₂ ) ₂ -OON 3-437 H Pyr (3) H Me-(CH ₂ ) ₂ -OS CH 3-438 H Pyr (3) H Me -CH (Me)-OO CH 3-439 H Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 3-440 H Pyr (3) H Et -CH ₂ -OO CH 3-441 H Pyr (3) H Et -CH ₂ -OON 3-442 H Pyr (3) H Et -CH ₂ -OS CH 3-443 H Pyr (3) H Et -CH ₂ -OSN 3-444 H Pyr (3) H Et-(CH ₂ ) ₂ -OO CH 3-445 H Pyr (3) H tBu -CH ₂ -OO CH 3-446 H Pyr (3) H tBu -CH ₂ -OS CH 3-447 H Pyr (3) H Pn-(CH ₂ ) ₃ -OO CH 3-448 H Pyr (3) H Ph -CH ₂ -OO CH 3-449 H Pyr (3) H Ph -CH ₂ -OON 3-450 H Pyr (3) H Ph -CH ₂ -OS CH 3-451 H Pyr (3) H Bz -CH ₂ -OO CH 3-452 H Pyr (3) 5-Cl Me -CH ₂ -OO CH 3-453 H Pyr (3) 5-Me Me -CH ₂ -OO CH 3-454 H Pyr (3) 5-MeO Me -CH ₂ -OO CH 3-455 2-Cl Pyr (3) H Me -CH ₂ -OO CH 3-456 3 -Cl Pyr (3) H Me -CH ₂ -OO CH 3-457 2-Me Pyr (3) H Me -CH ₂ -OO CH 3-458 3-Me Pyr (3) H Me -CH ₂ -OO CH 3-459 2-MeO Pyr (3) H Me -CH ₂ -OO CH 3-460 3-MeO Pyr (3) H Me -CH ₂ -OO CH 3-461 H 6-Cl-Pyr (3) H Me -CH ₂ -OO CH 3-462 H 6-Me-Pyr (3) H Me -CH ₂ -OO CH 3-463 H 5-MeO-Pyr (3) H Me -CH ₂ -OO CH 3-464 H 5-MeO-Pyr (3) H Me -CH ₂ -OS CH 3-465 H 6-MeO-Pyr (3) H Me -CH ₂ -OO CH 3-466 H 6-MeO-Pyr (3) H Me -CH ₂ -OON 3-467 H 6-MeO-Pyr (3) H Me -CH ₂ -OS CH 3-468 H 6-MeO-Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 3- 469 H 6-MeO-Pyr (3) H Et -CH ₂ -OO CH 3-470 H 6-MeO-Pyr (3) H Et -CH ₂ -OS CH 3-471 H 6-EtO-Pyr (3) H Me -CH ₂ -OO CH 3-472 H 6-iPrO-Pyr (3) H Me -CH ₂ -OO CH 3-473 H 6-iPrO-Pyr (3) H Me -CH ₂ -OS CH 3-474 H 6-MeO-5-Me-Pyr (3) H Me -CH ₂ -OO CH 3-475 H 6-MeO-5-Me-Pyr (3) H Me- CH ₂ -OS CH 3-476 H 2-NO ₂ -6-Me-Pyr (3) H Me -CH ₂ -OO CH 3-477 H 2-NO ₂ -6-Me-Pyr (3) H Me- CH ₂ -OS CH 3-478 H Pyr (4) HH -CH ₂ -OO CH 3-479 H Pyr (4) H Me -CH ₂ -OO CH 3-480 H Pyr (4) H Me -CH _2- OON 3-481 H Pyr (4) H Me -CH ₂ -OS CH 3-482 H Pyr (4) H Me -CH ₂ -OSN 3-483 H Pyr (4) H Me -CH ₂ -SO CH 3- 484 H Pyr (4) H Me -CH ₂ -SS CH 3-485 H Pyr (4) H Me-(CH ₂ ) ₂ -OO CH 3-486 H Pyr (4) H Me-(CH ₂ ) _2- OON 3-487 H Pyr (4) H Me-(CH ₂ ) ₂ -OS CH 3-488 H Pyr (4) H Me -CH (Me)-OO CH 3-489 H Pyr (4) H Me-( CH ₂ ) ₃ -OO CH 3-490 H Pyr (4) H Et -CH ₂ -OO CH 3-491 H Pyr (4) H Et -CH ₂ -OON 3-492 H Pyr (4) H Et -CH ₂ -OS CH 3-493 H Pyr (4) H Et-(CH ₂ ) ₂ -OO CH 3-494 H Pyr (4) H tBu -CH ₂ -OO CH 3-495 H Pyr (4) H tBu- CH ₂ -OS CH 3-496 H Pyr (4) H Ph -CH ₂ -OO CH 3-497 H Pyr (4) H Bz -CH ₂ -OO CH 3-498 H Pyr (4) H Bz -CH ₂ -OS CH 3-499 H Pyr (4) 5-Cl Me -CH ₂ -OO CH 3-500 H Pyr (4) 5-Me Me -CH ₂ -OO CH 3-501 H Pyr (4) 5-MeO Me -CH ₂ -OO CH 3-502 2-Cl Pyr (4) H Me -CH ₂ -OO CH 3-503 3-Cl Pyr (4) H Me -CH ₂ -OO CH 3-504 2-Me Pyr (4) H Me -CH ₂ -OO CH 3-505 3-Me Pyr (4) H Me -CH ₂ -OO CH 3-506 2-MeO Pyr (4) H Me -CH ₂ -OO CH 3-507 3-MeO Pyr (4) H Me -CH ₂ -OO CH 3-508 H 2-F-Pyr (4) H Me -CH ₂ -OO CH 3 -509 H 2-Cl-Pyr (4) H Me -CH ₂ -OO CH 3-510 H 2-Me-Pyr (4) H Me -CH ₂ -OO CH 3-511 H 2-Me-Pyr (4 ) H Me -CH ₂ -OS CH 3-512 H 2-Et-Pyr (4) H Me -CH ₂ -OO CH 3-513 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 3-514 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OON 3-515 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OS CH 3-516 H 2, 6-diMe-Pyr (4) H Et -CH ₂ -OO CH 3-517 H 2,6-diMe-Pyr (4) H Et -CH ₂ -OS CH 3-518 H 3,6-diMe-Pyr ( 4) H Me -CH ₂ -OO CH 3-519 H 3,6-diMe-Pyr (4) H Me -CH ₂ -OS CH 3-520 H 2-MeO-Pyr (4) H Me -CH _2- OO CH 3-521 H 2-MeO-Pyr (4) H Me -CH ₂ -OS CH 3-522 H 4-Imid (1) -Ph H Me -CH ₂ -OO CH 3-523 H 4-Imid ( 1) -Ph H Me -CH ₂ -OON 3-524 H 4-Imid (1) -Ph H Me -CH ₂ -OS CH 3-525 H 4-Imid (1) -Ph H Me -CH ₂ -OSN Three -526 H 4-Tz-Ph H Me -CH ₂ -OO CH 3-527 H 4-Tz-Ph H Me -CH ₂ -OON 3-528 H 4-Tz-Ph H Me -CH ₂ -OS CH 3 -529 H 4-Tz-Ph H Me -CH ₂ -OSN 3-530 H 4-Ada (1) -Ph H Me -CH ₂ -OO CH 3-531 H 4-Ada (1) -Ph H Me- CH ₂ -OON 3-532 H 4-Ada (1) -Ph H Me -CH ₂ -OS CH 3-533 H 4-Ada (1) -Ph H Me -CH ₂ -OSN 3-534 H 4-CN -Ph H Me -CH ₂ -OO CH 3-535 H 4-CN-Ph H Me -CH ₂ -OON 3-536 H 4-CN-Ph H Me -CH ₂ -OS CH 3-537 H 4-CN -Ph H Me -CH ₂ -OSN 3-538 H 4-Bz-3-OH-Ph H Me -CH ₂ -OO CH 3-539 H 4-Bz-3-OH-Ph H Me -CH ₂ -OON 3-540 H 4-OH-2,5-ditBu-Ph H Me -CH ₂ -OO CH 3-541 H pentaF-Ph H Me -CH ₂ -OO CH 3-542 H 4-NHCOPh-Ph H Me- CH ₂ -OO CH 3-543 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH ₂ -OO CH 3-544 H 4-NHCO (2,4-diF-Ph) -Ph H Me- CH ₂ -OO CH 3-545 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH ₂ -OO CH 3-546 H 4-NHCONp (1) -Ph H Me- CH ₂ -OO CH 3-547 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH ₂ -OO CH 3-548 H 4-NHCOcPn-Ph H Me -CH ₂ -OO CH 3-549 H 4-NHCOcHx-Ph H Me -CH ₂ -OO CH 3-550 H 4-NHCOPyr (3) -Ph H Me -CH ₂ -OO CH 3-551 H 4-NHCOPy r (4) -Ph H Me -CH ₂ -OO CH 3-552 H 4-NHHx-Ph H Me -CH ₂ -OO CH 3-553 H 4-NH (Ac) Hx-Ph H Me -CH _2- OO CH .

[0085]

[Table 4]

[0086]

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[0087] Cpd.No.R ² R ⁴ R ⁵ R ⁶ -A- BDE 4-1 H 4-F-Ph H Me -CH ₂ -OO CH 4-2 H 4-Cl-Ph H Me -CH ₂ -OO CH 4-3 H 2-OH-Ph H Me -CH ₂ -OO CH 4-4 H 2-OH-Ph H Me -CH ₂ -OS CH 4-5 H 2-OH-Ph H Et -CH ₂ -OO CH 4-6 H 2-OH-Ph H Et -CH _2- OS CH 4-7 H 3-OH-Ph H Me -CH ₂ -OO CH 4-8 H 3-OH-Ph H Me -CH ₂ -OS CH 4-9 H 3-OH-Ph H Et -CH ₂ -OO CH 4-10 H 3-OH-Ph H Et -CH ₂ -OS CH 4-11 H 4-OH-Ph H Me -CH ₂ -OO CH 4-12 H 4-OH-Ph H Me -CH ₂ -OON 4-13 H 4-OH-Ph H Me -CH ₂ -OS CH 4-14 H 4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 4-15 H 4-OH-Ph H Et -CH ₂ -OO CH 4-16 H 4-OH-Ph H Et -CH ₂ -OS CH 4-17 H 4-OH-Ph H tBu -CH ₂ -OO CH 4-18 H 3-CF _3- Ph H Me -CH ₂ -OO CH 4-19 H 4-iPrO-Ph H Me -CH ₂ -OO CH 4-20 H 4-MeS-Ph H Me -CH ₂ -OO CH 4-21 H 2-NH ₂ -Ph H Me -CH ₂ -OO CH 4-22 H 3-NH ₂ -Ph H Me -CH ₂ -OO CH 4-23 H 4-NH ₂ -Ph H Me -CH ₂ -OO CH 4-24 H 4-NHMe-Ph H Me -CH ₂ -OO CH 4-25 H 4-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 4-26 H 4-N (Me) ₂ -Ph H Et -CH ₂ -OO CH 4-27 H 4-Ph-Ph H Me -CH ₂ -OO CH 4-28 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH ₂ -OO CH 4-29 H 4- ( 4-OH-3,5-ditBu-Ph) Ph H Me -CH ₂ -OO CH 4-30 H 4- (4-OH-Bz) Ph H Me -CH ₂ -OO CH 4-31 H 4-PhS -Ph H Me -CH ₂ -OO CH 4-32 H 2-Pyrd (1) -Ph H Me -CH ₂ -OO CH 4-33 H 2-Pyrd (1) -Ph H Me -CH ₂ -OS CH 4-34 H 3-Pyrd (1) -Ph H Me -CH ₂ -OO CH 4-35 H 3-Pyrd (1) -Ph H Me -CH ₂ -OS CH 4-36 H 3-Pyrd (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 4-37 H 3-Pyrd (1) -Ph H Et -CH ₂ -OO CH 4-38 H 4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 4-39 H 4-Pyrd (1) -Ph H Me -CH ₂ -OON 4-40 H 4-Pyrd (1) -Ph H Me -CH ₂ -OS CH 4-41 H 4-Pyrd ( 1) -Ph H Me-(CH ₂ ) ₃ -OO CH 4-42 H 4-Pyrd (1) -Ph H Et -CH ₂ -OO CH 4-43 H 4-Pyrd (1) -Ph H Et- CH ₂ -OS CH 4-44 H 2-Pip (1) -Ph H Me -CH ₂ -OO CH 4-45 H 2-Pip (1) -Ph H Me -CH ₂ -OS CH 4-46 H 3 -Pip (1) -Ph H Me -CH ₂ -OO CH 4-47 H 3-Pip (1) -Ph H Me -CH ₂ -OS CH 4-48 H 3-Pip (1) -Ph H Et- (CH ₂ ) ₃ -SO CH 4-49 H 4-Pip (1) -Ph H Me -CH ₂ -OO CH 4-50 H 4-Pip (1) -Ph H Me -CH ₂ -OON 4-51 H 4-Pip (1) -Ph H Me -CH ₂ -OS CH 4-52 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 4-53 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 4-54 H 4-Pip (1)- Ph H Et -CH ₂ -OO CH 4-55 H 4-Pip (1) -Ph H Et -CH ₂ -OS CH 4-56 H 4-Pip (1) -Ph H tBu -CH ₂ -OO CH 4 -57 H 4-Pip (1) -Ph 4-Cl Me -CH ₂ -OO CH 4-58 2-MeO 4-Pip (1) -Ph H Me -CH ₂ -OO CH 4-59 H 2-Mor (4) -Ph H Me -CH ₂ -OO CH 4-60 H 2-Mor (4) -Ph H Me -CH ₂ -OS CH 4-61 H 2-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 4-62 H 3-Mor (4) -Ph H Me -CH ₂ -OO CH 4-63 H 3-Mor (4) -Ph H Me -CH ₂ -OS CH 4-64 H 3-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 4-65 H 3-Mor (4) -Ph H Et -CH ₂ -OO CH 4-66 H 4-Mor (4)- Ph H Me -CH ₂ -OO CH 4-67 H 4-Mor (4) -Ph H Me -CH ₂ -OON 4-68 H 4-Mor (4) -Ph H Me -CH ₂ -OS CH 4- 69 H 4-Mor (4) -Ph H Et -CH ₂ -OO CH 4-70 H 4-Mor (4) -Ph H Et -CH ₂ -OS CH 4-71 H 4-TioMor (4) -Ph H Me -CH ₂ -OO CH 4-72 H 4-Pipra (1) -Ph H Me -CH ₂ -OO CH 4-73 H 4-Pipra (1) -Ph H Me -CH ₂ -OS CH 4- 74 H 4-Pipra (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 4-75 H 4-Pipra (1) -Ph H Et -CH ₂ -OO CH 4-76 H 4-NO _2- Ph H Me -CH ₂ -OO CH 4-77 H 3-Cl-4-OH-Ph H Me -CH ₂ -OO CH 4-78 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 4-79 H 2-Cl-4-OH-3,5-diM e-Ph H Me -CH ₂ -OON 4-80 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 4-81 H 2-Cl-4-OH-3 , 5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 4-82 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₄ -OO CH 4-83 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 4-84 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OS CH 4-85 H 2-Cl-4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 4-86 H 2-Cl-4-OH-3,5-diMe-Ph 6-MeO Me -CH ₂ -OO CH 4-87 3-Cl 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 4-88 2-MeO 2-Cl-4-OH- 3,5-diMe-Ph H Me -CH ₂ -OO CH 4-89 H 3-Cl-5-OH-2,6-diMe-Ph H Me -CH ₂ -OO CH 4-90 H 4-Cl- 3-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 4-91 H 3-Cl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 4-92 H 3,5-diCl -4-NH ₂ -Ph H Me -CH ₂ -OO CH 4-93 H 4-NHMe-3-Cl-Ph H Me -CH ₂ -OO CH 4-94 H 3-Cl-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 4-95 H 3-OH-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 4-96 H 3-Cl-6-Me-4-Pyrd ( 1) -Ph H Me -CH ₂ -OO CH 4-97 H 2-Me-4-Mor (4) -Ph H Me -CH ₂ -OO CH 4-98 H 2-OH-3-Me-Ph H Me -CH ₂ -OO CH 4-99 H 2-OH-4-Me-Ph H Me -CH ₂ -OO CH 4-100 H 2-OH-3,4-diMe-Ph H Me -CH ₂ -OO CH 4-101 H 3-OH-2-Me-Ph H Me -CH ₂ -OO CH 4-102 H 3-OH-4-Me-Ph H Me -CH ₂ -OO CH 4-103 H 3-OH -5-Me-Ph H Me -CH ₂ -OO CH 4-104 H 3-OH-6-Me-Ph H Me -CH ₂ -OO CH 4-105 H 3-OH-2,4-diMe-Ph H Me -CH ₂ -OO CH 4-106 H 4-OH-2-Me-Ph H Me -CH ₂ -OO CH 4-107 H 4-OH-3-Me-Ph H Me -CH ₂ -OO CH 4-108 H 4-OH-3-Me-Ph H Me -CH ₂ -OS CH 4-109 H 4-OH-3-Me-Ph H Et -CH ₂ -OO CH 4-110 H 4-OH- 3-Me-Ph 6-Cl Me -CH ₂ -OO CH 4-111 H 4-OH-2-tBu-Ph H Me -CH ₂ -OO CH 4-112 H 4-OH-3-tBu-Ph H Me -CH ₂ -OO CH 4-113 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OO CH 4-114 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OS CH 4-115 H 4-OH-2,3-diMe-Ph H Me-(CH ₂ ) ₃ -SO CH 4-116 H 4-OH-2,3-diMe-Ph H Et -CH _2- OO CH 4-117 H 4-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 4-118 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 4- 119 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 4-120 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 4-121 H 4-OH -3,5-diMe-Ph H Me -CH ₂ -SO CH 4-122 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 4-123 H 4-OH- 3,5-diMe-Ph H Et -CH ₂ -OO CH 4-124 H 4-OH-3,5 -diMe-Ph H Et -CH ₂ -OS CH 4-125 H 4-OH-3,5-diMe-Ph H sBu -CH ₂ -OO CH 4-126 H 4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 4-127 H 4-OH-3,5-diMe-Ph H Ph -CH ₂ -OO CH 4-128 H 3,5-diEt-4-OH-Ph H Me -CH ₂ -OO CH 4-129 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OO CH 4-130 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OS CH 4-131 H 4-OH-3,5-diPr-Ph H Me -CH ₂ -OO CH 4-132 H 4-OH-3,5-diiPr-Ph H Me -CH ₂ -OO CH 4-133 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 4-134 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OON 4-135 H 3 , 5-ditBu-4-OH-Ph H Me -CH ₂ -OS CH 4-136 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -SS CH 4-137 H 3,5-ditBu -4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 4-138 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 4-139 H 3,5 -ditBu-4-OH-Ph H Me-(CH ₂ ) ₃ -OS CH 4-140 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OO CH 4-141 H 3,5- ditBu-4-OH-Ph H Et -CH ₂ -OS CH 4-142 H 3,5-ditBu-4-OH-Ph H tBu -CH ₂ -OO CH 4-143 H 3,5-ditBu-4- OH-Ph 6-Cl Me -CH ₂ -OS CH 4-144 H 4-OH-2,3,5-triMe-Ph HH -CH ₂ -OS CH 4-145 H 4-OH-2,3,5 -triMe-Ph H Me -CH ₂ -OO CH 4-146 H 4 -OH-2,3,5-triMe-Ph H Me -CH ₂ -OON 4-147 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OS CH 4-148 H 4- OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₂ -OO CH 4-149 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₃ -OO CH 4-150 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OO CH 4-151 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OS CH 4-152 H 4-OH-2,3,5-triMe-Ph H iPr -CH ₂ -OO CH 4-153 H 4-OH-2,3,5-triMe-Ph H tBu -CH ₂ -OO CH 4-154 H 4-OH-2,3,5-triMe-Ph H Ph -CH ₂ -OO CH 4-155 H 4-OH-2,3,5-triMe-Ph H Bz -CH ₂ -OO CH 4-156 H 4-OH-2,3,5-triMe-Ph 6-Cl Me -CH ₂ -OO CH 4-157 2-Cl 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 4-158 2-MeO 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 4-159 H 4-OH-2,3,6-triMe-Ph H Me -CH ₂ -OO CH 4-160 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH ₂ -OO CH 4-161 H 4-OH-3,5-diMeO-Ph H Me -CH ₂ -OO CH 4-162 H 3-NH ₂ -4-Me-Ph H Me -CH ₂ -OO CH 4-163 H 4-NH ₂ -2,3-diMe-Ph H Me -CH _2- OO CH 4-164 H 4-NH ₂ -2,6-diMe-Ph H Me -CH ₂ -OO CH 4-165 H 4-NH ₂ -3,5-diMe-Ph HH -CH ₂ -OO CH 4 -166 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 4-167 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OON 4-168 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 4-169 H 4- NH ₂ -3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 4-170 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OO CH 4-171 H 4 -NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OS CH 4-172 H 4-NH ₂ -3,5-diMe-Ph H tBu -CH ₂ -OO CH 4-173 H 4-NH ₂ -3,5-diMe-Ph H Ph -CH ₂ -OO CH 4-174 H 4-NH ₂ -3,5-diMe-Ph H Bz -CH ₂ -OO CH 4-175 H 4-NH _2- 3,5-diEt-Ph H Me -CH ₂ -OO CH 4-176 H 4-NHMe-3,5-diMe-Ph H Me -CH ₂ -OO CH 4-177 H 4-NHAc-3,5- diMe-Ph H Me -CH ₂ -OO CH 4-178 H 4-NO ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 4-179 H 4-NO ₂ -3,5-diMe- _{Ph H Me -CH 2 - OS CH} 4-180 H Pyr (2) H Me -CH 2 - OO CH 4-181 H Pyr (2) H Me -CH 2 - OON 4-182 H Pyr (2) H Me -CH ₂ -OS CH 4-183 H Pyr (2) H Me-(CH ₂ ) ₂ -OO CH 4-184 H Pyr (2) H Me-(CH ₂ ) ₃ -OO CH 4-185 H Pyr ( 2) H Et -CH ₂ -OO CH 4-186 H Pyr (2) H Et -CH ₂ -OS CH 4-187 H Pyr (2) H tBu -CH ₂ -OO CH 4-188 H Pyr (2) H Ph -CH ₂ -OO CH 4-189 H Pyr (2) 6-Cl Me -CH ₂ -OO CH 4-190 H 5-Cl-Pyr (2) H Me -CH ₂ -OO CH 4- 191 H 6-Cl-Pyr (2) H Me -CH ₂ -OO CH 4-192 H 6-Me-Pyr (2) H Me -CH ₂ -OO CH 4-193 H 6-MeO-Pyr (2) H Me -CH ₂ -OO CH 4-194 H 3-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 4-195 H 5-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH _{4-196 H 3-NO 2 -Pyr (} 2) H Me -CH 2 - OO CH 4-197 H 5-NO 2 -Pyr (2) H Me -CH 2 - OO CH 4-198 H 5-NH 2 -6-Cl-Pyr (2) H Me -CH ₂ -OO CH 4-199 3-MeO 5-NH ₂ -6-Cl-Pyr (2) 6-MeO Et-(CH ₂ ) ₄ -SS CH 4 -200 H Pyr (3) H Me -CH ₂ -OO CH 4-201 H Pyr (3) H Me -CH ₂ -OON 4-202 H Pyr (3) H Me -CH ₂ -OS CH 4-203 H Pyr (3) H Me-(CH ₂ ) ₂ -OO CH 4-204 H Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 4-205 H Pyr (3) H Et -CH ₂ -OO CH 4-206 H Pyr (3) H Et -CH ₂ -OS CH 4-207 H Pyr (3) H tBu -CH ₂ -OO CH 4-208 H Pyr (3) H Pn-(CH ₂ ) ₃ -OO CH 4-209 H Pyr (3) H Ph -CH ₂ -OO CH 4-210 H Pyr (3) H Ph -CH ₂ -OS CH 4-211 H Pyr (3) H Bz -CH ₂ -OO CH 4 -212 2-Cl Pyr (3) H Me -CH ₂ -OO CH 4-213 H 5-MeO-Pyr (3) H Me -CH ₂ -OO CH 4-214 H 6-MeO-Pyr (3) H Me -CH ₂ -OO CH 4-215 H 6-MeO-Pyr (3) H Me -CH ₂ -OS CH 4-216 H 6-MeO-Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 4-217 H 6-iPrO-Pyr (3) H Me -CH ₂ -OO CH 4-218 H 6-MeO-5-Me-Pyr (3) H Me -CH ₂ -OO CH 4-219 H 2-NO ₂ -6-Me-Pyr (3) H Me -CH ₂ -OO CH 4-220 H Pyr (4) H Me -CH ₂ -OO CH 4-221 H Pyr (4) H _{Me -CH 2 - OON 4-222 H Pyr} (4) H Me -CH 2 - OS CH 4-223 H Pyr (4) H Me -CH 2 - SS CH 4-224 H Pyr (4) H Me - ( CH ₂ ) ₂ -OO CH 4-225 H Pyr (4) H Et -CH ₂ -OO CH 4-226 H Pyr (4) H Et -CH ₂ -OS CH 4-227 H Pyr (4) H tBu- CH ₂ -OO CH 4-228 H Pyr (4) H Ph -CH ₂ -OO CH 4-229 H Pyr (4) H Bz -CH ₂ -OS CH 4-230 3-Cl Pyr (4) H Me- CH ₂ -OO CH 4-231 H 2-Me-Pyr (4) H Me -CH ₂ -OO CH 4-232 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 4-233 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OS CH 4-234 H 3,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 4-235 H 2-MeO-Pyr (4) H Me -CH ₂ -OO CH 4-236 H 4-Imid (1) -Ph H Me -CH ₂ -OO CH 4-237 H 4-Tz-Ph H Me -CH ₂ -OO CH 4- 238 H 4-Ada (1) -Ph H Me -CH ₂ -OO CH 4-239 H 4-CN-Ph H Me -CH ₂ -OO CH 4-240 H 4-Bz-3-OH-Ph H Me -CH ₂ -OO CH 4-241 H pentaF-Ph H Me -CH ₂ -OO CH 4-242 H 4-NHCOPh-Ph H Me -CH ₂ -OO C H 4-243 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH ₂ -OO CH 4-244 H 4-NHCO (2,4-diF-Ph) -Ph H Me -CH ₂ -OO CH 4-245 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH ₂ -OO CH 4-246 H 4-NHCONp (1) -Ph H Me -CH ₂ -OO CH 4-247 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH ₂ -OO CH 4-248 H 4-NHCOcPn-Ph H Me -CH ₂ -OO CH 4-249 H 4-NHCOcHx- Ph H Me -CH ₂ -OO CH 4-250 H 4-NHCOPyr (3) -Ph H Me -CH ₂ -OO CH 4-251 H 4-NHCOPyr (4) -Ph H Me -CH ₂ -OO CH 4 -252 H 4-NHHx-Ph H Me -CH ₂ -OO CH 4-253 H 4-NH (Ac) Hx-Ph H Me -CH ₂ -OO CH .

[0088]

[Table 5]

[0089]

Embedded image

[0090] Cpd.No.R ² R ⁴ R ⁵ R ⁶ -A- BDE 5-1 H 4-F-Ph H Me -CH ₂ -OO CH 5-2 H 4-Cl-Ph H Me -CH ₂ -OO CH 5-3 H 2-OH-Ph H Me -CH ₂ -OO CH 5-4 H 2-OH-Ph H Me -CH ₂ -OS CH 5-5 H 2-OH-Ph H Et -CH ₂ -OO CH 5-6 H 2-OH-Ph H Et -CH _2- OS CH 5-7 H 3-OH-Ph H Me -CH ₂ -OO CH 5-8 H 3-OH-Ph H Me -CH ₂ -OS CH 5-9 H 3-OH-Ph H Et -CH ₂ -OO CH 5-10 H 3-OH-Ph H Et -CH ₂ -OS CH 5-11 H 4-OH-Ph H Me -CH ₂ -OO CH 5-12 H 4-OH-Ph H Me -CH ₂ -OON 5-13 H 4-OH-Ph H Me -CH ₂ -OS CH 5-14 H 4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 5-15 H 4-OH-Ph H Et -CH ₂ -OO CH 5-16 H 4-OH-Ph H Et -CH ₂ -OS CH 5-17 H 4-OH-Ph H tBu -CH ₂ -OO CH 5-18 H 3-CF _3- Ph H Me -CH ₂ -OO CH 5-19 H 4-iPrO-Ph H Me -CH ₂ -OO CH 5-20 H 4-MeS-Ph H Me -CH ₂ -OO CH 5-21 H 2-NH ₂ -Ph H Me -CH ₂ -OO CH 5-22 H 3-NH ₂ -Ph H Me -CH ₂ -OO CH 5-23 H 4-NH ₂ -Ph H Me -CH ₂ -OO CH 5-24 H 4-NHMe-Ph H Me -CH ₂ -OO CH 5-25 H 4-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 5-26 H 4-N (Me) ₂ -Ph H Et -CH ₂ -OO CH 5-27 H 4-Ph-Ph H Me -CH ₂ -OO CH 5-28 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH ₂ -OO CH 5-29 H 4- ( 4-OH-3,5-ditBu-Ph) Ph H Me -CH ₂ -OO CH 5-30 H 4- (4-OH-Bz) Ph H Me -CH ₂ -OO CH 5-31 H 4-PhS -Ph H Me -CH ₂ -OO CH 5-32 H 2-Pyrd (1) -Ph H Me -CH ₂ -OO CH 5-33 H 2-Pyrd (1) -Ph H Me -CH ₂ -OS CH 5-34 H 3-Pyrd (1) -Ph H Me -CH ₂ -OO CH 5-35 H 3-Pyrd (1) -Ph H Me -CH ₂ -OS CH 5-36 H 3-Pyrd (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 5-37 H 3-Pyrd (1) -Ph H Et -CH ₂ -OO CH 5-38 H 4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 5-39 H 4-Pyrd (1) -Ph H Me -CH ₂ -OON 5-40 H 4-Pyrd (1) -Ph H Me -CH ₂ -OS CH 5-41 H 4-Pyrd ( 1) -Ph H Me-(CH ₂ ) ₃ -OO CH 5-42 H 4-Pyrd (1) -Ph H Et -CH ₂ -OO CH 5-43 H 4-Pyrd (1) -Ph H Et- CH ₂ -OS CH 5-44 H 2-Pip (1) -Ph H Me -CH ₂ -OO CH 5-45 H 2-Pip (1) -Ph H Me -CH ₂ -OS CH 5-46 H 3 -Pip (1) -Ph H Me -CH ₂ -OO CH 5-47 H 3-Pip (1) -Ph H Me -CH ₂ -OS CH 5-48 H 3-Pip (1) -Ph H Et- (CH ₂ ) ₃ -SO CH 5-49 H 4-Pip (1) -Ph H Me -CH ₂ -OO CH 5-50 H 4-Pip (1) -Ph H Me -CH ₂ -OON 5-51 H 4-Pip (1) -Ph H Me -CH ₂ -OS CH 5-52 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 5-53 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 5-54 H 4-Pip (1)- Ph H Et -CH ₂ -OO CH 5-55 H 4-Pip (1) -Ph H Et -CH ₂ -OS CH 5-56 H 4-Pip (1) -Ph H tBu -CH ₂ -OO CH 5 -57 H 4-Pip (1) -Ph 4-Cl Me -CH ₂ -OO CH 5-58 2-MeO 4-Pip (1) -Ph H Me -CH ₂ -OO CH 5-59 H 2-Mor (4) -Ph H Me -CH ₂ -OO CH 5-60 H 2-Mor (4) -Ph H Me -CH ₂ -OS CH 5-61 H 2-Mor (4) -Ph H Me-(CH _{2) 3 - OO CH 5-62 H} 3-Mor (4) -Ph H Me -CH 2 - OO CH 5-63 H 3-Mor (4) -Ph H Me -CH 2 - OS CH 5-64 H 3-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 5-65 H 3-Mor (4) -Ph H Et -CH ₂ -OO CH 5-66 H 4-Mor (4)- Ph H Me -CH ₂ -OO CH 5-67 H 4-Mor (4) -Ph H Me -CH ₂ -OON 5-68 H 4-Mor (4) -Ph H Me -CH ₂ -OS CH 5- 69 H 4-Mor (4) -Ph H Et -CH ₂ -OO CH 5-70 H 4-Mor (4) -Ph H Et -CH ₂ -OS CH 5-71 H 4-TioMor (4) -Ph H Me -CH ₂ -OO CH 5-72 H 4-Pipra (1) -Ph H Me -CH ₂ -OO CH 5-73 H 4-Pipra (1) -Ph H Me -CH ₂ -OS CH 5- 74 H 4-Pipra (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 5-75 H 4-Pipra (1) -Ph H Et -CH ₂ -OO CH 5-76 H 4-NO _2- Ph H Me -CH ₂ -OO CH 5-77 H 3-Cl-4-OH-Ph H Me -CH ₂ -OO CH 5-78 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 5-79 H 2-Cl-4-OH-3,5-diM e-Ph H Me -CH ₂ -OON 5-80 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 5-81 H 2-Cl-4-OH-3 , 5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 5-82 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₄ -OO CH 5-83 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 5-84 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OS CH 5-85 H 2-Cl-4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 5-86 H 2-Cl-4-OH-3,5-diMe-Ph 5-MeO Me -CH ₂ -OO CH 5-87 3-Cl 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 5-88 2-MeO 2-Cl-4-OH- 3,5-diMe-Ph H Me -CH ₂ -OO CH 5-89 H 3-Cl-5-OH-2,6-diMe-Ph H Me -CH ₂ -OO CH 5-90 H 4-Cl- 3-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 5-91 H 3-Cl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 5-92 H 3,5-diCl -4-NH ₂ -Ph H Me -CH ₂ -OO CH 5-93 H 4-NHMe-3-Cl-Ph H Me -CH ₂ -OO CH 5-94 H 3-Cl-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 5-95 H 3-OH-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 5-96 H 3-Cl-6-Me-4-Pyrd ( 1) -Ph H Me -CH ₂ -OO CH 5-97 H 2-Me-4-Mor (4) -Ph H Me -CH ₂ -OO CH 5-98 H 2-OH-3-Me-Ph H Me -CH ₂ -OO CH 5-99 H 2-OH-4-Me-Ph H Me -CH ₂ -OO CH 5-100 H 2-OH-3,4-diMe-Ph H Me -CH ₂ -OO CH 5-101 H 3-OH-2-Me-Ph H Me -CH ₂ -OO CH 5-102 H 3-OH-4-Me-Ph H Me -CH ₂ -OO CH 5-103 H 3-OH -5-Me-Ph H Me -CH ₂ -OO CH 5-104 H 3-OH-6-Me-Ph H Me -CH ₂ -OO CH 5-105 H 3-OH-2,4-diMe-Ph H Me -CH ₂ -OO CH 5-106 H 4-OH-2-Me-Ph H Me -CH ₂ -OO CH 5-107 H 4-OH-3-Me-Ph H Me -CH ₂ -OO CH 5-108 H 4-OH-3-Me-Ph H Me -CH ₂ -OS CH 5-109 H 4-OH-3-Me-Ph H Et -CH ₂ -OO CH 5-110 H 4-OH- 3-Me-Ph 5-Cl Me -CH ₂ -OO CH 5-111 H 4-OH-2-tBu-Ph H Me -CH ₂ -OO CH 5-112 H 4-OH-3-tBu-Ph H Me -CH ₂ -OO CH 5-113 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OO CH 5-114 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OS CH 5-115 H 4-OH-2,3-diMe-Ph H Me-(CH ₂ ) ₃ -SO CH 5-116 H 4-OH-2,3-diMe-Ph H Et -CH _2- OO CH 5-117 H 4-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 5-118 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 5- 119 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 5-120 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 5-121 H 4-OH -3,5-diMe-Ph H Me -CH ₂ -SO CH 5-122 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 5-123 H 4-OH- 3,5-diMe-Ph H Et -CH ₂ -OO CH 5-124 H 4-OH-3,5 -diMe-Ph H Et -CH ₂ -OS CH 5-125 H 4-OH-3,5-diMe-Ph H sBu -CH ₂ -OO CH 5-126 H 4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 5-127 H 4-OH-3,5-diMe-Ph H Ph -CH ₂ -OO CH 5-128 H 3,5-diEt-4-OH-Ph H Me -CH ₂ -OO CH 5-129 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OO CH 5-130 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OS CH 5-131 H 4-OH-3,5-diPr-Ph H Me -CH ₂ -OO CH 5-132 H 4-OH-3,5-diiPr-Ph H Me -CH ₂ -OO CH 5-133 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 5-134 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OON 5-135 H 3 , 5-ditBu-4-OH-Ph H Me -CH ₂ -OS CH 5-136 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -SS CH 5-137 H 3,5-ditBu -4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 5-138 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 5-139 H 3,5 -ditBu-4-OH-Ph H Me-(CH ₂ ) ₃ -OS CH 5-140 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OO CH 5-141 H 3,5- ditBu-4-OH-Ph H Et -CH ₂ -OS CH 5-142 H 3,5-ditBu-4-OH-Ph H tBu -CH ₂ -OO CH 5-143 H 3,5-ditBu-4- OH-Ph 5-Cl Me -CH ₂ -OS CH 5-144 H 4-OH-2,3,5-triMe-Ph HH -CH ₂ -OS CH 5-145 H 4-OH-2,3,5 -triMe-Ph H Me -CH ₂ -OO CH 5-146 H 4 -OH-2,3,5-triMe-Ph H Me -CH ₂ -OON 5-147 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OS CH 5-148 H 4- OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₂ -OO CH 5-149 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₃ -OO CH 5-150 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OO CH 5-151 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OS CH 5-152 H 4-OH-2,3,5-triMe-Ph H iPr -CH ₂ -OO CH 5-153 H 4-OH-2,3,5-triMe-Ph H tBu -CH ₂ -OO CH 5-154 H 4-OH-2,3,5-triMe-Ph H Ph -CH ₂ -OO CH 5-155 H 4-OH-2,3,5-triMe-Ph H Bz -CH ₂ -OO CH 5-156 H 4-OH-2,3,5-triMe-Ph 5-Cl Me -CH ₂ -OO CH 5-157 2-Cl 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 5-158 2-MeO 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 5-159 H 4-OH-2,3,6-triMe-Ph H Me -CH ₂ -OO CH 5-160 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH ₂ -OO CH 5-161 H 4-OH-3,5-diMeO-Ph H Me -CH ₂ -OO CH 5-162 H 3-NH ₂ -4-Me-Ph H Me -CH ₂ -OO CH 5-163 H 4-NH ₂ -2,3-diMe-Ph H Me -CH _{2- OO CH 5-164 H 4-NH 2} -2,6-diMe-Ph H Me -CH 2 - OO CH 5-165 H 4-NH 2 -3,5-diMe-Ph HH -CH 2 - OO CH 5 -166 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 5-167 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OON 5-168 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 5-169 H 4- NH ₂ -3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 5-170 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OO CH 5-171 H 4 -NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OS CH 5-172 H 4-NH ₂ -3,5-diMe-Ph H tBu -CH ₂ -OO CH 5-173 H 4-NH ₂ -3,5-diMe-Ph H Ph -CH ₂ -OO CH 5-174 H 4-NH ₂ -3,5-diMe-Ph H Bz -CH ₂ -OO CH 5-175 H 4-NH _2- 3,5-diEt-Ph H Me -CH ₂ -OO CH 5-176 H 4-NHMe-3,5-diMe-Ph H Me -CH ₂ -OO CH 5-177 H 4-NHAc-3,5- diMe-Ph H Me -CH ₂ -OO CH 5-178 H 4-NO ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 5-179 H 4-NO ₂ -3,5-diMe- Ph H Me -CH ₂ -OS CH 5-180 H Pyr (2) H Me -CH ₂ -OO CH 5-181 H Pyr (2) H Me -CH ₂ -OON 5-182 H Pyr (2) H Me -CH ₂ -OS CH 5-183 H Pyr (2) H Me-(CH ₂ ) ₂ -OO CH 5-184 H Pyr (2) H Me-(CH ₂ ) ₃ -OO CH 5-185 H Pyr ( 2) H Et -CH ₂ -OO CH 5-186 H Pyr (2) H Et -CH ₂ -OS CH 5-187 H Pyr (2) H tBu -CH ₂ -OO CH 5-188 H Pyr (2) H Ph -CH ₂ -OO CH 5-189 H Pyr (2) 5-Cl Me -CH ₂ -OO CH 5-190 H 5-Cl-Pyr (2) H Me -CH ₂ -OO CH 5- 191 H 6-Cl-Pyr (2) H Me -CH ₂ -OO CH 5-192 H 6-Me-Pyr (2) H Me -CH ₂ -OO CH 5-193 H 6-MeO-Pyr (2) H Me -CH ₂ -OO CH 5-194 H 3-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 5-195 H 5-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 5-196 H 3-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 5-197 H 5-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 5-198 H 5-NH ₂ -6-Cl-Pyr (2) H Me -CH ₂ -OO CH 5-199 3-MeO 5-NH ₂ -6-Cl-Pyr (2) 5-MeO Et-(CH ₂ ) ₄ -SS CH 5 -200 H Pyr (3) H Me -CH ₂ -OO CH 5-201 H Pyr (3) H Me -CH ₂ -OON 5-202 H Pyr (3) H Me -CH ₂ -OS CH 5-203 H Pyr (3) H Me-(CH ₂ ) ₂ -OO CH 5-204 H Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 5-205 H Pyr (3) H Et -CH ₂ -OO CH 5-206 H Pyr (3) H Et -CH ₂ -OS CH 5-207 H Pyr (3) H tBu -CH ₂ -OO CH 5-208 H Pyr (3) H Pn-(CH ₂ ) ₃ -OO CH 5-209 H Pyr (3) H Ph -CH ₂ -OO CH 5-210 H Pyr (3) H Ph -CH ₂ -OS CH 5-211 H Pyr (3) H Bz -CH ₂ -OO CH 5 -212 2-Cl Pyr (3) H Me -CH ₂ -OO CH 5-213 H 5-MeO-Pyr (3) H Me -CH ₂ -OO CH 5-214 H 6-MeO-Pyr (3) H Me -CH ₂ -OO CH 5-215 H 6-MeO-Pyr (3) H Me -CH ₂ -OS CH 5-216 H 6-MeO-Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 5-217 H 6-iPrO-Pyr (3) H Me -CH ₂ -OO CH 5-218 H 6-MeO-5-Me-Pyr (3) H Me -CH ₂ -OO CH 5-219 H 2-NO ₂ -6-Me-Pyr (3) H Me -CH ₂ -OO CH 5-220 H Pyr (4) H Me -CH ₂ -OO CH 5-221 H Pyr (4) H Me -CH ₂ -OON 5-222 H Pyr (4) H Me -CH ₂ -OS CH 5-223 H Pyr (4) H Me -CH ₂ -SS CH 5-224 H Pyr (4) H Me-( CH ₂ ) ₂ -OO CH 5-225 H Pyr (4) H Et -CH ₂ -OO CH 5-226 H Pyr (4) H Et -CH ₂ -OS CH 5-227 H Pyr (4) H tBu- CH ₂ -OO CH 5-228 H Pyr (4) H Ph -CH ₂ -OO CH 5-229 H Pyr (4) H Bz -CH ₂ -OS CH 5-230 3-Cl Pyr (4) H Me- CH ₂ -OO CH 5-231 H 2-Me-Pyr (4) H Me -CH ₂ -OO CH 5-232 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 5-233 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OS CH 5-234 H 3,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 5-235 H 2-MeO-Pyr (4) H Me -CH ₂ -OO CH 5-236 H 4-Imid (1) -Ph H Me -CH ₂ -OO CH 5-237 H 4-Tz-Ph H Me -CH ₂ -OO CH 5- 238 H 4-Ada (1) -Ph H Me -CH ₂ -OO CH 5-239 H 4-CN-Ph H Me -CH ₂ -OO CH 5-240 H 4-Bz-3-OH-Ph H Me -CH ₂ -OO CH 5-241 H pentaF-Ph H Me -CH ₂ -OO CH 5-242 H 4-NHCOPh-Ph H Me -CH ₂ -OO C H 5-243 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH ₂ -OO CH 5-244 H 4-NHCO (2,4-diF-Ph) -Ph H Me -CH ₂ -OO CH 5-245 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH ₂ -OO CH 5-246 H 4-NHCONp (1) -Ph H Me -CH ₂ -OO CH 5-247 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH ₂ -OO CH 5-248 H 4-NHCOcPn-Ph H Me -CH ₂ -OO CH 5-249 H 4-NHCOcHx- Ph H Me -CH ₂ -OO CH 5-250 H 4-NHCOPyr (3) -Ph H Me -CH ₂ -OO CH 5-251 H 4-NHCOPyr (4) -Ph H Me -CH ₂ -OO CH 5 -252 H 4-NHHx-Ph H Me -CH ₂ -OO CH 5-253 H 4-NH (Ac) Hx-Ph H Me -CH ₂ -OO CH .

[0091]

[Table 6]

[0092]

Embedded image

[0093] Cpd.No.R ² R ⁴ R ⁵ R ⁶ -A- BDE 6-1 H 4-F-Ph H Me -CH ₂ -OO CH 6-2 H 4-Cl-Ph H Me -CH ₂ -OO CH 6-3 H 2-OH-Ph H Me -CH ₂ -OO CH 6-4 H 2-OH-Ph H Me -CH ₂ -OS CH 6-5 H 3-OH-Ph H Me -CH ₂ -OO CH 6-6 H 3-OH-Ph H Me -CH _2- OS CH 6-7 H 4-OH-Ph H Me -CH ₂ -OO CH 6-8 H 4-OH-Ph H Me -CH ₂ -OON 6-9 H 4-OH-Ph H Me -CH _2- OS CH 6-10 H 4-OH-Ph H Et -CH ₂ -OO CH 6-11 H 4-OH-Ph H Et -CH ₂ -OS CH 6-12 H 3-CF ₃ -Ph H Me -CH ₂ -OO CH 6-13 H 4-iPrO-Ph H Me -CH ₂ -OO CH 6-14 H 4-MeS-Ph H Me -CH ₂ -OO CH 6-15 H 2-NH ₂ -Ph H Me -CH ₂ -OO CH 6-16 H 3-NH ₂ -Ph H Me -CH ₂ -OO CH 6-17 H 4-NH ₂ -Ph H Me -CH ₂ -OO CH 6-18 H 4-NHMe- Ph H Me -CH ₂ -OO CH 6-19 H 4-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 6-20 H 4-N (Me) ₂ -Ph H Et -CH ₂ -OO CH 6-21 H 4-Ph-Ph H Me -CH ₂ -OO CH 6-22 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH ₂ -OO CH 6-23 H 4- (4-OH-3,5-ditBu-Ph) Ph H Me -CH ₂ -OO CH 6-24 H 4- (4-OH-Bz) Ph H Me -CH ₂ -OO CH 6-25 H 4-PhS-Ph H Me -CH ₂ -OO CH 6-26 H 2-Pyrd (1) -Ph H Me -CH ₂ -OO CH 6-27 H 3-Pyrd (1) -Ph H Me -CH ₂ -OO CH 6-28 H 3-Pyrd (1)- Ph H Me -CH ₂ -OS CH 6-29 H 3-Pyrd (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 6-30 H 3-Pyrd (1) -Ph H Et -CH _2- OO CH 6-31 H 4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 6-32 H 4-Pyrd (1) -Ph H Me -CH ₂ -OS CH 6-33 H 4-Pyrd ( 1) -Ph H Me-(CH ₂ ) ₃ -OO CH 6-34 H 2-Pip (1) -Ph H Me -CH ₂ -OO CH 6-35 H 3-Pip (1) -Ph H Me- CH ₂ -OO CH 6-36 H 3-Pip (1) -Ph H Me -CH ₂ -OS CH 6-37 H 3-Pip (1) -Ph H Et-(CH ₂ ) ₃ -SO CH 6- 38 H 4-Pip (1) -Ph H Me -CH ₂ -OO CH 6-39 H 4-Pip (1) -Ph H Me -CH ₂ -OS CH 6-40 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 6-41 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 6-42 H 4-Pip (1) -Ph H tBu -CH ₂ -OO CH 6-43 H 4-Pip (1) -Ph 4-Cl Me -CH ₂ -OO CH 6-44 2-MeO 4-Pip (1) -Ph H Me -CH ₂ -OO CH 6- 45 H 2-Mor (4) -Ph H Me -CH ₂ -OO CH 6-46 H 2-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 6-47 H 3-Mor (4 ) -Ph H Me -CH ₂ -OO CH 6-48 H 3-Mor (4) -Ph H Me -CH ₂ -OS CH 6-49 H 3-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 6-50 H 3-Mor (4) -Ph H Et -CH ₂ -OO CH 6-51 H 4-Mor (4) -Ph H Me -CH ₂ -OO CH 6-52 H 4- Mor (4) -Ph H Me -CH ₂ -OS CH 6-53 H 4-TioMor (4) -Ph H Me -CH ₂ -OO CH 6-54 H 4-Pipra (1) -Ph H Me -CH ₂ -OO CH 6-55 H 4-Pipra (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 6-56 H 4-Pipra (1) -Ph H Et -CH ₂ -OO CH 6-57 H 4-NO ₂ -Ph H Me -CH ₂ -OO CH 6-58 H 2-Cl-4 -OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 6-59 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 5-60 H 2- Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 5-61 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₄ -OO CH 6-62 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 6-63 H 2-Cl-4-OH-3,5-diMe-Ph H Et- CH ₂ -OS CH 6-64 H 2-Cl-4-OH-3,5-diMe-Ph 6-MeO Me -CH ₂ -OO CH 6-65 3-Cl 2-Cl-4-OH-3, 5-diMe-Ph H Me -CH ₂ -OO CH 6-66 2-MeO 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 6-67 H 4-Cl- 3-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 6-68 H 3-Cl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 6-69 H 3,5-diCl -4-NH ₂ -Ph H Me -CH ₂ -OO CH 6-70 H 4-NHMe-3-Cl-Ph H Me -CH ₂ -OO CH 6-71 H 3-Cl-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 6-72 H 3-OH-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 6-73 H 3-Cl-6-Me-4-Pyrd ( 1) -Ph H Me -CH ₂ -OO CH 6-74 H 2-Me-4-Mor (4) -Ph H Me -CH ₂ -OO CH 6-75 H 2-OH- 3-Me-Ph H Me -CH ₂ -OO CH 6-76 H 2-OH-4-Me-Ph H Me -CH ₂ -OO CH 6-77 H 2-OH-3,4-diMe-Ph H Me -CH ₂ -OO CH 6-78 H 3-OH-2-Me-Ph H Me -CH ₂ -OO CH 6-79 H 3-OH-4-Me-Ph H Me -CH ₂ -OO CH 6 -80 H 3-OH-5-Me-Ph H Me -CH ₂ -OO CH 6 -81 H 3-OH-6-Me-Ph H Me -CH ₂ -OO CH 6-82 H 3-OH-2 , 4-diMe-Ph H Me -CH ₂ -OO CH 6-83 H 4-OH-2-Me-Ph H Me -CH ₂ -OO CH 6-84 H 4-OH-3-Me-Ph H Me -CH ₂ -OO CH 6-85 H 4-OH-3-Me-Ph H Et -CH ₂ -OO CH 6-86 H 4-OH-3-Me-Ph 6-Cl Me -CH ₂ -OO CH 6-87 H 4-OH-2-tBu-Ph H Me -CH ₂ -OO CH 6-88 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OO CH 6-89 H 4- OH-2,3-diMe-Ph H Me -CH ₂ -OS CH 6-90 H 4-OH-2,3-diMe-Ph H Me-(CH ₂ ) ₃ -SO CH 6-91 H 4-OH -2,3-diMe-Ph H Et -CH ₂ -OO CH 6-92 H 4-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 6-93 H 4-OH-3,5 -diMe-Ph H Me -CH ₂ -OO CH 6-94 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 6-95 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 6-96 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -SO CH 6-97 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 6-98 H 4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 6-99 H 4-OH- 3,5-diMe-Ph H Et -CH ₂ -OS CH 6-100 H 4-OH-3,5-diMe-Ph H sBu -CH ₂ -OO CH 6-101 H 4-OH-3,5- diMe-Ph H Ph -CH ₂ -OO CH 6-102 H 3,5-diEt-4-OH-Ph H Me -CH ₂ -OO CH 6-103 H 3-tBu-4-OH-5-Me- Ph H Me -CH ₂ -OO CH 6-104 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OS CH 6-105 H 4-OH-3,5-diPr-Ph H Me -CH ₂ -OO CH 6-106 H 4-OH-3,5-diiPr-Ph H Me -CH ₂ -OO CH 6-107 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 6-108 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OON 6-109 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OS CH 6- 110 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -SS CH 6-111 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 6-112 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₃ -OS CH 6-113 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OO CH 6-114 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OS CH 6-115 H 3,5-ditBu-4-OH-Ph 6-Cl Me -CH ₂ -OS CH 6-116 H 4- OH-2,3,5-triMe-Ph HH -CH ₂ -OS CH 6-117 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 6-118 H 4-OH -2,3,5-triMe-Ph H Me -CH ₂ -OON 6-119 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OS CH 6-120 H 4-OH- 2,3,5-triMe-Ph H Me-(CH ₂ ) ₂ -OO CH 6-1 21 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₃ -OO CH 6-122 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OO CH 6-123 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OS CH 6-124 H 4-OH-2,3,5-triMe-Ph H iPr -CH ₂ -OO CH 6-125 H 4-OH-2,3,5-triMe-Ph H Ph -CH ₂ -OO CH 6-126 H 4-OH-2,3,5-triMe-Ph H Bz -CH ₂ -OO CH 6-127 H 4-OH-2,3,5-triMe-Ph 6-Cl Me -CH ₂ -OO CH 6-128 2-Cl 4-OH-2,3,5-triMe-Ph H Me- CH ₂ -OO CH 6-129 2-MeO 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 6-130 H 4-OH-2,3,6-triMe-Ph H Me -CH ₂ -OO CH 6-131 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH ₂ -OO CH 6-132 H 4-OH-3,5-diMeO-Ph H Me -CH ₂ -OO CH 6-133 H 3-NH ₂ -4-Me-Ph H Me -CH ₂ -OO CH 6-134 H 4-NH ₂ -2,3-diMe-Ph H Me -CH ₂ -OO CH 6-135 H 4-NH ₂ -2,6-diMe-Ph H Me -CH ₂ -OO CH 6-136 H 4-NH ₂ -3,5-diMe-Ph HH -CH ₂ -OO CH 6-137 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 6-138 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OON 6-139 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 6-140 H 4-NH ₂ -3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 6- 141 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OO CH 6 -142 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OS CH 6-143 H 4-NH ₂ -3,5-diMe-Ph H Ph -CH ₂ -OO CH 6-144 H 4-NH ₂ -3,5-diMe-Ph H Bz -CH ₂ -OO CH 6-145 H 4-NHMe-3,5-diMe-Ph H Me -CH ₂ -OO CH 6-146 H 4- NHAc-3,5-diMe-Ph H Me -CH ₂ -OO CH 6-147 H 4-NO ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 6-148 H 4-NO _2- 3,5-diMe-Ph H Me -CH ₂ -OS CH 6-149 H Pyr (2) H Me -CH ₂ -OO CH 6-150 H Pyr (2) H Me -CH ₂ -OON 6-151 H Pyr (2) H Me -CH ₂ -OS CH 6-152 H Pyr (2) H Me-(CH ₂ ) ₂ -OO CH 6-153 H Pyr (2) H Me-(CH ₂ ) ₃ -OO CH 6-154 H Pyr (2) H Et -CH ₂ -OO CH 6-155 H Pyr (2) H Et -CH ₂ -OS CH 6-156 H Pyr (2) H Ph -CH ₂ -OO CH 6- 157 H Pyr (2) 6-Cl Me -CH ₂ -OO CH 6-158 H 5-Cl-Pyr (2) H Me -CH ₂ -OO CH 6-159 H 6-Cl-Pyr (2) H Me -CH ₂ -OO CH 6-160 H 6-MeO-Pyr (2) H Me -CH ₂ -OO CH 6-161 H 3-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 6-162 H 5-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 6-163 H 3-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 6-164 H 5-NO ₂ -Pyr ( 2) H Me -CH ₂ -OO CH 6-165 3-MeO 5-NH ₂ -6-Cl-Pyr (2) 6-MeO Et-(CH ₂ ) ₄ -SS CH 6-166 H Pyr (3) H Me -CH ₂ -OO CH 6-167 H Pyr (3) H Me -CH ₂ -OON 6-168 H Pyr (3) H Me -CH ₂ -OS CH 6-169 H Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 6-170 H Pyr (3) H Et -CH ₂ -OO CH 6-171 H Pyr (3) H Et -CH ₂ -OS CH 6-172 H Pyr (3 ) H Pn-(CH ₂ ) ₃ -OO CH 6-173 H Pyr (3) H Ph -CH ₂ -OO CH 6-174 H Pyr (3) H Ph -CH ₂ -OS CH 6-175 2-Cl Pyr (3) H Me -CH ₂ -OO CH 6-176 H 6-MeO-Pyr (3) H Me -CH ₂ -OO CH 6-177 H 6-MeO-Pyr (3) H Me -CH _2- OS CH 6-178 H 6-MeO-Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 6-179 H 6-iPrO-Pyr (3) H Me -CH ₂ -OO CH 6-180 H 6 -MeO-5-Me-Pyr (3) H Me -CH ₂ -OO CH 6-181 H 2-NO ₂ -6-Me-Pyr (3) H Me -CH ₂ -OO CH 6-182 H Pyr ( 4) H Me -CH ₂ -OO CH 6-183 H Pyr (4) H Me -CH ₂ -OON 6-184 H Pyr (4) H Me -CH ₂ -OS CH 6-185 H Pyr (4) H Me -CH ₂ -SS CH 6-186 H Pyr (4) H Me-(CH ₂ ) ₂ -OO CH 6-187 H Pyr (4) H Et -CH ₂ -OO CH 6-188 H Pyr (4) H Et -CH ₂ -OS CH 6-189 H Pyr (4) H Ph -CH ₂ -OO CH 6-190 H Pyr (4) H Bz -CH ₂ -OS CH 6-191 3-Cl Pyr (4) H Me -CH ₂ -OO CH 6-192 H 2-Me-Pyr (4) H Me -CH ₂ -OO CH 6-193 H 2,6-diMe- Pyr (4) H Me -CH ₂ -OO CH 6-194 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OS CH 6-195 H 3,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 6-196 H 2-MeO-Pyr (4) H Me -CH ₂ -OO CH 6-197 H 4-Imid (1) -Ph H Me -CH ₂ -OO CH 6-198 H 4-Tz-Ph H Me -CH ₂ -OO CH 6-199 H 4-Ada (1) -Ph H Me -CH ₂ -OO CH 6-200 H 4-CN-Ph H Me -CH ₂ -OO CH 6-201 H 4-Bz-3-OH-Ph H Me -CH ₂ -OO CH 6-202 H pentaF-Ph H Me -CH ₂ -OO CH 6-203 H 4-NHCOPh-Ph H Me -CH ₂ -OO CH 6-204 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH ₂ -OO CH 6-205 H 4-NHCO (2,4-diF-Ph) -Ph H Me -CH ₂ -OO CH 6-206 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH ₂ -OO CH 6-207 H 4-NHCONp (1) -Ph H Me -CH ₂ -OO CH 6-208 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH ₂ -OO CH 6-209 H 4-NHCOcPn-Ph H Me -CH ₂ -OO CH 6-210 H 4- NHCOcHx-Ph H Me -CH ₂ -OO CH 6-211 H 4-NHCOPyr (3) -Ph H Me -CH ₂ -OO CH 6-212 H 4-NHCOPyr (4) -Ph H Me -CH ₂ -OO CH 6-213 H 4-NHHx-Ph H Me -CH 2 - OO CH 6-214 H 4-NH (Ac) Hx-Ph H Me -CH 2 - OO CH.

[0094]

[Table 7]

[0095]

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[0096] Cpd.No.R ² R ⁴ R ⁵ R ⁶ -A- BDE 7-1 H 4-F-Ph H Me -CH ₂ -OO CH 7-2 H 4-Cl-Ph H Me -CH ₂ -OO CH 7-3 H 2-OH-Ph H Me -CH ₂ -OO CH 7-4 H 2-OH-Ph H Me -CH ₂ -OS CH 7-5 H 2-OH-Ph H Et -CH ₂ -OO CH 7-6 H 2-OH-Ph H Et -CH _2- OS CH 7-7 H 3-OH-Ph H Me -CH ₂ -OO CH 7-8 H 3-OH-Ph H Me -CH ₂ -OS CH 7-9 H 3-OH-Ph H Et -CH ₂ -OO CH 7-10 H 3-OH-Ph H Et -CH ₂ -OS CH 7-11 H 4-OH-Ph H Me -CH ₂ -OO CH 7-12 H 4-OH-Ph H Me -CH ₂ -OON 7-13 H 4-OH-Ph H Me -CH ₂ -OS CH 7-14 H 4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 7-15 H 4-OH-Ph H Et -CH ₂ -OO CH 7-16 H 4-OH-Ph H Et -CH ₂ -OS CH 7-17 H 4-OH-Ph H tBu -CH ₂ -OO CH 7-18 H 3-CF _3- Ph H Me -CH ₂ -OO CH 7-19 H 4-iPrO-Ph H Me -CH ₂ -OO CH 7-20 H 4-MeS-Ph H Me -CH ₂ -OO CH 7-21 H 2-NH ₂ -Ph H Me -CH ₂ -OO CH 7-22 H 3-NH ₂ -Ph H Me -CH ₂ -OO CH 7-23 H 4-NH ₂ -Ph H Me -CH ₂ -OO CH 7-24 H 4-NHMe-Ph H Me -CH ₂ -OO CH 7-25 H 4-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 7-26 H 4-N (Me) ₂ -Ph H Et -CH ₂ -OO CH 7-27 H 4-Ph-Ph H Me -CH ₂ -OO CH 7-28 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH ₂ -OO CH 7-29 H 4- ( 4-OH-3,5-ditBu-Ph) Ph H Me -CH ₂ -OO CH 7-30 H 4- (4-OH-Bz) Ph H Me -CH ₂ -OO CH 7-31 H 4-PhS -Ph H Me -CH ₂ -OO CH 7-32 H 2-Pyrd (1) -Ph H Me -CH ₂ -OO CH 7-33 H 2-Pyrd (1) -Ph H Me -CH ₂ -OS CH 7-34 H 3-Pyrd (1) -Ph H Me -CH ₂ -OO CH 7-35 H 3-Pyrd (1) -Ph H Me -CH ₂ -OS CH 7-36 H 3-Pyrd (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 7-37 H 3-Pyrd (1) -Ph H Et -CH ₂ -OO CH 7-38 H 4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 7-39 H 4-Pyrd (1) -Ph H Me -CH ₂ -OON 7-40 H 4-Pyrd (1) -Ph H Me -CH ₂ -OS CH 7-41 H 4-Pyrd ( 1) -Ph H Me-(CH ₂ ) ₃ -OO CH 7-42 H 4-Pyrd (1) -Ph H Et -CH ₂ -OO CH 7-43 H 4-Pyrd (1) -Ph H Et- CH ₂ -OS CH 7-44 H 2-Pip (1) -Ph H Me -CH ₂ -OO CH 7-45 H 2-Pip (1) -Ph H Me -CH ₂ -OS CH 7-46 H 3 -Pip (1) -Ph H Me -CH ₂ -OO CH 7-47 H 3-Pip (1) -Ph H Me -CH ₂ -OS CH 7-48 H 3-Pip (1) -Ph H Et- (CH ₂ ) ₃ -SO CH 7-49 H 4-Pip (1) -Ph H Me -CH ₂ -OO CH 7-50 H 4-Pip (1) -Ph H Me -CH ₂ -OON 7-51 H 4-Pip (1) -Ph H Me -CH ₂ -OS CH 7-52 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 7-53 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 7-54 H 4-Pip (1)- Ph H Et -CH ₂ -OO CH 7-55 H 4-Pip (1) -Ph H Et -CH ₂ -OS CH 7-56 H 4-Pip (1) -Ph H tBu -CH ₂ -OO CH 7 -57 H 4-Pip (1) -Ph 4-Cl Me -CH ₂ -OO CH 7-58 2-MeO 4-Pip (1) -Ph H Me -CH ₂ -OO CH 7-59 H 2-Mor (4) -Ph H Me -CH ₂ -OO CH 7-60 H 2-Mor (4) -Ph H Me -CH ₂ -OS CH 7-61 H 2-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 7-62 H 3-Mor (4) -Ph H Me -CH ₂ -OO CH 7-63 H 3-Mor (4) -Ph H Me -CH ₂ -OS CH 7-64 H 3-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 7-65 H 3-Mor (4) -Ph H Et -CH ₂ -OO CH 7-66 H 4-Mor (4)- Ph H Me -CH ₂ -OO CH 7-67 H 4-Mor (4) -Ph H Me -CH ₂ -OON 7-68 H 4-Mor (4) -Ph H Me -CH ₂ -OS CH 7- 69 H 4-Mor (4) -Ph H Et -CH ₂ -OO CH 7-70 H 4-Mor (4) -Ph H Et -CH ₂ -OS CH 7-71 H 4-TioMor (4) -Ph H Me -CH ₂ -OO CH 7-72 H 4-Pipra (1) -Ph H Me -CH ₂ -OO CH 7-73 H 4-Pipra (1) -Ph H Me -CH ₂ -OS CH 7- 74 H 4-Pipra (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 7-75 H 4-Pipra (1) -Ph H Et -CH ₂ -OO CH 7-76 H 4-NO _2- Ph H Me -CH ₂ -OO CH 7-77 H 3-Cl-4-OH-Ph H Me -CH ₂ -OO CH 7-78 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 7-79 H 2-Cl-4-OH-3,5-diM e-Ph H Me -CH ₂ -OON 7-80 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 7-81 H 2-Cl-4-OH-3 , 5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 7-82 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₄ -OO CH 7-83 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 7-84 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OS CH 7-85 H 2-Cl-4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 7-86 H 2-Cl-4-OH-3,5-diMe-Ph 5-MeO Me -CH ₂ -OO CH 7-87 3-Cl 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 7-88 2-MeO 2-Cl-4-OH- 3,5-diMe-Ph H Me -CH ₂ -OO CH 7-89 H 3-Cl-5-OH-2,6-diMe-Ph H Me -CH ₂ -OO CH 7-90 H 4-Cl- 3-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 7-91 H 3-Cl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 7-92 H 3,5-diCl -4-NH ₂ -Ph H Me -CH ₂ -OO CH 7-93 H 4-NHMe-3-Cl-Ph H Me -CH ₂ -OO CH 7-94 H 3-Cl-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 7-95 H 3-OH-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 7-96 H 3-Cl-6-Me-4-Pyrd ( 1) -Ph H Me -CH ₂ -OO CH 7-97 H 2-Me-4-Mor (4) -Ph H Me -CH ₂ -OO CH 7-98 H 2-OH-3-Me-Ph H Me -CH ₂ -OO CH 7-99 H 2-OH-4-Me-Ph H Me -CH ₂ -OO CH 7-100 H 2-OH-3,4-diMe-Ph H Me -CH ₂ -OO CH 7-101 H 3-OH-2-Me-Ph H Me -CH ₂ -OO CH 7-102 H 3-OH-4-Me-Ph H Me -CH ₂ -OO CH 7-103 H 3-OH -5-Me-Ph H Me -CH ₂ -OO CH 7-104 H 3-OH-6-Me-Ph H Me -CH ₂ -OO CH 7-105 H 3-OH-2,4-diMe-Ph H Me -CH ₂ -OO CH 7-106 H 4-OH-2-Me-Ph H Me -CH ₂ -OO CH 7-107 H 4-OH-3-Me-Ph H Me -CH ₂ -OO CH 7-108 H 4-OH-3-Me-Ph H Me -CH ₂ -OS CH 7-109 H 4-OH-3-Me-Ph H Et -CH ₂ -OO CH 7-110 H 4-OH- 3-Me-Ph 5-Cl Me -CH ₂ -OO CH 7-111 H 4-OH-2-tBu-Ph H Me -CH ₂ -OO CH 7-112 H 4-OH-3-tBu-Ph H Me -CH ₂ -OO CH 7-113 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OO CH 7-114 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OS CH 7-115 H 4-OH-2,3-diMe-Ph H Me-(CH ₂ ) ₃ -SO CH 7-116 H 4-OH-2,3-diMe-Ph H Et -CH _2- OO CH 7-117 H 4-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 7-118 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 7- 119 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 7-120 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 7-121 H 4-OH -3,5-diMe-Ph H Me -CH ₂ -SO CH 7-122 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 7-123 H 4-OH- 3,5-diMe-Ph H Et -CH ₂ -OO CH 7-124 H 4-OH-3,5 -diMe-Ph H Et -CH ₂ -OS CH 7-125 H 4-OH-3,5-diMe-Ph H sBu -CH ₂ -OO CH 7-126 H 4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 7-127 H 4-OH-3,5-diMe-Ph H Ph -CH ₂ -OO CH 7-128 H 3,5-diEt-4-OH-Ph H Me -CH ₂ -OO CH 7-129 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OO CH 7-130 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OS CH 7-131 H 4-OH-3,5-diPr-Ph H Me -CH ₂ -OO CH 7-132 H 4-OH-3,5-diiPr-Ph H Me -CH ₂ -OO CH 7-133 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 7-134 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OON 7-135 H 3 , 5-ditBu-4-OH-Ph H Me -CH ₂ -OS CH 7-136 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -SS CH 7-137 H 3,5-ditBu -4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 7-138 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 7-139 H 3,5 -ditBu-4-OH-Ph H Me-(CH ₂ ) ₃ -OS CH 7-140 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OO CH 7-141 H 3,5- ditBu-4-OH-Ph H Et -CH ₂ -OS CH 7-142 H 3,5-ditBu-4-OH-Ph H tBu -CH ₂ -OO CH 7-143 H 3,5-ditBu-4- OH-Ph 5-Cl Me -CH ₂ -OS CH 7-144 H 4-OH-2,3,5-triMe-Ph HH -CH ₂ -OS CH 7-145 H 4-OH-2,3,5 -triMe-Ph H Me -CH ₂ -OO CH 7-146 H 4 -OH-2,3,5-triMe-Ph H Me -CH ₂ -OON 7-147 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OS CH 7-148 H 4- OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₂ -OO CH 7-149 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₃ -OO CH 7-150 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OO CH 7-151 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OS CH 7-152 H 4-OH-2,3,5-triMe-Ph H iPr -CH ₂ -OO CH 7-153 H 4-OH-2,3,5-triMe-Ph H tBu -CH ₂ -OO CH 7-154 H 4-OH-2,3,5-triMe-Ph H Ph -CH ₂ -OO CH 7-155 H 4-OH-2,3,5-triMe-Ph H Bz -CH ₂ -OO CH 7-156 H 4-OH-2,3,5-triMe-Ph 5-Cl Me -CH ₂ -OO CH 7-157 2-Cl 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 7-158 2-MeO 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 7-159 H 4-OH-2,3,6-triMe-Ph H Me -CH ₂ -OO CH 7-160 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH ₂ -OO CH 7-161 H 4-OH-3,5-diMeO-Ph H Me -CH ₂ -OO CH 7-162 H 3-NH ₂ -4-Me-Ph H Me -CH ₂ -OO CH 7-163 H 4-NH ₂ -2,3-diMe-Ph H Me -CH _2- OO CH 7-164 H 4-NH ₂ -2,6-diMe-Ph H Me -CH ₂ -OO CH 7 -165 H 4-NH ₂ -3,5-diMe-Ph HH -CH ₂ -OO CH 7 -166 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 7-167 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OON 7-168 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 7-169 H 4- NH ₂ -3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 7-170 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OO CH 7-171 H 4 -NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OS CH 7-172 H 4-NH ₂ -3,5-diMe-Ph H tBu -CH ₂ -OO CH 7-173 H 4-NH ₂ -3,5-diMe-Ph H Ph -CH ₂ -OO CH 7-174 H 4-NH ₂ -3,5-diMe-Ph H Bz -CH ₂ -OO CH 7-175 H 4-NH _2- 3,5-diEt-Ph H Me -CH ₂ -OO CH 7-176 H 4-NHMe-3,5-diMe-Ph H Me -CH ₂ -OO CH 7-177 H 4-NHAc-3,5- diMe-Ph H Me -CH ₂ -OO CH 7-178 H 4-NO ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 7-179 H 4-NO ₂ -3,5-diMe- Ph H Me -CH ₂ -OS CH 7-180 H Pyr (2) H Me -CH ₂ -OO CH 7-181 H Pyr (2) H Me -CH ₂ -OON 7-182 H Pyr (2) H Me -CH ₂ -OS CH 7-183 H Pyr (2) H Me-(CH ₂ ) ₂ -OO CH 7-184 H Pyr (2) H Me-(CH ₂ ) ₃ -OO CH 7-185 H Pyr ( 2) H Et -CH ₂ -OO CH 7-186 H Pyr (2) H Et -CH ₂ -OS CH 7-187 H Pyr (2) H tBu -CH ₂ -OO CH 7-188 H Pyr (2) H Ph -CH ₂ -OO CH 7-189 H Pyr (2) 5-Cl Me -CH ₂ -OO CH 7-190 H 5-Cl-Pyr (2) H Me -CH ₂ -OO CH 7- 191 H 6-Cl-Pyr (2) H Me -CH ₂ -OO CH 7-192 H 6-Me-Pyr (2) H Me -CH ₂ -OO CH 7-193 H 6-MeO-Pyr (2) H Me -CH ₂ -OO CH 7-194 H 3-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 7-195 H 5-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 7-196 H 3-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 7-197 H 5-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 7-198 H 5-NH ₂ -6-Cl-Pyr (2) H Me -CH ₂ -OO CH 7 -199 3-MeO 5-NH ₂ -6-Cl-Pyr (2) 5-MeO Et-(CH ₂ ) ₄ -SS CH 7 -200 H Pyr (3) H Me -CH ₂ -OO CH 7-201 H Pyr (3) H Me -CH ₂ -OON 7-202 H Pyr (3) H Me -CH ₂ -OS CH 7-203 H Pyr (3) H Me-(CH ₂ ) ₂ -OO CH 7-204 H Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 7-205 H Pyr (3) H Et -CH ₂ -OO CH 7-206 H Pyr (3) H Et -CH ₂ -OS CH 7-207 H Pyr (3) H tBu -CH ₂ -OO CH 7-208 H Pyr (3) H Pn-(CH ₂ ) ₃ -OO CH 7-209 H Pyr (3) H Ph -CH ₂ -OO CH 7-210 H Pyr (3) H Ph -CH ₂ -OS CH 7-211 H Pyr (3) H Bz -CH ₂ -OO CH 7 -212 2-Cl Pyr (3) H Me -CH ₂ -OO CH 7-213 H 5-MeO-Pyr (3) H Me -CH ₂ -OO CH 7-214 H 6-MeO-Pyr (3) H Me -CH ₂ -OO CH 7-215 H 6-MeO-Pyr (3) H Me -CH ₂ -OS CH 7-216 H 6-MeO-Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 7-217 H 6-iPrO-Pyr (3) H Me -CH ₂ -OO CH 7-218 H 6-MeO-5-Me-Pyr (3) H Me -CH ₂ -OO CH 7-219 H 2-NO ₂ -6-Me-Pyr (3) H Me -CH ₂ -OO CH 7-220 H Pyr (4) H Me -CH ₂ -OO CH 7-221 H Pyr (4) H Me -CH ₂ -OON 7-222 H Pyr (4) H Me -CH ₂ -OS CH 7-223 H Pyr (4) H Me -CH ₂ -SS CH 7-224 H Pyr (4) H Me-( CH ₂ ) ₂ -OO CH 7-225 H Pyr (4) H Et -CH ₂ -OO CH 7-226 H Pyr (4) H Et -CH ₂ -OS CH 7-227 H Pyr (4) H tBu- CH ₂ -OO CH 7-228 H Pyr (4) H Ph -CH ₂ -OO CH 7-229 H Pyr (4) H Bz -CH ₂ -OS CH 7-230 3-Cl Pyr (4) H Me- CH ₂ -OO CH 7-231 H 2-Me-Pyr (4) H Me -CH ₂ -OO CH 7-232 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 7-233 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OS CH 7-234 H 3,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 7-235 H 2-MeO-Pyr (4) H Me -CH ₂ -OO CH 7-236 H 4-Imid (1) -Ph H Me -CH ₂ -OO CH 7-237 H 4-Tz-Ph H Me -CH ₂ -OO CH 7- 238 H 4-Ada (1) -Ph H Me -CH ₂ -OO CH 7-239 H 4-CN-Ph H Me -CH ₂ -OO CH 7-240 H 4-Bz-3-OH-Ph H Me -CH ₂ -OO CH 7-241 H pentaF-Ph H Me -CH ₂ -OO CH 7-242 H 4-NHCOPh-Ph H Me -CH ₂ -OO C H 7-243 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH ₂ -OO CH 7-244 H 4-NHCO (2,4-diF-Ph) -Ph H Me -CH ₂ -OO CH 7-245 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH ₂ -OO CH 7-246 H 4-NHCONp (1) -Ph H Me -CH ₂ -OO CH 7-247 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH ₂ -OO CH 7-248 H 4-NHCOcPn-Ph H Me -CH ₂ -OO CH 7-249 H 4-NHCOcHx- Ph H Me -CH ₂ -OO CH 7-250 H 4-NHCOPyr (3) -Ph H Me -CH ₂ -OO CH 7-251 H 4-NHCOPyr (4) -Ph H Me -CH ₂ -OO CH 7 -252 H 4-NHHx-Ph H Me -CH ₂ -OO CH 7 -253 H 4-NH (Ac) Hx-Ph H Me -CH ₂ -OO CH .

[0097]

[Table 8]

[0098]

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[0099] Cpd.No.R ² R ⁴ R ⁵ R ⁶ -A- BDE 8-1 H 4-F-Ph H Me -CH ₂ -OO CH 8-2 H 4-Cl-Ph H Me -CH ₂ -OO CH 8-3 H 2-OH-Ph H Me -CH ₂ -OO CH 8-4 H 2-OH-Ph H Me -CH ₂ -OS CH 8-5 H 3-OH-Ph H Me -CH ₂ -OO CH 8-6 H 3-OH-Ph H Me -CH _2- OS CH 8-7 H 4-OH-Ph H Me -CH ₂ -OO CH 8-8 H 4-OH-Ph H Me -CH ₂ -OON 8-9 H 4-OH-Ph H Me -CH _2- OS CH 8-10 H 4-OH-Ph H Et -CH ₂ -OO CH 8-11 H 4-OH-Ph H Et -CH ₂ -OS CH 8-12 H 3-CF ₃ -Ph H Me -CH ₂ -OO CH 8-13 H 4-iPrO-Ph H Me -CH ₂ -OO CH 8-14 H 4-MeS-Ph H Me -CH ₂ -OO CH 8-15 H 2-NH ₂ -Ph H Me -CH ₂ -OO CH 8-16 H 3-NH ₂ -Ph H Me -CH ₂ -OO CH 8-17 H 4-NH ₂ -Ph H Me -CH ₂ -OO CH 8-18 H 4-NHMe- Ph H Me -CH ₂ -OO CH 8-19 H 4-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 8-20 H 4-N (Me) ₂ -Ph H Et -CH ₂ -OO CH 8-21 H 4-Ph-Ph H Me -CH ₂ -OO CH 8-22 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH ₂ -OO CH 8-23 H 4- (4-OH-3,5-ditBu-Ph) Ph H Me -CH ₂ -OO CH 8-24 H 4- (4-OH-Bz) Ph H Me -CH ₂ -OO CH 8-25 H 4-PhS-Ph H Me -CH ₂ -OO CH 8-26 H 2-Pyrd (1) -Ph H Me -CH ₂ -OO CH 8-27 H 3-Pyrd (1) -Ph H Me -CH ₂ -OO CH 8-28 H 3-Pyrd (1)- Ph H Me -CH ₂ -OS CH 8-29 H 3-Pyrd (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 8-30 H 3-Pyrd (1) -Ph H Et -CH _2- OO CH 8-31 H 4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 8-32 H 4-Pyrd (1) -Ph H Me -CH ₂ -OS CH 8-33 H 4-Pyrd ( 1) -Ph H Me-(CH ₂ ) ₃ -OO CH 8-34 H 2-Pip (1) -Ph H Me -CH ₂ -OO CH 8-35 H 3-Pip (1) -Ph H Me- CH ₂ -OO CH 8-36 H 3-Pip (1) -Ph H Me -CH ₂ -OS CH 8-37 H 3-Pip (1) -Ph H Et-(CH ₂ ) ₃ -SO CH 8- 38 H 4-Pip (1) -Ph H Me -CH ₂ -OO CH 8-39 H 4-Pip (1) -Ph H Me -CH ₂ -OS CH 8-40 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 8-41 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 8-42 H 4-Pip (1) -Ph H tBu -CH ₂ -OO CH 8-43 H 4-Pip (1) -Ph 4-Cl Me -CH ₂ -OO CH 8-44 2-MeO 4-Pip (1) -Ph H Me -CH ₂ -OO CH 8- 45 H 2-Mor (4) -Ph H Me -CH ₂ -OO CH 8-46 H 2-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 8-47 H 3-Mor (4 ) -Ph H Me -CH ₂ -OO CH 8-48 H 3-Mor (4) -Ph H Me -CH ₂ -OS CH 8-49 H 3-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 8-50 H 3-Mor (4) -Ph H Et -CH ₂ -OO CH 8-51 H 4-Mor (4) -Ph H Me -CH ₂ -OO CH 8-52 H 4- Mor (4) -Ph H Me -CH ₂ -OS CH 8-53 H 4-TioMor (4) -Ph H Me -CH ₂ -OO CH 8-54 H 4-Pipra (1) -Ph H Me -CH ₂ -OO CH 8-55 H 4-Pipra (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 8-56 H 4-Pipra (1) -Ph H Et -CH ₂ -OO CH 8-57 H 4-NO ₂ -Ph H Me -CH ₂ -OO CH 8-58 H 2-Cl-4 -OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 8-59 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 8-60 H 2- Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 8-61 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₄ -OO CH 8-62 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 8-63 H 2-Cl-4-OH-3,5-diMe-Ph H Et- CH ₂ -OS CH 8-64 H 2-Cl-4-OH-3,5-diMe-Ph 6-MeO Me -CH ₂ -OO CH 8-65 3-Cl 2-Cl-4-OH-3, 5-diMe-Ph H Me -CH ₂ -OO CH 8-66 2-MeO 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 8-67 H 4-Cl- 3-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 8-68 H 3-Cl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 8-69 H 3,5-diCl -4-NH ₂ -Ph H Me -CH ₂ -OO CH 8-70 H 4-NHMe-3-Cl-Ph H Me -CH ₂ -OO CH 8-71 H 3-Cl-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 8-72 H 3-OH-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 8-73 H 3-Cl-6-Me-4-Pyrd ( 1) -Ph H Me -CH ₂ -OO CH 8-74 H 2-Me-4-Mor (4) -Ph H Me -CH ₂ -OO CH 8-75 H 2-OH- 3-Me-Ph H Me -CH ₂ -OO CH 8-76 H 2-OH-4-Me-Ph H Me -CH ₂ -OO CH 8-77 H 2-OH-3,4-diMe-Ph H Me -CH ₂ -OO CH 8-78 H 3-OH-2-Me-Ph H Me -CH ₂ -OO CH 8-79 H 3-OH-4-Me-Ph H Me -CH ₂ -OO CH 8 -80 H 3-OH-5-Me-Ph H Me -CH ₂ -OO CH 8-81 H 3-OH-6-Me-Ph H Me -CH ₂ -OO CH 8-82 H 3-OH-2 , 4-diMe-Ph H Me -CH ₂ -OO CH 8-83 H 4-OH-2-Me-Ph H Me -CH ₂ -OO CH 8-84 H 4-OH-3-Me-Ph H Me -CH ₂ -OO CH 8-85 H 4-OH-3-Me-Ph H Et -CH ₂ -OO CH 8-86 H 4-OH-3-Me-Ph 6-Cl Me -CH ₂ -OO CH 8-87 H 4-OH-2-tBu-Ph H Me -CH ₂ -OO CH 8-88 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OO CH 8-89 H 4- OH-2,3-diMe-Ph H Me -CH ₂ -OS CH 8-90 H 4-OH-2,3-diMe-Ph H Me-(CH ₂ ) ₃ -SO CH 8-91 H 4-OH -2,3-diMe-Ph H Et -CH ₂ -OO CH 8-92 H 4-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 8-93 H 4-OH-3,5 -diMe-Ph H Me -CH ₂ -OO CH 8-94 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 8-95 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 8-96 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -SO CH 8-97 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 8-98 H 4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 8-99 H 4-OH- 3,5-diMe-Ph H Et -CH ₂ -OS CH 8-100 H 4-OH-3,5-diMe-Ph H sBu -CH ₂ -OO CH 8-101 H 4-OH-3,5- diMe-Ph H Ph -CH ₂ -OO CH 8-102 H 3,5-diEt-4-OH-Ph H Me -CH ₂ -OO CH 8-103 H 3-tBu-4-OH-5-Me- Ph H Me -CH ₂ -OO CH 8-104 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OS CH 8-105 H 4-OH-3,5-diPr-Ph H Me -CH ₂ -OO CH 8-106 H 4-OH-3,5-diiPr-Ph H Me -CH ₂ -OO CH 8-107 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 8-108 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OON 8-109 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OS CH 8- 110 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -SS CH 8-111 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 8-112 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₃ -OS CH 8-113 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OO CH 8-114 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OS CH 8-115 H 3,5-ditBu-4-OH-Ph 6-Cl Me -CH ₂ -OS CH 8-116 H 4- OH-2,3,5-triMe-Ph HH -CH ₂ -OS CH 8-117 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 8-118 H 4-OH -2,3,5-triMe-Ph H Me -CH ₂ -OON 8-119 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OS CH 8-120 H 4-OH- 2,3,5-triMe-Ph H Me-(CH ₂ ) ₂ -OO CH 8-1 21 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₃ -OO CH 8-122 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OO CH 8-123 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OS CH 8-124 H 4-OH-2,3,5-triMe-Ph H iPr -CH ₂ -OO CH 8-125 H 4-OH-2,3,5-triMe-Ph H Ph -CH ₂ -OO CH 8-126 H 4-OH-2,3,5-triMe-Ph H Bz -CH ₂ -OO CH 8-127 H 4-OH-2,3,5-triMe-Ph 6-Cl Me -CH ₂ -OO CH 8-128 2-Cl 4-OH-2,3,5-triMe-Ph H Me- CH ₂ -OO CH 8-129 2-MeO 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 8-130 H 4-OH-2,3,6-triMe-Ph H Me -CH ₂ -OO CH 8-131 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH ₂ -OO CH 8-132 H 4-OH-3,5-diMeO-Ph H Me -CH ₂ -OO CH 8-133 H 3-NH ₂ -4-Me-Ph H Me -CH ₂ -OO CH 8-134 H 4-NH ₂ -2,3-diMe-Ph H Me -CH ₂ -OO CH 8-135 H 4-NH ₂ -2,6-diMe-Ph H Me -CH ₂ -OO CH 8-136 H 4-NH ₂ -3,5-diMe-Ph HH -CH ₂ -OO CH 8-137 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 8-138 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OON 8-139 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 8-140 H 4-NH ₂ -3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 8- 141 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OO CH 8 -142 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OS CH 8-143 H 4-NH ₂ -3,5-diMe-Ph H Ph -CH ₂ -OO CH 8-144 H 4-NH ₂ -3,5-diMe-Ph H Bz -CH ₂ -OO CH 8-145 H 4-NHMe-3,5-diMe-Ph H Me -CH ₂ -OO CH 8-146 H 4- NHAc-3,5-diMe-Ph H Me -CH ₂ -OO CH 8-147 H 4-NO ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 8-148 H 4-NO _2- 3,5-diMe-Ph H Me -CH ₂ -OS CH 8-149 H Pyr (2) H Me -CH ₂ -OO CH 8-150 H Pyr (2) H Me -CH ₂ -OON 8-151 H Pyr (2) H Me -CH ₂ -OS CH 8-152 H Pyr (2) H Me-(CH ₂ ) ₂ -OO CH 8-153 H Pyr (2) H Me-(CH ₂ ) ₃ -OO CH 8-154 H Pyr (2) H Et -CH ₂ -OO CH 8-155 H Pyr (2) H Et -CH ₂ -OS CH 8-156 H Pyr (2) H Ph -CH ₂ -OO CH 8- 157 H Pyr (2) 6-Cl Me -CH ₂ -OO CH 8-158 H 5-Cl-Pyr (2) H Me -CH ₂ -OO CH 8-159 H 6-Cl-Pyr (2) H Me -CH ₂ -OO CH 8-160 H 6-MeO-Pyr (2) H Me -CH ₂ -OO CH 8-161 H 3-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 8-162 H 5-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 8-163 H 3-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 8-164 H 5-NO ₂ -Pyr ( 2) H Me -CH ₂ -OO CH 8-165 3-MeO 5-NH ₂ -6-Cl-Pyr (2) 6-MeO Et-(CH ₂ ) ₄ -SS CH 8-166 H Pyr (3) H Me -CH ₂ -OO CH 8-167 H Pyr (3) H Me -CH ₂ -OON 8-168 H Pyr (3) H Me -CH ₂ -OS CH 8-169 H Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 8-170 H Pyr (3) H Et -CH ₂ -OO CH 8-171 H Pyr (3) H Et -CH ₂ -OS CH 8-172 H Pyr (3 ) H Pn-(CH ₂ ) ₃ -OO CH 8-173 H Pyr (3) H Ph -CH ₂ -OO CH 8-174 H Pyr (3) H Ph -CH ₂ -OS CH 8-175 2-Cl Pyr (3) H Me -CH ₂ -OO CH 8-176 H 6-MeO-Pyr (3) H Me -CH ₂ -OO CH 8-177 H 6-MeO-Pyr (3) H Me -CH _2- OS CH 8-178 H 6-MeO-Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 8-179 H 6-iPrO-Pyr (3) H Me -CH ₂ -OO CH 8-180 H 6 -MeO-5-Me-Pyr (3) H Me -CH ₂ -OO CH 8-181 H 2-NO ₂ -6-Me-Pyr (3) H Me -CH ₂ -OO CH 8-182 H Pyr ( 4) H Me -CH ₂ -OO CH 8-183 H Pyr (4) H Me -CH ₂ -OON 8-184 H Pyr (4) H Me -CH ₂ -OS CH 8-185 H Pyr (4) H Me -CH ₂ -SS CH 8-186 H Pyr (4) H Me-(CH ₂ ) ₂ -OO CH 8-187 H Pyr (4) H Et -CH ₂ -OO CH 8-188 H Pyr (4) H Et -CH ₂ -OS CH 8-189 H Pyr (4) H Ph -CH ₂ -OO CH 8-190 H Pyr (4) H Bz -CH ₂ -OS CH 8-191 3-Cl Pyr (4) H Me -CH ₂ -OO CH 8-192 H 2-Me-Pyr (4) H Me -CH ₂ -OO CH 8-193 H 2,6-diMe- Pyr (4) H Me -CH ₂ -OO CH 8-194 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OS CH 8-195 H 3,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 8-196 H 2-MeO-Pyr (4) H Me -CH ₂ -OO CH 8-197 H 4-Imid (1) -Ph H Me -CH ₂ -OO CH 8-198 H 4-Tz-Ph H Me -CH ₂ -OO CH 8-199 H 4-Ada (1) -Ph H Me -CH ₂ -OO CH 8-200 H 4-CN-Ph H Me -CH ₂ -OO CH 8-201 H 4-Bz-3-OH-Ph H Me -CH ₂ -OO CH 8-202 H pentaF-Ph H Me -CH ₂ -OO CH 8-203 H 4-NHCOPh-Ph H Me -CH ₂ -OO CH 8-204 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH ₂ -OO CH 8-205 H 4-NHCO (2,4-diF-Ph) -Ph H Me -CH ₂ -OO CH 8-206 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH ₂ -OO CH 8-207 H 4-NHCONp (1) -Ph H Me -CH ₂ -OO CH 8-208 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH ₂ -OO CH 8-209 H 4-NHCOcPn-Ph H Me -CH ₂ -OO CH 8-210 H 4- NHCOcHx-Ph H Me -CH ₂ -OO CH 8-211 H 4-NHCOPyr (3) -Ph H Me -CH ₂ -OO CH 8-212 H 4-NHCOPyr (4) -Ph H Me -CH ₂ -OO CH 8-213 H 4-NHHx-Ph H Me -CH ₂ -OO CH 8-214 H 4-NH (Ac) Hx-Ph H Me -CH ₂ -OO CH .

[0100]

[Table 9]

[0101]

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[0102] Cpd.No.R ² R ⁴ R ⁵ R ⁶ -A- BDE 9-1 H 4-F-Ph H Me -CH ₂ -OO CH 9-2 H 4-Cl-Ph H Me -CH ₂ -OO CH 9-3 H 2-OH-Ph H Me -CH ₂ -OO CH 9-4 H 2-OH-Ph H Me -CH ₂ -OS CH 9-5 H 2-OH-Ph H Et -CH ₂ -OO CH 9-6 H 2-OH-Ph H Et -CH _2- OS CH 9-7 H 3-OH-Ph H Me -CH ₂ -OO CH 9-8 H 3-OH-Ph H Me -CH ₂ -OS CH 9-9 H 3-OH-Ph H Et -CH ₂ -OO CH 9-10 H 3-OH-Ph H Et -CH ₂ -OS CH 9-11 H 4-OH-Ph H Me -CH ₂ -OO CH 9-12 H 4-OH-Ph H Me -CH ₂ -OON 9-13 H 4-OH-Ph H Me -CH ₂ -OS CH 9-14 H 4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 9-15 H 4-OH-Ph H Et -CH ₂ -OO CH 9-16 H 4-OH-Ph H Et -CH ₂ -OS CH 9-17 H 4-OH-Ph H tBu -CH ₂ -OO CH 9-18 H 3-CF _3- Ph H Me -CH ₂ -OO CH 9-19 H 4-iPrO-Ph H Me -CH ₂ -OO CH 9-20 H 4-MeS-Ph H Me -CH ₂ -OO CH 9-21 H 2-NH ₂ -Ph H Me -CH ₂ -OO CH 9-22 H 3-NH ₂ -Ph H Me -CH ₂ -OO CH 9-23 H 4-NH ₂ -Ph H Me -CH ₂ -OO CH 9-24 H 4-NHMe-Ph H Me -CH ₂ -OO CH 9-25 H 4-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 9-26 H 4-N (Me) ₂ -Ph H Et -CH ₂ -OO CH 9-27 H 4-Ph-Ph H Me -CH ₂ -OO CH 9-28 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH ₂ -OO CH 9-29 H 4- ( 4-OH-3,5-ditBu-Ph) Ph H Me -CH ₂ -OO CH 9-30 H 4- (4-OH-Bz) Ph H Me -CH ₂ -OO CH 9-31 H 4-PhS -Ph H Me -CH ₂ -OO CH 9-32 H 2-Pyrd (1) -Ph H Me -CH ₂ -OO CH 9-33 H 2-Pyrd (1) -Ph H Me -CH ₂ -OS CH 9-34 H 3-Pyrd (1) -Ph H Me -CH ₂ -OO CH 9-35 H 3-Pyrd (1) -Ph H Me -CH ₂ -OS CH 9-36 H 3-Pyrd (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 9-37 H 3-Pyrd (1) -Ph H Et -CH ₂ -OO CH 9-38 H 4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 9-39 H 4-Pyrd (1) -Ph H Me -CH ₂ -OON 9-40 H 4-Pyrd (1) -Ph H Me -CH ₂ -OS CH 9-41 H 4-Pyrd ( 1) -Ph H Me-(CH ₂ ) ₃ -OO CH 9-42 H 4-Pyrd (1) -Ph H Et -CH ₂ -OO CH 9-43 H 4-Pyrd (1) -Ph H Et- CH ₂ -OS CH 9-44 H 2-Pip (1) -Ph H Me -CH ₂ -OO CH 9-45 H 2-Pip (1) -Ph H Me -CH ₂ -OS CH 9-46 H 3 -Pip (1) -Ph H Me -CH ₂ -OO CH 9-47 H 3-Pip (1) -Ph H Me -CH ₂ -OS CH 9-48 H 3-Pip (1) -Ph H Et- (CH ₂ ) ₃ -SO CH 9-49 H 4-Pip (1) -Ph H Me -CH ₂ -OO CH 9-50 H 4-Pip (1) -Ph H Me -CH ₂ -OON 9-51 H 4-Pip (1) -Ph H Me -CH ₂ -OS CH 9-52 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 9-53 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 9-54 H 4-Pip (1)- Ph H Et -CH ₂ -OO CH 9-55 H 4-Pip (1) -Ph H Et -CH ₂ -OS CH 9-56 H 4-Pip (1) -Ph H tBu -CH ₂ -OO CH 9 -57 H 4-Pip (1) -Ph 4-Cl Me -CH ₂ -OO CH 9-58 2-MeO 4-Pip (1) -Ph H Me -CH ₂ -OO CH 9-59 H 2-Mor (4) -Ph H Me -CH ₂ -OO CH 9-60 H 2-Mor (4) -Ph H Me -CH ₂ -OS CH 9-61 H 2-Mor (4) -Ph H Me-(CH _{2) 3 - OO CH 9-62 H} 3-Mor (4) -Ph H Me -CH 2 - OO CH 9-63 H 3-Mor (4) -Ph H Me -CH 2 - OS CH 9-64 H 3-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 9-65 H 3-Mor (4) -Ph H Et -CH ₂ -OO CH 9-66 H 4-Mor (4)- Ph H Me -CH ₂ -OO CH 9-67 H 4-Mor (4) -Ph H Me -CH ₂ -OON 9-68 H 4-Mor (4) -Ph H Me -CH ₂ -OS CH 9- 69 H 4-Mor (4) -Ph H Et -CH ₂ -OO CH 9-70 H 4-Mor (4) -Ph H Et -CH ₂ -OS CH 9-71 H 4-TioMor (4) -Ph H Me -CH ₂ -OO CH 9-72 H 4-Pipra (1) -Ph H Me -CH ₂ -OO CH 9-73 H 4-Pipra (1) -Ph H Me -CH ₂ -OS CH 9- 74 H 4-Pipra (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 9-75 H 4-Pipra (1) -Ph H Et -CH ₂ -OO CH 9-76 H 4-NO _2- Ph H Me -CH ₂ -OO CH 9-77 H 3-Cl-4-OH-Ph H Me -CH ₂ -OO CH 9-78 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 9-79 H 2-Cl-4-OH-3,5-diM e-Ph H Me -CH ₂ -OON 9-80 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 9-81 H 2-Cl-4-OH-3 , 5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 9-82 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₄ -OO CH 9-83 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 9-84 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OS CH 9-85 H 2-Cl-4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 9-86 H 2-Cl-4-OH-3,5-diMe-Ph 5-MeO Me -CH ₂ -OO CH 9-87 3-Cl 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 9-88 2-MeO 2-Cl-4-OH- 3,5-diMe-Ph H Me -CH ₂ -OO CH 9-89 H 3-Cl-5-OH-2,6-diMe-Ph H Me -CH ₂ -OO CH 9-90 H 4-Cl- 3-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 9-91 H 3-Cl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 9-92 H 3,5-diCl -4-NH ₂ -Ph H Me -CH ₂ -OO CH 9-93 H 4-NHMe-3-Cl-Ph H Me -CH ₂ -OO CH 9-94 H 3-Cl-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 9-95 H 3-OH-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 9-96 H 3-Cl-6-Me-4-Pyrd ( 1) -Ph H Me -CH ₂ -OO CH 9-97 H 2-Me-4-Mor (4) -Ph H Me -CH ₂ -OO CH 9-98 H 2-OH-3-Me-Ph H Me -CH ₂ -OO CH 9-99 H 2-OH-4-Me-Ph H Me -CH ₂ -OO CH 9-100 H 2-OH-3,4-diMe-Ph H Me -CH ₂ -OO CH 9-101 H 3-OH-2-Me-Ph H Me -CH ₂ -OO CH 9-102 H 3-OH-4-Me-Ph H Me -CH ₂ -OO CH 9-103 H 3-OH -5-Me-Ph H Me -CH ₂ -OO CH 9-104 H 3-OH-6-Me-Ph H Me -CH ₂ -OO CH 9-105 H 3-OH-2,4-diMe-Ph H Me -CH ₂ -OO CH 9-106 H 4-OH-2-Me-Ph H Me -CH ₂ -OO CH 9-107 H 4-OH-3-Me-Ph H Me -CH ₂ -OO CH 9-108 H 4-OH-3-Me-Ph H Me -CH ₂ -OS CH 9-109 H 4-OH-3-Me-Ph H Et -CH ₂ -OO CH 9-110 H 4-OH- 3-Me-Ph 5-Cl Me -CH ₂ -OO CH 9-111 H 4-OH-2-tBu-Ph H Me -CH ₂ -OO CH 9-112 H 4-OH-3-tBu-Ph H Me -CH ₂ -OO CH 9-113 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OO CH 9-114 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OS CH 9-115 H 4-OH-2,3-diMe-Ph H Me-(CH ₂ ) ₃ -SO CH 9-116 H 4-OH-2,3-diMe-Ph H Et -CH _2- OO CH 9-117 H 4-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 9-118 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 9- 119 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 9-120 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 9-121 H 4-OH -3,5-diMe-Ph H Me -CH ₂ -SO CH 9-122 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 9-123 H 4-OH- 3,5-diMe-Ph H Et -CH ₂ -OO CH 9-124 H 4-OH-3,5 -diMe-Ph H Et -CH ₂ -OS CH 9-125 H 4-OH-3,5-diMe-Ph H sBu -CH ₂ -OO CH 9-126 H 4-OH-3,5-diMe-Ph H tBu -CH ₂ -OO CH 9-127 H 4-OH-3,5-diMe-Ph H Ph -CH ₂ -OO CH 9-128 H 3,5-diEt-4-OH-Ph H Me -CH ₂ -OO CH 9-129 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OO CH 9-130 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OS CH 9-131 H 4-OH-3,5-diPr-Ph H Me -CH ₂ -OO CH 9-132 H 4-OH-3,5-diiPr-Ph H Me -CH ₂ -OO CH 9-133 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 9-134 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OON 9-135 H 3 , 5-ditBu-4-OH-Ph H Me -CH ₂ -OS CH 9-136 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -SS CH 9-137 H 3,5-ditBu -4-OH-Ph H Me-(CH ₂ ) ₂ -OO CH 9-138 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 9-139 H 3,5 -ditBu-4-OH-Ph H Me-(CH ₂ ) ₃ -OS CH 9-140 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OO CH 9-141 H 3,5- ditBu-4-OH-Ph H Et -CH ₂ -OS CH 9-142 H 3,5-ditBu-4-OH-Ph H tBu -CH ₂ -OO CH 9-143 H 3,5-ditBu-4- OH-Ph 5-Cl Me -CH ₂ -OS CH 9-144 H 4-OH-2,3,5-triMe-Ph HH -CH ₂ -OS CH 9-145 H 4-OH-2,3,5 -triMe-Ph H Me -CH ₂ -OO CH 9-146 H 4 -OH-2,3,5-triMe-Ph H Me -CH ₂ -OON 9-147 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OS CH 9-148 H 4- OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₂ -OO CH 9-149 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₃ -OO CH 9-150 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OO CH 9-151 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OS CH 9-152 H 4-OH-2,3,5-triMe-Ph H iPr -CH ₂ -OO CH 9-153 H 4-OH-2,3,5-triMe-Ph H tBu -CH ₂ -OO CH 9-154 H 4-OH-2,3,5-triMe-Ph H Ph -CH ₂ -OO CH 9-155 H 4-OH-2,3,5-triMe-Ph H Bz -CH ₂ -OO CH 9-156 H 4-OH-2,3,5-triMe-Ph 5-Cl Me -CH ₂ -OO CH 9-157 2-Cl 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 9-158 2-MeO 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 9-159 H 4-OH-2,3,6-triMe-Ph H Me -CH ₂ -OO CH 9-160 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH ₂ -OO CH 9-161 H 4-OH-3,5-diMeO-Ph H Me -CH ₂ -OO CH 9-162 H 3-NH ₂ -4-Me-Ph H Me -CH ₂ -OO CH 9-163 H 4-NH ₂ -2,3-diMe-Ph H Me -CH _2- OO CH 9-164 H 4-NH ₂ -2,6-diMe-Ph H Me -CH ₂ -OO CH 9 -165 H 4-NH ₂ -3,5-diMe-Ph HH -CH ₂ -OO CH 9 -166 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 9-167 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OON 9-168 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 9-169 H 4- NH ₂ -3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 9-170 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OO CH 9-171 H 4 -NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OS CH 9-172 H 4-NH ₂ -3,5-diMe-Ph H tBu -CH ₂ -OO CH 9-173 H 4-NH ₂ -3,5-diMe-Ph H Ph -CH ₂ -OO CH 9-174 H 4-NH ₂ -3,5-diMe-Ph H Bz -CH ₂ -OO CH 9-175 H 4-NH _2- 3,5-diEt-Ph H Me -CH ₂ -OO CH 9-176 H 4-NHMe-3,5-diMe-Ph H Me -CH ₂ -OO CH 9-177 H 4-NHAc-3,5- diMe-Ph H Me -CH ₂ -OO CH 9-178 H 4-NO ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 9-179 H 4-NO ₂ -3,5-diMe- Ph H Me -CH ₂ -OS CH 9-180 H Pyr (2) H Me -CH ₂ -OO CH 9-181 H Pyr (2) H Me -CH ₂ -OON 9-182 H Pyr (2) H Me -CH ₂ -OS CH 9-183 H Pyr (2) H Me-(CH ₂ ) ₂ -OO CH 9-184 H Pyr (2) H Me-(CH ₂ ) ₃ -OO CH 9-185 H Pyr ( 2) H Et -CH ₂ -OO CH 9-186 H Pyr (2) H Et -CH ₂ -OS CH 9-187 H Pyr (2) H tBu -CH ₂ -OO CH 9-188 H Pyr (2) H Ph -CH ₂ -OO CH 9-189 H Pyr (2) 5-Cl Me -CH ₂ -OO CH 9-190 H 5-Cl-Pyr (2) H Me -CH ₂ -OO CH 9- 191 H 6-Cl-Pyr (2) H Me -CH ₂ -OO CH 9-192 H 6-Me-Pyr (2) H Me -CH ₂ -OO CH 9-193 H 6-MeO-Pyr (2) H Me -CH ₂ -OO CH 9-194 H 3-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 9-195 H 5-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 9-196 H 3-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 9-197 H 5-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 9-198 H 5-NH ₂ -6-Cl-Pyr (2) H Me -CH ₂ -OO CH 9 -199 3-MeO 5-NH ₂ -6-Cl-Pyr (2) 5-MeO Et-(CH ₂ ) ₄ -SS CH 9 -200 H Pyr (3) H Me -CH ₂ -OO CH 9-201 H Pyr (3) H Me -CH ₂ -OON 9-202 H Pyr (3) H Me -CH ₂ -OS CH 9-203 H Pyr (3) H Me-(CH ₂ ) ₂ -OO CH 9-204 H Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 9-205 H Pyr (3) H Et -CH ₂ -OO CH 9-206 H Pyr (3) H Et -CH ₂ -OS CH 9-207 H Pyr (3) H tBu -CH ₂ -OO CH 9-208 H Pyr (3) H Pn-(CH ₂ ) ₃ -OO CH 9-209 H Pyr (3) H Ph -CH ₂ -OO CH 9-210 H Pyr (3) H Ph -CH ₂ -OS CH 9-211 H Pyr (3) H Bz -CH ₂ -OO CH 9 -212 2-Cl Pyr (3) H Me -CH ₂ -OO CH 9-213 H 5-MeO-Pyr (3) H Me -CH ₂ -OO CH 9-214 H 6-MeO-Pyr (3) H Me -CH ₂ -OO CH 9-215 H 6-MeO-Pyr (3) H Me -CH ₂ -OS CH 9-216 H 6-MeO-Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 9-217 H 6-iPrO-Pyr (3) H Me -CH ₂ -OO CH 9-218 H 6-MeO-5-Me-Pyr (3) H Me -CH ₂ -OO CH 9-219 H 2-NO ₂ -6-Me-Pyr (3) H Me -CH ₂ -OO CH 9-220 H Pyr (4) H Me -CH ₂ -OO CH 9-221 H Pyr (4) H Me -CH ₂ -OON 9-222 H Pyr (4) H Me -CH ₂ -OS CH 9-223 H Pyr (4) H Me -CH ₂ -SS CH 9-224 H Pyr (4) H Me-( CH ₂ ) ₂ -OO CH 9-225 H Pyr (4) H Et -CH ₂ -OO CH 9-226 H Pyr (4) H Et -CH ₂ -OS CH 9-227 H Pyr (4) H tBu- CH ₂ -OO CH 9-228 H Pyr (4) H Ph -CH ₂ -OO CH 9-229 H Pyr (4) H Bz -CH ₂ -OS CH 9-230 3-Cl Pyr (4) H Me- CH ₂ -OO CH 9-231 H 2-Me-Pyr (4) H Me -CH ₂ -OO CH 9-232 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 9-233 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OS CH 9-234 H 3,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 9-235 H 2-MeO-Pyr (4) H Me -CH ₂ -OO CH 9-236 H 4-Imid (1) -Ph H Me -CH ₂ -OO CH 9-237 H 4-Tz-Ph H Me -CH ₂ -OO CH 9- 238 H 4-Ada (1) -Ph H Me -CH ₂ -OO CH 9-239 H 4-CN-Ph H Me -CH ₂ -OO CH 9-240 H 4-Bz-3-OH-Ph H Me -CH ₂ -OO CH 9-241 H pentaF-Ph H Me -CH ₂ -OO CH 9-242 H 4-NHCOPh-Ph H Me -CH ₂ -OO C H 9-243 H 4-NHCO (3-Cl-Ph) -Ph H Me -CH ₂ -OO CH 9-244 H 4-NHCO (2,4-diF-Ph) -Ph H Me -CH ₂ -OO CH 9-245 H 4-NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH ₂ -OO CH 9-246 H 4-NHCONp (1) -Ph H Me -CH ₂ -OO CH 9-247 H 4-NHCO (3-Cl-Bz) -Ph H Me -CH ₂ -OO CH 9-248 H 4-NHCOcPn-Ph H Me -CH ₂ -OO CH 9-249 H 4-NHCOcHx- Ph H Me -CH ₂ -OO CH 9-250 H 4-NHCOPyr (3) -Ph H Me -CH ₂ -OO CH 9-251 H 4-NHCOPyr (4) -Ph H Me -CH ₂ -OO CH 9 -252 H 4-NHHx-Ph H Me -CH ₂ -OO CH 9 -253 H 4-NH (Ac) Hx-Ph H Me -CH ₂ -OO CH .

[0103]

[Table 10]

[0104]

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[0105] Cpd.No.R ² R ⁴ R ⁵ R ⁶ -A- BDE 10-1 H 4-F-Ph H Me -CH ₂ -OO CH 10-2 H 4-Cl-Ph H Me -CH ₂ -OO CH 10-3 H 2-OH-Ph H Me -CH ₂ -OO CH 10-4 H 2-OH-Ph H Me -CH ₂ -OS CH 10-5 H 3-OH-Ph H Me -CH ₂ -OO CH 10-6 H 3-OH-Ph H Me -CH _2- OS CH 10-7 H 4-OH-Ph H Me -CH ₂ -OO CH 10-8 H 4-OH-Ph H Me -CH ₂ -OON 10-9 H 4-OH-Ph H Me -CH _2- OS CH 10-10 H 4-OH-Ph H Et -CH ₂ -OO CH 10-11 H 4-OH-Ph H Et -CH ₂ -OS CH 10-12 H 3-CF ₃ -Ph H Me -CH ₂ -OO CH 10-13 H 4-iPrO-Ph H Me -CH ₂ -OO CH 10-14 H 4-MeS-Ph H Me -CH ₂ -OO CH 10-15 H 2-NH ₂ -Ph H Me -CH ₂ -OO CH 10-16 H 3-NH ₂ -Ph H Me -CH ₂ -OO CH 10-17 H 4-NH ₂ -Ph H Me -CH ₂ -OO CH 10-18 H 4-NHMe- Ph H Me -CH ₂ -OO CH 10-19 H 4-N (Me) ₂ -Ph H Me -CH ₂ -OO CH 10-20 H 4-N (Me) ₂ -Ph H Et -CH ₂ -OO CH 10-21 H 4-Ph-Ph H Me -CH ₂ -OO CH 10-22 H 4- (4-OH-3,5-diMe-Ph) Ph H Me -CH ₂ -OO CH 10-23 H 4- (4-OH-3,5-ditBu-Ph) Ph H Me -CH ₂ -OO CH 10-24 H 4- (4-OH-Bz) Ph H Me -CH ₂ -OO CH 10-25 H 4-PhS-Ph H Me -CH ₂ -OO CH 10-26 H 2-Pyrd (1) -Ph H Me -CH ₂ -OO CH 10-27 H 3-Pyrd (1) -Ph H Me -CH ₂ -OO CH 10-28 H 3-Pyrd (1) -Ph H Me -CH ₂ -OS CH 10-29 H 3-Pyrd (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 10-30 H 3-Pyrd (1) -Ph H Et -CH ₂ -OO CH 10-31 H 4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 10-32 H 4-Pyrd (1) -Ph H Me -CH ₂ -OS CH 10-33 H 4-Pyrd (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 10-34 H 2-Pip (1) -Ph H Me -CH ₂ -OO CH 10-35 H 3-Pip (1) -Ph H Me -CH ₂ -OO CH 10-36 H 3-Pip (1) -Ph H Me -CH ₂ -OS CH 10-37 H 3-Pip (1) -Ph H Et-(CH ₂ ) ₃ -SO CH 10-38 H 4-Pip (1) -Ph H Me -CH ₂ -OO CH 10-39 H 4-Pip (1) -Ph H Me -CH ₂ -OS CH 10-40 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₂ -OO CH 10 -41 H 4-Pip (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 10 -42 H 4-Pip (1) -Ph H tBu -CH ₂ -OO CH 10 -43 H 4-Pip (1) -Ph 4-Cl Me -CH ₂ -OO CH 10-44 2-MeO 4-Pip (1) -Ph H Me -CH ₂ -OO CH 10-45 H 2-Mor (4) -Ph H Me -CH ₂ -OO CH 10-46 H 2-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 10-47 H 3-Mor (4) -Ph H Me -CH ₂ -OO CH 10-48 H 3-Mor (4) -Ph H Me -CH ₂ -OS CH 10-49 H 3-Mor (4) -Ph H Me-(CH ₂ ) ₃ -OO CH 10-50 H 3-Mor (4) -Ph H Et -CH ₂ -OO CH 10-51 H 4-Mor (4)- Ph H Me -CH ₂ -OO CH 10-52 H 4-Mor (4) -Ph H Me -CH ₂ -OS CH 10-53 H 4-TioMor (4) -Ph H Me -CH ₂ -OO CH 10-54 H 4-Pipra (1) -Ph H Me -CH ₂ -OO CH 10-55 H 4-Pipra (1) -Ph H Me-(CH ₂ ) ₃ -OO CH 10-56 H 4-Pipra (1) -Ph H Et -CH ₂ -OO CH 10-57 H 4-NO ₂ -Ph H Me -CH ₂ -OO CH 10-58 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 10-59 H 2 -Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 10-60 H 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 10- 61 H 2-Cl-4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₄ -OO CH 10-62 H 2-Cl-4-OH-3,5-diMe-Ph H Et- CH ₂ -OO CH 10-63 H 2-Cl-4-OH-3,5-diMe-Ph H Et -CH ₂ -OS CH 10-64 H 2-Cl-4-OH-3,5-diMe- Ph 6-MeO Me -CH ₂ -OO CH 10-65 3-Cl 2-Cl-4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 10-66 2-MeO 2-Cl- 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 10-67 H 4-Cl-3-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 10-68 H 3-Cl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 10-69 H 3,5-diCl-4-NH ₂ -Ph H Me -CH ₂ -OO CH 10-70 H 4-NHMe- 3-Cl-Ph H Me -CH ₂ -OO CH 10-71 H 3-Cl-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 10-72 H 3-OH-4-Pyrd (1 ) -Ph H Me -CH ₂ -OO CH 10-73 H 3-Cl-6-Me-4-Pyrd (1) -Ph H Me -CH ₂ -OO CH 10-74 H 2-Me-4-Mor (4) -Ph H Me -CH ₂ -OO CH 10-75 H 2-OH-3-Me-Ph H Me -CH _2- OO CH 10-76 H 2-OH-4-Me-Ph H Me -CH ₂ -OO CH 10-77 H 2-OH-3,4-diMe-Ph H Me -CH ₂ -OO CH 10-78 H 3-OH-2-Me-Ph H Me -CH ₂ -OO CH 10-79 H 3-OH-4-Me-Ph H Me -CH ₂ -OO CH 10-80 H 3-OH-5-Me- Ph H Me -CH ₂ -OO CH 10-81 H 3-OH-6-Me-Ph H Me -CH ₂ -OO CH 10-82 H 3-OH-2,4-diMe-Ph H Me -CH ₂ -OO CH 10-83 H 4-OH-2-Me-Ph H Me -CH ₂ -OO CH 10-84 H 4-OH-3-Me-Ph H Me -CH ₂ -OO CH 10-85 H 4 -OH-3-Me-Ph H Et -CH ₂ -OO CH 10-86 H 4-OH-3-Me-Ph 6-Cl Me -CH ₂ -OO CH 10-87 H 4-OH-2-tBu -Ph H Me -CH ₂ -OO CH 10-88 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OO CH 10-89 H 4-OH-2,3-diMe-Ph H Me -CH ₂ -OS CH 10-90 H 4-OH-2,3-diMe-Ph H Me-(CH ₂ ) ₃ -SO CH 10-91 H 4-OH-2,3-diMe-Ph H Et- CH ₂ -OO CH 10-92 H 4-OH-2,5-diMe-Ph H Me -CH ₂ -OO CH 10-93 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OO CH 10-94 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OON 10-95 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -OS CH 10-96 H 4-OH-3,5-diMe-Ph H Me -CH ₂ -SO CH 10-97 H 4-OH-3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 10-98 H 4-OH-3,5-diMe-Ph H Et -CH ₂ -OO CH 10-99 H 4 -OH-3,5-diMe-Ph H Et -CH ₂ -OS CH 10-100 H 4-OH-3,5-diMe-Ph H sBu -CH ₂ -OO CH 10-101 H 4-OH-3 , 5-diMe-Ph H Ph -CH ₂ -OO CH 10-102 H 3,5-diEt-4-OH-Ph H Me -CH ₂ -OO CH 10-103 H 3-tBu-4-OH-5 -Me-Ph H Me -CH ₂ -OO CH 10-104 H 3-tBu-4-OH-5-Me-Ph H Me -CH ₂ -OS CH 10-105 H 4-OH-3,5-diPr -Ph H Me -CH ₂ -OO CH 10-106 H 4-OH-3,5-diiPr-Ph H Me -CH ₂ -OO CH 10-107 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OO CH 10-108 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OON 10-109 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -OS CH 10-110 H 3,5-ditBu-4-OH-Ph H Me -CH ₂ -SS CH 10-111 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₂ -OS CH 10-112 H 3,5-ditBu-4-OH-Ph H Me-(CH ₂ ) ₃ -OS CH 10 -113 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OO CH 10 -114 H 3,5-ditBu-4-OH-Ph H Et -CH ₂ -OS CH 10-115 H 3,5-ditBu-4-OH-Ph 6-Cl Me -CH ₂ -OS CH 10-116 H 4-OH-2,3,5-triMe-Ph HH -CH ₂ -OS CH 10-117 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 10-118 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OON 10-119 H 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OS CH 10-120 H 4-OH-2,3,5-triMe-Ph H Me -(CH ₂ ) ₂ -OO CH 10-121 H 4-OH-2,3,5-triMe-Ph H Me-(CH ₂ ) ₃ -OO CH 10-122 H 4-OH-2,3,5 -triMe-Ph H Et -CH ₂ -OO CH 10-123 H 4-OH-2,3,5-triMe-Ph H Et -CH ₂ -OS CH 10-124 H 4-OH-2,3,5 -triMe-Ph H iPr -CH ₂ -OO CH 10-125 H 4-OH-2,3,5-triMe-Ph H Ph -CH ₂ -OO CH 10-126 H 4-OH-2,3,5 -triMe-Ph H Bz -CH ₂ -OO CH 10-127 H 4-OH-2,3,5-triMe-Ph 6-Cl Me -CH ₂ -OO CH 10-128 2-Cl 4-OH-2 , 3,5-triMe-Ph H Me -CH ₂ -OO CH 10-129 2-MeO 4-OH-2,3,5-triMe-Ph H Me -CH ₂ -OO CH 10-130 H 4-OH -2,3,6-triMe-Ph H Me -CH ₂ -OO CH 10-131 H 4-OH-2,3,5,6-tetraMe-Ph H Me -CH ₂ -OO CH 10-132 H 4 -OH-3,5-diMeO-Ph H Me -CH ₂ -OO CH 10-133 H 3-NH ₂ -4-Me-Ph H Me -CH ₂ -OO CH 10-134 H 4-NH ₂ -2 , 3-diMe-Ph H Me -CH 2 - OO CH 10-135 H 4-NH 2 -2,6-diMe-Ph H Me -CH 2 - OO CH 10-136 H 4-NH 2 -3,5 -diMe-Ph HH -CH ₂ -OO CH 10-137 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OO CH 10-138 H 4-NH ₂ -3,5-diMe- Ph H Me -CH ₂ -OON 10-139 H 4-NH ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 10-140 H 4-NH ₂ -3,5-diMe-Ph H Me-(CH ₂ ) ₂ -OO CH 10-141 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OO CH 10-142 H 4-NH ₂ -3,5-diMe-Ph H Et -CH ₂ -OS CH 10-143 H 4 -NH ₂ -3,5-diMe-Ph H Ph -CH ₂ -OO CH 10-144 H 4-NH ₂ -3,5-diMe-Ph H Bz -CH ₂ -OO CH 10-145 H 4-NHMe -3,5-diMe-Ph H Me -CH ₂ -OO CH 10-146 H 4-NHAc-3,5-diMe-Ph H Me -CH ₂ -OO CH 10-147 H 4-NO ₂ -3, 5-diMe-Ph H Me -CH ₂ -OO CH 10-148 H 4-NO ₂ -3,5-diMe-Ph H Me -CH ₂ -OS CH 10-149 H Pyr (2) H Me -CH ₂ -OO CH 10-150 H Pyr (2) H Me -CH ₂ -OON 10-151 H Pyr (2) H Me -CH ₂ -OS CH 10-152 H Pyr (2) H Me-(CH ₂ ) ₂ -OO CH 10-153 H Pyr (2) H Me-(CH ₂ ) ₃ -OO CH 10-154 H Pyr (2) H Et -CH ₂ -OO CH 10-155 H Pyr (2) H Et -CH ₂ -OS CH 10-156 H Pyr (2) H Ph -CH ₂ -OO CH 10-157 H Pyr (2) 6-Cl Me -CH ₂ -OO CH 10-158 H 5-Cl-Pyr (2) H Me -CH ₂ -OO CH 10-159 H 6-Cl-Pyr (2) H Me -CH ₂ -OO CH 10-160 H 6-MeO-Pyr (2) H Me -CH ₂ -OO CH 10- 161 H 3-NH ₂ -Pyr (2) H Me -CH ₂ -OO CH 10-162 H 5-NH ₂ -Pyr (2) H Me -CH _2- OO CH 10-163 H 3-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 10-164 H 5-NO ₂ -Pyr (2) H Me -CH ₂ -OO CH 10-165 3-MeO 5-NH ₂ -6-Cl-Pyr (2) 6-MeO Et-(CH ₂ ) ₄ -SS CH 10-166 H Pyr (3) H Me -CH ₂ -OO CH 10-167 H Pyr (3) H Me -CH ₂ -OON 10-168 H Pyr (3) H Me -CH ₂ -OS CH 10-169 H Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 10-170 H Pyr (3) H Et -CH ₂ -OO CH 10-171 H Pyr (3) H Et -CH ₂ -OS CH 10-172 H Pyr (3) H Pn-(CH ₂ ) ₃ -OO CH 10-173 H Pyr (3 ) H Ph -CH ₂ -OO CH 10-174 H Pyr (3) H Ph -CH ₂ -OS CH 10-175 2-Cl Pyr (3) H Me -CH ₂ -OO CH 10-176 H 6-MeO -Pyr (3) H Me -CH ₂ -OO CH 10-177 H 6-MeO-Pyr (3) H Me -CH ₂ -OS CH 10-178 H 6-MeO-Pyr (3) H Me-(CH ₂ ) ₃ -OO CH 10-179 H 6-iPrO-Pyr (3) H Me -CH ₂ -OO CH 10-180 H 6-MeO-5-Me-Pyr (3) H Me -CH ₂ -OO CH 10-181 H 2-NO ₂ -6-Me-Pyr (3) H Me -CH ₂ -OO CH 10-182 H Pyr (4) H Me -CH ₂ -OO CH 10-183 H Pyr (4) H Me -CH ₂ -OON 10-184 H Pyr (4) H Me -CH ₂ -OS CH 10-185 H Pyr (4) H Me -CH ₂ -SS CH 10-186 H Pyr (4) H Me-( CH ₂ ) ₂ -OO CH 10-187 H Pyr (4) H Et -CH ₂ -OO CH 10-188 H Pyr (4) H Et -CH ₂ -OS CH 10-189 H Pyr (4) H Ph -CH ₂ -OO CH 10-190 H Pyr (4) H Bz -CH ₂ -OS CH 10-191 3-Cl Pyr (4) H Me -CH ₂ -OO CH 10-192 H 2-Me-Pyr (4) H Me -CH ₂ -OO CH 10-193 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 10-194 H 2,6-diMe-Pyr (4) H Me -CH ₂ -OS CH 10-195 H 3,6-diMe-Pyr (4) H Me -CH ₂ -OO CH 10- 196 H 2-MeO-Pyr (4) H Me -CH ₂ -OO CH 10-197 H 4-Imid (1) -Ph H Me -CH ₂ -OO CH 10-198 H 4-Tz-Ph H Me- CH ₂ -OO CH 10-199 H 4-Ada (1) -Ph H Me -CH ₂ -OO CH 10-200 H 4-CN-Ph H Me -CH ₂ -OO CH 10-201 H 4-Bz- 3-OH-Ph H Me -CH ₂ -OO CH 10-202 H pentaF-Ph H Me -CH ₂ -OO CH 10-203 H 4-NHCOPh-Ph H Me -CH ₂ -OO CH 10-204 H 4 -NHCO (3-Cl-Ph) -Ph H Me -CH ₂ -OO CH 10-205 H 4-NHCO (2,4-diF-Ph) -Ph H Me -CH ₂ -OO CH 10-206 H 4 -NHCO (4-OH-3,5-ditBu-Ph) -Ph H Me -CH ₂ -OO CH 10-207 H 4-NHCONp (1) -Ph H Me -CH ₂ -OO CH 10-208 H 4 -NHCO (3-Cl-Bz) -Ph H Me -CH ₂ -OO CH 10-209 H 4-NHCOcPn-Ph H Me -CH ₂ -OO CH 10-210 H 4-NHCOcHx-Ph H Me -CH ₂ -OO CH 10-211 H 4-NHCOPyr (3) -Ph H Me -CH ₂ -OO CH 10-212 H 4 -NHCOPyr (4) -Ph H Me -CH ₂ -OO CH 10-213 H 4-NHHx-Ph H Me -CH ₂ -OO CH 10-214 H 4-NH (Ac) Hx-Ph H Me -CH ₂ -OO CH In Tables 1 to 10, preferably, compound numbers 1-2, 1-3, 1-6, 1-7, 1-8, 1-10, 1-1
1, 1-13, 1-18, 1-25, 1-41, 1-42, 1-43, 1-48, 1-5
1, 1-60, 1-68, 1-69, 1-70, 1-71, 1-72, 1-77, 1-8
0, 1-86, 1-89, 1-90, 1-94, 1-97, 1-104, 1-127, 1
-128, 1-129, 1-130, 1-131, 1-132, 1-133, 1-1
34, 1-135, 1-136, 1-137, 1-141, 1-142, 1-143
, 1-144, 1-148, 1-149, 1-150, 1-153, 1-154
, 1-155, 1-156, 1-157, 1-159, 1-160, 1-161
, 1-162, 1-163, 1-164, 1-165, 1-168, 1-169
, 1-170, 1-171, 1-172, 1-175, 1-181, 1-182
, 1-184, 1-185, 1-186, 1-191, 1-193, 1-195
, 1-199, 1-200, 1-201, 1-206, 1-208, 1-213
, 1-214, 1-215, 1-216, 1-221, 1-223, 1-230
, 1-236, 1-241, 1-242, 1-243, 1-244, 1-245
, 1-246, 1-248, 1-249, 1-250, 1-251, 1-253
, 1-256, 1-257, 1-258, 1-259, 1-260, 1-264
, 1-267, 1-269, 1-282, 1-284, 1-285, 1-286
, 1-287, 1-288, 1-289, 1-290, 1-292, 1-293
, 1-294, 1-295, 1-296, 1-297, 1-298, 1-299
, 1-300,1-302,1-303,1-304,1-305,1-307
, 1-309, 1-312, 1-325, 1-329, 1-330, 1-331
, 1-332,1-333,1-335,1-339,1-342,1-344
, 1-351,1-354,1-357,1-358,1-359,1-362
, 1-363, 1-366, 1-367, 1-368, 1-369, 1-370
, 1-371,1-375,1-378,1-408,1-421,1-429
, 1-430, 1-433, 1-438, 1-439, 1-440, 1-441
, 1-442, 1-447, 1-458, 1-463, 1-465, 1-468
, 1-469,1-470,1-476,1-481,1-482,1-483
, 1-486,1-487,1-488,1-489,1-497,1-499
, 1-501,1-502,1-503,1-504,1-506,1-507
, 1-508,1-513,1-514,1-515,1-519,1-520
, 1-521,1-522,1-523,1-528,1-538,1-540
, 1-541,1-543,1-544,1-560,1-561,1-565
, 1-566,1-567,1-569,1-572,1-574,1-575
, 1-577, 1-578, 1-579, 1-590, 1-592, 1-593
, 1-594, 1-595, 1-597, 1-598, 1-599, 1-600
, 1-601, 1-602, 1-603, 1-607, 1-608, 1-609
, 1-610, 1-613, 1-624, 1-627, 1-631, 1-633
, 1-634, 1-635, 1-636, 1-637, 1-638, 1-639
, 1-640, 1-641, 1-642, 1-643, 1-644, 1-645
, 1-646, 1-647, 1-650, 1-651, 1-652, 1-653
, 1-660, 1-661, 1-666, 1-668, 1-669, 1-670
, 1-671, 1-690, 1-692, 1-693, 1-696, 1-697
, 1-698, 1-705, 1-706, 1-707, 1-708, 1-710
, 1-711, 1-713, 1-715, 1-722, 1-723, 1-724
, 1-727, 1-728, 1-729, 1-738, 1-739, 1-740
, 1-741, 1-742, 1-743, 1-747, 1-748, 1-749
, 1-757, 1-758, 1-759, 1-764, 1-765, 1-767
, 1-773, 1-777, 1-779, 1-786, 1-796, 1-800
, 1-808, 1-809, 1-812, 1-814, 1-820, 1-821
, 1-822, 1-823, 1-824, 1-829, 1-830, 1-831
, 1-832, 1-839, 1-840, 1-841, 1-846, 1-859
, 1-877, 1-878, 1-879, 1-881, 1-883, 1-888
, 1-895, 1-897, 1-907, 1-909, 1-910, 1-911
, 1-912, 1-913, 1-916, 1-917, 1-920, 1-922
, 1-925, 1-926, 1-927, 1-930, 1-932, 1-937
, 1-938, 1-939, 1-940, 1-941, 1-946, 1-948
, 1-954, 1-956, 1-957, 1-958, 1-979, 1-984
, 1-988, 1-989, 1-994, 1-998, 1-1001, 1-100
6, 1-1010, 1-1018, 1-1019, 1-1020, 1-1021, 1-102
6, 1-1028, 1-1030, 1-1110, 1-1111, 1-1112, 1-111
5, 1-1126, 1-1127, 1-1128, 1-1154, 1-1182, 1-118
3, 1-1184, 1-1185, 1-1210, 1-1211, 1-1212, 1-121
3, 1-1230, 1-1234, 1-1235, 1-1236, 1-1237, 1-124
2, 1-1248, 1-1249, 1-1256, 1-1263, 1-1264, 1-126
5, 1-1269, 1-1270, 1-1271, 1-1277, 1-1285, 1-128
6, 1-1287, 1-1292, 1-1293, 1-1294, 1-1298, 1-129
9, 1-1305, 1-1306, 1-1307, 1-1311, 1-1312, 1-131
3, 1-1318, 1-1319, 1-1320, 1-1327, 2-18, 2-19, 2-2
0, 2-21, 2-22, 2-55, 2-56, 2-57, 2-58, 2-59, 2-6
0, 2-76, 2-77, 2-78, 2-81, 2-83, 2-86, 2-87, 2-8
8, 2-94, 2-95, 2-96, 2-99, 2-105, 2-115, 2-116,
2-117, 2-119, 2-121, 2-122, 2-123, 2-127, 2-
134, 2-135, 2-153, 2-154, 2-155, 2-173, 2-185
, 2-186, 2-187, 2-205, 2-206, 2-218, 2-219,
2-229, 2-230, 2-231, 2-232, 2-233, 2-234, 2-2
62, 2-263, 2-264, 2-265, 2-266, 2-267, 2-270
, 2-286, 2-292, 2-296, 2-297, 2-298, 2-299,
2-300, 2-325, 2-326, 2-334, 2-335, 2-339, 2-3
40, 2-341, 2-342, 2-378, 2-379, 2-380, 2-381
, 2-384, 2-385, 2-406, 2-430, 2-431, 2-432,
2-433, 2-513, 2-534, 2-541, 2-545, 2-547, 2-5
48, 2-549, 2-552, 2-553, 3-1, 3-2, 3-3, 3-
4, 3-6, 3-10, 3-19, 3-20, 3-21, 3-22, 3-53, 3-5
4, 3-55, 3-56, 3-57, 3-58, 3-59, 3-60, 3-69, 3-7
6, 3-78, 3-81, 3-83, 3-86, 3-87, 3-88, 3-94, 3-9
5, 3-96, 3-105, 3-106, 3-107, 3-115, 3-116, 3
-117, 3-119, 3-120, 3-127, 3-134, 3-136, 3-1
37, 3-142, 3-148, 3-149, 3-153, 3-154, 3-155
, 3-156, 3-184, 3-188, 3-189, 3-205, 3-206
, 3-218, 3-219, 3-229, 3-230, 3-231, 3-232
, 3-234, 3-239, 3-241, 3-248, 3-250, 3-263
, 3-264, 3-265, 3-266, 3-267, 3-272, 3-275
, 3-276, 3-296, 3-297, 3-298, 3-299, 3-306
, 3-326, 3-334, 3-335, 3-338, 3-339, 3-340
, 3-341, 3-342, 3-344, 3-349, 3-351, 3-378
, 3-379, 3-380, 3-381, 3-383, 3-385, 3-388
, 3-406, 3-408, 3-430, 3-431, 3-432, 3-433
, 3-521, 3-522, 3-530, 3-531, 3-532, 3-534
, 3-540, 3-541, 3-542, 3-545, 3-547, 3-552
, 3-553, 4-11, 4-13, 4-24, 4-25, 4-32, 4-38, 4-4
4, 4-49, 4-59, 4-60, 4-62, 4-63, 4-66, 4-87, 4-9
0, 4-105, 4-118, 4-120, 4-121, 4-131, 4-132,
4-133, 4-134, 4-135, 4-145, 4-146, 4-147, 4-15
9, 4-166, 4-167, 4-168, 4-180, 4-181, 4-182
, 4-200, 4-201, 4-202, 4-238, 4-239, 4-243,
4-245, 4-247, 4-252, 5-11, 5-13, 5-24, 5-25, 5-
32, 5-33, 5-35, 5-39, 5-44, 5-45, 5-49, 5-50, 5-5
1, 5-59, 5-60, 5-62, 5-63, 5-65, 5-66, 5-71, 5-7
7, 5-78, 5-79, 5-80, 5-105, 5-112, 5-118, 5-119
, 5-120, 5-122, 5-131, 5-132, 5-133, 5-134,
5-135, 5-137, 5-145, 5-146, 5-147, 5-148, 5-
159, 5-163, 5-166, 5-167, 5-168, 5-170, 5-171
, 5-180, 5-181, 5-182, 5-183, 5-192, 5-200,
5-201, 5-202, 5-236, 5-238, 5-242, 5-245, 5-
247, 5-252, 5-253, 6-7, 6-8, 6-9, 6-26, 6-4
5, 6-47, 6-48, 6-58, 6-59, 6-60, 6-67, 6-82, 6-9
3, 6-107, 6-108, 6-109, 6-116, 6-117, 6-134
, 6-149, 6-166, 6-199, 6-200, 6-208, 7-1, 7
-2, 7-3, 7-4, 7-11, 7-13, 7-24, 7-25, 7-32, 7-3
8, 7-44, 7-49, 7-59, 7-60, 7-62, 7-63, 7-66, 7-8
7, 7-90, 7-105, 7-118, 7-120, 7-121, 7-131, 7
-132, 7-133, 7-134, 7-135, 7-145, 7-146, 7-14
7, 7-159, 7-166, 7-167, 7-168, 7-180, 7-18
1, 7-182, 7-200, 7-201, 7-202, 7-236, 7-238
, 7-239, 7-241, 7-242, 7-243, 7-244, 7-245,
7-247, 7-248, 7-249, 7-250, 7-251, 7-252, 7-2
53, 8-7, 8-9, 8-19, 8-26, 8-31, 8-34, 8-38, 8-4
5, 8-47, 8-48, 8-51, 8-58, 8-67, 8-82, 8-93, 8-9
5, 8-96, 8-105, 8-106, 8-107, 8-108, 8-109, 8
-117, 8-118, 8-119, 8-130, 8-137, 8-138, 8-1
39, 8-149, 8-150, 8-151, 8-166, 8-167, 8-168
, 8-199, 8-206, 8-213, 9-11, 9-13, 9-24, 9-3
2, 9-33, 9-35, 9-39, 9-44, 9-45, 9-49, 9-50, 9-5
1, 9-59, 9-60, 9-62, 9-63, 9-65, 9-66, 9-71, 9-7
7, 9-78, 9-79, 9-80, 9-105, 9-118, 9-119, 9-120
, 9-122, 9-131, 9-132, 9-133, 9-134, 9-135
, 9-137, 9-145, 9-146, 9-147, 9-148, 9-159,
9-163, 9-166, 9-167, 9-168, 9-170, 9-171, 9-1
80, 9-181, 9-182, 9-183, 9-192, 9-200, 9-20
1, 9-202, 9-236, 9-238, 9-239, 9-242, 9-245
, 9-247, 9-250, 9-252, 10-7, 10-8, 10-9, 10-26
, 10-45, 10-47, 10-48, 10-58, 10-59, 10-60
, 10-67, 10-82, 10-93, 10-107, 10-108, 10-10
9, 10-116, 10-117, 10-133, 10-149, 10-166, 10-19
Compounds of 7, 10-200, 10-203, 10-211 and 10-213 can be mentioned, and more preferably, compound numbers 1-69, 1-70, 1-72, 1-131, 1- 132, 1-136
, 1-137, 1-142, 1-149, 1-150, 1-153, 1-154
, 1-155, 1-157, 1-160, 1-161, 1-164, 1-168
, 1-169, 1-171, 1-172, 1-184, 1-185, 1-193
, 1-199, 1-200, 1-201, 1-214, 1-215, 1-216
, 1-221, 1-241, 1-242, 1-243, 1-246, 1-257
, 1-258, 1-259, 1-284, 1-285, 1-286, 1-290
, 1-292, 1-302, 1-329, 1-330, 1-357, 1-368
, 1-369,1-370,1-371,1-375,1-378,1-408
, 1-476,1-481,1-486,1-501,1-502,1-503
, 1-506, 1-513, 1-514, 1-515, 1-520, 1-521
, 1-522,1-523,1-560,1-577,1-593,1-594
, 1-595, 1-603, 1-607, 1-609, 1-633, 1-634
, 1-640, 1-650, 1-651, 1-652, 1-653, 1-660
, 1-708, 1-727, 1-729, 1-739, 1-740, 1-741
, 1-742,1-747,1-757,1-759,1-808,1-821
, 1-822, 1-823, 1-824, 1-831, 1-877, 1-878
, 1-879, 1-938, 1-939, 1-940, 1-1126, 1-118
2, 1-1210, 1-1211, 1-1212, 1-1234, 1-1235, 1-123
6, 1-1237, 1-1242, 1-1248, 1-1263, 1-1269, 1-127
0, 1-1271, 1-1277, 1-1285, 1-1292, 1-1298, 1-130
5, 1-1306, 1-1307, 1-1311, 1-1312, 1-1313, 1-131
8, 2-19, 2-76, 2-115, 2-121, 2-153, 2-185, 2-2
05, 2-229, 2-233, 2-264, 2-266, 2-267, 2-296
, 2-298, 2-339, 2-378, 2-545, 2-547, 3-94, 3
-115, 3-153, 3-229, 3-231, 3-263, 3-266, 3-2
67, 3-298, 3-339, 3-340, 3-341, 3-342, 3-430
, 3-432, 3-530, 5-11, 5-44, 5-78, 5-118, 5-133
, 5-135, 5-145, 5-146, 5-147, 5-166, 5-180
, 5-236, 5-245, 9-11, 9-44, 9-78, 9-118, 9-133
, 9-135, 9-145, 9-147, 9-180, 9-238 and 9-239
Compound No. 1-70: 5- {4- [6- (4-hydroxyphenoxy) -1-methyl-1H-benzimidazole-] is particularly preferable.
2-ylmethoxy] benzyl} thiazolidine-2,4-
Dione, compound number 1-131: 5- {4- [1-methyl-6- (4
-Trifluoromethylphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione, compound number 1-132: 5- {4- [1-methyl-6- (4
-Methoxyphenoxy) -1H-benzimidazole-
2-ylmethoxy] benzyl {thiazolidine-2,4-
Dione, compound number 1-136: 5- {4- [1-methyl-6- (4
-Methylthiophenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4
-Dione, compound number 1-142: 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazole-2
-Ylmethoxy] benzyl {thiazolidine-2,4-dione, compound number 1-153: 5- {4- [6- (3-dimethylaminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} Thiazolidine-
2,4-dione, compound No. 1-164: 5- {4- [6- (4-acetylaminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-
2,4-dione, compound number 1-169: 5- {4- [1-methyl-6- (4
-Phenylphenoxy) -1H-benzimidazole-
2-ylmethoxy] benzyl {thiazolidine-2,4-
Dione, Compound No. 1-171: 5- {4- [6- (4′-hydroxybiphenyl-4-yloxy) -1-methyl-1H-
Benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, compound number 1-184: 5- {4- [6- (4-benzylphenoxy) -1-methyl-1H-benzimidazole-
2-ylmethoxy] benzyl {thiazolidine-2,4-
Dione, compound number 1-199: 5- {4- (6- [2- (pyrrolidin-1-yl) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl} thiazolidine-2,4- Dione, compound number 1-241: 5- ｛4
-(6- [2- (piperidin-1-yl) phenoxy]
-1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl} thiazolidine-2,4-dione, compound number 1-284: 5- {4- (6- [2- (morpholin-4-yl) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl} thiazolidine-2,4-dione, compound number 1-292: 5- {4- (1-methyl-6- [3
-(Morpholin-4-yl) phenoxy] -1H-benzimidazol-2-ylmethoxy) benzyl {thiazolidine-2,4-dione; Compound No. 1-368: 5- {4- [6- (2-chloro-4)
-Hydroxy-3,5-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy]
Benzyl thiazolidine-2,4-dione, compound No. 1-481: 5- {4- [6- (4-hydroxy-2-methylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} Thiazolidine-2,4-dione, Compound No. 1-486: 5- {4- [6- (4-hydroxy-3-methylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine- 2,4-dione, compound number 1-513: 5- {4- [6- (4-hydroxy-2,5-dimethylphenoxy) -1-methyl-1H-
Benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, compound number 1-520: 5- {4- [6- (4-hydroxy-3,5-dimethylphenoxy) -1-methyl-1H-
Benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione, Compound No. 1-593: 5- {4- [6- (3,5-di-t)
-Butyl-4-hydroxyphenoxy) -1-methyl-
1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione, compound number 1-595: 5- {4- [6- (3,5-di-t)
-Butyl-4-hydroxyphenylthio) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, compound number 1-650: 5- {4- [6- (4- Hydroxy-2,3,5-trimethylphenoxy) -1-methyl-
1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione, compound number 1-651: 5- {4- [5- (4-hydroxy-2,3,5-trimethylphenoxy) -3- Methyl-
3H-imidazo [4,5-b] pyridin-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, compound number 1-739: 5- {4- [6- (4-amino-
3,5-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, compound number 1-808: 5- {4- [6- (4-acetylamino) -3,5-dimethylphenoxy) -1-methyl-1
H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione, Compound No. 1-221: 5- {4- [6- (pyridine-2-
Yloxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4
-Dione, compound number 1-823: 5- {4- [1-methyl-6- (pyridin-2-ylthio) -1H-benzimidazole-
2-ylmethoxy] benzyl {thiazolidine-2,4-
Dione, compound number 1-938: 5- {4- [1-methyl-6- (pyridin-3-yloxy) -1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4
-Dione, compound number 1-1126: 5- {4- (6- [4- (imidazol-1-yl) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl} thiazolidine-2,4 -Dione, compound number 1-1182: 5- {4- (6- [4- (1-adamantyl) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl} thiazolidine-2,4-dione Compound No. 1-1210: 5- {4- [6- (4-cyanophenoxy) -1-methyl-1H-benzimidazole-2
-Ylmethoxy] benzyl} thiazolidine-2,4-dione, compound number 1-1234: 5- {4- [6- (2,5-di-t)
-Butyl-4-hydroxyphenoxy) -1-methyl-
1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, compound number 1-1235: 5- [4- (6-pentafluorophenoxy-1-methyl-1H-benzimidazole-2
-Ylmethoxy) benzyl] thiazolidine-2,4-dione, compound no. 1-1248: 5- {4- [6- (4-benzoylaminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} Thiazolidine-
2,4-dione, compound number 1-1263: 5- [4- {6- [4- (2,4-
Difluorobenzoylamino) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy {benzyl] thiazolidine-2,4-dione, compound number 1-1292: 5- {4- [6- (4-cyclopentanoyl) Aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, compound number 1-1305: 5- {4- [6- (4-nicotinoylaminophenoxy)- 1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione, and compound No. 5-135: 5- {4- [6- (3,5-di-t)
-Butyl-4-hydroxyphenylthio) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzylidenedithiazolidine-2,4-dione.

[0106]

BEST MODE FOR CARRYING OUT THE INVENTION The compound having the general formula (I) of the present invention can be easily produced according to the following method.

[0107]

Embedded image

In the above formula, R ¹ , R ² , A and B have the same meanings as described above, and R ^1a is a group in which the amino group and / or hydroxyl group included in the definition of R ¹ is protected. Other than an amino group and / or a hydroxyl group which may be represented by the same group as the group in the definition of the group of R ¹ , R ^2a represents an amino group and / or a hydroxyl group included in the definition of the group of R ² ; In addition to an amino group and / or a hydroxyl group which may be protected, it represents the same group as the group in the definition of R ² , and R ^3a is

[0109]

Embedded image

(Wherein R ⁸ represents a triphenylmethyl group), and R ^3b represents

[0111]

Embedded image

Is shown.

In the above, the "protecting group" of the "optionally protected amino group" in the definition of R ^1a and R ^2a is not particularly limited as long as it is an amino group protecting group used in the field of synthetic organic chemistry. but not, for example, the C ₁ -C ₇ aliphatic acyl group, chloroacetyl, dichloroacetyl, trichloroacetyl, halogeno C ₂ -C ₇ alkylcarbonyl group such as trifluoroacetyl, C ₁ -C such as methoxyacetyl ₆ "aliphatic acyl such" such C ₂ -C ₇ alkylcarbonyl group substituted with an alkoxy; said C ₇
-C ₁₁ aromatic acyl group, 2-bromobenzoyl, 4-chlorobenzoyl halogeno C ₇ -C ₁₁ aromatic acyl group such as yl, 2,4,6-trimethylbenzoyl, C ₁ -C such as 4-toluoyl C ₇ -C substituted with ₆ alkyl
₁₁ aromatic acyl groups, C ₁ -C ₆ such as 4-anisoyl
A C ₇ -C ₁₁ aromatic acyl group substituted with alkoxy, 4
- nitrobenzoyl, 2-nitro C ₇ -C ₁₁ aromatic acyl group substituted by such nitration as benzoyl, 2- (methoxycarbonyl) C ₂ -C ₇ alkoxycarbonyl C ₇ substituted with a carbonyl, such as benzoyl - C ₁₁ aromatic acyl group, C ₆ -C ₁₀ aryl such as 4-phenylbenzoyl
The C ₂ -C ₇ alkoxycarbonyl group; "aromatic acyl such" of C ₇ -C ₁₁ aromatic acyl group substituted by Le
2,2,2-trichloroethoxycarbonyl, C ₂ -C ₇ substituted by halogen or tri C ₁ -C ₆ alkylsilyl, such as 2-trimethylsilyl-ethoxycarbonyl
"Alkoxycarbonyls" such as an alkoxycarbonyl group; "alkenyloxycarbonyls" such as vinyloxycarbonyl and allyloxycarbonyl; benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, "1-2 C atoms, such as nitrobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl,
Ali at ₁ -C ₆ alkoxy or nitro - Good aralkyloxycarbonyl such even Le ring substituted "; trimethylsilyl, triethylsilyl, isopropyl dimethylsilyl, t- butyl dimethylsilyl, methyl diisopropylsilyl, methyldi -t- butylsilyl, A tri-C ₁ -C ₆ alkylsilyl group such as triisopropylsilyl, an aryl such as diphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl, phenyldiisopropylsilyl and a group selected from C ₁ -C ₆ alkyl. "Silyls" such as 3-substituted silyl groups; benzyl, phenethyl, 3-phenylpropyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, 9-anthryl 1 to 3 of ants, such as chill - Le C ₁ -C ₆ alkyl groups substituted with one, 4-
Methylbenzyl, 2,4,6-trimethylbenzyl,
3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, 4-cyanobenzyl _{1 to 3} aryls whose aryl ring is substituted by C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, nitro, halogen, cyano such as diphenylmethyl, bis (2-nitrophenyl) methyl, piperonyl - "aralkyl such" such as C ₁ -C ₆ alkyl group substituted with Le group;
Or N, N-dimethylaminomethylene, benzylidene,
4-methoxybenzylidene, 4-nitrobenzylidene,
Sarishiriden, 5-chloro-butylsalicylidene, diphenylmethylene, (5-chloro-2-hydroxyphenyl) "substituted methylene group forming a Schiff base" such as phenylmethylene; a and, preferably, C ₁ - A C ₇ aliphatic acyl group, a C ₇ -C ₁₁ aromatic acyl group or a C ₂ -C ₇ alkoxycarbonyl group, more preferably a C ₂ -C ₇
It is an alkoxycarbonyl group, particularly preferably a t-butoxycarbonyl group.

In the above, the “protecting group” of the “optionally protected hydroxyl group” in R ^1a and R ^2a is not particularly limited as long as it is a hydroxyl protecting group used in the field of synthetic organic chemistry. The C ₁ -C ₇ aliphatic acyl group,
Succinoyl, glutaroyl, C ₂ -C ₇ alkylcarbonyl group substituted by a carboxy, such as adipoyl,
Chloroacetyl, dichloroacetyl, trichloroacetyl, halogeno C ₂ -C such as trifluoroacetyl ₇
Alkylcarbonyl group, C ₁ such as methoxyacetyl
“Aliphatic acyls” such as a C ₂ -C ₇ alkylcarbonyl group substituted with —C ₆ alkoxy; halogeno C such as the aforementioned C ₇ -C ₁₁ aromatic acyl group, 2-bromobenzoyl and 4-chlorobenzoyl; ₇ -C ₁₁ aromatic acyl group, 2,
C ₇ -C ₁₁ aromatic acyl groups substituted with C ₁ -C ₆ alkyl, such as 4,6-trimethylbenzoyl, 4-toluoyl, C ₁ -C ₆ alkoxy substituted, such as 4-anisoyl ₇ -C ₁₁ aromatic acyl group, a 2-carboxybenzoyl, 3-carboxybenzoyl, 4-carboxyphenyl C ₇ substituted by carboxy, such as benzoyl -
C ₁₁ -C ₁₁ aromatic acyl group, C ₇ -C ₁₁ aromatic acyl group substituted by nitro such as 4-nitrobenzoyl, 2-nitrobenzoyl, C ₂ -C ₇ alkoxy such as 2- (methoxycarbonyl) benzoyl “Aromatic acyls” such as a C ₇ -C ₁₁ aromatic acyl group substituted with a carbonyl and a C ₇ -C ₁₁ aromatic acyl group substituted with a C ₆ -C ₁₀ aryl such as 4-phenylbenzoyl; Such as tetrahydropyran-2-yl, 3-bromotetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl, 4-methoxytetrahydrothiopyran-4-yl "Tetrahydropyranyl or tetrahydrothiopyranyls"; such as "tetrahydrofuran-2-yl, tetrahydrothiofuran-2-yl, Rofuraniru or tetrahydrothiofuranyl acids "; trimethylsilyl, triethylsilyl,
Tri C _1- such as isopropyldimethylsilyl, t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-t-butylsilyl, triisopropylsilyl
C ₆ alkylsilyl group, diphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl,
Aryls such as phenyldiisopropylsilyl and C
₁ -C ₆ "silyl ethers", such as three-substituted silyl group a group selected from alkyl, methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, iso-propoxymethyl, butoxy Methyl,
(C ₁ -C ₆ alkoxy) such as t-butoxymethyl
Methyl group, C _1- such as 2-methoxyethoxymethyl
Substituted with C ₆ alkoxy (C ₁ -C ₆ alkoxy)
A halogeno (C) such as a methyl group, 2,2,2-trichloroethoxymethyl, bis (2-chloroethoxy) methyl
₁ -C ₆ alkoxy) "alkoxymethyl such" such as methyl; 1-ethoxyethyl, 1- (isopropoxy) ethyl, such as (C ₁ -C ₆ alkoxy) ethyl group, 2,
"Substituted ethyls" such as an ethyl halide group such as 2,2-trichloroethyl; benzyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, 9-anthryl C ₁ -C ₆ alkyl substituted with one to three aryl, such as methyl, 4-methylbenzyl, 2,
4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl,
C ₁ such as 4-cyanobenzyl, methyl, piperonyl
"Aralkyl such" such as C ₁ -C ₆ alkyl group substituted with Le group - -C ₆ alkyl, C ₁ -C ₆ alkoxy, halogen, cyano Ali - Le ring of 1 to 3 substituted ants The aforementioned C ₂ -C ₇ alkoxycarbonyl group, 2,
“Alkoxycarbonyls” such as halogen such as 2,2-trichloroethoxycarbonyl and 2-trimethylsilylethoxycarbonyl or a C ₂ -C ₇ alkoxycarbonyl group substituted with a tri-C ₁ -C ₆ alkylsilyl group; vinyloxycarbonyl And "alkenyloxycarbonyls" such as allyloxycarbonyl; such as benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, and 4-nitrobenzyloxycarbonyl , One or two C ₁
An aralkyloxycarbonyl group in which the aryl ring may be substituted with -C ₆ alkoxy or nitro,
Preferably, it is a C ₁ -C ₇ aliphatic acyl group, a C ₇ -C ₁₁ aromatic acyl group, a C ₂ -C ₇ alkoxycarbonyl group or a (C ₁ -C ₆ alkoxy) methyl group, more preferably a C ₇ -C ₁₁ aromatic acyl group or a (C ₁ -C ₆ alkoxy) methyl group, particularly preferably a benzoyl group or a methoxymethyl group.

Method A is a method for producing compound (Ia) in which R ³ is a group having formulas (IV-1) to (IV-4) in compound (I). Step A1 is a step for producing a compound having the general formula (VII), and a phosphine (preferably, tributylphosphine or triphenylphosphine) and an azodicarboxylic acid compound (preferably, in an inert solvent). In the presence of diethyl azodicarboxylate or dipiperidine 1,1-azodicarboxylate.) In the presence of a compound having the general formula (V ′) and a compound having the general formula (VI).

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; benzene , Toluene, xylene; aromatic hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, and carbon tetrachloride; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether And amides such as dimethylformamide, dimethylacetamide, and hexamethylphosphoric triamide; or a mixed solvent of the above solvents; preferably, aliphatic hydrocarbons, aromatic hydrocarbons, and halogens. Hydrocarbons, Athe A mixed solvent of s or the solvent (more preferably, an aromatic hydrocarbon or an ether, particularly preferably toluene or tetrahydrofuran) is.

The reaction temperature varies depending on the starting compound, solvent and the like, but is usually from -20 ° C to 150 ° C (preferably 0 ° C
To 60 ° C.). The reaction time depends on the starting compound, solvent,
Although it depends on the reaction temperature and the like, it is usually 30 minutes to 5 days (preferably 5 hours to 72 hours).

After completion of the reaction, the target compound (VI
I) is collected from the reaction mixture according to a conventional method. For example, if insolubles are present, they are removed by filtration,
Add an immiscible organic solvent such as water and ethyl acetate, separate the organic layer containing the target compound, wash with water, etc., dry over anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate, etc., and evaporate the solvent. Obtained by leaving. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

Step A2 is a step of preparing a compound having the general formula (Ia), in which compound (VII) is reacted with an acid in the presence or absence (preferably in the presence) of an inert solvent. To remove the triphenylmethyl group in R ⁸ and, if desired, the amino group in R ^1a and R ^2a and / or
Alternatively, it is carried out by removing a protecting group of a hydroxyl group.

The acid used in the above-mentioned first-stage reaction is not particularly limited as long as it is used as an acid catalyst in a usual reaction. Examples thereof include hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, and phosphoric acid. Inorganic acids such as acetic acid, formic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, trifluoroacetic acid, Bronsted acids such as organic acids such as trifluoromethanesulfonic acid; zinc chloride,
Lewis acids such as tin tetrachloride, boron trichloride, boron trifluoride, boron tribromide; acidic ion exchange resins; preferably inorganic or organic acids (particularly preferably hydrochloric acid, acetic acid or trifluoro Acetic acid).

The inert solvent used in the first-stage reaction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin, and petroleum ether. Aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; methyl acetate, ethyl acetate, propyl acetate, butyl acetate, carbonic acid Esters such as diethyl; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, and n-butanol. , Isobutanol, t-butanol, Soamiruaruko - le, diethylene glycol, glycerin, octanol, cyclohexanol, alcohol such as methyl cellosolve - Le acids;
Amides such as formamide, dimethylformamide, dimethylacetamide, and hexamethylphosphoric triamide; water; or water or a mixed solvent of the above solvents; preferably ethers, alcohols or water (particularly preferable). Is dioxane, tetrahydrofuran, ethanol or water).

The reaction temperature depends on the starting compound, the acid used,
Although it depends on the solvent and the like, it is usually from -20 ° C to the boiling point (preferably 0 ° C to 100 ° C). The reaction time is
Although it depends on the starting compound, the acid used, the solvent, the reaction temperature, etc., it is usually 15 minutes to 48 hours (preferably 30 minutes
Minutes to 20 hours).

In this step, the compound (VII) is subjected to catalytic reduction in an inert solvent under atmospheric pressure or under pressure (preferably, under pressure) to remove the triphenylmethyl group in R ⁸ . If desired, the protecting group for the amino group and / or hydroxyl group in R ^1a and R ^2a can be removed to produce the desired compound (Ia). The catalyst used in the catalytic reduction reaction is not particularly limited as long as it is used in a usual catalytic reduction reaction. For example, palladium-carbon, Raney-nickel, rhodium-aluminum oxide, triphenylphosphine-oxidation Rhodium, palladium-barium sulfate, palladium black, platinum oxide, platinum black, and preferably palladium-carbon.

The inert solvent used in the above catalytic reduction reaction is not particularly limited as long as it is inert to the present reaction. For example, aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether are used. Aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, Ethers such as diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin , Octanol, cyclohex Alcohols such as phenol and methyl cellosolve; amides such as formamide, dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; organic acids such as acetic acid and trifluoroacetic acid; or a mixed solvent of the above solvents. Preferred are ethers, alcohols or organic acids (particularly preferred are alcohols).

The reaction temperature depends on the starting compound, the catalyst used, the solvent, etc., but is usually from 0 ° C. to 100 ° C.
(Preferably 10 ° C. to 50 ° C.). The reaction time is
It varies depending on the starting compound, the catalyst used, the solvent, the reaction temperature and the like, but is usually from 30 minutes to 48 hours (preferably 1
Hours to 24 hours).

The removal of the protecting groups for the amino group and the hydroxyl group depends on the type of the protecting group.
upsin Organic Synthesis), John Wiley & Sons: JFW
McOmis, (Protective Groups in OrganicChemistry),
It can be performed as follows by the method described in Plenum Press.

When the amino-protecting group is a silyl, a compound which generates a fluorine anion, such as tetrabutylammonium fluoride, hydrofluoric acid, hydrofluoric acid-pyridine and potassium fluoride, is usually used. And is removed by treating with The solvent used in the above reaction is not particularly limited as long as it does not inhibit the reaction, for example, diethyl ether, diisopropyl ether, tetrahydrofuran,
Ethers such as dioxane, dimethoxyethane, diethylene glycol dimethyl ether are preferred. The reaction temperature and reaction time are not particularly limited, but are usually 0 ° C.
It is carried out at a temperature of -50 ° C for 10-18 hours.

When the protecting group for the amino group is an aliphatic acyl, an aromatic acyl, an alkoxycarbonyl or a substituted methylene group forming a Schiff base, an acid or a base is added in the presence of an aqueous solvent. Can be removed. As the acid used in the above reaction,
There is no particular limitation as long as it does not inhibit the reaction and is usually used as an acid, for example, hydrobromic acid, hydrochloric acid,
Inorganic acids such as sulfuric acid, perchloric acid, phosphoric acid and nitric acid, preferably hydrochloric acid.

The base used in the above reaction is not particularly limited as long as it does not affect the other parts of the compound, but is preferably an alkali metal such as lithium carbonate, sodium carbonate or potassium carbonate. Carbonates; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide and potassium-t-butoxide; ammonia water ,
Ammonia, such as concentrated ammonia-methanol.

The solvent used in the above reaction is not particularly limited as long as it is a solvent used in a usual hydrolysis reaction. Examples thereof include methanol, ethanol, n-propanol and isopropanol. Alcohols such as toluene, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve;
Ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether;
Water; a mixed solvent of water and the above organic solvent; and preferably ethers (particularly preferably dioxane). The reaction temperature and reaction time vary depending on the starting compound, the solvent, the acid or base used, and the like, and are not particularly limited. Let react.

When the amino-protecting group is an aralkyl or aralkyloxycarbonyl, it is usually brought into contact with a reducing agent in an inert solvent (preferably by catalytic reduction at room temperature under a catalyst at room temperature). ) A method of removing or using an oxidizing agent is preferred.

The solvent used for the removal by catalytic reduction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; Aromatic hydrocarbons such as toluene, benzene, xylene; methyl acetate,
Esters such as ethyl acetate, propyl acetate, butyl acetate, diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n- Alcohols such as propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve; Such organic acids; water; a mixed solvent of the above solvent and water; preferably alcohols, ethers,
Organic acids or water (particularly preferably, alcohols or organic acids).

The catalyst used for the removal by catalytic reduction is not particularly limited as long as it is usually used for the catalytic reduction reaction.
Carbon, Raney-nickel, platinum oxide, platinum black, rhodium-
Aluminum oxide, triphenylphosphine-rhodium chloride, palladium-barium sulfate are used. The pressure is not particularly limited, but it is usually 1 to 10 atm. The reaction temperature and reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually carried out at 0 ° C to 100 ° C for 5 minutes to 24 hours.

The solvent used in the removal by oxidation is not particularly limited as long as it does not participate in the present reaction, but is preferably a water-containing organic solvent. Examples of such organic solvents include halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; nitriles such as acetonitrile, diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxy Ethers such as ethane, diethylene glycol dimethyl ether; ketones such as acetone; amides such as formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide; and sulfoxides such as dimethylsulfoxide; Preferred are halogenated hydrocarbons, ethers or sulfoxides (particularly preferred are halogenated hydrocarbons or sulfoxides).

The oxidizing agent to be used is not particularly limited as long as it is a compound used for oxidation. Preferably, potassium persulfate, sodium persulfate, ammonium cerium nitrate (CAN), 2,3- Dichloro-5,6-
Dicyano-p-benzoquinone (DDQ) is used.
The reaction temperature and the reaction time vary depending on the starting compound, the catalyst, the solvent and the like, but are usually carried out at 0 ° C to 150 ° C for 10 minutes to 24 hours.

When the protecting group for the amino group is an alkenyloxycarbonyl, the protecting group for the amino group is usually substituted with an aliphatic acyl, an aromatic acyl, an alkoxycarbonyl or a Schiff base. It is carried out by treating with a base in the same manner as the conditions for the removal reaction in the case of a methylene group. In the case of an allyloxycarbonyl group, the removal method using palladium and triphenylphosphine or nickel tetracarbonyl is particularly simple and can be carried out with few side reactions.

When a silyl is used as the protecting group for the hydroxyl group, a compound which generates a fluorine anion, such as tetrabutylammonium fluoride, hydrofluoric acid, hydrofluoric acid-pyridine or potassium fluoride, is usually used. Processing, or
Inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, phosphoric acid or acetic acid, formic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid It can be removed by treating with an organic acid. In addition, when removing with a fluorine anion, the reaction may be accelerated by adding an organic acid such as formic acid, acetic acid, or propionic acid.

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Preferably, diethyl ether or diisopropyl ether is used.
Ethers such as ter, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; nitriles such as acetonitrile and isobutyronitrile; organic acids such as acetic acid; water; The reaction temperature and the reaction time vary depending on the starting compound, the catalyst, the solvent, and the like.
0 ° C (preferably 10 ° C to 50 ° C) for 1 hour to 2 hours
Run for 4 hours.

When the protecting group for the hydroxyl group is an aralkyl or aralkyloxycarbonyl, it is usually contacted with a reducing agent in an inert solvent (preferably,
A method of removing by catalytic reduction at room temperature under a catalyst or a method of removing with an oxidizing agent is preferable. The solvent used for removal by catalytic reduction is not particularly limited as long as it does not participate in the present reaction, but aliphatic hydrocarbons such as hexane, heptane, ligroin, and petroleum ether; toluene, benzene, and xylene Aromatic hydrocarbons; esters such as ethyl acetate and propyl acetate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether;
, Ethanol, n-propanol, isopropanol
, N-butanol, isobutanol, t-butanol
Alcohols such as methyl, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; such as formamide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, and hexamethylphosphoric triamide. Amides; fatty acids such as formic acid and acetic acid; water; mixed solvents of the above solvents; and preferably alcohols (particularly preferably methanol).

As the catalyst used for the removal by the catalytic reduction, if it is usually used for the catalytic reduction reaction,
Although not particularly limited, for example, palladium-carbon, palladium-black, Raney-nickel, platinum oxide, platinum black, rhodium-aluminum oxide, triphenylphosphine-rhodium chloride, palladium-barium sulfate, and preferably palladium- Carbon. The pressure is not particularly limited,
Usually, it is performed at 1 to 10 atm. The reaction temperature and reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually 0 ° C to 100 ° C (preferably 20 ° C to 70 ° C).
° C), 5 minutes to 48 hours (preferably 1 hour to 24 hours)
Time).

The solvent used in the removal by oxidation is not particularly limited as long as it does not participate in the present reaction, but is preferably a water-containing organic solvent. Suitable examples of such organic solvents include ketones such as acetone, methylene chloride, chloroform, halogenated hydrocarbons such as carbon tetrachloride, nitriles such as acetonitrile, diethyl ether, tetrahydrofuran, and dioxane. And ethers, amides such as dimethylformamide, dimethylacetamide, and hexamethylphosphoric triamide, and sulfoxides such as dimethylsulfoxide.

The oxidizing agent to be used is not particularly limited as long as it is a compound used for oxidation. Preferably, potassium persulfate, sodium persulfate, ammonium cerium nitrate (CAN), 2,3- Dichloro-5,6-
Dicyano-p-benzoquinone (DDQ) is used.
The reaction temperature and the reaction time vary depending on the starting compound, the catalyst, the solvent and the like, but are usually carried out at 0 ° C to 150 ° C for 10 minutes to 24 hours.

In liquid ammonia or methanol
, Ethanol, n-propanol, isopropanol
, N-butanol, isobutanol, t-butanol
In alcohols such as alcohol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve at -78 ° C.
At 0 to 0 ° C, it can also be removed by the action of alkali metals such as metallic lithium and metallic sodium.

Furthermore, it can be removed by using an alkylsilyl halide such as aluminum chloride-sodium iodide or trimethylsilyl iodide in a solvent.
The solvent used is not particularly limited as long as it does not participate in this reaction, but preferably, methylene chloride,
Halogenated hydrocarbons such as chloroform and carbon tetrachloride; nitriles such as acetonitrile; mixed solvents of the above solvents. The reaction temperature and reaction time vary depending on the starting compound, the solvent and the like, but are usually 0 ° C to 50 ° C.
For 5 to 72 hours. Incidentally, when the reaction substrate has a sulfur atom, preferably, aluminum chloride-
Sodium iodide is used.

When the protecting group for a hydroxyl group is an aliphatic acyl group, an aromatic acyl group or an alkoxycarbonyl group, it is removed by treating with a base in a solvent. The base used in the above reaction is not particularly limited as long as it does not affect the other parts of the compound,
For example, alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate; alkali metal bicarbonates such as lithium hydrogen carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate; lithium hydroxide, sodium hydroxide;
Alkali metal hydroxides such as potassium hydroxide; metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide and potassium tert-butoxide; ammonia such as aqueous ammonia and concentrated ammonia-methanol And preferably alkali metal hydroxides, metal alkoxides or ammonia (particularly preferred are alkali metal hydroxides or metal alkoxides).

The solvent to be used is not particularly limited as long as it is used in a usual hydrolysis reaction. Examples of the solvent include diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether. Ethers; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve; water; mixed solvents of the above solvents are preferred. The reaction temperature and reaction time vary depending on the starting compound, the base to be used, the solvent, and the like, and are not particularly limited.
The heating is performed at 20 ° C. to 150 ° C. for 1 hour to 10 hours.

When the protecting group for a hydroxyl group is an alkoxymethyl group,
In the case of tetrahydropyranyls, tetrahydrothiopyranyls, tetrahydrofuranyls, tetrahydrothiofuranyls or substituted ethyls, they are usually removed by treating with an acid in a solvent. The acid used is not particularly limited as long as it is generally used as a Bronsted acid or Lewis acid, and preferably,
Hydrogen chloride; inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid; or Bronsted acid such as acetic acid, trifluoroacetic acid, methanesulfonic acid, organic acid such as p-toluenesulfonic acid: Lewis acid such as boron trifluoride But Dowex 5
Strongly acidic cation exchange resins such as 0 W can also be used.

The solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction.
Aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether; aromatic hydrocarbons such as benzene, toluene, xylene; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene,
Halogenated hydrocarbons such as dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate and diethyl carbonate; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether Such ethers; methanol, ethanol
Alcohols such as toluene, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve Ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; water; a mixed solvent of the above solvents; preferably ethers (particularly preferably tetrahydrofuran) or alcohols ( Particularly preferred is methanol). The reaction temperature and reaction time vary depending on the starting compound, the acid used, the solvent, and the like, but are usually -10 ° C to 20 ° C.
0 ° C (preferably 0 to 150 ° C) for 5 minutes to 48
Time (preferably 30 minutes to 10 hours).

When the protecting group for the hydroxyl group is an alkenyloxycarbonyl, the same conditions as those for the removal reaction when the protecting group for the hydroxyl group is the above-mentioned aliphatic acyl, aromatic acyl or alkoxycarbonyl are usually used. And by treating with a base. In the case of an allyloxycarbonyl group, in particular, palladium and triphenylphosphine or bis (methyldiphenylphosphine) (1,5-cyclooctadiene) iridium (I)
-The method of removing using hexafluorophosphate is simple and can be carried out with few side reactions.

The above-mentioned reaction of bringing the compound (VII) into contact with an acid or the catalytic reduction reaction of the compound (VII) may simultaneously remove the protecting groups for the amino group and / or the hydroxyl group. . In addition, an amino group and / or
Alternatively, the removal of the hydroxyl-protecting group can be carried out in any order by sequentially performing the desired removal reaction.

After completion of the reaction, the desired compound (Ia)
Is collected from the reaction mixture according to a conventional method. For example,
The reaction mixture is appropriately neutralized, and if insoluble matters are removed by filtration, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated. After drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate, etc., the solvent is distilled off. If necessary, the target compound obtained is eluted with a suitable eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds, and applying chromatography. Can be separated and purified.

[0152]

Embedded image

In the above formula, R ¹ , R ^1a , R ² , R ^2a , A and B have the same meanings as described above, X represents the halogen atom, and Y represents an oxygen atom or a sulfur atom. Is shown.

In the method B, R ³ in the compound (I) is
This is a step of producing a compound (Ib) which is a group having the formula (IV-2) or (IV-3) or a compound (Ic) which is a group having the formula (IV-1). Step B1 is a step for producing a compound having the general formula (IX), and after reacting the compound (V) with a base in the presence or absence (preferably in the presence) of an inert solvent, The reaction is performed by reacting with a compound having the general formula (VIII).

The base used in the above reaction includes, for example, alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate; alkali metal bicarbonates such as lithium hydrogen carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate; Alkali metal hydrides such as lithium hydride, sodium hydride and potassium hydride; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; lithium methoxide, sodium methoxide and sodium Alkali metal alkoxides such as ethoxide and potassium t-butoxide; triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N-
Dimethylamino) pyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-
Diazabicyclo [5.4.0] -7-undecene (DB
Organic amines such as U); preferably alkali metal hydrides (particularly preferably sodium hydride).

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the reaction. For example, aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; benzene Aromatic hydrocarbons such as toluene, xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; dimethylformamide;
Amides such as dimethylacetamide and hexamethylphosphoric triamide; or a mixed solvent of the above solvents;
Preferably, they are amides (particularly preferably, dimethylformamide).

The reaction temperature for reacting the compound (V) with a base varies depending on the starting compound, the base used, the solvent and the like, but is usually -50 ° C to 200 ° C (preferably 0 ° C).
To 120 ° C.). The reaction time for reacting the compound (V) with a base varies depending on the starting compound, the base used, the solvent, the reaction temperature and the like, but is usually from 15 minutes to 2 minutes.
4 hours (preferably 1 hour to 10 hours). The reaction temperature when reacting the compound (V) with the compound (VIII) is usually from -20 ° C to 200 ° C (preferably 0 ° C).
To 150 ° C.). Compound (V) and compound (VII)
The reaction time for reacting I) is usually 30 minutes to 48 hours (preferably 1 hour to 24 hours).

After completion of the reaction, the desired compound (IX) of this reaction
Is collected from the reaction mixture according to a conventional method. For example,
The reaction mixture is appropriately neutralized, and if insoluble matters are removed by filtration, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated. After drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate, etc., the solvent is distilled off. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

Step B2 is a step of producing a compound having the general formula (XI), in an inert solvent in the presence or absence of a catalyst such as sodium acetate, piperidinium acetate, piperidinium benzoate. The reaction is carried out below (preferably in the presence) by reacting compound (IX) with a compound having general formula (X).

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; benzene Aromatic hydrocarbons such as toluene, xylene; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; methyl acetate, ethyl acetate, propyl acetate, butyl acetate and diethyl carbonate. Esters such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol; Isobutanol, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; nitriles such as acetonitrile and isobutyronitrile; formamide, dimethylformamide, dimethylacetamide, hexamethyl Amides such as phosphoric acid triamide;
Or a mixed solvent of the above solvents; preferably, amides (particularly preferably, dimethylformamide or dimethylacetamide).

The reaction temperature varies depending on the starting compound, the catalyst used, the solvent and the like, but is usually from 0 ° C. to 200 ° C.
(Preferably 10 ° C. to 150 ° C.). The reaction time varies depending on the raw material compound, the catalyst used, the solvent, the reaction temperature and the like, but is usually from 1 hour to 50 hours (preferably,
2 hours to 24 hours).

After completion of the reaction, the desired compound (XI)
Is collected from the reaction mixture according to a conventional method. For example,
The reaction mixture is appropriately neutralized, and if insoluble matters are removed by filtration, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated. After drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate, etc., the solvent is distilled off. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

Step B3 is a step for producing a compound having the general formula (Ib), and the compound (X) is prepared in an inert solvent.
After the catalytic reduction reaction in I), R ^1a and R ^1
It is carried out by removing the protecting group for the amino group and / or the hydroxyl group in ^2a . The catalytic reduction reaction and the reaction for removing an amino group and / or a hydroxyl-protecting group if desired are carried out in the same manner as in the above-mentioned Method A, Step A2. Also, this step
After reacting the compound (XI) with the metal hydride, the reaction is also carried out by removing the protecting group for the amino group and / or the hydroxyl group in R ^1a and R ^2a if desired. Compound (X
The method of reacting I) with a metal hydride is described in WO 93/1.
309A can be carried out according to the method disclosed therein.

Step B4 is a step for producing a compound having the general formula (Ic).
This step is performed by removing the protecting group for the amino group and / or the hydroxyl group in R ^1a and R ^2a of the compound (XIa) wherein Y is a sulfur atom. It is carried out in the same manner as in the method of removing the hydroxyl-protecting group.

[0165]

Embedded image

In the above formula, R ¹ , R ^1a , R ² , R ^2a , A and B have the same meanings as described above.

Method C produces a compound (Id) in which R ³ is a group having the formula (IV-4) or a compound (Ie) in which R ³ is a group having the formula (IV-5) in the compound (I). Is the way. Step C1 is a step for producing a compound having the general formula (XII), which is carried out by reacting compound (IX) with hydroxylamine (hydrochloride) in an inert solvent and then contacting with a reducing agent. Will be

The inert solvent used for reacting compound (IX) with hydroxylamine (hydrochloride) is not particularly limited as long as it is inert to the reaction. For example, hexane, heptane, ligroin Aliphatic hydrocarbons such as petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; methyl acetate Esters such as ethyl acetate, propyl acetate, butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; methanol, ethanol and n-propanol -Isopropanol, n- Tano - le, isobutanol - Le, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; nitriles such as acetonitrile and isobutyronitrile; formamide, dimethylformamide, dimethylacetamide, hexamethyl Amides such as phosphoric acid triamide;
Water; or a mixed solvent of the above solvents; and preferably a mixed solvent with alcohols (particularly preferably, methanol or ethanol).

The reaction temperature for reacting the compound (IX) with hydroxylamine (hydrochloride) varies depending on the starting compound, the catalyst used, the solvent and the like, but is usually from -20 ° C to 200 ° C (preferably, 10 ° C to 120 ° C).
The reaction time for reacting the compound (IX) with hydroxylamine (hydrochloride) is based on the starting compound, the catalyst used,
Although it depends on the solvent, the reaction temperature, etc., it is usually 1 hour to 5 hours.
0 hours (preferably 2 hours to 24 hours).

The reducing agent used in the subsequent reaction is as follows:
For example, aluminum hydride compounds such as sodium borohydride, lithium borohydride, alkali metal borohydrides such as sodium cyanoborohydride, diisobutylaluminum hydride, lithium aluminum hydride, lithium triethoxide aluminum hydride And preferably alkali metal borohydrides (particularly preferably sodium borohydride).

The solvent used in contacting the reducing agent with the reducing agent in the latter reaction is not particularly limited as long as it is inert to the present reaction. Preferably, compound (IX) and hydroxylamine (hydrochloride) are used. ) Is the same as the solvent used in the reaction. The reaction temperature at the time of contacting with the reducing agent in the subsequent reaction, the starting compound, the reducing agent used,
Usually varies from -50 ° C to 200 ° C, depending on the solvent etc.
(Preferably 0 ° C. to 120 ° C.). The reaction time for contacting with the reducing agent in the subsequent reaction varies depending on the starting compound, the reducing agent used, the solvent, the reaction temperature and the like, but is usually 15 minutes to 24 hours (preferably 1 hour to 12 hours). ).

After completion of the reaction, the desired compound (XI)
I) is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and, if insolubles are present, they are removed by filtration. It is obtained by washing with water and the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate and the like, and distilling off the solvent. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

Step C2 is a step for producing a compound having the general formula (XIII), which is carried out by reacting compound (XII) with trimethylsilyl isocyanate in an inert solvent. The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. For example, hexane, heptane, ligroin, aliphatic hydrocarbons such as petroleum ether; benzene, toluene, Aromatic hydrocarbons such as xylene; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, carbon tetrachloride; such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether Ethers; amides such as formamide, dimethylformamide, dimethylacetamide, and hexamethylphosphoric triamide; or mixed solvents of the above solvents; preferably aromatic hydrocarbons, ethers or amides (particularly preferred) The Dieci Ether, tetrahydrofuran or dimethylformamide).

The reaction temperature varies depending on the starting compound, solvent and the like, but is usually -50 ° C to 200 ° C (preferably 0 ° C
To 120 ° C.). The reaction time varies depending on the starting compound, solvent, reaction temperature and the like, but is usually from 15 minutes to 4 minutes.
8 hours (preferably 1 hour to 24 hours).

After completion of the reaction, the desired compound of the present reaction (XII
I) is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and, if insolubles are present, they are removed by filtration. It is obtained by washing with water and the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate and the like, and distilling off the solvent. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

Step C3 is a step for producing a compound having the general formula (Id), and in an inert solvent, the compound (X)
After the reaction of III) with the carbonylating agent, the reaction is optionally carried out by removing the protecting group for the amino group and / or the hydroxyl group in R ^1a and R ^2a . The carbonylating agent used in the above reaction is not particularly limited as long as it is usually used in the carbonylation reaction, and examples thereof include phosgene, diphosgene, triphosgene, and 1,1′-carbonyldiimidazole.

The inert solvent used in reacting the compound (XIII) with the carbonylating agent is not particularly limited as long as it is inert to the reaction. For example, hexane, heptane, ligroin, petroleum ether Aliphatic hydrocarbons such as benzene, toluene, xylene; chloroform, dichloromethane,
Halogenated hydrocarbons such as 1,2-dichloroethane and carbon tetrachloride; esters such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate and diethyl carbonate; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane Ethers such as diethylene glycol dimethyl ether; nitriles such as acetonitrile and isobutyronitrile;
Amides such as formamide, dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; or a mixed solvent of the above solvents; preferably, aromatic hydrocarbons, halogenated hydrocarbons, ethers or amides (Particularly preferably, tetrahydrofuran, dioxane or dimethylformamide).

The reaction temperature for reacting the compound (XIII) with the carbonylating agent varies depending on the starting compound, the solvent and the like, but is usually -50 ° C to 200 ° C (preferably 0 ° C).
To 120 ° C.). The reaction time for reacting the compound (XIII) with the carbonylating agent varies depending on the starting compound, the solvent, the reaction temperature and the like, but is usually from 15 minutes to 5 minutes.
0 hours (preferably 1 hour to 24 hours). If desired, the method for removing the protecting group for the amino group and / or the hydroxyl group in R ^1a and R ^2a is performed in the same manner as the method for removing the protecting group for the amino group and / or the hydroxyl group in the above-mentioned Method A, Step A2.

After the completion of the reaction, the target compound (Id) of this reaction
Is collected from the reaction mixture according to a conventional method. For example,
The reaction mixture is appropriately neutralized, and if insoluble matters are removed by filtration, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated. After drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate, etc., the solvent is distilled off. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

Step C4 is a step of producing a compound having the general formula (Ie), and the compound (X) is prepared in an inert solvent.
III) The removal of the protecting group for the amino group and / or the hydroxyl group in R ^1a and R ^2a in this step is carried out by removing the protecting group for the amino group and / or the hydroxyl group in the above-mentioned step A2 of the method A. The same is done.

Step C5 is a step of separately preparing a compound having the general formula (Id), and converting the compound (XII) into N- After reacting with (chlorocarbonyl) isocyanate, the reaction is carried out by removing a protecting group for an amino group and / or a hydroxyl group in R ^1a and R ^2a if desired.

The inert solvent used when reacting compound (XII) with N- (chlorocarbonyl) isocyanate is not particularly limited as long as it is inert to the reaction. For example, hexane, heptane, Aliphatic hydrocarbons such as ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; acetic acid Esters such as methyl, ethyl acetate, propyl acetate, butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; nitriles such as acetonitrile and isobutyronitrile Kind Amides such as formamide, dimethylformamide, dimethylacetamide, and hexamethylphosphoric triamide; or a mixed solvent of the above solvents; preferably, aromatic hydrocarbons, halogenated hydrocarbons, ethers or amides (Particularly preferably, tetrahydrofuran, dioxane or dimethylformamide).

The reaction temperature depends on the starting compound, the solvent and the like, but is usually from -50 ° C to 100 ° C (preferably -2 ° C.
0 ° C to 50 ° C). The reaction time varies depending on the starting compound, solvent, reaction temperature and the like, but is usually from 15 minutes to 5 minutes.
0 hours (preferably 1 hour to 24 hours). If desired, the method for removing the protecting group for the amino group and / or the hydroxyl group in R ^1a and R ^2a is performed in the same manner as the method for removing the protecting group for the amino group and / or the hydroxyl group in the above-mentioned Method A, Step A2.

After completion of the reaction, the desired compound (Id) of this reaction
Is collected from the reaction mixture according to a conventional method. For example,
The reaction mixture is appropriately neutralized, and if insoluble matters are removed by filtration, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated. After drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate, etc., the solvent is distilled off. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

[0185]

Embedded image

In the above formula, R ² , R ^2a , R ⁴ , R ⁵ , R
⁶ , A, B, D, E and Y have the same meanings as described above, and R ^4a is an amino group and / or a hydroxyl group which may be protected, wherein the amino group and / or the hydroxyl group included in the definition of the group of R ⁴ Group and /
And R ^5a is the same as the group in the definition of the group R ⁴ , ^except that the amino group and / or the hydroxyl group included in the definition of the group R ⁵ may be a protected amino group. and / or other a hydroxyl group, indicates the same groups in the definition of group R ^5, R ⁷ represents a formyl group, a carboxy group or a C ₂ -C ₇ alkoxycarbonyl group, Boc
Represents a t-butoxycarbonyl group.

In the method D, in the compound (I), R ¹ is a group having the general formula (II), and R ³ is a group represented by the formula (IV-2)
Or compound (Ifa), which is a group having (IV-3), or R ¹ is a group having the general formula (III), and R ³ is a group having the formula (IV-2) or (IV-3). This is a method for producing a compound (Ifb). Step D1 is a step for producing a compound having the general formula (Ifa). After reacting the compound having the general formula (XIV) with the compound having the general formula (XVa), R ^2a and R ^{4a are} optionally added. And the removal of the protecting group for the amino group and / or the hydroxyl group in R ^5a .

When R ⁷ in the compound (XIV) is a formyl group, after reacting the compound (XIV) with the compound (XVa) in an inert solvent, a t-butoxycarbonyl group which is a protecting group for an amino group is added. This is carried out by removing the ring with an acid, closing the ring, and further reacting with an oxidizing agent.

This step can be obtained by reacting compound (XIV) with compound (XVa), and then removing the t-butoxycarbonyl group, which is a protecting group for the amino group, with an acid to effect ring closure. The intermediate can also be isolated and purified, and then contacted with an oxidizing agent.

The inert solvent used in reacting the compound (XIV) with the compound (XVa) is not particularly limited as long as it is inert to the present reaction. For example, hexane, heptane, ligroin, petroleum Aliphatic hydrocarbons such as ether; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol Alcohols such as n-propanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve. Le; formamide, Amides such as methylformamide, dimethylacetamide, and hexamethylphosphoric acid triamide; acids such as acetic acid and propionic acid; sulfoxides such as dimethylsulfoxide; sulfolane; or a mixed solvent of the above solvents; Ethers (particularly preferably tetrahydrofuran).

The reaction temperature at the time of reacting the compound (XIV) with the compound (XVa) depends on the starting compound, the base used, the solvent and the like, but is usually 0 ° C. to 200 ° C.
(Preferably 10 ° C. to 120 ° C.). Compound (X
The reaction time for the reaction of (IV) with the compound (XVa) varies depending on the starting compound, the base used, the solvent, the reaction temperature and the like, but is usually 1 hour to 50 hours (preferably,
5 hours to 24 hours). The method for removing the t-butoxycarbonyl group which is an amino-protecting group using an acid includes a method for removing the amino-protecting group using an acid in the case where the amino-protecting group is an alkoxycarboxy in step A2 of Method A. The same is done.

The oxidizing agent used in the above reaction is not particularly limited as long as it is usually used in the oxidizing reaction. Examples thereof include manganese oxides such as potassium permanganate and manganese dioxide; Ruthenium oxides such as ruthenium; selenium compounds such as selenium dioxide; iron compounds such as iron chloride; osmium such as osmium tetroxide, potassium osmate dihydrate (K ₂ OsO ₄ .2H ₂ O) Compounds: Silver compounds such as silver oxide; Mercury compounds such as mercury acetate; Lead oxide compounds such as lead oxide and lead tetraacetate; Chromium such as potassium chromate, chromate-sulfuric acid complex, and chromate-pyridine complex Acid compounds, inorganic metal oxidizing agents such as cerium compounds such as ammonium cerium nitrate (CAN); halogen molecules such as chlorine molecules, bromine molecules and iodine molecules; Periodic acids such as sodium iodate; ozone; aqueous hydrogen peroxide; nitrous acid compounds such as nitrous acid; chlorite compounds such as potassium chlorite and sodium chlorite; potassium persulfate, sodium persulfate Inorganic oxidizing agents such as persulfuric acid compounds; reagents used for DMSO oxidation (complexes of dimethyl sulfoxide and dicyclohexylcarbodiimide, oxalyl chloride, acetic anhydride or phosphorus pentoxide, or pyridine-sulfuric anhydride complexes); t -Combinations of peroxides such as butyl hydroperoxide with vanadium or molybdenum complexes; stable cations such as triphenylmethyl cation;
Combinations of succinimides such as N-bromosuccinimide and alkali; oxiranes such as dimethyldioxirane; hypochlorous compounds such as t-butyl hypochlorite; azos such as azodicarboxylate Dicarboxylic acid compounds; peracids such as m-chloroperbenzoic acid and perphthalic acid; disulfides such as dimethyl disulfide, diphenyl disulfide and dipyridyl disulfide and triphenylphosphine; nitrites such as methyl nitrite; Organic oxidizing agents such as tetrahalogenated carbon such as methane bromide and quinone compounds such as 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ); Particularly preferred is iodine molecule).

The solvent used in contact with the oxidizing agent is not particularly limited as long as it is inert to the present reaction. Preferably, the solvent is used when reacting compound (XIV) with compound (XVa). The solvent used. The reaction temperature and reaction time when contacting with an oxidizing agent are the same as the reaction temperature and reaction time when reacting compound (XIV) with compound (XVa).

When R ⁷ is a carboxy group in compound (XIV), a compound having the general formula (XIV) or a reactive derivative thereof (acid halides, active esters or mixed acid anhydrides) in an inert solvent And the general formula (XV
After reacting the compound having a) or an acid addition salt thereof (for example, a mineral acid salt such as hydrochloride, nitrate, sulfate),
This is carried out by removing the t-butoxycarbonyl group, which is a protecting group for the amino group, using an acid and closing the ring.

In this step, after the amide compound as an intermediate is isolated and purified, the t-butoxycarbonyl group, which is a protecting group for the amino group, is removed using an acid and the ring is closed in the same manner as in the above reaction. It is also done by doing.

In the acid halide method, compound (XIV) is halogenated (for example, thionyl chloride, thionyl bromide, oxalic chloride, oxalic dichloride) in an inert solvent.
Acid oxychloride, phosphorus trichloride, phosphorus pentachloride, etc.) to produce an acid halide, and the acid halide and compound (XVa) or an acid addition salt thereof in an inert solvent in the presence of a base or The reaction is carried out in the absence (preferably in the presence).

Bases used in the above reaction include, for example, alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate; alkali metal bicarbonates such as lithium hydrogen carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate; Alkali metal hydrides such as lithium hydride, sodium hydride and potassium hydride; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; lithium methoxide, sodium methoxide and sodium Alkali metal alkoxides such as ethoxide and potassium t-butoxide; triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N-
Dimethylamino) pyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-
Diazabicyclo [5.4.0] -7-undecene (DB
Organic amines such as U), preferably organic amines (particularly preferably triethylamine).

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction.
Aliphatic hydrocarbons such as hexane, heptane, ligroin or petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogens such as dichloromethane, chloroform, 1,2-dichloroethane and carbon tetrachloride Hydrocarbons; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; ketones such as acetone; amides such as formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide Kind;
Sulfoxides such as dimethylsulfoxide; sulfolane; and preferably halogenated hydrocarbons, ethers or amides (particularly preferably, dichloromethane, chloroform, tetrahydrofuran or dimethylformamide).

The reaction temperature varies depending on the starting compounds, reagents and the like, but the reaction between the halogenating agent and the compound (XIV) and the reaction between the acid halides and the compound (XVa) or the acid addition salt thereof are usually -20 ° C. To 150 ° C., and preferably, the reaction between the halogenating agent and the compound (XIV) is −1
0 ° C. to 100 ° C., and acid halides and a compound (XV
a) or its acid addition salt is reacted at -20 ° C to 100 ° C.
° C. The reaction time varies depending on the starting compound, the reagent, the reaction temperature and the like, but the reaction between the halogenating agent and the compound (XIV) and the reaction between the acid halides and the compound (XVa) or the acid addition salt thereof are usually from 30 minutes to 30 minutes. 80 hours (preferably 1 hour to 48 hours).

In the active ester method, the compound (XIV) is reacted with an active esterifying agent in an inert solvent to produce active esters, and then, in an inert solvent in the presence or absence of a base (preferably). In the presence of), compound (XVa) or an acid addition salt thereof.

The active esterifying agent used in the above reaction includes, for example, N-hydroxysuccinimide, 1-hydroxybenzotriazole, N-hydroxy-5-norbornene-2,3-dicarboximide, and the like. Compounds; disulfide compounds such as dipyridyl disulfide; carbodiimides such as dicyclohexylcarbodiimide; carbonyldiimidazole; triphenylphosphine;

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether. Aromatic hydrocarbons such as benzene, toluene and xylene; dichloromethane,
Halogenated hydrocarbons such as 1,2-dichloroethane and carbon tetrachloride; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; ketones such as acetone; formamide, dimethylformamide Amides such as dimethylacetamide, hexamethylphosphoric triamide; sulfoxides such as dimethylsulfoxide; sulfolane;
And preferably ethers or amides (particularly preferred are dioxane, tetrahydrofuran or dimethylformamide).

Examples of the base used in the above reaction include the same bases as those used in the above-mentioned acid halide method. The reaction temperature varies depending on the starting compounds, reagents, and the like, but is usually -7
0 ° C to 150 ° C (preferably -10 ° C to 100 ° C)
In the reaction of the active ester with the compound (XVa) or an acid addition salt thereof, the temperature is −20 ° C. to 100 ° C. (preferably 0 ° C. to 50 ° C.). The reaction time varies depending on the starting compound, the reagent, the reaction temperature and the like, but is usually 30 minutes to 80 hours (preferably 30 minutes to 80 hours) in both the active esterification reaction and the reaction of the active ester with the compound (XVa) or the acid addition salt thereof. , 1 hour to 48 hours).

In the mixed acid anhydride method, the compound (X) is prepared in an inert solvent in the presence or absence (preferably in the presence) of a base.
The mixed acid anhydride is produced by reacting IV) with a mixed acid anhydride agent, and then reacting the mixed acid anhydride with the compound (XVa) or an acid addition salt thereof in an inert solvent. Bases used in the above reaction include, for example, alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate; alkali metal bicarbonates such as lithium hydrogen carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate; lithium hydride Alkali metal hydrides such as sodium hydride, potassium hydride; lithium hydroxide;
Alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkali metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide and potassium t-butoxide; triethylamine, tributylamine, diisopropylethylamine;
N-methylmorpholine, pyridine, 4- (N, N-dimethylamino) pyridine, N, N-dimethylaniline,
N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo [5. 4.0] -7-undecene (DB
Organic amines such as U), preferably organic amines (particularly preferably triethylamine).

Examples of the mixed anhydride agent used in the above reaction include C ₁ -C ₄ alkyl halides such as ethyl chlorocarbonate and isobutyl chlorocarbonate; C ₁ -C ₅ alkanoyl such as pivaloyl chloride. Halide; di-C ₁ -C ₄ alkyl or di-C ₆ -C ₁₄ arylcyanophosphate such as diethyl cyanophosphonate, diphenyl cyanophosphonate, preferably di-C ₁ -C ₄ alkyl or di-C ₆ —C ₁₄ arylcyanophosphate (particularly preferably diethyl cyanophosphonate).

The inert solvent used for producing the mixed acid anhydrides is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. For example, hexane, heptane, ligroin Aliphatic hydrocarbons such as petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and carbon tetrachloride; diethyl ether Ethers such as, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; ketones such as acetone; amides such as formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide; and dimethyl sulfoxide Sulfoxy S; sulfolane; are, preferably, ethers or amides (particularly preferably include tetrahydrofuran or dimethylformamide) it is.

The reaction temperature in the reaction for producing the mixed acid anhydrides varies depending on the starting compounds, reagents and the like.
It is -50 ° C to 100 ° C (preferably 0 ° C to 60 ° C).

The reaction time in the reaction for producing the mixed acid anhydrides varies depending on the starting compounds, reagents, reaction temperature and the like, but is usually 30 minutes to 72 hours (preferably 1 hour to 24 hours). is there.

The reaction between the mixed acid anhydrides and the compound (XVa) or an acid addition salt thereof is carried out in an inert solvent in the presence or absence (preferably in the presence) of a base and used. The base and the inert solvent are the same as those used in the reaction for producing the mixed anhydrides described above. The reaction temperature in the reaction between the mixed acid anhydrides and the compound (XVa) or an acid addition salt thereof varies depending on the starting compounds, reagents and the like, but is usually from -30 ° C to 100 ° C (preferably from 0 ° C to 80 ° C). ° C). The reaction time in the reaction of the mixed acid anhydrides with the compound (XVa) or an acid addition salt thereof varies depending on the starting compound, the reagent, the reaction temperature and the like, but is usually 5 minutes to 24 hours (preferably 30 minutes). To 16
Time). In the case where di C ₁ -C ₄ alkyl cyanophosphoric acid or di C ₆ -C ₁₄ aryl cyanophosphoric acid is used in this reaction, the compound (X) is added in the presence of a base.
IV) can be directly reacted with compound (XVa).

The method of removing the t-butoxycarbonyl group which is a protecting group for the amino group with an acid to effect ring closure is described in the above A.
It is carried out in the same manner as the method of removing with an acid when the amino-protecting group is an alkoxycarboxy in step A2 of the method.

In the compound (XIV), R ⁷ is C ₂ -C
_{7 When} it is an alkoxycarbonyl group, after reacting compound (XIV) with compound (XVa) in the presence or absence (preferably absence) of an inert solvent or in the presence or absence of a base T- which is an amino-protecting group using an acid
This is carried out by removing the butoxycarbonyl group and closing the ring.

In this step, after the amide compound as an intermediate is isolated and purified, the t-butoxycarbonyl group, which is a protecting group for the amino group, is removed with an acid in the same manner as in the above reaction, followed by ring closure. It is also done by doing.

The base used in the reaction for reacting the compound (XIV) with the compound (XVa) includes, for example, alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate; lithium hydrogen carbonate, sodium hydrogen carbonate, carbonate Alkali metal bicarbonates such as potassium hydrogen; alkali metal hydrides such as lithium hydride, sodium hydride, potassium hydride; lithium hydroxide;
Alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkali metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide and potassium t-butoxide; triethylamine, tributylamine, diisopropylethylamine;
N-methylmorpholine, pyridine, 4- (N, N-dimethylamino) pyridine, N, N-dimethylaniline,
N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo [5. 4.0] -7-undecene (DB
Organic amines such as U), preferably organic amines (particularly preferably triethylamine).

The inert solvent used in the reaction for reacting the compound (XIV) with the compound (XVa) is not particularly limited as long as it is inert to this reaction. Aliphatic hydrocarbons such as ether; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol Alcohols such as n-propanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve. Le; formamide Dimethylformamide, dimethylacetamide, amides such as hexamethylphosphoric triamide; or a mixed solvent of the above solvents; is, preferably,
Ethers or amides (particularly preferred are tetrahydrofuran, dioxane or dimethylformamide).

The reaction temperature depends on the starting compound, the base used, the solvent and the like, but is usually from 0 ° C. to 200 ° C.
(Preferably 50 ° C. to 150 ° C.). The reaction time varies depending on the starting compound, the base used, the solvent, the reaction temperature and the like, but is usually 1 hour to 50 hours (preferably
5 hours to 24 hours). The method of removing the t-butoxycarbonyl group, which is an amino-protecting group, using an acid and closing the ring is performed by using an acid when the amino-protecting group in step A2 of Method A is an alkoxycarboxy group. It is performed in the same way as the method.

If desired, the method for removing the protecting group for the amino group and / or the hydroxyl group in R ^2a , R ^4a and R ^5a includes the method for removing the protecting group for the amino group and / or the hydroxyl group in the above-mentioned Method A, Step A2. The same is done.

After the completion of the reaction, the target compound (If
a) is collected from the reaction mixture in a conventional manner. For example, the reaction mixture is appropriately neutralized, and, if insolubles are present, they are removed by filtration. It is obtained by washing with water and the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate and the like, and distilling off the solvent. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

Step D2 is a step for producing a compound having the general formula (Ifb), and is carried out in the same manner as in the above-mentioned Method D, step D1 to obtain a compound having the general formula (XIV) This is a step carried out by reacting the compound having the compound and then removing the protecting group for the amino group and / or the hydroxyl group in R ^2a , R ^4a and R ^5a if desired.

Compounds (Ia), (Ib), (Ic) and (Ic) obtained by the above methods A, B, C and D
d) When R ^{4 of} (Ie), (Ifa) and (Ifb) is a phenyl group or a pyridyl group substituted with an amino group, alkylation, arylation, aralkylation or acylation may be further performed on the amino group, if desired. Can be performed. These reactions are known or are readily prepared according to known or analogous methods [The Chemistry of the
Amino Group, chapter6, 1968, John Wiley & Sons, T
he Chemistry of the Amino Group, chapter2, 1970, J
ohn Wiley & Sons etc. ].

Starting compounds (V), (V '), (VI),
(VIII), (X), (XIV), (XVa) and (XVb) are known or are easily produced according to known methods or methods analogous thereto.

Starting compounds (V), (V '), (XI
V), (XVa) and (XVb) can also be produced, for example, by the following method.

[0222]

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In the above formula, R ^4a , R ^5a , R ⁶ , R ⁷ , A,
B, D, E and Boc have the same meanings as described above.

Method E is a process for producing compounds (Va) and (Vb). The step E1 is a step for producing a compound (Va), in which the compound having the general formula (XVI) is reacted with the compound (XVa), and a t-butoxycarbonyl group which is a protecting group for an amino group is reacted with an acid. This is done by removing and closing the ring. This step is the same as the method of reacting compound (XIV) with compound (XVa) in the above-mentioned Method D Step D1 to remove the t-butoxycarbonyl group which is a protecting group for the amino group using an acid, and to close the ring. Done in In particular, when E in the compound (XVa) is a nitrogen atom, the ring-closing method is preferably carried out in a large excess of the compound (XVI) in the absence of a solvent.

Step E2 is a step for producing a compound (Vb). The compound (XVI) is reacted with the compound (XVb), and the t-butoxycarbonyl group which is a protecting group for an amino group is removed with an acid. It is done by doing. In this step, the compound (XIV) and the compound (XVa) in the case where R ⁷ is a carboxy group in the above-mentioned Method D Step D1 are reacted with an acid to use a t-butoxycarbonyl group which is an amino-protecting group. Is performed in the same manner as in the method for removing. The ring-closing method is also carried out in the same manner as in the above-mentioned Method D, Step D1. However, when E is a nitrogen atom in compound (XVa), compound (XVI) is preferably used in a large excess in the absence of a solvent. Done.

After completion of the reaction, the desired compound (Va)
And (Vb) are collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and, if insolubles are present, they are removed by filtration. It is obtained by washing with water and the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate and the like, and distilling off the solvent. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

[0227]

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In the above formula, R ^2a , R ⁷ , R ⁸ , A, B, X
And Y have the same meanings as described above, and R ^7a is a formyl group or a carboxy group in which the formyl group or carboxy group included in the definition of R ⁷ is optionally protected,
The same groups as the groups in the definition of R ⁷ are shown.

In the above, the “protecting group” of the “optionally protected formyl group” is not particularly limited as long as it is a protecting group for a formyl group used in the field of organic synthetic chemistry.
For example, the above C ₁ -C such as dimethoxymethyl, diethoxymethyl, dipropoxymethyl, dibutoxymethyl
Methyl group substituted with ₆ alkoxy, 1,3-dioxan-2-yl, 1,3-dioxolan-2-yl, 1,
3-dithian-2-yl, 1,3-dithiolan-2-yl, preferably dimethoxymethyl, diethoxymethyl, 1,3-dioxolan-2-yl or 1,3-dithian-2-yl It is.

In the above, the “protecting group” of the “optionally protected carboxy group” is not particularly limited as long as it is a protecting group for a carboxy group used in the field of organic synthetic chemistry. C ₁ -C such as, propyl, isopropyl, butyl, s-butyl, t-butyl
₆ alkyl group, benzyl, phenethyl, 3-phenylpropyl, 1-naphthylmethyl, diphenylmethyl, triphenylmethyl, 4-methylbenzyl, 4-methoxybenzyl, 4-nitrobenzyl, 4-fluorobenzyl,
C ₁ -C ₆ alkyl, such as 4-cyanobenzyl, C ₁
-C ₆ alkoxy, nitro, halogen or cyano 1 may be substituted with substituted with 1-3 C ₆ -C ₁₀ aryl C ₁ -C ₆ alkyl group, preferably, C ₁
—C ₆ alkyl or benzyl.

Method F is a method for producing compound (XIV). Step F1 is a step of producing compound (XIV), which is carried out in an inert solvent in the presence of a base using a compound represented by the general formula (XV)
After reacting the compound having the formula II) with the compound having the general formula (XVIII), when the formyl group or the carboxy group in R ^7a is a protected formyl group or a carboxy group, the protecting group is removed. Will be

The base used when reacting the compound having the general formula (XVII) with the compound having the general formula (XVIII) is the same as that used in the above-mentioned Method B, Step B1, and is preferably An alkali metal hydride (particularly preferably sodium hydride). The solvent used when the compound having the general formula (XVII) is reacted with the compound having the general formula (XVIII) is the same as that used in the above-mentioned Method B, Step B1, and preferably an amide. Or an amide and another mixed solvent (particularly preferably dimethylformamide). The reaction temperature at the time of reacting the compound having the general formula (XVII) with the compound having the general formula (XVIII) varies depending on the starting compound, the base used, the solvent and the like, but is usually -50 ° C to 200 ° C (preferably Is from 0 ° C. to 120 ° C.). The reaction time when the compound having the general formula (XVII) is reacted with the compound having the general formula (XVIII) varies depending on the starting compound, the base used, the solvent, the reaction temperature, and the like, but is usually 30 minutes to 24 hours. (Preferably 1 hour to 10 hours).

The removal of the protecting group for the formyl group or the carboxy group as desired depends on the kind thereof, and is generally a method well known in the art of synthetic organic chemistry, for example, TWGree.
n, (Protective Groups in Organic Synthesis), John
Wiley &Sons; JFWMcomie, (Protective Groups in
Organic Synthesis), which can be performed according to Plenum Press.

Further, a compound wherein R ⁷ of compound (XIV) or R ^7a of compound (XVIII) is a carboxy group,
The compound can be easily produced from a compound wherein R ⁷ or R ^7a is a formyl group or a protected formyl group according to a conventional method. After completion of the reaction, the target compound (XIV) of the reaction is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and if insolubles are present, they are removed by filtration, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated.
It is obtained by washing with water and the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate and the like, and distilling off the solvent. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

[0235]

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In the above formula, R ^2a , R ⁷ , R ^7a , A, B, X
And Y have the same significance as described above, and R ⁹ represents a carboxy-protecting group (having the same significance as described above).

The method G is a method for producing the compound (XIV) separately from the method F. The step G1 is represented by the general formula (XXI)
Is a step of producing a compound having, in an inert solvent,
The reaction is carried out by reacting a compound having the general formula (XIX) with a compound having the general formula (XX) in the presence of a base, and this step is carried out in the same manner as the above-mentioned Method F, Step F1.

Step G2 is a step for producing a compound having the general formula (XXII), and is carried out by reducing the compound (XXI). This reaction is a catalytic reduction reaction or a general nitro group reduction method, zinc-acetic acid method, tin-acetic acid method.
It is performed by using an alcohol method or a tin-hydrochloric acid method.

Step G3 is a step for producing a compound having the general formula (XXIII),
This is achieved by performing a Meerwein Arylation reaction. The Meerwein Arylation reaction is described in JP-A-55-2265.
No. 7 (US Pat. No. 4,258,193) and the method of S. Oae et al. [Bull. Chem. Soc. Jpn., 53, 1065 (1980) and the like. The method is performed according to the method described in [1].

Step G4 is a step for producing a compound (XIV), which comprises the compound (XXIII) and a compound of the general formula (XXI)
The reaction is carried out by reacting with a compound having V), hydrolyzing and, if desired, removing a formyl group or a carboxy group protecting group in the definition of R ^7a .

Compound (XXIII) and general formula (XXI)
The reaction of hydrolyzing after reacting with a compound having V) is described in JP-A-55-22657 (USP4258).
This is performed according to the method described in 193).

The method of removing the formyl or carboxy protecting group in the definition of R ^7a is the same as the method of removing the formyl or carboxy protecting group in the above-mentioned Method F.

After completion of the reaction, the desired compound (XI)
V) is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and, if insolubles are present, they are removed by filtration. It is obtained by washing with water and the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate and the like, and distilling off the solvent. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

[0244]

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In the above formula, R ^4a , R ^5a , R ⁶ , D, E, X
And Boc have the same meaning as described above.

In Method H, Compounds (XVa) and (XVb)
It is a method of manufacturing. The step H1 is performed according to the general formula (XXV)
IIa), wherein a compound having the general formula (XXV) is converted to a compound of the general formula (XXV) in an inert solvent in the presence of a base.
This step is carried out by reacting the compound with XVIa), and this step is carried out in the same manner as in the above-mentioned Method F, Step F1.

The step H2 is a step for producing a compound (XVa), which is carried out by reducing the compound (XXVIIa). This step is carried out in the same manner as in the G method step G2.

Step H3 is a step for producing a compound (XXVIIb). The compound having the compound (XXV) is reacted with a compound of the formula (XXVIb) in an inert solvent in the presence of a base.
This step is performed in the same manner as in the above-mentioned Method F, Step F1.

Step H4 is a step of producing compound (XVb), which is carried out by reducing compound (XXVIIb). This step is carried out in the same manner as in the above-mentioned Method G, Step G2.

After completion of the reaction, the desired compound (XV
a) and (XVb) are collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and, if insolubles are present, they are removed by filtration. It is obtained by washing with water and the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate and the like, and distilling off the solvent. If necessary, the obtained target compound is subjected to a conventional method, for example, recrystallization,
Ordinary methods such as reprecipitation can be separated and purified by appropriately combining methods commonly used for separation and purification of organic compounds, applying chromatography, and eluting with an appropriate eluent.

[0251]

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In the above formula, R ^5a , R ⁶ , E, X and Boc
Has the same meaning as described above.

In Method I, Compounds (XXVIa) and (XXVIa)
VIb).

Step I1 is a step for producing a compound having the general formula (XXIXa),
This is carried out by protecting the amino group of the compound having Ia) with a t-butoxycarbonyl group, which is generally a method well known in the art of synthetic organic chemistry, for example, TW.
Green, (Protective Groups in Organic Synthesis),
John Wiley &Sons; JFWMcomie, (Protective Group
s in Organic Synthesis), which can be performed according to Plenum Press.

Step I2 is a step for producing a compound (XXVIa), which is carried out by reacting the compound (XXIXa) with a compound having the general formula (XXX) in an inert solvent in the presence of a base. The base used in the above reaction is the same as that used in the above-mentioned Method B, Step B1, and is preferably an alkali metal hydride (particularly preferably sodium hydride). The solvent used in the above reaction is the same as that used in the above-mentioned Method B, Step B1, and is preferably an ether or an amide (particularly preferably, tetrahydrofuran, dioxane or dimethylformamide). is there.

The reaction temperature varies depending on the starting compound, the base used, the solvent and the like, but is usually from -50 ° C to 200 ° C.
° C (preferably 0 ° C to 120 ° C). The reaction time varies depending on the starting compound, the base used, the solvent, the reaction temperature and the like, but is usually 30 minutes to 24 hours (preferably 1 hour to 10 hours).

Step I3 is a step for producing a compound having the general formula (XXIXb),
This step is carried out by protecting the amino group of the compound having Ib) with a t-butoxycarbonyl group, and this step is carried out in the same manner as in the above-mentioned Method I, Step I1.

Step I4 is a step for producing a compound (XXVIb), which is carried out by reacting the compound (XXIXb) with a compound having the general formula (XXX) in an inert solvent in the presence of a base. This step is the same as the method I-12
It is performed in the same manner as the process.

After the completion of the reaction, the desired compound (XXV)
Ia) and (XXVIb) are collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized,
If any insoluble matter is removed by filtration,
Add an immiscible organic solvent such as water and ethyl acetate, separate the organic layer containing the target compound, wash with water, etc., dry over anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate, etc., and evaporate the solvent. Obtained by leaving. If necessary, the obtained target compound is eluted with an appropriate eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds as appropriate and applying chromatography. Can be separated and purified.

[0260]

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In the above formula, R ^5a , R ⁶ , D, E and Boc
Has the same meaning as described above; R ¹⁰ represents a hydrogen atom or a triphenylmethyl group;

[0262]

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Is a phenyl group which may be substituted by 1 to 4 groups selected from the substituent group α or 1 to 3 pyridyl groups which may be substituted by a group selected from the substituent group α. Represents a group.

Method J is a method for producing a compound (XVd) or (XVf) in which R ^4a is a phenyl group or a pyridyl group substituted with an optionally protected tetrazolyl group separately from Method H.

Step J1 is a step for producing a compound having the general formula (XVd). In an inert solvent, the compound (XVa) is a compound wherein R ^4a is a phenyl group or a pyridyl group in which R ^4a is substituted by a cyano group. After reacting (XVc) with an azide compound, if necessary, the reaction is carried out by protecting the tetrazolyl group of the obtained compound.

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; benzene Aromatic hydrocarbons such as toluene, xylene; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, carbon tetrachloride; nitriles such as acetonitrile; diethyl ether, diisopropyl ether, tetrahydrofuran; Ethers such as dioxane, dimethoxyethane, diethylene glycol dimethyl ether; ketones such as acetone; amides such as formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide; and dimethylsulfoxide Sulfoxide such; a and, preferably an aromatic hydrocarbon (particularly preferably toluene).

The azide compound used in the above reaction is, for example, a diaryl phosphate azide derivative such as diphenyl phosphate azide; a trialkylsilyl azide such as trimethylsilyl azide or triethylsilyl azide, or sodium azide or potassium azide. Alkali metal azides; trialkyltin azides such as tri-n-butyltin azide; and preferably trialkyltin azide (particularly preferably tri-n-butyltin azide).

In the above reaction, the azide compound may be used alone, for example, trimethylsilyl trifluoromethane.
Trialkylsilyl triflates such as triethylsilyl triflate, trifluoroborane ether
, Aluminum chloride and zinc chloride.

The reaction temperature varies depending on the starting compound, the azide used, the type of the solvent and the like, but is usually from -10 ° C to 200 ° C (preferably from 50 ° C to 150 ° C).
The reaction time varies depending on the starting compound, the azides used, the type of solvent, the reaction temperature and the like, but is usually from 15 minutes to 4 minutes.
8 hours (preferably 30 minutes to 30 hours).

The reaction for protecting the tetrazolyl group, which is carried out as desired, is carried out by reacting the compound obtained by the above reaction with a halogenated triphenylmethane in an inert solvent in the presence of a base.

The base used is the same as that used in Step B1 of Method B, and is preferably an organic amine (particularly preferably, triethylamine). The inert solvent used is the same as that used when reacting the compound (XVc) with the azide compound.
Mixed solvent of ethers and amides (particularly preferably mixed solvent of tetrahydrofuran and dimethylformamide)
It is.

The reaction temperature varies depending on the type of the starting compound, base, solvent and the like, but is usually from -10 ° C to 150 ° C (preferably from 0 ° C to 60 ° C). The reaction time varies depending on the starting compound, base, type of solvent, reaction temperature, etc.,
Usually, it is 15 minutes to 48 hours (preferably 30 minutes to 30 hours).

Step J2 is a step for producing a compound having the general formula (XVf), and in a compound (XVb), a compound having a phenyl group or a pyridyl group in which R ^4a is substituted with a cyano group in an inert solvent. After reacting (XVe) with the azide compound, if necessary, the reaction is carried out by protecting the tetrazolyl group of the obtained compound, and this step is carried out in the same manner as the J method step J1.

After completion of the reaction, the desired compound (XV
d) and (XVf) are collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and, if insolubles are present, they are removed by filtration. It is obtained by washing with water and the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate and the like, and distilling off the solvent. If necessary, the obtained target compound is subjected to a conventional method, for example, recrystallization,
Ordinary methods such as reprecipitation can be separated and purified by appropriately combining methods commonly used for separation and purification of organic compounds, applying chromatography, and eluting with an appropriate eluent.

Starting compounds (XVI), (XVII),
(XVIII), (XIX), (XX), (XXI
V), (XXV), (XXVIIIa), (XXVII)
Ib) and (XXX) are known or easily produced according to a known method or a method similar thereto [for example, JP-A-9-188669 (EP 543662A)
etc].

The compound of the present invention having the above general formula (I) or a pharmaceutically acceptable salt thereof is excellent in improving insulin resistance, lowering blood glucose, anti-inflammatory, immunomodulating, inhibiting aldose reductase. Has an action, 5-lipoxygenase inhibitory action, lipid peroxide production inhibitory action, PPAR activating action, anti-osteoporosis action, leukotriene antagonism, adipocyte promotion action, cancer cell growth inhibitory action, calcium antagonism, and diabetes, Lipemia, obesity, impaired glucose tolerance, hypertension, fatty liver, diabetic complications (eg, retinopathy, nephropathy, neuropathy, cataract, coronary artery disease, etc.),
Cell damage (eg, stroke) caused by arteriosclerosis, gestational diabetes, polycystic ovary syndrome, cardiovascular disease (eg, ischemic heart disease, etc.), non-atherosclerotic disease or ischemic heart disease Gout, inflammatory diseases (eg, osteoarthritis, pain,
Fever, rheumatoid arthritis, inflammatory bowel disease, acne, sunburn, psoriasis, eczema, allergic disease, asthma, GI ulcer,
Cachexia, autoimmune disease, pancreatitis. ), Cancer, osteoporosis, cataract and the like.

Further, the compound of the present invention having the above general formula (I) or a pharmaceutically acceptable salt thereof, an α-glucosidase inhibitor, an aldose reductase inhibitor, a biguanide agent, a statin compound, a squalene synthesis inhibitor , A pharmaceutical composition comprising at least one of a fibrate compound, an LDL catabolism promoter and an angiotensin converting enzyme inhibitor (particularly preferably a prophylactic and / or therapeutic agent for diabetes or diabetic complications). Useful.

When the compound of the present invention having the above general formula (I) or a pharmaceutically acceptable salt thereof is used as the above-mentioned therapeutic or prophylactic agent, the compound itself or an appropriate pharmaceutically acceptable salt may be used. For example, they can be mixed with excipients, diluents and the like, and administered orally, for example, in tablets, capsules, granules, powders or syrups, or parenterally in injections or suppositories.

These preparations contain excipients (eg, lactose,
Sugar derivatives such as white sugar, glucose, mannitol, sorbitol; corn starch, potato starch,
α-starch, starch derivatives such as dextrin; cellulose derivatives such as crystalline cellulose; gum arabic; dextran; organic excipients such as pullulan: and light anhydrous silicic acid, synthetic aluminum silicate, calcium silicate, and metasilicate aluminate Inorganic excipients such as silicate derivatives such as magnesium; phosphates such as calcium hydrogen phosphate; carbonates such as calcium carbonate; sulfates such as calcium sulfate. ), Lubricants (eg, stearic acid metal salts such as stearic acid, calcium stearate, magnesium stearate; talc; colloidal silica; waxes such as veegum, gay wax; boric acid; adipic acid; Sodium sulfate; DL leucine; fatty acid sodium salt; lauryl sulfate such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as anhydrous silicic acid and silicic acid hydrate; Derivatives can be mentioned.) Binders (for example, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, macrogol, and the same compounds as the above-mentioned excipients), disintegrants (for example, , Low-substituted hydroxypropyl Cellulose derivatives such as loin, carboxymethylcellulose, carboxymethylcellulose calcium, and internally crosslinked sodium carboxymethylcellulose; and chemically modified starch celluloses such as carboxymethylstarch, sodium carboxymethylstarch, and crosslinked polyvinylpyrrolidone.) Stabilizers (paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol; thimerosal;
Dehydroacetic acid; and sorbic acid. ), Flavoring agents (for example, commonly used sweeteners, sour agents, flavors, etc.) and diluents can be used in a well-known method.

The dosage varies depending on the condition, age, administration method and the like. For example, in the case of oral administration,
The lower limit is 0.001 mg / kg body weight (preferably 0.0
1 mg / kg body weight), up to 500 mg / kg body weight (preferably 50 mg / kg body weight).
In each case, the lower limit is 0.005 mg / kg body weight (preferably 0.05 mg / kg body weight), and the upper limit is 50 mg / kg body weight (preferably 5 mg / kg body weight), depending on the symptoms once or several times a day. Administration.

[0281]

The present invention will be described in more detail with reference to the following Examples, Reference Examples and Test Examples, but the scope of the present invention is not limited thereto.

Example 1 5- {4- [5- (4-hydroxy-2,3,5-trimethylphenoxy) -3-methyl-3H-imidazo [4,5-b] pyridin-2-ylmethoxy] benzyl {Thiazolidine-2,4-dione and its hydrochloride (Exemplary Compound No. 1-651) (1-1) 5- {4- [5- (4-acetoxy-2,
3,5-trimethylphenoxy) -3-methyl-3H-
Imidazo [4,5-b] pyridin-2-ylmethoxy]
Benzyl} -3-triphenylmethylthiazolidine-
2,4-dione 16.4 g of 5- (4-acetoxy-2,3,5-trimethylphenoxy) -2-hydroxymethyl-3-methyl-3H-imidazo [4,5-b] pyridine, 32.2
17.2 ml of tributylphosphine in a mixture of g of 5- (4-hydroxybenzyl) -3-triphenylmethylthiazolidine-2,4-dione, 17.5 g of azodicarbonyldipiperidine and 400 ml of toluene.
Was added dropwise at room temperature, and the mixture was stirred by ultrasonic irradiation for 1 hour and at room temperature for 3 hours, and then allowed to stand at room temperature overnight. After insoluble matter was filtered off from the reaction solution and the filtrate was concentrated, the obtained residue was subjected to silica gel column chromatography (elution solvent: n-hexane / ethyl acetate = 2/1 → 1/1).
And crystallized with a mixed solvent of n-hexane / ethyl acetate (2/1). The obtained crystals are collected by filtration, and 3
1.7 g of the title compound were obtained. Melting point: 190-191C.

(1-2a) 5- {4- [5- (4-hydroxy-2,3,5-trimethylphenoxy) -3-methyl-3H-imidazo [4,5-b] pyridin-2-ylmethoxy Benzyl} thiazolidine-2,4-dione 27.0 g of 5- {4- [5- (4-acetoxy-2,
3,5-trimethylphenoxy) -3-methyl-3H-
Imidazo [4,5-b] pyridin-2-ylmethoxy]
Benzyl} -3-triphenylmethylthiazolidine-
2,4-dione, 150 ml of 6N hydrochloric acid and 200
After stirring the mixed solution of acetic acid at 80 ° C. for 5 hours, the mixture was poured into ice water and neutralized by adding sodium carbonate. Ethyl acetate was added to the mixture, and the insolubles were filtered off, followed by washing with ethanol to obtain 10.2 g of the title compound. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, washed with brine, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure.
The obtained residue is subjected to silica gel column chromatography (elution solvent: n-hexane / ethyl acetate = 1/1 → 1 /
(2 → ethyl acetate), crystallized from ethanol, and the crystals were collected by filtration to give 6.90 g of the title compound. Melting point: 21-1217 ° C.

(1-2b) 5- {4- [5- (4-hydroxy-2,3,5-trimethylphenoxy) -3-methyl-3H-imidazo [4,5-b] pyridin-2-ylmethoxy Benzyl} thiazolidine-2,4-dione hydrochloride 10.2 g of 5- {4- [5- (4-hydroxy-2,
3,5-trimethylphenoxy) -3-methyl-3H-
Imidazo [4,5-b] pyridin-2-ylmethoxy]
Benzyl thiazolidine-2,4-dione, 100ml
Of ethyl acetate and 100 ml of a mixture of 4N hydrochloric acid / ethyl acetate were stirred at room temperature for 6 hours, and the reaction solution was left at room temperature overnight. 9. Collect crystals from the reaction mixture by filtration.
7 g of the title compound were obtained. Melting point: 148-150C.

Example 2 5- {4- [6- (4-hydroxy-2,3,5-trimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-
2,4-dione and its hydrochloride (Exemplary Compound No. 1-
650) (2-1) N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino]
-5- (4-methoxymethoxy-2,3,5-trimethylphenoxy) phenyl} -N-methylcarbamic acid
t-butyl ester 18.7 g of N- [2-amino-5- (4-methoxymethoxy-2,3,5-trimethylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester
12.6 g of 4- (2,4-dioxothiazolidine-5
To a mixture of -ylmethyl) phenoxyacetic acid, 4.55 g of triethylamine and 300 ml of anhydrous tetrahydrofuran, 7.34 g of diethyl cyanophosphonate was added, and the mixture was stirred at room temperature for 17 hours. The reaction solution was concentrated, water was added, extracted with ethyl acetate, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/1) to give 23.1 g.
The title compound was obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/3): Rf value = 0.41.

(2-2a) 5- {4- [6- (4-hydroxy-2,3,5-trimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy]
Benzyl} thiazolidine-2,4-dione 0.49 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-methoxymethoxy-2,3 , 5-Trimethylphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester was dissolved in 10 ml of a 4N hydrochloric acid / dioxane solution and left at room temperature for 2 days. Water and sodium bicarbonate solution were added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was separated and purified by silica gel column chromatography using ethyl acetate as an eluent.
27 g of the title compound were obtained. Softening point: 137-147 ° C Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.21.

(2-2b) 5- {4- [6- (4-hydroxy-2,3,5-trimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy]
Benzyl} thiazolidine-2,4-dione hydrochloride 18.0 g of 5- {4- [6- (4-hydroxy-2,
3,5-trimethylphenoxy) -1-methyl-1H-
The crude product of [benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione was separated and purified by silica gel column chromatography using ethyl acetate as an eluting solvent, and suspended in 100 ml of 4N hydrochloric acid / ethyl acetate solution. And stirred at room temperature overnight. The crystals were collected from the mixture by filtration and washed with ethyl acetate to obtain 14.7 g of the title compound. Melting point: 160-165 [deg.] C.

Example 3 5- {4- [6- (4-hydroxyphenoxy) -1-]
Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione (Exemplary Compound No. 1-70) (3-1) N- {2- [4- (2,4-dioxothiazolidine-)] 5-ylmethyl) phenoxyacetylamino]
-5- (4-hydroxyphenoxy) phenyl} -N-
Methylcarbamic acid t-butyl ester 0.79 g of N- [2-amino-5- (4-hydroxyphenoxy) phenyl] -N-methylcarbamic acid t
-Butyl ester, 0.84 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid,
Using 0.49 g of diethyl cyanophosphonate, 0.30 g of triethylamine and 60 ml of anhydrous tetrahydrofuran, the reaction was carried out in the same manner as in Example (2-1) and purification was performed to obtain 1.49 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.35.

(3-2) 5- {4- [6- (4-hydroxyphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-
2,4-dione 1.49 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-hydroxyphenoxy) phenyl}-
N-methylcarbamic acid t-butyl ester and 1
Using 0 ml of a 4N hydrochloric acid / dioxane solution, the reaction was carried out in the same manner as in Example (2-2a), and the mixture was purified to give 0.26 g.
The title compound was obtained. Melting point: 126-131 ° C. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/3): Rf = 0.13.

Example 4 5- {4- [6- (4-hydroxy-3,5-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4
-Dione and its hydrochloride (Exemplary Compound No. 1-52)
0) (4-1) N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino]
-5- (4-methoxymethoxy-3,5-dimethylphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester 0.96 g of N- [2-amino-5- (4-methoxymethoxy-3,5- Dimethylphenoxy) phenyl] -N
-Methylcarbamic acid t-butyl ester, 0.84
g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid, 0.49 g of diethyl cyanophosphonate, 0.30 g of triethylamine and 60 m
l of anhydrous tetrahydrofuran,
The reaction was carried out in the same manner as in 1) and purification was carried out to obtain 1.44 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.27.

(4-2a) 5- {4- [6- (4-hydroxy-3,5-dimethylphenoxy) -1-methyl-
1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione 1.44 g of N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino] -5 (4-methoxymethoxy-3,5-dimethylphenoxy) phenyl} -N-methylcarbamic acid t
Using -butyl ester and 10 ml of a 4N hydrochloric acid / dioxane solution, the reaction was carried out in the same manner as in Example (2-2a) and purification was performed to obtain 0.62 g of the title compound. Melting point: 147-157 ° C Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.21.

(4-2b) 5- {4- [6- (4-hydroxy-3,5-dimethylphenoxy) -1-methyl-
1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride 3.11 g of 5- {4- [6- (4-hydroxy-3,
5-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione and 50 ml of a 4N hydrochloric acid / ethyl acetate solution were used to prepare Example (2-2b). Reaction and purification were carried out in the same manner to give 3.18 g of the title compound. Melting point: 206-209 [deg.] C.

Example 5 5- {4- [6- (2-chloro-4-hydroxy-3,
5-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione and its hydrochloride (Exemplified Compound No. 1-368) (5a) 5- {4- [6 -(2-chloro-4-hydroxy-3,5-dimethylphenoxy) -1
-Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione 9.19 g of N- [5- (2-chloro-4-methoxymethoxy-3,5-dimethylphenoxy) -2- Nitrophenyl] -N-methylcarbamic acid t-butyl ester, 2.5 g of 10% palladium on carbon and 400 m
of methanol at room temperature under a hydrogen atmosphere at room temperature.
After vigorous stirring for minutes, the catalyst was filtered off and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 250 ml of anhydrous tetrahydrofuran, and 15.8 g of 4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid was added.
9.18 g of diethyl cyanophosphonate and 5.69
g of triethylamine was added, and the mixture was stirred at room temperature for 64 hours. After concentrating the reaction solution, adding water and extracting with ethyl acetate, the extract was dried over anhydrous sodium sulfate, and
The solvent was distilled off. The obtained residue was separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/1), dissolved in 200 ml of a 2N hydrochloric acid / dioxane solution, and allowed to stand at room temperature for 19 hours. The reaction solution was concentrated, neutralized with aqueous sodium hydrogen carbonate, and extracted with a mixed solvent of ethyl acetate and tetrahydrofuran. The obtained extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue is subjected to silica gel column chromatography (elution solvent: n-hexane / ethyl acetate = 1 /
2) Separation and purification by reverse phase preparative high performance liquid chromatography (developing solvent: acetonitrile / water = 7/3)
2.56 g of the title compound were obtained. Melting point: 240-243 ° C Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.21.

(5b) 5- {4- [6- (2-chloro-
4-hydroxy-3,5-dimethylphenoxy) -1-
Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride 2.54 g of 5- {4- [6- (2-chloro-4-hydroxy-3,5-dimethylphenoxy) -1-methyl-
[1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione and 50 ml of 4
Example (2-2) was performed using a normal hydrochloric acid / ethyl acetate solution.
The reaction was carried out in the same manner as in b) and purification was performed to give the title compound in 2.6.
7 g were obtained. Melting point: 174-176C.

Example 6 5- {4- [6- (pyridin-2-yloxy) -1-]
Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione (Exemplary Compound No. 1-821) (6-1) N- {2- [4- (2,4-dioxothiazolidine-)] 5-ylmethyl) phenoxyacetylamino]
-5- (pyridin-2-yloxy) phenyl} -N-
Methylcarbamic acid t-butyl ester 0.34 g of N- [2-nitro-5- (pyridine-2-
Yloxy) phenyl] -N-methylcarbamic acid t
A mixture of -butyl ester, 50 mg of 10% palladium-carbon and 10 ml of methanol was stirred vigorously under a hydrogen atmosphere at room temperature for 90 minutes. The catalyst was removed by filtration from the reaction solution, and the solvent was distilled off under reduced pressure. The residue obtained is 10
0.34 g dissolved in anhydrous tetrahydrofuran
Of 4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.20 g of diethyl cyanophosphonate and 0.12 g of triethylamine were added, and the mixture was stirred at room temperature for 18 hours. The reaction solution was concentrated, water was added, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/2) to give 0.37.
g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.36.

(6-2) 5- {4- [6- (pyridine-
2-yloxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione 0.37 g of N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino] -5- (pyridin-2-yloxy) phenyl}-
N-methylcarbamic acid t-butyl ester and 2
Using 0 ml of a 4 N hydrochloric acid / dioxane solution, the reaction was carried out in the same manner as in Example (2-2a), followed by purification to give 0.20 g.
The title compound was obtained. Melting point: 200-210 ° C Silica gel thin layer chromatography (developing solvent: ethyl acetate): Rf value = 0.28.

Example 7 5- {4- [6- (3,5-Di-tert-butyl-4-hydroxyphenylthio) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2 , 4-dione 1/2 hydrochloride and hydrochloride (Exemplified Compound No. 1-595) (7-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino]
-5- (3,5-Di-t-butyl-4-hydroxyphenylthio) phenyl} -N-methylcarbamic acid t-
359 mg of butyl ester in N- [2-nitro-5-
(3,5-Di-t-butyl-4-hydroxyphenylthio) phenyl] -N-methylcarbamic acid t-butyl ester, a mixture of 360 mg of 10% palladium on carbon and 50 ml of methanol at room temperature under a hydrogen atmosphere. Stir vigorously for 9 hours. The catalyst was removed by filtration from the reaction solution, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 20 ml of anhydrous tetrahydrofuran, and 248 mg of 4-
(2,4-Dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 144 mg of diethyl cyanophosphonate and 89 mg of triethylamine were added, and the mixture was added at room temperature for 15 minutes.
Left for hours. The reaction solution was concentrated, water was added, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 3/2) to obtain 275 mg of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.44.

(7-2a) 5- {4- [6- (3,5-
Di-tert-butyl-4-hydroxyphenylthio) -1-
Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione 1/2 hydrochloride 259 mg of N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetyl] Amino] -5- (3,5-di-t-butyl-4-hydroxyphenylthio) phenyl} -N-methylcarbamic acid
The t-butyl ester was dissolved in 10 ml of a 4N hydrochloric acid / dioxane solution and left at room temperature for 18 hours. The reaction solution was evaporated to dryness under reduced pressure, ether was added thereto, and the insoluble matter was collected by filtration, followed by washing with ether. The obtained solid substance was separated and purified by reverse phase preparative thin layer chromatography (developing solvent: acetonitrile / water = 5/1) to obtain 115 mg of the title compound. Melting point: 120-123 [deg.] C.

(7-2b) 5- {4- [6- (3,5-
Di-tert-butyl-4-hydroxyphenylthio) -1-
Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride 2.29 g of 5- {4- [6- (3,5-di-tert-butyl-4-hydroxyphenylthio) ) -1-Methyl-1H
-Benzimidazol-2-ylmethoxy] benzyl}
The reaction was carried out in the same manner as in Example (2-2b) using thiazolidine-2,4-dione and a 4N hydrochloric acid / ethyl acetate solution, followed by purification to obtain 1.25 g of the title compound. Melting point: 144-146 [deg.] C.

Example 8 5- {4- [6- (4-amino-3,5-dimethylphenoxy) -1-methyl-1H-benzimidazole-2
-Ylmethoxy] benzyl} thiazolidine-2,4-dione and its dihydrochloride (Exemplary Compound No. 1-739) (8-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) ) Phenoxyacetylamino]
-5- (4-t-butoxycarbonylamino-3,5-
Dimethylphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester 1.56 g of N- [2-amino-5- (4-t-butoxycarbonylamine-3,5-dimethylphenoxy) phenyl] -N-methylcarbamic acid Using t-butyl ester, 1.05 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid, 0.61 g of diethyl cyanophosphonate, 0.38 g of triethylamine and 30 ml of anhydrous tetrahydrofuran, The reaction was carried out and purified in the same manner as in Example (2-1) to obtain 1.89.
g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/2): Rf value = 0.19.

(8-2a) 5- {4- [6- (4-amino-3,5-dimethylphenoxy) -1-methyl-1H
-Benzimidazol-2-ylmethoxy] benzyl}
Thiazolidine-2,4-dione 1.88 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-t-butoxycarbonylamino-3,
Using 5-t-ylphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester and 20 ml of a 4N hydrochloric acid / dioxane solution, the reaction was carried out in the same manner as in Example (2-2a), and purified. The title compound was obtained. Melting point: 209-211 ° C. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.29.

(8-2b) 5- {4- [6- (4-amino-3,5-dimethylphenoxy) -1-methyl-1H
-Benzimidazol-2-ylmethoxy] benzyl}
Thiazolidine-2,4-dione dihydrochloride 0.25 g of 5- {4- [6- (4-amino-3,5-
Dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione and 50 ml of a 4N hydrochloric acid / ethyl acetate solution were used in the same manner as in Example (2-2b). React and purify to give 0.25 g of the title compound. Melting point: 165-175C.

Example 9 5- {4- [6- (4-acetylamino-3,5-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-
2,4-dione hydrochloride (Exemplified Compound No. 1-808) 155 mg of 5- {4- [6- (4-amino-3,5-
Dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione dihydrochloride, 36 mg of acetic anhydride,
A mixture of 07 mg of pyridine, 7.3 mg of 4- (N, N-dimethylamino) pyridine and 5 ml of anhydrous tetrahydrofuran was heated under reflux for 2 hours. Concentrate the reaction,
After adding water, the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. 10 ml of 4N hydrochloric acid / ethyl acetate was added to the obtained residue, and the mixture was stirred at room temperature for 21 hours. The insoluble product was collected by filtration and washed with ether to give 97 mg of the title compound. Softening point: 160-165 ° C.

Example 10 5- {4- (1-methyl-6- [2- (morpholine-4)
-Yl) phenoxy] -1H-benzimidazole-2
-Ylmethoxy) benzyl} thiazolidine-2,4-dione and its dihydrochloride (Exemplary Compound No. 1-284) (10-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) ) Phenoxyacetylamino] -5- [2- (morpholin-4-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester 1.18 g of N- {2-amino-5- [2- (morpholine- 4-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester, 0.92 g of 4-
Reaction was carried out in the same manner as in Example (2-1) using (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.53 g of diethyl cyanophosphonate, 0.33 g of triethylamine and 30 ml of anhydrous tetrahydrofuran. And purified to give 1.47 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.30.

(10-2a) 5- {4- (1-methyl-
6- [2- (morpholin-4-yl) phenoxy] -1
H-benzimidazol-2-ylmethoxy) benzyl {thiazolidine-2,4-dione 1.45 g of N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino] -5 The reaction was carried out in the same manner as in Example 2a using [2- (morpholin-4-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester and 20 ml of 4N hydrochloric acid / dioxane, followed by purification. 94
g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.33.

(10-2b) 5- {4- (1-methyl-
6- [2- (morpholin-4-yl) phenoxy] -1
H-benzimidazol-2-ylmethoxy) benzyl {thiazolidine-2,4-dione dihydrochloride 0.64 g of 5- {4- (1-methyl-6- [2- (morpholin-4-yl) phenoxy] [1H-benzimidazol-2-ylmethoxy) benzyl} thiazolidine-2,4-dione was dissolved in a mixture of 30 ml of concentrated hydrochloric acid and 30 ml of 1,4-dioxane, and the mixture was stirred at room temperature for 90 minutes. The obtained reaction solution was dried under reduced pressure, and ether was added. The insoluble product was collected by filtration and washed with ether to give 0.71 g of the title compound. Softening point: 120-130 ° C.

Example 11 5- {4- (1-methyl-6- [3- (morpholine-4)
-Yl) phenoxy] -1H-benzimidazole-2
-Ylmethoxy) benzyl} thiazolidine-2,4-dione dihydrochloride (Exemplary Compound No. 1-292) (11-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) Phenoxyacetylamino] -5- [3- (morpholin-4-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester 1.18 g of N- {2-amino-5- [3- (morpholine-4) -Yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester, 0.92 g of 4-
Using (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.53 g of diethyl cyanophosphonate, 0.33 g of triethylamine and 30 ml of anhydrous tetrahydrofuran, the same reaction as in Example (2-1). And purified to give 1.48 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.26.

(11-2) 5- {4- (1-methyl-6)
-[3- (morpholin-4-yl) phenoxy] -1H
-Benzimidazol-2-ylmethoxy) benzyl
Thiazolidine-2,4-dione dihydrochloride 1.44 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- [3- (morpholine-4 -Yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester and 20 ml of a mixture of 4N hydrochloric acid / dioxane were stirred at room temperature for 3 hours. The reaction solution was dried under reduced pressure,
Ether was added. The insoluble product was collected by filtration and washed with ether to give 1.27 g of the title compound. Softening point: 150-160 ° C.

Example 12 5- {4- (1-methyl-6- [2- (piperidine-1)
-Yl) phenoxy] -1H-benzimidazole-2
-Ylmethoxy) benzyl} thiazolidine-2,4-dione dihydrochloride (Exemplary Compound No. 1-241) (12-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) Phenoxyacetylamino] -5- [2- (piperidin-1-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester 1.19 g of N- {2-amino-5- [2- (piperidin-1) -Yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester, 0.93 g of 4-
Reaction was performed in the same manner as in Example (2-1) using (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.54 g of diethyl cyanophosphonate, 0.33 g of triethylamine and 20 ml of anhydrous tetrahydrofuran. And purified to give 1.80 g of the title compound.

Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value =
0.39.

(12-2) 5- {4- (1-methyl-6)
-[2- (piperidin-1-yl) phenoxy] -1H
-Benzimidazol-2-ylmethoxy) benzyl
Thiazolidine-2,4-dione dihydrochloride 1.80 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- [2- (piperidine-1) -Yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester and 20 ml of a mixture of 4N hydrochloric acid / dioxane were stirred at room temperature for 19 hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. After filtering off the insoluble product, reverse-phase preparative high-performance liquid chromatography (elution solvent:
(Acetonitrile / water = 1/1) and treated with 4N hydrochloric acid / ethyl acetate to obtain 0.47 g of the title compound.

Melting point 151-154 ° C.

Example 13 5- {4- [1-Methyl-6- (pyridin-2-ylthio) -1H-benzimidazol-2-ylmethoxy]
Benzyldithiazolidine-2,4-dione and its 2
Hydrochloride (Exemplified Compound No. 1-823) (13-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (pyridin-2-ylthio) Phenyl @ -N
-Methylcarbamic acid t-butyl ester 0.78 g of N- [2-amino-5- (pyridine-2-
Ylthio) phenyl] -N-methylcarbamic acid t-
Butyl ester, 1.06 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid.
The reaction was carried out in the same manner as in Example (2-1) using 61 g of diethyl cyanophosphonate, 0.38 g of triethylamine and 20 ml of anhydrous tetrahydrofuran, and purified to obtain 0.68 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.51.

(13-2a) 5- {4- [1-methyl-
6- (pyridin-2-ylthio) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione 0.63 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (pyridin-2-ylthio) phenyl} -N
-Methyl carbamic acid t-butyl ester and 20
Example 4 (ml) using 4N hydrochloric acid / dioxane.
Reacted and purified as in 2a) to give 0.20 g of the title compound. Silica gel thin layer chromatography (developing solvent: ethyl acetate): Rf value = 0.26.

(13-2b) 5- {4- [1-methyl-
6- (pyridin-2-ylthio) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione dihydrochloride 0.20 g of 5- {4- [1-methyl-6- (pyridin-2-ylthio) -1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4- The reaction was carried out in the same manner as in Example (2-2b) using dione and 50 ml of 4N hydrochloric acid / ethyl acetate, and the mixture was purified to give 0.2%.
1 g of the title compound was obtained. Melting point: 139-147 [deg.] C.

Example 14 5- {4- (1-methyl-6- [2- (pyrrolidine-1)]
-Yl) phenoxy] -1H-benzimidazole-2
-Ylmethoxy) benzyl} thiazolidine-2,4-dione (Exemplary Compound No. 1-199) (14-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- [2- (pyrrolidin-1-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester 0.77 g of N- {2-amino-5- [2- (pyrrolidin-1-yl) phenoxy] ] Phenyl} -N-methylcarbamic acid t-butyl ester, 0.90 g of 4-
Reaction was performed in the same manner as in Example (2-1) using (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.52 g of diethyl cyanophosphonate, 0.32 g of triethylamine and 30 ml of anhydrous tetrahydrofuran. And purified to give 1.26 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.40.

(14-2) 5- {4- (1-methyl-6)
-[2- (pyrrolidin-1-yl) phenoxy] -1H
-Benzimidazol-2-ylmethoxy) benzyl
Thiazolidine-2,4-dione 1.25 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- [2- (pyrrolidin-1-yl) phenoxy The reaction was carried out in the same manner as in Example (2-2a) using phenyl} -N-methylcarbamic acid t-butyl ester and 25 ml of 4N hydrochloric acid / dioxane, followed by purification to obtain 0.94 g of the title compound. . Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.27.

Example 15 5- {4- [6- (2-hydroxyphenoxy) -1-]
Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride (Exemplary Compound No. 1-11) (15-1) N- {2- [4- (2,4-dioxo) Thiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (2-hydroxyphenoxy) phenyl}-
N-methylcarbamic acid t-butyl ester 0.99 g of N- [2-amino-5- (2-hydroxyphenoxy) phenyl] -N-methylcarbamic acid t
-Butyl ester, 0.93 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid,
The reaction was carried out in the same manner as in Example (2-1) using 0.54 g of diethyl cyanophosphonate, 0.33 g of triethylamine and 20 ml of anhydrous tetrahydrofuran, followed by purification to obtain 1.18 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/3): Rf value = 0.47.

(15-1) 5- {4- [1-methyl-6
-(2-hydroxyphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione hydrochloride 1.16 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (2-hydroxyphenoxy) phenyl}-
N-methylcarbamic acid t-butyl ester and 2
Example (2) was prepared using 0 ml of 4N hydrochloric acid / dioxane.
Reaction and purification were carried out in the same manner as in -2a). Continue 20m
Example 1 (2-2) using 1 l of 4N hydrochloric acid / ethyl acetate.
Reacted and purified as in b) to give 0.79 g of the title compound. Melting point: 155-165C.

Example 16 5- {4- (6- [4- (1-adamantyl) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl} thiazolidine-2,4-dione hydrochloride ( Exemplified Compound No. 1-1182) (16-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- [4- (1-adamantyl) phenoxy] Phenyl} -N-methylcarbamic acid t-butyl ester 1.34 g of N- {2-amino-5- [4- (1-adamantyl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester, 0.93 g 4- (2,
4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid, 0.54 g of diethyl cyanophosphonate, 0.1.
The reaction was carried out in the same manner as in Example (2-1) using 33 g of triethylamine and 20 ml of anhydrous tetrahydrofuran, followed by purification to obtain 1.83 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.29.

(16-2) 5- {4- (6- [4- (1
-Adamantyl) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl {thiazolidine-2,4-dione hydrochloride 1.82 g of N- {2- [4- (2,4-dioxothiazolidine) -5-ylmethyl) phenoxyacetylamino] -5- [4- (1-adamantyl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester and a mixture of 20 ml of 4N hydrochloric acid / dioxane were stirred at room temperature for 29 hours. . The reaction solution was dried under reduced pressure, and ether was added. The insoluble product was collected by filtration and washed with ether to give 1.35 g of the title compound. Melting point: 160-165 [deg.] C.

Example 17 5- {4- [6- (3-dimethylaminophenoxy)-
1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione (Exemplary Compound No. 1-153) (17-1) N- {5- (3-dimethylaminophenoxy) -2- [4- (2,4-dioxothiazolidine-5)
-Ylmethyl) phenoxyacetylamino] phenyl}
-N-methylcarbamic acid t-butyl ester 1.00 g of N- [2-amino-5- (3-dimethylaminophenoxy) phenyl] -N-methylcarbamic acid t-butyl ester, 1.57 g of 4- (2, 4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.91 g of diethyl cyanophosphonate, 0.57
The reaction was carried out in the same manner as in Example (2-1) using g of triethylamine and 40 ml of anhydrous tetrahydrofuran, and purified to obtain 1.69 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.26.

(17-2) 5- {4- [6- (3-dimethylaminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione 1.68 g N- {5- (3-dimethylaminophenoxy) -2- [4- (2,4-dioxothiazolidine-5)
-Ylmethyl) phenoxyacetylamino] phenyl}
Using -N-methylcarbamic acid t-butyl ester and 30 ml of 4N hydrochloric acid / dioxane, the reaction was carried out in the same manner as in Example (2-2a), followed by purification to give 0.57 g.
The title compound was obtained. Melting point: 180-186 ° C.

Example 18 5- {4- [1-Methyl-6- (pyridin-3-yloxy) -1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione dihydrochloride (exemplified) Compound No. 1-938) (18-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (pyridin-3-yloxy) phenyl}-
N-methylcarbamic acid t-butyl ester 0.63 g of N- [2-amino-5- (pyridine-3-
Yloxy) phenyl] -N-methylcarbamic acid t
-Butyl ester, 0.62 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid,
The reaction was carried out in the same manner as in Example (2-1) using 0.36 g of diethyl cyanophosphonate, 0.22 g of triethylamine, and 15 ml of anhydrous tetrahydrofuran, followed by purification to obtain 0.88 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.38.

(18-2) 5- {4- [1-methyl-6
-(Pyridin-3-yloxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione dihydrochloride 0.87 g of N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino] -5- (pyridin-3-yloxy) phenyl} −
N-methylcarbamic acid t-butyl ester and 1
3. Add 5 ml of 4N hydrochloric acid / dioxane mixture at room temperature.
After stirring for 5 hours, the mixture was left at the same temperature for 9 days. The insoluble product was collected by filtration and washed with ethyl acetate to obtain 0.77 g of the title compound. Melting point: 146-156 [deg.] C.

Example 19 5- {4- (6- [4- (Imidazol-1-yl) phenoxy] -1-methyl-1H-benzimidazole-
2-ylmethoxy) benzyl {thiazolidine-2,4-
Dione dihydrochloride (Exemplified Compound No. 1-1126) (19-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- [4- ( Imidazol-1-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester 1.14 g of N- {2-amino-5- [4- (imidazol-1-yl) phenoxy] phenyl} -N-methylcarbamine Acid t-butyl ester, 0.93 g of 4-
Reaction was carried out in the same manner as in Example (2-1) using (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.54 g of diethyl cyanophosphonate, 0.33 g of triethylamine and 30 ml of anhydrous tetrahydrofuran. And purified to give 1.75 g of the title compound. Silica gel thin layer chromatography (developing solvent: ethyl acetate / methanol = 10/1): Rf value = 0.51.

(19-2) 5- {4- (6- [4- (imidazol-1-yl) phenoxy] -1-methyl-1
H-benzimidazol-2-ylmethoxy) benzyl {thiazolidine-2,4-dione dihydrochloride 1.75 g of N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino] ] -5- [4- (Imidazol-1-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester and a mixture of 20 ml of 4N hydrochloric acid / dioxane were stirred at room temperature for 19 hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. After filtering off the insoluble product, reverse-phase preparative high-performance liquid chromatography (elution solvent:
(Acetonitrile / water = 7/13), followed by treatment with 4N hydrochloric acid / ethyl acetate to obtain 0.20 g of the title compound.

Melting point: 183-186 ° C.

Example 20 5- {4- [1-Methyl-6- (2-phenylphenoxy) -1H-benzimidazol-2-ylmethoxy]
Benzyl @ thiazolidine-2,4-dione hydrochloride (Exemplified Compound No. 1-1327) (20-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino]- 5- (2-phenylphenoxy) phenyl} -N
-Methylcarbamic acid t-butyl ester 1.60 g of N- [2-amino-5- (2-phenylphenoxy) phenyl] -N-methylcarbamic acid t-
Butyl ester, 1.26 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid.
The reaction was carried out in the same manner as in Example (2-1) using 73 g of diethyl cyanophosphonate, 0.45 g of triethylamine and 20 ml of anhydrous tetrahydrofuran, followed by purification to obtain 2.33 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/2): Rf value = 0.25.

(20-2) 5- {4- [1-methyl-6
-(2-phenylphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione hydrochloride 2.33 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (2-phenylphenoxy) phenyl} -N
-Methyl carbamic acid t-butyl ester and 20
A 4 ml mixture of 4N hydrochloric acid / dioxane was stirred at room temperature for 20 hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. The insoluble product was collected by filtration and washed with ethyl acetate to obtain 1.87 g of the title compound. Melting point: 142-152 [deg.] C.

Example 21 5- {4- [6- (4-hydroxy-2,3-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4
-Dione hydrochloride (Exemplified Compound No. 1-506) (21-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-hydroxy- 2,3-Dimethylphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester 1.60 g of N- [2-amino-5- (4-hydroxy-2,3-dimethylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester, 1.38 g of 4
-(2,4-dioxothiazolidine-5-ylmethyl)
Using phenoxyacetic acid, 0.80 g of diethyl cyanophosphonate, 0.50 g of triethylamine and 20 ml of anhydrous tetrahydrofuran, the reaction was carried out in the same manner as in Example (2-1) and purification was performed to obtain 2.35 g of the title compound. Obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.54.

(21-2) 5- {4- [6- (4-hydroxy-2,3-dimethylphenoxy) -1-methyl-
1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride 2.35 g of N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino]- A mixture of 5- (4-hydroxy-2,3-dimethylphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester and 20 ml of 4N hydrochloric acid / dioxane was stirred at room temperature for 44 hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. The insoluble product was collected by filtration and washed with ethyl acetate to obtain 1.82 g of the title compound. Melting point: 168-170C.

Example 22 5- {4- [1-Methyl-6- (4-phenoxyphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione hydrochloride (Exemplified Compound No. 1) -193) (22-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-phenoxyphenoxy) phenyl}-
N-methylcarbamic acid t-butyl ester 1.66 g of N- [2-amino-5- (4-phenoxyphenoxy) phenyl] -N-methylcarbamic acid t
-Butyl ester, 1.26 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid,
The reaction was carried out in the same manner as in Example (2-1) using 0.73 g of diethyl cyanophosphonate, 0.45 g of triethylamine and 20 ml of anhydrous tetrahydrofuran, followed by purification to obtain 1.99 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.62.

(22-2) 5- {4- [1-methyl-6
-(4-phenoxyphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione hydrochloride 1.99 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-phenoxyphenoxy) phenyl}-
N-methylcarbamic acid t-butyl ester and 2
0 ml of a 4N hydrochloric acid / dioxane mixture was added at room temperature for 22 minutes.
Stirred for hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. The insoluble product was collected by filtration and washed with ethyl acetate to give 1.57 g of the title compound. Melting point: 190-200 <0> C.

Example 23 5- {4- [6- (4-hydroxyphenylthio) -1
-Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione and its hydrochloride (Exemplified Compound No. 1-72) (23-2a) 5- {4- [6- (4-hydroxy) Phenylthio) -1-methyl-1H-benzimidazole-
2-ylmethoxy] benzyl {thiazolidine-2,4-
2.36 g of N- [2-amino-5- (4-hydroxyphenylthio) phenyl] -N-methylcarbamic acid
t-butyl ester, 2.87 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid,
The reaction was carried out in the same manner as in Example (2-1) using 1.67 g of diethyl cyanophosphonate, 1.03 g of triethylamine, and 60 ml of anhydrous tetrahydrofuran, and purified. Subsequently, the reaction was carried out in the same manner as in Example (2-2a) using 20 ml of 4N hydrochloric acid / dioxane, followed by purification to obtain 0.72 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.19.

(23-2b) 5- {4- [6- (4-hydroxyphenylthio) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione hydrochloride 72 g of 5- {4- [6- (4-hydroxyphenylthio) -1-methyl-1H-benzimidazole-2
-Ylmethoxy] benzyl} thiazolidine-2,4-dione and 40 ml of 4N hydrochloric acid / ethyl acetate were reacted in the same manner as in Example (2-2b) and purified.
0.63 g of the title compound was obtained. Melting point: 204-207 ° C.

Example 24 5- {4- [1-Methyl-6- (3-phenylphenoxy) -1H-benzimidazol-2-ylmethoxy]
Benzyl} thiazolidine-2,4-dione hydrochloride (Exemplary Compound No. 1-168) (24-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino]- 5- (3-phenylphenoxy) phenyl} -N
-Methylcarbamic acid t-butyl ester 1.60 g of N- [2-amino-5- (3-phenylphenoxy) phenyl] -N-methylcarbamic acid t-
Butyl ester, 1.26 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid.
The reaction was carried out in the same manner as in Example (2-1) using 73 g of diethyl cyanophosphonate, 0.45 g of triethylamine and 20 ml of anhydrous tetrahydrofuran, followed by purification to obtain 2.57 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.32.

(24-2) 5- {4- [1-methyl-6
-(3-phenylphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione hydrochloride 2.57 g of N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino] -5- (3-phenylphenoxy) phenyl} -N
-Methylcarbamic acid t-butyl ester and 30
The mixture of 4 ml of 4N hydrochloric acid / dioxane was stirred at room temperature for 63 hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. The insoluble product was collected by filtration and washed with ethyl acetate to give 2.01 g of the title compound. Melting point: 150-160 ° C.

Example 25 5- {4- [6- (3-tert-butyl-4-hydroxyphenoxy) -1-methyl-1H-benzimidazole-
2-ylmethoxy] benzyl {thiazolidine-2,4-
Dione hydrochloride (Exemplary Compound No. 1-501) (25-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (3-t-butyl) -4-Hydroxyphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester 1.11 g of N- [2-amino-5- (3-t-butyl-4-hydroxyphenoxy) phenyl] -N-methylcarbamic acid t -Butyl ester, 0.89 g of 4-
Reaction was performed in the same manner as in Example (2-1) using (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.52 g of diethyl cyanophosphonate, 0.32 g of triethylamine and 20 ml of anhydrous tetrahydrofuran. And purified to give 1.75 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.26.

(25-2) 5- {4- [6- (3-t-
Butyl-4-hydroxyphenoxy) -1-methyl-1
H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride 1.75 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino]- A mixture of 5- (3-t-butyl-4-hydroxyphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester and 20 ml of 4N hydrochloric acid / dioxane was stirred at room temperature for 14 hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. The insoluble product was collected by filtration and washed with ethyl acetate to give 1.11 g of the title compound. Melting point: 160-170 ° C.

Example 26 5- {4- [6- (2-tert-butyl-4-hydroxyphenoxy) -1-methyl-1H-benzimidazole-
2-ylmethoxy] benzyl {thiazolidine-2,4-
Dione hydrochloride (Exemplified Compound No. 1-499) (26-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (2-t-butyl) -4-Hydroxyphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester 0.95 g of N- [2-amino-5- (2-t-butyl-4-hydroxyphenoxy) phenyl] -N-methylcarbamic acid t -Butyl ester, 0.76 g of 4-
Using (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.44 g of diethyl cyanophosphonate, 0.27 g of triethylamine and 20 ml of anhydrous tetrahydrofuran, the same reaction as in Example (2-1). And purified to give 1.24 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.19.

(26-2) 5- {4- [6- (2-t-
Butyl-4-hydroxyphenoxy) -1-methyl-1
H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride 1.24 g of N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino]- A mixture of 5- (2-t-butyl-4-hydroxyphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester and 20 ml of 4N hydrochloric acid / dioxane was stirred at room temperature for 14 hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. The insoluble product was collected by filtration and washed with ethyl acetate to obtain 0.75 g of the title compound. Melting point: 167-172C.

Example 27 5- {4- [1-Methyl-6- (4-phenylphenoxy) -1H-benzimidazol-2-ylmethoxy]
Benzyl @ thiazolidine-2,4-dione hydrochloride (Exemplary Compound No. 1-169) (27-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino]- 5- (4-phenylphenoxy) phenyl} -N
-Methylcarbamic acid t-butyl ester 1.60 g of N- [2-amino-5- (4-phenylphenoxy) phenyl] -N-methylcarbamic acid t-
Butyl ester, 1.26 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid.
The reaction was carried out in the same manner as in Example (2-1) using 73 g of diethyl cyanophosphonate, 0.45 g of triethylamine and 20 ml of anhydrous tetrahydrofuran, followed by purification to obtain 2.39 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.32.

(27-2) 5- {4- [1-methyl-6
-(4-phenylphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione hydrochloride 2.39 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-phenylphenoxy) phenyl} -N
-Methyl carbamic acid t-butyl ester and 20
A 4N mixture of 4N hydrochloric acid / dioxane was stirred at room temperature for 21 hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. The insoluble product was collected by filtration and washed with ethyl acetate to obtain 1.90 g of the title compound. Melting point: 170-180 ° C.

Example 28 5- {4- [6- (4-hydroxy-2,5-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4
-Dione hydrochloride (Exemplified Compound No. 1-513) (28-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-hydroxy- 2,5-dimethylphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester 0.54 g of N- [2-amino-5- (4-hydroxy-2,5-dimethylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester, 0.51 g of 4
-(2,4-dioxothiazolidine-5-ylmethyl)
Using phenoxyacetic acid, 0.29 g of diethyl cyanophosphonate, 0.18 g of triethylamine and 10 ml of anhydrous tetrahydrofuran, the reaction was carried out in the same manner as in Example (2-1), and the mixture was purified to give 0.71 g of the title compound. Obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.68.

(28-2) 5- {4- [6- (4-hydroxy-2,5-dimethylphenoxy) -1-methyl-
1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride 0.71 g of N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino]- A mixture of 5- (4-hydroxy-2,5-dimethylphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester and 10 ml of 4N hydrochloric acid / dioxane was stirred at room temperature for 17 hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. After filtering off the insoluble product, reverse-phase preparative high-performance liquid chromatography (elution solvent:
(Acetonitrile / water = 9/11), followed by treatment with 4N hydrochloric acid / ethyl acetate to obtain 0.41 g of the title compound. Melting point: 170-171 [deg.] C.

Example 29 5- {4- [6- (3,5-Di-tert-butyl-4-hydroxyphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-
2,4-dione hydrochloride (Exemplary Compound No. 1-593) (29-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (3 , 5-Di-t-butyl-4-hydroxyphenoxy) phenyl} -N-methylcarbamic acid t
-Butyl ester 0.55 g of N- [2-amino-5-
(3,5-di-t-butyl-4-hydroxyphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester, 0.42 g of 4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.24g
Using diethyl cyanophosphonate, 0.15 g of triethylamine and 20 ml of anhydrous tetrahydrofuran in the same manner as in Example (2-1), followed by purification.
0.72 g of the title compound was obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.68.

(29-2) 5- {4- [6- (3,5-
Di-tert-butyl-4-hydroxyphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy]
Benzyl} thiazolidine-2,4-dione hydrochloride 0.72 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (3,5-di- t-butyl-4-hydroxyphenoxy) phenyl {-N-methylcarbamic acid t
-Butyl ester and a mixture of 20 ml of 4N hydrochloric acid / dioxane were stirred at room temperature for 17 hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. The insoluble product was collected by filtration and washed with ethyl acetate to give 0.41 g of the title compound. Melting point: 173-178 [deg.] C.

Example 30 5- {4- [6- (4′-hydroxybiphenyl-4-)
Yloxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4
-Dione hydrochloride (Exemplified Compound No. 1-171) (30-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4'-hydroxy Biphenyl-4-yloxy) phenyl {-N-methylcarbamic acid t-butyl ester 0.61 g of N- [2-amino-5- (4'-hydroxybiphenyl-1-yloxy) phenyl] -N-methylcarbamic acid t- Butyl ester, 0.51 g of 4
-(2,4-dioxothiazolidine-5-ylmethyl)
A mixture of phenoxyacetic acid, 0.29 g of diethyl cyanophosphonate, 0.18 g of triethylamine and 10 ml of anhydrous tetrahydrofuran was stirred at room temperature for 2 days. The reaction solution was concentrated, water was added, extracted with ethyl acetate, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (developing solvent: n-hexane / ethyl acetate = 1/1).
And the title compound was obtained. (30-2) 5- {4- [6- (4'-hydroxybiphenyl-4-yloxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione hydrochloride 20 ml N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino]
-5- (4'-Hydroxybiphenyl-4-yloxy) phenyl} -N-methylcarbamic acid t-butyl ester was dissolved in 4N hydrochloric acid / dioxane, and dissolved at room temperature.
Left for days. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. The insoluble product was collected by filtration and washed with ethyl acetate to obtain 0.23 g of the title compound. Melting point: 160-163 [deg.] C.

Example 31 5- {4- [6- (4-hydroxy-2-methylphenoxy) -1-methyl-1H-benzimidazole-2-
Ilmethoxy] benzyl} thiazolidine-2,4-dione hydrochloride (Exemplary Compound No. 1-481) and 5- {4
-[6- (4-hydroxy-3-methylphenoxy)-
1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride (Exemplary Compound No. 1-486) (31-1) N- {2- [4- (2,4- Dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-hydroxy-2-methylphenoxy)
1.88 g of N- [2-amino-5- (4-hydroxy-2-methylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester and N- [2 -Amino-5- (4-hydroxy-3-methylphenoxy) phenyl] -N-methylcarbamic acid mixture of t-butyl esters, 1.69 g of 4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid , 0.98g
Using diethyl cyanophosphonate, 0.61 g of triethylamine and 20 ml of anhydrous tetrahydrofuran in the same manner as in Example (2-1), followed by purification.
1.57 g of a mixture of the title compounds were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.53.

(31-2a) 5- {4- [6- (4-hydroxy-2-methylphenoxy) -1-methyl-1H
-Benzimidazol-2-ylmethoxy] benzyl}
Thiazolidine-2,4-dione hydrochloride and (31-2b) 5- {4- [6- (4-hydroxy-3)
-Methylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride 1.57 g of N- {2- [4- (2,4-dioxothiazolidine-)] 5-ylmethyl) phenoxyacetylamino] -5- (4-hydroxy-2-methylphenoxy)
Phenyl} -N-methylcarbamic acid t-butyl ester and N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino]
A mixture of -5- (4-hydroxy-3-methylphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester was dissolved in 20 ml of 4N hydrochloric acid / dioxane and stirred at room temperature for 66 hours. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. 1.24 g of the insoluble product was collected by filtration, and then separated and purified by reverse phase preparative high performance liquid chromatography [elution solvent: acetonitrile / water (containing 0.2% acetic acid and 0.2% triethylamine) = 2/3]. And
Treatment with 4N hydrochloric acid / ethyl acetate gave 50 mg of 5-
{4- [6- (4-Hydroxy-2-methylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione hydrochloride and 183 mg of 5- {4- [ 6- (4-hydroxy-3-methylphenoxy) -1-methyl-1H-
[Benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione hydrochloride was obtained.

(31-2a) Melting point: 165-168 ° C (31-2b) Melting point: 165-168 ° C.

Example 32 5- [4- {6- [4- (3,5-di-tert-butyl-4)
-Hydroxybenzoylamino) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy}
Benzyl] thiazolidine-2,4-dione (Exemplified Compound No. 1-1269) 400 mg of 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine -2,4-dione dihydrochloride, 204 mg of cyclopentanecarboxylic acid and 304 mg of triethylamine in 8 ml of anhydrous N,
After dissolving in N-dimethylformamide, 287 mg
1-ethyl-3- (3'-dimethylaminopropyl)
Carbodiimide hydrochloride was added, and the mixture was stirred at room temperature for 1 hour and left at the same temperature for 2 nights. After concentrating the reaction solution, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off.
The obtained residue is subjected to silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/2 to 1 /
Separated and purified in 3). The fraction containing the desired product was concentrated, and the obtained residue was recrystallized from n-hexane-ethyl acetate (1: 3) to obtain 176 mg of the title compound. Melting point: 159.8-162.0C.

Example 33 5- {4- [6- (4-benzyl-3-hydroxyphenoxy) -1-methyl-1H-benzimidazole-2
-Ylmethoxy] benzyl} thiazolidine-2,4-dione hydrochloride (Exemplary Compound No. 1-1230) (33-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetyl] Amino] -5- (4-benzyl-3-hydroxyphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester and N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetyl] Amino] -5- (4-hydroxy-3-methylphenoxy)
Phenylｇ-N-methylcarbamic acid t-butyl ester 1.8 g of N- [2-amino-5- (4-benzyl-3)
-Hydroxyphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester, 1.16 g of 4-
Reaction was carried out in the same manner as in Example (2-1) using (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.99 g of diethyl cyanophosphonate, 0.76 g of triethylamine and 30 ml of anhydrous tetrahydrofuran. And purified to give 1.5 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.32.

(33-2) 5- {4- [6- (4-benzyl-3-hydroxyphenoxy) -1-methyl-1H
-Benzimidazol-2-ylmethoxy] benzyl}
Thiazolidine-2,4-dione hydrochloride 1.4 g of N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino]
A mixture of -5- (4-benzyl-3-hydroxyphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester and 20 ml of 4N hydrochloric acid / dioxane was stirred at room temperature for 3 days. Ethyl acetate and n-
Hexane was added, and the insoluble product was collected by filtration and 1.5 g
The title compound was obtained. Melting point: 205-219 [deg.] C.

Example 34 5- {4- [1-Methyl-6- (4-methylthiophenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione and its hydrochloride (exemplified compound) No. 1-136) (34-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-methylthiophenoxy) phenyl}-
N-methylcarbamic acid t-butyl ester 1.93 g of N- [2-amino-5- (4-methylthiophenoxy) phenyl] -N-methylcarbamic acid t
-Butyl ester, 3.01 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid,
The reaction was carried out in the same manner as in Example (2-1) using 1.75 g of diethyl cyanophosphonate, 1.08 g of triethylamine and 80 ml of anhydrous tetrahydrofuran, and purified to obtain 2.96 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 7/3): Rf value = 0.11.

(34-2a) 5- {4- [1-methyl-
6- (4-Methylthiophenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione 2.95 g of N- {2- [4- (2,4-dioxothiazolidine-5) Ylmethyl) phenoxyacetylamino] -5- (4-methylthiophenoxy) phenyl}-
N-methylcarbamic acid t-butyl ester and 6
Example (2) was prepared using 0 ml of 4N hydrochloric acid / dioxane.
The reaction was carried out in the same manner as in -2a) and purification was carried out to obtain 2.15 g of the title compound. Melting point: 199-200 <0> C.

(34-2b) 5- {4- [1-methyl-
6- (4-methylthiophenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride 1.15 g of 5- {4- [1-methyl-6- (4-methylthio) Phenoxy) -1H-benzimidazole-2-
Ylmethoxy] benzyl @ thiazolidine-2,4-dione and 20 ml of 4N hydrochloric acid / ethyl acetate,
Reaction and purification were carried out in the same manner as in Example (2-2b).
06 g of the title compound were obtained. Melting point: 137-147 [deg.] C.

Example 35 5- {4- [1-Methyl-6- (4-methoxyphenoxy) -1H-benzimidazol-2-ylmethoxy]
Benzyl @ thiazolidine-2,4-dione and its hydrochloride (Exemplified Compound No. 1-132) (35-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] ] -5- (4-Methoxyphenoxy) phenyl} -N
-Methylcarbamic acid t-butyl ester 2.0 g of N- [2-amino-5- (4-methoxyphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester, 2.0 g of 4- (2,4-di- Oxothiazolidine-5-ylmethyl) phenoxyacetic acid, 1.3 g
Using diethyl cyanophosphonate, 0.81 g of triethylamine and 50 ml of anhydrous tetrahydrofuran in the same manner as in Example (2-1), followed by purification.
3.3 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.61.

(35-2a) 5- {4- [1-methyl-
6- (4-methoxyphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione 3.28 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-methoxyphenoxy) phenyl} -N
-50 ml of t-butyl carbamic acid methyl ester
Was stirred at 65 ° C. for 8 hours, and then left at room temperature overnight. The reaction solution was concentrated, water was added, the mixture was neutralized with 5% aqueous sodium hydrogen carbonate, and extracted with ethyl acetate.
The extract was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue obtained is ether-
A mixed solvent of ethyl acetate (1: 1) was added, and the precipitated crystals were collected by filtration to obtain 1.91 g of the title compound. Melting point: 122-126 [deg.] C.

(35-2b) 5- {4- [1-methyl-
6- (4-methoxyphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione hydrochloride 1.8 g of 5- {4- [1-methyl-6- (4-methoxyphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione and Using 50 ml of 4N hydrochloric acid / ethyl acetate, the reaction was carried out in the same manner as in Example (2-2b), followed by purification to give 1.85.
g of the title compound were obtained. Melting point: 148-151 [deg.] C.

Example 36 5- {4- [1-Methyl-6- (4-trifluoromethylphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione and its hydrochloride ( Exemplified Compound No. 1-131) (36-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-trifluoromethylphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester 0.68 g of N- [2-amino-5- (4-trifluoromethylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester, 0.73 g of 4- (2 , 4
-Dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.49 g of diethyl cyanophosphonate, 0.3
The reaction was carried out in the same manner as in Example (2-1) using 0 g of triethylamine and 50 ml of anhydrous tetrahydrofuran, followed by purification to obtain 0.97 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/1): Rf value = 0.23.

(36-2a) 5- {4- [1-methyl-
6- (4-trifluoromethylphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione 0.95 g of N- {2- [4- (2,4-dioxothiazolidine-)] 5-ylmethyl) phenoxyacetylamino] -5- (4-trifluoromethylphenoxy) phenyl} -N-methylcarbamic acid t-butyl ester was dissolved in 20 ml of trifluoroacetic acid,
After stirring for hours, it was left at room temperature overnight. The reaction solution was concentrated, water was added, the mixture was neutralized with 5% aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue is subjected to silica gel column chromatography (elution solvent: n-
Hexane / ethyl acetate = 1/2) to give 0.60
g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.29.

(36-2b) 5- {4- [1-methyl-
6- (4-trifluoromethylphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride 0.58 g of 5- {4- [1-methyl-6- (4 -Trifluoromethylphenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2;
Using 4-dione and 20 ml of 4N hydrochloric acid / ethyl acetate, the reaction was carried out in the same manner as in Example (2-2b), and purification was performed to obtain 0.55 g of the title compound. Melting point: 145-147 [deg.] C.

Example 37 5- {4- [6- (4-benzylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy]
Benzyl @ thiazolidine-2,4-dione hydrochloride (Exemplary Compound No. 1-184) (37-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino]- 5- (4-benzylphenoxy) phenyl} -N
-Methylcarbamic acid t-butyl ester 0.61 g of N- [2-amino-5- (4-benzylphenoxy) phenyl] -N-methylcarbamic acid t-
Butyl ester, 0.51 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid.
Using 29 g of diethyl cyanophosphonate, 0.18 g of triethylamine and 10 ml of anhydrous tetrahydrofuran, the reaction was carried out in the same manner as in Example (2-1) and purification was performed to obtain 0.91 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.26.

(37-2) 5- {4- [6- (4-benzylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-
2,4-dione hydrochloride 0.91 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (4-benzylphenoxy) phenyl} -N
-Methylcarbamic acid t-butyl ester and 10
ml of a mixture of 4N hydrochloric acid / dioxane was left at room temperature for 3 days. The reaction solution was evaporated to dryness under reduced pressure, and ethyl acetate was added. The insoluble product was collected by filtration and washed with ethyl acetate to obtain 0.69 g of the title compound. Melting point: 170-180 ° C.

Example 38 5- {4- [6- (3-hydroxyphenoxy) -1-]
Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride (Exemplary Compound No. 1-41) (38-1) N- {2- [4- (2,4-dioxo) Thiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (3-hydroxyphenoxy) phenyl}-
N-methylcarbamic acid t-butyl ester 0.95 g of N- [2-amino-5- (3-hydroxyphenoxy) phenyl] -N-methylcarbamic acid t
-Butyl ester, 0.89 g of 4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetic acid,
The reaction was carried out in the same manner as in Example (2-1) using 0.52 g of diethyl cyanophosphonate, 0.32 g of triethylamine and 30 ml of anhydrous tetrahydrofuran, followed by purification to obtain 1.18 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.28.

(38-2) 5- {4- [6- (3-hydroxyphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-
2,4-dione hydrochloride 1.18 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- (3-hydroxyphenoxy) phenyl}-
N-methylcarbamic acid t-butyl ester and 2
0 ml of 4N hydrochloric acid / dioxane mixture was added at room temperature for 18 hours.
Left for hours. After concentrating the reaction solution, ethyl acetate was added and the mixture was irradiated with ultrasonic waves. After filtering the insoluble grade,
Washing with ethyl acetate gave 0.86 g of the title compound. Melting point: 192-195C.

Example 39 5- [4- {6- [4- (tetrazol-5-yl) phenoxy] -1-methyl-1H-benzimidazole-
2-ylmethoxy {benzyl] thiazolidine-2,4-
Dione hydrochloride (Exemplified Compound No. 1-1154) (39-1) N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] -5- [4- (tetrazole- 5-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester 0.69 g of N- {2-amino-5- [4- (tetrazol-5-yl) phenoxy] phenyl} -N-methylcarbamic acid t -Butyl ester, 0.37 g of 4-
(2,4-Dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.21 g of diethyl cyanophosphonate, 0.13 g of triethylamine and 30 ml of anhydrous tetrahydrofuran were reacted in the same manner as in Example (2-1). And purified to give 0.76 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.49.

(39-2) 5- [4- {6- [4- (tetrazol-5-yl) phenoxy] -1-methyl-1
H-benzimidazol-2-ylmethoxy {benzyl] thiazolidine-2,4-dione hydrochloride 0.76 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino]- A mixture of 5- [4- (tetrazol-5-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester and 20 ml of 4N hydrochloric acid / dioxane was stirred at room temperature for 24 hours. The reaction solution was concentrated, and ethyl acetate was added. The insoluble product was collected by filtration and washed with ethyl acetate to give 0.44 g of the title compound. Melting point: 232-235 ° C.

Example 40 5- {4- [6- (4-cyanophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione hydrochloride (Exemplified Compound No. 1) -1210) 0.69 g of 5- {4- [6- (4-cyanophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} -3-triphenylmethylthiazolidine-2,4-dione A mixture of 25 ml of 80% aqueous acetic acid was stirred at 70 ° C. for 3 hours. Concentrate the reaction mixture and add 2
After adding 50 ml of 10% aqueous sodium bicarbonate and stirring at room temperature for several hours, the insoluble product was collected by filtration, washed with water and air-dried. The obtained 5- {4- [6- (4-cyanophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy]
10 ml of 4N hydrochloric acid / dioxane was added to benzyl dithiazolidine-2,4-dione, and the mixture was stirred at room temperature for 2 hours. The insoluble product was collected by filtration and washed with ethyl acetate.
0.41 g of the title product was obtained. Melting point: 215-218 [deg.] C.

Example 41 5- [4- (6-Pentafluorophenoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione hydrochloride (Exemplary Compound No. 1-1235) (41-1a) 5- [4- (6-Pentafluorophenoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione 1.17 g of 2-hydroxymethyl-1- Methyl-6-
Pentafluorophenoxy-1H-benzimidazole, 1.86 g of 5- (4-hydroxybenzyl) -3
-Triphenylmethylthiazolidine-2,4-dione,
1.01 g of azodicarbonyl dipiperidine, 0.81
A mixture of g of tri-n-butylphosphine and 50 ml of toluene was stirred at room temperature for 16 hours. The reaction solution was subjected to silica gel column chromatography, fractions eluted with n-hexane / ethyl acetate = 3/2 were collected, and the solvent was distilled off. The resulting 5- [4- (6-pentafluorophenoxy-1-methyl-1H-benzimidazole-2
-Ylmethoxy) benzyl] -3-triphenylmethylthiazolidine-2,4-dione, 100 ml of 80% aqueous acetic acid was added, and the mixture was stirred at 70 ° C for 1 hour. After concentrating the reaction solution, the mixture was neutralized with 10% aqueous sodium bicarbonate, and the precipitated crystals were collected by filtration and washed with water. The obtained crude crystals were separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/1) to give 1.29 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.42.

(41-1b) 5- [4- (6-pentafluorophenoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl] thiazolidine
2,4-dione hydrochloride 1.29 g of 5- [4- (6-pentafluorophenoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione and 30 ml of 4N The reaction was carried out in the same manner as in Example (2-2b) using hydrochloric acid / ethyl acetate, and purified to give 1.13.
g of the title compound were obtained. Melting point: 169-172 [deg.] C.

Example 42 5- {4- [6- (2,5-Di-tert-butyl-4-hydroxyphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-
2,4-dione and its hydrochloride (Exemplary Compound No. 1-
1234) (42-1) N- {2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino] -5- (2,5-di-t-butyl-4-hydroxyphenoxy) ) Phenyl} -N-methylcarbamic acid t
-Butyl ester 0.71 g of N- [2-amino-5-
(2,5-di-t-butyl-4-hydroxyphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester, 0.68 g of 4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetic acid, 0.39g
The reaction was carried out in the same manner as in Example (2-1) using diethyl cyanophosphonate, 0.24 g of triethylamine and 30 ml of anhydrous tetrahydrofuran, followed by purification.
1.13 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.41.

(42-2a) 5- {4- [6- (2,5
-Di-t-butyl-4-hydroxyphenoxy) -1-
Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione 1.12 g of N- {2- [4- (2,4-dioxothiazolidine-5-ylmethyl) phenoxyacetylamino]- 5- (2,5-di-t-butyl-4-hydroxyphenoxy) phenyl} -N-methylcarbamic acid t
Using butyl ester and 25 ml of 4N hydrochloric acid / dioxane in the same manner as in Example (2-2a),
Purification gave 0.73 g of the title compound.

Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value =
0.19.

(42-2b) 5- {4- [6- (2,5
-Di-t-butyl-4-hydroxyphenoxy) -1-
Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione hydrochloride 0.73 g of 5- {4- [6- (2,5-di-t-butyl-4-hydroxyphenoxy) ) -1-Methyl-1H-
[Benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione and 20 ml of 4N hydrochloric acid / ethyl acetate were treated in the same manner as in Example (2-2b) to give 0.31 g of the title compound. Obtained. Melting point: 182-195C.

Example 43 5- {4- [6- (3,5-Di-tert-butyl-4-hydroxyphenylthio) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzylidene} thiazolidine-2 , 4-dione (Exemplified Compound No. 5-135) 502 mg of 4- [6- (3,5-di-t-butyl-4)
-Hydroxyphenylthio) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzaldehyde, 234 mg of thiazolidine-2,4-dione, 17
A mixture of 0 mg piperidine and 60 ml ethanol was heated at reflux for 19 hours. After completion of the reaction, the obtained reaction solution was dried and poured. The insoluble product was collected by filtration and washed with water and diisopropyl ether to give 517 mg of the title compound. Melting point: 247-249 [deg.] C.

Example 44 5- {4- [6- (4-n-hexylaminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione (exemplary compound number 1-1242) 4.10 g of N- [2-amino-5- (4-t-butoxycarbonyl-n-hexylaminophenoxy) phenyl] -N-methylcarbamic acid t-butyl ester,
2.81 g of 4- (2,4-dioxothiazolidine-5
A mixture of -ylmethyl) phenoxyacetic acid, 1.63 g diethyl cyanophosphonate, 1.01 g triethylamine and 100 ml anhydrous tetrahydrofuran was stirred at room temperature for 28 hours. After concentrating the reaction solution, water was added,
The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off from the extract, and 50
Then, 4 ml of 4N hydrochloric acid / dioxane was added, and the mixture was stirred at room temperature for 66 hours. After pouring the reaction mixture into water and neutralizing with sodium bicarbonate,
Extracted with ethyl acetate. After the extract was dried over anhydrous sodium sulfate, the solvent was distilled off, and the obtained residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 2/3) to give 2.89 g of the title compound. The compound was obtained. Melting point: 177-179 [deg.] C.

Example 45 5- {4- (6- [4- (N-acetyl-NN-hexylamino) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl} thiazolidine-2 , 4-dione hydrochloride (Exemplary Compound No. 1-13)
18) 502 mg of 5- {4- [6- (4-n-hexylaminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,
4-dione, 112 mg acetic anhydride, 356 mg pyridine, 37 mg 4-dimethylaminopyridine and 3
0 ml of a mixed solution of anhydrous tetrahydrofuran was added at room temperature for 1 hour.
Left for 4 hours. After concentrating the reaction solution, water was added, the mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off from the extract, and the obtained residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/3) and treated with 20 ml of 4N hydrochloric acid / ethyl acetate. 410 mg of the title compound were obtained.

Example 46 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione dihydrochloride (exemplified compound) No. 1-142) (46-1) N- {5- (4-aminophenoxy) -2
-[4- (2,4-Dioxothiazolidine-5-ylmethyl) phenoxyacetylamino] phenyl} -N-methylcarbamic acid t-butyl ester 500 mg of N- [2-amino-5- (4-t-butoxycarbonyl) Aminophenoxy) phenyl] -N-methylcarbamic acid t-butyl ester, 366 mg 4
-(2,4-dioxothiazolidine-5-ylmethyl)
The reaction was carried out in the same manner as in Example (2-1) using phenoxyacetic acid, 212 mg of diethyl cyanophosphonate, 132 mg of triethylamine, and 10 ml of anhydrous tetrahydrofuran, followed by purification to obtain 395 mg of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/3): Rf value = 0.51.

(46-2) 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2;
4-dione dihydrochloride 27.08 g of N- {5- (4-aminophenoxy)-
2- [4- (2,4-dioxothiazolidin-5-ylmethyl) phenoxyacetylamino] phenyl} -N-
Methyl carbamic acid t-butyl ester was dissolved in 50 ml of 1,4-dioxane, 150 ml of 4N hydrochloric acid / dioxane was added, and the mixture was stirred at room temperature for 2 days. The precipitated product was collected by filtration and washed with ethyl acetate to obtain 14.43 g.
The title compound was obtained. Melting point: 195 DEG C. (decomposition point).

Example 47 5- {4- [6- (4-acetylaminophenoxy)-
1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione (Exemplary Compound No. 1-164) 400 mg of 5- {4- [6- (4-aminophenoxy) -1-methyl -1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione dihydrochloride, 71 mg of acetyl chloride, 263 mg of triethylamine and 8 ml of anhydrous N, N-dimethylformamide were stirred at room temperature for 1 hour. did. After completion of the reaction, the reaction solution was concentrated, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated saline, dried over anhydrous sodium sulfate, the solvent was distilled off, and the obtained residue was subjected to silica gel column chromatography (elution solvent: n-hexane / ethyl acetate = 1/4 → acetic acid). Purification by ethyl → ethyl acetate / methanol = 1/10) gave 320 mg of the title compound. Melting point: 92.2-95.0C.

Example 48 5- {4- [6- (4-benzoylaminophenoxy)
-1-Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione (Exemplary Compound No. 1-1248) 400 mg of 5- {4- [6- (4-aminophenoxy) -1-] Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione dihydrochloride, 126 mg benzoyl chloride, 263 mg
And purified using 8 ml of triethylamine and 8 ml of anhydrous N, N-dimethylformamide as in Example 47 to give 247 mg of the title compound. Melting point: 200.2-204.4C.

Example 49 5- [4- {6- [4- (3-chlorobenzoylamino) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy} benzyl] thiazolidine-
2,4-dione (Exemplified Compound No. 1-1256) 400 mg of 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4 -Dione dihydrochloride, 123 mg of 3-chlorobenzoyl chloride,
263 mg of triethylamine and 8 ml of anhydrous N,
The reaction was carried out in the same manner as in Example 47 using N-dimethylformamide, and purified to obtain 232 mg of the title compound. Melting point: 237.8-238.8C.

Example 50 5- {4- [6- (4-Isonicotinoylaminophenoxy) -1-methyl-1H-benzimidazole-2-
Ilmethoxy] benzyl} thiazolidine-2,4-dione (Exemplary Compound No. 1-1131) 400 mg of 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl Using thiazolidine-2,4-dione dihydrochloride, 142 mg of isonicotinoyl chloride hydrochloride, 232 mg of triethylamine and 8 ml of anhydrous N, N-dimethylformamide in the same manner as in Example 47, purification was carried out. 306 mg of the title compound were obtained. Melting point: 222 ° C (decomposition point).

Example 51 5- {4- [6- (4-nicotinoylaminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione (Exemplified Compound No. 1) -1305) 400 mg of 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione dihydrochloride, 195 mg of chloride Nicotinoyl hydrochloride, 3
54 mg of triethylamine and 8 ml of anhydrous N, N
The reaction was carried out in the same manner as in Example 47 using -dimethylformamide, and purified to obtain 297 mg of the title compound. Melting point: 213.0-214.7C.

Example 52 5- [4- {6- [4- (2,4-difluorobenzoylamino) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy} benzyl] thiazolidine-2,4- Dione (Exemplified Compound No. 1-1263) 400 mg of 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione-2 Example 4 was prepared using the hydrochloride, 141 mg 2,4-difluorobenzoyl chloride, 232 mg triethylamine and 8 ml anhydrous N, N-dimethylformamide.
Reacted and purified as in 7 to give 251 mg of the title compound.

Melting point: 171.5-174.2 ° C.

Example 53 5- [4- {6- [4- (2-naphthoylamino) phenoxy] -1-methyl-1H-benzimidazole-2
-Ylmethoxy {benzyl} thiazolidine-2,4-dione (Exemplary Compound No. 1-1277) 400 mg of 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] Benzyl dithiazolidine-2,4-dione dihydrochloride, 153 mg of 2-naphthoyl chloride, 232
The reaction was conducted in the same manner as in Example 47 using mg of triethylamine and 8 ml of anhydrous N, N-dimethylformamide, and purified to obtain 337 mg of the title compound. Melting point: 220.7-222.7C.

Example 54 5- {4- [6- (4-cyclohexanoylaminophenoxy) -1-methyl-1H-benzimidazole-2
-Ylmethoxy] benzyl} thiazolidine-2,4-dione (Exemplary Compound No. 1-1298) 90 mg of cyclohexanecarboxylic acid and 232 mg
Was dissolved in 8 ml of anhydrous N, N-dimethylformamide, and 87 mg of ethyl chloroformate was added dropwise at room temperature, followed by stirring at the same temperature for 1.5 hours. Next, 400 mg of 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione dihydrochloride was added little by little, and the mixture was stirred at room temperature. For 2 hours and at 50 ° C. for 1.5 hours. After concentrating the reaction solution, water was added,
The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off from the extract, ethyl acetate was added to the obtained residue, and the precipitated crystals were collected by filtration and washed with ethyl acetate to obtain 262 mg of the title compound. Melting point: 181.7-183.7C.

Example 55 5- {4- [6- (4-Cyclopentanoylaminophenoxy) -1-methyl-1H-benzimidazole-2
-Ylmethoxy] benzyl} thiazolidine-2,4-dione (Exemplary Compound No. 1-1292) 90 mg of cyclopentanecarboxylic acid and 232 mg
Was dissolved in 8 ml of anhydrous N, N-dimethylformamide, and 87 mg of ethyl chloroformate was added dropwise at room temperature, followed by stirring at the same temperature for 1.5 hours. Next, 400 mg of 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione dihydrochloride was added little by little, and the mixture was stirred at room temperature. After stirring for 5 hours at
It was left overnight at the same temperature. After concentrating the reaction solution, water was added,
The precipitated crystals were collected by filtration and washed with water and ethyl acetate to obtain 236 mg of the title compound. Melting point: 227.3-228.4C.

Reference Example 1 4-Methoxymethoxy-2,3,5-trimethylphenol 50 g of sodium hydride (55% by weight) was washed with n-hexane, and 2,000 ml of anhydrous tetrahydrofuran was added. Under cooling, a solution of 2,3,6-trimethyl-4-pivaloyloxyphenol (240 g) in anhydrous tetrahydrofuran (500 ml) was added dropwise over 90 minutes, and the mixture was stirred at room temperature for 2 hours. 86 ml of the reaction solution under ice-cooling
Was added dropwise over 30 minutes, and the mixture was stirred at room temperature for 1 hour. Then, about 50% of tetrahydrofuran was distilled off under reduced pressure, poured into ice water, and extracted with ethyl acetate. After the extract was washed with saturated saline and dried over anhydrous sodium acetate, the solvent was distilled off under reduced pressure to obtain 294 g.
To give a yellow oil. 1000 m to the obtained yellow oil
of methanol and added with potassium hydroxide 116 under ice-cooling.
g of methanol solution (500 ml) was added dropwise and stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure, and the obtained residue was poured into ice water, neutralized with a 6N aqueous hydrochloric acid solution, and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue is subjected to silica gel column chromatography (elution solvent: n-hexane / ethyl acetate = 5/1 → 3
/ 1) to give 193 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1): Rf value = 0.47.

Reference Example 2 6- (4-Methoxymethoxy-2,3,5-trimethylphenoxy) -2-methylamino-3-nitropyridine 4-methoxymethoxy-2,3,5-trimethylphenol 193 g of anhydrous N 300 ml of a solution of N, N-dimethylformamide in 50 g of sodium hydride (55% by weight, washed with n-hexane) and 1000 ml of anhydrous N, N
The mixture was added dropwise to the suspension of dimethylformamide over 1 hour under ice cooling, and then stirred at room temperature for 2 hours. 6 in the reaction solution
-Chloro-2-methylamino-3-nitropyridine 19
7 g of anhydrous N, N-dimethylformamide solution 800 m
was added dropwise over 1 hour under ice cooling, followed by stirring at room temperature for 2 hours. The solvent was distilled off under reduced pressure, the residue was poured into ice water, ethyl acetate and water were added, and the insoluble matter was collected by filtration, followed by washing with water and ethanol to obtain 141 g of the title compound. The organic layer was separated from the filtrate, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, washed with saturated saline, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was washed with ethanol to obtain 126 g of the title compound. Melting point: 102-103 ° C.

Reference Example 3 2-hydroxymethyl-5- (4-hydroxy-2,
3,5-trimethylphenoxy) -3-methyl-3H-
Imidazo [4,5-b] pyridine 288 g of 6- (4-methoxymethoxy-2,3,5-
Trimethylphenoxy) -2-methylamino-3-nitropyridine, 14 g of 10% palladium on carbon and 1
A mixture of 500 ml of methanol was stirred at room temperature under a hydrogen atmosphere for 2 hours. To the reaction solution, 14 g of 10% palladium-carbon, 500 ml of methanol and 500 ml
Of tetrahydrofuran and further added under a hydrogen atmosphere for a further 50
Stirred at C for 8 hours. After filtering off the catalyst from the reaction solution and concentrating the filtrate, 500 g of glycolic acid was added to the obtained residue, followed by stirring at 150 ° C. for 6 hours. 1000
To the mixture was added 4 ml of a 4N hydrochloric acid aqueous solution, and the mixture was stirred at 120 ° C. for 1 hour and left at room temperature overnight. The reaction solution was poured into ice water, neutralized with an aqueous sodium hydroxide solution and an aqueous sodium carbonate solution, and insolubles were filtered off. The obtained solid was separated and purified by silica gel column chromatography using tetrahydrofuran as an eluting solvent, and the obtained solid was washed with ethanol to obtain 45.5 g of the title compound. Melting point: 181-182C.

Reference Example 4 2-acetoxymethyl-5- (4-acetoxy-2,
3,5-trimethylphenoxy) -3-methyl-3H-
Imidazo [4,5-b] pyridine 2-hydroxymethyl-5- (4-hydroxy-2,
3,5-trimethylphenoxy) -3-methyl-3H-
69 ml of acetic anhydride was added dropwise to 400 ml of a pyridine solution of 38.0 g of imidazo [4,5-b] pyridine under ice-cooling, and the mixture was stirred at room temperature for 3 hours and then left at room temperature overnight. The solvent was distilled off under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (eluent: n-solvent).
Hexane / ethyl acetate = 1/2).
5 g of the title compound were obtained. Melting point: 128-129 [deg.] C.

Reference Example 5 5- (4-acetoxy-2,3,5-trimethylphenoxy) -2-hydroxymethyl-3-methyl-3H-imidazo [4,5-b] pyridine 2-acetoxymethyl-5- (4-acetoxy-2,
3,5-trimethylphenoxy) -3-methyl-3H-
To a methanol solution (500 ml) of imidazo [4,5-b] pyridine (26.0 g), 1.2 ml of a methanol solution of sodium methoxide (28%) was added dropwise at -18 ° C, and the mixture was stirred at the same temperature for 1 hour. After water was added to the reaction solution and the mixture was extracted with ethyl acetate, the extract was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was crystallized with ethanol.
0.5 g of the title compound was obtained. Melting point: 179-180 [deg.] C.

Reference Example 6 N- [5- (4-methoxymethoxy-2,3,5-trimethylphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 6.11 g of sodium hydride (55%) % By weight)
and suspended in 2 ml of N, N-dimethylformamide.
7.5 g of 4-methoxymethoxy-2,3,5-trimethylphenol was added and stirred at room temperature for 1 hour. Next, 40.1 g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester was added little by little to the reaction solution, stirred at 120 ° C. for 2 hours, concentrated, and then water was added. And extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the obtained residue was separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 5/1). 2.0 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 4/1): Rf value = 0.55.

Reference Example 7 N- [2-amino-5- (4-methoxymethoxy-2,
3,5-Trimethylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 57.0 g of N- [5- (4-methoxymethoxy-2,
3,5-trimethylphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester,
A mixture of 3 g of 10% palladium on carbon and 500 ml of methanol was vigorously stirred at room temperature under a hydrogen atmosphere for 8 hours. After removing the catalyst from the reaction solution by filtration and concentrating the filtrate,
The obtained residue was separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 3/1) to obtain 52.5 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1): Rf value = 0.31.

Reference Example 8 2-chloro-3,5-dimethylbenzene-1,4-diol 12.08 g of 3,5-dimethyl-4-nitrophenol, 11.45 g of cuprous oxide, 100 ml of 1, 4-
Dioxane, 10 ml acetone and 100 ml 6
The mixture of normal hydrochloric acid was heated to reflux for 2 hours. The reaction solution was poured into ice water and extracted with ether. The obtained extract was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 150 ml of dichloromethane, and after adding 3.61 g of sodium borohydride under ice-cooling, 50 ml of methanol was added dropwise at an internal temperature of 10 ° C. or lower, followed by stirring at room temperature for 90 minutes. The reaction solution was concentrated, poured into ice water, acidified with 3N hydrochloric acid, and the precipitated product was collected by filtration, washed with water, and further washed with n-hexane to obtain 5.93 g of the title compound. . Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 4/1): Rf value = 0.35.

Reference Example 9 3-chloro-2,6-dimethyl-4-pivaloyloxyphenol 5.91 g of 2-chloro-3,5-dimethylbenzene-
1,4-diol, 8.13 g of pyridine and 30 m
l of a dichloromethane solution containing 4.54 g of pivalic acid chloride under ice-cooling.
1 was added dropwise, and the mixture was stirred at the same temperature for 1 hour and at room temperature for 90 minutes.
After concentrating the reaction solution, adding water and extracting with ethyl acetate,
After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue is subjected to silica gel column chromatography (elution solvent: n-hexane / ethyl acetate = 10/1).
And 8.02 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 4/1): Rf value = 0.53.

Reference Example 10 2-Chloro-4-methoxymethoxy-3,5-dimethylphenol To a suspension of 1.78 g of sodium hydride (55% by weight) in 20 ml of anhydrous tetrahydrofuran was added 3-chloro-2. Solution of 8.02 g of 2,6-dimethyl-4-pivaloyloxyphenol in 30 ml of anhydrous tetrahydrofuran
Was added dropwise and stirred at room temperature for 30 minutes. 3.28 g in the reaction solution
Was added, and the mixture was stirred at room temperature for 13 hours. The reaction mixture was concentrated, water was added, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.
Dissolve in 0 ml of methanol and add potassium hydroxide 3.5
30 ml of a 1 g methanol solution was added dropwise, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated, neutralized with 3N hydrochloric acid and sodium bicarbonate, and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.
The obtained residue was separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 10/1) to obtain 5.65 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 10/1): Rf value = 0.29.

Reference Example 11 2,6-Dimethyl-4-pivaloyloxyphenol 6.90 g of 2,6-dimethylbenzene-1,4-diol, 6.63 g of pivalic acid chloride, 11.85 g
Of pyridine and 60 ml of dichloromethane,
The reaction was carried out in the same manner as in Reference Example 9 and purification was performed to obtain 6.77 g of the title compound. Melting point: 92-94 [deg.] C.

Reference Example 12 4-methoxymethoxy-3,5-dimethylphenol 5 containing 1.72 g of sodium hydride (55% by weight)
To a suspension of 0 ml of anhydrous tetrahydrofuran, add 6.75
g of 2,6-dimethyl-4-pivaloyloxypheno-
After stirring at room temperature for 30 minutes, 3.18 g of chloromethyl methyl ether was added to the reaction solution, and the mixture was stirred at the same temperature for 3 hours. After adding water to the reaction solution and extracting with ethyl acetate, the extract was dried over anhydrous sodium sulfate,
The solvent was distilled off under reduced pressure to obtain 8.17 g of crude pivalic acid.
4-methoxymethoxy-3,5-dimethylphenyl ester was obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 10/1): Rf value = 0.39 8.09 g of crude 4-methoxymethoxy-pivalic acid-
3,5-Dimethylphenyl ester was dissolved in 30 ml of methanol, 30 ml of a methanol solution of 3.40 g of potassium hydroxide was added dropwise, and the mixture was stirred at room temperature for 4 hours. The reaction solution was concentrated, water was added, neutralized with 3N hydrochloric acid and sodium bicarbonate, extracted with ethyl acetate, and the extract was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 4/1) to obtain 5.58 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 10/1): Rf value = 0.10.

Reference Example 13 N- [5- (4-benzyloxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 1.60 g of 4-benzyloxyphenol, 2.29
g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.35 g of sodium hydride (55% by weight) and 20 ml of anhydrous N, N-dimethylformamide. The reaction was carried out in the same manner as in Reference Example 6, and purification was carried out to obtain 3.33 g of the title compound. Melting point: 108-110 ° C. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 5/1): Rf = 0.36.

Reference Example 14 N- [5- (4-methoxymethoxy-3,5-dimethylphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 1.46 g of 4-methoxymethoxy-3, 5-dimethylphenol, 2.29 g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.35 g of sodium hydride (55% by weight)
And purified using 30 ml of anhydrous N, N-dimethylformamide in the same manner as in Reference Example 6.
4 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 5/1): Rf value = 0.29.

Reference Example 15 N- [5- (2-chloro-4-methoxymethoxy-3,
5-dimethylphenoxy) -2-nitrophenyl] -N
-Methylcarbamic acid t-butyl ester 5.65 g of 2-chloro-4-methoxymethoxy-3,
5-dimethylphenol, 8.88 g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid
Reaction was carried out in the same manner as in Reference Example 6 using t-butyl ester, 1.35 g of sodium hydride (55% by weight) and 100 ml of anhydrous N, N-dimethylformamide.
Purification provided 9.19 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 4/1): Rf value = 0.47.

Reference Example 16 N- [5- (pyridin-2-yloxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 0.76 g of 2-hydroxypyridine, 2.29 g of N
-(5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.35 g of sodium hydride (55% by weight) and 10 ml of anhydrous N, N
Using -dimethylformamide, the reaction was carried out in the same manner as in Reference Example 6, and purification was performed to obtain 0.36 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 4/1): Rf value = 0.32.

Reference Example 17 N- [5- (3,5-di-t-butyl-4-hydroxyphenylthio) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 476 mg of 3,5-diethyl -T-butyl-4-hydroxybenzenethiol, 573 mg of N- (5-chloro-2
-Nitrophenyl) -N-methylcarbamic acid t-butyl ester, reacted in the same manner as in Reference Example 6 using 175 mg of sodium hydride (55% by weight) and 10 ml of anhydrous N, N-dimethylformamide, and purified. , 3
71 mg of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 4/1): Rf value = 0.59.

Reference Example 18 N- [5- (4-amino-3,5-dimethylphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 1.10 g of 4-amino-3,5- Dimethylphenol, 2.29 g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester,
0.35 g sodium hydride (55% by weight) and 3
Using 0 ml of anhydrous N, N-dimethylformamide,
The reaction was carried out in the same manner as in Reference Example 6 and purified to obtain 2.27 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1): Rf value = 0.24.

Reference Example 19 N- [5- (4-t-butoxycarbonylamino-3,
5-dimethylphenoxy) -2-nitrophenyl] -N
-Methylcarbamic acid t-butyl ester 2.27 g of N- [5- (4-amino-3,5-dimethylphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester, 1.28 g of bicarbonate A mixture of di-t-butyl, 0.59 g of triethylamine and 20 ml of anhydrous tetrahydrofuran was heated at reflux for 6 hours. The reaction solution was concentrated, water was added, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 10/1) to obtain 1.74 g of the title compound. Melting point: 154-156 [deg.] C.

Reference Example 20 N- [2-amino-5- (4-hydroxyphenoxy)
Phenyl] -N-methylcarbamic acid t-butyl ester 3.32 g of N- [5- (4-benzyloxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester, 0.39 g of 10% palladium Reaction was carried out in the same manner as in Reference Example 7 using carbon, 100 ml of methanol and 100 ml of 1,4-dioxane, followed by purification to obtain 2.40 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.59.

Reference Example 21 N- [2-amino-5- (4-methoxymethoxy-3,
5-dimethylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 3.12 g of N- [5- (4-methoxymethoxy-3,
5-dimethylphenoxy) -2-nitrophenyl] -N
-Methylcarbamic acid t-butyl ester, 0.33
g of 10% palladium-carbon and 30 ml of methanol, reacted and purified in the same manner as in Reference Example 7.
2.72 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1): Rf value = 0.14.

Reference Example 22 N- [2-amino-5- (4-t-butoxycarbonylamino-3,5-dimethylphenoxy) phenyl] -N
-Methylcarbamic acid t-butyl ester 1.71 g
N- [5- (4-t-butoxycarbonylamino-
3,5-dimethylphenoxy) -2-nitrophenyl]
-N-methylcarbamic acid t-butyl ester;
A mixture of 2 g of 10% palladium-carbon and 100 ml of methanol was stirred vigorously under a hydrogen atmosphere at room temperature for 11 hours. The catalyst was removed by filtration from the reaction solution, and the filtrate was concentrated.
1.56 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1): Rf value = 0.14.

Reference Example 23 N- {5- [2- (morpholin-4-yl) phenoxy] -2-nitrophenyl} -N-methylcarbamic acid t-butyl ester 0.72 g of 2- (4-morpholino) phenol 1.
15 g of N- (5-chloro-2-nitrophenyl) -N
-Methylcarbamic acid t-butyl ester, 0.17
The reaction was carried out in the same manner as in Reference Example 6 using g of sodium hydride (55% by weight) and 10 ml of anhydrous N, N-dimethylformamide, and purified to obtain 1.44 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 4/1): Rf value = 0.34.

Reference Example 24 N- {5- [3- (morpholin-4-yl) phenoxy] -2-nitrophenyl} -N-methylcarbamic acid t-butyl ester 2.16 g of 3- (4-morpholino) phenol 3.
37 g of N- (5-chloro-2-nitrophenyl) -N
-Methylcarbamic acid t-butyl ester and 15 m
Using 1 l of anhydrous N, N-dimethylformamide, the reaction was carried out in the same manner as in Reference Example 6, followed by purification to obtain 5.0 g of the title compound. Silica gel thin layer chromatography (developing solvent: benzene / ethyl acetate = 10/1): Rf value = 0.34.

Reference Example 25 N- {2-amino-5- [2- (morpholin-4-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester 1.44 g of N- {5- [2- (Morpholin-4-yl) phenoxy] -2-nitrophenyl} -N-methylcarbamic acid t-butyl ester, 0.20 g of 10
% Palladium-carbon and 50 ml of methanol, and reacted and purified as in Reference Example 7.
The title compound was obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/1): Rf value = 0.25.

Reference Example 26 N- {2-amino-5- [3- (morpholin-4-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester 5.0 g of N- {5- [3- (Morpholin-4-yl)
Phenoxy] -2-nitrophenyl} -N-methylcarbamic acid t-butyl ester, 0.5 g of 10% palladium-carbon, 30 ml of methanol and 70 ml of a mixed solvent of toluene were reacted in the same manner as in Reference Example 7,
Purification gave 4.5 g of the title compound.

Silica gel thin layer chromatography (developing solvent: benzene / ethyl acetate = 4/1): Rf = 0.
23.

Reference Example 27 N- [2-amino-5- (2-piperidinophenoxy)
Phenyl] -N-methylcarbamic acid t-butyl ester 1.04 g of sodium hydride (55% by weight) in nitrogen atmosphere and 3.4 g of 2-piperidinophenol in 35 ml of N, N-dimethyl It was added to formamide and stirred at room temperature for 15 minutes. Then, the reaction solution was added in 5.2.
5 g of N- (5-chloro-2-nitrophenyl) -N-
Methyl carbamic acid t-butyl ester was added little by little, and the mixture was stirred at about 60 ° C for 2 hours. After completion of the reaction, the solvent was distilled off, water was added, the mixture was neutralized with concentrated hydrochloric acid, and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the obtained residue was separated and purified by silica gel column chromatography (eluent: c-hexane / isopropyl ether = 5/1) to give Rf Value =
N having 0.27 [silica gel thin layer chromatography (c-hexane / isopropyl ether = 5/1)]
-[2-Nitro-5- (2-piperidinophenoxy) phenyl] -N-methylcarbamic acid t-butyl ester was obtained. This nitro compound was added to 100 ml of toluene-
It was dissolved in a methanol (7: 3) mixed solvent, 0.63 g of 10% palladium-carbon was added, and the mixture was vigorously stirred under a hydrogen atmosphere at room temperature for 14.5 hours. After the catalyst was filtered off from the reaction solution, the solvent was distilled off, and the obtained residue was washed with ice-cooled methanol and n-hexane to obtain 4.2 g of the title compound. Melting point: 108-110 ° C.

Reference Example 28 N-methyl-N- [2-nitro-5- (pyridine-2-
Ilthio) phenyl] carbamic acid t-butyl ester 0.89 g of 2-mercaptopyridine, 2.29 g of N
-(5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.11 g of sodium hydride (55% by weight) and 40 ml of anhydrous N, N
Using -dimethylformamide, the reaction was carried out in the same manner as in Reference Example 6 and purified to obtain 1.13 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 5/1): Rf value = 0.20.

Reference Example 29 N- [2-amino-5- (2-pyrrolidinophenoxy)
Phenyl] -N-methylcarbamic acid t-butyl ester 1.88 g of 2-pyrrolidinophenol, 3.34 g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.52 g Of sodium hydride (55% by weight) and 22 ml of anhydrous N, N-dimethylformamide in the same manner as in Reference Example 27, followed by purification. Rf value = 0.25 [silica gel thin layer chromatography ( c-hexane / ethyl acetate = 10/1)] and N- [2-nitro-5- (2
-Pyrrolidinophenoxy) phenyl] -N-methylcarbamic acid t-butyl ester was obtained. In addition, 0.4
Reference Example 2 using 5 g of 10% palladium-carbon and 50 ml of a mixed solvent of toluene-methanol (7: 3).
The reaction was carried out in the same manner as in No. 7 and purified to obtain 3.0 g of the title compound. Melting point: 136-138 [deg.] C.

Reference Example 30 N- [5- (2-benzyloxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 2.00 g of 2-benzyloxyphenol, 2.87
g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.44 g of sodium hydride (55% by weight) and 20 ml of anhydrous N, N-dimethylformamide. The reaction was carried out and purified in the same manner as in Reference Example 6 to obtain 4.16 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1): Rf value = 0.62.

Reference Example 31 N- {5- [4- (1-adamantyl) phenoxy]-
2-nitrophenyl} -N-methylcarbamic acid t-
Butyl ester 2.28 g of 4- (1-adamantyl) phenol,
2.87 g of N- (5-chloro-2-nitrophenyl)
-N-methylcarbamic acid t-butyl ester;
44 g of sodium hydride (55% by weight) and 40 m
Using 1 l of anhydrous N, N-dimethylformamide, the reaction was carried out in the same manner as in Reference Example 6 and purified to obtain 4.30 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1): Rf value = 0.76.

Reference Example 32 N- [5- (3-dimethylaminophenoxy) -2-nitrophenyl} -N-methylcarbamic acid t-butyl ester 0.82 g of 3-dimethylaminophenol, 1.72
g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.26 g of sodium hydride (55% by weight) and 50 ml of anhydrous N, N-dimethylformamide. The reaction was carried out in the same manner as in Reference Example 6 and purification was performed to obtain 2.17 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 9/1): Rf value = 0.21.

Reference Example 33 N- [2-amino-5- (pyridin-3-yloxy)
Phenyl] -N-methylcarbamic acid t-butyl ester 3.1 g of 3-hydroxypyridine, 9.3 g of N-
(5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 1.4 g of sodium hydride (55% by weight), and 25 ml of anhydrous N, N-
The reaction was carried out in the same manner as in Reference Example 27 using dimethylformamide and purified, and 9.2 g of N- [2-nitro-5- (pyridin-3-yloxy) phenyl] -N-methylcarbamic acid t-butyl ester was purified. Obtained. Further, 1.
The reaction was carried out in the same manner as in Reference Example 27 using 0 g of 10% palladium-carbon and 100 ml of a mixed solvent of toluene-methanol (7: 3), and purified to obtain 7.5 g of the title compound. Melting point: 101-102 ° C.

Reference Example 34 N- {5- [4- (Imidazol-1-yl) phenoxy] -2-nitrophenyl} -N-methylcarbamic acid t-butyl ester 4.1 g of 4- (imidazol-1-yl) ) Phenol, 7.85 g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester,
1.25 g of sodium hydride (55% by weight) and 4
Using 5 ml of anhydrous N, N-dimethylformamide,
The reaction was carried out in the same manner as in Reference Example 6 and purified to obtain 8.8 g of the title compound. Melting point: 182-184C.

Reference Example 35 N-methyl-N- [2-nitro-5- (2-phenylphenoxy) phenyl] carbamic acid t-butyl ester 3.5 g of 2-phenylphenol and 5.6 g of N-
(5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 1.08 g of sodium hydride (55% by weight) and 35 ml of anhydrous N, N-
The reaction was carried out in the same manner as in Reference Example 6 using dimethylformamide, followed by purification to obtain 8.3 g of the title compound. Silica gel thin layer chromatography (developing solvent: toluene / ethyl acetate = 10/1): Rf value = 0.56.

Reference Example 36 N- [5- (4-hydroxy-2,3-dimethylphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 1.38 g of 2,3-dimethylhydroquinone, .87
g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.87 g of sodium hydride (55% by weight) and 20 ml of anhydrous N, N-dimethylformamide. The reaction was carried out in the same manner as in Reference Example 6 and purified to obtain 1.92 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1): Rf value = 0.35.

Reference Example 37 N-methyl-N- [2-nitro-5- (4-phenoxyphenoxy) phenyl] carbamic acid t-butyl ester 4.0 g of 4-phenoxyphenol and 5.8 g of N-
Reference Example 6 was prepared using (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 1.1 g of sodium hydride (55% by weight) and 35 ml of anhydrous N, N-dimethylformamide. Reacted and purified in the same manner to obtain 8.6 g of the title compound. Silica gel thin layer chromatography (developing solvent: toluene / isopropyl ether = 20/1): Rf value = 0.
41.

Reference Example 38 N- [5- (4-hydroxyphenylthio) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 1.26 g of 4-hydroxythiophenol, 2.87
g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.87 g of sodium hydride (55% by weight) and 20 ml of anhydrous N, N-dimethylformamide. The reaction was carried out in the same manner as in Reference Example 6 and purified to obtain 2.86 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1): Rf value = 0.27.

Reference Example 39 N-methyl-N- [2-nitro-5- (3-phenylphenoxy) phenyl] carbamic acid t-butyl ester 4.0 g of 3-phenylphenol, 6.5 g of N-
(5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 1.13 g of sodium hydride (55% by weight) and 35 ml of anhydrous N, N-
The reaction was carried out in the same manner as in Reference Example 6 using dimethylformamide, followed by purification to obtain 8.7 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 10/1): Rf value = 0.22.

Reference Example 40 N- [5- (3-tert-butyl-4-hydroxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester and N- [5- (2-tert-butyl) -4-Hydroxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 1.66 g of t-butylhydroquinone, 2.87 g of N
-(5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.87 g of sodium hydride (55% by weight) and 20 ml of anhydrous N, N
-Dimethylformamide was reacted in the same manner as in Reference Example 6, separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 4/1), and 1.35 g of N- [5- (3-t-butyl-4-hydroxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester [silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1): Rf Value = 0.45] and 1.11
g of N- [5- (2-t-butyl-4-hydroxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester [silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate) = 3 /
1): Rf value = 0.35] was obtained.

Reference Example 41 N-methyl-N- [2-nitro-5- (4-phenylphenoxy) phenyl] carbamic acid t-butyl ester 4.0 g of 4-phenylphenol, 6.5 g of N-
(5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 1.13 g of sodium hydride (55% by weight) and 35 ml of anhydrous N, N-
The reaction was carried out in the same manner as in Reference Example 6 using dimethylformamide, followed by purification to obtain 5.5 g of the title compound. Melting point: 166-167C.

Reference Example 42 N- [5- (3,5-di-t-butyl-4-hydroxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 4.44 g of 2,6- Di-t-butylhydroquinone,
8.60 g of N- (5-chloro-2-nitrophenyl)
-N-methylcarbamic acid t-butyl ester;
18 g of sodium hydride (55% by weight) and 50 m
Using 1 l of anhydrous N, N-dimethylformamide, the reaction was carried out in the same manner as in Reference Example 6 and purified to obtain 0.60 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 10/1): Rf value = 0.22.

Reference Example 43 N- [5- (4-hydroxy-2,5-dimethylphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 1.38 g of 2,5-dimethylhydroquinone, .87
g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.87 g of sodium hydride (55% by weight) and 20 ml of anhydrous N, N-dimethylformamide. The reaction was carried out in the same manner as in Reference Example 6, and purification was carried out to obtain 1.72 g of the title compound. Silica gel thin layer chromatography (developing solvent: toluene / ethyl acetate = 5/1): Rf value = 0.58.

Reference Example 44 N- [2-amino-5- (4-hydroxy-2-methylphenoxy) phenyl] -N-methylcarbamic acid t
-Butyl ester and N- [2-amino-5- (4-
Hydroxy-3-methylphenoxy) phenyl] -N-
Methyl carbamic acid t-butyl ester 0.87 g of sodium hydride (55% by weight)
1 in N, N-dimethylformamide, 1.2
4 g of methylhydroquinone was added and stirred at room temperature for 15 minutes. Then, 2.87 g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t was added to the reaction solution.
-Butyl ester was added little by little, the mixture was stirred at 120 ° C. for 2 hours, concentrated, water was added, and extracted with ethyl acetate.
The extract was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (elution solvent: n-hexane / eryl acetate =
3/1) and purified by N- [5- (4-hydroxy-
2-methylphenoxy) -2-nitrophenyl] -N-
Methylcarbamic acid t-butyl ester and N-
[5- (4-hydroxy-3-methylphenoxy) -2
2.20 g of a mixture of -nitrophenyl] -N-methylcarbamic acid t-butyl ester was obtained. This mixture was dissolved in 40 ml of methanol, 0.21 g of 10% palladium-carbon was added, and the mixture was vigorously stirred under a hydrogen atmosphere at room temperature for 2 hours. After completion of the reaction, the catalyst was removed by filtration from the reaction solution,
The solvent was distilled off to obtain 1.88 g of a mixture of the title compounds. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/1): Rf value = 0.16.

Reference Example 45 N- [5- (4'-benzyloxybiphenyl-4-yloxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 11.07 g of 4'-benzyloxybiphenyl-4 −
All, 11.5 g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 2.2 g of sodium hydride (55% by weight), 36
Using 0 ml of a mixed solvent of anhydrous N, N-dimethylformamide-anhydrous tetrahydrofuran-anhydrous toluene (1: 1: 1), the reaction was carried out in the same manner as in Reference Example 6, and purification was carried out.
4.75 g of the title compound were obtained. Melting point: 123-125 [deg.] C.

Reference Example 46 N- [5- (4-cyanophenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 5.1 g of 4-cyanophenol and 11.5 g of N-
(5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 1.19 g of sodium hydride (55% by weight) and 80 ml of anhydrous N, N-
Dimethylformamide-anhydrous tetrahydrofuran (5:
3) Using the mixed solvent, the reaction was carried out in the same manner as in Reference Example 6, and the mixture was purified to obtain 8.45 g of the title compound. Melting point: 141-143 [deg.] C.

Reference Example 47 N-methyl-N- [2-nitro-5- (pentafluorophenoxy) phenyl] amine 1.66 g of sodium hydride (55% by weight) was added to 50 m
l of anhydrous N, N-dimethylformamide,
6.38 g of pentafluorophenol was added and stirred at room temperature for several minutes. Next, 10 g of N- (5-
Chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester was added little by little, the mixture was heated at 150 ° C for 15 hours, the solvent was distilled off, water was added, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the obtained residue was separated and purified by silica gel column chromatography (elution solvent: n-hexane / toluene = 4/1). 2 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / toluene = 2/1): Rf value = 0.14.

Reference Example 48 N- [2-amino-5- (pyridin-2-ylthio) phenyl] -N-methylcarbamic acid t-butyl ester 1.08 g of N-methyl-N- [2-nitro-5- (Pyridin-2-ylthio) phenyl] carbamic acid t-
The reaction was carried out in the same manner as in Reference Example 7 using butyl ester, 1.00 g of 10% palladium-carbon and 20 ml of methanol, followed by purification to obtain 0.78 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/2): Rf value = 0.33.

Reference Example 49 N- [2-amino-5- (2-hydroxyphenoxy)
Phenyl] -N-methylcarbamic acid t-butyl ester 4.14 g of N- [5- (2-benzyloxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester, 0.41 g of 10% palladium Reference Example 7 using carbon and 60 ml of methanol
And purified to give 2.89 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/1): Rf value = 0.26.

Reference Example 50 N- {5- [4- (1-adamantyl) phenoxy]-
2-aminophenyl} -N-methylcarbamic acid t-
Butyl ester 4.28 g of N- {5- [4- (1-adamantyl) phenoxy] -2-nitrophenyl} -N-methylcarbamic acid t-butyl ester, 0.42 g of 10% palladium-carbon and 60 ml of methanol And purified in the same manner as in Reference Example 7 to obtain 4.00 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/1): Rf value = 0.49.

Reference Example 51 N- [2-amino-5- (3-dimethylaminophenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 2.14 g of N- [5- (3-dimethylaminophenoxy)- Reference Example 7 using 2-nitrophenyl] -N-methylcarbamic acid t-butyl ester, 2.14 g of 10% palladium-carbon and 40 ml of methanol.
And purified to give 1.63 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/1): Rf value = 0.41.

Reference Example 52 N- {2-amino-5- [4- (imidazol-1-yl) phenoxy] phenyl} -N-methylcarbamic acid t-butyl ester 8.8 g of N- {5- [4- (Imidazol-1-yl) phenoxy] -2-nitrophenyl} -N-methylcarbamic acid t-butyl ester, 0.8 g, 10%
The reaction was carried out in the same manner as in Reference Example 7 using palladium-carbon and 160 ml of N, N-dimethylformamide, followed by purification to obtain 5.7 g of the title compound. Melting point: 115-116 [deg.] C.

Reference Example 53 N- [2-amino-5- (2-phenylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 8.3 g of N-methyl-N- [2-nitro-5- ( 2-
Using phenylphenoxy) phenyl] carbamic acid t-butyl ester, 0.66 g of 10% palladium-carbon and 100 ml of a mixed solvent of toluene-methanol (7: 3) in the same manner as in Reference Example 7, purification was performed. ,
6.9 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: benzene / ethyl acetate = 4/1): Rf value = 0.30.

Reference Example 54 N- [2-amino-5- (4-hydroxy-2,3-dimethylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 1.90 g of N- [5- (4- Hydroxy-2,3-dimethylphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester, 0.20 g of 1
The reaction was carried out in the same manner as in Reference Example 7 using 0% palladium-carbon and 20 ml of methanol, followed by purification and 1.61.
g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/1): Rf value = 0.13.

Reference Example 55 N- [2-amino-5- (4-phenoxyphenoxy)
Phenyl] -N-methylcarbamic acid t-butyl ester 8.6 g of N- [2-nitro-5- (4-phenoxyphenoxy) phenyl] -N-methylcarbamic acid t-butyl
The reaction was carried out in the same manner as in Reference Example 7 using butyl ester, 0.6 g of 10% palladium-carbon and 190 ml of a mixed solvent of toluene-methanol (16: 3), followed by purification to obtain 7.2 g of the title compound. Was. Melting point: 105-106 ° C.

Reference Example 56 N- [2-amino-5- (4-hydroxyphenylthio) phenyl] -N-methylcarbamic acid t-butyl ester 2.84 g of N- [5- (4-hydroxyphenylthio)- Reference Example 7 using 2-nitrophenyl] -N-methylcarbamic acid t-butyl ester, 1.52 g of 10% palladium-carbon and 50 ml of methanol.
And purified to give 2.37 g of the title compound. Melting point: 62-67 [deg.] C. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/2): Rf value = 0.59.

Reference Example 57 N- [2-amino-5- (3-phenylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 8.7 g of N- [2-nitro-5- (3-phenylphenoxy) ) Phenyl] -N-methylcarbamic acid t-butyl ester, 0.69 g of 10% palladium-carbon and 100 ml of a mixed solvent of toluene-methanol (7: 3) were reacted and purified in the same manner as in Reference Example 7. hand,
6.06 g of the title compound were obtained. Melting point: 114-115 [deg.] C.

Reference Example 58 N- [2-amino-5- (3-t-butyl-4-hydroxyphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 1.29 g of N- [5- (3- t-butyl-4-hydroxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester, 0.16 g of 10
% Palladium-carbon and 40 ml of methanol, and reacted and purified as in Reference Example 7.
The title compound was obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/1): Rf = 0.18.

Reference Example 59 N- [2-amino-5- (2-t-butyl-4-hydroxyphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 1.09 g of N- [5- (2- t-butyl-4-hydroxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester, 0.15 g of 10
% Palladium-carbon and 20 ml of methanol, reacted in the same manner as in Reference Example 7 and purified to give 0.95 g.
The title compound was obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/1): Rf = 0.18.

Reference Example 60 N- [2-amino-5- (4-phenylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 5.32 g of N- [2-nitro-5- (4-phenylphenoxy) ) Phenyl] -N-methylcarbamic acid t-
The reaction was carried out in the same manner as in Reference Example 7 using butyl ester, 0.68 g of 10% palladium-carbon and 140 ml of a mixed solvent of toluene-ethyl acetate (1: 1), and the mixture was purified to give 4.82 g of the title compound. Obtained. Melting point: 122-123 [deg.] C.

Reference Example 61 N- [2-amino-5- (4-hydroxy-2,5-dimethylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 1.73 g of N- [5- (4- Hydroxy-2,5-dimethylphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester, 0.17 g of 1
The reaction was carried out in the same manner as in Reference Example 7 using 0% palladium-carbon and 50 ml of methanol, followed by purification and 1.44.
g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/1): Rf value = 0.17.

Reference Example 62 N- [2-amino-5- (4'-hydroxybiphenyl-4-yloxy) phenyl] -N-methylcarbamic acid t-butyl ester 14.75 g of N- [5- (4'- Benzyloxybiphenyl-4-yloxy) -2-nitrophenyl] -N
-Methylcarbamic acid t-butyl ester, 0.86
g of 10% palladium-carbon and 140 ml of a mixed solvent of toluene and ethyl acetate (1: 1) were used to obtain Reference Example 7.
And purified to give 10.2 g of the title compound. Melting point: 89-91C.

Reference Example 63 N- [2-amino-5- (4-hydroxy-3,5-di-t-butylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 0.58 g of N- [5 -(4-hydroxy-3,5-di-t-butylphenoxy) -2-nitrophenyl] -N
-Methylcarbamic acid t-butyl ester, 0.12
g of 10% palladium-carbon and 20 ml of methanol, and reacted and purified in the same manner as in Reference Example 7.
0.55 g of the title compound was obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 3/1): Rf value = 0.29.

Reference Example 64 [2-Amino-5- (4-cyanophenoxy) phenyl] methylamine 3.29 g of N- [5- (4-cyanophenoxy) -2
-Nitrophenyl] -N-methylcarbamic acid t-butyl ester and 10.06 g of tin (II) chloride dihydrate in 100 ml of t-butanol-ethyl acetate (1:
9) After dissolving in a mixed solvent and stirring at 60 ° C. for 1 hour,
0.17 g of sodium borohydride was added, and the mixture was further stirred at the same temperature for 2.5 hours. After concentrating the reaction solution, it was poured into ice water and neutralized with sodium bicarbonate. Ethyl acetate was added, and the insolubles were removed by filtration through Celite. Then, the organic layer was separated from the aqueous layer and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 3/2) to obtain 1.49 g of the title compound. Melting point: 80-82 [deg.] C.

Reference Example 65 N- [5- (4-benzoyl-3-hydroxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 4.5 g of 2,4-dihydroxybenzophenone;
0 g of N- (5-chloro-2-nitrophenyl) -N-
Methyl carbamic acid t-butyl ester, 1.75 g
Reference Example 6 using sodium hydride (55% by weight) and 130 ml of anhydrous N, N-dimethylformamide.
And purified to give 2.2 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 5/1): Rf value = 0.36.

Reference Example 66 N- [2-amino-5- (4-benzyl-3-hydroxyphenoxy) phenyl] -N-methylcarbamic acid
t-butyl ester 2.1 g of N- [5- (4-benzoyl-3-hydroxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester mixed with 80 ml of methanol-tetrahydrofuran (5: 3) The mixture was dissolved in a solvent, 0.5 g of 20% palladium-carbon was added, and the mixture was stirred at room temperature for 4 hours under a hydrogen atmosphere. After removing the catalyst from the reaction solution by filtration, the solvent was distilled off from the filtrate to obtain 1.8 g of the title compound.

Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 2/1): Rf value =
0.26.

Reference Example 67 N-methyl-N- [5- (4-methylthiophenoxy)
-2-nitrophenyl] carbamic acid t-butyl ester 0.98 g of 4-methylthiophenol, 2.00 g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.31 g Sodium hydride (55% by weight) and 60 ml of anhydrous N,
The reaction was carried out in the same manner as in Reference Example 6 using N-dimethylformamide, followed by purification to obtain 2.56 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 9/1): Rf value = 0.17.

Reference Example 68 N-methyl-N- [5- (4-methoxyphenoxy)-
2-nitrophenyl] carbamic acid t-butyl ester 5.0 g of 4-methoxyphenol, 10.9 g of N-
(5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 2.2 g of sodium hydride (55% by weight) and 120 ml of anhydrous N, N-
The reaction was carried out in the same manner as in Reference Example 6 using dimethylformamide, followed by purification to obtain 12.2 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 8/1): Rf value = 0.32.

Reference Example 69 N-methyl-N- [2-nitro-5- (4-trifluoromethylphenoxy) phenyl] carbamic acid t-butyl ester 3.0 g of 4-trifluoromethylphenol, 4.3
g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 1.1 g of sodium hydride (55% by weight) and 70 ml of anhydrous N, N-dimethylformamide, The reaction was carried out in the same manner as in Reference Example 6 and purification was performed to obtain 1.26 g of the title compound. Melting point: 92-93C.

Reference Example 70 N-methyl-N- [5- (4-benzylphenoxy)-
2-nitrophenyl] carbamic acid t-butyl ester 7 g of 4-benzylphenol, 9.15 g of N- (5
-Chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, as in Reference Example 6, using 1.74 g of sodium hydride (55% by weight) and 70 ml of anhydrous N, N-dimethylformamide. React and purify to give 12.2 g of the title compound. Silica gel thin layer chromatography (developing solvent: toluene / diisopropyl ether = 20/1): Rf value =
0.40.

Reference Example 71 N-methyl-N- [5- (3-benzyloxyphenoxy) -2-nitrophenyl] carbamic acid t-butyl ester 5 g of 3-benzyloxyphenol, 6 g of N- (5
-Chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 1.1 g of sodium hydride (55% by weight) and 40 ml of anhydrous N, N-dimethylformamide in the same manner as in Reference Example 6. React
Purification provided 7.8 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 5/1): Rf value = 0.32.

Reference Example 72 N- [2-amino-5- (4-methylthiophenoxy)
Phenyl] -N-methylcarbamic acid t-butyl ester 2.53 g of N-methyl-N- [5- (4-methylthiophenoxy) -2-nitrophenyl] carbamic acid t
Using -butyl ester, 2.5 g of 10% palladium-carbon and 55 ml of methanol, the reaction was carried out and purified in the same manner as in Reference Example 7, to obtain 1.94 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 4/1): Rf value = 0.15.

Reference Example 73 N- [2-amino-5- (4-methoxyphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 7.2 g of N- [5- (4-methoxyphenoxy) -2
-Nitrophenyl] -N-methylcarbamic acid t-butyl ester, 0.5 g of 10% palladium-carbon and 100 ml of methanol were reacted and purified in the same manner as in Reference Example 7 to give 6.23 g of the title compound. I got Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 5/1): Rf value = 0.18.

Reference Example 74 N- [2-amino-5- (4-trifluoromethylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 1.24 g of N-methyl-N- [5- (4- After dissolving trifluoromethylphenoxy) -2-nitrophenyl] carbamic acid t-butyl ester in 60 ml of a mixed solvent of water-dioxane (1: 5), 4.2 g of sodium bicarbonate and 3.5 g of dithionous acid Sodium was added and the mixture was heated under reflux for 1 hour. After completion of the reaction, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated saline and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography (eluent:
Purification with n-hexane / ethyl acetate = 3/1 to 2/1) gave 0.7 g of the title compound. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 4/1): Rf value = 0.27.

Reference Example 75 N- [2-amino-5- (4-benzylphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 12.2 g of N- [5- (4-benzylphenoxy)-
2-nitrophenyl] -N-methylcarbamic acid t-
Using butyl ester, 0.91 g of 10% palladium-carbon and 140 ml of a mixed solvent of toluene and ethyl acetate (1: 1), the reaction was carried out in the same manner as in Reference Example 7, and the mixture was purified to obtain 10.1 g of the title compound. Obtained. Melting point: 114-115 [deg.] C.

Reference Example 76 N- [2-amino-5- (3-hydroxyphenoxy)
Phenyl] -N-methylcarbamic acid t-butyl ester 7.8 g of N- [5- (3-hydroxyphenoxy)-
2-nitrophenyl] -N-methylcarbamic acid t-
Using butyl ester, 0.9 g of 10% palladium-carbon and 140 ml of a mixed solvent of toluene and ethyl acetate (1: 1), the reaction was carried out in the same manner as in Reference Example 7, and the mixture was purified.
6 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: n-hexane / ethyl acetate = 1/1): Rf value = 0.50.

Reference Example 77 N-methyl-N- [2-nitro-5- (4-tetrazol-5-ylphenoxy) phenyl] carbamic acid t
-Butyl ester 2.95 g of N- [5- (4-cyanophenoxy) -2
A mixture of -nitrophenyl] -N-methylcarbamic acid t-butyl ester, 7.97 g of tri-n-butyltin azide and 30 ml of anhydrous toluene was heated under reflux for 23 hours. The reaction solution was concentrated, water was added, extracted with ethyl acetate, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by reverse phase preparative liquid chromatography (elution solvent: water / acetonitrile = 1/1) to obtain 3.20 g of the title compound. Melting point: 81-84 [deg.] C.

Reference Example 78 N-methyl-N- {2-nitro-5- [4- (2-triphenylmethyltetrazol-5-yl) phenoxy]
Phenyl dicarbamic acid t-butyl ester 3.22 g of N-methyl-N- [2-nitro-5- (4
-Tetrazol-5-ylphenoxy) phenyl] carbamic acid t-butyl ester, 2.18 g of triphenylmethane chloride, 0.79 g of triethylamine, 30
A mixture of ml of anhydrous tetrahydrofuran and 30 ml of anhydrous N, N-dimethylformamide was stirred at room temperature for 24 hours. The reaction solution was concentrated, water was added, extracted with ethyl acetate, and dried over anhydrous sodium sulfate. Under reduced pressure,
The solvent was distilled off, and the obtained residue was subjected to silica gel column chromatography (elution solvent: n-hexane / ethyl acetate =
Purification by 5/1) afforded 3.15 g of the title compound. Melting point: 161-163C.

Reference Example 79 N-methyl-N- {2-amino-5- [4- (2-triphenylmethyltetrazol-5-yl) phenoxy]
Phenyl dicarbamic acid t-butyl ester 0.98 g of N-methyl-N- {2-nitro-5- [4
-(2-triphenylmethyltetrazol-5-yl)
[Phenoxy] phenyl} carbamic acid t-butyl ester, 0.13 g of 10% palladium-carbon and 10%
The reaction was carried out in the same manner as in Reference Example 7 using 0 ml of ethyl acetate, and purified to obtain 0.70 g of the title compound. Melting point: 192-193C.

Reference Example 80 2-hydroxymethyl-1-methyl-6-pentafluorophenoxy-1H-benzimidazole 2.10 g of N-methyl-N- [2-nitro-5- (pentafluorophenoxy) phenyl] amine , 0.23
A mixture of 10 g of 10% palladium-carbon and 300 ml of methanol was stirred under a hydrogen atmosphere at room temperature for 4 hours. After filtering off the catalyst from the reaction solution and concentrating the filtrate, the obtained residue was subjected to silica gel column chromatography (elution solvent: n
-Hexane / ethyl acetate = 3/1).
f value 0.26 (developing solvent: n-hexane / ethyl acetate =
4/1) with N- [2-amino-5- (pentafluorophenoxy) phenyl] -N-methylamine.
48 g were obtained. To this intermediate 0.76 g glycolic acid,
25 ml of 4N hydrochloric acid and 25 ml of dioxane were added, and the mixture was heated under reflux for 16 hours. The reaction solution was concentrated, water was added, neutralized with sodium bicarbonate, and extracted with ethyl acetate. After the extract was dried over anhydrous sodium sulfate, the solvent was distilled off,
The obtained residue was subjected to silica gel column chromatography (elution solvent: ethyl acetate / methanol = 20/1). After evaporating the solvent, the crystals precipitated from n-hexane under ultrasonic irradiation were collected by filtration, washed with n-hexane, and washed with 1.17.
g of the title compound were obtained. Melting point: 121-128 [deg.] C.

Reference Example 81 4-cyanophenoxy-2-hydroxymethyl-1-methyl-1H-benzimidazole 1.08 g of N- [2-amino-5- (4-cyanophenoxy) phenyl] -N-methylamine , 0.68 g of glycolic acid, 20 ml of 4N hydrochloric acid and 20 ml of 1,4-dioxane were heated at reflux for 9 hours. The reaction solution was concentrated, water was added, neutralized with sodium bicarbonate, and extracted with ethyl acetate. After the extract was dried over anhydrous sodium sulfate, the solvent was distilled off, and the obtained residue was purified by silica gel column chromatography (elution solvent: ethyl acetate / methanol = 20/1) to obtain 0.86 g of the title compound. I got Melting point: 183-185C.

Reference Example 82 5- {4- [6- (4-cyanophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} -3-triphenylmethylthiazolidine-2,
4-dione 279 mg of 4-cyanophenoxy-2-hydroxymethyl-1-methyl-1H-benzimidazole, 558
mg of 5- (4-hydroxybenzyl) -3-triphenylmethylthiazolidine-2,4-dione, 378 mg
Azodicarbonyl dipiperidine, 303 mg of tri-
A mixture of n-butylphosphine and 20 ml of toluene was stirred at room temperature for 15 hours. The reaction solution was separated and purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/1) to obtain 706 mg of the title compound. Melting point: 135-138 [deg.] C.

Reference Example 83 Acetic acid 4-benzyloxy-2,5-di-t-butylphenyl ester 5.3 g of acetic acid 2,5-di-t-butyl-4-hydroxyphenyl ester was dissolved in 40 ml of acetone. After that, 5.17 g of benzyl bromide and 4.15 g of potassium carbonate were added, and the mixture was stirred at room temperature for 48 hours. After the completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. After the extract was dried over anhydrous sodium sulfate, the solvent was distilled off, and the obtained residue was purified by silica gel column chromatography (eluent: c-hexane / diisopropyl ether = 10/1) to give 4.9 g of the title compound. The compound was obtained. Silica gel thin layer chromatography (developing solvent: c-hexane / diisopropyl ether = 10/1): Rf value = 0.35.

Reference Example 84 4-benzyloxy-2,5-di-t-butylphenol 1.51 g of potassium hydroxide was dissolved in 12 ml of methanol, and then 4.9 g of 4-benzyloxy-acetic acid was dissolved.
2,5-Di-t-butylphenyl ester was added and left at room temperature overnight. The reaction mixture was neutralized by adding dilute hydrochloric acid, and extracted with ethyl acetate. After the extract was dried over anhydrous sodium sulfate, the solvent was distilled off to obtain 4.3 g of the title compound. Silica gel thin layer chromatography (developing solvent: c-hexane / diisopropyl ether = 10/1): Rf value = 0.44.

Reference Example 85 N- [5- (4-benzyloxy-2,5-di-tert-butylphenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 4.3 g of 4-benzyl Oxy-2,5-di-t-butylphenol, 3.51 g of N- (5-chloro-2-nitrophenyl) -N-methylcarbamic acid t-butyl ester, 0.72 g of sodium hydride (55% by weight) And purified using 15 ml of anhydrous N, N-dimethylformamide in the same manner as in Reference Example 6.
7.1 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: c-hexane / diisopropyl ether = 10/1): Rf value = 0.20.

Reference Example 86 N- [2-amino-5- (2,5-di-t-butyl-4)
-Hydroxyphenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 7.1 g of N- [5- (4-benzyloxy-2,5-
Di-tert-butylphenoxy) -2-nitrophenyl]-
N-methylcarbamic acid t-butyl ester, 0.7
g of 10% palladium-carbon and 57 ml of a mixed solvent of toluene-methanol-ethyl acetate (16:16:25) in the same manner as in Reference Example 7, followed by purification.
3.65 g of the title compound were obtained. Melting point: 208-210 [deg.] C.

Reference Example 87 6- (3,5-Di-tert-butyl-4-hydroxy) phenylthio-2-hydroxymethyl-1-methyl-1H-
Benzimidazole N- [5- (3,5-di-t-butyl-4-hydroxyphenoxy) -2-nitrophenyl] -N-methylcarbamic acid obtained by hydrogenation and acid treatment of t-butyl ester [ 2-amino-5- (3,5-
11.68 g of di-t-butyl-4-hydroxyphenylthio) phenyl] methylamine was added to 4N hydrochloric acid (300).
Then, 7.43 g of glycolic acid was added, and the mixture was heated under reflux for 6 hours. The reaction mixture was poured into ice water, neutralized with sodium bicarbonate, and extracted with ethyl acetate. After the extract was dried over anhydrous sodium sulfate, the solvent was distilled off, and the obtained residue was purified by silica gel column chromatography (eluent: ethyl acetate / methanol = 20/1) to obtain 8.66.
g of the title compound were obtained. Melting point: 195-198C.

Reference Example 88 4- [6- (3,5-Di-tert-butyl-4-hydroxyphenylthio) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzaldehyde 5.33 g of 6- (3,5-di-tert-butyl-4-hydroxy) phenylthio-2-hydroxymethyl-1-methyl-1H-benzimidazole, 2.22 g of 4-hydroxybenzaldehyde, 4.59 g of 1,1′-
A mixture of (azodicarbonyl) dipiperidine, 3.68 g of tri-n-butylphosphine and 300 ml of anhydrous toluene was stirred at room temperature for 64 hours. After the reaction mixture was concentrated, it was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/1) to obtain 3.74 g of the title compound. Melting point: 219-221 [deg.] C.

Reference Example 89 N- [5- (4-t-butoxycarbonylaminophenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester 15.6 g of (4-hydroxyphenyl) carbamic acid t-butyl ester Butyl ester, 21 g of N- (5-chloro-2
-Nitrophenyl) -N-methylcarbamic acid t-butyl ester, 3.22 g of sodium hydride (55% by weight) and 130 ml of anhydrous N, N-dimethylformamide were reacted and purified in the same manner as in Reference Example 6. do it,
27.7 g of the title compound were obtained. Silica gel thin layer chromatography (developing solvent: toluene / diisopropyl ether = 10/1): Rf value =
0.33.

Reference Example 90 N- [2-amino-5- (4-t-butoxycarbonylaminophenoxy) phenyl] -N-methylcarbamic acid t-butyl ester 27.7 g of N- [5- (4-t- Butoxycarbonylaminophenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester, 1.07 g of 1
The reaction was carried out in the same manner as in Reference Example 7 using 0% palladium-carbon and 170 ml of a mixed solvent of tetrahydrofuran-ethyl acetate (9: 8) and purified to obtain 26.2 g of the title compound. Silica gel thin layer chromatography (developing solvent: c-hexane / tetrahydrofuran = 2/1): Rf value = 0.
37.

Reference Example 91 N- {5- [4- (t-butoxycarbonyl-n-hexylamino) phenoxy] -2-nitrophenyl} -N
-Methylcarbamic acid t-butyl ester 1.26 g of sodium hydride (55% by weight)
suspended in ml of anhydrous N, N-dimethylformamide,
12.1 g of N- [5- (4-t-butoxycarbonylaminophenoxy) -2-nitrophenyl] -N-methylcarbamic acid t-butyl ester was added, and the mixture was stirred at room temperature for several minutes. Next, 6.5 g of hexyl bromide was added under ice cooling, and the mixture was stirred at the same temperature for 30 minutes and further at room temperature for 1 hour. After concentrating the reaction mixture, it was poured into water and extracted with ethyl acetate.
After the extract was dried over anhydrous sodium sulfate, the solvent was distilled off, and the obtained residue was subjected to silica gel column chromatography (elution solvent: toluene / diisopropyl ether =
Purification by 100/7) gave 13.8 g of the title product. Silica gel thin layer chromatography (developing solvent: toluene / diisopropyl ether = 100/7): Rf value =
0.32.

Reference Example 92 N- {2-amino-5- [4- (t-butoxycarbonyl-n-hexylamino) phenoxy] phenyl} -N
-Methylcarbamic acid t-butyl ester 13.8 g of N- {5- [4- (t-butoxycarbonyl-n-hexylamino) phenoxy] -2-nitrophenyl} -N-methylcarbamic acid t-butyl ester; 0 g of 10% palladium on carbon and 140 m
The reaction was carried out in the same manner as in Reference Example 7 using 1 l of a mixed solvent of toluene and ethyl acetate (1: 1), followed by purification to obtain 13.1 g.
The title compound was obtained. Silica gel thin layer chromatography (developing solvent: toluene / ethyl acetate = 3/1): Rf value = 0.44.

Test Example 1 Anti-Lipid Peroxide Action The inhibitory effect of lipid peroxide production on rat liver microsomes was examined. Buffer solution [aqueous solution adjusted to pH 7.4 by adding hydrochloric acid to 0.1 M aqueous solution of tris (hydroxymethyl) aminomethane] and 0.15 M aqueous potassium chloride solution at a ratio of 1: 2
To 400 μl of the mixture, 5 μl of a dimethyl sulfoxide solution of a test compound at a fixed concentration was added to a Wister rat (10
100 μl of liver microsomes prepared from
Stirred at 37 ° C. for 5 minutes. To start the reaction, 0.5 mM ferrous sulfate heptahydrate aqueous solution and 50 mM
10 μl of a 1: 1 mixed solution of cysteine aqueous solution was added, and 37
Stirred at C for 30 minutes. 1 ml of a 10% aqueous solution of trichloroacetic acid was added to the stirred liquid to stop the reaction. Reaction solution
The mixture was centrifuged at 3000 rpm for 10 minutes at ℃, and the supernatant was collected. 1.0 ml of 50% aqueous acetic acid containing 0.67% thiobarbituric acid was added to 1.0 ml of the supernatant, and the mixture was boiled at 100 ° C. for 15 minutes. After standing at room temperature for 15 minutes, 535
The absorbance at a wavelength of nm was measured. The inhibition rate (%) was determined from the absorbance of the control obtained without using the test compound and the absorbance when the test compound at a certain concentration was used, and the concentration of the test compound that inhibited lipid peroxide by 50% was examined. Table 11 shows the results.

[0488]

[Table 11] Example Compound No. IC ₅₀ (μg / ml) 1-2a 0.97 2-2a 0.54 4-2a 0.83 5b 1.3 7-2a 0.65 8-2b 3.2 . From the above results, it has been clarified that the compound of the present invention exhibits excellent anti-lipid peroxide activity.

Test Example 2 5-lipoxygenase inhibitory action 5 μl of test compound dissolved in dimethyl sulfoxide was added to
1/15 M phosphoric acid buffer solution (an aqueous solution prepared by dissolving 1 package of powder for phosphoric acid buffer solution (yatron) in 10 ml of water and adjusting to pH 7.4) 750 μl, 30 mM calcium chloride aqueous solution 40 μl, 20 mM GSH (reduced glutathione) 50 μl of an aqueous solution, 50 μl of a 40 mM ATP (adenosine-5-triphosphate) aqueous solution and 100 μl of guinea pig polymorphonuclear leukocyte enzyme were added, and the mixture was stirred at 25 ° C. for 5 minutes.
To start the reaction, add arachidonic acid (10 mg
/ Ml ethanol) and stirred at 25 ° C for 5 minutes. The reaction was stopped by adding 50 μl of 2N hydrochloric acid to the stirred solution. After adding 2.0 ml of ethyl acetate containing an internal standard substance (internal standard substance: isoamyl paraben 2 μg / ml), extraction was performed for 1 minute using a mixer, and then 3000 rpm
and centrifuged for 5 minutes. After separating the ethyl acetate layer,
After evaporating to dryness under reduced pressure and dissolving in 200 μl of acetonitrile, 5-
HETE was quantified. Quantification of 5-HETE in the control without the test compound and 5 when the test compound was used.
The inhibition rate (%) was determined from the quantification of -HETE, and the concentration of the test compound that inhibited 5-lipoxygenase by 50% was examined. Table 12 shows the results.

[0490]

[Table 12]  Example number IC₅₀(Μg / ml)  1-2a 0.59 2-2a 0.10 4-2a 0.20 5b 0.53 . From the above results, the compound of the present invention is excellent in 5-lipo
It has been clarified that it exhibits a xigenase inhibitory action.

Test Example 3 Blood Glucose-Lowering Action Blood was collected from the tail vein of a KK mouse (4-5 months) that developed diabetes, and its blood glucose level was measured. Next, the mice were grouped (four mice per group) so that the average of the blood glucose levels of the mice in each group was the same, and then a mouse powder feed (F- 1, Funabashi Farm)
Was given to mice for 3 days. The group of mice receiving the test compound was designated as the drug-administered group. In addition, the group which received the powder feed which does not contain a test compound was set as the control group. Three days later, blood was collected from the tail vein of the mouse, and the glucose concentration in the plasma obtained by centrifugation was measured with a glucose analyzer (GlucoLoader, A & T). The blood glucose lowering rate was determined from the following equation.

Blood glucose lowering rate (%) = (average blood glucose level of control group−average blood glucose level of drug-administered group) × 100 / blood glucose level of control group

[0493]

[Table 13] Example number Blood sugar lowering rate (%) 1-2b 48.1 2-2b 49.2 3-2 60.1 4-2a 67.5 6-2 62.6 7-2a 71.7 13-2b 68.1 19-2 66.8 34- 2b 71.2 40 66.4 51 63.6 . From the above results, it was revealed that the compound of the present invention exhibits an excellent blood glucose lowering effect.

[0494]

EFFECT OF THE INVENTION The compound having the above general formula (I) or a pharmaceutically acceptable salt thereof according to the present invention is excellent in improving insulin resistance, lowering blood glucose, anti-inflammatory, immunomodulating, reducing aldoses. Enzyme inhibitory action, 5-lipoxygenase inhibitory action, lipid peroxide production inhibitory action, PPAR activating action, anti-osteoporosis action, leukotriene antagonism, adipocyte promotion action, cancer cell growth inhibitory action, calcium antagonistic action, diabetes Hyperlipidemia, obesity, impaired glucose tolerance, hypertension, fatty liver, diabetic complications (eg, retinopathy, nephropathy, neuropathy, cataract, coronary artery disease, etc.),
Cell damage (eg, stroke) caused by arteriosclerosis, gestational diabetes, polycystic ovary syndrome, cardiovascular disease (eg, ischemic heart disease, etc.), non-atherosclerotic disease or ischemic heart disease Gout, inflammatory diseases (eg, osteoarthritis, pain,
Fever, rheumatoid arthritis, inflammatory bowel disease, acne, sunburn, psoriasis, eczema, allergic disease, asthma, GI ulcer,
Cachexia, autoimmune disease, pancreatitis. ), Cancer, osteoporosis, cataract and the like.

Further, the compound of the present invention having the above general formula (I) or a pharmaceutically acceptable salt thereof, an α-glucosidase inhibitor, an aldose reductase inhibitor, a biguanide agent, a statin compound, a squalene synthesis inhibitor , A pharmaceutical composition comprising a combination of at least one of a fibrate compound, an LDL catabolism promoter and an angiotensin converting enzyme inhibitor (particularly preferred is a prophylactic and / or therapeutic agent for diabetes or diabetic complications). Useful.

────────────────────────────────────────────────── ⁶ Continuation of the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/00 609 A61K 31/00 609J 609G 609F 620 629C 619A 627 627A 629 629 629A 643 643D 31/415 613 31/415 614 614 614 614 614 614 614 614 614 31/42 602 31/42 602 31/425 602 31/425 602 31/435 605 31/435 605 31/445 31/445 31/495 31/495 31/535 31/535 31/54 31/54 C07D 401 / 12 235 C07D 401/12 235 403/12 233 403/12 233 235 235 413/12 235 413/12 235 413/14 213 413/14 213 233 233 417/12 235 417/12 235 417/14 213 417 / 14 213 233 233 471/04 107 471/04 107E

Claims (53)

[Claims] 1. A compound of the general formula (I) [In the above formula, R ¹ is a general formula: Or a general formula: [In the formula, R ⁴ is a phenyl group substituted with 1 to 5 substituents selected from a substituent group α or a group selected from a substituent group α.
Represents a pyridyl group which may be substituted by 4 to 4, R ⁵ represents a hydrogen atom or a group selected from a substituent group α, R ⁶ represents a hydrogen atom, a C ₁ -C ₆ alkyl group, a substituent group β
C _6- which may be substituted by 1 to 3 groups selected from
A C ₁₀ aryl group or a C ₇ -C ₁₆ aralkyl group which may be substituted by 1 to 3 groups selected from a substituent group β, D represents an oxygen atom or a sulfur atom, and E represents CH And a nitrogen atom. R ² represents a hydrogen atom or a group selected from substituent group α, and R ³ represents a group represented by the formula: A represents a C ₁ -C ₆ alkylene group, and B represents an oxygen atom or a sulfur atom. However, 5- ｛4- [5- (3,5
-Di-t-butyl-4-hydroxyphenylthio) -3
-Methyl-3H-imidazo [4,5-b] pyridine-2
-Ylmethoxy] benzyl} thiazolidine-2,4-dione is excluded. Or a pharmacologically acceptable salt thereof. <Substituent group α> Halogen atom; hydroxy group; C ₁ -C
₆ alkyl groups; halogeno C ₁ -C ₆ alkyl groups; C _1-
A C ₆ alkoxy group; a C ₁ -C ₆ alkylthio group; an amino group which may be substituted with a group selected from the substituent group γ; 1 to 3 substituents which may be substituted with a group selected from the substituent group β , C ₃ -C ₁₀ cycloalkyl, C ₆ -C ₁₀ aryl,
C ₇ -C ₁₆ aralkyl, C ₆ -C ₁₀ aryloxy, C
₇ -C ₁₆ aralkyloxy and C ₆ -C ₁₀ arylthio group; 5 or 6-membered aromatic heterocyclic containing nitrogen atom; C ₁ -C ₇ aliphatic acyloxy group; a nitrogen atom 4 to 7-membered saturated heterocyclic group containing A ring group; a nitro group; and a cyano group. <Substituent group β> halogen atom, hydroxy group, C ₁ -C
₆ alkyl group, halogeno C ₁ -C ₆ alkyl group, C _1-
A C ₆ alkoxy group, an amino group optionally substituted with a group selected from the substituent group γ, a C ₆ -C ₁₀ aryl group, and a nitro group. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 2. The substituted fused heterocyclic compound according to claim 1, wherein R ¹ is a group having the general formula (II) or a pharmacologically acceptable salt thereof. 3. The method according to claim 1, wherein R
² and R ⁵ are the same or different and are a hydrogen atom, a halogen atom, a hydroxy group, a C ₁ -C ₆ alkyl group, a halogeno C ₁ -C ₆ alkyl group, a C ₁ -C ₆ alkoxy group, a C ₁
A substituted fused heterocyclic compound which is an amino group which may be substituted with a C ₆ alkylthio group or a group selected from the substituent group γ, or a pharmaceutically acceptable salt thereof. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 4. The method according to claim 1, wherein R
² and R ⁵ are the same or different and are a hydrogen atom, a fluorine atom, a chlorine atom, a hydroxy group, a methyl group, an ethyl group, a trifluoromethyl group, a methoxy group, a methylthio group or an amino group, Its pharmacologically acceptable salts. 5. The method according to claim 1, wherein R
^A substituted fused heterocyclic compound wherein ² and R ⁵ are hydrogen atoms, or a pharmaceutically acceptable salt thereof. 6. The method according to claim 1, wherein R
^A substituted fused heterocyclic compound wherein 3 is a group having the formulas (IV-1) to (IV-3), or a pharmaceutically acceptable salt thereof. 7. The method according to claim 1, wherein R
^A substituted fused heterocyclic compound wherein 3 is a group having the formula (IV-2) or (IV-3), or a pharmaceutically acceptable salt thereof. 8. The method according to claim 1, wherein R
^A substituted fused heterocyclic compound wherein ³ is a group having the formula (IV-2) or a pharmacologically acceptable salt thereof. 9. The method according to claim 1, wherein R
⁴ is a pyridyl group optionally substituted by one of the following substituents (the substituents are halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ —C ₆ alkylthio, amino or nitro which may be substituted with a group selected from substituent group γ.)
Or a pharmacologically acceptable salt thereof. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 10. The method according to claim 1, wherein:
R ⁴ is a pyridyl group which may be substituted by one of the following substituents (the substituent is fluorine, chlorine, hydroxy, methyl, ethyl, t-butyl, trifluoromethyl, methoxy, methylthio, amino, methylamino, Or a pharmaceutically acceptable salt thereof. 11. The method according to claim 1, wherein:
A substituted fused heterocyclic compound wherein R ⁴ is a pyridyl group, or a pharmaceutically acceptable salt thereof. 12. The method according to claim 1, wherein
R ⁴ is a group selected from the following substituent group and at least 1
Individually substituted phenyl group (the substituent group may be substituted with 1 to 3 C _3-
C ₁₀ cycloalkyl, C ₆ -C ₁₀ aryl and C ₇ -C
_{It is} composed of ₁₆ aralkyl, a 4- to 7-membered saturated heterocyclic ring containing a nitrogen atom and a 5- or 6-membered aromatic heterocyclic ring containing a nitrogen atom. Or a pharmacologically acceptable salt thereof. <Substituent group β> halogen atom, hydroxy group, C ₁ -C
₆ alkyl group, halogeno C ₁ -C ₆ alkyl group, C _1-
A C ₆ alkoxy group, an amino group optionally substituted with a group selected from the substituent group γ, a C ₆ -C ₁₀ aryl group, and a nitro group. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 13. The method according to claim 12, wherein R ⁴ is
A phenyl group substituted by one with the following substituents (the substituent group may be substituted with one group selected from a substituent group β, C ₃ -C ₁₀ cycloalkyl, C ₆ -C ₁₀ aryl Or a C ₇ -C ₁₆ aralkyl, a 4- to 7-membered saturated heterocyclic ring containing a nitrogen atom or a 5- or 6-membered aromatic heterocyclic ring containing a nitrogen atom.) Or a pharmaceutically acceptable derivative thereof. Salt. <Substituent group β> halogen atom, hydroxy group, C ₁ -C
₆ alkyl group, halogeno C ₁ -C ₆ alkyl group, C _1-
A C ₆ alkoxy group, an amino group optionally substituted with a group selected from the substituent group γ, a C ₆ -C ₁₀ aryl group, and a nitro group. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 14. The method according to claim 12, wherein R ⁴ is
A phenyl group substituted with one of the following substituents (the substituent is
_One may be substituted with halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy or amino which may be substituted with a group selected from substituent group γ. , C ₃ -C ₁₀ cycloalkyl, C ₆ -
C ₁₀ aryl or C ₇ -C ₁₆ aralkyl, a 4- to 7-membered saturated heterocycle containing a nitrogen atom or a 5- or 6-membered aromatic heterocycle containing a nitrogen atom. Or a pharmacologically acceptable salt thereof. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 15. The method according to claim 12, wherein R ⁴ is
A phenyl group substituted with one of the following substituents (the substituent is
Halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy or amino optionally substituted with a group selected from substituent group γ
A phenyl or benzyl, adamantyl, pyrrolidinyl, morpholinyl, piperidinyl, imidazolyl, tetrazolyl or pyridinyl group which may be substituted by one. Or a pharmacologically acceptable salt thereof. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 16. The method according to claim 12, wherein R ⁴ is
A phenyl group substituted with one of the following substituents (the substituent is
One may be substituted with fluorine, chlorine, hydroxy, methyl, ethyl, t-butyl, trifluoromethyl, methoxy, amino, methylamino or dimethylamino;
It is a phenyl or benzyl, adamantyl, pyrrolidinyl, morpholinyl, piperidinyl, imidazolyl, tetrazolyl or pyridinyl group. Or a pharmacologically acceptable salt thereof. 17. The method according to claim 12, wherein R ⁴ is
4-biphenylyl, 4-benzylphenyl, 4'-hydroxybiphenylyl, (pyrrolidin-1-yl) phenyl, (morpholin-4-yl) phenyl, (piperidin-1-yl) phenyl, (pyridin-2-yl) A substituted fused heterocyclic compound which is a phenyl, (pyridin-3-yl) phenyl or 4- (1-adamantyl) phenyl group, or a pharmaceutically acceptable salt thereof. 18. The method according to claim 1, wherein
R ⁴ is substituted with one acylamino which may be substituted with a group selected from the substituent group γ, and further may be substituted with 1 to 3 phenyl groups which may be substituted with a group selected from the following substituent group ( The substituent group includes halogen, hydroxy, C ₁ -C ₆
Alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy and C ₁ -C ₆ alkylthio. Or a pharmacologically acceptable salt thereof. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 19. The method according to claim 18, wherein R ⁴ is
A phenyl group substituted with one acylamino which may be substituted with a group selected from the substituent group γ, and further substituted with one to three substituents selected from the following substituent group (the substituent group Consists of halogen and C ₁ -C ₆ alkyl.) Or a pharmaceutically acceptable salt thereof. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 20. The method according to claim 18, wherein R ⁴ is
C ₁ -C ₁₀ alkyl or optionally substituted C ₇ -C ₁₂
Is one substituted in which may be acylamino substituted aralkyl, furthermore, C ₁ -C ₆ substituted fused heterocyclic compound or a pharmacologically acceptable salt thereof is an alkyl with 1 to 3 substituents which may be a phenyl group. 21. The method according to claim 18, wherein R ⁴ is
A phenyl group substituted with one of the following substituents (the substituent is
Optionally substituted C ₇ -C ₁₁ aromatic acylamino, C
₄ -C ₁₁ cycloalkyl carbonylamino or 5 or 6-membered aromatic heterocyclic carbonylamino containing a nitrogen atom. Or a pharmacologically acceptable salt thereof. 22. The method according to claim 18, wherein R ⁴ is
Benzoylamino, 3-chlorobenzoylamino, 2,
4-difluorobenzoylamino, 4-hydroxy-
Substituted with 3,5-di-t-butylbenzoylamino, naphthoylamino, cyclopentanoylamino, cyclohexanoylamino, nicotinoylamino, isonicotinoylamino, N-acetyl-N-hexylamino or adamantylcarbonylamino Or a pharmaceutically acceptable salt thereof. 23. The method according to claim 1, wherein
R ⁴ is amino, amino substituted with 1 to 2 groups, wherein the substituents are the same or different and are C ₁ -C ₁₀ alkyl and optionally substituted C ₆ -C ₁₀ aryl and
It consists ₇ -C ₁₆ aralkyl. ), Nitro or cyano
1 group is substituted, and further, a group selected from the following substituent group
1 to 3 phenyl groups which may be substituted (the substituent groups include halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy,
Consisting of ₁ -C ₆ alkylthio. Or a pharmacologically acceptable salt thereof. 24. The method according to claim 23, wherein R ⁴ is
A substituted condensed heterocyclic compound which is a phenyl group substituted with one amino group, mono- or di-C ₁ -C ₁₀ alkylamino or cyano, and further optionally substituted with one or two C ₁ -C ₆ alkyl groups or Its pharmacologically acceptable salts. 25. The method according to claim 23, wherein R ⁴ is
4-aminophenyl, 4-amino-3,5-dimethylphenyl, 4-amino-3,5-di-t-butylphenyl, 3-dimethylaminophenyl, 4-dimethylaminophenyl or 4-cyanophenyl group. A substituted fused heterocyclic compound or a pharmaceutically acceptable salt thereof. 26. A method according to claim 1, wherein:
R ⁴ may be 1 to 3 substituted with a group selected from the substituent group beta, C ₆ -C ₁₀ aryloxy, C ₇ -C ₁₆
One substituted with aralkyloxy or C ₆ -C ₁₀ arylthio, and further substituted with one to
3 phenyl groups which may be substituted (the substituent groups include halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁
-C ₆ alkyl, C ₁ -C ₆ alkoxy and C ₁ -C ₆
Consists of alkylthio. Or a pharmacologically acceptable salt thereof. <Substituent group β> halogen atom, hydroxy group, C ₁ -C
₆ alkyl group, halogeno C ₁ -C ₆ alkyl group, C _1-
A C ₆ alkoxy group, an amino group optionally substituted with a group selected from the substituent group γ, a C ₆ -C ₁₀ aryl group, and a nitro group. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 27. The method according to claim 26, wherein R ⁴ is
Substituted with 1 to 3 optionally substituted C ₆ -C ₁₀ aryloxy with a group selected from substituent group β,
A substituted condensed heterocyclic compound which is a phenyl group which may be substituted by 1 to 2 C ₁ -C ₆ alkyl, or a pharmacologically acceptable salt thereof. <Substituent group β> halogen atom, hydroxy group, C ₁ -C
₆ alkyl group, halogeno C ₁ -C ₆ alkyl group, C _1-
A C ₆ alkoxy group, an amino group optionally substituted with a group selected from the substituent group γ, a C ₆ -C ₁₀ aryl group, and a nitro group. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 28. The method according to claim 26, wherein R ⁴ is
C which may be substituted by one group selected from substituent group β
₆ -C ₁₀ substituted fused heterocyclic compound or a pharmacologically acceptable salt thereof or an aryloxy one to substituted phenyl group. <Substituent group β> halogen atom, hydroxy group, C ₁ -C
₆ alkyl group, halogeno C ₁ -C ₆ alkyl group, C _1-
A C ₆ alkoxy group, an amino group optionally substituted with a group selected from the substituent group γ, a C ₆ -C ₁₀ aryl group, and a nitro group. <Substituent group γ> A C ₁ -C ₁₀ alkyl group, an optionally substituted C ₆ -C ₁₀ aryl and a C ₇ -C ₁₆ aralkyl group, and an acyl group (the acyl group is a C ₁ -C ₇ aliphatic family acyl group and may be substituted, C ₇ -C ₁₁ aromatic acyl, C8-C ₁₂ araliphatic acyl, C ₄ -C ₁₁ 5 to 6-membered aromatic heterocyclic carbonyl containing cycloalkylcarbonyl and nitrogen atom Represents a group). 29. The method according to claim 26, wherein R ⁴ is
A substituted fused heterocyclic compound which is 4-phenoxyphenyl or a pharmacologically acceptable salt thereof. 30. The method according to claim 1, wherein
R ⁴ is a phenyl group substituted by 1 to 5 groups selected from the following substituent groups (the substituent groups include halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, ₁ -C ₆ alkoxy, C ₁ -C ₆ alkylthio and C ₁ -C ₇ aliphatic acyloxy.) substituted fused heterocyclic compound or a pharmacologically acceptable salt thereof is. 31. The method according to claim 30, wherein R ⁴ is
Halogen, hydroxy, C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C
₆ alkylthio or C ₁ -C ₇ aliphatic acyloxy with 1
Substituted with one or more groups selected from the following substituent groups.
A phenyl group which may be substituted with 4 to 4 groups (the substituent group is
Halogen, C ₁ -C ₆ alkyl and halogeno C ₁ -C ₆
Consists of alkyl. Or a pharmacologically acceptable salt thereof. 32. The method according to claim 30, wherein R ⁴ is
C ₁ -C ₆ alkyl, halogeno C ₁ -C ₆ alkyl, C
In ₁ -C ₆ alkoxy or C ₁ -C ₆ alkylthio
A substituted condensed heterocyclic compound which is a phenyl group substituted by 1 or a phenyl group substituted by 1 to 5 halogens, or a pharmaceutically acceptable salt thereof. 33. The method according to claim 30, wherein R ⁴ is
Substitution condensation which is a phenyl group substituted by ₁ halogeno C ₁ -C ₂ alkyl, C ₁ -C ₂ alkoxy or C ₁ -C ₂ alkylthio or a phenyl group substituted by 1 to 5 fluorine or chlorine atoms A heterocyclic compound or a pharmacologically acceptable salt thereof. 34. The method according to claim 30, wherein R ⁴ is
A substituted condensed heterocyclic compound which is a 4-trifluoromethylphenyl, 4-methylthiophenyl, 4-methoxyphenyl or pentafluorophenyl group, or a pharmaceutically acceptable salt thereof. 35. The method according to claim 30, wherein R ⁴ is
Hydroxy or C ₁ -C ₇ aliphatic acyloxy with 1
Substituted with one or more groups selected from the following substituent groups.
A phenyl group which may be substituted with 3 to 3 substituents (the substituent group is
Consisting of halogen and C ₁ -C ₆ alkyl. Or a pharmacologically acceptable salt thereof. 36. The method according to claim 30, wherein R ⁴ is
A phenyl group which is substituted by 1 hydroxy and may be further substituted by 1 to 3 substituents selected from the following substituent group (the substituent group consists of halogen and C ₁ -C ₆ alkyl). A certain substituted fused heterocyclic compound or a pharmaceutically acceptable salt thereof. 37. The method according to claim 30, wherein R ⁴ is
A phenyl group which is substituted by one with hydroxy and may be further substituted with one to three groups selected from the following substituent groups (the substituent group is composed of fluorine, chlorine, methyl and t-butyl); Or a pharmacologically acceptable salt thereof. 38. The method according to claim 30, wherein R ⁴ is
4-hydroxyphenyl, 4-hydroxy-3,5-dimethylphenyl, 4-hydroxy-3,5-di-t-butylphenyl, 4-hydroxy-2,3,5-trimethylphenyl or 2-chloro-4- Hydroxy-3,5-
A substituted fused heterocyclic compound which is a dimethylphenyl group or a pharmacologically acceptable salt thereof. 39. The method according to claim 1, wherein R ⁶ is substituted by 1 to 3 hydrogen atoms, C ₁ -C ₆ alkyl groups, or groups selected from the following substituent groups. Or a substituted phenyl or benzyl group (the substituent group consisting of halogen, hydroxy, C ₁ -C ₆ alkyl and halogeno C ₁ -C ₆ alkyl) or a substituted fused heterocyclic compound thereof, Pharmacologically acceptable salt. 40. The method according to claim 1, wherein R ⁶ is a hydrogen atom, a C ₁ -C ₄ alkyl group, or a phenyl or benzyl group (optionally substituted with one of the following substituents). The substituent is fluorine, chlorine, hydroxy, methyl or ethyl.) Or a pharmacologically acceptable salt thereof. 41. The substituted condensed heterocyclic compound according to claim 1, wherein R ⁶ is a hydrogen atom or a C ₁ -C ₄ alkyl group, or a pharmaceutically acceptable salt thereof. 42. The substituted condensed heterocyclic compound according to any one of claims 1 to 38, wherein R ⁶ is a C ₁ -C ₂ alkyl group, or a pharmaceutically acceptable salt thereof. 43. The substituted fused heterocyclic compound according to claim 1 wherein R ⁶ is a methyl group, or a pharmacologically acceptable salt thereof. 44. The substituted condensed heterocyclic compound according to claim 1, wherein A is a C ₁ -C ₄ alkylene group, or a pharmaceutically acceptable salt thereof. 45. The substituted condensed heterocyclic compound according to any one of claims 1 to 43, wherein A is a C ₁ -C ₂ alkylene group, or a pharmaceutically acceptable salt thereof. 46. The substituted fused heterocyclic compound according to claim 1 wherein A is a methylene group or a pharmacologically acceptable salt thereof. 47. The substituted condensed heterocyclic compound according to claim 1, wherein B is an oxygen atom, or a pharmaceutically acceptable salt thereof. 48. The substituted condensed heterocyclic compound according to any one of claims 1 to 47, wherein D is an oxygen atom, or a pharmaceutically acceptable salt thereof. 49. The substituted condensed heterocyclic compound according to any one of claims 1 to 47, wherein D is a sulfur atom, or a pharmaceutically acceptable salt thereof. 50. The substituted fused heterocyclic compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 49, wherein E is a group having CH. 51. The substituted condensed heterocyclic compound or a pharmacologically acceptable salt thereof according to any one of claims 1 to 49, wherein E is a nitrogen atom. 52. The compound according to claim 1, or a pharmacologically acceptable salt thereof, selected from the group consisting of the following compounds. 5- {4- [6- (4-hydroxyphenoxy)-
1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, 5- {4- [1-methyl-6- (4-trifluoromethylphenoxy) -1H-benzimidazole-2 -Ylmethoxy] benzyl} thiazolidine-2,4-dione, 5- {4- [1-methyl-6- (4-methoxyphenoxy) -1H-benzimidazol-2-ylmethoxy]
Benzyl {thiazolidine-2,4-dione, 5- {4- [1-methyl-6- (4-methylthiophenoxy) -1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione, 5- {4- [6- (4-aminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione, 5- {4- [6- (3-dimethylaminophenoxy) )-
1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, 5- {4- [6- (4-acetylaminophenoxy)-
1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, 5- {4- [1-methyl-6- (4-phenylphenoxy) -1H-benzimidazol-2-ylmethoxy] ]
Benzyl @ thiazolidine-2,4-dione, 5- {4- [6- (4′-hydroxybiphenyl-4-)
Yloxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4
-Dione, 5- {4- [6- (4-benzylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy]
Benzyl @ thiazolidine-2,4-dione, 5- {4- (6- [2- (pyrrolidin-1-yl) phenoxy] -1-methyl-1H-benzimidazole-2
-Ylmethoxy) benzyl} thiazolidine-2,4-dione, 5- {4- (6- [2- (piperidin-1-yl) phenoxy] -1-methyl-1H-benzimidazole-2
-Ylmethoxy) benzyl} thiazolidine-2,4-dione, 5- {4- (6- [2- (morpholin-4-yl) phenoxy] -1-methyl-1H-benzimidazole-2
-Ylmethoxy) benzyl} thiazolidine-2,4-dione, 5- {4- (1-methyl-6- [3- (morpholine-4)
-Yl) phenoxy] -1H-benzimidazole-2
-Ylmethoxy) benzyl} thiazolidine-2,4-dione, 5- {4- [6- (2-chloro-4-hydroxy-3,
5-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, 5- {4- [6- (4-hydroxy-2-methylphenoxy) -1-) Methyl-1H-benzimidazole-2-
Ylmethoxy] benzyl} thiazolidine-2,4-dione, 5- {4- [6- (4-hydroxy-3-methylphenoxy) -1-methyl-1H-benzimidazole-2-
Ylmethoxy] benzyl {thiazolidine-2,4-dione, 5- {4- [6- (4-hydroxy-2,5-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine- Two, four
-Dione, 5- {4- [6- (4-hydroxy-3,5-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4
-Dione, 5- {4- [6- (3,5-di-tert-butyl-4-hydroxyphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-
2,4-dione, 5- {4- [6- (3,5-di-tert-butyl-4-hydroxyphenylthio) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2 , 4-dione, 5- {4- [6- (4-hydroxy-2,3,5-trimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-
2,4-dione, 5- {4- [5- (4-hydroxy-2,3,5-trimethylphenoxy) -3-methyl-3H-imidazo [4,5-b] pyridin-2-ylmethoxy] benzyl ｝ Thiazolidine-2,4-dione, 5- ｛4- [6- (4-amino-3,5-dimethylphenoxy) -1-methyl-1H-benzimidazole-2
-Ylmethoxy] benzyl {thiazolidine-2,4-dione, 5- {4- [6- (4-acetylamino-3,5-dimethylphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} Thiazolidine-
2,4-dione, 5- {4- [6- (pyridin-2-yloxy) -1-
Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, 5- {4- [1-methyl-6- (pyridin-2-ylthio) -1H-benzimidazol-2-ylmethoxy]
Benzyl {thiazolidine-2,4-dione, 5- {4- [1-methyl-6- (pyridin-3-yloxy) -1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione, 5 -{4- (6- [4- (imidazol-1-yl) phenoxy] -1-methyl-1H-benzimidazole-
2-ylmethoxy) benzyl {thiazolidine-2,4-
Dione, 5- {4- (6- [4- (1-adamantyl) phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl} thiazolidine-2,4-dione, 5- {4- [ 6- (4-cyanophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4-dione, 5- {4- [6- (2,5-di-t-butyl) -4-hydroxyphenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-
2,4-dione, 5- [4- (6-pentafluorophenoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) benzyl] thiazolidine-2,4-dione, 5- {4- [6- ( 4-benzoylaminophenoxy)
-1-Methyl-1H-benzimidazol-2-ylmethoxy] benzyl {thiazolidine-2,4-dione, 5- [4- {6- [4- (2,4-difluorobenzoylamino) phenoxy] -1-methyl -1H-benzimidazol-2-ylmethoxy {benzyl] thiazolidine-2,4-dione, 5- {4- [6- (4-cyclopentanoylaminophenoxy) -1-methyl-1H-benzimidazole-2
-Ylmethoxy] benzyl {thiazolidine-2,4-dione, 5- {4- [6- (4-nicotinoylaminophenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzyl} thiazolidine-2,4 -Dione, and 5- {4- [6- (3,5-di-t-butyl-
4-hydroxyphenylthio) -1-methyl-1H-benzimidazol-2-ylmethoxy] benzylidene
Thiazolidine-2,4-dione. 53. A medicament comprising the substituted condensed heterocyclic compound or the pharmaceutically acceptable salt thereof according to any one of claims 1 to 52 as an active ingredient.