JP2001131175A - New isoindole derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new isoindole derivative exhibiting an activity of showing a high GLP-1 concentration in blood and hence useful for the treatment of diabetes mellitus, prevention of chronic complication of the diabetes mellitus and treatment of obesity. SOLUTION: This new isoindole derivative is a compound expressed by the general formula (I) (wherein R is azido or the like; R1 and R2 are each the same or different H or the like; R3 and R4 are each the same or different H or the like; X1 is O or the like; X2 is O or the like; Y is O or the like; and Z is a condensed aryl group or the like) or its pharmaceutically permissible salt, and the method for producing the same compound is provided.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel isoindole derivative useful as a pharmaceutical and a method for producing the same.

[0002]

2. Description of the Related Art The blood sugar level of a healthy person is constantly controlled by the action of insulin. Diabetes refers to a chronic hyperglycemic state in which this control is ineffective and a disease caused thereby.

[0003] The basis of diabetes treatment is to correct the hyperglycemia state, that is, to return the blood glucose concentration to a normal value. It has been recognized that how to control the rise is of great therapeutic importance.

[0004] At present, there are three major therapeutic agents for diabetes used in clinical practice in addition to various insulin preparations. The first is a group of drugs called insulin-releasing drugs represented by sulfonylurea drugs, which directly promote insulin secretion from the pancreas and lower blood sugar levels. The second is an insulin sensitizer recently marketed, which is a drug that lowers blood glucose levels by promoting glucose uptake in peripheral tissues without directly promoting insulin release. The third α-glucosidase inhibitor is a drug that controls a rapid rise in blood sugar level by delaying digestion and absorption of carbohydrates in the digestive tract and suppressing a temporary rise in blood sugar level after eating.

On the other hand, glucagon-like peptide-1 (hereinafter referred to as "glucagon-like peptide-1")
GLP-1. ) Is a hormone secreted by L cells, which are endocrine cells present in the small intestinal intestinal epithelium upon stimulation of a meal or the like, and acts on β cells present in the islets of Langerhans of the pancreas to promote insulin secretion, thereby promoting blood glucose. (Eur. JC)
lin. Invest, vol. 22, p. 154, 199
2 years). It has been reported that the insulin secretion action of GLP-1 depends on the blood glucose level, and that insulin secretion by GLP-1 is not observed during normal blood glucose, and that insulin secretion is enhanced only during hyperglycemia ( Lanc
et., Vol. 2, p. 1300, 1987). GLP-
1 not only enhances insulin secretion but also enhances insulin biosynthesis (Endocrinology, 13
0, p. 159, 1992) and promotes β-cell proliferation (Diabetologia, 42, 85).
6, p. 1999), which is an essential factor for the maintenance of β cells.

As a result of maintaining the blood GLP-1 concentration at a high level by administering GLP-1 to general type II diabetes patients,
It has been shown that the hyperglycemic state is significantly improved, and its efficacy against diabetes has been confirmed even in medical practice (Diabetologia, Vol. 36, No. 7).
41 pages, 1994 or same, vol. 39, p. 1546,
(1996)

[0007] Furthermore, the action point of GLP-1 is not limited to β cells, and it is recognized that glucose utilization is enhanced in peripheral tissues (Endocrinology, No. 13).
5, 2070, 1994 or Diabetol
OGIA, Vol. 37, p. 1163, 1994), and it has been reported that intracerebroventricular administration of GLP-1 exerts an antifeedant effect (Digestion, 54).
Vol. 360, 1993). Furthermore, it has been reported that GLP-1 administration has a gastrointestinal motility inhibitory effect (Dig. Dis. Sci., Vol. 43, No. 1113).
P. 1998).

The compound whose structure is most similar to the compound of the present invention is disclosed in US Pat. No. 4,717,414 (hereinafter referred to as Reference A).
That. ) And J. et al. Chem. Soc. , Perkin
Trans. 1, p. 1547, 1979 (hereinafter referred to as
Refer to Reference B. )It is described in.

The compound of Reference A has an imidazoisoindole-dione skeleton having an oxo group at the imidazo moiety condensed with the isoindole skeleton.

However, the compound of the present invention is different from the compound of Reference A in that the imidazoisoindole-dione skeleton has a functional group such as an aryl group at the 9-position substituent on the skeleton. Alkyl group (R ⁴ C
(Z) R ⁵ ), specifically, for example, a nitromethyl group, 1-
The compound of Reference A having a nitro-1-ethylmethyl group or the like is a compound having a completely different structure. Further, the use of Reference A is a herbicide, and the present invention is a use having no relevance in industrial application fields. Furthermore, the production method of Reference A is based on a nucleophilic reaction of an alkyl carbon anion or the like to dihydroimidazoisoindole-dione or the like, and is completely different from the production method of the present invention involving a ring-forming reaction.

Reference B describes a compound having an oxazoloisoindole-dione skeleton having an oxo group at the oxazolo moiety condensed with the isoindole skeleton.

However, Reference B mainly discloses a novel method for producing an isoindolobenzazepine derivative. In the reaction step, only a compound having an oxazoloisoindole-dione skeleton is produced as a reaction by-product. It merely discloses what is done. The compound of the present invention has an oxazoloisoindole-dione skeleton common to the compound described in Reference B, but has a substituent at the 9-position substituent on the skeleton, for example, having a functional group such as an aryl group. The compound of Reference B which is the compound (11) which is an α-bromobenzyl group is a compound having a completely different structure.

Further, Japanese Patent Application Laid-Open No. 6-507388 (hereinafter referred to as Reference C) and US Pat. No. 3,507,863 (hereinafter referred to as Reference D) describe a 6-membered ring, a 5-membered ring and a 5-membered ring. Are described as a tricyclic heteroaromatic ring.

Reference C describes a compound having an oxazoloisoindole skeleton and an imidazoisoindole skeleton in which an oxazolo or imidazo moiety is condensed to an isoindole skeleton.

However, the compound of the present invention has an oxazoloisoindole skeleton or an imidazoisoindole skeleton common to the compound of Reference C, but an oxazolo or imidazo moiety condensed with the isoindole skeleton such as an oxo group or a thioxo group. Is a compound having a completely different structure from the compound of Reference C having no oxo group or the like in that it has a functional group such as The use of Reference C is
It is an antiviral drug and has the same industrial field of application, but is completely unrelated to the use of the present invention.

Reference D describes a compound having an oxazoloisoindole skeleton, an imidazoisoindole skeleton or a thiazoloisoindole skeleton in which an oxazolo moiety, an imidazo moiety or a thiazolo moiety is condensed to an isoindole skeleton.

However, the compound of the present invention has an oxazoloisoindole skeleton, an imidazoisoindole skeleton and a thiazoloisoindole skeleton common to the compound of Reference D, but an oxazolo moiety, an imidazo moiety or a thiazolo moiety condensed to the isoindole skeleton. It is a compound having a completely different structure from the compound of Reference D having no oxo group or the like in that it has a functional group such as an oxo group or a thioxo group in the portion. The use of Reference D is an anti-inflammatory drug or an anticonvulsant, and has the same industrial application field, but has no relation to the use of the present invention.

As prior art disclosing the invention relating to the use of the present invention, there is US Pat. No. 3,928,597 (hereinafter referred to as Reference E). Reference E is characterized in that an imidazo moiety condensed to an isoindole skeleton is substituted with a lower alkyl group for a lower alkyl group, and a 2,3-dihydroimidazoisoindoleol compound and an imidazolylphenylphenyl ketone compound are orally or parenterally administered. It is an invention of a method for treating glycemia.

However, the compound of the present invention is characterized in that although the imidazoisoindolone skeleton is common to the compound of Reference E, the imidazo moiety condensed with the isoindole skeleton has a functional group such as an oxo group or a thioxo group.
The compound of Reference E having no oxo group or the like is a compound having a completely different structure. Moreover, the feature of the invention of Reference E is that it does not show a hyperglycemic effect by itself, as described in the specification, column 4, lines 39 to 45,
The present invention is a use invention by the interaction of two kinds of compounds, which is achieved by co-administering a 2,3-dihydroimidazoisoindoleol compound and an imidazolylphenylphenyl ketone compound. Are different.

[0020]

At present, drugs such as sulfonylurea drugs, insulin sensitizers, α-glucosidase inhibitors and the like are widely used in clinical practice as drugs for treating diabetes. However, these are not sufficient drugs. That is,
Sulfonylurea agents have a slow onset of action and a long duration of action, which makes it difficult to develop a synergistic effect during postprandial hyperglycemia, and further reduces severe fasting blood sugar, which is often life-threatening. It can also cause a glycemic attack. Insulin sensitizers often have side effects on the liver, and require careful use under strict control. In addition, side effects such as edema may be caused. In addition, α-glucosidase inhibitors have a problem of side effects such as bloating and diarrhea.

Therefore, with the recent increase in the number of diabetic patients, there is a current demand from clinical sites for the development of more beneficial antidiabetic drugs that have no side effects and can control the blood glucose level depending on the blood glucose level.

[0022]

Means for Solving the Problems The present inventors have made intensive studies for the purpose of creating a therapeutic agent for diabetes, a preventive agent for chronic complications of diabetes or an anti-obesity drug which can control blood glucose level depending on the blood glucose level. As a result, they have found that the compound of the general formula [I] achieves a high blood GLP-1 concentration in vivo, and have completed the present invention.

The present invention relates to an isoindole derivative and a method for producing the same, and these inventions are novel ones not described in the literature.

Next, definitions of various symbols and terms described in this specification will be described.

The aryl group may have 6 to 15 carbon atoms.
Are preferred, for example, a naphthyl group,
A phenyl group and the like can be mentioned, and among them, for example, a phenyl group and the like are preferable.

The monocyclic to tricyclic C ₇ -C ₁₅ carbon aromatic ring group is preferably an aromatic ring group having 1 to 3 cyclic groups containing 7 to 15 carbon atoms, for example, acenaphthylenyl group, adamantyl group, Anthryl group, indenyl group,
Examples thereof include a norbornyl group and a phenanthryl group, and among them, for example, an anthryl group and a phenanthryl group are preferable.

Examples of the 5- or 6-membered heterocyclic group include isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, thienyl, triazinyl,
Triazolyl group, pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, pyrazolyl group, pyrrolyl group,
Pyranyl group, furyl group, furazanyl group, imidazolidinyl group, imidazolinyl group, tetrahydrofuranyl group, pyrazolidinyl group, pyrazolinyl group, piperazinyl group, piperidinyl group, pyrrolidinyl group, pyrrolinyl group, morpholino group and the like, among which, for example, thienyl group, tetrahydrofuran Nyl, pyridyl, pyrazinyl, pyrimidinyl, furyl, morpholino and the like are preferred.

Examples of the mono- to tricyclic heteroaromatic group having 1 to 5 heteroatoms per ring system selected from the group consisting of nitrogen, oxygen and sulfur are, for example, acridinyl, isoquinolyl, isoindolyl Group,
Indazolyl group, indolyl group, indolizinyl group, ethylenedioxyphenyl group, carbazolyl group, quinazolinyl group, quinoxalinyl group, quinolizinyl group, quinolyl group, cumaronyl group, chromenyl group, phenanthridinyl group, phenanthrolinyl group, dibenzofura Nyl group, dibenzothiophenyl group, cinnolinyl group, thionaphthenyl group, naphthyridinyl group, phenazinyl group, phenaxazinyl group, phenothiazinyl group, phthalazinyl group, pteridinyl group, purinyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, benzotria Zolyl group, benzofuranyl group, methylenedioxyphenyl group and the like, among which, for example, ethylenedioxyphenyl group, dibenzofuranyl group, dibenzothiophenyl group,
A methylenedioxyphenyl group is preferred.

The halogen atom means, for example, a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, among which a fluorine atom, a chlorine atom, an iodine atom and the like are preferable, and a fluorine atom, a chlorine atom and the like are more preferable.

As the cyclic saturated C ₃ -C ₉ aliphatic group, a cyclic alkyl group having 3 to 9 carbon atoms is preferable, and a cyclic alkyl group having 3 to 6 carbon atoms is particularly preferable. is there.

Examples of the cyclic alkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group and a cyclononyl group. Among them, for example, a cyclopropyl group, a cyclobutyl group and a cyclopentyl group are exemplified. And cyclohexyl groups.

As the cyclic unsaturated C ₃ -C ₉ aliphatic group,
A cyclic alkenyl group having 3 to 9 carbon atoms is preferable, and a cyclic alkenyl group having 3 to 6 carbon atoms is particularly preferable.

Examples of the cyclic alkenyl group include a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, a cycloheptenyl group, a cyclooctenyl group, a cyclononenyl group and the like. Pentenyl, cyclohexenyl and the like are preferred.

The aralkyl group is preferably an aralkyl group having 7 to 15 carbon atoms, and specific examples thereof include a benzyl group, an α-methylbenzyl group, a phenethyl group,
Phenylpropyl group, 1-naphthylmethyl group, 2-naphthylmethyl group, α-methyl (1-naphthyl) methyl group,
α-methyl (2-naphthyl) methyl group, α-ethyl (1
-Naphthyl) methyl group, α-ethyl (2-naphthyl) methyl group, diphenylmethyl group and the like, and dinaphthylmethyl group. Methylbenzyl group,
Phenethyl groups and the like are preferred.

The N-aralkylamino group means a group in which an amino group is substituted with the above-mentioned aralkyl group. Specifically, for example, N-benzylamino group, N- (α-methylbenzyl) amino group, Phenethylamino group, N- (3-phenylpropyl) amino group, N- (1-naphthylmethyl) amino group, N- (2-naphthylmethyl) amino group,
An N- [α-methyl (1-naphthyl) methyl] amino group,
An N- [α-methyl (2-naphthyl) methyl] amino group,
An N- [α-ethyl (1-naphthyl) methyl] amino group,
An N- [α-ethyl (2-naphthyl) methyl] amino group,
Diphenylmethylamino group, N- (dinaphthylmethyl)
Examples include an amino group and the like, and particularly, for example, an N-benzylamino group, an N- (α-methylbenzyl) amino group, an N-phenethylamino group, and the like are preferable.

The N, N-di-aralkylamino group means a group in which an amino group is disubstituted with the above aralkyl group.
Specifically, for example, N, N-dibenzylamino group, N, N
-Di (α-methylbenzyl) amino group, N, N-diphenethylamino group, N, N-di (3-phenylpropyl)
An amino group, an N, N-di (1-naphthylmethyl) amino group, an N, N-di (2-naphthylmethyl) amino group,
N-di [α-methyl (1-naphthyl) methyl] amino group, N, N-di [α-methyl (2-naphthyl) methyl]
Amino group, N-benzyl-N- (α-methylbenzyl)
Amino group, N-benzyl-N-phenethylamino group, N
-Benzyl-N- (3-phenylpropyl) amino group; and for example, N, N-dibenzylamino group, N, N-di (α-methylbenzyl) amino group,
An N-diphenethylamino group and the like are preferred.

The aralkyloxy group means a group in which an oxygen atom is substituted by the above aralkyl group, and specifically, for example, benzyloxy group, α-methylbenzyloxy group, phenethyloxy group, 3-phenylpropoxy group, 1-naphthylmethoxy group, 2-naphthylmethoxy group, α-methyl (1-naphthyl) methoxy group, α-methyl (2-naphthyl) methoxy group, α-ethyl (1-naphthyl) methoxy group, α-ethyl (2 -Naphthyl) methoxy group, diphenylmethoxy group, dinaphthylmethoxy group and the like,
Particularly, for example, a benzyloxy group, an α-methylbenzyloxy group, a phenethyloxy group and the like are preferable.

The aralkylcarbonyl group means a group in which the above aralkyl group is substituted on the carbonyl group, and specifically, for example, benzylcarbonyl group, α-methylbenzylcarbonyl group, phenethylcarbonyl group, 3-phenylpropylcarbonyl group , 1-naphthylmethylcarbonyl group, 2-naphthylmethylcarbonyl group, α-methyl (1
-Naphthyl) methylcarbonyl group, α-methyl (2-naphthyl) methylcarbonyl group, α-ethyl (1-naphthyl) methylcarbonyl group, α-ethyl (2-naphthyl)
Methylcarbonyl group, diphenylmethylcarbonyl group,
Examples thereof include a dinaphthylmethylcarbonyl group and the like, and particularly preferable examples include a benzylcarbonyl group, an α-methylbenzylcarbonyl group, and a phenethylcarbonyl group.

The term "N-aralkylcarbamoyl group" means a group in which a carbamoyl group is substituted with the above-mentioned aralkyl group.
-(Α-methylbenzyl) carbamoyl group, N-phenethylcarbamoyl group, N- (3-phenylpropyl) carbamoyl group, N- (1-naphthylmethyl) carbamoyl group, N- (2-naphthylmethyl) carbamoyl group, N
-(Α-methyl (1-naphthyl) methyl) carbamoyl group, N- (α-methyl (2-naphthyl) methyl) carbamoyl group, N- (α-ethyl (1-naphthyl) methyl)
Carbamoyl group, N- (α-ethyl (2-naphthyl) methyl) carbamoyl group, N- (diphenylmethyl) carbamoyl group, N- (dinaphthylmethyl) carbamoyl group, and the like. N- (α-methylbenzyl) carbamoyl group, N-
Phenethylcarbamoyl groups and the like are preferred.

The N-arylamino group means a group in which an amino group is substituted by the above-mentioned aryl group. Specifically, for example, N-phenylamino group, N- (1-naphthyl) amino group, N- ( 2-naphthyl) amino group and the like, among which an N-phenylamino group and the like are preferable.

The N, N-diarylamino group means a group in which the above-mentioned aryl group is disubstituted on the amino group, and specifically, for example, N, N-diphenylamino group, N, N-di (1- Naphthyl) amino group, N, N-di (2-naphthyl) amino group, N-phenyl-N- (1-naphthyl) amino group, N-phenyl-N- (2-naphthyl) amino group, N- (1 -Naphthyl) -N- (2-naphthyl) amino group and the like. Among them, for example, N, N-diphenylamino group, N, N-di (1-naphthyl) amino group, N, N
-Di (2-naphthyl) amino group and the like are preferable.

The aryloxy group means a group in which an oxygen atom is substituted by the above-mentioned aryl group, and specific examples include a phenoxy group and a naphthyloxy group. Among them, a phenoxy group is preferable.

The arylsulfonyl group means a group in which the above-mentioned aryl group is substituted on the sulfonyl group, and specific examples include a phenylsulfonyl group and a naphthylsulfonyl group. Among them, for example, a phenylsulfonyl group is preferable.

The arylsulfonyloxy group means a group in which a sulfonyloxy group is substituted by the above-mentioned aryl group. Specific examples include a phenylsulfonyloxy group and a naphthylsulfonyloxy group. And the like.

The N-arylsulfonylamino group means a group in which the above-mentioned arylsulfonyl group is N-substituted on an amino group, specifically, for example, N-phenylsulfonylamino group, N- (1-naphthylsulfonyl) Amino group,
N- (2-naphthylsulfonyl) amino group and the like. Among them, for example, N-phenylsulfonylamino group,
A-(2-naphthylsulfonyl) amino group and the like are preferable.

N-arylsulfonylamino C ₁ -C ₁₀
The alkylamino group is preferably an N-substituted amino group having the above arylsulfonylamino group and an alkyl group having 1 to 10 carbon atoms, specifically, for example, an N-phenylsulfonylaminomethylamino group, N- (1-phenylsulfonylaminoethyl) amino group, N- (2-phenylsulfonylaminoethyl) amino group, N-naphthylsulfonylaminomethylamino group, N- (1-naphthylsulfonylaminoethyl) amino group, N- (2-naphthylsulfonylaminoethyl)
Examples include an amino group, and among them, for example, an N-phenylsulfonylaminomethylamino group, an N- (2-phenylsulfonylaminoethyl) amino group, and the like are preferable.

N-arylsulfonylamino C ₁ -C ₁₀
As the alkylcarbamoyl group, a group in which an alkyl group having 1 to 10 carbon atoms and having the above arylsulfonylamino group is N-substituted in the carbamoyl group is preferable, and specifically, for example, an N-phenylsulfonylaminomethylcarbamoyl group, N- (1-phenylsulfonylaminoethyl) carbamoyl group, N- (2-phenylsulfonylaminoethyl) carbamoyl group, N-naphthylsulfonylaminomethylcarbamoyl group, N- (1-naphthylsulfonylaminoethyl) carbamoyl group, N-
(2-Naphthylsulfonylaminoethyl) carbamoyl group and the like. Among them, for example, N-phenylsulfonylaminomethylcarbamoyl group, N- (2-phenylsulfonylaminoethyl) carbamoyl group, N- (2-naphthylsulfonylaminoethyl) carbamoyl group Groups and the like are preferred.

As the N-arylsulfonylamino C ₁ -C ₆ alkoxycarbonyl group, a group in which the above-mentioned N-arylsulfonylamino group is substituted by an alkoxycarbonyl group having 1 to 6 carbon atoms is preferable. Examples thereof include an N-phenylsulfonylaminomethoxycarbonyl group, an N-naphthylsulfonylaminomethoxycarbonyl group, a 1- (N-phenylsulfonylamino) ethoxycarbonyl group, and a 2- (N-phenylsulfonylamino) ethoxycarbonyl group. For example, an N-phenylsulfonylaminomethoxycarbonyl group,
An N-naphthylsulfonylaminomethoxycarbonyl group and the like are preferable.

The arylsulfamoyl group means a group in which a sulfamoyl group is substituted with the above-mentioned aryl group, and specific examples include a phenylsulfamoyl group and a naphthylsulfamoyl group. Sulfamoyl groups and the like are preferred.

The arylsulfamoyloxy group means a group in which a sulfamoyloxy group is substituted by the above-mentioned aryl group. Specifically, for example, a phenylsulfamoyloxy group, a naphthylsulfamoyloxy group, etc. Among them, for example, a phenylsulfamoyloxy group is preferable.

The N-arylsulfamoyl C ₁ -C ₁₀ alkylcarbamoyl group is preferably a group in which the above-mentioned arylsulfamoyl is substituted by an alkylcarbamoyl group having 1 to 10 carbon atoms. Examples include a phenylsulfamoylmethylcarbamoyl group and an N-naphthylsulfamoylmethylcarbamoyl group, and among them, for example, an N-phenylsulfamoylmethylcarbamoyl group is preferable.

The arylsulfamoyl C ₁ -C ₆ alkoxycarbonyl group is preferably a group in which the above-mentioned arylsulfamoyl is substituted by an alkoxycarbonyl group having 1 to 6 carbon atoms. Examples thereof include a famoylmethoxycarbonyl group and a naphthylsulfamoylmethoxycarbonyl group. Among them, for example, a phenylsulfamoylmethoxycarbonyl group is preferable.

The N-arylcarbamoyl group means a group in which the above-mentioned aryl group is N-substituted with a carbamoyl group, and specific examples include a phenylcarbamoyl group and a naphthylcarbamoyl group. Are preferred.

As the C ₂ -C ₆ alkanoyl group, a group in which a carbonyl group is substituted by an alkyl group having 1 to 5 carbon atoms is preferable. Examples thereof include a valeryl group, an isovaleryl group, a pivaloyl group, and a pentanoyl group. Among them, for example, an acetyl group, a propionyl group, and a pivaloyl group are preferable.

The N—C ₂ -C ₆ alkanoylamino group is
It means a group in which an amino group is substituted with the above-mentioned C ₂ -C ₆ alkanoyl group, specifically, for example, N-acetylamino group, N
-Propionylamino group, N-butyrylamino group, N-
Isobutyrylamino group, N-valerylamino group, N-isovalerylamino group, N-pivaloylamino group, N-pentanoylamino group and the like. Among them, for example, N-acetylamino group, N-propionylamino group, -Pivaloylamino group and the like are preferable.

The N, N-di-C ₂ -C ₆ alkanoylamino group means a group in which the above-mentioned C ₂ -C ₆ alkanoyl group is disubstituted on the amino group, and specifically, for example, N, N-diacetyl Amino group, N, N-dipropionylamino group, N, N
-Dibutyrylamino group, N, N-diisobutyrylamino group, N, N-divalerylamino group, N, N-diisovalerylamino group, N, N-dipivaloylamino group, N, N
-Dipentanoylamino group, N-acetyl-N-propionylamino group, N-acetyl-N-butyrylamino group, N-acetyl-N-pivaloylamino group and the like. Among them, for example, N, N-diacetylamino group, N , N
-Dipropionylamino, N, N-dibutyrylamino, N, N-dipivaloylamino and the like are preferred.

The aroyl group means a group in which a carbonyl group is substituted by the above-mentioned aryl group, and specific examples include a benzoyl group and a naphthylcarbonyl group. Among them, for example, a benzoyl group is preferable.

The alloxy group means a group in which the above-mentioned aroyl group is substituted with an oxygen atom, and specific examples include a benzoyloxy group and a naphthylcarbonyloxy group.

The N-aroylamino group means a group in which the above-mentioned aroyl group is N-substituted on an amino group, and specific examples thereof include N-benzoylamino group and N-naphthylcarbonylamino group. For example, an N-benzoylamino group is preferred.

The N-aroyl C ₁ -C ₁₀ alkylamino group is preferably a group in which the amino group is an N-substituted alkyl group having 1 to 10 carbon atoms and having the above-mentioned aroyl group. -Benzoylmethylamino group, N- (1-benzoylethyl) amino group, N- (2
-Benzoylethyl) amino group, N-naphthylcarbonylamino group, N- (1-naphthylcarbonylethyl) amino group, N- (2-naphthylcarbonylethyl) amino group and the like. Among them, for example, N-benzoylmethylamino group And an N- (2-benzoylethyl) amino group and the like.

[0061] The N- aroyl C ₁ -C ₁₀ alkylcarbamoyl groups, carbamoyl groups above N- aroyl C ₁
—C ₁₀ alkyl group is substituted, specifically, for example, N-benzoylmethylcarbamoyl group, N- (1-
Benzoylethyl) carbamoyl, N- (2-benzoylethyl) carbamoyl, N-naphthylmethylcarbonylcarbamoyl, N- (1-naphthylcarbonylethyl) carbamoyl, N- (2-naphthylcarbonylethyl) carbamoyl and the like. Among them, for example, an N-benzoylmethylcarbamoyl group, an N- (2-benzoylethyl) carbamoyl group and the like are preferable.

An N- (N-aroylamino) C ₁ -C ₁₀ alkylcarbamoyl group is a carbamoyl group represented by
-Aroylamino C ₁ -C ₁₀ alkyl group means a group, specifically, for example, N- (N-benzoylaminomethyl) carbamoyl group, N- (1- (N-benzoylamino) ethyl) carbamoyl group, N- (2- (N-benzoyl) aminoethyl) carbamoyl group, N- (N-
Naphthylcarbonylaminomethyl) carbamoyl group, N
-(1- (N-naphthylcarbonylamino) ethyl) carbamoyl group, N- (2- (N-naphthylcarbonylamino) ethyl) carbamoyl group and the like. Among them, for example, N- (N-benzoylaminomethyl) carbamoyl group And an N- (2- (N-benzoylamino) ethyl) carbamoyl group and the like.

The N-aroylamino C ₁ -C ₁₀ alkoxycarbonyl group means a group in which an oxycarbonyl group is substituted by the above-mentioned N-aroylamino C ₁ -C ₁₀ alkyl group, and specifically, for example, N-benzoylamino A methoxycarbonyl group, a 1- (N-benzoylamino) ethoxycarbonyl group, a 2- (N-benzoylamino) ethoxycarbonyl group, an N-naphthylcarbonylaminomethoxycarbonyl group, a 1- (N-naphthylcarbonylamino) ethoxycarbonyl group, 2- (N-naphthylcarbonylamino) ethoxycarbonyl group and the like. Among them, for example, N-benzoylaminomethoxycarbonyl group and 2-
(N-benzoylamino) ethoxycarbonyl group and the like are preferable.

The N—C ₁ -C ₆ alkylamino group includes
An amino group having an alkyl group having 1 to 6 carbon atoms is N
-Substituted groups are preferred, specifically, for example, N-methylamino, N-ethylamino, N-propylamino, N-isopropylamino, N-butylamino,
N-isobutylamino group, N-sec-butylamino group, N-tert-butylamino group, N-pentylamino group, N-neopentylamino group, N-hexylamino group, N-isohexylamino group and the like. Among them, for example, N-methylamino group, N-ethylamino group, N-propylamino group, N-isopropylamino group, N-butylamino group, N-isobutylamino group, N-tert-
A butylamino group and the like are preferred.

The N, N-di-C ₁ -C ₆ alkylamino group is preferably an amino group in which an alkyl group having 1 to 6 carbon atoms is N, N-disubstituted. N, N-dimethylamino group, N, N-diethylamino group, N, N-dipropylamino group, N, N-diisopropylamino group, N, N-dibutylamino group, N, N-
Di-tert-butylamino group, N, N-dipentylamino group, N, N-dihexylamino group, N-ethyl-N
-Methylamino group, N-methyl-N-propylamino group, N-isopropyl-N-methylamino group, N-te
rt-butyl-N-methylamino group, N-ethyl-N
-Isopropylamino group and the like. Among them, for example, N, N-dimethylamino group, N, N-diethylamino group, N, N-diisopropylamino group, N, N-dibutylamino group, N, N-ditert-butyl Amino group,
N-ethyl-N-methylamino group, N-methyl-N-propylamino group, N-isopropyl-N-methylamino group, N-ethyl-N-isopropylamino group and the like are preferable.

The N-C ₁ -C ₁₀ alkylcarbamoyl group is preferably a group in which a carbamoyl group is N-substituted with an alkyl group having 1 to 10 carbon atoms. -Ethylcarbamoyl group, N-propylcarbamoyl group, N-isopropylcarbamoyl group, N-butylcarbamoyl group, N-isobutylcarbamoyl group, N-sec-butylcarbamoyl group, N-tert-butylcarbamoyl group, N-pentylcarbamoyl group , N-neopentylcarbamoyl group, N-hexylcarbamoyl group, N-isohexylcarbamoyl group, N-octylcarbamoyl group, N-decylcarbamoyl group and the like. Among them, for example, N-methylcarbamoyl group, N-ethylcarbamoyl group , N-propylcarbamoy Group, N- isopropylcarbamoyl group, N- iso-butylcarbamoyl group, N-sec-butylcarbamoyl group, N-tert-butylcarbamoyl group, N- octylcarbamoyl group, N- dodecylcarbamoyl group and the like.

The N, N-di-C ₁ -C ₁₀ alkylcarbamoyl group includes a carbamoyl group having 1 to 10 carbon atoms.
And N, N-disubstituted alkyl groups are preferred. Specifically, for example, N, N-dimethylcarbamoyl, N, N-diethylcarbamoyl, N, N-dipropylcarbamoyl, N, N -Diisopropylcarbamoyl group, N, N-dibutylcarbamoyl group, N, N-ditert-butylcarbamoyl group, N, N-dipentylcarbamoyl group, N, N-dihexylcarbamoyl group,
N-ethyl-N-methylcarbamoyl, N-isopropyl-N-methylcarbamoyl, N-tert-butyl-N-methylcarbamoyl, N-ethyl-N-isopropylcarbamoyl and the like. N-dimethylcarbamoyl group, N, N-diethylcarbamoyl group, N, N-diisopropylcarbamoyl group, N, N-dibutylcarbamoyl group, N, N-dite
An rt-butylcarbamoyl group, an N-ethyl-N-methylcarbamoyl group, an N-isopropyl-N-methylcarbamoyl group, an N-ethyl-N-isopropylcarbamoyl group and the like are preferable.

The N—C ₁ -C ₁₀ alkylthiocarbamoyl group includes a thiocarbamoyl group having 1 to 10 carbon atoms.
And N-substituted alkyl groups are preferred. Specific examples include N-methylthiocarbamoyl, N-ethylthiocarbamoyl, N-propylthiocarbamoyl, N-isopropylthiocarbamoyl, and N-butylthio. Carbamoyl group, N-isobutylthiocarbamoyl group, N-sec-butylthiocarbamoyl group, Nt
tert-butylthiocarbamoyl group, N-pentylthiocarbamoyl group, N-neopentylthiocarbamoyl group, N-hexylthiocarbamoyl group, N-isohexylthiocarbamoyl group, N-octylthiocarbamoyl group, N-decylthiocarbamoyl group And the like, among which, for example, N-methylthiocarbamoyl group, N-ethylthiocarbamoyl group, N-propylthiocarbamoyl group,
N-isopropylthiocarbamoyl group, N-isobutylthiocarbamoyl group, N-sec-butylthiocarbamoyl group, N-tert-butylthiocarbamoyl group,
N-octylthiocarbamoyl, N-decylthiocarbamoyl and the like are preferred.

The N, N-di-C ₁ -C ₁₀ alkylthiocarbamoyl group is preferably a thiocarbamoyl group in which an alkyl group having 1 to 10 carbon atoms is N, N-disubstituted. For example, an N, N-dimethylthiocarbamoyl group, an N, N-diethylthiocarbamoyl group,
N, N-dipropylthiocarbamoyl, N, N-diisopropylthiocarbamoyl, N, N-dibutylthiocarbamoyl, N, N-ditert-butylthiocarbamoyl, N, N-dipentylthiocarbamoyl,
N, N-dihexylthiocarbamoyl group, N-ethyl-
N-methylthiocarbamoyl group, N-isopropyl-N
-Methylthiocarbamoyl group, N-tert-butyl-
Examples include an N-methylthiocarbamoyl group, an N-ethyl-N-isopropylthiocarbamoyl group, and among them, for example, an N, N-dimethylthiocarbamoyl group, an N, N-diethylthiocarbamoyl group, an N, N-diisopropylthiocarbamoyl group, N, N-dibutylthiocarbamoyl group, N, N-ditert-butylthiocarbamoyl group,
N-ethyl-N-methylthiocarbamoyl, N-isopropyl-N-methylthiocarbamoyl, N-ethyl-N-isopropylthiocarbamoyl and the like are preferable.

The N-amino C ₁ -C ₁₀ alkylcarbamoyl group is preferably a group in which a carbamoyl group is N-substituted with an aminoalkyl group having 1 to 10 carbon atoms, and specifically, for example, N-aminomethylcarbamoyl Group, N-aminoethylcarbamoyl group, N-aminopropylcarbamoyl group, N-aminomethylethylcarbamoyl group, N-aminobutylcarbamoyl group, N-aminopropylcarbamoyl group, N-aminopentylcarbamoyl group, N-aminohexylcarbamoyl group And the like, among which, for example, an N-aminomethylcarbamoyl group,
N-aminoethylcarbamoyl, N-aminopropylcarbamoyl, N-aminomethylethylcarbamoyl and the like are preferred.

The N-C ₁ -C ₆ alkoxy C ₁ -C ₁₀ alkylcarbamoyl group includes the above-mentioned N-C ₁ -C ₁₀ alkylcarbamoyl group substituted by an alkoxy group having 1 to 6 carbon atoms. Preferably, specifically, for example, N
-Methoxymethylcarbamoyl group, N-methoxyethylcarbamoyl group, N-methoxypropylcarbamoyl group, N-methoxybutylcarbamoyl group, N-ethoxypentylcarbamoyl group, N-butoxyhexylcarbamoyl group and the like. Methylcarbamoyl, N-methoxyethylcarbamoyl, N-methoxypropylcarbamoyl, N-methoxybutylcarbamoyl and the like are preferred.

NC ₁ -C ₆ alkoxycarbonyl C _1-
As the C ₁₀ alkylcarbamoyl group, the above-mentioned N—C ₁
-C ₁₀ group 1 -C on alkylcarbamoyl group in which the alkoxycarbonyl group composed of six was substituted are preferable, specifically, for example, N- methoxycarbonyl-methylcarbamoyl group, N- methoxycarbonyl-ethylcarbamoyl group, N- methoxycarbonyl Propylcarbamoyl group, N-methoxycarbonylbutylcarbamoyl group,
N-ethoxycarbonylpentylcarbamoyl group, N-
Butoxycarbonylhexylcarbamoyl group, N-te
rt-butoxycarbonylethylcarbamoyl group and the like. Among them, for example, N-methoxycarbonylmethylcarbamoyl group, N-methoxycarbonylethylcarbamoyl group, N-methoxycarbonylpropylcarbamoyl group, N-methoxycarbonylbutylcarbamoyl group,
A -tert-butoxycarbonylethylcarbamoyl group is preferred.

As the amino C ₁ -C ₆ alkoxycarbonyl group, a group in which a carbonyl group is substituted by an aminoalkoxy group having 1 to 6 carbon atoms is preferable. An aminopropoxycarbonyl group, a 2-amino-2-methylpropoxycarbonyl group, a 2-aminomethylethoxycarbonyl group, an aminobutoxycarbonyl group, a 2-aminopropoxycarbonyl group, an aminopentyloxycarbonyl group, an aminohexyloxycarbonyl group, and the like. Among them, for example, an aminomethoxycarbonyl group, an aminoethoxycarbonyl group, an aminopropoxycarbonyl group, a 2-aminomethylethoxycarbonyl group, a 2-amino-2-methylpropoxycarbonyl group and the like are preferable.

The N—C ₁ -C ₆ alkoxycarbonylamino C ₁ -C ₁₀ alkylcarbamoyl group includes the aforementioned N
A group in which a C ₁ -C ₁₀ alkylcarbamoyl group is substituted by an alkoxycarbonylamino group having 1 to 6 carbon atoms is preferable. Group, N-methoxycarbonylaminopropylcarbamoyl group, N-methoxycarbonylaminobutylcarbamoyl group, N-ethoxycarbonylaminopentylcarbamoyl group, N-butoxycarbonylaminohexylcarbamoyl group, N-ter
a t-butoxycarbonylaminoethylcarbamoyl group and the like. And an N-tert-butoxycarbonylaminoethylcarbamoyl group and the like.

The C ₁ -C ₆ alkoxycarbonylamino C ₁ -C ₆ alkoxycarbonyl group may be a C ₁ -C ₆ alkoxycarbonyl group containing an N ₁ -C ₆ alkoxycarbonyl group.
A group substituted by an -alkoxycarbonylamino group, and specifically, for example, N-methoxycarbonylaminomethoxycarbonyl group, N-methoxycarbonylaminoethoxycarbonyl group, N-methoxycarbonylaminopropoxycarbonyl group, N-methoxycarbonylaminobutoxy Carbonyl group, N-ethoxycarbonylaminopentyloxycarbonyl group, N-butoxycarbonylaminohexyloxycarbonyl group, N-tert
-Butoxycarbonylaminoethoxycarbonyl group and the like, among which, for example, N-methoxycarbonylaminomethoxycarbonyl group, N-methoxycarbonylaminoethoxycarbonyl group, N-methoxycarbonylaminopropoxycarbonyl group, N-methoxycarbonylaminobutoxycarbonyl group, An N-tert-butoxycarbonylaminoethoxycarbonyl group and the like are preferable.

The N—C ₂ -C ₆ alkenylcarbamoyl group is preferably a carbamoyl group in which an alkenyl group having 2 to 6 carbon atoms is N-substituted. Specifically, for example, N-vinylcarbamoyl group, -Allylcarbamoyl group, N- (1-propenyl) carbamoyl group, N-
Isopropenylcarbamoyl group, N- (2-butenyl)
Carbamoyl group, N-isobutenylcarbamoyl group, N
-(2-pentenyl) carbamoyl group, N- (2-hexenyl) carbamoyl group, N- (2-heptenyl) carbamoyl group, N- (2-octenyl) carbamoyl group, and the like. Among them, for example, N-vinylcarbamoyl group ,
An N-allylcarbamoyl group, an N- (1-propenyl) carbamoyl group and the like are preferable.

The N, N-di-C ₂ -C ₆ alkenylcarbamoyl group is preferably a carbamoyl group in which an alkenyl group having 2 to 6 carbon atoms is N, N-disubstituted. N, N-divinylcarbamoyl group, N, N-diallylcarbamoyl group, N, N-di (1
-Propenyl) carbamoyl group, N, N-diisopropenylcarbamoyl group, N-allyl-N-vinylcarbamoyl group, N-allyl-N-isobutenylcarbamoyl group, N-allyl-N- (2-pentenyl) carbamoyl Group, N-allyl-N- (2-hexenyl) carbamoyl group, N-allyl-N- (2-heptenyl) carbamoyl group, N-allyl-N- (2-octenyl) carbamoyl group and the like. N-allyl-N-vinylcarbamoyl group, N, N-diallylcarbamoyl group, N
-Allyl-N- (1-propenyl) carbamoyl group and the like are preferable.

The N-C ₁ -C ₆ alkylsulfamoyl group is preferably a sulfamoyl group in which an alkyl group having 1 to 6 carbon atoms is N-substituted, and specifically, for example, N-methylsulfamoyl group Moyl group, N-ethylsulfamoyl group, N-propylsulfamoyl group, N-isopropylsulfamoyl group, N-butylsulfamoyl group, N-isobutylsulfamoyl group, N-sec-butylsulfa Moyl group, N-tert-butylsulfamoyl group, N-pentylsulfamoyl group, N-neopentylsulfamoyl group, N-hexylsulfamoyl group, N-isohexylsulfamoyl group and the like. ,
Among them, for example, N-methylsulfamoyl, N-ethylsulfamoyl, N-isopropylsulfamoyl, N-tert-butylsulfamoyl and the like are preferable.

The N, N-di-C ₁ -C ₆ alkylsulfamoyl group is preferably a sulfamoyl group disubstituted by an alkyl group having 1 to 6 carbon atoms. An N-dimethylsulfamoyl group,
N, N-diethylsulfamoyl group, N, N-dipropylsulfamoyl group, N, N-diisopropylsulfamoyl group, N, N-dibutylsulfamoyl group, N, N
-Di-tert-butylsulfamoyl group, N, N-dipentylsulfamoyl group, N, N-dihexylsulfamoyl group, N-ethyl-N-methylsulfamoyl group,
N-isopropyl-N-methylsulfamoyl group, N-
tert-butyl-N-methylsulfamoyl group, N-
Ethyl-N-isopropylsulfamoyl group and the like. Among them, for example, N, N-dimethylsulfamoyl group,
N, N-diethylsulfamoyl group, N, N-diisopropylsulfamoyl group, N, N-dibutylsulfamoyl group, N, N-ditert-butylsulfamoyl group, N-ethyl-N-methyl Sulfamoyl, N-isopropyl-N-methylsulfamoyl, N-ethyl-N-isopropylsulfamoyl and the like are preferred.

The C ₁ -C ₆ alkylsulfinyl group is preferably a group in which a sulfinyl group is substituted by an alkyl group having 1 to 6 carbon atoms, and specifically, for example, a methylsulfinyl group, an ethylsulfinyl group, a propylsulfinyl group Isopropylsulfinyl group, butylsulfinyl group, isobutylsulfinyl group, sec-butylsulfinyl group, tert-butylsulfinyl group, pentylsulfinyl group, neopentylsulfinyl group, hexylsulfinyl group, isohexylsulfinyl group and the like. Sulfinyl group, ethylsulfinyl group, propylsulfinyl group,
Isopropylsulfinyl group, butylsulfinyl group,
A tert-butylsulfinyl group and the like are preferred.

The C ₁ -C ₆ alkylsulfonyl group includes
A group in which a sulfonyl group is substituted by an alkyl group having 1 to 6 carbon atoms is preferable. Specifically, for example, a methylsulfonyl group, an ethylsulfonyl group, a propylsulfonyl group, an isopropylsulfonyl group, a butylsulfonyl group,
Isobutylsulfonyl group, sec-butylsulfonyl group, tert-butylsulfonyl group, pentylsulfonyl group, neopentylsulfonyl group, hexylsulfonyl group, isohexylsulfonyl group and the like. Group, butylsulfonyl group, tert-butylsulfonyl group and the like.

The N—C ₁ -C ₆ alkylsulfonylamino group is preferably an amino group in which an alkylsulfonyl group having 1 to 6 carbon atoms is N-substituted, and specifically, for example, N-methylsulfonylamino Group, N-ethylsulfonylamino group, N-propylsulfonylamino group, N-isopropylsulfonylamino group, N-butylsulfonylamino group, N-isobutylsulfonylamino group, N-sec-butylsulfonylamino group, N-te
rt-butylsulfonylamino group, N-pentylsulfonylamino group, N-neopentylsulfonylamino group,
N-hexylsulfonylamino group, N-isohexylsulfonylamino group and the like, among which, for example, N-methylsulfonylamino group, N-ethylsulfonylamino group, N-propylsulfonylamino group, N-butylsulfonylamino group, N-butylsulfonylamino group, -Tert-butylsulfonylamino group and the like are preferable.

The C ₁ -C ₆ alkylthio group is preferably a group in which a sulfur atom is substituted by an alkyl group having 1 to 6 carbon atoms, and specifically, for example, a methylthio group, an ethylthio group, a propylthio group, an isopropylthio group Butylthio group, isobutylthio group, sec-butylthio group, t
tert-butylthio group, pentylthio group, neopentylthio group, hexylthio group, isohexylthio group and the like. Among them, for example, methylthio group, ethylthio group, propylthio group, isopropylthio group, isopropylthio group, butylthio group, te
An rt-butylthio group and the like are preferred.

The C ₁ -C ₆ alkoxy group is preferably a group in which an oxygen atom is substituted by an alkyl group having 1 to 6 carbon atoms. Specific examples include a methoxy group, an ethoxy group, a propoxy group and an isopropoxy group. A butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, a neopentyloxy group, a hexyloxy group, an isohexyloxy group, and the like. Among them, for example, a methoxy group, an ethoxy group, a propoxy group, Isopropoxy group, butoxy group, isobutoxy group, ter
A t-butoxy group and the like are preferred.

The C ₁ -C ₆ alkoxycarbonyl group is preferably a group in which a carbonyl group is substituted by an alkoxy group having 1 to 5 carbon atoms, and specifically, for example, a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group , Isopropoxycarbonyl group, butoxycarbonyl group, isobutoxycarbonyl group, sec-butoxycarbonyl group, tert-butoxycarbonyl group, pentyloxycarbonyl group, neopentyloxycarbonyl group and the like. Among them, for example, methoxycarbonyl group, ethoxycarbonyl Groups, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl and the like.

[0086] As the N-C ₃ -C ₆ cycloalkylamino group, preferably a group in which the alkyl group is N- substituted 6 comprising cyclic C 3 -C amino group, such as N- cyclopropylamino group, N- Examples thereof include a cyclobutylamino group, an N-cyclopentylamino group, an N-cyclohexylamino group, and among others, an N-cyclopropylamino group, an N-cyclopentylamino group, an N-cyclohexylamino group and the like are preferable.

The N, N-di-C ₃ -C ₆ cycloalkylamino group is preferably an amino group in which a cyclic alkyl group having 3 to 6 carbon atoms is N, N-disubstituted. Is, for example, an N, N-dicyclopropylamino group, N,
N-dicyclobutylamino group, N, N-dicyclopentylamino group, N, N-dicyclohexylamino group, N-
Cyclobutyl-N-cyclopropylamino group, N-cyclopentyl-N-cyclopropylamino group, N-cyclohexyl-N-cyclopropylamino group, and the like. Among them, for example, N, N-dicyclopropylamino group,
N, N-dicyclobutylamino group, N, N-dicyclopentylamino group and the like are preferable.

The C ₃ -C ₆ cycloalkyloxy group is preferably a group in which an oxygen atom is substituted by a cyclic alkyl group having 3 to 6 carbon atoms, for example, N-cyclopropoxy group, N-cyclobutoxy group, -Cyclopentyloxy group, N-cyclohexyloxy group and the like,
Among them, for example, N-cyclopropoxy group, N-cyclopentyloxy group, N-cyclohexyloxy group and the like are preferable.

The N—C ₃ -C ₆ cycloalkylcarbamoyl group is preferably a group in which a carbamoyl group is N-substituted with a cyclic alkyl group having 3 to 6 carbon atoms, for example, an N-cyclopropylcarbamoyl group, A cyclobutylcarbamoyl group, an N-cyclopentylcarbamoyl group, an N-cyclohexylcarbamoyl group, and the like. Among them, for example, an N-cyclopropylcarbamoyl group,
N-cyclopentylcarbamoyl, N-cyclohexylcarbamoyl and the like are preferred.

The N, N-di-C ₃ -C ₆ cycloalkylcarbamoyl group is preferably a group in which a cyclic alkyl group having 3 to 6 carbon atoms is substituted with N, N-disubstituted carbamoyl group. Are, for example, N, N-dicyclopropylcarbamoyl, N, N-dicyclobutylcarbamoyl, N, N-dicyclopentylcarbamoyl, N, N
-Dicyclohexylcarbamoyl group, N-cyclobutyl-N-cyclopropylcarbamoyl group, N-cyclopentyl-N-cyclopropylcarbamoyl group, N-cyclohexyl-N-cyclopropylcarbamoyl group and the like. Among them, for example, N, N-dicyclo A propylcarbamoyl group, an N, N-dicyclobutylcarbamoyl group,
An N, N-dicyclopentylcarbamoyl group is preferred.

The saturated C ₁ -C ₉ aliphatic group is preferably an alkyl group having 1 to 9 carbon atoms, and may be linear or branched. Among them, a linear or branched alkyl group having 1 to 6 carbon atoms is preferable.

Examples of the alkyl group include a methyl group,
Ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group,
Examples include a pentyl group, a neopentyl group, a hexyl group, an isohexyl group, a heptyl group, an octyl group, and a nonyl group.
An rt-butyl group and the like are preferred.

An unsaturated C ₁ -C ₉ aliphatic group is one having 1 carbon atom.
An alkenyl group or alkynyl group of 9 to 9 groups is preferable, and may be linear or branched. Among them, a linear or branched alkenyl group or alkynyl group having 1 to 6 carbon atoms is preferable.

Examples of the alkenyl group include a vinyl group, an allyl group, a 1-propenyl group, an isopropenyl group,
2-butenyl group, isobutenyl group, 2-pentenyl group,
Examples thereof include a 2-hexenyl group, a 2-heptenyl group, and a 2-octenyl group.
-A propenyl group and the like are preferred.

Examples of the alkynyl group include an ethynyl group, a 1-propynyl group, a 1-butenyl group, a 1-pentenyl group, a 1-hexynyl group, a 1-heptynyl group and a 1-octynyl group. Group, 1-
A propynyl group and the like are preferred.

The 5- or 6-membered saturated carbocyclic group includes, for example, a cyclopentyl group and a cyclohexyl group, among which a cyclopentyl group is preferable.

The 5- or 6-membered unsaturated carbocyclic group is
Examples thereof include a cyclopentenyl group and a cyclohexenyl group, and among them, for example, a cyclopentenyl group is preferable.

A 5- or 6-membered heterocyclic group substituted
N-C ₁ -C ₁₀ alkylcarbamoyl, N-C ₁ -C ₁₀
An alkylthiocarbamoyl group, a thiocarbonyl group or a carbonyl group refers to N-substituted by the above heterocyclic group.
Preferred are a C ₁ -C ₁₀ alkylcarbamoyl group, an N-C ₁ -C ₁₀ alkylthiocarbamoyl group, a thiocarbonyl group and a carbonyl group, and specific examples include N-isoxazolyl groups such as N-isoxazolylmethylcarbamoyl group. N-isothiazolylalkylcarbamoyl groups, such as N-isothiazolylalkylcarbamoyl groups, N-imidazolylmethylcarbamoyl groups, etc.
N-oxazolylalkylcarbamoyl groups such as imidazolylalkylcarbamoyl group and N-oxazolylmethylcarbamoyl group; N-oxadiazolylalkylcarbamoyl groups such as N-oxadiazolylmethylcarbamoyl group; N-thiazolylmethylcarbamoyl N-thiazolylalkylcarbamoyl groups such as N-thiadiazolylalkylcarbamoyl group, N-thiadiazolylalkylcarbamoyl group such as N-thiadiazolylmethylcarbamoyl group, N-thienylalkylcarbamoyl group such as N-thienylmethylcarbamoyl group, N-triazi N-triazinylalkylcarbamoyl groups such as N-methylcarbamoyl group; N-triazolylalkylcarbamoyl groups such as N-triazolylmethylcarbamoyl group;
N-pyridylalkylcarbamoyl group such as pyridylmethylcarbamoyl group, N-pyrazinylalkylcarbamoyl group such as N-pyrazinylmethylcarbamoyl group, N-pyrimidinylalkylcarbamoyl group such as N-pyrimidinylmethylcarbamoyl group, N-pyri N-pyridazinylalkylcarbamoyl group such as dazinylmethylcarbamoyl group, N-pyrazolylalkylcarbamoyl group such as N-pyrazolylmethylcarbamoyl group, N-pyrrolylalkylcarbamoyl group such as N-pyrrolylmethylcarbamoyl group, N-pyranylalkylcarbamoyl groups such as N-pyranylmethylcarbamoyl group, N-furylalkylcarbamoyl groups such as N-furylmethylcarbamoyl group, and N-furzanylalkylcarbamoyl groups such as N-furazanylmethylcarbamoyl group N-tetrahydrofuran such as N-imidazolidinylmethylcarbamoyl group such as N-imidazolidinylmethylcarbamoyl group, N-imidazolinylalkylcarbamoyl group such as N-imidazolinylmethylcarbamoyl group, and N-tetrahydrofuranylmethylcarbamoyl group N-pyrazolidinylalkylcarbamoyl groups such as N-pyrazolidinylalkylcarbamoyl group, N-pyrazolinylmethylcarbamoyl group, N-pyrazolinylalkylcarbamoyl group such as N-pyrazolidinylmethylcarbamoyl group, and N-piperazinyl N-piperazinylalkylcarbamoyl such as methylcarbamoyl, N-piperidinylalkylcarbamoyl such as N-piperidinylmethylcarbamoyl, N-pyrrolidinylalkylcarba such as N-pyrrolidinylmethylcarbamoyl Mo N-pyrrolinylalkylcarbamoyl group such as N-pyrrolinylmethylcarbamoyl group, N-morpholinoalkylcarbamoyl group such as N-morpholinomethylcarbamoyl group; and N-morpholinoalkylcarbamoyl group such as N-isoxazolylmethylthiocarbamoyl group. Isoxazolylalkylthiocarbamoyl group,
N- such as N-isothiazolylmethylthiocarbamoyl group
N-imidazolylalkylthiocarbamoyl group, N-imidazolylalkylthiocarbamoyl group such as N-imidazolylmethylthiocarbamoyl group, N-oxazolylalkylthiocarbamoyl group such as N-oxazolylmethylthiocarbamoyl group, N-oxadiazolylmethylthiocarbamoyl group, etc. N-oxadiazolylalkylthiocarbamoyl group, N-thiazolylmethylthiocarbamoyl group and the like;
N-thiadiazolylalkylthiocarbamoyl groups such as N-thiadiazolylmethylthiocarbamoyl groups, N-thiazylalkylthiocarbamoyl groups such as N-thienylmethylthiocarbamoyl groups, and N-triazinylalkylthiocarbamoyl groups such as N-triazinylmethylthiocarbamoyl groups. An N-triazolylalkylthiocarbamoyl group such as an N-triazolylmethylthiocarbamoyl group;
N-pyridylalkylthiocarbamoyl group such as pyridylmethylthiocarbamoyl group, N-pyrazinylalkylthiocarbamoyl group such as N-pyrazinylmethylthiocarbamoyl group, N-pyrimidinylalkylthiocarbamoyl group such as N-pyrimidinylmethylthiocarbamoyl group, N
N-pyridazinylalkylthiocarbamoyl groups such as N-pyridazinylmethylthiocarbamoyl groups, N-pyrazolylalkylthiocarbamoyl groups such as N-pyrazolylthiothioamoyl groups, and N-pyrrolylalkylthiocarbamoyl groups such as N-pyrrolylmethylthiocarbamoyl groups Group,
N-pyranylalkylthiocarbamoyl groups such as N-pyranylmethylthiocarbamoyl group, N-furylalkylthiocarbamoyl groups such as N-furylmethylthiocarbamoyl group, and N-pyranylmethylthiocarbamoyl groups such as N-furazanylmethylthiocarbamoyl group
N-imidazolidinylalkylthiocarbamoyl groups, N-imidazolidinylalkylthiocarbamoyl groups such as N-imidazolidinylmethylthiocarbamoyl groups, N-imidazolinylalkylthiocarbamoyl groups such as N-imidazolinylmethylthiocarbamoyl groups, N-tetrahydrofuranyl N-tetrahydrofuranylalkylthiocarbamoyl groups such as methylthiocarbamoyl groups, N-pyrazolidinylalkylthiocarbamoyl groups such as N-pyrazolidinylmethylthiocarbamoyl groups, and N-pyrazolinylalkylthio groups such as N-pyrazolinylmethylthiocarbamoyl groups N-piperazinylalkylthiocarbamoyl groups such as carbamoyl group, N-piperazinylmethylthiocarbamoyl group,
N-pyrrolidinylalkylthiocarbamoyl, such as N-piperidinylmethylthiocarbamoyl, N-pyrrolidinylmethylthiocarbamoyl, N-pyrrolidinylalkylthiocarbamoyl, N-pyrrolinylmethylthiocarbamoyl, and other N-pyrrolids N-morpholinoalkylthiocarbamoyl groups such as n-alkylthiocarbamoyl group and N-morpholinomethylthiocarbamoyl group; for example, isoxazolylthiocarbonyl group, isothiazolylthiocarbonyl group, imidazolylthiocarbonyl group, oxazolylthiocarbonyl group, oxadiazoli Luthiocarbonyl group, thiazolylthiocarbonyl group, thiadiazolylthiocarbonyl group, thienylthiocarbonyl group, triazinylthiocarbonyl group, triazolylthiocarbonyl group, pyridyl O carbonyl group, pyrazinyl thiocarbonyl group, pyrimidinylthio group, pyridazinyl thiocarbonyl group, a pyrazolyl thiocarbonyl group,
Pyrrolylthiocarbonyl group, pyranylthiocarbonyl group, furylthiocarbonyl group, furazanylthiocarbonyl group, imidazolidinylthiocarbonyl group, imidazolinylthiocarbonyl group, tetrahydrofuranylthiocarbonyl group, pyrazolidinylthiocarbonyl group, pyrazolinylthio Carbonyl group, piperazinylthiocarbonyl group, piperidinylthiocarbonyl group, pyrrolidinylthiocarbonyl group, pyrrolinylthiocarbonyl group, morpholinothiocarbonyl group, etc .; for example, isoxazolylcarbonyl group, isothiazolylcarbonyl group, imidazolylcarbonyl group , Oxazolylcarbonyl group, oxadiazolylcarbonyl group, thiazolylcarbonyl group, thiadiazolylcarbonyl group, thienylcarbonyl group, triazinylcarbonyl group, Azolylcarbonyl, pyridylcarbonyl, pyrazylcarbonyl, pyrazinylcarbonyl, pyrimidinylcarbonyl, pyridazinylcarbonyl, pyrazolylcarbonyl, pyrrolylcarbonyl, pyranylcarbonyl, furylcarbonyl, furylcarbonyl Zanylcarbonyl group, imidazolidinylcarbonyl group, imidazolinylcarbonyl group, tetrahydrofuranylcarbonyl group, pyrazolidinylcarbonyl group, pyrazolinylcarbonyl group, piperazinylcarbonyl group,
Piperidinylcarbonyl group, pyrrolidinylcarbonyl group, pyrrolinylcarbonyl group, morpholinocarbonyl group and the like, among which, for example, thienyl group, pyridyl group,
N ₁ -C ₁ -substituted by a pyrazinyl group, a pyrimidinyl group, a furyl group, a tetrahydrofuranyl group, a morpholino group, etc.
C _{1 0} alkylcarbamoyl group, N-C ₁ -C ₁₀ alkylthiocarbamoyl groups, such as thiocarbonyl group or a carbonyl group.

A mono- to tri-cyclic heteroaromatic group having 1 to 5 heteroatoms per ring system selected from the group consisting of nitrogen, oxygen and sulfur (excluding 5- or 6-membered heterocyclic groups) ) -Substituted N—C ₁ -C ₁₀ alkylcarbamoyl group, N—C ₁ -C ₁₀ alkylthiocarbamoyl group, thiocarbonyl group or carbonyl group refers to N-C ₁ -C ₁₀ alkylcarbamoyl group, thiocarbonyl group or carbonyl group, A C ₁ -C ₁₀ alkylcarbamoyl group, an N-C ₁ -C ₁₀ alkylthiocarbamoyl group, a thiocarbonyl group or a carbonyl group, specifically, for example, N-acridinyl such as N-acridinylmethylcarbamoyl group Alkylcarbamoyl group,
N-isoquinolylalkylcarbamoyl groups such as N-isoquinolylmethylcarbamoyl groups, N-isoindolylalkylcarbamoyl groups such as N-isoindolylmethylcarbamoyl groups, and N-isoalkyl groups such as N-indazolylmethylcarbamoyl groups. N-indolylalkylcarbamoyl group such as indazolylalkylcarbamoyl group, N-indolylmethylcarbamoyl group, N-indolizinylalkylcarbamoyl group such as N-indolizinylmethylcarbamoyl group, N-ethylenedioxyphenylmethyl N-ethylenedioxyphenylalkylcarbamoyl group such as carbamoyl group, N-carbazolylmethylcarbamoyl group
N-quinazolinylalkylcarbamoyl group such as carbazolylalkylcarbamoyl group, N-quinazolinylmethylcarbamoyl group, N-quinoxalinylalkylcarbamoyl group such as N-quinoxalinylmethylcarbamoyl group, N- N-quinolidinylalkylcarbamoyl groups such as quinolidinylmethylcarbamoyl groups, N-quinolylalkylcarbamoyl groups such as N-quinolylmethylcarbamoyl groups, and N-coumaronylalkylcarbamoyl groups such as N-coumaronylmethylcarbamoyl groups N-chromenylalkylcarbamoyl groups such as N-chromenylmethylcarbamoyl group, N-phenanthridinylalkylcarbamoyl groups such as N-phenanthridinylmethylcarbamoyl group,
N- such as N-phenanthrolinylmethylcarbamoyl group
N-dibenzofuranylalkylcarbamoyl group such as phenanthrolinylalkylcarbamoyl group, N-dibenzofuranylmethylcarbamoyl group, N-dibenzothiophenylalkylcarbamoyl group such as N-dibenzothiophenylmethylcarbamoyl group, N-cinnori N-cinnolinylalkylcarbamoyl groups such as N-methylcarbamoyl group and N-thionaphthenylmethylcarbamoyl groups
N-naphthyridinylalkylcarbamoyl group, N-naphthyridinylalkylcarbamoyl group such as N-naphthyridinylmethylcarbamoyl group, N-phenazinylalkylcarbamoyl group such as N-phenazinylmethylcarbamoyl group, N-phenaxa N such as dinylmethylcarbamoyl group
N-phenothiazinylalkylcarbamoyl group such as phenoxazinylalkylcarbamoyl group, N-phenothiazinylmethylcarbamoyl group, N-phthalazylalkylcarbamoyl group such as N-phthalazylmethylcarbamoyl group, N-pteridinylmethylcarbamoyl N- such as a group
Pteridinylalkylcarbamoyl group, N-purinylalkylcarbamoyl group such as N-purinylmethylcarbamoyl group, N-benzimidazolylalkylcarbamoyl group such as N-benzimidazolylmethylcarbamoyl group,
N- such as N-benzoxazolylmethylcarbamoyl group
Benzoxazolylalkylcarbamoyl group, N-benzothiazolylalkylcarbamoyl group such as N-benzothiazolylmethylcarbamoyl group, N-benzotriazolylalkylcarbamoyl group such as N-benzotriazolylmethylcarbamoyl group, N-benzofuranylalkylcarbamoyl group such as N-benzofuranylmethylcarbamoyl group, N-methylenedioxyphenylalkylcarbamoyl group such as N-methylenedioxyphenylmethylcarbamoyl group; N-acridinylmethylthiocarbamoyl group and the like N-acridinylalkylthiocarbamoyl group, N
N-isoquinolylalkylthiocarbamoyl groups such as isoquinolylmethylthiocarbamoyl group, N-isoindolylalkylthiocarbamoyl groups such as N-isoindolylmethylthiocarbamoyl group, and N-in groups such as N-indazolylmethylthiocarbamoyl group. N-indolylalkylthiocarbamoyl groups such as dazolylalkylthiocarbamoyl group and N-indolylmethylthiocarbamoyl group;
N- such as N-indolizinylmethylthiocarbamoyl group
N such as an indolizinylalkylthiocarbamoyl group and an N-ethylenedioxyphenylmethylthiocarbamoyl group
N such as an ethylenedioxyphenylalkylthiocarbamoyl group and an N-carbazolylmethylthiocarbamoyl group;
N-quinazolinylalkylthiocarbamoyl group such as N-quinazolinylalkylthiocarbamoyl group, N-quinazolinylmethylthiocarbamoyl group, N-quinoxalinylalkylthiocarbamoyl group such as N-quinoxalinylmethylthiocarbamoyl group, N- N-quinolidinylalkylthiocarbamoyl groups such as quinolidinylmethylthiocarbamoyl groups, N-quinolylalkylthiocarbamoyl groups such as N-quinolylmethylthiocarbamoyl groups, and N-coumalonylalkylthiocarbamoyl groups such as N-coumaronylmethylthiocarbamoyl groups N-chromenylalkylthiocarbamoyl groups such as N-chromenylmethylthiocarbamoyl group, N-phenanthridinylalkylthiocarbamoyl groups such as N-phenanthridinylmethylthiocarbamoyl group, N-phenyl N-dibenzofuranylalkylthiocarbamoyl groups such as N-phenanthrolinylalkylthiocarbamoyl groups, N-dibenzofuranylalkylthiocarbamoyl groups such as N-dibenzofuranylmethylthiocarbamoyl groups, N-dibenzothiophenylmethylthiocarbamoyl groups, etc. An N-cinnolinylalkylthiocarbamoyl group such as a thiophenylalkylthiocarbamoyl group and an N-cinnolinylmethylthiocarbamoyl group;
N-phenadienylalkylthiocarbamoyl groups such as thionaphthenylmethylthiocarbamoyl groups, N-naphthyridinylalkylthiocarbamoyl groups such as N-naphthyridinylmethylthiocarbamoyl groups, and N-phenadinyl groups such as N-phenadinylmethylthiocarbamoyl groups. N-phenaxazinylalkylthiocarbamoyl groups, such as N-phenoxazinylmethylthiocarbamoyl groups, N-phenothiadinylalkylthiocarbamoyl groups, such as N-phenoxazinylmethylthiocarbamoyl groups, and N-phthalazylmethylthiocarbamoyl groups N-phthalidylalkylthiocarbamoyl group such as N-pteridinylalkylthiocarbamoyl group, N-pteridinylalkylthiocarbamoyl group such as N-pteridinylmethylthiocarbamoyl group And N-benzoimidazolylalkylthiocarbamoyl groups, such as N-benzoimidazolylmethylthiocarbamoyl group, N-benzooxazolylalkylthiocarbamoyl group, such as N-benzoimidazolylmethylthiocarbamoyl group, and N-benzothia. N-benzothiazolylalkylthiocarbamoyl groups such as zolylmethylthiocarbamoyl group, N-benzotriazolylalkylthiocarbamoyl groups such as N-benzotriazolylmethylthiocarbamoyl group, and N-benzofuranylmethylthiocarbamoyl groups such as N-benzofuranylmethylthiocarbamoyl group Benzofuranylalkylthiocarbamoyl group,
N-methylenedioxyphenylmethylthiocarbamoyl group such as N-methylenedioxyphenylalkylthiocarbamoyl group; for example, acridinylthiocarbonyl group, isoquinolylthiocarbonyl group, isoindolylthiocarbonyl group, indazolylthiocarbonyl group, indolylthiocarbonyl group Group, indolizinylthiocarbonyl group,
Ethylenedioxyphenylthiocarbonyl group, carbazolylthiocarbonyl group, quinazolinylthiocarbonyl group, quinoxalinylthiocarbonyl group, quinolidinylthiocarbonyl group, quinolylthiocarbonyl group, coumalonylthiocarbonyl group, chromenylthiocarbonyl Group, phenanthridinylthiocarbonyl group, phenanthrolinylthiocarbonyl group, dibenzofuranylthiocarbonyl group, dibenzothiophenylthiocarbonyl group, cinnolinylthiocarbonyl group, thionaphthenylthiocarbonyl group, naphthyridinylthiocarbonyl group, phena A dinylthiocarbonyl group, a phenaxazinylthiocarbonyl group,
Phenothiazinylthiocarbonyl group, phthalazylthiocarbonyl group, pteridinylthiocarbonyl group, purinylthiocarbonyl group, benzimidazolylthiocarbonyl group, benzoxazolylthiocarbonyl group, benzothiazolylthiocarbonyl group, benzotriazolylthiocarbonyl group, benzotriazolylthiocarbonyl group, Benzofuranylthiocarbonyl group or methylenedioxyphenylthiocarbonyl group and the like; for example, acridinylcarbonyl group, isoquinolylcarbonyl group, isoindolylcarbonyl group, indazolylcarbonyl group,
Indolylcarbonyl group, indolizinylcarbonyl group, ethylenedioxyphenylcarbonyl group, carbazolylcarbonyl group, quinazolinylcarbonyl group, quinoxalinylcarbonyl group, quinolizinylcarbonyl group, quinolylcarbonyl group, cumaronyl Carbonyl group, chromenylcarbonyl group, phenanthridinylcarbonyl group,
Phenanthrolinylcarbonyl group, dibenzofuranylcarbonyl group, dibenzothiophenylcarbonyl group, cinnolinylcarbonyl group, thionaphthenylcarbonyl group,
Naphthyridinylcarbonyl group, phenazinylcarbonyl group, phenaxazinylcarbonyl group, phenothiazinylcarbonyl group, phthalazylcarbonyl group, pteridinylcarbonyl group, purinylcarbonyl group, benzimidazolylcarbonyl group, benzooxazolylcarbonyl group ,
A benzothiazolylcarbonyl group, a benzotriazolylcarbonyl group, a benzofuranylcarbonyl group, a methylenedioxyphenylcarbonyl group, and the like, among which, for example, an ethylenedioxyphenyl group, a dibenzofuranyl group, a dibenzothiophenyl group, and methylene dioxy phenyl group is substituted, N-C ₁ -C ₁₀ alkylcarbamoyl, N-C ₁ -C ₁₀ alkylthiocarbamoyl groups, such as thiocarbonyl group or a carbonyl group.

The condensed aryl group is, for example, a group in which a phenyl group or a naphthyl group is bonded to another ring to form a condensed benzene ring or a condensed naphthalene ring.

Bicyclic or tricyclic saturated or unsaturated C _6-
Specific examples of the C ₁₅ condensed carbocyclic group include an acenaphthylenyl group, an adamantyl group, an anthryl group, an indanyl group, an indenyl group, a C ₆ -C ₈ cycloalkanyl group,
₆ -C ₈ cycloalkadienyl group, C ₆ -C ₈ cycloalkenyl group, a norbornyl group, a phenanthryl group, etc. Fureoreniru group. Among them for example an anthryl group, C ₆
-C ₈ cycloalkanyl group, C ₆ -C ₈ cycloalkadienyl group, C ₆ -C ₈ cycloalkenyl group and the like.

The C ₆ -C ₈ cycloalkanyl group includes:
Examples thereof include a cyclohexanyl group, a cycloheptanyl group, and a cyclooctanyl group, and among them, for example, a cyclohexanyl group is preferable.

The C ₆ -C ₈ cycloalkadienyl group includes, for example, a cyclohexadienyl group, a cycloheptadienyl group, a cyclooctadienyl group and the like, among which a cyclohexadienyl group and the like are preferable.

As the C ₆ -C ₈ cycloalkenyl group,
For example, a cyclohexenyl group, a cycloheptenyl group, a cyclooctenyl group and the like can be mentioned, and for example, a cyclohexenyl group and the like are preferable.

As a 6-membered heterocyclic group or a bicyclic to tricyclic condensed heteroaromatic group having 1 to 5 heteroatoms per ring system selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, For example, isoquinolyl group, isoindolyl group, indazolyl group, indolyl group, indolizinyl group, ethylenedioxyphenyl group, quinazolinyl group,
Quinoxalinyl group, quinolizinyl group, quinolyl group, cumaronyl group, chromenyl group, thionaphthenyl group, naphthyridinyl group, pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, pyranyl group, phthalazyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group Benzotriazolyl group, benzofuranyl group or methylenedioxyphenyl group. Group, a benzotriazolyl group, a benzofuranyl group or a methylenedioxyphenyl group. In particular, for example, an ethylenedioxyphenyl group, a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl, a methylenedioxyphenyl group, and the like are preferable.

R is, for example, an aryl group, a monocyclic to tricyclic C ₇ -C ₁₅ carbon aromatic ring group or a 5- or 6-membered heterocyclic group or a heterocyclic group selected from the group consisting of nitrogen, oxygen and sulfur. And a mono- to tri-cyclic heteroaromatic group having 1 to 5 atoms per ring system.

Specifically, the aryl group is preferably an aryl group having 6 to 15 carbon atoms, such as a naphthyl group and a phenyl group.

[0108] As the C ₇ -C ₁₅ carbon ring group of the 1 to tricyclic, preferably an aromatic ring group containing from 1 to 3 cyclic group containing 15 having 7 to carbon atoms, for example acenaphthylenyl group, an adamantyl group , Anthryl group, indenyl group, norbornyl group, phenanthryl group and the like,
Among them, for example, anthryl group, phenanthryl group and the like are preferable.

Examples of the 5- or 6-membered heterocyclic group include isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, thienyl, triazinyl, triazolyl, pyridyl, pyrazinyl and the like. Group, pyrimidinyl group, pyridazinyl group, pyrazolyl group, pyrrolyl group, pyranyl group, furyl group, furazanyl group, imidazolidinyl group, imidazolinyl group, tetrahydrofuranyl group, pyrazolidinyl group, pyrazolinyl group, piperazinyl group, piperidinyl group, pyrrolidinyl group, pyrrolinyl group ,
Morpholino group and the like, among which, for example, thienyl group,
Tetrahydrofuranyl group, pyridyl group, pyrazinyl group,
Pyrimidinyl, furyl, morpholino and the like are preferred.

A heteroatom selected from the group consisting of nitrogen, oxygen and sulfur is present in an amount of 1 to 5 hetero atoms per ring system.
Examples of the mono- to tricyclic heteroaromatic ring groups include acridinyl group, isoquinolyl group, isoindolyl group, indazolyl group, indolyl group, indolizinyl group, ethylenedioxyphenyl group, carbazolyl group, quinazolinyl group, quinoxalinyl group, quinolidinyl Group, quinolyl group, coumalonyl group, chromenyl group, phenanthridinyl group, phenanthrolinyl group, dibenzofuranyl group, dibenzothiophenyl group, cinnolinyl group, thionaphthenyl group, naphthyridinyl group, phenazinyl group, phenaxazinyl group, phenothiazinyl Group, phthalazinyl group, pteridinyl group, purinyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, benzotriazolyl group, benzofuranyl group, methylenedioxyphenyl group, etc. Among them, for example, ethylene dioxy phenyl group, dibenzofuranyl group, dibenzothiophenyl group, methylenedioxyphenyl group, and the like are preferable.

As R, for example, an aryl group and the like are preferable, and particularly, for example, a phenyl group and the like are preferable.
In addition, each substituent of R can have one or more substituents as appropriate.

Specific examples of the substituent include, for example, azide group, amino group, carbamoyl group, carbamoylamino group, carbamoyloxy group, carboxyl group, cyano group, sulfamoyl group, sulfo group, nitro group, halogen atom, hydroxy group, Formyl group, formylamino group,
Cyclic saturated C ₃ -C ₉ aliphatic groups, cyclic unsaturated C ₃ -C ₉ aliphatic group, aralkyl group, N- aralkylamino group, N,
N-diaaralkylamino group, aralkyloxy group, aralkylcarbonyl group, N-aralkylcarbamoyl group,
Aryl group, N-arylamino group, N, N-diarylamino group, aryloxy group, arylsulfonyl group, arylsulfonyloxy group, N-arylsulfonylamino group, N-arylsulfonylamino C ₁ -C
₁₀ alkylamino group, N-arylsulfonylamino C
₁ -C ₁₀ alkylcarbamoyl, N- arylsulfonylamino C ₁ -C ₆ alkoxycarbonyl group, an aryl sulfamoyl group, an arylsulfamoyl group,
N-arylsulfamoyl C ₁ -C ₁₀ alkylcarbamoyl group, arylsulfamoyl C ₁ -C ₆ alkoxycarbonyl group, N-arylcarbamoyl group, aroyl group, alloxy group, N- (N-aroylamino) C _1- C
₁₀ alkylcarbamoyl group, N-aroylamino C _1-
C ₁₀ alkoxycarbonyl group, C ₂ -C ₆ alkanoyl group, N-C ₂ -C ₆ alkanoylamino group, N, N-di -
C ₂ -C ₆ alkanoylamino group, N-C ₁ -C ₆ alkylamino group, N, N-di -C ₁ -C ₆ alkylamino group, N
—C ₁ -C ₁₀ alkylcarbamoyl group, N—C ₁ -C ₁₀ alkylthiocarbamoyl group, N, N-di-C ₁ -C ₁₀ alkylcarbamoyl group, N, N-di-C ₁ -C ₁₀ alkylthiocarbamoyl group , N-C ₂ -C ₆ alkenyl carbamoylmethyl group, N, N- di -C ₂ -C ₆ alkenyl carbamoylmethyl group, N- amino C ₁ -C ₁₀ alkylcarbamoyl groups,
N-C ₁ -C ₆ alkoxy C ₁ -C ₁₀ alkylcarbamoyl, N-C ₁ -C ₆ alkoxycarbonyl C ₁ -C ₁₀ alkylcarbamoyl, N-C ₁ -C ₆ alkoxycarbonylamino C ₁ -C ₁₀ alkylcarbamoyl group, N-C ₁
-C ₆ alkoxycarbonylamino C ₁ -C ₆ alkoxycarbonyl group, C ₁ -C ₆ alkylthio group, N-C ₁ -C ₆
Alkylsulfamoyl group, N, N-di -C ₁ -C ₆ alkylsulfamoyl group, C ₁ -C ₆ alkylsulfinyl group, C ₁ -C ₆ alkylsulfonyl group, N-C ₁ -C ₆ alkylsulfonyl Amino group, C ₁ -C ₆ alkoxy group, C ₁
-C ₆ alkoxycarbonyl group, amino C ₁ -C ₆ alkoxycarbonyl group, N—C ₃ -C ₆ cycloalkylamino group, N, N-di-C ₃ -C ₆ cycloalkylamino group,
C ₃ -C ₆ cycloalkyloxy group, N-C ₃ -C ₆ cycloalkyl alkylcarbamoyl and N, N- di -C ₃ -C ₆ substituents selected from the group consisting of cycloalkyl alkylcarbamoyl group, isoxazolyl group, Isothiazolyl, imidazolyl, oxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, thienyl, triazinyl, triazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, pyrrolyl, pyranyl, furyl A 5- or 6-membered heterocyclic group selected from the group consisting of a furazanyl group, an imidazolidinyl group, an imidazolinyl group, a tetrahydrofuranyl group, a pyrazolidinyl group, a pyrazolinyl group, a piperazinyl group, a piperidinyl group, a pyrrolidinyl group, a pyrrolinyl group and a morpholino group; Clidinyl group, isoquinolyl group, isoindolyl group, indazolyl group, indolyl group, indolizinyl group, ethylenedioxyphenyl group, carbazolyl group, quinazolinyl group, quinoxalinyl group, quinolizinyl group, quinolyl group, cumaronyl group, chromenyl group, phenanthridinyl group , Phenanthrolinyl group, dibenzofuranyl group, dibenzothiophenyl group, cinnolinyl group, thionaphthenyl group, naphthyridinyl group, phenazinyl group,
A nitrogen selected from the group consisting of phenaxazinyl, phenothiazinyl, phthalazinyl, pteridinyl, purinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, benzofuranyl, and methylenedioxyphenyl groups atom,
A mono- to tricyclic heteroaromatic group having 1 to 5 heteroatoms per ring system selected from the group consisting of an oxygen atom and a sulfur atom, and N-substituted by the heterocyclic group or the heteroaromatic ring group; C ₁ -C ₁₀ alkylcarbamoyl group, N
A substituent selected from the group consisting of a -C ₁ -C ₁₀ alkylthiocarbamoyl group, a thiocarbonyl group and a carbonyl group, and a linear saturated C ₁ -C ₉ aliphatic group which may be substituted with the substituent; A linear unsaturated C ₁ -C ₉ aliphatic group,
Branched saturated C ₁ -C ₉ aliphatic radical, branched unsaturated C ₁
-C ₉ aliphatic group substitutions is selected from the group consisting of C ₁ -C ₆ alkoxy group, a substituent selected from the group consisting of C ₁ -C ₆ alkylthio group and a N-C ₁ -C ₆ alkylamino group The groups can be listed.

Among the substituents for R, for example, an amino group,
Rubamoyl group, carbamoylamino group, carbamoylo
Xy, carboxyl, nitro, halogen,
Droxy group, cyclic saturated C_Three-C₉Aliphatic group, cyclic unsaturated
Sum C_Three-C₉Aliphatic group, aralkyl group, N-aralkyl group
Mino group, aralkyloxy group, aralkylcarbonyl
Group, N-aralkylcarbamoyl group, aryl group, N-
Arylamino group, aryloxy group, arylsulfo
Nyl group, arylsulfonyloxy group, N-aryls
Ruphonylamino group, N-arylsulfonylamino C₁
-C_TenAlkylamino group, N-arylsulfonylamido
No C₁-C_TenAlkylcarbamoyl group, N-aryls
Ruphonylamino C₁-C₆Alkoxycarbonyl group, ant
Arylsulfamoyl group, arylsulfamoyloxy
Group, N-arylsulfamoyl C ₁-C_TenAlkylka
Rubamoyl group, arylsulfamoyl C₁-C₆Arco
Xycarbonyl group, N-arylcarbamoyl group, allo
Yl group, alloxy group, N- (N-aroylamino) C₁
-C_TenAlkylcarbamoyl group, N-aroylamino C
₁-C_TenAlkoxycarbonyl group, C_Two-C₆Arcanoy
Group, N-C_Two-C₆Alkanoylamino group, NC₁−
C₆Alkylamino group, N, N-di-C₁-C₆Alkyl
Amino group, N-C₁-C_TenAlkylcarbamoyl group, N
-C₁-C_TenAlkylthiocarbamoyl group, N, N-di
-C₁-C_TenAlkylcarbamoyl group, N, N-di-C₁
-C_TenAlkylthiocarbamoyl group, NC_Two-C₆Al
Kenylcarbamoyl group, N, N-di-C_Two-C₆Alkene
Rucarbamoyl group, N-amino C₁-C_TenAlkyl cal
Bamoyl group, NC₁-C₆Alkoxy C₁-C_TenArchi
Rucarbamoyl group, NC₁-C₆Alkoxycarbonyl
C₁-C_TenAlkylcarbamoyl group, NC₁-C₆Al
Coxycarbonylamino C₁-C_TenAlkyl carbamoy
Group, N-C₁-C₆Alkoxycarbonylamino C₁−
C₆Alkoxycarbonyl group, C₁-C₆Alkylthio
Group, C₁-C₆Alkylsulfinyl group, C₁-C₆Archi
Rusulfonyl group, NC₁-C₆Alkylsulfonylami
No group, C₁-C₆Alkoxy group, C₁-C₆Alkoxycal
Bonyl group, amino C₁-C₆An alkoxycarbonyl group,
N-C_Three-C₆Cycloalkylamino group, N, N-di-C
_Three-C₆Cycloalkylamino group, C_Three-C₆Cycloal
Killoxy group, N-C_Three-C₆Cycloalkyl carbamoy
And N, N-di-C_Three-C₆Cycloalkylcarbamo
A substituent selected from the group consisting of
Ryl, isothiazolyl, imidazolyl, oxazo
Ryl group, oxadiazolyl group, thiazolyl group, thiadia
Zolyl, thienyl, triazolyl, pyridyl,
Pyrazinyl group, pyrimidinyl group, pyridazinyl group, pyra
Zolyl, pyrrolyl, pyranyl, furyl, imida
Zolidinyl group, imidazolinyl group, tetrahydrofurani
, Pyrazolidinyl, pyrazolinyl, piperazini
Group, piperidinyl group, pyrrolidinyl group, pyrrolinyl group
And 5 or 6 members selected from the group consisting of morpholino groups
A heterocyclic group, an isoquinolyl group, an isoindolyl group,
Ndazolyl group, indolyl group, ethylenedioxyphenyl
Group, carbazolyl group, quinazolinyl group, quinoxalini
Group, quinolidinyl group, quinolyl group, coumalonyl group,
Romenyl group, phenanthridinyl group, phenanthrolini
Group, dibenzofuranyl group, dibenzothiophenyl group,
Cinnolinyl group, thionaphthenyl group, naphthyridinyl
Group, phenazinyl group, phenaxazinyl group, benzimi
Dazolyl group, benzoxazolyl group, benzothiazolyl
Group, benzotriazolyl group, benzofuranyl group and methyl
Nitrogen selected from the group consisting of rangeoxyphenyl groups
Atoms selected from the group consisting of atoms, oxygen atoms and sulfur atoms
1 to 3 having 1 to 5 telo atoms per ring system
Cyclic heteroaromatic group and said heterocyclic group or said heteroaromatic
N—C substituted with a ring group₁-C_TenAlkyl carbamoyl
Group, NC₁-C_TenAlkylthiocarbamoyl group, thio
Selected from the group consisting of carbonyl groups and carbonyl groups
Substituents which may be substituted with the substituents,
Chain saturation C₁-C₉Aliphatic group, linear unsaturated C₁-C₉fat
Group, branched saturated C₁-C₉Aliphatic groups, branched chain unsaturation
C₁-C₉Aliphatic group, C₁-C₆Alkoxy group and C₁−
C₆A substituent selected from the group consisting of alkylthio groups
Substituents selected from the group consisting of
Amino group, carbamoyl group, carboxyl group, nitro
Group, halogen atom, hydroxy group, aralkyl carbonyl
Group, N-aralkylcarbamoyl group, aryl group,
Royl group, C_Two-C₆Alkanoyl group, NC₁-C₆Al
Killamino group, N-C₁-C_TenAlkyl carbamoyl
Group, NC₁-C_TenAlkylthiocarbamoyl group, N,
N-di-C₁-C_TenAlkylcarbamoyl group, N, N-
Di-C₁-C_TenAlkylthiocarbamoyl group, NC_Two−
C₆Alkenylcarbamoyl group, N, N-di-C_Two-C₆
Alkenylcarbamoyl group, N-amino C₁-C_TenAl
Kill carbamoyl group, NC₁-C₆Alkoxy C₁-C
_TenAlkylcarbamoyl group, NC₁-C₆Alkoxyka
Rubonil C₁-C_TenAlkylcarbamoyl group, C₁-C₆
Alkoxy group, amino C₁-C₆Alkoxycarbonyl
Group, NC_Three-C₆Cycloalkylamino group, N, N-di
-C_Three-C₆Cycloalkylamino group, C_Three-C₆Cyclo
Alkyloxy group, N-C_Three-C₆Cycloalkyl carb
Moyl group and N, N-di-C_Three-C₆Cycloalkylcal
Thienyl, a substituent selected from the group consisting of a bamoyl group
Group, pyridyl group, pyrazinyl group, pyrimidinyl group, free
Group, tetrahydrofuranyl group and morpholino group.
A 5- or 6-membered heterocyclic group selected from the group consisting of
Dioxyphenyl group, dibenzofuranyl group, dibenzothi
Consists of an ophenyl group and a methylenedioxyphenyl group
From nitrogen, oxygen and sulfur selected from the group
A heteroatom selected from the group consisting of 1 to
5- to 5-cyclic heteroaromatic ring groups and
N-C substituted with a heterocyclic group or the heteroaromatic group₁-C_Ten
Alkylcarbamoyl group, NC₁-C_TenAlkylthio
Carbamoyl group, thiocarbonyl group and carbonyl group
And a substituent selected from the group consisting of
Straight-chain saturated C₁-C₉Aliphatic group, straight chain
Of unsaturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉fat
Group, branched chain unsaturated C₁-C₉Aliphatic group and C₁-C₆
Consisting of a substituent selected from the group consisting of alkoxy groups
Substituents selected from the group are preferred.

That is, for example, an amino group, a carbamoyl group,
Carbamoylamino group, carbamoyloxy group, carbo
Xyl group, nitro group, halogen atom, hydroxy group, ring
Saturated C_Three-C₉Aliphatic group, cyclic unsaturated C_Three-C₉fat
Group, aralkyl group, N-aralkylamino group, aralkyl
Killoxy group, aralkylcarbonyl group, N-aralkyl
Rucarbamoyl group, aryl group, N-arylamino
Group, aryloxy group, arylsulfonyl group, aryl
Rusulfonyloxy group, N-arylsulfonylamino
Group, N-arylsulfonylamino C₁-C_TenAlkyl
Amino group, N-arylsulfonylamino C₁-C_TenA
Alkylcarbamoyl group, N-arylsulfonylamino
C₁-C₆Alkoxycarbonyl group, arylsulfamo
Yl group, arylsulfamoyloxy group, N-ary
Rusulfamoyl C₁-C_TenAlkylcarbamoyl group,
Aryl sulfamoyl C₁-C₆Alkoxycarbonyl
Group, N-arylcarbamoyl group, aroyl group, alloki
Group, N- (N-aroylamino) C₁-C_TenAlkyl
Carbamoyl group, N-aroylamino C₁-C_TenArco
Xycarbonyl group, C_Two-C₆Alkanoyl group, NC_Two
-C₆Alkanoylamino group, NC₁-C₆Alkyria
Mino group, N, N-di-C₁-C₆Alkylamino group, N-
C₁-C_TenAlkylcarbamoyl group, NC₁-C_TenAl
Kirthiocarbamoyl group, N, N-di-C₁-C_TenAl
Kill carbamoyl group, N, N-di-C₁-C _TenAlkyl
Thiocarbamoyl group, NC_Two-C₆Alkenyl carbamo
Yl group, N, N-di-C_Two-C₆Alkenylcarbamoyl
Group, N-amino C₁-C_TenAlkylcarbamoyl group, N
-C₁-C₆Alkoxy C₁-C_TenAlkyl carbamoyl
Group, NC₁-C₆Alkoxycarbonyl C₁-C_TenAl
Kill carbamoyl group, NC₁-C₆Alkoxycarboni
Lumino C₁-C_TenAlkylcarbamoyl group, NC₁−
C₆Alkoxycarbonylamino C₁-C₆Alkoxyka
Rubonyl group, C₁-C₆Alkylthio group, C₁-C₆Archi
Rusulfinyl group, C₁-C₆Alkylsulfonyl group, N
-C₁-C₆Alkylsulfonylamino group, C₁-C₆Al
Coxy group, C₁-C₆Alkoxycarbonyl group, amino
C₁-C₆Alkoxycarbonyl group, N-C _Three-C₆Cyclo
Alkylamino group, N, N-di-C_Three-C₆Cycloalkyl
Ruamino group, C_Three-C₆Cycloalkyloxy group, N-
C_Three-C₆Cycloalkylcarbamoyl group and N, N-di
-C_Three-C₆Group consisting of cycloalkylcarbamoyl groups
Selected substituent, isoxazolyl group, isothiazo
Ryl group, imidazolyl group, oxazolyl group, oxadia
Zolyl, thiazolyl, thiadiazolyl, thienyl
Group, triazolyl group, pyridyl group, pyrazinyl group, pyriyl group
Midinyl group, pyridazinyl group, pyrazolyl group, pyrrolyl
Group, pyranyl group, furyl group, imidazolidinyl group, imi
Dazolinyl group, tetrahydrofuranyl group, pyrazolidini
, Pyrazolinyl, piperazinyl, piperidinyl
Group, pyrrolidinyl group, pyrrolinyl group and morpholino group
A 5- or 6-membered heterocyclic group selected from the group consisting of
Quinolyl group, isoindolyl group, indazolyl group,
Drill group, ethylenedioxyphenyl group, carbazolyl
Group, quinazolinyl group, quinoxalinyl group, quinolizinyl
Group, quinolyl group, cumaronyl group, chromenyl group, phena
Suridinyl group, phenanthrolinyl group, dibenzofura
Nil group, dibenzothiophenyl group, cinnolinyl group,
Onaphthenyl group, naphthyridinyl group, phenazinyl group,
Phenaxazinyl, benzimidazolyl, benzoo
Xazolyl group, benzothiazolyl group, benzotriazolyl group
Group, benzofuranyl group and methylenedioxyphenyl
Nitrogen, oxygen and sulfur selected from the group consisting of
A heteroatom selected from the group consisting of yellow atoms
1 to 3 cyclic heteroaromatic ring groups having 1 to 5
And the heterocyclic group or the heteroaromatic ring group is substituted with N-
C₁-C_TenAlkylcarbamoyl group, NC₁-C_TenAl
Quilthiocarbamoyl, thiocarbonyl, and car
A substituent selected from the group consisting of a bonyl group;
Straight-chain saturated C which may be substituted with₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic group, branched unsaturated C₁-C₉Aliphatic groups,
C₁-C₆Alkoxy group and C₁-C₆From the alkylthio group
Selected from the group consisting of substituents selected from the group consisting of
Aryl which may have one or more substituents
Group, adamantyl group, anthryl group, indenyl group,
Select from the group consisting of rubornyl group and phenanthryl group
1- to 3-cyclic C₇-C_FifteenA carbon aromatic ring group or a
Soxazolyl group, isothiazolyl group, imidazolyl
Group, oxazolyl group, oxadiazolyl group, thiazolyl
Group, thiadiazolyl group, thienyl group, triazolyl group,
Pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazi
Nil, pyrazolyl, pyrrolyl, pyranyl, free
Group, imidazolidinyl group, imidazolinyl group, tetra
Hydrofuranyl group, pyrazolidinyl group, pyrazolinyl
Group, piperazinyl group, piperidinyl group, pyrrolidinyl
Selected from the group consisting of a group, a pyrrolinyl group and a morpholino group
5- or 6-membered heterocyclic group or isoquinolyl
Group, isoindolyl group, indazolyl group, indolyl group
Group, ethylenedioxyphenyl group, carbazolyl group,
Nazolinyl group, quinoxalinyl group, quinolizinyl group,
Noryl group, coumalonyl group, chromenyl group, phenanthry
Dinyl group, phenanthrolinyl group, dibenzofuranyl
Group, dibenzothiophenyl group, cinnolinyl group, thiona
Phenyl, naphthyridinyl, phenazinyl,
Naxazinyl group, benzimidazolyl group, benzoxa
Zolyl, benzothiazolyl, benzotriazolyl
Group, benzofuranyl group and methylenedioxyphenyl group
Nitrogen, oxygen and sulfur selected from the group consisting of
Heteroatoms selected from the group consisting of atoms per ring system
1 to 5 monocyclic to 3 cyclic heteroaromatic groups, etc.
(R^a) Are suitable groups, especially for example amino groups,
Bamoyl group, carboxyl group, nitro group, halogen source
, An hydroxy group, an aralkylcarbonyl group, N-ara
Alkylcarbamoyl, aryl, aroyl, C_Two
-C₆Alkanoyl group, NC₁-C₆Alkylamino
Group, NC₁-C_TenAlkylcarbamoyl group, NC₁−
C_TenAlkylthiocarbamoyl group, N, N-di-C₁−
C_TenAlkylcarbamoyl group, N, N-di-C₁-C_Ten
Alkylthiocarbamoyl group, NC_Two-C₆Alkenyl
Carbamoyl group, N, N-di-C_Two-C₆Alkenylcal
Bamoyl group, N-amino C₁-C_TenAlkyl carbamoy
Group, N-C₁-C₆Alkoxy C₁-C_TenAlkyl cal
Bamoyl group, NC₁-C₆Alkoxycarbonyl C₁−
C_TenAlkylcarbamoyl group, C₁-C₆An alkoxy group,
 Amino C₁-C₆Alkoxycarbonyl group, N-C_Three-C
₆Cycloalkylamino group, N, N-di-C_Three-C₆Shiku
Loalkylamino group, C _Three-C₆Cycloalkyloxy
Group, NC_Three-C₆A cycloalkylcarbamoyl group and
N, N-di-C_Three-C₆Is it a cycloalkylcarbamoyl group
Substituents, thienyl groups, pyridyls selected from the group consisting of
Group, pyrazinyl group, pyrimidinyl group, furyl group, tetra
Select from the group consisting of hydrofuranyl and morpholino groups
5- or 6-membered heterocyclic group, ethylenedioxyphene
Nil group, dibenzofuranyl group, dibenzothiophenyl group
And methylenedioxyphenyl groups
Selected from the group consisting of nitrogen, oxygen and sulfur atoms
1 to 5 heteroatoms per ring system
To a tricyclic heteroaromatic ring group and the heterocyclic group or the
N-C substituted with a heteroaromatic group₁-C_TenAlkyl cal
Bamoyl group, NC₁-C_TenAlkylthiocarbamoyl
Group consisting of a carbonyl group, a thiocarbonyl group and a carbonyl group
Substituents selected from the above, and even if
Good, straight-chain saturated C₁-C₉Aliphatic group, linear unsaturated C₁
-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic groups, branched
Chain unsaturated C₁-C₉Aliphatic group and C₁-C₆Alkoxy
Selected from the group consisting of substituents selected from the group consisting of groups
Having one or more substituents
Group consisting of a thiol group, anthryl group and a phenanthryl group
A mono- to tricyclic C selected from₇-C_FifteenCarbon aromatic ring
Group or thienyl group, pyridyl group, pyrazinyl group, pirimi
Dinyl group, furyl group, tetrahydrofuranyl group and mol
5- or 6-membered hetero selected from the group consisting of holino groups
Ring group or ethylenedioxyphenyl group, dibenzof
Ranyl group, dibenzothiophenyl group and methylenedioxy
Nitrogen atom or oxygen selected from the group consisting of cyphenyl groups
A heteroatom selected from the group consisting of
1 to 5 heterocyclic groups having 1 to 5 rings per ring system
Aromatic ring group (R^b) Is a more preferred group.

R¹And R^TwoAre the same or different, for example
Hydrogen atom, azide group, amino group, carbamoyl group, car
Bamoylamino group, carbamoyloxy group, carboxy
, Cyano, sulfamoyl, sulfo, nitro
Group, halogen atom, hydroxy group, formyl group, formi group
Ruamino group, cyclic saturated C_Three-C₉Aliphatic group, cyclic unsaturated
Sum C_Three-C₉Aliphatic group, aralkyl group, N-aralkyl group
Mino group, aralkyloxy group, aralkylcarbonyl
Group, aryl group, N-arylamino group, aryloxy
Si group, arylsulfonyl group, N-arylsulfonyl
Amino group, N-arylsulfonylamino C₁-C_TenA
Alkylamino group, N-arylsulfonylamino C₁−
C_TenAlkylcarbamoyl group, N-arylsulfonyl
Amino C₁-C₆Alkoxycarbonyl group, C_Two-C₆Al
Canoyl group, NC_Two-C₆Alkanoylamino group, allo
Yl group, N-aroylamino group, N-aroyl C₁-C
_TenAlkylamino group, N-aroyl C₁-C_TenAlkyl
Carbamoyl group, NC₁-C ₆Alkylamino group, N,
N-di-C₁-C₆Alkylamino group, N-C₁-C_TenA
Alkylcarbamoyl group, N, N-di-C₁-C_TenArchi
Rucarbamoyl group, NC₁-C₆Alkylsulfamoy
Group, C₁-C₆Alkylsulfinyl group, C₁-C₆Al
Killsulfonyl group, N-C₁-C₆Alkylsulfonylua
Mino group, C₁-C ₆Alkylthio group, C₁-C₆Alkoxy
Group, C₁-C₆Alkoxycarbonyl group, N-C_Three-C₆Shi
Chloroalkylamino group, C_Three-C₆Cycloalkyloxy
Group and NC_Three-C₆From cycloalkylcarbamoyl group
Or a substituent selected from the group consisting of
A linear saturated C₁-C₉Aliphatic group, straight-chain unsaturated
Sum C₁-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic groups,
Branched unsaturated C₁-C₉Aliphatic group, N-C₁-C₆Al
Killamino group, C₁-C₆Alkylthio group or C ₁−
C₆Represents an alkoxy group or the like;
Mino group, carboxyl group, cyano group, sulfamoyl
Group, sulfo group, nitro group, halogen atom, hydroxy
Group, formyl group, cyclic saturated C_Three-C₉Aliphatic group, cyclic
Unsaturated C_Three-C₉Aliphatic groups, aralkyl groups, aryl groups,
N-arylamino group, aryloxy group, C_Two-C₆A
Lucanoyl group, NC_Two-C₆Alkanoylamino group,
Royl group, NC₁-C₆Alkylamino group, N, N-di
-C₁-C₆Alkylamino group, N-C ₁-C_TenAlkyl
Carbamoyl group, NC₁-C₆Alkylsulfamoyl
Group, C₁-C₆Alkylsulfinyl group, C₁-C₆Archi
Rusulfonyl group, NC₁-C₆Alkylsulfonylami
No group, C₁-C₆Alkoxy group, C₁-C₆Alkoxycal
Bonyl group, N-C_Three-C₆Cycloalkylamino group, C_Three
-C₆Cycloalkyloxy group and N-C_Three-C₆Cyclo
Substitution selected from the group consisting of alkylcarbamoyl groups
Or a straight-chain saturated C which may be substituted with
₁-C₉Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups, branched
Chain saturation C₁-C₉Aliphatic group, branched unsaturated C₁-C₉
Aliphatic group or C₁-C₆Alkoxy groups and the like are preferred,
Particularly, for example, hydrogen atom, amino group, nitro group, halogen atom
, Hydroxy group, aryl group, N-arylamino
Group, NC₁-C₆Alkylamino group, N, N-di-C₁
-C₆Alkylamino group, N-C₁-C_TenAlkyl carba
Moyl group, C₁-C₆Alkoxy group, C₁-C₆Alkoxy
Carbonyl group and N-C_Three-C₆Cycloalkylamino group
Or a substituent selected from the group consisting of
Straight-chain saturated C₁-C₉Aliphatic group, linear
Unsaturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic
Group, branched, unsaturated C₁-C₉Aliphatic group or C₁−
C₆Alkoxy groups and the like are preferred.

R^ThreeAnd R^FourAre the same or different, and (1)
For example, hydrogen atom, azide group, amidino group, amino group,
Rubamoyl group, carbamoylamino group, carbamoylo
Xy, carboxyl, guanidino, cyano,
Rufamoyl group, sulfo group, nitro group, halogen atom,
Hydroxy, formyl, formylamino, cyclic
Saturated C_Three-C₉Aliphatic group, cyclic unsaturated C_Three-C₉Aliphatic
Group, C_Two-C₆Alkanoyl group, NC_Two-C₆Arcanoy
Ruamino group, NC₁-C₆Alkylamino group, N, N-
Di-C₁-C₆Alkylamino group, N-C₁-C_TenArchi
Rucarbamoyl group, N, N-di-C₁-C_TenAlkylka
Rubamoyl group, C₁-C₆Alkylthio group, N-C₁-C₆
Alkylsulfamoyl group, C₁-C₆Alkylsulfi
Nyl group, C₁-C₆Alkylsulfonyl group, NC ₁-C₆
Alkylsulfonylamino group, C₁-C₆An alkoxy group,
C₁-C₆Alkoxycarbonyl group, N-C_Three-C₆Cyclo
Alkylamino group, C_Three-C₆Cycloalkyloxy group and
And NC_Three-C₆Consists of a cycloalkylcarbamoyl group
A substituent selected from the group, (2) for example, substitution with the substituent
Straight-chain saturated C₁-C₉Aliphatic group, straight chain
Of unsaturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉fat
Group and branched unsaturated C₁-C₉Group consisting of aliphatic groups
(3) For example, an aryl group, ace
Naphthylenyl, adamantyl, anthryl,
It consists of a benzyl group, a norbornyl group and a phenanthryl group.
One to three ring C selected from the group₇-C_FifteenCarbon good
Aromatic ring group, isoxazolyl group, isothiazolyl group, a
Midazolyl group, oxazolyl group, oxadiazolyl group,
Thiazolyl group, thiadiazolyl group, thienyl group, tria
Dinyl group, triazolyl group, pyridyl group, pyrazinyl
Group, pyrimidinyl group, pyridazinyl group, pyrazolyl group,
Pyrrolyl, pyranyl, furyl, furazanyl, i
Midazolidinyl group, imidazolinyl group, tetrahydrof
Ranyl group, pyrazolidinyl group, pyrazolinyl group, pipera
Dinyl group, piperidinyl group, pyrrolidinyl group, pyrrolini
5 or a morpholino group selected from the group consisting of
6-membered heterocyclic group or acridinyl group, isoquinolyl
, Isoindolyl, indazolyl, indolyl
Group, indolizinyl group, ethylenedioxyphenyl group,
Carbazolyl group, quinazolinyl group, quinoxalinyl group,
Quinolizinyl, quinolyl, coumalonyl, chromeni
Phenanthridinyl group, phenanthrolinyl group,
Dibenzofuranyl group, dibenzothiophenyl group, Shinno
Linyl, thionaphthenyl, naphthyridinyl,
Nadinyl group, phenaxazinyl group, phenothiazinyl
Group, phthalazinyl group, pteridinyl group, purinyl group,
Benzoimidazolyl group, benzoxazolyl group, benzothi
Azolyl group, benzotriazolyl group, benzofuranyl group
And methylenedioxyphenyl groups
Selected from the group consisting of nitrogen, oxygen and sulfur atoms
1 to 5 heteroatoms per ring system
To a tricyclic heteroaromatic group or the aryl group,
Substituted with an aromatic ring group, the heterocyclic group or the heteroaromatic group
Straight-chain saturated C₁-C₉Aliphatic group, straight chain
Of unsaturated C ₁-C₉Aliphatic groups, branched saturated C₁-C₉fat
Group or branched unsaturated C₁-C₉Shows aliphatic group, etc.
Or (4) R^ThreeAnd R^FourTogether form a linear
Saturated C₁-C₉Aliphatic group, linear unsaturated C₁-C₉Aliphatic
Group, branched chain saturated C₁-C₉No aliphatic groups or branched chains
Saturated C₁-C₉Aliphatic group or 5- or 6-membered saturated carbon
Forming a cyclic group or a 5- or 6-membered unsaturated carbocyclic ring
You.

Specific examples of the substituents of R ³ and R ⁴ are as follows. Preferred substituents in (1) are, for example, a hydrogen atom, an azido group, an amidino group, an amino group, a carbamoyl group, a carbamoylamino group, a carbamoylamino group. Oxy, carboxyl, guanidino, cyano, sulfamoyl, sulfo, nitro, halogen, hydroxy, formyl, formylamino, cyclic saturated C _3-
C ₉ aliphatic group, cyclic unsaturated C ₃ -C ₉ aliphatic group, C ₂ -C
₆ alkanoyl group, N-C ₁ -C ₆ alkylamino group, N
—C ₁ -C ₁₀ alkylcarbamoyl group, C ₁ -C ₆ alkylthio group, N—C ₁ -C ₆ alkylsulfamoyl group, C
₁ -C ₆ alkylsulfinyl group, C ₁ -C ₆ alkylsulfonyl group, N-C ₁ -C ₆ alkylsulfonylamino group,
Substituents selected from the group consisting of C ₁ -C ₆ alkoxy groups, C ₁ -C ₆ alkoxycarbonyl groups, and N—C ₃ -C ₆ cycloalkylamino groups, and the like. Among them, for example, a hydrogen atom, an azide group , amidino group, an amino group, a carbamoyl group, a carboxyl group, a guanidino group, a cyano group, a sulfamoyl group, a sulfo group, a nitro group, a halogen atom, hydroxy group, formyl group, a cyclic saturated C ₃ -C ₉ aliphatic groups, cyclic unsaturated C ₃ -C ₉ aliphatic groups, N-C ₁ -C ₆ alkylamino group, N-C ₁ -C ₁₀ alkylcarbamoyl groups, C ₁ -C ₆ alkylthio group, C ₁ -C ₆ alkoxy group and And a substituent selected from the group consisting of C ₁ -C ₆ alkoxycarbonyl groups.

Preferred substituents in (2) are, for example,
Direct substituents which may be substituted with the substituents mentioned in (1)
Chain saturation C₁-C₉Aliphatic group, linear unsaturated C₁-C₉fat
Group, branched saturated C₁-C₉Unsaturation of aliphatic groups and branches
Sum C₁-C₉Substitution selected from the group consisting of aliphatic groups
Groups, e.g., hydrogen, azide, amidino,
Group, carbamoyl group, carbamoylamino group, carb
Moyloxy group, carboxyl group, guanidino group, shea
, Sulfamoyl, sulfo, nitro, halogen
Atom, hydroxy group, formyl group, formylamino
Group, cyclic saturated C_Three-C₉Aliphatic group, cyclic unsaturated C_Three−
C₉Aliphatic group, C_Two-C₆Alkanoyl group, NC₁-C₆
Alkylamino group, N-C₁-C_TenAlkyl carbamoy
Group, C₁-C ₆Alkylthio group, N-C₁-C₆Alkyl
Sulfamoyl group, C₁-C₆Alkylsulfinyl group,
C₁-C₆Alkylsulfonyl group, NC₁-C₆Alkyl
Sulfonylamino group, C₁-C₆Alkoxy group, C₁-C₆
Alkoxycarbonyl group and N-C_Three-C₆Cycloalkyl
Substituted with a substituent selected from the group consisting of
A linear saturated C₁-C₉Aliphatic group, straight chain
Saturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group
And branched unsaturated C₁-C₉From the group consisting of aliphatic groups
Substituents and the like to be selected may be mentioned.
, Azide group, amidino group, amino group, carbamoyl
Group, carboxyl group, guanidino group, cyano group, sulf
Amoyl group, sulfo group, nitro group, halogen atom, hydride
Roxy group, formyl group, cyclic saturated C_Three-C₉Aliphatic groups,
Cyclic unsaturated C_Three-C₉Aliphatic group, N-C₁-C₆Alkyl
Amino group, N-C₁-C_TenAlkylcarbamoyl group, C₁
-C₆Alkylthio group, C₁-C₆Alkoxy group and C₁−
C₆Selected from the group consisting of alkoxycarbonyl groups
Straight-chain saturated C which may be substituted with a substituent₁-C₉Fat
Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups, branched chain saturation
C₁-C₉Aliphatic groups and branched unsaturated C₁-C₉Aliphatic
And a substituent selected from the group consisting of groups.

The preferred substituent in (3) is, for example, a monocyclic to tricyclic C ₇ -C ₁₅ carbon aromatic selected from the group consisting of aryl, adamantyl, anthryl, indenyl, norbornyl and phenanthryl. Ring group or isoxazolyl group, isothiazolyl group, imidazolyl group, oxazolyl group, oxadiazolyl group, thiazolyl group, thiadiazolyl group, thienyl group, triazolyl group, pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, pyrazolyl group, pyrrolyl group, pyranyl group 5 or 6 selected from the group consisting of a furyl group, an imidazolidinyl group, an imidazolinyl group, a tetrahydrofuranyl group, a pyrazolidinyl group, a pyrazolinyl group, a piperazinyl group, a piperidinyl group, a pyrrolidinyl group, a pyrrolinyl group and a morpholino group Heterocyclic group or an isoquinolyl group, an isoindolyl group, an indazolyl group, an indolyl group, ethylenedioxy phenyl group, a carbazolyl group,
Quinazolinyl group, quinoxalinyl group, quinolizinyl group,
Quinolyl group, coumalonyl group, chromenyl group, phenanthridinyl group, phenanthrolinyl group, dibenzofuranyl group, dibenzothiophenyl group, cinnolinyl group, thionaphthenyl group, naphthyridinyl group, phenazinyl group, phenaxazinyl group, benzimidazolyl group, benzo Hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur atoms selected from the group consisting of oxazolyl, benzothiazolyl, benzotriazolyl, benzofuranyl and methylenedioxyphenyl per ring system 1 to 5 mono- to tricyclic heteroaromatic ring groups or the aryl group, the carbon aromatic ring group, the heterocyclic group or the straight-chain saturated C which may be substituted with the heteroaromatic group.
₁ -C ₉ aliphatic groups, unsaturated C ₁ -C ₉ aliphatic group, straight chain, saturated C ₁ -C ₉ aliphatic groups or branched unsaturated branched C
Preferably such ₁ -C ₉ aliphatic groups, in particular such as an aryl group,
1 to tricyclic C ₇ -C ₁₅ carbon ring group or a thienyl group selected from the group consisting of anthryl and phenanthryl group, a pyridyl group, pyrazinyl group, pyrimidinyl group, furyl group, a tetrahydrofuranyl group and a morpholino group A nitrogen atom, an oxygen atom and a sulfur selected from the group consisting of a 5- or 6-membered heterocyclic group or an ethylenedioxyphenyl group, a dibenzofuranyl group, a dibenzothiophenyl group and a methylenedioxyphenyl group selected from the group consisting of A mono- to tricyclic heteroaromatic group having 1 to 5 heteroatoms per ring system selected from the group consisting of atoms, or the aryl group, the carbon aromatic ring group, the heterocyclic group or the heteroaromatic group A linear saturated C ₁ -C ₉ aliphatic group, a linear unsaturated C ₁ -C ₉ aliphatic group, and a branched saturated C ₁ -C ₉ aliphatic group or branched C ₁ -C ₉ aliphatic group unsaturation and the like.

In (3), said aryl group, said 1 to 3 cyclic C ₇ -C ₁₅ carbon aromatic ring group, said 5- or 6-membered heterocyclic group, said nitrogen atom, oxygen atom and sulfur atom A mono- to tricyclic heteroaromatic group having 1 to 5 heteroatoms per ring system selected from the group or substituted with the aryl group, the carbon aromatic ring group, the heterocyclic group or the heteroaromatic group. A linear saturated C ₁ -C ₉ aliphatic group, a linear unsaturated C ₁ -C ₉ aliphatic group, a branched saturated C _1
1 -C ₉ aliphatic group or branched C ₁ -C ₉ aliphatic group unsaturation such may have one or more substituents. In addition, as the substituent, the same substituents as the substituents of the substituent R can be listed.

In a preferred embodiment of (4), R
³ and R ⁴ together form a linear saturated C ₁ -C ₉ aliphatic group, a linear unsaturated C ₁ -C ₉ aliphatic group, a branched saturated C ₁
-C ₉ a case of forming a carbon ring aliphatic group or a branched unsaturated C ₁ -C ₉ aliphatic group or a 5- or 6-membered saturated carbocyclic group or a 5- or 6-membered unsaturated, Particularly, a case where a linear unsaturated C ₁ -C ₉ aliphatic group or a 5- or 6-membered saturated carbocyclic group is formed is preferable.

Therefore, R^ThreeAnd R^FourAre the same or different
(1a) for example, a hydrogen atom, an azide group, an amidino group,
Amino group, carbamoyl group, carbamoylamino group,
Rubamoyloxy group, carboxyl group, guanidino group,
Cyano group, sulfamoyl group, sulfo group, nitro group,
Rogen atom, hydroxy group, formyl group, formylamine
Group, cyclic saturated C_Three-C₉Aliphatic group, cyclic unsaturated C_Three
-C₉Aliphatic group, C_Two-C₆Alkanoyl group, NC₁-C
₆Alkylamino group, N-C₁-C_TenAlkyl carbamoy
Group, C₁-C₆Alkylthio group, N-C₁-C₆Alkyl
Sulfamoyl group, C₁-C₆Alkylsulfinyl group,
C₁-C₆Alkylsulfonyl group, NC₁-C₆Alkyl
Sulfonylamino group, C₁-C₆Alkoxy group, C₁-C₆
Alkoxycarbonyl group and N-C_Three-C₆Cycloalkyl
Such as a substituent selected from the group consisting of
a) straight chain saturated, which may be substituted, for example
Sum C₁-C₉Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups,
Branched saturated C₁-C₉Aliphatic groups and branched unsaturated C
₁-C₉A substituent selected from the group consisting of aliphatic groups (3
a) For example, amino group, carbamoyl group, carbamoylua
Mino group, carbamoyloxy group, carboxyl group, nitro
Group, halogen atom, hydroxy group, cyclic saturated C_Three−
C₉Aliphatic group, cyclic unsaturated C_Three-C₉Aliphatic group, aral
Kill group, N-aralkylamino group, aralkyloxy
Group, aralkylcarbonyl group, N-aralkylcarbamo
Yl group, aryl group, N-arylamino group, aryl
Oxy group, arylsulfonyl group, arylsulfonyl
Oxy group, N-arylsulfonylamino group, N-ali
Rusulfonylamino C₁-C_TenAlkylamino group, N
-Arylsulfonylamino C₁-C_TenAlkyl carba
Moyl group, N-arylsulfonylamino C₁-C₆Al
Coxycarbonyl group, arylsulfamoyl group, ant
Sulfamoyloxy group, N-arylsulfamo
Il C₁-C_TenAlkyl carbamoyl group, aryl sulf
Famoyl C₁-C₆Alkoxycarbonyl group, N-ali
Carbamoyl group, aroyl group, alloxy group, N-
(N-aroylamino) C₁-C_TenAlkyl carbamoy
Group, N-aroylamino C₁-C_TenAlkoxycarbo
Nyl group, C_Two-C₆Alkanoyl group, NC_Two-C₆Arca
Noylamino group, NC₁-C₆Alkylamino group, N,
N-di-C₁-C₆Alkylamino group, N-C₁-C_TenA
Alkylcarbamoyl group, NC₁-C_TenAlkylthioca
Rubamoyl group, N, N-di-C₁-C_TenAlkyl carba
Moyl group, N, N-di-C₁-C _TenAlkylthiocarba
Moyl group, NC_Two-C₆Alkenylcarbamoyl group,
N, N-di-C_Two-C₆Alkenylcarbamoyl group, N-
Amino C₁-C_TenAlkylcarbamoyl group, NC₁-C
₆Alkoxy C₁-C_TenAlkylcarbamoyl group, NC
₁-C₆Alkoxycarbonyl C₁-C_TenAlkyl carba
Moyl group, NC₁-C₆Alkoxycarbonylamino C
₁-C_TenAlkylcarbamoyl group, NC₁-C₆Arco
Xycarbonylamino C₁-C₆Alkoxycarbonyl
Group, C₁-C₆Alkylthio group, C₁-C₆Alkylsulf
Inyl group, C₁-C₆Alkylsulfonyl group, NC₁−
C₆Alkylsulfonylamino group, C₁-C₆Alkoxy
Group, C₁-C₆Alkoxycarbonyl group, amino C₁-C
₆Alkoxycarbonyl group, N-C _Three-C₆Cycloalkyl
Ruamino group, N, N-di-C_Three-C₆Cycloalkylamide
No group, C_Three-C₆Cycloalkyloxy group, N-C_Three-C
₆Cycloalkylcarbamoyl group and N, N-di-C_Three−
C₆Select from the group consisting of cycloalkylcarbamoyl groups
Substituent, isoxazolyl group, isothiazolyl
Group, imidazolyl group, oxazolyl group, oxadiazoli
Group, thiazolyl group, thiadiazolyl group, thienyl group,
Triazolyl group, pyridyl group, pyrazinyl group, pyrimidi
Nil group, pyridazinyl group, pyrazolyl group, pyrrolyl group,
Pyranyl group, furyl group, imidazolidinyl group, imidazo
Linyl group, tetrahydrofuranyl group, pyrazolidinyl
Group, pyrazolinyl group, piperazinyl group, piperidinyl
Group, pyrrolidinyl group, pyrrolinyl group and morpholino group
A 5- or 6-membered heterocyclic group selected from the group consisting of
Quinolyl group, isoindolyl group, indazolyl group,
Drill group, ethylenedioxyphenyl group, carbazolyl
Group, quinazolinyl group, quinoxalinyl group, quinolizinyl
Group, quinolyl group, cumaronyl group, chromenyl group, phena
Suridinyl group, phenanthrolinyl group, dibenzofura
Nil group, dibenzothiophenyl group, cinnolinyl group,
Onaphthenyl group, naphthyridinyl group, phenazinyl group,
Phenaxazinyl, benzimidazolyl, benzoo
Xazolyl group, benzothiazolyl group, benzotriazolyl group
Group, benzofuranyl group and methylenedioxyphenyl
Nitrogen, oxygen and sulfur selected from the group consisting of
A heteroatom selected from the group consisting of yellow atoms
1 to 3 cyclic heteroaromatic ring groups having 1 to 5
And the heterocyclic group or the heteroaromatic ring group is substituted with N-
C₁-C_TenAlkylcarbamoyl group, NC₁-C_TenAl
Quilthiocarbamoyl, thiocarbonyl, and car
A substituent selected from the group consisting of a bonyl group;
Straight-chain saturated C which may be substituted with₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic group, branched unsaturated C₁-C₉Aliphatic groups,
C₁-C₆Alkoxy group and C₁-C₆From the alkylthio group
Selected from the group consisting of substituents selected from the group consisting of
Aryl which may have one or more substituents
Group, adamantyl group, anthryl group, indenyl group,
Select from the group consisting of rubornyl group and phenanthryl group
1- to 3-cyclic C₇-C_FifteenA carbon aromatic ring group or a
Soxazolyl group, isothiazolyl group, imidazolyl
Group, oxazolyl group, oxadiazolyl group, thiazolyl
Group, thiadiazolyl group, thienyl group, triazolyl group,
Pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazi
Nil, pyrazolyl, pyrrolyl, pyranyl, free
Group, imidazolidinyl group, imidazolinyl group, tetra
Hydrofuranyl group, pyrazolidinyl group, pyrazolinyl
Group, piperazinyl group, piperidinyl group, pyrrolidinyl
Selected from the group consisting of a group, a pyrrolinyl group and a morpholino group
5- or 6-membered heterocyclic group or isoquinolyl
Group, isoindolyl group, indazolyl group, indolyl group
Group, ethylenedioxyphenyl group, carbazolyl group,
Nazolinyl group, quinoxalinyl group, quinolizinyl group,
Noryl group, coumalonyl group, chromenyl group, phenanthry
Dinyl group, phenanthrolinyl group, dibenzofuranyl
Group, dibenzothiophenyl group, cinnolinyl group, thiona
Phenyl, naphthyridinyl, phenazinyl,
Naxazinyl group, benzimidazolyl group, benzoxa
Zolyl, benzothiazolyl, benzotriazolyl
Group, benzofuranyl group and methylenedioxyphenyl group
Nitrogen, oxygen and sulfur selected from the group consisting of
Heteroatoms selected from the group consisting of atoms per ring system
1 to 5 monocyclic to 3 cyclic heteroaromatic ring groups or
The aryl group, the carbon aromatic ring group, the heterocyclic group or
Straight-chain saturated C which may be substituted with the heteroaromatic group
₁-C₉Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups, branched
Chain saturation C₁-C₉Aliphatic or branched unsaturated C
₁-C₉Represents an aliphatic group or the like, or (4a) R^ThreeAnd R
^FourTogether form a linear saturated C₁-C₉Aliphatic group, straight
Chain unsaturation C₁-C₉Aliphatic groups, branched saturated C₁-C₉Fat
Aliphatic or branched unsaturated C₁-C₉Aliphatic group or
5- or 6-membered saturated carbocyclic group or 5- or 6-membered
And the like when an unsaturated carbocycle is formed (R^3aPassing
And R^4a), Especially R^ThreeAnd R^FourAre the same or different, (1
b) For example, hydrogen atom, azide group, amidino group, amino
Group, carbamoyl group, carboxyl group, guanidino group,
Cyano group, sulfamoyl group, sulfo group, nitro group,
Rogen atom, hydroxy group, formyl group, cyclic saturated C
_Three-C₉Aliphatic group, cyclic unsaturated C_Three-C₉Aliphatic group, N-
C₁-C₆Alkylamino group, N-C₁-C_TenAlkylka
Rubamoyl group, C₁-C₆Alkylthio group and C₁-C₆A
Lucoxy group, C₁-C₆Consists of an alkoxycarbonyl group
(2b) for example a substituent selected from the group
Optionally substituted straight-chain saturated C₁-C₉Aliphatic groups,
Linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉
Aliphatic groups and branched unsaturated C₁-C₉From aliphatic groups
(3b) for example, a substituent selected from the group
Group, carbamoyl group, carboxyl group, nitro group, halo
Gen atom, hydroxy group, aralkylcarbonyl group, N
Aralkylcarbamoyl, aryl, aroyl
Group, C_Two-C₆Alkanoyl group, NC₁-C₆Alkyria
Mino group, NC₁-C_TenAlkylcarbamoyl group, N-
C₁-C_TenAlkylthiocarbamoyl group, N, N-di-
C₁-C_TenAlkylcarbamoyl group, N, N-di-C₁−
C_TenAlkylthiocarbamoyl group, NC_Two-C₆Arche
Nylcarbamoyl group, N, N-di-C_Two-C₆Alkenyl
Carbamoyl group, N-amino C₁-C_TenAlkyl carba
Moyl group, NC₁-C₆Alkoxy C₁-C_TenAlkyl
Carbamoyl group, NC₁-C₆Alkoxycarbonyl C
₁-C_TenAlkylcarbamoyl group, C₁-C₆Alkoxy
Group, amino C₁-C₆Alkoxycarbonyl group, N-C_Three
-C₆Cycloalkylamino group, N, N-di-C_Three-C₆
Cycloalkylamino group, C_Three-C₆Cycloalkyloxy
Group, N-C_Three-C₆A cycloalkylcarbamoyl group and
N, N-di-C_Three-C₆Is it a cycloalkylcarbamoyl group
Substituents, thienyl groups, pyridyls selected from the group consisting of
Group, pyrazinyl group, pyrimidinyl group, furyl group, tetra
Select from the group consisting of hydrofuranyl and morpholino groups
5- or 6-membered heterocyclic group, ethylenedioxyphene
Nil group, dibenzofuranyl group, dibenzothiophenyl group
And methylenedioxyphenyl groups
Selected from the group consisting of nitrogen, oxygen and sulfur atoms
1 to 5 heteroatoms per ring system
To a tricyclic heteroaromatic ring group and the heterocyclic group or the
N-C substituted with a heteroaromatic group₁-C_TenAlkyl cal
Bamoyl group, NC₁-C _TenAlkylthiocarbamoyl
Group consisting of a carbonyl group, a thiocarbonyl group and a carbonyl group
Substituents selected from the above, and even if
Good, straight-chain saturated C ₁-C₉Aliphatic group, linear unsaturated C₁
-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic groups, branched
Chain unsaturated C₁-C₉Aliphatic group and C₁-C₆Alkoxy
Selected from the group consisting of substituents selected from the group consisting of groups
Having one or more substituents
Group consisting of a thiol group, anthryl group and a phenanthryl group
A mono- to tricyclic C selected from₇-C_FifteenCarbon aromatic ring
Group or thienyl group, pyridyl group, pyrazinyl group, pirimi
Dinyl group, furyl group, tetrahydrofuranyl group and mol
5- or 6-membered hetero selected from the group consisting of holino groups
Ring group or ethylenedioxyphenyl group, dibenzof
Ranyl group, dibenzothiophenyl group and methylenedioxy
Nitrogen atom or oxygen selected from the group consisting of cyphenyl groups
A heteroatom selected from the group consisting of
1 to 5 heterocyclic groups having 1 to 5 rings per ring system
An aromatic ring group or the aryl group, the carbon aromatic ring group, the hetero
May be substituted with a ring group or the heteroaromatic ring group,
Linear saturated C₁-C₉Aliphatic group, linear unsaturated C₁-C₉Fat
Aliphatic group, branched saturated C₁-C₉Aliphatic group or branched chain
Of unsaturated C₁-C₉Represents an aliphatic group, or (4b)
R^ThreeAnd R^FourTogether form a linear unsaturated C₁-C₉Fat
When forming an aliphatic group or a 5- or 6-membered saturated carbocyclic group
Equality (R^3bAnd R^4b) Are preferred.

X ₁ is, for example, an oxygen atom, a sulfur atom or a group: NR ⁵ (where R ⁵ is a hydrogen atom, a halogen atom, a hydroxy group, an N—C ₁ -C ₆ alkylsulfonylamino group, a C _1- A substituent selected from the group consisting of a C ₆ alkoxy group, a C ₁ -C ₆ alkoxycarbonyl group, a C ₂ -C ₆ alkanoyl group, a carbamoyl group, and an N—C ₁ -C ₁₀ alkylcarbamoyl group, or a substituent with the substituent A straight-chain saturated C ₁ -C ₉ aliphatic group, a straight-chain unsaturated C
_A C ₁ -C ₉ aliphatic group, a branched saturated C ₁ -C ₉ aliphatic group or a branched unsaturated C ₁ -C ₉ aliphatic group). Atom or group: NR
^5a (where R ^5a is a hydrogen atom, a halogen atom,
Hydroxy group, N-C ₁ -C ₆ alkylsulfonylamino group, C ₁ -C ₆ alkoxy group, C ₁ -C ₆ alkoxycarbonyl group, C ₂ -C ₆ alkanoyl group, a carbamoyl group, and N-C ₁ -C ₁₀ A substituent selected from the group consisting of an alkylcarbamoyl group or a linear saturated C ₁ -C ₉ aliphatic group which may be substituted with the substituent, or a linear unsaturated C _1-
A C ₉ aliphatic group, a branched saturated C ₁ -C ₉ aliphatic group or a branched unsaturated C ₁ -C ₉ aliphatic group), and the like, and particularly an oxygen atom or group: NR ^5b (where R ^5b represents a hydrogen atom, a hydroxy group, a C ₁ -C ₆ alkoxy group, a C ₁ -C ₆ alkoxycarbonyl group, and an N—C ₁
-C ₁₀ substituent or the selected from the group consisting of an alkylcarbamoyl group may be substituted with a substituent, a saturated C ₁ -C ₉ aliphatic groups, straight-chain, straight-chain unsaturated C ₁ -C ₉ Aliphatic groups, branched saturated C ₁ -C ₉ aliphatic groups or branched unsaturated C ₁ -C ₉ aliphatic groups), and the like.

X ₂ represents, for example, an oxygen atom or a sulfur atom.

Y is, for example, an oxygen atom, a sulfur atom or a group:
NR^FiveOr group: CR⁶R⁷(Where R⁶Is the water
Element atom, halogen atom, hydroxy group, N-C₁-C₆A
Rukylsulfonylamino group, C₁-C₆Alkoxy group, C
₁-C₆Alkoxycarbonyl group, C_Two-C₆Alkanoyl
Group, carbamoyl group and N-C₁-C_TenAlkyl carba
A substituent selected from the group consisting of moyl groups or the substituent
Linear saturated C which may be substituted with₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic or branched unsaturated C₁-C₉fat
Group, R⁷Is a hydrogen atom or C₁-C₆Represents an alkyl group
Then R^FiveHas the meaning described above), etc.
For example, oxygen atom, sulfur atom or group: NR^5aOr group: C
R^6aR^7a(Where R^6aIs a hydrogen atom, a halogen
Atom, hydroxy group, N-C₁-C₆Alkylsulfonyl
Amino group, C₁-C₆Alkoxy group, C₁-C₆Alkoxy
Carbonyl group, C_Two-C₆Alkanoyl group, carbamoyl
Group and NC₁-C_TenConsists of an alkylcarbamoyl group
A substituent selected from the group or substituted with the substituent,
A straight-chain saturated C₁-C₉Aliphatic group, linear unsaturated C
₁-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group
Is a branched unsaturated C₁-C₉Aliphatic group, R^7aIs a hydrogen source
Child or C₁-C₆Represents an alkyl group;^5aMeans the above
And the like, and particularly, for example, oxygen atom, sulfur atom
Child or group: CR^6bR^7b(Where R ^6bIs a hydrogen source
Child, hydroxy group, C₁-C₆Alkoxy group, C₁-C₆A
Alkoxycarbonyl group and N-C₁-C_TenAlkyl cal
A substituent selected from the group consisting of a bamoyl group or the substituent
Straight-chain saturated C which may be substituted with₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic or branched unsaturated C₁-C₉fat
Group, R^7bIs a hydrogen atom or C₁-C₆Represents an alkyl group
Are preferred.

Z is, for example, a fused aryl group, acenaphthylenyl group, adamantyl group, anthryl group, indanyl group, indenyl group, C ₆ -C ₈ cycloalkanyl group, C ₆
-C ₈ cycloalkadienyl group, C ₆ -C ₈ cycloalkenyl group, a norbornyl group, C ₆ -C ₁₅ condensation of 2 to be selected from the group consisting of a phenanthryl group and Fureoreniru group tricyclic saturated or unsaturated Carbocyclic group or isoquinolyl group, isoindolyl group, indazolyl group, indolyl group, indolizinyl group, ethylenedioxyphenyl group, quinazolinyl group, quinoxalinyl group, quinolizinyl group, quinolyl group, coumalonyl group, chromenyl group, thionaphthenyl group, naphthyridinyl group, pyridyl Group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, pyranyl group,
Phthalazyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, benzotriazolyl group,
A 6-membered heterocyclic group selected from the group consisting of a benzofuranyl group and a methylenedioxyphenyl group, or a heterocyclic group having 1 to 5 heteroatoms per ring system selected from the group consisting of nitrogen, oxygen and sulfur And a tricyclic fused heteroaromatic group and the like. Among them, for example, a fused aryl group, an adamantyl group, an anthryl group, an indanyl group, an indenyl group, a C ₆ -C ₈ cycloalkanyl group, a C ₆
-C ₈ cycloalkadienyl group, C ₆ -C ₈ cycloalkenyl group, C ₆ -C ₁₅ condensed carbocyclic group having 2 to be selected from the group consisting of a norbornyl group, and a phenanthryl group tricyclic saturated or unsaturated Or ethylenedioxyphenyl group, pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, benzotriazolyl group,
A 6-membered heterocyclic group selected from the group consisting of a benzofuranyl group and a methylenedioxyphenyl group, or a heterocyclic group having 1 to 5 heteroatoms per ring system selected from the group consisting of nitrogen, oxygen and sulfur tricyclic condensed heteroaromatic ring group, etc. are preferred, for example, fused aryl group, an anthryl group, C ₆ -C ₈ cycloalkanyl group, C ₆ -C ₈ cycloalkadienyl group and C ₆ -C ₈ cycloalkenyl C ₆ -C ₁₅ condensed carbocyclic group or an ethylene dioxy phenyl group of 2 to be selected from the group consisting of group tricyclic saturated or unsaturated, pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, and methylenedioxy A 6-membered heterocyclic group selected from the group consisting of a phenyl group or a group selected from the group consisting of nitrogen, oxygen and sulfur 2 to be five Yes to 1 per ring system heteroatom such as tricyclic condensed heteroaromatic ring groups are preferred.

Next, the compound of the general formula [I] of the present invention will be described.

Formula [I]

Embedded image [Wherein R, R ¹ , R ² , R ³ , R ⁴ , X ₁ , X ₂ , Y and Z
Has the above-mentioned meaning], and preferred compounds are those represented by the general formula [Ia]

Embedded image[Wherein, R^aRepresents an amino group, a carbamoyl group, a carbamo
Ylamino group, carbamoyloxy group, carboxyl
Group, nitro group, halogen atom, hydroxy group, cyclic
Sum C_Three-C₉Aliphatic group, cyclic unsaturated C_Three-C₉Aliphatic groups,
Aralkyl group, N-aralkylamino group, aralkyl group
Xy group, aralkylcarbonyl group, N-aralkylcal
Bamoyl group, aryl group, N-arylamino group, ant
Oxy, arylsulfonyl, arylsulfo
Nyloxy group, N-arylsulfonylamino group, N-
Arylsulfonylamino C₁-C_TenAlkylamino
Group, N-arylsulfonylamino C₁-C_TenAlkyl
Carbamoyl group, N-arylsulfonylamino C₁−
C₆Alkoxycarbonyl group, arylsulfamoyl
Group, arylsulfamoyloxy group, N-aryls
Rufamoyl C₁-C_TenAlkyl carbamoyl group, ant
Rusulfamoyl C₁-C₆An alkoxycarbonyl group,
N-arylcarbamoyl group, aroyl group, alloxy
Group, N- (N-aroylamino) C₁-C_TenAlkylka
Rubamoyl group, N-aroylamino C₁-C_TenAlkoki
Cicarbonyl group, C_Two-C₆Alkanoyl group, NC_Two−
C₆Alkanoylamino group, NC₁-C₆Alkylam
No group, N, N-di-C₁-C₆Alkylamino group, N-C
₁-C_TenAlkylcarbamoyl group, NC₁-C_TenArchi
Luthiocarbamoyl group, N, N-di-C₁-C_TenArchi
Rucarbamoyl group, N, N-di-C₁-C_TenAlkyl
Ocarbamoyl group, NC_Two-C₆Alkenylcarbamoy
Group, N, N-di-C_Two-C₆Alkenylcarbamoyl
Group, N-amino C₁-C_TenAlkylcarbamoyl group, N
-C₁-C₆Alkoxy C₁-C_TenAlkyl carbamoyl
Group, NC₁-C₆Alkoxycarbonyl C₁-C_TenAl
Kill carbamoyl group, NC₁-C₆Alkoxycarboni
Lumino C₁-C_TenAlkylcarbamoyl group, NC₁−
C₆Alkoxycarbonylamino C₁-C₆Alkoxyka
Rubonyl group, C₁-C₆Alkylthio group, C₁-C₆Archi
Rusulfinyl group, C₁-C₆Alkylsulfonyl group, N
-C₁-C₆Alkylsulfonylamino group, C₁-C₆Al
Coxy group, C₁-C₆Alkoxycarbonyl group, amino
C₁-C₆Alkoxycarbonyl group, N-C_Three-C₆Cyclo
Alkylamino group, N, N-di-C_Three-C₆Cycloalkyl
Ruamino group, C_Three-C₆Cycloalkyloxy group, N-
C_Three-C₆Cycloalkylcarbamoyl group and N, N-di
-C_Three-C₆Group consisting of cycloalkylcarbamoyl groups
Selected substituent, isoxazolyl group, isothiazo
Ryl group, imidazolyl group, oxazolyl group, oxadia
Zolyl, thiazolyl, thiadiazolyl, thienyl
Group, triazolyl group, pyridyl group, pyrazinyl group, pyriyl group
Midinyl group, pyridazinyl group, pyrazolyl group, pyrrolyl
Group, pyranyl group, furyl group, imidazolidinyl group, imi
Dazolinyl group, tetrahydrofuranyl group, pyrazolidini
, Pyrazolinyl, piperazinyl, piperidinyl
Group, pyrrolidinyl group, pyrrolinyl group and morpholino group
A 5- or 6-membered heterocyclic group selected from the group consisting of
Quinolyl group, isoindolyl group, indazolyl group,
Drill group, ethylenedioxyphenyl group, carbazolyl
Group, quinazolinyl group, quinoxalinyl group, quinolizinyl
Group, quinolyl group, cumaronyl group, chromenyl group, phena
Suridinyl group, phenanthrolinyl group, dibenzofura
Nil group, dibenzothiophenyl group, cinnolinyl group,
Onaphthenyl group, naphthyridinyl group, phenazinyl group,
Phenaxazinyl, benzimidazolyl, benzoo
Xazolyl group, benzothiazolyl group, benzotriazolyl group
Group, benzofuranyl group and methylenedioxyphenyl
Nitrogen, oxygen and sulfur selected from the group consisting of
A heteroatom selected from the group consisting of yellow atoms
1 to 3 cyclic heteroaromatic ring groups having 1 to 5
And the heterocyclic group or the heteroaromatic ring group is substituted with N-
C₁-C_TenAlkylcarbamoyl group, NC₁-C_TenAl
Quilthiocarbamoyl, thiocarbonyl, and car
A substituent selected from the group consisting of a bonyl group;
Straight-chain saturated C which may be substituted with₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic group, branched unsaturated C₁-C₉Aliphatic groups,
C₁-C₆Alkoxy group and C₁-C₆From the alkylthio group
Selected from the group consisting of substituents selected from the group consisting of
Aryl which may have one or more substituents
Group, adamantyl group, anthryl group, indenyl group,
Select from the group consisting of rubornyl group and phenanthryl group
1- to 3-cyclic C₇-C_FifteenA carbon aromatic ring group or a
Soxazolyl group, isothiazolyl group, imidazolyl
Group, oxazolyl group, oxadiazolyl group, thiazolyl
Group, thiadiazolyl group, thienyl group, triazolyl group,
Pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazi
Nil, pyrazolyl, pyrrolyl, pyranyl, free
Group, imidazolidinyl group, imidazolinyl group, tetra
Hydrofuranyl group, pyrazolidinyl group, pyrazolinyl
Group, piperazinyl group, piperidinyl group, pyrrolidinyl
Selected from the group consisting of a group, a pyrrolinyl group and a morpholino group
5- or 6-membered heterocyclic group or isoquinolyl
Group, isoindolyl group, indazolyl group, indolyl group
Group, ethylenedioxyphenyl group, carbazolyl group,
Nazolinyl group, quinoxalinyl group, quinolizinyl group,
Noryl group, coumalonyl group, chromenyl group, phenanthry
Dinyl group, phenanthrolinyl group, dibenzofuranyl
Group, dibenzothiophenyl group, cinnolinyl group, thiona
Phenyl, naphthyridinyl, phenazinyl,
Naxazinyl group, benzimidazolyl group, benzoxa
Zolyl, benzothiazolyl, benzotriazolyl
Group, benzofuranyl group and methylenedioxyphenyl group
Nitrogen, oxygen and sulfur selected from the group consisting of
Heteroatoms selected from the group consisting of atoms per ring system
A mono- to tricyclic heteroaromatic group having 1 to 5 R
^1aAnd R^2aIs the same or different and is a hydrogen atom, amino
Group, carboxyl group, cyano group, sulfamoyl group,
Ruho, nitro, halogen, hydroxy, phor
Mill group, cyclic saturated C_Three-C₉Aliphatic group, cyclic unsaturated C
_Three-C₉Aliphatic group, aralkyl group, aryl group, N-ali
Amino group, aryloxy group, C_Two-C₆Arcanoy
Group, N-C_Two-C₆Alkanoylamino group, aroyl
Group, NC₁-C₆Alkylamino group, N, N-di-C₁
-C₆Alkylamino group, N-C₁-C_TenAlkyl carba
Moyl group, NC₁-C₆Alkylsulfamoyl group, C
₁-C₆Alkylsulfinyl group, C₁-C₆Alkylsul
Honyl group, N-C₁-C₆Alkylsulfonylamino group,
C₁-C₆Alkoxy group, C₁-C₆Alkoxycarbonyl
Group, NC_Three-C₆Cycloalkylamino group, C_Three-C₆Shi
Chloroalkyloxy group and N-C_Three-C₆Cycloalkyl
A substituent selected from the group consisting of a carbamoyl group or
Straight-chain saturated C which may be substituted with a substituent₁-C₉Fat
Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups, branched chain saturation
C₁-C₉Aliphatic group, branched unsaturated C₁-C₉Aliphatic group
Or C ₁-C₆Alkoxy group, R^3aAnd R^4aAre the same
Or differently, a hydrogen atom, an azide group, an amidino group,
Group, carbamoyl group, carbamoylamino group, carb
Moyloxy group, carboxyl group, guanidino group, shea
, Sulfamoyl, sulfo, nitro, halogen
Atom, hydroxy group, formyl group, formylamino
Group, cyclic saturated C_Three-C₉Aliphatic group, cyclic unsaturated C_Three−
C₉Aliphatic group, C_Two-C₆Alkanoyl group, NC₁-C₆
Alkylamino group, N-C₁-C_TenAlkyl carbamoy
Group, C₁-C₆Alkylthio group, N-C₁-C₆Alkyl
Sulfamoyl group, C₁-C₆Alkylsulfinyl group,
C₁-C₆Alkylsulfonyl group, NC₁-C₆Alkyl
Sulfonylamino group, C₁-C₆Alkoxy group, C₁-C₆
Alkoxycarbonyl group and N-C_Three-C₆Cycloalkyl
A substituent selected from the group consisting of
Linear saturated C which may be substituted with₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic groups and branched unsaturated C₁-C₉Aliphatic group
A substituent amino group selected from the group consisting of: carbamoy
Carbamoylamino group, carbamoyloxy group,
Carboxyl group, nitro group, halogen atom, hydroxy
Group, cyclic saturated C_Three-C₉Aliphatic group, cyclic unsaturated C _Three−
C₉Aliphatic group, aralkyl group, N-aralkylamino
Group, aralkyloxy group, aralkylcarbonyl group, N
-Aralkylcarbamoyl group, aryl group, N-aryl
Amino group, aryloxy group, arylsulfonyl
Group, arylsulfonyloxy group, N-arylsulfo
Nylamino group, N-arylsulfonylamino C₁-C
_TenAlkylamino group, N-arylsulfonylamino C
₁-C_TenAlkylcarbamoyl group, N-arylsulfo
Nilamino C₁-C₆Alkoxycarbonyl group, aryl
A sulfamoyl group, an arylsulfamoyloxy group,
N-arylsulfamoyl C₁-C_TenAlkyl carba
Moyl group, arylsulfamoyl C₁-C₆Alkoxy
Carbonyl group, N-arylcarbamoyl group, aroyl
Group, alloxy group, N- (N-aroylamino) C₁-C
_TenAlkylcarbamoyl group, N-aroylamino C₁−
C_TenAlkoxycarbonyl group, C_Two-C₆Alkanoyl
Group, NC_Two-C₆Alkanoylamino group, NC₁-C₆
Alkylamino group, N, N-di-C₁-C₆Alkylam
No group, NC₁-C_TenAlkylcarbamoyl group, NC₁
-C_TenAlkylthiocarbamoyl group, N, N-di-C₁
-C_TenAlkylcarbamoyl group, N, N-di-C₁-C
_TenAlkylthiocarbamoyl group, NC_Two-C₆Alkene
Rucarbamoyl group, N, N-di-C_Two-C₆Alkenylka
Rubamoyl group, N-amino C₁-C_TenAlkyl carbamo
Il group, N-C₁-C₆Alkoxy C₁-C_TenAlkylka
Rubamoyl group, NC₁-C₆Alkoxycarbonyl C₁
-C _TenAlkylcarbamoyl group, NC₁-C₆Alkoki
Cicarbonylamino C₁-C_{1 0}Alkyl carbamoyl
Group, NC₁-C₆Alkoxycarbonylamino C₁-C₆
Alkoxycarbonyl group, C₁-C₆Alkylthio group, C
₁-C₆Alkylsulfinyl group, C₁-C₆Alkylsul
Honyl group, N-C₁-C₆Alkylsulfonylamino group,
C₁-C₆Alkoxy group, C₁-C₆Alkoxycarbonyl
Group, amino C₁-C₆Alkoxycarbonyl group, N-C_Three
-C₆Cycloalkylamino group, N, N-di-C_Three-C₆
Cycloalkylamino group, C_Three-C₆Cycloalkyl
Xy group, N-C_Three-C₆Cycloalkylcarbamoyl group and
And N, N-di-C_Three-C₆Cycloalkylcarbamoyl group
Isoxazolyl, a substituent selected from the group consisting of
Group, isothiazolyl group, imidazolyl group, oxazolyl
Group, oxadiazolyl group, thiazolyl group, thiadiazoli
Group, thienyl group, triazolyl group, pyridyl group, pyra
Dinyl group, pyrimidinyl group, pyridazinyl group, pyrazoly
, Pyrrolyl, pyranyl, furyl, imidazolyl
Dinyl group, imidazolinyl group, tetrahydrofuranyl
Group, pyrazolidinyl group, pyrazolinyl group, piperazinyl
Group, piperidinyl group, pyrrolidinyl group, pyrrolidinyl group and
And a 5- or 6-membered member selected from the group consisting of
Heterocyclic group, isoquinolyl group, isoindolyl group,
Dazolyl group, indolyl group, ethylenedioxyphenyl
Group, carbazolyl group, quinazolinyl group, quinoxalinyl
Group, quinolidinyl group, quinolyl group, coumalonyl group,
Menyl group, phenanthridinyl group, phenanthrolinyl
Group, dibenzofuranyl group, dibenzothiophenyl group,
Nonolinyl group, thionaphthenyl group, naphthyridinyl group,
Phenazinyl group, phenaxazinyl group, benzimidazo
Ryl group, benzoxazolyl group, benzothiazolyl group,
Benzotriazolyl group, benzofuranyl group and methylene
Nitrogen source selected from the group consisting of dioxyphenyl groups
Selected from the group consisting of oxygen, oxygen and sulfur
1 to 3 rings having 1 to 5 ring atoms per ring system
Heteroaromatic ring group and the heterocyclic group or the heteroaromatic ring
N—C substituted with a group₁-C_TenAlkyl carbamoyl
Group, NC₁-C_TenAlkylthiocarbamoyl group, thio
Selected from the group consisting of carbonyl groups and carbonyl groups
Substituents which may be substituted with the substituents,
Chain saturation C₁-C₉Aliphatic group, linear unsaturated C₁-C₉fat
Group, branched saturated C₁-C₉Aliphatic groups, branched chain unsaturation
C ₁-C₉Aliphatic group, C₁-C₆Alkoxy group and C₁−
C₆A substituent selected from the group consisting of alkylthio groups
Having one or more substituents selected from the group consisting of
Aryl, adamantyl, anthryl
Group, indenyl group, norbornyl group and phenanthryl
Mono- to tricyclic C selected from the group consisting of ₇-C
_FifteenCarbon aromatic ring group or isoxazolyl group, isothiazolyl
Group, imidazolyl group, oxazolyl group, oxadiazo
Ryl, thiazolyl, thiadiazolyl, thienyl
Group, triazolyl group, pyridyl group, pyrazinyl group, pyriyl group
Midinyl group, pyridazinyl group, pyrazolyl group, pyrrolyl
Group, pyranyl group, furyl group, imidazolidinyl group, imi
Dazolinyl group, tetrahydrofuranyl group, pyrazolidini
, Pyrazolinyl, piperazinyl, piperidinyl
Group, pyrrolidinyl group, pyrrolinyl group and morpholino group
A 5- or 6-membered heterocyclic group selected from the group consisting of
Is isoquinolyl, isoindolyl, indazolyl
Group, indolyl group, ethylenedioxyphenyl group,
Bazolyl group, quinazolinyl group, quinoxalinyl group, quino
Lysinyl group, quinolyl group, coumalonyl group, chromenyl
Group, phenanthridinyl group, phenanthrolinyl group,
Benzofuranyl group, dibenzothiophenyl group, Shinnori
Nyl, thionaphthenyl, naphthyridinyl, phena
Dinyl group, phenaxazinyl group, benzimidazolyl
Group, benzoxazolyl group, benzothiazolyl group, ben
Zotriazolyl, benzofuranyl and methylenedi
Nitrogen atom or acid selected from the group consisting of xylphenyl groups
Heteroatoms selected from the group consisting of elemental atoms and sulfur atoms
From 1 to 3 rings having 1 to 5 rings per ring system
An aromatic ring group or the aryl group, the carbon aromatic ring group,
Or a heterocyclic group.
Straight-chain saturated C₁-C₉Aliphatic group, linear unsaturated C₁−
C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group or
Branched unsaturated C₁-C ₉Represents an aliphatic group, or R^3a
And R^4aTogether form a linear saturated C₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic or branched unsaturated C₁-C₉fat
Group or 5- or 6-membered saturated carbocyclic group or 5 or less
Or a 6-membered unsaturated carbocyclic ring, X_1aIs an oxygen source
Child, sulfur atom or group: NR^5a(Where R^5aIs
Hydrogen atom, halogen atom, hydroxy group, N-C₁-C₆
Alkylsulfonylamino group, C₁-C₆An alkoxy group,
C₁-C₆Alkoxycarbonyl group, C_Two-C₆Arcanoy
Carbamoyl group and N-C ₁-C_TenAlkyl cal
A substituent selected from the group consisting of a bamoyl group or the substituent
Straight-chain saturated C which may be substituted with₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic or branched unsaturated C₁-C₉fat
Represents a group), X_2aIs an oxygen or sulfur atom, Y
_aIs an oxygen atom, a sulfur atom or a group: NR^5aOr group:
CR^6aR^7a(Where R^6aIs a hydrogen atom, halogen
Atom, hydroxy group, N-C₁-C₆Alkylsulfoni
Ruamino group, C₁-C₆Alkoxy group, C₁-C₆Alkoki
Cicarbonyl group, C_Two-C₆Alkanoyl group, carbamoy
And N-C₁-C_TenAlkyl carbamoyl group
Or a substituent selected from the group consisting of
A linear saturated C₁-C₉Aliphatic group, linear unsaturated
C₁-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group
Or branched, unsaturated C₁-C₉Aliphatic group, R^7aIs hydrogen
Atom or C₁-C₆Represents an alkyl group;^5aMeans the above
Taste), Z_aIs a fused aryl group, adamantyl
Group, anthryl group, indanyl group, indenyl group, C₆
-C₈Cycloalkanyl group, C₆-C₈Cycloalkadie
Nyl group, C₆-C₈Cycloalkenyl group, norbornyl group
2 selected from the group consisting of and phenanthryl groups
Tricyclic saturated or unsaturated C₆-C_FifteenFused carbocycle
Group or ethylenedioxyphenyl group, pyridyl group, pyra
Dinyl, pyrimidinyl, pyridazinyl, benzoy
Midazolyl group, benzoxazolyl group, benzothiazoly
Group, benzotriazolyl group, benzofuranyl group and
6 selected from the group consisting of tylenedioxyphenyl groups
Membered heterocyclic group or nitrogen atom, oxygen atom and sulfur atom
One heteroatom selected from the group consisting of
And 5 to 5 bicyclic or 3-cyclic fused heteroaromatic groups
In particular, a compound represented by the general formula [Ib]

Embedded image[Wherein, R^bRepresents an amino group, a carbamoyl group,
Sil group, nitro group, halogen atom, hydroxy group, ara
Alkylcarbonyl group, N-aralkylcarbamoyl group,
Aryl group, aroyl group, C_Two-C₆Alkanoyl group, N
-C₁-C₆Alkylamino group, N-C₁-C_TenAlkyl
Carbamoyl group, NC₁-C_TenAlkylthiocarbamo
Yl group, N, N-di-C₁-C_TenAlkyl carbamoyl
Group, N, N-di-C₁-C_TenAlkylthiocarbamoyl
Group, NC_Two-C₆Alkenylcarbamoyl group, N, N-
Di-C_Two-C₆Alkenylcarbamoyl group, N-amino C
₁-C_{1 0}Alkylcarbamoyl group, NC₁-C₆Arco
Kishi C₁-C_TenAlkylcarbamoyl group, NC₁-C₆
Alkoxycarbonyl C₁-C_TenAlkyl carbamoyl
Group, C₁-C₆Alkoxy group, amino C₁-C₆Alkoki
Cicarbonyl group, N-C_Three-C₆Cycloalkylamino
Group, N, N-di-C_Three-C₆Cycloalkylamino group, C
_Three-C₆Cycloalkyloxy group, N-C_Three-C₆Cycloa
Alkylcarbamoyl group and N, N-di-C_Three-C₆Cyclo
Substitution selected from the group consisting of alkylcarbamoyl groups
Group, thienyl group, pyridyl group, pyrazinyl group, pyrimidi
Nyl, furyl, tetrahydrofuranyl and morpho
5- or 6-membered heterocycle selected from the group consisting of lino groups
Group, ethylenedioxyphenyl group, dibenzofuranyl
Group, dibenzothiophenyl group and methylenedioxyphene
A nitrogen atom, an oxygen atom and a nitrogen atom selected from the group consisting of
A heteroatom selected from the group consisting of
1 to 5 mono- to 3-cyclic heteroaromatic rings per 1 to 5
Group and the heterocyclic group or the heteroaromatic ring group is substituted,
N-C₁-C_TenAlkylcarbamoyl group, NC₁-C _Ten
Alkylthiocarbamoyl group, thiocarbonyl group and
A substituent selected from the group consisting of a carbonyl group;
Straight-chain saturated C which may be substituted with a substituent ₁-C₉Fat
Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups, branched chain saturation
C₁-C₉Aliphatic group, branched unsaturated C₁-C₉Aliphatic group
And C₁-C₆A position selected from the group consisting of alkoxy groups
One or more substituents selected from the group consisting of
Aryl group, anthryl group and
Mono- to tricyclic selected from the group consisting of nanthryl groups
C₇-C_FifteenCarbon aromatic ring group or thienyl group, pyridyl
Group, pyrazinyl group, pyrimidinyl group, furyl group, tetra
Select from the group consisting of hydrofuranyl and morpholino groups
5- or 6-membered heterocyclic group or ethylene dioxy
Cyphenyl group, dibenzofuranyl group, dibenzothiophene
From the group consisting of a nyl group and a methylenedioxyphenyl group
The group consisting of selected nitrogen, oxygen and sulfur atoms
1 to 5 hetero atoms per ring system
A mono- to tricyclic heteroaromatic group, R^1bAnd R^2bIs
Same or different, hydrogen atom, amino group, nitro group,
Logen atom, hydroxy group, aryl group, N-aryl
Amino group, N-C₁-C₆Alkylamino group, N, N-di
-C₁-C₆Alkylamino group, N-C₁-C_TenAlkyl
Carbamoyl group, C₁-C₆Alkoxy group, C₁-C₆Al
Coxycarbonyl group and N-C_Three-C₆Cycloalkylua
A substituent selected from the group consisting of a mino group or
Optionally substituted straight-chain saturated C₁-C₉Aliphatic groups,
Linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉
Aliphatic group, branched unsaturated C₁-C₉Aliphatic group or
C₁-C₆Alkoxy group, R^3bAnd R^4bAre the same or different
Are hydrogen, azide, amidino, amino,
Rubamoyl group, carboxyl group, guanidino group, cyano
Group, sulfamoyl group, sulfo group, nitro group, halogen
Atom, hydroxy group, formyl group, cyclic saturated C_Three-C₉
Aliphatic group, cyclic unsaturated C_Three-C₉Aliphatic group, N-C₁−
C₆Alkylamino group, N-C₁-C_TenAlkyl carbamo
Il group, C₁-C₆Alkylthio group and C₁-C₆Alkoki
Si group, C₁-C₆From the group consisting of alkoxycarbonyl groups
Selected substituents, which may be substituted with the substituents,
Linear saturated C₁-C₉Aliphatic group, linear unsaturated C₁-C₉Fat
Aliphatic group, branched saturated C₁-C₉Aliphatic groups and branched chains
Saturated C₁-C₉Substitution selected from the group consisting of aliphatic groups
Group, amino group, carbamoyl group, carboxyl group, nitro
B group, halogen atom, hydroxy group, aralkyl carb
A nyl group, an N-aralkylcarbamoyl group, an aryl group,
Aroyl group, C_Two-C₆Alkanoyl group, NC₁-C₆A
Alkylamino group, N-C₁-C_TenAlkyl carbamoyl
Group, NC₁-C_TenAlkylthiocarbamoyl group, N,
N-di-C₁-C_TenAlkylcarbamoyl group, N, N-
Di-C₁-C_TenAlkylthiocarbamoyl group, NC_Two−
C₆Alkenylcarbamoyl group, N, N-di-C_Two-C₆
Alkenylcarbamoyl group, N-amino C₁-C_TenAl
Kill carbamoyl group, NC₁-C₆Alkoxy C₁-C
_TenAlkylcarbamoyl group, NC₁-C₆Alkoxyka
Rubonil C₁-C _TenAlkylcarbamoyl group, C₁-C₆
Alkoxy group, amino C₁-C₆Alkoxycarbonyl
Group, NC_Three-C₆Cycloalkylamino group, N, N-di
-C_Three-C₆Cycloalkylamino group, C_Three-C₆Cyclo
Alkyloxy group, N-C_Three-C₆Cycloalkyl carb
Moyl group and N, N-di-C_Three-C₆Cycloalkylcal
Thienyl, a substituent selected from the group consisting of a bamoyl group
Group, pyridyl group, pyrazinyl group, pyrimidinyl group, free
Group, tetrahydrofuranyl group and morpholino group.
A 5- or 6-membered heterocyclic group selected from the group consisting of
Dioxyphenyl group, dibenzofuranyl group, dibenzothi
Consists of an ophenyl group and a methylenedioxyphenyl group
From nitrogen, oxygen and sulfur selected from the group
A heteroatom selected from the group consisting of 1 to
5- to 5-cyclic heteroaromatic ring groups and
N-C substituted with a heterocyclic group or the heteroaromatic group₁-C_Ten
Alkylcarbamoyl group, NC₁-C_TenAlkylthio
Carbamoyl group, thiocarbonyl group and carbonyl group
And a substituent selected from the group consisting of
Straight-chain saturated C₁-C₉Aliphatic group, straight chain
Of unsaturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉fat
Group, branched chain unsaturated C₁-C₉Aliphatic group and C₁-C₆
Consisting of a substituent selected from the group consisting of alkoxy groups
Even if it has one or more substituents selected from the group
Good aryl, anthryl and phenanthryl groups
1- to 3-cyclic C selected from the group consisting of₇-C_Fifteen
Carbon aromatic ring group or thienyl group, pyridyl group, pyrazinyl
Group, pyrimidinyl group, furyl group, tetrahydrofuranyl
Or 6 selected from the group consisting of a group and a morpholino group
Membered heterocyclic group or ethylenedioxyphenyl group,
Dibenzofuranyl, dibenzothiophenyl and methyl
Nitrogen selected from the group consisting of rangeoxyphenyl groups
Atoms selected from the group consisting of atoms, oxygen atoms and sulfur atoms
1 to 3 having 1 to 5 telo atoms per ring system
Cyclic heteroaromatic ring group or the aryl group, the carbon aromatic ring
Substituted with the group, the heterocyclic group or the heteroaromatic group
A linear saturated C₁-C₉Aliphatic group, straight-chain unsaturated
Sum C₁-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group
Or branched unsaturated C₁-C₉Indicates an aliphatic group, or
Is R^3bAnd R^4bTogether form a linear unsaturated C₁−
C₉Forming an aliphatic group or a 5- or 6-membered saturated carbocyclic group
Then X_1bIs an oxygen atom or group: NR^5b(put it here,
R^5bIs a hydrogen atom, a hydroxy group, C₁-C₆Alkoxy
Group, C₁-C₆Alkoxycarbonyl group and N-C₁-C
_TenA position selected from the group consisting of alkylcarbamoyl groups
Linear group, which may be substituted or may be substituted with the substituent.
C₁-C₉Aliphatic group, linear unsaturated C₁-C₉Aliphatic group, minute
Branched saturated C₁-C₉Aliphatic or branched unsaturated
C₁-C₉An aliphatic group), X_2bIs an oxygen atom or sulfur
Atom, Y_bRepresents an oxygen atom, a sulfur atom or a group: CR^6bR^7b
(Where R^6bIs a hydrogen atom, a hydroxy group, C
₁-C₆Alkoxy group, C₁-C₆Alkoxycarbonyl group
And N-C₁-C_TenGroup consisting of alkylcarbamoyl groups
Or a substituent selected from the group consisting of
Good, straight-chain saturated C₁-C₉Aliphatic group, linear unsaturated C₁
-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group
Is a branched unsaturated C₁-C ₉Aliphatic group, R^7bIs a hydrogen source
Child or C₁-C₆An alkyl group), Z_bIs the condensation ant
Group, anthryl group, C₆-C₈Cycloalkanyl group,
C₆-C₈Cycloalkadienyl group and C₆-C₈Cycloa
Bicyclic to tricyclic selected from the group consisting of alkenyl groups
Saturated or unsaturated C₆-C_FifteenFused carbocyclic group or ethyl
Rangeoxyphenyl group, pyridyl group, pyrazinyl group,
Pyrimidinyl group, pyridazinyl group and methylenedioxy
6-membered heterocyclic group selected from the group consisting of phenyl groups
Or a group consisting of nitrogen, oxygen and sulfur
1 to 5 heteroatoms per ring system
A bicyclic or tricyclic fused heteroaromatic group.
Are preferred.

Further, the general formula

Embedded image[Wherein, R^cIs an aryl which may have a substituent
Group, 1 to 3 cyclic C₇-C_FifteenCarbon aromatic ring group (however,
Excludes aryl groups. ) Or 5- or 6-membered heterocyclic group
Or a group consisting of nitrogen, oxygen and sulfur
1 to 5 heteroatoms per ring system
A 1 to 3 ring heteroaromatic group (provided that the group is a 5- or 6-membered heteroaromatic group)
Excludes heterocyclic groups. ), R^1cAnd R^2cAre the same or different
Represents a hydrogen atom, an azide group, an amino group, carbamoyl
Group, carbamoylamino group, carbamoyloxy group,
Ruboxyl group, cyano group, sulfamoyl group, sulfo
Group, nitro group, halogen atom, hydroxy group, formyl
Group, formylamino group, cyclic saturated or unsaturated C
_Three-C₉Aliphatic group, aralkyl group, N-aralkylamino
Group, aralkyloxy group, aralkylcarbonyl group,
Reel group, N-arylamino group, aryloxy group,
Arylsulfonyl group, N-arylsulfonylamino
Group, N-arylsulfonylamino C₁-C₆Alkyria
Mino group, N-arylsulfonylamino C₁-C_TenAl
Kilcarbamoyl group, arylsulfonylamino C₁−
C₆Alkoxycarbonyl group, C_Two-C₆Alkanoyl
Group, NC_Two-C₆Alkanoylamino group, aroyl group,
N-aroylamino group, N-aroyl C₁-C₆Alkyl
Amino group, N-aroyl C₁-C_TenAlkyl carbamoy
Group, N-C ₁-C₆Alkylamino group, N, N-di-C
₁-C₆Alkylamino group, N-C₁-C_TenAlkyl cal
Bamoyl group, N, N-di-C₁-C_TenAlkyl carbamo
Il group, N-C₁-C₆Alkylsulfamoyl group, C₁
-C₆Alkylsulfinyl group, C₁-C₆Alkylsul
Honyl group, C₁-C₆Alkylthio group, C₁-C₆Alkoki
Si group, C₁-C₆Alkoxycarbonyl group, N-C_Three-C₆
Cycloalkylamino group, C_Three-C₆Cycloalkyloxy
Si group and NC_Three-C₆Is it a cycloalkylcarbamoyl group
Or a substituent selected from the group consisting of
Straight or branched chain saturated or unsaturated
Sum C₁-C₉Aliphatic group, N-C₁-C₆Alkylamino
Group, C₁-C₆Alkylthio group or C₁-C₆Alkoki
Si group, R^3cAnd R^4cAre the same or different and are a hydrogen atom,
Azide, amidino, amino, carbamoyl,
Rubamoylamino group, carbamoyloxy group, carboxy
A sil group, a guanidino group, a cyano group, a sulfamoyl group,
Sulfo group, nitro group, halogen atom, hydroxy group,
Lumyl group, formylamino group, cyclic saturated or unsaturated
Sum C_Three-C₉Aliphatic group, C_Two-C₆Alkanoyl group, N-
C_Two-C₆Alkanoylamino group, NC₁-C₆Alkyl
Amino group, N, N-di-C₁-C₆Alkylamino group, N
-C₁-C_TenAlkylcarbamoyl group, N, N-di-C
₁-C_TenAlkylcarbamoyl group, C₁-C₆Alkyl
O group, NC₁-C₆Alkylsulfamoyl group, C₁−
C₆Alkylsulfinyl group, C₁-C₆Alkylsulfo
Nyl group, C₁-C₆Alkoxy group, C₁-C₆Alkoxyka
Rubonyl group, N-C_Three-C₆Cycloalkylamino group, C
_Three-C₆Cycloalkyloxy group and N-C_Three-C₆Cyclo
Substitution selected from the group consisting of alkylcarbamoyl groups
Group, which may be substituted with the substituent, linear or branched
Branched or unsaturated C₁-C₉Aliphatic group, substituent
An aryl group, mono- to tricyclic C
₇-C_FifteenA carbon aromatic ring group (excluding an aryl group),
5- or 6-membered heterocyclic group or nitrogen atom, oxygen atom
1 heteroatom selected from the group consisting of
1 to 3 heterocyclic heteroaromatics having 1 to 5 ring systems
Aromatic ring group (excluding 5- or 6-membered heterocyclic group) or
The aryl group, the carbon aromatic ring group, the heterocyclic group or
Linear or linear, which may be substituted with the heteroaromatic group;
Branched or unsaturated C₁-C₉Indicates an aliphatic group
Or R^3cAnd R^4cAre together, linear or
Branched unsaturated C₁-C₉Aliphatic group or 5 or 6 members
Forms a saturated or unsaturated carbocyclic ring of_1cAnd X_2c
Are the same or different and are an oxygen atom or a sulfur atom, Y
_cIs an oxygen atom, a sulfur atom or a group: CHR^5cOr
Group: NR^5c(Where R^5cIs hydrogen atom, halogen
Atom, hydroxy group, C₁-C₆Alkoxy group, C_Two-C₆
Alkanoyl group, carbamoyl group and N-C₁-C_TenA
Substituents selected from the group consisting of alkylcarbamoyl groups
Or linear or branched, which may be substituted with the substituent.
Branched or unsaturated C₁-C₉Indicates an aliphatic group
S), Z_cIs a fused aryl group, bicyclic or tricyclic saturated
Or unsaturated C₆-C_FifteenCondensed carbocyclic group (however,
Excludes aryl groups. ) Or 6-membered heterocyclic group or nitrogen
Selected from the group consisting of elementary atoms, oxygen atoms and sulfur atoms
2 to 2 having 1 to 5 hetero atoms per ring system
Tricyclic fused heteroaromatic group (provided that a 6-membered heterocyclic group is
except. )]] Is a compound of the priority of the present application
A compound described in the basic application and having the general formula [I]
Are included in the compound.

Further, the compound of the general formula [I] has the general formula [I-1]

Embedded image [Wherein R, R ¹ , R ² , R ³ , R ⁴ and Z have the above-mentioned meanings], a general formula [I-2]

Embedded image [Wherein, R, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and Z have the same meanings], a general formula [I-3]

Embedded image [Wherein, X ′ ₁ is an oxygen atom or a group: N (R ⁵ ), X ′ ₂
Represents an oxygen atom or a sulfur atom, and R, R ¹ , R ² ,
R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and Z have the meaning given above. And a general formula [I-4]

Embedded image [Wherein, R, R ¹ , R ² , R ³ , R ⁴ and Z have the above-mentioned meanings. Preferred compounds among these compounds include compounds of the general formula [I-1], compounds of the general formula [I-3] and compounds of the general formula [I-4]. In particular, the compound of the general formula [I-1] and the compound of the general formula [I-3] are preferable.

Tables 1 to 45 show typical examples of the compounds of the general formula [I] of the present invention.

[0132]

[Table 1]

[0133]

[Table 2]

[0134]

[Table 3]

[0135]

[Table 4]

[0136]

[Table 5]

[0137]

[Table 6]

[0138]

[Table 7]

[0139]

[Table 8]

[0140]

[Table 9]

[0141]

[Table 10]

[0142]

[Table 11]

[0143]

[Table 12]

[0144]

[Table 13]

[0145]

[Table 14]

[0146]

[Table 15]

[0147]

[Table 16]

[0148]

[Table 17]

[0149]

[Table 18]

[0150]

[Table 19]

[0151]

[Table 20]

[0152]

[Table 21]

[0153]

[Table 22]

[0154]

[Table 23]

[0155]

[Table 24]

[0156]

[Table 25]

[0157]

[Table 26]

[0158]

[Table 27]

[0159]

[Table 28]

[0160]

[Table 29]

[0161]

[Table 30]

[0162]

[Table 31]

[0163]

[Table 32]

[0164]

[Table 33]

[0165]

[Table 34]

[0166]

[Table 35]

[0167]

[Table 36]

[0168]

[Table 37]

[0169]

[Table 38]

[0170]

[Table 39]

[0171]

[Table 40]

[0172]

[Table 41]

[0173]

[Table 42]

[0174]

[Table 43]

[0175]

[Table 44]

[0176]

[Table 45]

Of these compounds, suitable compounds are, for example, 1002, 1011, 1014, 1023, 102
4, 1033, 1035, 1037, 1046, 105
0, 1056, 1063, 1070, 1071, 107
2,1073,1074,1075,1076,107
7, 1078, 1081, 1082, 1083, 108
5, 1091, 1092, 1093, 1094, 109
5, 1096, 1098, 1102, 1104, 110
7, 1119, 1122, 1126, 1129, 113
0, 1137, 1150, 1152, 1182, 118
3, 1184, 1185, 1209, 1210, 121
9, 1251, 1257, 1268, 1276, 128
5, 1295, 1310, 1316, 1413, 142
6, 1429, 1430, 1432, 1433, 143
5, 1328, 1333, 1338, 1348, 135
6, 1364, 1371, 1380, 1383, 138
8, 1391, 1404, 2002, 2011, 202
3, 2024, 2050, 2056, 2074, 209
2, 2094, 2096, 2251, 2268, 228
5, 2295, 2316, 2333, 2348, 236
4, 2380, 2388, 2391, 2410, 242
2, 2456, 2462, 2467, 2468, 247
1, 2474, 2476, 3001, 3002, 300
7, 3011, 3014, 3015, 3020, 302
3, 3024, 3033, 3039, 3047, 305
0, 3051, 3056, 3057, 3058, 306
3, 3065, 3072, 3073, 3074, 307
6, 3078, 3082, 3083, 3092, 309
3, 3094, 3095, 3096, 3103, 310
4, 3107, 3117, 3226, 3241, 324
6, 3258, 3266, 3296, 3307, 331
9, 3412, 3418, 3464, 3468, 347
1, 3475, 3476, 3377, 3479, 348
0, 3481, 3482, 3484, 3485, 348
6, 3487, 3488, 3489, 3492, 349
3,3495,3499,3500,3501,350
5, 3506, 3509, 3510, 3511, 351
3, 3515, 3516, 3517, 3518, 400
2, 4011, 4023, 4024, 4050, 405
6, 4063, 4073, 4074, 4092, 409
4, 4096, 4257, 4276, 4295, 431
6, 4333, 4348, 4364, 4380, 438
8, 4404, 4410, 4416, 4417, 441
9, 4420, etc., of which, for example, 1002, 101
4, 1024, 1033, 1050, 1063, 107
1, 1072, 1073, 1074, 1075, 107
6, 1078, 1081, 1082, 1083, 109
1, 1092, 1093, 1094, 1095, 109
8, 1102, 1104, 1209, 1429, 143
0, 1432, 1433, 1435, 2002, 201
1, 2050, 2074, 2094, 2268, 229
5, 2333, 2364, 2380, 2391, 241
0, 2422, 2456, 2462, 2471, 300
1, 3002, 3007, 3011, 3014, 301
5, 3024, 3050, 3056, 3063, 307
4, 3078, 3082, 3092, 3093, 309
4, 3095, 3103, 3104, 3475, 347
6,3377, 3479, 3480, 3481, 348
2, 3488, 3489, 3499, 3511, 400
2, 4011, 4050, 4063, 4073, 407
4, 4094, 4257, 4295, 4333, 434
8, 4380, 4388, 4404 and the like are preferred.

In particular, 2- (4- (3-isopropyl-
2,5-dioxo-2,3-dihydro [1,3] oxazolo [2,3-a] isoindole-9 (5H) -yl) phenoxy) -N-propylacetamide (102
4), 9b- (3-Iodo-4-methoxyphenyl) -3-isopropyl [1,3] oxazolo [2,
3-a] isoindole-2,5 (3H, 9bH) -dione (compound of 1063), 2- (2-iodo-4-
(3-isopropyl-2,5-dioxo-2,3-dihydro [1,3] oxazolo [2,3-a] isoindole-9 (5H) -yl) phenoxy) -N-methylacetamide (Compound of 1072 ), N-ethyl-2- (2
-Iodo-4- (3-isopropyl-2,5-dioxo-2,3-dihydro [1,3] oxazolo [2,3-
a] Isoindole-9 (5H) -yl) phenoxy)
Acetamide (compound of 1073), 2- (2-iodo-4- (3-isopropyl-2,5-dioxo-2,3)
-Dihydro [1,3] oxazolo [2,3-a] isoindole-9 (5H) -yl) phenoxy) -N-propylacetamide (1074 compound), 2- (2-chloro-4- (3- Isopropyl-2,5-dioxo-
2,3-dihydro [1,3] oxazolo [2,3-a]
Isoindole-9 (5H) -yl) phenoxy) -N
-Propylacetamide (compound of 1092), 2-
(2-Bromo-4- (3-isopropyl-2,5-dioxo-2,3-dihydro [1,3] oxazolo [2,3
-A] isoindole-9 (5H) -yl) phenoxy) -N-propylacetamide (compound 1093), 2- (2-fluoro-4- (3-isopropyl-
2,5-dioxo-2,3-dihydro [1,3] oxazolo [2,3-a] isoindole-9 (5H) -yl) phenoxy) -N-propylacetamide (109
4), 2- (4- (3-isopropyl-2,5)
-Dioxo-2,3-dihydro [1,3] oxazolo [2,3-a] isoindole-9 (5H) -yl)-
2-methylphenoxy) -N-propylacetamide (1095 compound), 2- (2-ethyl-4- (3-
Isopropyl-2,5-dioxo-2,3-dihydro [1,3] oxazolo [2,3-a] isoindole-
9 (5H) -yl) phenoxy) -N-propylacetamide (1435 compound), 2- (2-iodo-4-
(3-isopropyl-2,5-dioxo-2,3-dihydro-1H-imidazo [2,1-a] isoindole-
9 (5H) -yl) phenoxy) -N-propylacetamide (the compound of 2074), 2- (4- (3-isopropyl-1-methyl-2,5-dioxo-2,3-dihydro-1H-imidazo [ 2,1-a] isoindole-
9 (5H) -yl) phenoxy) -N-propylacetamide (the compound of 2471);

3-Isopropyl-9b- (4-methoxyphenyl) -1H-pyrrolo [2,1-a] isoindole-2,5 (3H, 9bH) -dione (compound 3011), 2- (4- (3-isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo [2,1-a] isoindole-9 (5H) -yl) phenoxy) -N-
Propylacetamide (compound of 3024), 9b-
(3-Fluoro-4-methylphenyl) -3-isopropyl-1H-pyrrolo [2,1-a] isoindole-
2,5 (3H, 9bH) -dione (compound of 3056), 2- (2-iodo-4- (3-isopropyl-
2,5-dioxo-2,3-dihydro-1H-pyrrolo [2,1-a] isoindole-9 (5H) -yl) phenoxy) -N-propylacetamide (3074 compound), 2- (2- Chloro-4- (3-isopropyl-
2,5-dioxo-2,3-dihydro-1H-pyrrolo [2,1-a] isoindole-9 (5H) -yl) phenoxy) -N-propylacetamide (compound 3092), 2- (2- Bromo-4- (3-isopropyl-
2,5-dioxo-2,3-dihydro-1H-pyrrolo [2,1-a] isoindole-9 (5H) -yl) phenoxy) -N-propylacetamide (compound 3093), 2- (2- Fluoro-4- (3-isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo [2,1-a] isoindole-9 (5H) -yl) phenoxy) -N-propylacetamide (3094) Compound), 2- (4- (3-isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo [2,1-a]
Isoindole-9 (5H) -yl) -2-methylphenoxy) -N-propylacetamide (compound 3095), 2- (4- (3-isopropyl-2,5-dioxo-2,3-dihydro-1H) -Pyrrolo [2,1-a] isoindole-9 (5H) -yl) -2-methylphenoxy) -N-propylethanethioamide (3476 compound), 2- (2,6-dichloro-4- (3 -Isopropyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo [2,1-a] isoindole-9 (5H) -yl) phenoxy) -N-propylethanethioamide (3
477), 2- (4- (3-isopropyl-1)
-Methyl-2,5-dioxo-2,3-dihydro-1H
-Pyrrolo [2,1-a] isoindole-9 (5H)-
Yl) phenoxy) -N-propylacetamide (34
81 compound), 2- (2,6-dichloro-4- (3-
Isopropyl-2-oxo-5-thioxo-2,3-dihydro-1H-pyrrolo [2,1-a] isoindole-
9 (5H) -yl) phenoxy) -N-propylethanethioamide (3489 compound), 2- (4- (3-isopropyl-2- (methoxyimino) -5-oxo-1)
H-pyrrolo [2,1-a] isoindole-9 (3H,
5H) -yl) -2-methylphenoxy) -N-propylacetamide (3499 compound), 2- (4- (3
-Isopropyl-1,1-dimethyl-2,5-dioxo-2,3-dihydro-1H-pyrrolo [2,1-a] isoindole-9 (5H) -yl) phenoxy) -N-propylacetamide (3511 Compound), 9b- (3
-Iodo-4-methoxyphenyl) -3-isopropyl [1,3] thiazolo [2,3-a] isoindole-
2,5 (3H, 9bH) -dione (compound of 4063), N-ethyl-2- (2-iodo-4- (3-isopropyl-2,5-dioxo-2,3-dihydro [1,
3] thiazolo [2,3-a] isoindole-9 (5
H) -yl) phenoxy) acetamide (compound of 4073) and 2- (2-iodo-4- (3-isopropyl-2,5-dioxo-2,3-dihydro [1,3] thiazolo [2,3- a] Isoindole-9 (5H) -yl) phenoxy) -N-propylacetamide (407
4) are more preferred compounds.

Next, a method for producing the compound of the general formula [I] of the present invention will be described.

The compound of the general formula [I] can be prepared by the following production method A
Or it can be manufactured by the manufacturing method B.

Production Method A In this production method, among the compounds of the general formula [I], Y represents an oxygen atom or a group: NR ⁵ or a group: CR ⁶ R ⁷ (where R ⁵ , R ⁶ and R ⁷ are And a compound of the general formula [I-1] of the present invention or a compound of the general formula [I
-2] or a compound of the general formula [I-3]. In addition, the compound of the general formula [I-1] or the compound of the general formula [I-2] of the present invention is not only synthesized in a usual liquid phase, but also has a remarkable development in recent years such as a combinatorial synthesis method and a parallel synthesis method. It can also be produced by synthesis using a solid phase.

(First Step) The general formula [II]

Embedded image[Wherein, R⁰Represents an azide group, an optionally protected amino group.
Group, carbamoyl group, carbamoylamino group, carb
Moyloxy group, carboxyl which may be protected
Group, cyano group, sulfamoyl group, sulfo group, nitro
Group, halogen atom, hydroxy which may be protected
Group, formyl group, formylamino group, cyclic saturated C_Three−
C₉Aliphatic group, cyclic unsaturated C_Three-C₉Aliphatic group, aral
Kill group, N-aralkylamino group, N, N-diaralkyl
Ruamino group, aralkyloxy group, aralkyl carbonyl
Group, N-aralkylcarbamoyl group, aryl group, N
-Arylamino group, N, N-diarylamino group,
Reeloxy, arylsulfonyl, arylsul
Honyloxy group, N-arylsulfonylamino group, N
-Arylsulfonylamino C₁-C_TenAlkylamino
Group, N-arylsulfonylamino C₁-C_TenAlkyl
Carbamoyl group, N-arylsulfonylamino C₁−
C ₆Alkoxycarbonyl group, arylsulfamoyl
Group, arylsulfamoyloxy group, N-aryls
Rufamoyl C₁-C_TenAlkyl carbamoyl group, ant
Rusulfamoyl C₁-C₆An alkoxycarbonyl group,
N-arylcarbamoyl group, aroyl group, alloxy
Group, N- (N-aroylamino) C₁-C_TenAlkylka
Rubamoyl group, N-aroylamino C₁-C_TenAlkoki
Cicarbonyl group, C_Two-C₆Alkanoyl group, NC_Two−
C₆Alkanoylamino group, N, N-di-C_Two-C₆Al
Canoylamino group, NC₁-C₆Alkylamino group,
N, N-di-C₁-C₆Alkylamino group, N-C₁-C
_TenAlkylcarbamoyl group, NC₁-C_TenAlkyl
Ocarbamoyl group, N, N-di-C₁-C_TenAlkylka
Rubamoyl group, N, N-di-C₁-C_TenAlkylthioca
Rubamoyl group, NC_Two-C₆Alkenylcarbamoyl
Group, N, N-di-C_Two-C₆Alkenylcarbamoyl group,
Optionally protected N-amino C₁-C_TenAlkylka
Rubamoyl group, NC₁-C₆Alkoxy C₁-C_TenAl
Kill carbamoyl group, NC₁-C₆Alkoxycarboni
Le C₁-C_TenAlkylcarbamoyl group, NC₁-C₆A
Lucoxycarbonylamino C₁-C_TenAlkyl carbamo
Il group, N-C₁-C₆Alkoxycarbonylamino C₁
-C₆Alkoxycarbonyl group, C₁-C₆Alkylthio
Group, NC₁-C₆Alkylsulfamoyl group, N, N-
Di-C₁-C₆Alkylsulfamoyl group, C₁-C₆Al
Killsulfinyl group, C₁-C₆Alkylsulfonyl group,
N-C₁-C₆Alkylsulfonylamino group, C₁-C₆A
Lucoxy group, C₁-C₆Alkoxycarbonyl group, protection
Amino C which may be₁-C₆Alkoxycarbonyl
Group, NC_Three-C₆Cycloalkylamino group, N, N-di
-C_Three-C₆Cycloalkylamino group, C_Three-C₆Cycloa
Alkyloxy group, N-C_Three-C₆Cycloalkylcarbamo
Yl group and N, N-di-C_Three-C₆Cycloalkyl carb
A substituent selected from the group consisting of moyl groups,
Zolyl, isothiazolyl, imidazolyl, oxa
Zolyl group, oxadiazolyl group, thiazolyl group, thiazi
Azolyl, thienyl, triazinyl, triazolyl
Group, pyridyl group, pyrazinyl group, pyrimidinyl group,
Ridazinyl group, pyrazolyl group, pyrrolyl group, pyranyl
Group, furyl group, furazanyl group, imidazolidinyl group, i
Midazolinyl group, tetrahydrofuranyl group, pyrazolidi
Nil, pyrazolinyl, piperazinyl, piperidini
Group, pyrrolidinyl group, pyrrolinyl group and morpholino group
A 5- or 6-membered heterocyclic group selected from the group consisting of
Clidinyl group, isoquinolyl group, isoindolyl group, i
Ndazolyl group, indolyl group, indolizinyl group, ethyl
Rangeoxyphenyl group, carbazolyl group, quinazolini
Group, quinoxalinyl group, quinolizinyl group, quinolyl
Group, coumalonyl group, chromenyl group, phenanthridinyl
Group, phenanthrolinyl group, dibenzofuranyl group,
Benzothiophenyl group, cinnolinyl group, thionaphthenyl
Group, naphthyridinyl group, phenazinyl group, phenaxazi
Nil, phenothiazinyl, phthalazinyl, pteri
Dinyl, prenyl, benzimidazolyl, benzo
Oxazolyl group, benzothiazolyl group, benzotriazo
Ryl, benzofuranyl and methylenedioxyphenyl
Nitrogen atom, oxygen atom selected from the group consisting of
A heteroatom selected from the group consisting of sulfur
1 to 5 cyclic aromatic heterocyclic groups having 1 to 5
And N substituted with the heterocyclic group or the heteroaromatic group.
-C₁-C_TenAlkylcarbamoyl group, NC₁-C_TenA
Alkylthiocarbamoyl, thiocarbonyl and
A substituent selected from the group consisting of a rubonyl group;
Straight-chain saturated C which may be substituted with a substituent₁-C₉fat
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C
₁-C₉Aliphatic group, branched unsaturated C₁-C₉Aliphatic groups,
C₁-C₆Alkoxy group, C₁-C₆Alkylthio group and N
-C₁-C₆Selected from the group consisting of alkylamino groups
One or more substituents selected from the group consisting of
Aryl group, acenaphthylenyl which may have
Group, adamantyl group, anthryl group, indenyl group,
Select from the group consisting of rubornyl group and phenanthryl group
1- to 3-cyclic C₇-C_FifteenA carbon aromatic ring group or a
Soxazolyl group, isothiazolyl group, imidazolyl
Group, oxazolyl group, oxadiazolyl group, thiazolyl
Group, thiadiazolyl group, thienyl group, triazinyl group,
Triazolyl group, pyridyl group, pyrazinyl group, pyrimidi
Nil group, pyridazinyl group, pyrazolyl group, pyrrolyl group,
Pyranyl group, furyl group, furazanyl group, imidazolidini
Group, imidazolinyl group, tetrahydrofuranyl group,
Lazolidinyl, pyrazolinyl, piperazinyl,
Peridinyl group, pyrrolidinyl group, pyrrolinyl group and mol
5- or 6-membered hetero selected from the group consisting of holino groups
Ring group or acridinyl group, isoquinolyl group, isoyl
Indolyl, indazolyl, indolyl, indole
Dinyl group, ethylenedioxyphenyl group, carbazolyl
Group, quinazolinyl group, quinoxalinyl group, quinolizinyl
Group, quinolyl group, cumaronyl group, chromenyl group, phena
Suridinyl group, phenanthrolinyl group, dibenzofura
Nil group, dibenzothiophenyl group, cinnolinyl group,
Onaphthenyl group, naphthyridinyl group, phenazinyl group,
Phenaxazinyl, phenothiazinyl, phthalazinyl
Group, pteridinyl group, purinyl group, benzimidazoly
Group, benzoxazolyl group, benzothiazolyl group,
Benzotriazolyl, benzofuranyl and methylenedi
A nitrogen atom selected from the group consisting of an oxyphenyl group,
Heteroatoms selected from the group consisting of oxygen and sulfur atoms
1 to 3 ring groups having 1 to 5 rings per ring system
Heteroaromatic group, R^TenAnd R²⁰Are the same or different,
Atom, azide group, amino group which may be protected,
Rubamoyl group, carbamoylamino group, carbamoylo
Xy group, carboxyl group which may be protected, cyano
Group, sulfamoyl group, sulfo group, nitro group, halogen
Atom, hydroxy group which may be protected, formyl
Group, formylamino group, cyclic saturated C_Three-C₉Aliphatic groups,
Cyclic unsaturated C_Three-C₉Aliphatic group, aralkyl group, NA
Aralkylamino, aralkyloxy, aralkyl
Rubonyl group, aryl group, N-arylamino group, ant
Oxy group, arylsulfonyl group, N-aryls
Ruphonylamino group, N-arylsulfonylamino C₁
-C_TenAlkylamino group, N-arylsulfonylamido
No C₁-C_TenAlkylcarbamoyl group, N-aryls
Ruphonylamino C₁-C₆Alkoxycarbonyl group, C_Two
-C₆Alkanoyl group, NC_Two-C₆Alkanoylami
Group, aroyl group, N-aroylamino group, N-alloy
Le C₁-C_TenAlkylamino group, N-aroyl C₁-C_Ten
Alkylcarbamoyl group, NC₁-C₆Alkylamino
Group, N, N-di-C₁-C₆Alkylamino group, N-C₁
-C_TenAlkylcarbamoyl group, N, N-di-C₁-C
_TenAlkylcarbamoyl group, NC₁-C₆Alkylsul
Famoyl group, C₁-C₆Alkylsulfinyl group, C₁
-C₆Alkylsulfonyl group, NC₁-C₆Alkyls
Rufonylamino group, C₁-C₆Alkylthio group, C₁-C₆
Alkoxy group, C₁-C₆Alkoxycarbonyl group, N-
C_Three-C₆Cycloalkylamino group, C_Three-C₆Cycloal
Killoxy group and N-C_Three-C₆Cycloalkylcarbamo
Or a substituent selected from the group consisting of
Optionally substituted straight-chain saturated C₁-C₉Aliphatic groups,
Linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉
Aliphatic group, branched unsaturated C₁-C₉Aliphatic group, N-C
₁-C₆Alkylamino group, C₁-C₆Alkylthio group
Kuha C₁-C₆X represents an alkoxy group;_TwoAnd Z are
Carboxylic acid or thiocarbo represented by the formula:
Acid and general formula [III]

Embedded image[Where Y_TenIs an oxygen atom or group: NR⁵⁰Or group:
CR⁶⁰R⁷(Where R⁵⁰Is a hydrogen atom, amino
Group protecting group, halogen atom, hydrid which may be protected
Roxy group, N-C₁-C₆Alkylsulfonylamino group,
C₁-C₆Alkoxy group, C₁-C₆Alkoxycarbonyl
Group, C_Two-C₆Alkanoyl group, carbamoyl group and N-
C₁-C_TenSelect from the group consisting of alkylcarbamoyl groups
Or a substituent which may be substituted with the substituent,
Chain saturation C₁-C₉Aliphatic group, linear unsaturated C₁-C₉fat
Group, branched saturated C₁-C₉Aliphatic or branched
Unsaturated C₁-C₉Aliphatic group, R⁶⁰Is a hydrogen atom, halogen
Atom, an optionally protected hydroxy group, N-C₁
-C₆Alkylsulfonylamino group, C₁-C₆Alkoki
Si group, C₁-C₆Alkoxycarbonyl group, C_Two-C₆Al
Canoyl group, carbamoyl group and NC₁-C_TenArchi
A substituent selected from the group consisting of a rucarbamoyl group or
Linear saturated C which may be substituted with the substituent₁-C₉
Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups, branched chains
Sum C₁-C₉Aliphatic or branched unsaturated C₁-C₉
An aliphatic group;⁷Has the meaning described above), R³⁰
And R⁴⁰Are the same or different and are a hydrogen atom, an azide group,
Amidino group, optionally protected amino group, carbamo
Yl group, carbamoylamino group, carbamoyloxy
Group, carboxyl group which may be protected, guanidino
Group, cyano group, sulfamoyl group, sulfo group, nitro
Group, halogen atom, hydroxy which may be protected
Group, formyl group, formylamino group, cyclic saturated C_Three−
C₉Aliphatic group, cyclic unsaturated C _Three-C₉Aliphatic group, C_Two-C
₆Alkanoyl group, NC_Two-C₆Alkanoylamino
Group, NC₁-C₆Alkylamino group, N, N-di-C₁
-C₆Alkylamino group, N-C₁-C_TenAlkyl carba
Moyl group, N, N-di-C₁-C_TenAlkyl carbamoy
Group, C₁-C₆Alkylthio group, N-C₁-C₆Alkyl
Sulfamoyl group, C ₁-C₆Alkylsulfinyl group,
C₁-C₆Alkylsulfonyl group, NC₁-C₆Alkyl
Sulfonylamino group, C₁-C₆Alkoxy group, C₁-C₆
Alkoxycarbonyl group, N-C_Three-C₆Cycloalkyl
Amino group, C_Three-C₆Cycloalkyloxy group and N-C
_Three-C₆Selected from the group consisting of cycloalkylcarbamoyl groups
Selected substituents, which may be substituted with the substituents,
Chain saturation C₁-C₉Aliphatic group, linear unsaturated C₁-C₉fat
Group, branched saturated C₁-C₉Unsaturation of aliphatic groups and branches
Sum C₁-C₉Substitution selected from the group consisting of aliphatic groups
Group, azide group, optionally protected amino group, carb
Moyl group, carbamoylamino group, carbamoyloxy
Group, carboxyl group which may be protected, cyano group,
Sulfamoyl group, sulfo group, nitro group, halogen source
, An optionally protected hydroxy group, a formyl group,
Formylamino group, cyclic saturated C_Three-C₉Aliphatic group, cyclic
Of unsaturated C_Three-C₉Aliphatic group, aralkyl group, N-aral
Killamino group, N, N-diaralkylamino group, arral
Killoxy group, aralkylcarbonyl group, N-aralkyl
Rucarbamoyl group, aryl group, N-arylamino
Group, N, N-diarylamino group, aryloxy group,
Arylsulfonyl group, arylsulfonyloxy group,
N-arylsulfonylamino group, N-arylsulfo
Nilamino C₁-C_TenAlkylamino group, N-aryl
Sulfonylamino C₁-C_TenAlkylcarbamoyl group,
N-arylsulfonylamino C₁-C₆Alkoxycal
Bonyl group, aryl sulfamoyl group, aryl sulf
Amoyloxy group, N-arylsulfamoyl C₁−
C_TenAlkyl carbamoyl group, aryl sulfamoyl
C₁-C₆Alkoxycarbonyl group, N-arylcarba
Moyl group, aroyl group, alloxy group, N- (N-aro
Ilamino) C₁-C_TenAlkylcarbamoyl group, N-
Aroylamino C₁-C_TenAlkoxycarbonyl group, C_Two
-C₆Alkanoyl group, NC_Two-C₆Alkanoylami
Group, N, N-di-C_Two-C₆Alkanoylamino group,
N-C₁-C₆Alkylamino group, N, N-di-C₁-C₆
Alkylamino group, N-C₁-C _TenAlkyl carbamoy
Group, N-C₁-C_TenAlkylthiocarbamoyl group,
N, N-di-C₁-C_TenAlkylcarbamoyl group, N,
N-di-C₁-C_TenAlkylthiocarbamoyl group, N-
C_Two-C₆Alkenylcarbamoyl group, N, N-di-C_Two
-C₆Alkenylcarbamoyl group, protected
N-amino C₁-C_TenAlkylcarbamoyl group, N-
C₁-C₆Alkoxy C₁-C_TenAlkyl carbamoyl
Group, NC₁-C₆Alkoxycarbonyl C₁-C_TenAl
Kill carbamoyl group, NC₁-C₆Alkoxycarboni
Lumino C₁-C_TenAlkylcarbamoyl group, NC₁−
C₆Alkoxycarbonylamino C₁-C₆Alkoxyka
Rubonyl group, C ₁-C₆Alkylthio group, N-C₁-C₆A
Rukylsulfamoyl group, N, N-di-C₁-C₆Archi
Rusulfamoyl group, C₁-C₆Alkylsulfinyl
Group, C₁-C₆Alkylsulfonyl group, NC₁-C₆Al
Killsulfonylamino group, C₁-C ₆Alkoxy group, C₁
-C₆Alkoxycarbonyl group, which may be protected
Amino C₁-C₆Alkoxycarbonyl group, N-C_Three-C₆
Cycloalkylamino group, N, N-di-C_Three-C₆Cyclo
Alkylamino group, C_Three-C₆Cycloalkyloxy
Group, NC_Three-C₆A cycloalkylcarbamoyl group and
N, N-di-C_Three-C₆Is it a cycloalkylcarbamoyl group
A substituent selected from the group consisting of, an isoxazolyl group,
Isothiazolyl group, imidazolyl group, oxazolyl group,
Oxadiazolyl group, thiazolyl group, thiadiazolyl
Group, thienyl group, triazinyl group, triazolyl group,
Lysyl, pyrazinyl, pyrimidinyl, pyridazini
Group, pyrazolyl group, pyrrolyl group, pyranyl group, furyl
Group, furazanyl group, imidazolidinyl group, imidazolini
Group, tetrahydrofuranyl group, pyrazolidinyl group,
Lazolinyl group, piperazinyl group, piperidinyl group, pyro
Group consisting of lysinyl, pyrrolinyl and morpholino groups
Acridinyl, a 5- or 6-membered heterocyclic group selected from
Group, isoquinolyl group, isoindolyl group, indazolyl group
Group, indolyl group, indolizinyl group, ethylene dioxy group
Cyphenyl group, carbazolyl group, quinazolinyl group, quino
Xalinyl group, quinolizinyl group, quinolyl group, cumaroni
Group, chromenyl group, phenanthridinyl group, phenane
Slurolinyl group, dibenzofuranyl group, dibenzothiophene
Nil group, cinnolinyl group, thionaphthenyl group, naphthyl
Dinyl group, phenazinyl group, phenaxazinyl group,
Notiazinyl, phthalazinyl, pteridinyl,
Linyl group, benzimidazolyl group, benzoxazolyl
Group, benzothiazolyl group, benzotriazolyl group, ben
Consists of zofuranyl and methylenedioxyphenyl groups
From nitrogen, oxygen and sulfur selected from the group
A heteroatom selected from the group consisting of 1 to
5- to 5-cyclic heteroaromatic ring groups and
N-C substituted with a heterocyclic group or the heteroaromatic group₁-C_Ten
Alkylcarbamoyl group, NC₁-C_TenAlkylthio
Carbamoyl group, thiocarbonyl group and carbonyl group
And a substituent selected from the group consisting of
Straight-chain saturated C₁-C₉Aliphatic group, straight chain
Of unsaturated C ₁-C₉Aliphatic groups, branched saturated C₁-C₉fat
Group, branched chain unsaturated C₁-C₉Aliphatic group, C₁-C₆A
Lucoxy group, C₁-C₆Alkylthio group and N-C₁-C₆
From substituents selected from the group consisting of alkylamino groups
Having one or more substituents selected from the group consisting of
May be an aryl group, an acenaphthylenyl group, an adaman
Chill, anthryl, indenyl, norbornyl
And at least one selected from the group consisting of phenanthryl groups
Tricyclic C₇-C_FifteenCarbon aromatic ring group or isoxazoly
Group, isothiazolyl group, imidazolyl group, oxazolyl group
Group, oxadiazolyl group, thiazolyl group, thiadiazo
Ryl, thienyl, triazinyl, triazolyl
Group, pyridyl group, pyrazinyl group, pyrimidinyl group, pyri
Dazinyl group, pyrazolyl group, pyrrolyl group, pyranyl group,
Furyl, furazanyl, imidazolidinyl, imida
Zolinyl group, tetrahydrofuranyl group, pyrazolidinyl
Group, pyrazolinyl group, piperazinyl group, piperidinyl
Group, pyrrolidinyl group, pyrrolinyl group and morpholino group
A 5- or 6-membered heterocyclic group selected from the group consisting of
Is acridinyl group, isoquinolyl group, isoindolyl
Group, indazolyl group, indolyl group, indolizinyl
Group, ethylenedioxyphenyl group, carbazolyl group,
Nazolinyl group, quinoxalinyl group, quinolizinyl group,
Noryl group, coumalonyl group, chromenyl group, phenanthry
Dinyl group, phenanthrolinyl group, dibenzofuranyl
Group, dibenzothiophenyl group, cinnolinyl group, thiona
Phenyl, naphthyridinyl, phenazinyl,
Naxazinyl group, phenothiazinyl group, phthalazinyl
Group, pteridinyl group, purinyl group, benzimidazolyl
Group, benzoxazolyl group, benzothiazolyl group, ben
Zotriazolyl, benzofuranyl and methylenedi
Nitrogen atom or acid selected from the group consisting of xylphenyl groups
Heteroatoms selected from the group consisting of elemental atoms and sulfur atoms
From 1 to 3 rings having 1 to 5 rings per ring system
An aromatic ring group or the aryl group, the carbon aromatic ring group,
Or a heterocyclic group.
Straight-chain saturated C₁-C₉Aliphatic group, linear unsaturated C₁−
C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group or
Branched unsaturated C₁-C₉Represents an aliphatic group, or R³⁰
And R⁴⁰Together form a linear saturated C₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic or branched unsaturated C₁-C₉fat
Group or 5- or 6-membered saturated carbocyclic group or 5 or less
Or a 6-membered unsaturated carbocyclic ring,₁Is a hydrogen source
Protecting group for carboxyl group or protecting group for amino group
Or carboxyl groups in solid-phase synthesis of peptides or
Is an amino group resin carrier, X_TenIs an oxygen atom, a sulfur atom or
Is a group: NR⁵⁰(Where R⁵⁰Has the above meaning
Is reacted with an amine derivative represented by the following formula:
Amino-protecting group, hydroxy-protecting group or
A protecting group for a boxyl group [specifically, Y_Ten(Ie
R⁵⁰) Or L₁Is a protecting group for an amino group,
If it has a protecting group or a carboxyl protecting group,
Protective group] as appropriate (L₁Is a place of protecting group for amino group
If R⁵⁰Is linear or branched, saturated or unsaturated
C₁-C₉Only for aliphatic groups. ) By the general
Formula [IV ']

Embedded image[Where Y₁Is an oxygen atom or group: NR^FiveOr group: C
R⁶R⁷(Where R^Five, R⁶And R⁷Means the above
Having a taste), R⁰, R^Ten, R²⁰, R³⁰, R ⁴⁰,
L₁, X_Two, X_TenAnd Z have the meaning given above.
To a compound.

The compound represented by the general formula [IV '] can be prepared by reacting the compound represented by the general formula [V'] in a solvent.

Embedded image [Wherein R ⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , L ₁ , X ₂ , X
₁₀ , Y ₁ and Z have the above-mentioned meanings]. The compound of the general formula [IV '] and the compound of the general formula [V'] are useful as intermediates for producing the compound of the general formula [I] of the present invention, and are usually used as an equilibrium mixture when used in the reaction. .

Examples of the resin carrier having a carboxyl group or an amino group in the solid phase synthesis of a peptide include, for example, a polyethylene-divinylbenzene copolymer and a polystyrene-divinylbenzene copolymer.
In addition, resins in which polyethylene glycol is interposed between these polymers can be used. Among them, as the carboxyl group resin carrier, p-benzyloxybenzyl alcohol resin [Wang ^™ Resin] is preferable, and the amino group resin carrier is preferable. As trityl chloride resin [Tri
[tyl Chloride Resin] is preferable.

The reagent used in the reaction can be appropriately increased or decreased depending on the starting compounds and reaction conditions. Usually, the reaction is carried out in a dehydrated inert organic solvent with a carboxylic acid or thiocarboxylic acid of the general formula [II]. The amine derivative of the formula [III] is reacted with a solvent at a temperature of from -100 ° C to the boiling point of the solvent, preferably from 0 to 30 ° C for 0.5 to 96 hours, preferably in the presence of a base, a condensation auxiliary and / or a condensing agent. Is 3 to 24
Allow time to react. Next, when the condensed compound has an amino group-protecting group, a hydroxy group-protecting group or a carboxyl group-protecting group, the reaction is completed by appropriately removing the protecting group.

The inert organic solvent used in the reaction is not particularly limited as long as it does not adversely affect the reaction. Specific examples include methylene chloride, chloroform, 1,2-dichloroethane, trichloroethane, and the like.
N, N-dimethylformamide, ethyl acetate,
Acetic acid methyl ester, acetonitrile, acetic anhydride, methyl alcohol, ethyl alcohol, benzene, xylene, water, acetic acid, toluene, 1,4-dioxane, tetrahydrofuran and the like, but from the viewpoint of securing a suitable reaction temperature, particularly, for example, Methylene chloride, chloroform,
Preferred are 1,2-dichloroethane, acetonitrile, N, N-dimethylformamide, 1,4-dioxane, toluene and the like.

As the base used in the reaction, for example, trimethylamine, triethylamine, N, N-diisopropylethylamine, N-methylmorpholine, N-methylpyrrolidine, N-methylpiperidine, N, N-dimethylaniline, 1,8- Tertiary aliphatic amines such as diazabicyclo [5.4.0] undec-7-ene (DBU) and 1,5-azabicyclo [4.3.0] non-5-ene (DBN); Aromatic amines such as dimethylaminopyridine, picoline, lutidine, quinoline and isoquinoline; alkali metals such as metal potassium, sodium and lithium; alkali metal hydrides such as sodium hydride and potassium hydride; butyllithium Alkali metal alkylates such as potassium ter; Alkali metal alkoxides such as butyrate, sodium ethylate and sodium methylate; alkali metal hydroxides such as potassium hydroxide and sodium hydroxide; alkali metal carbonates such as potassium carbonate and the like; Grade aliphatic amines and the like are preferred, particularly, for example, triethylamine,
N, N-diisopropylethylamine and the like are preferred.

Examples of the condensation aid used in the reaction include N-hydroxybenzotriazole hydrate, N-hydroxysuccinimide, N-hydroxy-5-norbornene-2,3-dicarboximide, and 3-hydroxy-3 , 4-dihydro-4-oxo-1,2,3-benzotriazole and the like, among which N-hydroxybenzotriazole and the like are preferable.

Examples of the condensing agent used in the reaction include thionyl chloride, N, N-dicyclohexylcarbodiimide, 1-methyl-2-bromopyridinium iodide, N, N'-carbonyldiimidazole, diphenylphosphoryl chloride, Diphenylphosphoryl azide, N, N'-disuccinimidyl carbonate,
N, N'-disuccinimidyl oxalate, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, ethyl chloroformate, isobutyl chloroformate, benzotriazo-1-yl-oxy-tris (dimethylamino ) Phosphonium hexafluorophosphate, etc., among which N, N-dicyclohexylcarbodiimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, ethyl chloroformate, isobutyl chloroformate and the like are preferable. is there.

The reagent used in the reaction can be appropriately increased or decreased depending on the starting compounds and reaction conditions.
Usually, 0.02 to 50 equivalents, preferably 0.2 to 2 equivalents of the amine derivative of the general formula [III], 1 to 50 equivalents, preferably 0.2 to 2 equivalents to the carboxylic acid or thiocarboxylic acid of the general formula [II] 3 to 5 equivalents of base, 1 to 50 equivalents, preferably 1 to 5 equivalents of condensation aid and / or 1 to 50 equivalents, preferably 1 to 5 equivalents of condensing agent are used. The base, the condensation aid and the condensing agent can be used alone or in appropriate combination of two or more.

(Second Step) Next, the general formula [IV ']

Embedded image [Wherein R ⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , L ₁ , X ₂ , X
₁₀ , Y ₁ and Z have the above-mentioned meanings], and a compound represented by the general formula [V ′]

Embedded image [Wherein R ⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , L ₁ , X ₂ , X
₁₀ , Y ₁ and Z have the above-mentioned meanings], reacted with an acid in an inert organic solvent to obtain a compound of the general formula [VIII ′]

Embedded image [Wherein R ⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , X ₂ , X ₁₀ , Y
₁ and Z have the above-mentioned meanings], and then by removing the protecting group appropriately,
General formula [I ']

Embedded image [Wherein, R, R ¹ , R ² , R ³ , R ⁴ , X ₁ , X ₂ , Y ₁ and Z have the above-mentioned meanings]
The compound of the general formula [I-1], the compound of the general formula [I-2], the compound of the general formula [I-3] or a pharmaceutically acceptable salt thereof can be produced. When L ₁ is a resin carrier having a carboxyl group or an amino group in the solid phase synthesis of a peptide, the resin of the general formula [I-1] is removed by removing the resin carrier in the reaction with the acid. The compound of the formula [I-2] can be produced. Further, in the compound of the general formula [I '], X ₁
Is a compound of NR ⁵ (where R ⁵ has the above-mentioned meaning) or Y ₁ is NR ⁵ or a group: CR ⁶ R ⁷ (where R ⁵ , R ⁶ and R ⁷ have the above-mentioned meaning) Can be usually produced by using a starting compound having these substituents, wherein X ₁₀ is an oxygen atom or N
A compound of the general formula [VIII '], wherein the compound of H or Y ₁ is NH or a group of the group CHR ⁷ , wherein R ⁷ has the meaning given above, is then produced by means of a conventional method using an NR ⁵ (R ⁵ has the above-mentioned meaning) or NH or a group: CHR ⁷ (where R ⁷ has the above-mentioned meaning) is substituted with R ⁵ or R ⁶ (R ⁵
And R ⁶ has the same meaning as described above), and it is also possible to produce the desired compound of the general formula [I ′]. Examples of the above introduction method include a reaction in which a carbonyl group is reacted with methoxylamine hydrochloride to convert it into a methoxym group, and a group: CHR ⁷ (where R ⁷ has the above-mentioned meaning) is reacted with an alkyl metal reagent. And then treatment with an alkyl halide to give a group: CR ⁶ R ⁷ (where R ⁶ and R ⁷ have the same meaning as described above).

The reagent used in the reaction can be appropriately increased or decreased depending on the starting compounds and reaction conditions. Usually, the reaction is carried out in a dehydrated inert organic solvent using a compound of the general formula [IV] and a compound of the general formula [V] From the equilibrium mixture with the compound of formula (I) and a catalytic amount of acid at a temperature ranging from -100 ° C to the boiling point of the solvent,
The reaction can be carried out at ３０30 ° C. for 0.5-96 hours, preferably 2-24 hours. Next, when an amino-protecting group is present, the reaction is completed by appropriately removing the amino-protecting group.

The protecting group for protecting a functional group other than L ₁ can be, for example, an N-protecting group or a carboxyl group by appropriately selecting the type of protecting group, the method for removing the protecting group, or the reaction conditions. A protecting group, a protecting group for a hydroxy group, and the like can be simultaneously removed. Further, any one of an N-protecting group, a carboxyl protecting group, and a hydroxy protecting group can be selectively removed, and the order of removing the protecting groups is not particularly limited. .

Examples of the protecting group for the hydroxy group include, for example, t
lower alkylsilyl groups such as tert-butyldimethylsilyl group and tert-butyldiphenylsilyl group; lower alkoxymethyl groups such as methoxymethyl group and 2-methoxyethoxymethyl group; aralkyl groups such as benzyl group and p-methoxybenzyl group; A group; for example, an acyl group such as a formyl group and an acetyl group;

Examples of the amino-protecting group include aralkyl groups such as benzyl group and p-nitrobenzyl group; acyl groups such as formyl group and acetyl group; lower alkoxy groups such as ethoxycarbonyl group and tert-butoxycarbonyl group. A carbonyl group; for example, an aralkyloxycarbonyl group such as a benzyloxycarbonyl group and a p-nitrobenzyloxycarbonyl group;
Nitrobenzyl group, tert-butoxycarbonyl group,
A benzyloxycarbonyl group and the like are preferred.

Examples of the carboxyl-protecting group include a lower alkyl group such as a methyl group, an ethyl group and a tert-butyl group; an aralkyl group such as a benzyl group and a p-methoxybenzyl group; Ethyl, tert-butyl, benzyl and the like are preferred.

The removal of the protecting group depends on the type and the stability of the compound.
Groups in Organic Synthesis (Pro
tive Groups in Organic
Synthesis), T.W. W. Green (TW.
Greene), John Wiley & Son
company (1981)] or a method analogous thereto, for example, solvolysis using an acid or a base, chemical reduction using a metal hydride complex or a palladium carbon catalyst,
It can be carried out by catalytic reduction using a Raney nickel catalyst or the like.

The inert organic solvent used in the reaction is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include the above-mentioned inert solvents.

The acid used in the reaction includes, for example, inorganic acids such as hydrochloric acid, nitric acid, hydrobromic acid, sulfuric acid, hydrofluoric acid and perchloric acid; Lewis acids such as trifluoroboric acid;
Examples thereof include sulfonic acids such as p-toluenesulfonic acid, trifluoromethanesulfonic acid, and methanesulfonic acid; organic acids such as formic acid, trifluoroacetic acid, and acetic acid; Organic acids such as acetic acid are suitable.

After the completion of the reaction, the reaction is further carried out by a commonly known method.
By purifying the product, the compound of the general formula [I-1] or the compound of the general formula [I-2] or the general formula [I-
3] can be obtained. Isolation and purification of a compound of the general formula [I-1], a compound of the general formula [I-2] or a compound of the general formula [I-3] or a salt thereof from the reaction solution include:
It can be carried out by a known separation means such as solvent extraction, recrystallization, chromatography and the like.

Production Method B This production method employs the compound represented by the general formula [I]
Is a method for producing the compound of the general formula [I-4] of the present invention, wherein is a sulfur atom.

The general formula [IV ″]

Embedded image [Wherein, Y ₂ represents an oxygen atom, L ₂ represents a hydrogen atom,
⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , X ₂ , X ₁₀ and Z have the above-mentioned meanings] and a compound represented by the general formula [V ″]

Embedded image [Wherein, R ⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , L ₂ , X ₂ , X
₁₀ , Y ₂ and Z have the same meaning as described above], and a sulfurizing agent is reacted with the compound represented by the general formula [V
I '']

Embedded image [Wherein, Y ₃ represents a sulfur atom, and R ⁰ , R ¹⁰ , R ²⁰ ,
R ³⁰ , R ⁴⁰ , L ₂ , X ₂ , X ₁₀ and Z have the above-mentioned meanings] and a compound represented by the general formula [VII ″]

Embedded image [Wherein, R ⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , L ₂ , X ₂ , X
₁₀ , Y ₃ and Z have the meaning given above], followed by reaction with an acid in an inert organic solvent at room temperature to the boiling point of the solvent, General formula [VIII ″]

Embedded image [Wherein R ⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , X ₂ , X ₁₀ , Y
₃ and Z have the meanings described above], and the protecting group is appropriately removed to obtain a compound of the general formula [I ″]

Embedded image [Wherein R, R ¹ , R ² , R ³ , R ⁴ , X ₁ , X ₂ , Y ₃ and Z have the above-mentioned meanings] or a pharmaceutically acceptable salt thereof. Can be manufactured.

The reagent used in the reaction can be appropriately increased or decreased depending on the starting compounds and the reaction conditions. Usually, the reaction is carried out in a dehydrated inert organic solvent in the general formula [IV ″].
Of the compound of the formula [V ″] and the sulfidizing agent at a temperature ranging from -100 ° C to the boiling point of the solvent, preferably 0 to 30 ° C for 0.5 to 96 hours, preferably 1 to 12 hours.
The reaction is carried out for an hour to convert into an equilibrium mixture of the compound of the general formula [VI ″] and the compound of the general formula [VII ″]. Formula [VIII ″]

Embedded image [Wherein R ⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , X ₂ , X ₁₀ , Y
₃ and Z have the meanings described above], and after removing an appropriate protecting group and purifying by an appropriate method, the compound represented by the general formula [I ″]

Embedded image Wherein R, R ¹ , R ² , R ³ , R ⁴ , X ₁ , X ₂ , Y ₃ and Z have the above-mentioned meanings, that is, a compound represented by the general formula [I-4] Can be produced. The compound of the general formula [I-4] or a salt thereof can be isolated and purified from the reaction solution by a known separation means such as solvent extraction, recrystallization and chromatography in the same manner as in Production method A.

The carboxylic acid or thiocarboxylic acid of the general formula [II] is known in the literature or is represented by the general formula [I
X] R ⁰ -X [IX] [wherein, X represents a halogen atom and R ⁰ has the above-mentioned meaning] and the metal magnesium, for example, diethyl ether, tetrahydrofuran In a suitable ether-based dehydrating solvent, a Grignard reagent prepared by reacting from a low temperature to the boiling point of the solvent, and an acid anhydride which may be substituted, in the dehydrated inert organic solvent, at a low temperature. And at room temperature.

The compound of the general formula [II] includes an allene compound of the general formula [X] R ⁰ -H [X] wherein R ⁰ has the above-mentioned meaning;
A substituted or unsubstituted acid anhydride can also be produced by performing a Friedel-Crafts-acylation reaction in the presence of the above-mentioned acid as appropriate.

The compound of the general formula [III] is known in the literature or is a compound of the general formula [III]

Embedded image [In the formula, Y ₄ is an oxygen atom, L ₃ is a hydrogen atom or a protecting group for a carboxyl group or a resin carrier for a carboxyl group in solid phase synthesis of a peptide, and R ³⁰ , R ⁴⁰ and X ₁ have the above-mentioned meanings. Or an amino acid derivative derivable from the amino acid represented by the general formula [XI]

Embedded image [Wherein, L ₄ is a protecting group for a hydrogen atom or a carboxyl group, R ⁹⁰ is a protecting group for a hydrogen atom or an amino group, R ³⁰ and R
⁴⁰ and X ₁ and Y ₄ have the above-mentioned meanings] and a carboxylic acid or thiocarboxylic acid of an amino acid derivative derivable from the amino acid

Formula [XII] R ⁵⁰ NH-R ⁸⁰ [XII] wherein R ⁸⁰ represents a protecting group for an amino group or a resin carrier for an amino group in solid phase synthesis of a peptide, and R ⁵⁰ has the above-mentioned meaning. Wherein R ⁹⁰ is an amino-protecting group, and then the amino-protecting group is removed.

Further, the compound of the general formula [III] is represented by the general formula [XIII]

Embedded image Wherein Y ₅ is an oxygen atom or a nitrogen atom, L ₅ is a carboxyl-protecting group or a hydrogen atom or an amino-protecting group, and R ³⁰ , R ⁴⁰ , R ⁹⁰ and X ₁ have the above-mentioned meanings.
And an amino acid derivative represented by the general formula [XI
V] R ⁶⁰ R ⁷ CH—MgX [XIV] wherein X represents a halogen atom, R ⁶⁰ and R ⁷ have the same meanings as defined above, and then R ⁹⁰ is reacted with In the case of an amino-protecting group, it can also be produced by removing the amino-protecting group.

Next, in order to specifically demonstrate the usefulness of the present invention, the compound of Example 1002 was used as a representative compound, and the effect on GLP-1 concentration in plasma after administration of the compound was examined. The test method and results are shown below.

(Test Method) Male Wistar rats (9th week, n = 6) bred under free-feeding and water-feeding conditions were fasted the night before the test, and administered with a compound suspended in a 1% carboxymethylcellulose solution. did. In addition, as a control group,
Rats were orally administered a 1% carboxymethylcellulose solution. Blood was collected 30 minutes after administration of the test drug, and plasma was separated from the obtained blood by centrifugation. G in plasma
The LP-1 concentration was determined by a radioimmunoassay using a commercially available anti-GLP-1 antibody (Cosmo Bio Inc.).
The obtained numerical value was analyzed using the Student T test, and the statistically significant difference was calculated. The results are shown in the table below.

(Test results)

[Table 46]

From the above results, 30 minutes after administration,
In the plasma of the group to which 30 mg / kg of the compound was administered, significantly higher blood GLP-1 was observed compared to the control group. From these results, it was shown that the compound of the present invention has an activity capable of exhibiting a high blood GLP-1 concentration in rats.

Since the compound of the present invention has an activity of exhibiting a high blood GLP-1 concentration, it is useful as a therapeutic agent for diabetes, a preventive agent for chronic complications of diabetes, or an antiobesity agent.

The compound of the general formula [I] of the present invention can be used as a medicament containing it as an active ingredient, particularly as a therapeutic agent for diabetes, a preventive agent for chronic complications of diabetes or an antiobesity agent. In particular, the compound of the present invention in a therapeutic agent for diabetes, a preventive agent for chronic complications of diabetes or an antiobesity agent,
It means a pharmaceutically acceptable conventional one, for example, a compound of the general formula [I]

Embedded image [Wherein R, R ¹ , R ² , R ³ , R ⁴ , X ₁ , X ₂ , Y and Z
Has the meaning described above], R,
A pharmaceutically acceptable ester or salt at the carboxyl group on R ¹ , R ² , R ³ or R ⁴ , R, R ¹ , R ² ,
A salt at the hydroxyl group on R ³ or R ⁴ or R, R ¹ , R ² , R
Salts at the amino group on ³ or R ⁴ are included.

Examples of the salt at the carboxyl group or hydroxy group include alkali metal salts such as sodium salt and potassium salt; and alkaline earth metal salts such as calcium salt and magnesium salt.

Examples of the acid addition salt in the amino group include inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, carbonate, hydrogencarbonate, perchlorate, etc .; Organic acid salts such as, lactate, maleate, fumarate, tartrate, malate, citrate, ascorbate; methanesulfonate, isethionate, benzenesulfonate, toluenesulfonate Sulfonates such as salts; and acidic amino acid salts such as aspartate and glutamate.

When the compound of the present invention is used as a therapeutic agent for diabetes, a preventive agent for chronic complications of diabetes, or an antiobesity agent, it can be used as a pharmaceutically acceptable salt thereof. Typical examples of pharmaceutically acceptable salts include, for example, salts with alkali metals such as sodium and potassium.

The method for producing a pharmaceutically acceptable salt of the compound of the present invention can be carried out by appropriately combining methods generally used in the field of synthetic organic chemistry. Specific examples include neutralization titration of a free solution of the compound of the present invention with an alkaline solution.

When the compound of the present invention is used as a therapeutic agent for diabetes, a preventive agent for chronic complications of diabetes or an antiobesity agent, various administration forms can be selected.
Examples include oral preparations such as capsules, powders, granules, and liquid preparations, and sterilized liquid parenteral preparations such as solutions and suspensions.

A solid preparation can be produced as it is in the form of a tablet, capsule, granule or powder, but it can also be produced using an appropriate additive. Examples of the additives include sugars such as lactose and glucose, for example, starches such as corn, wheat and rice, fatty acids such as stearic acid, such as sodium metasilicate, magnesium aluminate, and inorganic salts such as anhydrous calcium phosphate.
For example, synthetic polymers such as polyvinylpyrrolidone and polyalkylene glycol, for example, calcium stearate, fatty acid salts such as magnesium stearate, for example, stearyl alcohol, alcohols such as benzyl alcohol,
Examples thereof include synthetic cellulose derivatives such as methylcellulose, carboxymethylcellulose, ethylcellulose, and hydroxypropylmethylcellulose, and other commonly used additives such as water, gelatin, talc, vegetable oil, and gum arabic.

These tablets, capsules, granules, powders and other solid preparations can generally contain 0.1 to 100% by weight, preferably 5 to 100% by weight, of the active ingredient. Liquid formulations include water, alcohols or soybean oil, for example.
It can be produced in the form of suspensions, syrups, injections and the like using appropriate additives usually used in liquid preparations such as vegetable-derived oils such as peanut oil and sesame oil.
In particular, suitable solvents for parenteral administration include:
For example, distilled water for injection, aqueous solution of lidocaine hydrochloride (for intramuscular injection), physiological saline, aqueous glucose solution, ethanol, liquid for intravenous injection (for example, aqueous solution of citric acid, sodium citrate, etc.), electrolyte solution (for example, intravenous drip) , Intravenous injection) and the like or a mixed solution thereof.

A liquid preparation such as a suspension or syrup for oral administration may contain 0.5 to 10% by weight of an active ingredient.

The actually preferred dose of the compound of the present invention can be appropriately increased or decreased depending on the kind of the compound to be used, the kind of the compounded composition, the frequency of application, the specific site to be treated, and the condition of the patient. For example, the daily dose per adult is 0.1% for oral administration.
The parenteral dose is 0.01 to 500 mg per day. The number of administrations varies depending on the administration method and symptoms, but can be administered once or divided into 2 to 5 times.

[0225]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

The thin-layer chromatograph of the example is a plate
Silicagel 60F ₂₄₅(Merck)
Was detected using a UV detector. Silica for column
As a gel, Wakogel^TM C-300 (Jun Wako
Drug) as a silica gel for reversed phase column, LC-SO
RB^TM SP-B-ODS (Chemco) or YM
C-GEL^TM ODS-AQ 120-S50 (Yamamura
Research Institute) was used.

I-Bu: isobutyl group n-Bu: n-butyl group t-Bu: t-butyl group Me: methyl group Et: ethyl group Ph: phenyl group i-Pr: isopropyl group n-Pr: n-propyl Group CDCl ₃ : deuterated chloroform methanol-d ₄ : deuterated methanol DMSO-d ₆ : deuterated dimethyl sulfoxide

[0228]

EXAMPLE 1001 9b- (2-methoxyphenyl) -3- (1-methylethyl
Tyl) [1,3] oxazolo [2,3-a] isoindo
-2,5 (3H, 9bH) -dione: (the following formula
In [I-1], R ¹ : H; R ² : H; R ³ : i-P
r: R ⁴ : H; Z: Ph; R: Compound of 2-MeO-Ph
Product) Magnesium 12 was added to a tetrahydrofuran solution (12 ml) containing 500 mg (3.4 mmol) of phthalic anhydride.
0 mg (5.1 mmol) and 2-bromoanisole.
A solution of a Grignard reagent in tetrahydrofuran (17 ml) prepared with 55 ml (4.4 mmol) was added dropwise over 10 minutes at -70 ° C under a nitrogen atmosphere. After stirring the reaction solution at -70 ° C for 2.5 hours, a saturated aqueous ammonium chloride solution was added to the reaction solution. The reaction solution was extracted with ethyl acetate and the organic layer was washed with a saturated saline solution, dried, concentrated under reduced pressure, and 770 mg of a crude product of 2- (2-methoxybenzoyl) benzoic acid (yield: 90
%).

A methylene chloride solution (40 ml) containing 750 mg (3.0 mmol) of 2- (2-methoxybenzoyl) benzoic acid, 550 mg (3.4 mmol) of D-valine methyl ester hydrochloride and 1.26 ml (9.1 mmol) of triethylamine. 490 mg (3.6 mmol) of 1-hydroxybenzotriazole hydrate and 1
690 mg (3.6 mmol) of-(3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride was added,
The reaction solution was stirred at room temperature for 3 hours. To the reaction solution was added a saturated aqueous solution of ammonium chloride, extracted with chloroform,
The organic layer was washed with a saturated saline solution, dried, and concentrated under reduced pressure. The obtained residue was dissolved in methanol (15 ml), a 4N aqueous sodium hydroxide solution (8 ml) was added, and the reaction solution was stirred at room temperature for 12 hours, and then concentrated under reduced pressure. A 1N aqueous hydrochloric acid solution (40 ml) and ethyl acetate were added to the obtained residue, and the organic layer was dried and concentrated under reduced pressure. The obtained unpurified carboxylic acid was dissolved in methylene chloride (6 ml), and trifluoroacetic acid (5 m
l) was added and the reaction solution was stirred at room temperature for 2 hours. After the reaction solution was concentrated under reduced pressure, the obtained residue was azeotropically repeated three times with toluene, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 2) to give the title compound 470.
mg (Yield: 46%) as a pale yellow oil.

¹ H NMR (CDCl ₃ ) δ: 0.85 (3
H, d, J = 6.6 Hz), 1.10 (3H, d, J =
6.6 Hz), 1.56-1.66 (1H, m), 3.
48 (3H, s), 4.17 (1H, d, J = 10.5
Hz), 6.83 (1H, d, J = 7.8 Hz), 7.
04 (1H, t, J = 7.8 Hz), 7.34-7.3
6 (1H, m), 7.38 (1H, t, J = 7.8H)
z), 7.53-7.60 (2H, m), 7.75 (1
H, d, J = 7.8 Hz), 7.89-7.92 (1
H, m) FAB-MS (m / e): 338 [M + H] ⁺

In the same manner as in Example 1001, Examples 1002 to 1222, 1413 and 1 corresponding to the compound numbers of the compounds of the general formula [I-1] in the above compound list were obtained.
Compounds 427 to 1439 were obtained. The physical constants are shown below.

[0232]

Embedded image

Example 1002 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: Ph) 1 HNMR (CDCl 3) δ: 0.92 (3H, d, J =
6.6 Hz), 1.11 (3H, d, J = 6.7H)
z), 1.56-1.67 (1H, m), 4.22 (1
H, d, J = 9.8 Hz), 7.33 (1H, dd, J
= 2.7, 5.8 Hz), 7.37-7.62 (7H,
m), 7.92 (1H, dd, J = 2.8, 5.8H
z) FAB-MS (m / e): 308 [M + H] ⁺

Example 1003 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 2-NH 2 -
Ph) ESI-MS (m / e): 323 [M + H] ⁺

Example 1004 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-F-P
h) ESI-MS (m / e): 326 [M + H] ⁺

Example 1005 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; Z: Ph; R: 4-Et ₂ N
-Ph) ESI-MS (m / e): 379 [M + H] ⁺

Example 1006 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-Cl-P
h) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, d, J =
6.6 Hz), 1.12 (3H, d, J = 7.2H)
z), 1.54-1.70 (1H, m), 4.21 (1
H, d, J = 9.4 Hz), 7.32 (1H, ddd,
J = 0.6, 2.4, 5.4 Hz), 7.37 (2H,
d, J = 9.0 Hz), 7.43 (2H, d, J = 9.
0 Hz), 7.58-7.62 (2H, m), 7.91
(1H, ddd, J = 0.6, 2.4, 5.4 Hz) FAB-MS (m / e): 342 [M + H] ⁺

Example 1007 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO-P
h) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.7 Hz), 1.11 (3H, d, J = 6.7H)
z), 1.59-1.75 (1H, m), 4.19 (1
H, d, J = 9.9 Hz), 6.85 (2H, d, J =
8.8 Hz), 7.33-7.37 (3H, m), 7.
57-7.60 (2H, m), 7.88-7.91 (1
H, m) FAB-MS (m / e): 324 [M + H] ⁺

Example 1008 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-MeO-
Ph) ¹ H NMR (CDCl ₃ ) δ: 0.96 (3H, d, J =
6.6 Hz), 1.12 (3H, d, J = 6.6H)
z), 1.63-1.71 (1H, m), 3.79 (3
H, s), 4.21 (1H, d, J = 9.9 Hz),
6.90 (1H, dd, J = 1.4, 8.0 Hz),
7.02 (1H, d, J = 1.4 Hz), 7.08 (1
H, d, J = 8.0 Hz), 7.31 (1H, t, J =
8.0 Hz), 7.36-7.38 (1H, m), 7.
56-7.62 (2H, m), 7.89-7.92 (1
H, m) FAB-MS (m / e): 338 [M + H] ⁺

Example 1009 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-HO-P
h) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.6 Hz), 1.12 (3H, d, J = 6.6H)
z), 1.67-1.72 (1H, m), 4.21 (1
H, d, J = 9.9 Hz), 6.85 (1H, ddd,
J = 0.9, 2.5, 7.9 Hz), 6.97 (1H,
d, J = 2.5 Hz), 7.06 (1H, dd, J =
0.9, 7.9 Hz), 7.27 (1H, t, J = 7.
9Hz), 7.34-7.38 (1H, m), 7.54
−7.62 (2H, m), 7.85-7.88 (1H,
m) FAB-MS (m / e): 324 [M + H] ⁺

Example 1010 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-NH 2 -
Ph) ESI-MS (m / e): 323 [M + H] ⁺

Example 1011 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-MeO-
Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.7 Hz), 1.11 (3H, d, J = 6.7H)
z), 1.63-1.69 (1H, m), 3.82 (3
H, s), 4.19 (1H, d, J = 9.9 Hz),
6.89 (2H, d, J = 8.8 Hz), 7.32-
7.37 (1H, m), 7.40 (2H, d, J = 8.
8Hz), 7.57-7.60 (2H, m), 7.89
−7.92 (1H, m) FAB-MS (m / e): 338 [M + H] ⁺

Example 1012 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-Me-P
h) ¹ H NMR (CDCl ₃ ) δ: 0.94 (3H, d, J =
6.6 Hz), 1.11 (3H, d, J = 6.7H)
z), 1.57-1.72 (1H, m), 2.36 (3
H, s), 4.20 (1H, d, J = 10.0 Hz),
7.22 (1H, d, J = 8.5 Hz), 7.32-
7.36 (1H, m), 7.37 (1H, d, J = 8.
5 Hz), 7.55-7.61 (2H, m), 7.88
−7.95 (1H, m) FAB-MS (m / e): 322 [M + H] ⁺

Example 1013 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Me-P
h) ¹ H NMR (CDCl ₃ ) δ: 0.86 (3H, d, J =
6.7 Hz), 1.03 (3H, d, J = 6.7H)
z), 1.52-1.60 (1H, m), 2.27 (3
H, s), 4.13 (1H, d, J = 9.9 Hz),
7.09-7.20 (4H, m,), 7.20-7.2
9 (1H, m), 7.47-7.53 (2H, m),
7.82-7.84 (1H, m) FAB-MS (m / e): 322 [M + H] ⁺

Example 1014 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; Z: Ph; R: t-BuO ₂
CCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, d, J =
6.7 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.47 (9H, s), 1.60-1.68 (1
H, m), 4.19 (1H, d, J = 9.9 Hz),
4.52 (2H, s), 6.89 (2H, d, J = 8.
8 Hz), 7.40 (2H, d, J = 8.8 Hz),
7.32-7.91 (4H, m) FAB-MS (m / e): 438 [M + H] ⁺

Example 1015 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; Z: Ph; R: HO ₂ CCH ₂
O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.6 Hz), 1.11 (3H, d, J = 6.6H)
z), 1.60-1.70 (1H, m), 4.19 (1
H, d, J = 9.9 Hz), 4.69 (2H, s),
6.84 (2H, d, J = 9.0 Hz), 7.43 (2
H, d, J = 9.0 Hz), 7.31-7.92 (4
H, m) FAB-MS (m / e): 382 [M + H] ⁺

Example 1016 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-tBuO
_{2 C (CH 2) 5 O} -Ph) 1 HNMR (CDCl 3) δ: 0.94 (3H, d, J =
6.6 Hz), 1.11 (3H, d, J = 6.6H)
z), 1.439-1.441 (9H, m), 1.49.
-1.84 (7H, m), 2.24 (2H, t, J =
7.2 Hz), 3.95 (2H, t, J = 6.4H)
z), 4.19 (1H, d, J = 10.1 Hz), 6.
87 (2H, d, J = 8.4 Hz), 7.32-7.3
5 (1H, m), 7.38 (2H, d, J = 8.4H
z), 7.55-7.60 (2H, m), 7.88-
7.91 (1H, m) FAB-MS (m / e): 494 [M + H] ⁺

Example 1017 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO 2 C
(CH ₂ ) ₅ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.83 (3H, d, J =
6.7 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.47-1.85 (7H, m), 2.39 (2
H, t, J = 7.8 Hz), 3.85 (2H, t, J =
7.2 Hz), 4.18 (1H, d, J = 10.7H)
z), 6.87 (2H, d, J = 8.9 Hz), 7.3
1-7.39 (1H, m), 7.39 (2H, d, J =
8.9 Hz), 7.54-7.61 (2H, m), 7.
87-7.92 (1H, m) FAB-MS (m / e): 438 [M + H] ⁺

Example 1018 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO (C
_{H 2) 3 O-Ph)} 1 HNMR (CDCl 3) δ: 0.93 (3H, d, J =
6.7 Hz), 1.11 (3H, d, J = 6.7H)
z), 1.61-1.71 (1H, m), 2.04 (2
H, quintet, J = 5.9 Hz), 3.86 (2
H, t, J = 5.9 Hz), 4.12 (2H, t, J =
5.9 Hz), 4.20 (1H, d, J = 9.8H)
z), 6.90 (2H, d, J = 8.8 Hz), 7.3
2-7.91 (6H, m) FAB-MS (m / e): 382 [M + H] ⁺

Example 1019 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO (C
_{H 2) 2 O-Ph)} 1 HNMR (CDCl 3) δ: 0.95 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.63-1.71 (1H, m), 3.99 (2
H, t, J = 4.4 Hz), 4.11 (2H, t, J =
4.4Hz), 4.22 (1H, d, J = 9.9H)
z), 6.94 (2H, d, J = 8.9 Hz), 7.2
9-7.93 (6H, m) FAB-MS (m / e): 368 [M + H] ⁺

Example 1020 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HOC
(Me) ₂ (CH ₂ ) ₂ O—Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.32 (6H, s), 1.61-1.68 (1
H, m), 2.01 (2H, t, J = 6.4 Hz),
4.19 (2H, t, J = 6.4 Hz), 4.21 (1
H, d, J = 9.9 Hz), 6.91 (2H, d, J =
8.9 Hz), 7.41 (2H, d, J = 8.9H)
z), 7.33-7.92 (4H, m) FAB-MS (m / e): 410 [M + H] ⁺

Example 1021 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-PhCH
₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.94 (3H, d, J =
6.6 Hz), 1.12 (3H, d, J = 6.6H)
z), 1.60-1.75 (1H, m), 4.20 (1
H, d, J = 9.9 Hz), 5.06 (2H, s),
6.98 (2H, d, J = 8.9 Hz), 7.33-
7.92 (11H, m) FAB-MS (m / e): 414 [M + H] ⁺

Example 1022 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-MeNH
COCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, d, J =
6.7 Hz), 1.11 (3H, d, J = 6.7H)
z), 1.60-1.68 (1H, m), 2.92 (3
H, d, J = 5.1 Hz), 4.20 (1H, d, J =
9.9 Hz), 4.50 (2H, s), 6.56-6.
59 (1H, m), 6.93 (2H, d, J = 8.9H)
z), 7.32-7.36 (1H, m), 7.45 (2
H, d, J = 8.9 Hz), 7.57-7.63 (2
H, m), 7.90-7.93 (1H, m) FAB-MS (m / e): 395 [M + H] ⁺

Example 1023 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-EtNH
COCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, d, J =
6.7 Hz), 1.11 (3H, d, J = 6.7 Hz)
1.18 (3H, t, J = 7.3 Hz), 1.60 −
1.70 (1H, m), 3.40 (2H, dt, J =
5.9, 7.3 Hz), 4.20 (1H, d, J = 9.
8Hz), 4.48 (2H, s), 6.53 (1H, b
rs), 6.93 (2H, d, J = 9.0 Hz), 7.
31-7.92 (6H, m) FAB-MS (m / e): 409 [M + H] ⁺

Example 1024 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Pr
^{_{NHCOCH 2 O-Ph) 1 HNMR}} (CDCl 3) δ: 0.89-0.94 (6
H, m), 1.12 (3H, d, J = 7.2 Hz),
1.53-1.66 (3H, m), 3.32 (2H, d
t, J = 7.2 Hz), 4.21 (1H, d, J = 9.
9Hz), 4.50 (2H, s), 6.53 (1H, b
r), 6.95 (2H, d, J = 8.9 Hz), 7.3
1-7.93 (6H, m) FAB-MS (m / e): 414 [M + H] ⁺

Example 1025 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Bu
NHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, t, J =
7.2 Hz), 0.92 (3H, d, J = 6.6H)
z), 1.11 (3H, d, J = 6.6 Hz), 1.2
6-1.40 (2H, m), 1.48-1.70 (3
H, m), 3.35 (2H, q, J = 6.8 Hz),
4.21 (1H, d, J = 9.8 Hz), 4.49 (2
H, s), 6.52-6.53 (1H, m), 6.94.
(2H, d, J = 9.0 Hz), 7.31-7.36
(1H, m), 7.45 (2H, d, J = 9.0H
z), 7.57-7.63 (2H, m), 7.88-
7.93 (1H, m) FAB-MS (m / e): 437 [M + H] ⁺

Example 1026 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-CH 2 =
CHCH ₂ NHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.61-1.67 (1H, m), 3.98-
4.02 (2H, m), 4.22 (1H, d, J = 9.
8 Hz), 4.54 (2H, s), 5.82-5.91
(1H, m), 6.65 (1H, br), 6.96 (2
H, d, J = 8.9 Hz), 7.33-7.94 (6
H, m) ESI-MS (m / e): 421 [M + H] ⁺

Example 1027 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-Me (C
_{H 2) 9 NHCOCH 2 O-} Ph) 1 HNMR (CDCl 3) δ: 0.87 (3H, t, J =
6.5 Hz), 0.92 (3H, d, J = 6.6H)
z), 1.11 (3H, d, J = 6.6 Hz), 1.2
5-1.67 (7H, m), 3.33 (2H, dt, J
= 6.8 Hz), 4.20 (1H, d, J = 9.8H)
z), 4.48 (2H, s), 6.61 (1H, b
r), 6.93 (2H, d, J = 9.0 Hz), 7.3
2-7.92 (6H, m) FAB-MS (m / e): 521 [M + H] ⁺

Example 1028 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-N 3 (C
_{H 2) 3 O-Ph)} 1 HNMR (CDCl 3) δ: 0.96 (3H, d, J =
6.6 Hz), 1.14 (3H, d, J = 6.6H)
z), 1.60-1.69 (1H, m), 2.07-
2.12 (2H, m), 3.54 (2H, t, J = 6.
6 Hz), 4.07 (2H, t, J = 6.2 Hz),
4.21 (1H, d, J = 9.9 Hz), 6.92 (2
H, d, J = 8.9 Hz), 7.34-7.94 (6
H, m) FAB-MS (m / e): 407 [M + H] ⁺

Example 1029 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-t-Bu
O ₂ CCH (Me) O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, d, J =
6.7 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.38-1.79 (13H, m), 4.19
(1H, d, J = 9.9 Hz), 4.61-4.64
(1H, m), 6.86 (2H, d, J = 8.9H)
z), 7.31-7.34 (1H, m), 7.38 (2
H, d, J = 8.9 Hz), 7.57-7.62 (2
H, m), 7.88-7.91 (1H, m) FAB-MS (m / e): 452 [M + H] ⁺

Example 1030 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Pr
NHCOCH (Me) O-Ph) 1 HNMR (CDCl 3) δ: 0.78-0.89 (3
H, m), 0.95 (3H, d, J = 6.8 Hz),
1.11 (3H, d, J = 6.8 Hz), 1.40 −
1.74 (6H, m), 3.11-3.32 (2H,
m), 4.20 (1H, d, J = 9.3 Hz), 4.6
4-4.70 (1H, m), 6.33-6.34 (1
H, m), 6.91 (2H, d, J = 8.2 Hz),
7.29-7.38 (1H, m), 7.39-7.43
(2H, m), 7.56-7.62 (2H, m), 7.
87-7.92 (1H, m) FAB-MS (m / e): 437 [M + H] ⁺

Example 1031 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; Z: Ph; R: 4-F ₃ CS
O ₃ -Ph) ¹ H NMR (CDCl ₃ ) δ: 0.89 (3H, d, J =
6.7 Hz), 1.12 (3H, d, J = 6.7H)
z), 1.59-1.67 (1H, m), 4.24 (1
H, d, J = 9.6 Hz), 7.31-7.34 (1
H, m), 7.33 (2H, d, J = 8.9 Hz),
7.59-7.66 (2H, m), 7.61 (2H,
d, J = 8.9 Hz), 7.92-7.95 (1H,
m) FAB-MS (m / e): 456 [M + H] ⁺

Example 1032 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-t-Bu
O ₂ CCH = CH-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, d, J =
6.6 Hz), 1.11 (3H, d, J = 6.6H)
z), 1.44 (9H, s), 1.50-1.66 (1
H, m), 4.21 (1H, d, J = 9.7 Hz),
6.38 (1H, d, J = 16.0 Hz), 7.32-
7.36 (1H, m), 7.51-7.55 (4H,
m), 7.58-7.64 (3H, m), 7.90-
7.94 (1H, m) FAB-MS (m / e): 434 [M + H] ⁺

Example 1033 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Pr
NHCOCH = CH-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, d, J =
6.7 Hz), 0.97 (3H, t, J = 7.4H)
z), 1.11 (3H, d, J = 6.7 Hz), 1.5
6-1.75 (3H, m), 3.36 (2H, q, J =
6.7 Hz), 4.22 (1H, d, J = 9.9H)
z), 5.69 (1H, s), 6.41 (1H, d, J
= 15.7 Hz), 7.31-7.36 (1H, m),
7.47-7.54 (4H, m), 7.59-7.63
(2H, m), 7.61 (1H, d, J = 15.7H
z), 7.90-7.95 (1H, m) FAB-MS (m / e): 419 [M + H] ⁺

Example 1034 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Pr
CH (Me) NHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, t, J =
5.3Hz), 0.93 (3H, d, J = 6.6H)
z), 1.12 (3H, d, J = 6.6 Hz), 1.1
6 (3H, d, J = 6.6 Hz), 1.27-1.48
(4H, m), 1.61-1.69 (1H, m), 4.
07-4.12 (1H, m), 4.22 (1H, d, J
= 9.8 Hz), 4.48 (2H, s), 6.26 (1
H, br), 6.95 (2H, d, J = 8.9 Hz),
7.32-7.94 (6H, m) FAB-MS (m / e): 451 [M + H] ⁺

Example 1035 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-EtCH
(Me) NHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.87 (3H, t, J =
7.5 Hz), 0.92 (3H, d, J = 6.6H)
z), 1.11 (3H, d, J = 6.7 Hz), 1.1
5 (3H, d, J = 6.6 Hz), 1.46-1.52
(2H, m), 1.60-1.70 (1H, m), 3.
98-4.03 (1H, m), 4.21 (1H, d, J
= 9.8 Hz), 4.48 (2H, s), 6.24 (1
H, br), 6.94 (2H, d, J = 8.9 Hz),
7.31-7.93 (6H, m) FAB-MS (m / e): 437 [M + H] ⁺

Example 1036 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-MeOC
^{_{H 2 O-Ph) 1 HNMR}} (CDCl 3) δ: 0.97 (3H, d, J =
6.9 Hz), 1.13 (3H, d, J = 6.9H)
z), 1.60-1.70 (1H, m), 3.49 (3
H, s), 4.20 (1H, d, J = 9.6 Hz),
5.19 (2H, s), 7.05 (2H, d, J = 8.
4Hz), 7.35-7.93 (6H, m) ESI-MS (m / e): 368 [M + H] ⁺

Example 1037 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-EtCO
CH ₂ O—Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.6 Hz), 1.12 (3H, d, J = 6.6H)
z), 1.12 (3H, t, J = 7.3 Hz), 1.6
0-1.68 (1H, m), 2.26 (2H, q, J =
7.3 Hz), 4.20 (1H, d, J = 9.9H)
z), 4.58 (2H, s), 6.89 (2H, d, J
= 8.9 Hz), 7.32-7.92 (6H, m) ESI-MS (m / e): 394 [M + H] ⁺

Example 1038 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-tBuO
₂ CCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.94 (3H, d, J =
6.7 Hz), 1.11 (3H, d, J = 6.7H)
z), 1.46 (9H, s), 1.61-1.73 (1
H, m), 4.20 (1H, d, J = 9.9 Hz),
4.50 (2H, s), 6.89 (1H, dd, J =
2.3, 8.1 Hz), 7.02 (1H, dd, J =
1.1, 2.3 Hz), 7.10 (1H, dd, J =
1.1, 8.1 Hz), 7.31 (1H, t, J = 8.
1Hz), 7.33-7.37 (1H, m), 7.56
−7.61 (2H, m), 7.87-7.92 (1H,
m) FAB-MS (m / e): 438 [M + H] ⁺

Example 1039 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-HO 2 C
CH ₂ O—Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.6 Hz), 1.10 (3H, d, J = 6.6H)
z), 1.59-1.69 (1H, m), 4.20 (1
H, d, J = 9.0 Hz), 4.68 (2H, s),
6.90-6.94 (1H, m), 7.08-7.26
(3H, m), 7.31-7.36 (1H, m), 7.
57-7.62 (2H, m), 7.88-7.93 (1
H, m) FAB-MS (m / e): 382 [M + H] ⁺

Example 1040 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-n-Pr
NHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, t, J =
7.4 Hz), 0.94 (3H, d, J = 6.6H)
z), 1.12 (3H, d, J = 6.6 Hz), 1.5
2-1.72 (3H, m), 3.32 (2H, q, J =
6.8 Hz), 4.22 (1H, d, J = 9.8H)
z), 4.47 (2H, s), 6.56-6.58 (1
H, m), 6.91 (1H, dd, J = 2.2, 7.6)
Hz), 7.11 (1H, dd, J = 1.1, 2.2H)
z), 7.14 (1H, dd, J = 1.1, 7.8H
z), 7.33-7.38 (2H, m), 7.58-
7.64 (2H, m), 7.91-7.94 (1H,
m) FAB-MS (m / e): 423 [M + H] ⁺

Example 1041 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-H 2 NC
(Me) ₂ CH ₂ O ₂ CCH ₂ O-Ph) FAB-MS (m / e): 453 [M + H] ⁺

Example 1042 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-morp
holinoCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.94 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.60-1.68 (1H, m), 3.59-
3.69 (8H, m), 4.21 (1H, d, J = 9.
8Hz), 4.72 (2H, s), 6.96 (2H,
d, J = 9.0 Hz), 7.33-7.93 (6H,
m) ESI-MS (m / e): 451 [M + H] ⁺

Example 1043 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4- (4-C
1-Ph) -COCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.6 Hz), 1.11 (3H, d, J = 6.6H)
z), 1.62-1.66 (1H, m), 4.19 (1
H, d, J = 9.9 Hz), 5.25 (2H, s),
6.93 (2H, d, J = 8.9 Hz), 7.32-
7.97 (10H, m) ESI-MS (m / e): 476 [M + H] ⁺

Example 1044 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-PhCO
CH ₂ O—Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.7 Hz), 1.11 (3H, d, J = 6.7H)
z), 1.61-1.70 (1H, m), 4.19 (1
H, d, J = 9.9 Hz), 5.31 (2H, s),
6.94 (2H, d, J = 9.0 Hz), 7.33-
8.01 (11H, m) ESI-MS (m / e): 442 [M + H] ⁺

Example 1045 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4- (4-p
yridyl) -CH ₂ NHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, d, J =
6.5 Hz), 1.12 (3H, d, J = 6.5H)
z), 1.61-1.67 (1H, m), 4.21 (1
H, d, J = 9.7 Hz), 4.57 (1H, d, J =
6.4 Hz), 4.60 (2H, s), 6.96 (2
H, d, J = 8.9 Hz), 7.20-8.57 (10
H, m) ESI-MS (m / e): 472 [M + H] ⁺

Example 1046 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-H 2 NC
_{H 2 CH 2 NHCOCH 2 O-} Ph) 1 HNMR (methanol-d 4) δ: 0.87-
1.09 (6H, m), 1.57-2.15 (1H,
m), 3.06-3.12 (2H, m), 3.52-
3.59 (2H, m), 4.20 (1H, d, J = 9.
5 Hz), 4.54-4.64 (2H, m), 6.90
-7.91 (8H, m) FAB-MS (m / e): 424 [M + H] ⁺

Example 1047 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-Cl-3
—NO ₂ —Ph) ESI-MS (m / e): 387 [M + H] ⁺

Example 1048 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-Cl-3
-F-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.94 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.59-1.72 (1H, m), 4.22 (1
H, d, J = 9.4 Hz), 7.24-7.36 (3
H, m), 7.44 (1H, t, J = 7.7 Hz),
7.59-7.65 (2H, m), 7.90-7.94
(1H, m) FAB-MS (m / e): 360 [M + H] ⁺

Example 1049 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-Cl-3
-Me-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.94 (3H, d, J =
6.7 Hz), 1.12 (3H, d, J = 6.7H)
z), 1.58-1.72 (1H, m), 2.38 (3
H, s), 4.20 (1H, d, J = 9.9 Hz),
7.21-7.27 (1H, m), 7.31-7.35
(1H, m), 7.35 (2H, d, J = 8.5H
z), 7.57-7.63 (2H, m), 7.88-
7.95 (1H, m) FAB-MS (m / e): 356 [M + H] ⁺

Example 1050 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-NH 2 -
^{4-Cl-Ph) 1 HNMR} (CDCl 3) δ: 0.96 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.5H)
z), 1.60-1.77 (1H, m), 4.19 (1
H, d, J = 9.9 Hz), 6.75 (1H, dd, J)
= 2.4, 8.2 Hz), 6.92 (1H, d, J =
2.4, Hz), 7.23 (1H, d, J = 8.2, H
z), 7.33-7.39 (1H, m), 7.57-
7.63 (2H, m), 7.86-7.93 (1H,
m) FAB-MS (m / e): 357 [M + H] ⁺

Example 1051 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Cl-4
-MeO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7 Hz)
1.57-1.65 (1H, m), 3.91 (3H,
s), 4.20 (1H, d, J = 9.9 Hz), 6.9
2 (1H, d, J = 8.6 Hz), 7.33-7.93
(6H, m) FAB-MS (m / e): 372 [M + H] ⁺

Example 1052 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Cl-4
-Me-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.7 Hz), 1.12 (3H, d, J = 6.7H)
z), 1.62-1.69 (1H, m), 2.37 (3
H, s), 4.20 (1H, d, J = 9.8 Hz),
7.26-7.33 (2H, m), 7.33-7.36
(1H, m), 7.49 (1H, s), 7.57-7.
62 (2H, m), 7.89-7.93 (1H, m) FAB-MS (m / e): 356 [M + H] ⁺

Example 1053 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-Br-3
^{-Cl-Ph) 1 HNMR (CDCl} 3) δ: 0.88 (3H, d, J =
6.7 Hz), 1.12 (3H, d, J = 6.7H)
z), 1.50-1.60 (1H, m), 4.24 (1
H, d, J = 9.6 Hz), 7.50-7.95 (7
H, m) FAB-MS (m / e): 420/422 [M + H] ⁺

Example 1054 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-Br-2
^{-Cl-Ph) 1 HNMR (CDCl} 3) δ: 0.94 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.5H)
z), 1.62-1.67 (1H, m), 4.22 (1
H, d, J = 9.7 Hz), 7.22-7.94 (7
H, m) FAB-MS (m / e): 420/422 [M + H] ⁺

Example 1055 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-F-3-
Me-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.7 Hz), 1.12 (3H, d, J = 6.7H)
z), 1.61-1.68 (1H, m), 2.28 (3
H, s), 4.20 (1H, d, J = 9.9 Hz),
7.01 (1H, t, J = 8.9 Hz), 7.27−
7.35 (3H, m), 7.59-7.62 (2H,
m), 7.90-7.93 (1H, m) FAB-MS (m / e): 340 [M + H] ⁺

Example 1056 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-F-4-
Me-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.94 (3H, d, J =
6.7 Hz), 1.12 (3H, d, J = 6.7H)
z), 1.63-1.70 (1H, m), 2.28 (3
H, s), 4.21 (1H, d, J = 9.9 Hz),
7.16 (1H, d, J = 7.2 Hz), 7.18 (1
H, s), 7.20 (1H, d, J = 7.2 Hz),
7.33-7.36 (1H, m), 7.57-7.63
(2H, m), 7.90-7.93 (1H, m) FAB-MS (m / e): 340 [M + H] ⁺

Example 1057 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Br-4
-HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.62-1.72 (1H, m), 4.20 (1
H, d, J = 9.9 Hz), 5.70 (1H, s),
7.02 (1H, d, J = 8.6 Hz), 7.30−
7.37 (1H, m), 7.32 (1H, d, J = 8.
6Hz), 7.58-7.65 (2H, m), 7.64
(1H, s), 7.90-7.93 (1H, m) FAB-MS (m / e): 402/404 [M + H] ⁺

Example 1058 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Br-4
-MeO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.61-1.73 (1H, m), 3.91 (3
H, s), 4.20 (1H, d, J = 9.9 Hz),
6.90 (1H, d, J = 8.6 Hz), 7.32-
7.38 (1H, m), 7.42 (1H, dd, J =
2.3, 8.6 Hz), 7.58-7.64 (2H,
m), 7.66 (1H, d, J = 2.3 Hz), 7.8
8-7.94 (1H, m) FAB-MS (m / e): 416/418 [M + H] ⁺

Example 1059 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Br-4
-F-Ph) ESI-MS (m / e): 404 [M + H] ⁺

Example 1060 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-F-4-
Ph-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.88 (3H, d, J =
6.5 Hz), 1.15 (3H, d, J = 6.5H)
z), 1.65-1.80 (1H, m), 4.23 (1
H, d, J = 9.9 Hz), 7.28-7.56 (9
H, m), 7.56-7.66 (2H, m), 7.91
−7.95 (1H, m) FAB-MS (m / e): 402 [M + H] ⁺

Example 1061 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO-3
-I-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.63-1.69 (1H, m), 4.19 (1
H, d, J = 9.9 Hz), 5.71 (1H, s),
6.98 (1H, d, J = 8.5 Hz), 7.32-
7.93 (6H, m) FAB-MS (m / e): 450 [M + H] ⁺

Example 1062 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 5-HO-2
-I-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.7 Hz), 1.12 (3H, d, J = 6.7H)
z), 1.63-1.75 (1H, m), 4.20 (1
H, d, J = 9.9 Hz), 6.04 (1H, br)
s), 6.82 (1H, dd, J = 2.1, 8.2H)
z), 7.11 (1H, d, J = 2.1 Hz), 7.3
3-7.36 (1H, m), 7.55-7.62 (2
H, m), 7.69 (1H, d, J = 8.2 Hz),
7.84-7.87 (1H, m) FAB-MS (m / e): 450 [M + H] ⁺

Example 1063 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
MeO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.96 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.59-1.68 (1H, m), 3.89 (3
H, s), 4.20 (1H, d, J = 9.9 Hz),
6.81 (1H, d, J = 8.6 Hz), 7.34-
7.93 (6H, m) FAB-MS (m / e): 464 [M + H] ⁺

Example 1064 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 2-I-5-
MeO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.98 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.63-1.71 (1H, m), 3.86 (3
H, s), 4.22 (1H, d, J = 10.1 Hz),
6.87 (1H, dd, J = 1.9, 8.0 Hz),
6.91 (1H, d, J = 1.9 Hz), 7.35-
7.37 (1H, m), 7.58-7.64 (2H,
m), 7.79 (1H, d, J = 8.0 Hz), 7.9
2 (1H, dd, J = 3.0, 5.7 Hz) FAB-MS (m / e): 464 [M + H] ⁺

Example 1065 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-MeO-
3-Me-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.6 Hz), 1.11 (3H, d, J = 6.6H)
z), 1.60-1.70 (1H, m), 2.18 (3
H, s), 3.83 (3H, s), 4.18 (1H,
d, J = 10.0 Hz), 6.80 (1H, d, J =
8.6 Hz), 7.20 (1H, d, J = 2.6H)
z), 7.30 (1H, dd, J = 2.6, 8.6H
z), 7.32-7.36 (1H, m), 7.54-
7.61 (2H, m), 7.88-7.92 (1H,
m) FAB-MS (m / e): 352 [M + H] ⁺

Example 1066 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO (C
_{H 2) 3 O-3-} I-Ph) 1 HNMR (CDCl 3) δ: 0.97 (3H, d, J =
6.7 Hz), 1.14 (3H, d, J = 6.7H)
z), 1.57-1.70 (1H, m), 2.13 (2
H, dt, J = 5.6 Hz), 3.95 (2H, t, J)
= 5.6 Hz), 4.20 (2H, t, J = 5.6H)
z), 4.21 (1H, d, J = 9.9 Hz), 6.8
3 (1H, d, J = 8.6 Hz), 7.35-7.94
(6H, m) FAB-MS (m / e): 508 [M + H] ⁺

Example 1067 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO (C
_{H 2) 2 O-3-} I-Ph) 1 HNMR (CDCl 3) δ: 0.96 (3H, d, J =
6.7 Hz), 1.15 (3H, d, J = 6.7H)
z), 1.58-1.68 (1H, m), 4.01 (2
H, t, J = 4.4 Hz), 4.15 (2H, t, J =
4.4Hz), 4.21 (1H, d, J = 9.9H)
z), 6.83 (1H, d, J = 8.6 Hz), 7.3
4-7.94 (6H, m) FAB-MS (m / e): 494 [M + H] ⁺

Example 1068 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HOC
(Me) ₂ (CH ₂ ) ₂ O-3-I-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.96 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.34 (6H, s), 1.60-1.65 (1
H, m), 2.08 (2H, t, J = 6.0 Hz),
4.19 (1H, d, J = 9.9 Hz), 4.23 (2
H, t, J = 6.0 Hz), 6.82 (1H, d, J =
8.7 Hz), 7.32-7.94 (6H, m) FAB-MS (m / e): 536 [M + H] ⁺

Example 1069 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-t-Bu
_{O 2 C (CH 2) 4} O-3-I-Ph) 1 HNMR (CDCl 3) δ: 0.95 (3H, d, J =
6.6 Hz), 1.12 (3H, d, J = 6.6H)
z), 1.44 (9H, s), 1.60-1.67 (1
H, m), 1.82-1.86 (4H, m), 2.32
(2H, t, J = 6.8 Hz), 4.01 (2H, t,
J = 5.3 Hz), 4.18 (1H, d, J = 10.0)
Hz), 6.75 (1H, d, J = 8.6 Hz), 7.
32-7.91 (6H, m) FAB-MS (m / e): 606 [M + H] ⁺

Example 1070 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
PhCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.96 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.60-1.75 (1H, m), 4.20 (1
H, d, J = 9.9 Hz), 5.16 (2H, s),
6.86 (1H, d, J = 8.6 Hz), 7.34-
7.93 (11H, m) FAB-MS (m / e): 540 [M + H] ⁺

Example 1071 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-H 2 NC
OCH ₂ O-3-I-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.61-1.69 (1H, m), 4.21 (1
H, d, J = 9.9 Hz), 4.53 (2H, s),
5.86 (1H, br), 6.78 (1H, d, J =
8.6Hz), 6.86 (1H, br), 7.33-
7.94 (6H, m) FAB-MS (m / e): 507 [M + H] ⁺

Example 1072 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
MeNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.61-1.69 (1H, m), 2.97 (3
H, d, J = 5.0 Hz), 4.21 (1H, d, J =
9.8 Hz), 4.53 (2H, s), 6.77 (1
H, d, J = 8.6 Hz), 6.87 (1H, br),
7.33-7.94 (6H, m) FAB-MS (m / e): 521 [M + H] ⁺

Example 1073 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-EtNH
COCH ₂ O-3-I-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.24 (3H, t, J = 7.3 Hz), 1.6
1-1.69 (1H, m), 3.44 (2H, dt, J
= 7.3 Hz), 4.21 (1H, d, J = 9.8H)
z), 4.51 (2H, s), 6.77 (1H, d, J
= 8.6 Hz), 6.89 (1H, br), 7.33-
7.94 (6H, m) FAB-MS (m / e): 535 [M + H] ⁺

Example 1074 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.97 (3H, t, J =
7.8 Hz), 1.00 (3H, d, J = 6.7H)
z), 1.13 (3H, d, J = 6.7 Hz), 1.5
7-1.69 (3H, m), 3.37 (2H, dt, J
= 7.0 Hz), 4.22 (1H, d, J = 9.8H)
z), 4.52 (2H, s), 6.78 (1H, d, J
= 8.6 Hz), 6.91 (1H, br), 7.33-
7.94 (6H, m) FAB-MS (m / e): 549 [M + H] ⁺

Example 1075 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
i-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.25 (6H, d, J = 6.3 Hz), 1.6
1-1.69 (1H, m), 4.11-4.20 (1
H, m), 4.21 (1H, d, J = 9.8 Hz),
4.49 (2H, s), 6.77 (1H, br), 6.
77 (1H, d, J = 9.8 Hz), 7.33-7.9
4 (6H, m) FAB-MS (m / e): 549 [M + H] ⁺

Example 1076 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Bu
_{NHCOCH 2 O-3-I-} Ph) 1 HNMR (CDCl 3) δ: 0.92-0.97 (6
H, m), 1.12 (3H, d, J = 6.8 Hz),
1.35-1.68 (5H, m), 3.39 (2H, d
t, J = 6.3 Hz), 4.20 (1H, d, J = 9.
9Hz), 4.51 (2H, s), 6.76 (1H,
d, J = 8.6 Hz), 6.90 (1H, br), 7.
32-7.93 (6H, m) FAB-MS (m / e): 563 [M + H] ⁺

Example 1077 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-t-Bu
NHCOCH ₂ O-3-I-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.94 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.44 (9H, s), 1.61-1.69 (1
H, m), 4.21 (1H, d, J = 9.8 Hz),
4.40 (2H, s), 6.76 (1H, d, J = 8.
6Hz), 6.86 (1H, br), 7.33-7.9
4 (6H, m) FAB-MS (m / e): 563 [M + H] ⁺

Example 1078 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-i-Bu
NHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.88-0.96 (9
H, m), 1.11 (3H, d, J = 6.7 Hz),
1.60-1.83 (2H, m), 3.18 (2H,
t, J = 6.5 Hz), 4.20 (1H, d, J = 9.
8Hz), 4.51 (2H, s), 6.54 (1H, b
r), 6.95 (2H, d, J = 8.9 Hz), 7.3
1-7.93 (6H, m) FAB-MS (m / e): 437 [M + H] ⁺

Example 1079 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-t-Bu
O ₂ CCH ₂ O-3-I-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.96 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.48 (9H, s), 1.51-1.68 (1
H, m), 4.20 (1H, d, J = 9.9 Hz),
4.61 (2H, s), 6.69 (1H, d, J = 8.
6 Hz), 7.34-7.94 (6H, m) FAB-MS (m / e): 564 [M + H] ⁺

Example 1080 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
PhCH ₂ NHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.94 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.63-1.66 (1H, m), 4.20 (1
H, d, J = 9.8 Hz), 4.58 (2H, s),
4.59 (2H, d, J = 5.5 Hz), 6.79 (1
H, d, J = 8.6 Hz), 7.27-7.94 (11
H, m) FAB-MS (m / e): 597 [M + H] ⁺

Example 1081 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
(2-tetrahydrofuryl) CH ₂ NHC
OCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.96 (3H, d, J =
6.6 Hz), 1.14 (3H, d, J = 6.6H)
z), 1.56-2.06 (5H, m), 3.38-
4.14 (5H, m), 4.22 (1H, d, J = 9.
8 Hz), 4.54 (2H, s), 6.78 (1H,
d, J = 8.6 Hz), 7.23 (1H, br), 7.
33-7.96 (6H, m) ESI-MS (m / e): 591 [M + H] ⁺

Example 1082 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-cycl
_{oPrNHCOCH 2 O-3-I-} Ph) 1 HNMR (CDCl 3) δ: 0.61-0.64 (2
H, m), 0.85-0.89 (2H, m), 0.95
(3H, d, J = 6.7 Hz), 1.14 (3H, d,
J = 6.7 Hz), 1.62-1.67 (1H, m),
2.84-2.88 (1H, m), 4.22 (1H,
d, J = 9.9 Hz), 4.51 (2H, s), 6.7
6 (1H, d, J = 8.6 Hz), 7.00 (1H, b
r), 7.33-7.95 (6H, m) FAB-MS (m / e): 547 [M + H] ⁺

Example 1083 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-cycl
_{oPentylNHCOCH 2 O-3-I-} Ph) 1 HNMR (CDCl 3) δ: 0.95 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.50-1.77 (7H, m), 2.00-
2.03 (2H, m), 4.22 (1H, d, J = 9.
6 Hz), 4.24-4.36 (1H, m), 4.50
(2H, s), 6.77 (1H, d, J = 8.6H)
z), 6.95 (1H, br), 7.33-7.94
(6H, m) FAB-MS (m / e): 575 [M + H] ⁺

Example 1084 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-cycl
_{oHexylNHCOCH 2 O-3-I-} P) 1 HNMR (CDCl 3) δ: 0.94 (3H, d, J =
6.7 Hz), 1.12 (3H, d, J = 6.7H)
z), 1.26-1.97 (11H, m), 3.89-
3.93 (1H, m), 4.21 (1H, d, J = 9.
7 Hz), 4.99 (2H, s), 6.77 (1H,
d, J = 8.6 Hz), 6.89 (1H, brd, J =
10.0 Hz), 7.33-7.93 (6H, m) FAB-MS (m / e): 589 [M + H] ⁺

Example 1085 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-cycl
oPrNHCOCH ₂ O-3-F-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.57-0.59 (2
H, m), 0.83-0.88 (2H, m), 0.93
(3H, d, J = 6.6 Hz), 1.13 (3H, d,
J = 6.6 Hz), 1.60-1.68 (1H, m),
2.75-2.83 (1H, m), 4.21 (1H,
d, J = 9.7 Hz), 4.51 (2H, s), 6.6.
8 (1H, br), 6.92-7.93 (7H, m) ESI-MS (m / e): 439 [M + H] ⁺

Example 1086 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-Me (C
_{H 2) 9 NHCOCH 2 O-} 3-I-Ph) 1 HNMR (CDCl 3) δ: 0.88 (3H, t, J =
6.3 Hz), 0.95 (3H, d, J = 6.6H)
z), 1.13 (3H, d, J = 6.6 Hz), 1.2
0-1.40 (14H, m), 1.56-1.70 (3
H, m), 3.38 (2H, dt, J = 6.6 Hz),
4.20 (1H, d, J = 9.9 Hz), 4.51 (2
H, s), 6.77 (1H, d, J = 8.6 Hz),
6.92 (1H, br), 7.33-7.94 (6H,
m) FAB-MS (m / e): 647 [M + H] ⁺

Example 1087 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO 2 C
_{CH 2 O-3-I-} Ph) 1 HNMR (CDCl 3) δ: 0.96 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.51-1.68 (1H, m), 4.20 (1
H, d, J = 9.9 Hz), 4.61 (2H, s),
6.69 (1H, d, J = 8.6 Hz), 7.34-
7.94 (6H, m) FAB-MS (m / e): 508 [M + H] ⁺

Example 1088 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-N 3 (C
_{H 2) 3 O-3-} I-Ph) 1 HNMR (CDCl 3) δ: 0.97 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.60-1.68 (1H, m), 2.09-
2.13 (2H, m), 3.63 (2H, t, J = 6.
5 Hz), 4.11 (2H, t, J = 5.3 Hz),
4.20 (1H, d, J = 9.9 Hz), 6.79 (1
H, d, J = 8.6 Hz), 7.34-7.94 (6
H, m) FAB-MS (m / e): 533 [M + H] ⁺

Example 1089 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
_{n-PrNHCO (CH 2) 4} O-Ph) 1 HNMR (CDCl 3) δ: 0.92 (3H, t, J =
7.4 Hz), 0.96 (3H, d, J = 6.7H)
z), 1.13 (3H, d, J = 6.7 Hz), 1.4
5-1.55 (2H, m), 1.62-1.69 (1
H, m), 1.87-1.92 (4H, m), 2.28
-2.32 (2H, m), 3.21 (2H, dt, J =
7.0 Hz), 4.02-4.09 (2H, br),
4.20 (1H, d, J = 9.9 Hz), 5.51 (1
H, br), 6.77 (1H, d, J = 8.6 Hz),
7.34-7.93 (6H, m) FAB-MS (m / e): 591 [M + H] ⁺

Example 1090 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-Et 2 N
COCH ₂ O-3-I-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.6 Hz), 1.12 (6H, m), 1.22 (3
H, t, J = 7.0 Hz), 1.60-1.68 (1
H, m), 3.39-3.45 (4H, m), 4.19
(1H, d, J = 9.9 Hz), 4.77 (2H,
s), 6.88 (1H, d, J = 8.7 Hz), 7.3
4-7.93 (6H, m) FAB-MS (m / e): 563 [M + H] ⁺

Example 1091 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
n-PrN (Me) COCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.84 (3H, t, J =
7.3 Hz), 0.98 (3H, d, J = 6.7H)
z), 1.15 (3H, d, J = 6.7 Hz), 1.5
0-1.69 (3H, m), 2.96 (3H, s, ro
tomer), 3.11 (3H, s, rotome)
r), 3.37 (2H, t, J = 7.3 Hz), 4.8
0 (1H, d, J = 10.0 Hz), 4.79 (2H,
s, rotomer), 4.81 (2H, s, rotomer)
mer), 6.87-7.94 (7H, m, rotom)
er) FAB-MS (m / e): 563 [M + H] ⁺

Example 1092 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Cl-4
_{-N-PrNHCOCH 2 O-Ph)} 1 HNMR (CDCl 3) δ: 0.93-0.98 (6
H, m), 1.13 (3H, d, J = 6.6 Hz),
1.56-1.70 (3H, m), 3.34 (2H, d
t, J = 6.6 Hz), 4.21 (1H, d, J = 9.
8 Hz), 4.54 (2H, s), 6.80 (1H, b
r), 6.92 (1H, d, J = 8.6 Hz), 7.3
3-7.94 (6H, m) ESI-MS (m / e): 457 [M + H] ⁺

Example 1093 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Br-4
_{-N-PrNHCOCH 2 O-Ph)} 1 HNMR (CDCl 3) δ: 0.97 (3H, t, J =
7.8 Hz), 0.97 (3H, d, J = 6.6H)
z), 1.13 (3H, d, J = 6.6 Hz), 1.5
6-1.69 (3H, m), 3.34 (2H, q, J =
6.6 Hz), 4.22 (1H, d, J = 10.0H)
z), 4.53 (2H, s), 6.87-6.89 (1
H, m), 6.87 (1H, d, J = 8.5 Hz),
7.34-7.36 (1H, m), 7.45 (1H,
d, J = 8.5 Hz), 7.60-7.63 (2H,
m), 7.72 (1H, s), 7.89-7.94 (1
H, m) FAB-MS (m / e): 501/503 [M + H] ⁺

Example 1094 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-F-4-
_{n-PrNHCOCH 2 O-Ph)} 1 HNMR (CDCl 3) δ: 0.90-0.95 (6
H, m), 1.12 (3H, d, J = 6.6 Hz),
1.54-1.70 (3H, m), 3.32 (2H, d
t, J = 6.6 Hz), 4.21 (1H, d, J = 9.
7Hz), 4.53 (2H, s), 6.65 (1H, b
r), 6.94-7.93 (7H, m) FAB-MS (m / e): 441 [M + H] ⁺

Example 1095 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Me-4
-N-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, t, J =
7.6 Hz), 0.95 (3H, d, J = 6.8H)
z), 1.11 (3H, d, J = 6.8 Hz), 1.5
3-1.74 (3H, m), 2.28 (3H, s),
3.33 (2H, q, J = 6.6 Hz), 4.21 (1
H, d, J = 9.9 Hz), 4.49 (2H, s),
6.51-6.52 (1H, m), 6.78 (1H,
d, J = 8.2 Hz), 7.29-7.36 (3H,
m), 7.56-7.62 (2H, m), 7.88-
7.92 (1H, m) FAB-MS (m / e): 437 [M + H] ⁺

Example 1096 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-EtNH
COCH ₂ O-3-F-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.94 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.20 (3H, t, J = 7.3 Hz), 1.6
0-1.68 (1H, m), 3.41 (2H, dt, J
= 7.3 Hz), 4.21 (1H, d, J = 9.8H)
z), 4.53 (2H, s), 6.63 (1H, b
r), 6.95-7.94 (7H, m) ESI-MS (m / e): 427 [M + H] ⁺

Example 1097 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
i-PrNHCOC (Me) ₂ CH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, t, J =
7.4 Hz), 0.96 (3H, d, J = 6.7H)
z), 1.13 (3H, d, J = 6.7 Hz), 1.5
2-1.69 (3H, m), 3.23 (2H, dt, J
= 5.7 Hz), 3.93-3.99 (2H, m),
4.19 (1H, d, J = 11.0 Hz), 6.27
(1H, br), 6.77 (1Hd, J = 8.7H)
z), 7.32-7.92 (6H, m) FAB-MS (m / e): 427 [M + H] ⁺

Example 1098 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Br-4
_{-CH 2 = CHCH 2 NHCOCH 2 O} -Ph) 1 HNMR (CDCl 3) δ: 0.94 (3H, t, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.60-1.70 (1H, m), 4.00-
4.04 (2H, m), 4.22 (1H, d, J = 9.
7Hz), 4.56 (2H, s), 5.18 (1H,
d, J = 10.3 Hz), 5.24 (1H, d, J = 1)
9.7 Hz), 5.81-5.96 (1H, m), 6.
88-6.92 (1H, m), 6.89 (1H, d, J
= 8.6 Hz), 7.33-7.37 (1H, m),
7.45 (1H, dd, J = 2.3, 8.6 Hz),
7.61-7.65 (2H, m), 7.72 (1H,
d, J = 2.3 Hz), 7.90-7.95 (1H,
m) FAB-MS (m / e): 499/501 [M + H] ⁺

Example 1099 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-i-Bu
NHCOCH ₂ O-3-F-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.90 (6H, d, J =
6.7 Hz), 0.93 (3H, d, J = 6.7H)
z), 1.12 (3H, d, J = 6.7 Hz), 1.5
9-1.69 (1H, m), 1.77-1.84 (1
H, m), 3.18 (2H, t, J = 6.7 Hz),
4.20 (1H, d, J = 9.7 Hz), 4.54 (2
H, s), 6.68 (1H, br), 6.94-7.9.
3 (7H, m) ESI-MS (m / e): 455 [M + H] ⁺

Example 1100 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-t-Bu
O ₂ CCH = CH-4-n-PrNHCOCH ₂ O-P
h) ¹ H NMR (CDCl ₃ ) δ: 0.88 (3H, t, J =
7.1 Hz), 0.92 (3H, d, J = 6.5H)
z), 1.12 (3H, d, J = 6.5 Hz), 1.4
1-1.68 (3H, m), 1.54 (9H, s),
3.31 (2H, q, J = 6.7 Hz), 4.22 (1
H, d, J = 9.4 Hz), 4.57 (2H, s),
6.39-6.44 (1H, m), 6.41 (1H,
d, J = 16.2 Hz), 6.89 (1H, d, J =
8.5Hz), 7.32-7.34 (1H, m), 7.
45 (1H, dd, J = 2.3, 8.5 Hz), 7.5
8-7.64 (2H, m), 7.67 (1H, d, J =
2.3 Hz), 7.86 (1H, d, J = 16.2H)
z), 7.93-7.94 (1H, m) FAB-MS (m / e): 549 [M + H] ⁺

Example 1101 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-HO 2 C
CH = CH-4-n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, t, J =
7.4 Hz), 0.93 (3H, d, J = 6.6H)
z), 1.12 (3H, d, J = 6.6 Hz), 1.5
3-1.64 (3H, m), 3.32 (2H, q, J =
6.7 Hz), 4.23 (1H, d, J = 9.8H)
z), 4.59 (2H, s), 6.46-6.48 (1
H, m), 6.51 (1H, d, J = 16.1 Hz),
6.92 (1H, d, J = 8.7 Hz), 7.32-
7.35 (1H, m), 7.50 (1H, dd, J =
2.3, 8.7 Hz), 7.59-7.63 (2H,
m), 7.70 (1H, d, J = 2.3 Hz), 7.9
2-7.95 (1H, m), 8.01 (1H, d, J =
16.1 Hz) FAB-MS (m / e): 493 [M + H] ⁺

Example 1102 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
_{MeOCH 2 CH 2 NHCOCH 2 O-} Ph) 1 HNMR (CDCl 3) δ: 0.95 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.60-1.70 (1H, m), 3.38 (3
H, s), 3.54-3.60 (4H, m), 4.21.
(1H, d, J = 9.8 Hz), 4.53 (2H,
s), 6.77 (1H, d, J = 8.6 Hz), 7.3
5-7.94 (6H, m) FAB-MS (m / e): 565 [M + H] ⁺

Example 1103 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-F-4-
HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.67-1.74 (1H, m), 4.21 (1
H, d, J = 9.8 Hz), 6.91-7.93 (7
H, m) FAB-MS (m / e): 342 [M + H] ⁺

Example 1104 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-F-4-
MeO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.63-1.69 (1H, m), 3.90 (3
H, s), 4.20 (1H, d, J = 9.8 Hz),
6.94-7.92 (7H, m) FAB-MS (m / e): 356 [M + H] ⁺

Example 1105 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,4-me
TylenedioxyPh) ¹ H NMR (CDCl ₃ ) δ: 0.97 (3H, d, J =
6.7 Hz), 1.13 (3H, d, J = 6.7H)
z), 1.65-1.79 (1H, m), 4.19 (1
H, d, J = 9.9 Hz), 5.99 (1H, d, J =
5.5 Hz), 6.81 (1H, d, J = 8.1H)
z), 6.86 (1H, d, J = 1.9 Hz), 7.0
5 (1H, dd, J = 1.9, 8.1 Hz), 7.33
−7.39 (1H, m), 7.57−7.63 (2H,
m), 7.87-7.93 (1H, m) FAB-MS (m / e): 352 [M + H] ⁺

Example 1106 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,4-et
hylendioxyPh) ¹ H NMR (CDCl ₃ ) δ: 0.97 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.67-1.72 (1H, m), 4.18 (1
H, d, J = 10.0 Hz), 4.26 (4H, s),
6.85 (1H, d, J = 8.4 Hz), 6.94 (1
H, dd, J = 2.2, 8.4 Hz), 7.00 (1
H, d, J = 2.2 Hz), 7.35-7.90 (4
H, m) FAB-MS (m / e): 366 [M + H] ⁺

Example 1107 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,4-Cl
_2- Ph) ¹ H NMR (CDCl ₃ ) δ: 0.94 (3H, d, J =
6.5 Hz), 1.13 (3H, d, J = 6.5H)
z), 1.53-1.70 (1H, m), 4.22 (1
H, d, J = 9.4 Hz), 7.29-7.36 (2
H, m), 7.48 (1H, d, J = 8.1, Hz),
7.59-7.66 (3H, m), 7.90-7.94
(1H, m) FAB-MS (m / e): 376 [M + H] ⁺

Example 1108 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,4-Me
_2- Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.7 Hz), 1.11 (3H, d, J = 6.7H)
z), 1.63-1.71 (1H, m), 2.25 (6
H, s), 4.18 (1H, d, J = 10.1 Hz),
7.12-7.92 (7H, m) FAB-MS (m / e): 336 [M + H] ⁺

Example 1109 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,4-F 2
-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.64 (1H, m), 4.22 (1H, d, J
= 9.6 Hz), 7.19-7.35 (4H, m),
7.61-7.64 (2H, m), 7.90-7.94
(1H, m) FAB-MS (m / e): 344 [M + H] ⁺

Example 1110 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,4- (M
eO) ₂ -Ph) ESI-MS (m / e): 368 [M + H] ⁺

Example 1111 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,5- (M
eO) ₂ -Ph) ESI-MS (m / e): 368 [M + H] ⁺

Example 1112 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,5-Me
_2- Ph) ESI-MS (m / e): 336 [M + H] ⁺

Example 1113 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,5-I 2
-4-HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.98 (3H, d, J =
6.6 Hz), 1.15 (3H, d, J = 6.6H)
z), 1.61-1.72 (1H, m), 4.20 (1
H, d, J = 9.9 Hz), 5.79 (1H, br)
s), 7.35-7.94 (6H, m) FAB-MS (m / e): 576 [M + H] ⁺

Example 1114 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 2,4-I 2
−5-HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.95 (3H, d, J =
6.6 Hz), 1.14 (3H, d, J = 6.6H)
z), 1.59-1.66 (1H, m), 4.26 (1
H, d, J = 9.7 Hz), 7.21-7.26 (1
H, m), 7.60-7.69 (2H, m), 7.70
(1H, s), 7.91-7.95 (1H, m), 8.
14 (1H, s) FAB-MS (m / e): 576 [M + H] ⁺

Example 1115 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,5-I 2
-4-MeO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.96 (3H, d, J =
6.6 Hz), 1.13 (3H, d, J = 6.6H)
z), 1.61-1.72 (1H, m), 3.89+
3.92 (3H, s + s, rotorer), 4.19
(1H, d, J = 9.8 Hz), 7.34-7.93
(6H, m) FAB-MS (m / e): 590 [M + H] ⁺

Example 1116 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 2,4-I 2
^{-5-MeO-Ph) 1 HNMR} (CDCl 3) δ: 0.94 (3H, d, J =
7.1 Hz), 1.14 (3H, d, J = 7.1H)
z), 1.51-1.64 (1H, m), 3.99 (3
H, s), 4.26 (1H, d, J = 9.5 Hz),
7.22-7.25 (1H, m), 7.45 (1H,
s), 7.61-7.70 (2H, m), 7.93-
7.95 (1H, m), 8.23 (1H, s) FAB-MS (m / e): 590 [M + H] ⁺

Example 1117 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 2,4,6-
_{Me 3 -Ph) ESI-MS (} m / e): 350 [M + H] +

Example 1118 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO (C
_{H 2) 3 O-3,5-} I 2 -Ph) 1 HNMR (CDCl 3) δ: 0.99 (3H, d, J =
6.6 Hz), 1.16 (3H, d, J = 6.6H)
z), 1.62-1.72 (1H, m), 2.17 (2
H, dt, J = 5.7 Hz), 4.00 (2H, t, J)
= 5.7 Hz), 4.16 (2H, t, J = 5.7H)
z), 4.21 (1H, d, J = 9.9 Hz), 7.3
8-7.96 (6H, m) FAB-MS (m / e): 634 [M + H] ⁺

Example 1119 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,5-I 2
-4-n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.97 (3H, d, J =
6.7 Hz), 1.00 (3H, t, J = 7.4H)
z), 1.15 (3H, d, J = 6.7 Hz), 1.5
8-1.73 (3H, m), 3.38 (2H, q, J =
6.6 Hz), 4.21 (1H, d, J = 9.8H)
z), 4.49 (2H, s), 6.79-6.82 (1
H, m), 7.38-7.40 (1H, m), 7.62.
-7.69 (2H, m), 7.90-7.95 (1H,
m), 7.92 (2H, s) FAB-MS (m / e): 675 [M + H] ⁺

Example 1120 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 2-thie
nyl) ¹ H NMR (CDCl ₃ ) δ: 1.04 (3H, d, J =
6.6 Hz), 1.17 (3H, d, J = 6.6H)
z), 1.75-1.90 (1H, m), 4.18 (1
H, d, J = 10.2 Hz), 7.02 (1H, dd,
J = 3.6, 5.0 Hz), 7.26 (1H, dd, J
= 1.1, 3.6 Hz), 7.35 (1H, dd, J =
1.1, 5.0 Hz), 7.45-7.55 (1H,
m), 7.56-7.68 (2H, m), 7.89-
7.92 (1H, m) FAB-MS (m / e): 314 [M + H] ⁺

Example 1121 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 2-fury
l) ¹ H NMR (CDCl ₃ ) δ: 1.01 (3H, d, J =
6.6 Hz), 1.21 (3H, d, J = 6.6H)
z), 1.92-2.06 (1H, m), 4.17 (1
H, d, J = 9.7 Hz), 6.39 (1H, dd, J)
= 1.8, 3.3 Hz), 6.40 (1H, d, J =
3.3Hz), 7.43 (1H, d, J = 1.8H)
z), 7.58-7.70 (3H, m), 7.88-
7.98 (1H, m) FAB-MS (m / e): 298 [M + H] ⁺

Example 1122 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-pyri
dyl) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, d, J =
6.7 Hz), 1.12 (3H, d, J = 6.7H)
z), 1.55-1.70 (1H, m), 4.24 (1
H, d, J = 9.6 Hz), 7.32-7.40 (2
H, m), 7.60-7.65 (2H, m), 7.79
−7.83 (1H, m), 7.92-7.96 (1H,
m), 8.66 (1H, d, J = 4.6 Hz), 8.7
8 (1H, brs) FAB-MS (m / e): 309 [M + H] ⁺

Example 1123 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 2-naph
thyl) ESI-MS (m / e): 358 [M + H] ⁺

Example 1124 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; Z: Ph; R: 5-F-1-
naphthyl) ESI-MS (m / e): 376 [M + H] ⁺

Example 1125 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: dibenz
othiophene-2-yl) ESI-MS (m / e): 414 [M + H] ⁺

Example 1126 (R ¹ : 6-F; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: Ph) 1 HNMR (CDCl 3) δ: 0.91 (3H, d, J =
6.6 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.52-1.67 (1H, m), 4.22 (1
H, d, J = 9.8 Hz), 7.13 (1H, d, J =
7.8 Hz), 7.22 (1H, dd, J = 8.5,
8.6 Hz), 7.38-7.43 (3H, m), 7.
47-7.51 (2H, m), 7.57 (1H, dd)
d, J = 4.7, 7.8, 8.5 Hz) FAB-MS (m / e): 326 [M + H] ⁺

Example 1127 (R ¹ : 7-F; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: Ph) 1 HNMR (CDCl 3) δ: 0.89 (3H, d, J =
6.6 Hz), 1.10 (3H, d, J = 6.6H)
z), 1.64 (1H, m), 4.20 (1H, d, J
= 9.8 Hz), 7.23-7.33 (2H, m),
7.35-7.51 (5H, m), 7.54-7.58
(1H, m) FAB-MS (m / e): 326 [M + H] ⁺

Example 1128 (R ¹ : 8-F; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: Ph) 1 HNMR (CDCl 3) δ: 0.92 (3H, d, J =
6.6 Hz), 1.12 (3H, d, J = 6.6H)
z), 1.61-1.65 (1H, m), 4.20 (1
H, d, J = 9.8 Hz), 6.98-7.00 (1
H, m), 7.22-7.31 (1H, m), 7.38
−7.49 (5H, m), 7.90 (1H, dd, J =
7.6, 11.1 Hz) FAB-MS (m / e): 326 [M + H] ⁺

Example 1129 (R ¹ : 9-F; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: Ph) 1 HNMR (CDCl 3) δ: 0.89 (3H, d, J =
6.6 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.53-1.64 (1H, m), 4.19 (1
H, d, J = 9.8 Hz), 7.24 (1H, dd, J)
= 7.8, 8.6 Hz), 7.37-7.41 (3H,
m), 7.50-7.54 (2H, m), 7.61 (1
H, ddd, J = 4.3, 7.8, 7.8 Hz), 7.
73 (1H, d, J = 7.8 Hz) FAB-MS (m / e): 326 [M + H] ⁺

Example 1130 (R ¹ : 6-MeO; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.88 (3H, d, J =
6.7 Hz), 1.09 (3H, d, J = 6.7H)
z), 1.58-1.68 (1H, m), 4.01 (3
H, s), 4.21 (1H, d, J = 9.7 Hz),
6.88 (1H, d, J = 7.3 Hz), 7.33-
7.60 (6H, m) FAB-MS (m / e): 338 [M + H] ⁺

Example 1131 (R ¹ : 9-MeO; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.85 (3H, d, J =
6.6 Hz), 1.08 (3H, d, J = 6.6H)
z), 1.52-1.59 (1H, m), 3.69 (3
H, s), 4.15 (1H, d, J = 9.7 Hz),
7.03 (1H, dd, 1.0, 8.0 Hz), 7.3
1-7.35 (3H, m), 7.46-7.59 (3
H, m), 7.55 (1H, d, J = 7.8 Hz) FAB-MS (m / e): 338 [M + H] ⁺

Example 1132 (R ¹ : 6-OH; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.90 (3H, d, J =
6.7 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.52-1.70 (1H, m), 4.15 (1
H, d, J = 9.7 Hz), 6.83 (1H, d, 7.
6 Hz), 7.00 (1H, d, J = 8.3 Hz),
7.34-7.51 (6H, m), 8.03 (1H, b
rs) FAB-MS (m / e): 324 [M + H] ⁺

Example 1133 (R ¹ : 9-OH; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.79 (3H, d, J =
6.7 Hz), 1.06 (3H, d, J = 6.7H)
z), 1.60-1.67 (1H, m), 4.17 (1
H, d, J = 9.5 Hz), 7.11 (1H, dd, J)
= 1.0, 8.2 Hz), 7.41-7.64 (7H,
m), 9.31 (1H, brs) FAB-MS (m / e): 324 [M + H] ⁺

Example 1134 (R ¹ : 7-NO ₂ ; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.6 Hz), 1.12 (3H, d, J = 6.6H)
z), 1.58-1.68 (1H, m), 4.25 (1
H, d, J = 9.9 Hz), 7.41-7.55 (5
H, m), 8.45 (1H, dd, J = 2.2, 8.4)
Hz), 8.74 (1H, d, J = 2.2 Hz) FAB-MS (m / e): 353 [M + H] ⁺

Example 1135 (R ¹ : 8-NO ₂ ; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.7 Hz), 1.12 (3H, d, J = 6.7H)
z), 1.58-1.68 (1H, m), 4.25 (1
H, d, J = 10.0 Hz), 7.42-7.55 (5
H, m), 8.09 (1H, d, J = 8.3 Hz),
8.16 (1H, d, J = 1.8 Hz), 8.46 (1
H, dd, J = 1.8, 8.3 Hz) FAB-MS (m / e): 353 [M + H] ⁺

Example 1136 (R ¹ : 9-NO ₂ ; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.76 (3H, d, J =
6.7 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.45-1.59 (1H, m), 4.19 (1
H, d, J = 10.0 Hz), 7.26-7.38 (5
H, m), 7.89 (1H, dd, J = 7.6, 8.1)
Hz), 8.30 (1H, dd, J = 0.9, 7.6H)
z), 8.40 (1H, dd, J = 0.9, 8.1H
z) FAB-MS (m / e): 353 [M + H] ⁺

Example 1137 (R ¹ : 6-NHPh;
^{R 2: H; R 3:} i-Pr; R 4: H; Z: Ph; R: P
h) ¹ H NMR (CDCl ₃ ) δ: 0.79 (3H, d, J =
6.7 Hz), 1.11 (3H, d, J = 6.6H)
z), 1.50-1.56 (1H, m), 4.20 (1
H, d, J = 9.5 Hz), 5.55 (1H, s),
6.79-6.81 (2H, m), 6.99-7.01
(1H, m), 7.19-7.27 (2H, m), 7.
28-7.37 (2H, m), 7.39-7.44 (4
H, m), 7.46-7.52 (2H, m) FAB-MS (m / e): 399 [M + H] ⁺

Example 1138 (R ¹ : 7-Me ₂ N;
^{R 2: H; R 3:} i-Pr; R 4: H; Z: Ph; R: P
h) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, d, J =
6.6 Hz), 1.10 (3H, d, J = 6.6H)
z), 1.55-1.66 (1H, m), 3.03 (6
H, s), 4.19 (1H, d, J = 9.9 Hz),
6.84 (1H, dd, J = 2.5, 8.6 Hz),
7.08-7.50 (7H, m) FAB-MS (m / e): 351 [M + H] ⁺

Example 1139 (R ¹ : 7-Me; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, d, J =
6.6 Hz), 1.10 (3H, d, J = 6.6H)
z), 1.55-1.65 (1H, m), 2.45 (3
H, s), 4.20 (1H, d, J = 9.8 Hz),
7.21 (1H, d, J = 7.9 Hz), 7.35-
7.42 (4H, m), 7.45-7.50 (2H,
m), 7.70 (1H, d, J = 0.7 Hz) FAB-MS (m / e): 322 [M + H] ⁺

Example 1140 (R ¹ : 8-Me; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, d, J =
6.6 Hz), 1.09 (3H, d, J = 6.6H)
z), 1.55-1.68 (1H, m), 2.38 (3
H, s), 4.19 (1H, d, J = 9.8 Hz),
7.11 (1H, s), 7.35-7.45 (4H,
m), 7.45-7.52 (2H, m), 7.79 (1
H, d, J = 7.6 Hz) FAB-MS (m / e): 322 [M + H] ⁺

Example 1141 (R ¹ : 7-t-Bu;
^{R 2: H; R 3:} i-Pr; R 4: H; Z: Ph; R: P
h) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, d, J =
6.7 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.35 (9H, s), 1.63-1.67 (1
H, m), 4.20 (1H, d, J = 9.9 Hz),
7.26 (1H, d, J = 8.4 Hz), 7.37 −
7.52 (5H, m), 7.62 (1H, dd, J =
1.5, 8.4 Hz), 7.92 (1H, d, J = 1.
5 Hz) FAB-MS (m / e): 364 [M + H] ⁺

Example 1142 (R ¹ : 8-t-Bu;
^{R 2: H; R 3:} i-Pr; R 4: H; Z: Ph; R: P
h) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, d, J =
6.7 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.27 (9H, s), 1.60-1.65 (1
H, m), 4.19 (1H, d, J = 9.9 Hz),
7.30 (1H, d, J = 1.6 Hz), 7.37-
7.52 (5H, m), 7.61 (1H, dd, J =
1.6, 8.1 Hz), 7.83 (1H, d, J = 8.
1 Hz) FAB-MS (m / e): 364 [M + H] ⁺

Example 1143 (R ¹ : 7-Br; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, d, J =
6.6 Hz), 1.09 (3H, d, J = 6.65H)
z), 1.58-1.65 (1H, m), 4.20 (1
H, d, J = 9.8 Hz), 7.40-7.50 (6
H, m), 7.70-7.79 (2H, m) FAB-MS (m / e): 386/388 [M + H] ⁺

Example 1144 (R ¹ : 8-Br; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, d, J =
6.7 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.61-1.63 (1H, m), 4.20 (1
H, d, J = 9.8 Hz), 7.21 (1H, d, J =
8.5Hz), 7.38-7.49 (5H, m), 7.
70 (1H, dd, J = 1.9, 8.1 Hz), 8.0
3-8.04 (1H, m) FAB-MS (m / e): 386/388 [M + H] ⁺

Example 1145 (R ¹ : 7-Cl; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, d, J =
6.6 Hz), 1.10 (3H, d, J = 6.6H)
z), 1.56-1.68 (1H, m), 4.21 (1
H, d, J = 9.8 Hz), 7.27 (1H, dd, J)
= 0.6, 8.2 Hz), 7.37-7.43 (3H,
m), 7.44-7.51 (2H, m), 7.55 (1
H, dd, J = 1.9, 8.2 Hz), 7.87 (1
H, dd, J = 0.6, 1.9 Hz) FAB-MS (m / e): 342 [M + H] ⁺

Example 1146 (R ¹ : 8-Cl; R ² :
H; R ³ : i-Pr; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.91 (3H, d, J =
6.6 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.53-1.72 (1H, m), 4.20 (1
H, d, J = 9.8 Hz), 7.31 (1H, dd, J)
= 0.6, 1.7 Hz), 7.39-7.48 (5H,
m), 7.56 (1H, dd, J = 1.7, 8.1H
z), 7.84 (1H, dd, J = 0.6, 8.1H
z) FAB-MS (m / e): 342 [M + H] ⁺

Example 1147 (R ¹ : 7-Cl; R ² : 8)
^{-Cl; R 3: i-Pr} ; R 4: H; Z: Ph; R: P
h) ¹ H NMR (CDCl ₃ ) δ: 0.90 (3H, d, J =
6.6 Hz), 1.09 (3H, d, J = 6.6H)
z), 1.60-1.64 (1H, m), 4.19 (1
H, d, J = 9.9 Hz), 7.40-7.48 (6
H, m), 7.98 (1H, s) FAB-MS (m / e): 376 [M + H] ⁺

Example 1148 (R ¹ : 6-Cl; R ² : 9
^{-Cl; R 3: i-Pr} ; R 4: H; Z: Ph; R: P
h) ¹ H NMR (CDCl ₃ ) δ: 0.76 (3H, d, J =
6.6 Hz), 1.09 (3H, d, J = 6.6H)
z), 1.49-1.59 (1H, m), 4.19 (1
H, d, J = 9.6 Hz), 7.36-7.48 (6
H, m), 7.52 (1H, d, J = 8.4 Hz) FAB-MS (m / e): 376 [M + H] ⁺

Example 1149 (R ¹ : 6-OH; R ² : 9
^{-I; R 3: i-Pr} ; R 4: H; Z: Ph; R: Ph) 1 HNMR (DMSO-d 6) δ: 0.64 (3H, d,
J = 6.7 Hz), 0.96 (3H, d, J = 6.7H)
z), 1.40-1.52 (1H, m), 4.19 (1
H, d, J = 8.9 Hz), 6.82 (1H, d, J =
8.5Hz), 7.30-7.40 (5H, m), 7.
85 (1H, d, J = 8.5 Hz), 10.56 (1
H, brs) FAB-MS (m / e): 450 [M + H] ⁺

Example 1150 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; Z: 1,2-naphthl
yl; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.80 (3H, d, J =
6.5 Hz), 1.13 (3H, d, J = 6.5H)
z), 1.55-1.70 (1H, m), 4.21 (1
H, d, J = 9.1 Hz), 7.30-7.40 (3
H, m), 7.40-7.50 (3H, m), 7.54
−7.60 (1H, m), 7.80 (1H, d, J =
8.6 Hz), 7.93 (1H, d, J = 8.2H)
z), 7.94 (1H, d, J = 8.2 Hz), 8.0
8 (1H, d, J = 8.2 Hz) FAB-MS (m / e): 358 [M + H] ⁺

Example 1151 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; Z: 2,3-naphthl
yl; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.96 (3H, d, J =
6.1 Hz), 1.13 (3H, d, J = 6.1H)
z), 1.59-1.67 (1H, m), 4.28 (1
H, d, J = 10.1 Hz), 7.34-7.43 (3
H, m), 7.54-7.76 (4H, m), 7.76
(1H, s), 7.83-7.85 (1H, m), 8.
04-8.06 (1H, m), 8.54 (1H, s) FAB-MS (m / e): 358 [M + H] ⁺

Example 1152 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: cyclohexeny
l; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.79 (3H, d, J =
6.0 Hz), 1.04 (3H, d, J = 6.0H)
z), 1.56-1.80 (5H, m), 2.28-
2.30 (4H, m), 4.04 (1H, d, J = 9.
0 Hz), 7.391-7.394 (5H, m) FAB-MS (m / e): 312 [M + H] ⁺

[0384]

Embedded image Here, R ³ represents a derived amino acid.

Example 1153 (R ¹ : H; R ² : H;
^{R 3: D-Leucine; R} 4: H; Z: Ph; R: P
h) ESI-MS (m / e): 322 [M + H] ⁺

Example 1154 (R ¹ : H; R ² : H;
^{R 3: L-Leucine; R} 4: H; Z: Ph; R: P
h) ESI-MS (m / e): 322 [M + H] ⁺

Example 1155 (R ¹ : H; R ² : H;
^{R 3: D-NorLeucine; R} 4: H; Z: Ph;
R: Ph) ESI-MS (m / e): 322 [M + H] ⁺

Example 1156 (R ¹ : H; R ² : H;
^{R 3: L-NorLeucine; R} 4: H; Z: Ph;
R: Ph) ESI-MS (m / e): 322 [M + H] ⁺

Example 1157 (R ¹ : H; R ² : H;
R ³ : D-AlloLeucine; R ⁴ : H; Z: P
h; R: Ph) ESI-MS (m / e): 322 [M + H] ⁺

Example 1158 (R ¹ : H; R ² : H;
R ³ : L-AlloLeucine; R ⁴ : H; Z: P
h; R: Ph) ESI-MS (m / e): 322 [M + H] ⁺

Example 1159 (R ¹ : H; R ² : H;
^{R 3: D-NorValine; R} 4: H; Z: Ph;
R: Ph) ESI-MS (m / e): 308 [M + H] ⁺

Example 1160 (R ¹ : H; R ² : H;
^{R 3: L-NorValine; R} 4: H; Z: Ph;
R: Ph) ESI-MS (m / e): 308 [M + H] ⁺

Example 1161 (R ¹ : H; R ² : H;
^{R 3: D-Alanine; R} 4: H; Z: Ph; R: P
h) ESI-MS (m / e): 280 [M + H] ⁺

Example 1162 (R ¹ : H; R ² : H;
^{R 3: L-Alanine; R} 4: H; Z: Ph; R: P
h) ESI-MS (m / e): 280 [M + H] ⁺

Example 1163 (R ¹ : H; R ² : H;
R ³ : D-Arginine; R ⁴ : H; Z: Ph; R:
Ph) ESI-MS (m / e): 365 [M + H] ⁺

Example 1164 (R ¹ : H; R ² : H;
R ³ : L-Arginine; R ⁴ : H; Z: Ph; R:
Ph) ESI-MS (m / e): 365 [M + H] ⁺

Example 1165 (R ¹ : H; R ² : H;
^{R 3: D-Asparagine; R} 4: H; Z: Ph;
R: Ph) ESI-MS (m / e): 323 [M + H] ⁺

Example 1166 (R ¹ : H; R ² : H;
R ³ : L-Asparagine; R ⁴ : H; Z: Ph;
R: Ph) ESI-MS (m / e): 323 [M + H] ⁺

Example 1167 (R ¹ : H; R ² : H;
^{R 3: L-Glutamic Acid;} R 4: H; Z:
Ph; R: Ph) ESI-MS (m / e): 338 [M + H] ⁺

Example 1168 (R ¹ : H; R ² : H;
^{R 3: L-Glutamic Acid;} R 4: H; Z:
Ph; R: Ph) ESI-MS (m / e): 338 [M + H] ⁺

Example 1169 (R ¹ : H; R ² : H;
R ³ : D-Glutamine; R ⁴ : H; Z: Ph;
R: Ph) ESI-MS (m / e): 337 [M + H] ⁺

Example 1170 (R ¹ : H; R ² : H;
^{R 3: L-Glutamine; R} 4: H; Z: Ph;
R: Ph) ESI-MS (m / e): 337 [M + H] ⁺

Example 1171 (R ¹ : H; R ² : H;
R ³ : D-Histidine; R ⁴ : H; Z: Ph;
R: Ph) ESI-MS (m / e): 346 [M + H] ⁺

Example 1172 (R ¹ : H; R ² : H;
^{R 3: L-Histidine; R} 4: H; Z: Ph;
R: Ph) ESI-MS (m / e): 346 [M + H] ⁺

Example 1173 (R ¹ : H; R ² : H;
^{R 3: D-Methionine; R} 4: H; Z: Ph;
R: Ph) ESI-MS (m / e): 340 [M + H] ⁺

Example 1174 (R ¹ : H; R ² : H;
R ³ : L-Methionine; R ⁴ : H; Z: Ph;
R: Ph) ESI-MS (m / e): 340 [M + H] ⁺

Example 1175 (R ¹ : H; R ² : H;
R ³ : D-Tryptophan; R ⁴ : H; Z: Ph;
R: Ph) ESI-MS (m / e): 395 [M + H] ⁺

Example 1176 (R ¹ : H; R ² : H;
^{R 3: L-Tryptophan; R} 4: H; Z: Ph;
R: Ph) ESI-MS (m / e): 395 [M + H] ⁺

Example 1177 (R ¹ : H; R ² : H;
^{R 3: D-Tyrosine; R} 4: H; Z: Ph; R:
Ph) ESI-MS (m / e): 372 [M + H] ⁺

Example 1178 (R ¹ : H; R ² : H;
^{R 3: L-Tyrosine; R} 4: H; Z: Ph; R:
Ph) ¹ H NMR (CDCl ₃ ) δ: 2.45 (1 H, dd, J
= 11.5, 14.5 Hz), 3.07 (1H, dd,
J = 4.4, 14.5 Hz), 4.92 (1H, dd,
J = 4.4, 11.5 Hz), 5.31 (1H, br)
s), 6.77 (2H, d, J = 8.6 Hz), 6.9
9 (2H, d, J = 8.6 Hz), 7.34-7.37
(1H, m), 7.39-7.44 (3H, m), 7.
46-7.50 (2H, m), 7.55-7.59 (2
H, m), 7.84-7.87 (1H, m) FAB-MS (m / e): 372 [M + H] ⁺

Example 1179 (R ¹ : H; R ² : H;
R ³ : D-HomoPhenylalanine; R ⁴ :
H; Z: Ph; R: Ph) ESI-MS (m / e): 370 [M + H] ⁺

Example 1180 (R ¹ : H; R ² : H;
R ³ : L-HomoPhenylalanine; R ⁴ :
H; Z: Ph; R: Ph) ESI-MS (m / e): 370 [M + H] ⁺

Example 1181 (R ¹ : H; R ² : H;
^{R 3: D-Leucine; R} 4: H; Z: Ph; R: 4
-Cl-Ph) ESI-MS (m / e): 356 [M + H] ⁺

Example 1182 (R ¹ : H; R ² : H;
^{R 3: L-Leucine; R} 4: H; Z: Ph; R: 4
-Cl-Ph) ESI-MS (m / e): 356 [M + H] ⁺

Example 1183 (R ¹ : H; R ² : H;
^{R 3: D-NorLeucine; R} 4: H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 356 [M + H] ⁺

Example 1184 (R ¹ : H; R ² : H;
^{R 3: L-NorLeucine; R} 4: H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 356 [M + H] ⁺

Example 1185 (R ¹ : H; R ² : H;
R ³ : D-AlloLeucine; R ⁴ : H; Z: P
h; R: 4-Cl-Ph) ESI-MS (m / e): 356 [M + H] ⁺

Example 1186 (R ¹ : H; R ² : H;
R ³ : L-AlloLeucine; R ⁴ : H; Z: P
h; R: 4-Cl-Ph) ESI-MS (m / e): 356 [M + H] ⁺

Example 1187 (R ¹ : H; R ² : H;
^{R 3: D-NorValine; R} 4: H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 342 [M + H] ⁺

Example 1188 (R ¹ : H; R ² : H;
^{R 3: L-NorValine; R} 4: H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 342 [M + H] ⁺

Example 1189 (R ¹ : H; R ² : H;
^{R 3: D-Alanine; R} 4: H; Z: Ph; R: 4
-Cl-Ph) ESI-MS (m / e): 314 [M + H] ⁺

Example 1190 (R ¹ : H; R ² : H;
^{R 3: L-Alanine; R} 4: H; Z: Ph; R: 4
-Cl-Ph) ESI-MS (m / e): 314 [M + H] ⁺

Example 1191 (R ¹ : H; R ² : H;
R ³ : D-Arginine; R ⁴ : H; Z: Ph; R:
4-Cl-Ph) ESI-MS (m / e): 399 [M + H] ⁺

Example 1192 (R ¹ : H; R ² : H;
R ³ : L-Arginine; R ⁴ : H; Z: Ph; R:
4-Cl-Ph) ESI-MS (m / e): 399 [M + H] ⁺

Example 1193 (R ¹ : H; R ² : H;
^{R 3: D-Asparagine; R} 4: H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 357 [M + H] ⁺

Example 1194 (R ¹ : H; R ² : H;
R ³ : L-Asparagine; R ⁴ : H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 357 [M + H] ⁺

Example 1195 (R ¹ : H; R ² : H;
R ³ : D-Glutamic Acid; R ⁴ : H; Z:
Ph; R: 4-Cl-Ph) ESI-MS (m / e): 372 [M + H] ⁺

Example 1196 (R ¹ : H; R ² : H;
^{R 3: L-Glutamic Acid;} R 4: H; Z:
Ph; R: 4-Cl-Ph) ESI-MS (m / e): 372 [M + H] ⁺

Example 1197 (R ¹ : H; R ² : H;
R ³ : D-Glutamine; R ⁴ : H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 371 [M + H] ⁺

Example 1198 (R ¹ : H; R ² : H;
^{R 3: L-Glutamine; R} 4: H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 371 [M + H] ⁺

Example 1199 (R ¹ : H; R ² : H;
R ³ : D-Histidine; R ⁴ : H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 380 [M + H] ⁺

Example 1200 (R ¹ : H; R ² : H;
^{R 3: L-Histidine; R} 4: H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 380 [M + H] ⁺

Example 1201 (R ¹ : H; R ² : H;
^{R 3: D-Methionine; R} 4: H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 374 [M + H] ⁺

Example 1202 (R ¹ : H; R ² : H;
R ³ : L-Methionine; R ⁴ : H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 374 [M + H] ⁺

Example 1203 (R ¹ : H; R ² : H;
R ³ : D-Tryptophan; R ⁴ : H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 429 [M + H] ⁺

Example 1204 (R ¹ : H; R ² : H;
^{R 3: L-Tryptophan; R} 4: H; Z: Ph;
R: 4-Cl-Ph) ESI-MS (m / e): 429 [M + H] ⁺

Example 1205 (R ¹ : H; R ² : H;
^{R 3: D-Tyrosine; R} 4: H; Z: Ph; R:
4-Cl-Ph) ESI-MS (m / e): 406 [M + H] ⁺

Example 1206 (R ¹ : H; R ² : H;
^{R 3: L-Tyrosine; R} 4: H; Z: Ph; R:
4-Cl-Ph) ESI-MS (m / e): 406 [M + H] ⁺

Example 1207 (R ¹ : H; R ² : H;
R ³ : D-HomoPhenylalanine; R ⁴ :
H; Z: Ph; R: 4-Cl-Ph) ESI-MS (m / e): 404 [M + H] ⁺

Example 1208 (R ¹ : H; R ² : H;
R ³ : L-HomoPhenylalanine; R ⁴ :
H; Z: Ph; R: 4-Cl-Ph) ESI-MS (m / e): 404 [M + H] ⁺

Example 1209 (R ¹ : H; R ² : H;
R ³ : t-Bu; R ⁴ : H; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 0.90 (9H, s),
4.29 (1H, s), 7.30 (1H, ddd, J =
0.8, 3.2, 5.6 Hz), 7.34-7.41
(3H, m), 7.42-7.44 (2H, m), 7.
54-7.59 (2H, m), 7.91 (1H, dd)
d, J = 0.8, 3.2, 5.6 Hz) ESI-MS (m / e): 322 [M + H] ⁺

Example 1210 (R ¹ : H; R ² : H;
_{^{R 3: Me 2 (OH)}} C; R 4: H; Z: Ph; R: P
h) ¹ H NMR (CDCl ₃ ) δ: 1.30 (3H, s),
1.45 (3H, s), 4.43 (1H, s), 7.3
3-7.64 (8H, m), 7.93 (1H, dd, J
= 6.0, 2.6 Hz) FAB-MS (m / e): 324 [M + H] ⁺

Example 1211 (R ¹ : H; R ² : H;
R ³ : Me (MeO) CH; R ⁴ : H; Z: Ph; R: P
h) ¹ H NMR (CDCl ₃ ) δ: 1.54 (3H, d, J =
6.1 Hz), 3.66 (3H, s), 4.33 (1
H, d, J = 7.3 Hz), 4.54 (1H, dt, J)
= 6.1, 7.3 Hz), 7.27-7.84 (9H,
m) FAB-MS (m / e): 324 [M + H] ⁺

Example 1212 (R ¹ : H; R ² : H;
^{R 3: 4-HO-Ph} ; R 4: H; Z: Ph; R: Ph) 1 HNMR (CDCl 3) δ: 4.95 (1H, br
s), 5.73 (1H, s), 6.59 (2H, d, J
= 8.4 Hz), 7.05 (2H, d, J = 8.4H)
z), 7.22-7.43 (6H, m), 7.60-
7.68 (2H, m), 7.96-7.98 (1H,
m) FAB-MS (m / e): 358 [M + H] ⁺

Example 1213 (R ¹ : H; R ² : H;
^{R 3: 4-HO-3} -I-Ph; R 4: H; Z: Ph;
R: Ph) ¹ H NMR (CDCl ₃ ) δ: 5.38 (1 H, br
s), 5.68 (1H, s), 6.76 (1H, d, J
= 8.5 Hz), 7.14 (1H, dd, J = 2.2,
8.5Hz), 7.30-7.45 (7H, m), 7.
62-7.70 (2H, m), 7.96-8.00 (1
H, m) FAB-MS (m / e): 484 [M + H] ⁺

Example 1214 (R¹: H; R^Two: H;
R^Three: 4-HO-3, 5-I_Two-Ph; R ^Four: H; Z: P
h; R: Ph)¹ HNMR (CDCl_Three) Δ: 5.62 (1H, s),
7.30-7.48 (8H, m), 7.62-7.80
(2H, m), 7.97-8.01 (1H, m) FAB-MS (m / e): 610 [M + H]⁺

Example 1215 (R¹: H; R^Two: H;
R^Three: 4-HO-3-I-PhCH_TwoR ^Four: H; Z: P
h; R: Ph)¹ HNMR (CDCl_Three) Δ: 2.45 (1H, dd, J
= 9.8, 14.5 Hz), 3.02 (1H, dd, J)
= 5.2, 14.5 Hz), 4.84 (1H, dd, J)
= 5.2, 9.8 Hz), 5.61 (1H, brs),
7.29-7.40 (5H, m), 7.42-7.43
(3H, m), 7.57-7.61 (2H, m), 7.
86-7.90 (1H, m) FAB-MS (m / e): 624 [M + H]⁺

Example 1216 (R¹: H; R^Two: H;
R^Three: 4-HO-3, 5-I_Two-PhCH _TwoR^Four: H;
Z: Ph; R: Ph)¹ HNMR (CDCl_Three) Δ: 2.48 (1H, dd, J
= 10.5, 14.5 Hz), 3.04 (1H, dd,
J = 4.9, 14.5 Hz), 4.86 (1H, dd,
J = 4.9, 10.5 Hz), 5.31 (1H, br)
s), 6.86 (1H, d, J = 8.3 Hz), 7.0
4 (1H, dd, J = 2.1, 8.3 Hz), 7.28
(1H, d, J = 2.1 Hz), 7.31-7.36
(1H, m), 7.41-7.42 (5H, m), 7.
57-7.60 (2H, m), 7.84-7.89 (1
H, m) FAB-MS (m / e): 498 [M + H]⁺

Example 1217 (R ¹ : H; R ² : H;
R ³ : 1-naphthylmethyl; R ⁴ : H;
Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 2.54 (1 H, dd, J
= 9.8, 14.5 Hz), 3.02 (1H, dd, J)
= 5.2, 14.5 Hz), 4.84 (1H, dd, J)
= 5.2, 9.8 Hz), 5.61 (1H, brs),
7.32-7.34 (1H, m), 7.33-7.36
(4H, m), 7.39-7.43 (3H, m), 7.
57-7.61 (2H, m), 7.87-7.89 (2
H, m) FAB-MS (m / e): 624 [M + H] ⁺

Example 1218 (R ¹ : H; R ² : H;
^{R 3: 4-F-PhCH} 2; R 4: H; Z: Ph; R: P
h) ESI-MS (m / e): 374 [M + H] ⁺

Example 1219 (R ¹ : H; R ² : H;
R ³ : 1-naphthylmethyl; R ⁴ : H;
Z: Ph; R: 4-Cl-Ph) ESI-MS (m / e): 406 [M + H] ⁺

Example 1220 (R ¹ : H; R ² : H;
^{R 3: 4-F-PhCH} 2; R 4: H; Z: Ph; R: 4
-Cl-Ph) ESI-MS (m / e): 408 [M + H] ⁺

Example 1221 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: Me; Z: Ph; R: Ph) 1 HNMR (CDCl 3) δ: 0.93 (3H, d, J =
6.8 Hz), 0.98 (3H, d, J = 6.8H)
z), 1.57-1.59 (1H, m), 1.70 (3
H, s), 7.31-7.56 (8H, m), 7.86.
−7.89 (1H, m) FAB-MS (m / e): 322 [M + H] ⁺

Example 1222 (R ¹ : H; R ² : H;
R ³ : Me; R ⁴ : Me; Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 1.27 (3H, s),
1.87 (3H, s), 7.35-7.40 (4H,
m), 7.49-7.58 (4H, m), 7.86-
7.89 (1H, m) FAB-MS (m / e): 294 [M + H] ⁺

[0455]

Embedded image

Example 1223 (R ¹ : H; R ² : H; R ³
And R ⁴ : ＣＨCH ₂ (R ³ and R ⁴ together form ＝ CH ₂
Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 5.97 (2H, d, J =
4.3 Hz), 7.35-7.42 (3H, m), 7.
45-7.53 (3H, m), 7.57-7.68 (2
H, m), 7.94-7.98 (1H, m) FAB-MS (m / e): 278 [M + H] ⁺

Example 1224 (R ¹ : H; R ² : H; R ³
And R ⁴ : = CHMe (R ³ and R ^{4 taken} together as ＣC
Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ: 2.25 (3H, d, J =
7.3 Hz), 6.66 (1H, q, J = 7.3H)
z), 7.37-7.42 (3H, m), 7.48-
7.54 (3H, m), 7.59-7.67 (2H,
m), 7.91-7.93 (2H, m) FAB-MS (m / e): 292 [M + H] ⁺

Example 1225 (R ¹ : H; R ² : H; R ³
And R ⁴ : — (CH ₂ ) ₄ — (R ³ and R ⁴ together form a — (CH ₂ ) ₄ — group); Z: Ph; R: Ph) ¹ H NMR (CDCl ₃ ) δ : 1.50-2.30 (7
H, m), 3.00-3.15 (1H, m), 7.30
-7.42 (4H, m), 7.43-7.52 (2H,
m), 7.52-7.62 (2H, m), 7.82-
7.92 (1H, m) FAB-MS (m / e): 320 [M + H] ⁺

Example 1413 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; Z: 2,3-pyrazin
yl; R: 4-n-PrNHCOCH ₂ O-Ph) FAB-MS (m / e): 425 [M + H] ⁺

Example 1427 (R ¹ : H; R ² : H;
R ³ : D-Glutamic Acid; R ⁴ : H; Z:
Ph; R: 3-Me-4-n-PrNHCOCH ₂ O-
Ph) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, t, J =
7.4-4), 1.54-1.61 (2H, m), 2.
14-2.24 (2H, m), 2.28 (3H, s),
2.58-2.65 (2H, m), 3.34 (2H,
q, J = 6.6 Hz), 4.50 (2H, s), 4.6
3 (1H, dd, J = 5.2, 11.0 Hz), 6.5
2-6.56 (1H, m), 6.78 (1H, d, J =
8.2 Hz), 7.27 (1H, s), 7.32 (1
H, d, J = 8.2 Hz), 7.35-7.39 (1
H, m), 7.58-7.63 (2H, m), 7.89.
−7.92 (1H, m) FAB-MS (m / e): 467 [M + H] ⁺

Example 1428 (R ¹ : H; R ² : H;
^{R 3: L-Glutamic Acid;} R 4: H; Z:
Ph; R: 3-Me-4-n-PrNHCOCH ₂ O-
Ph) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, t, J =
7.4-4), 1.54-1.61 (2H, m), 2.
14-2.24 (2H, m), 2.28 (3H, s),
2.58-2.65 (2H, m), 3.34 (2H,
q, J = 6.6 Hz), 4.50 (2H, s), 4.6
3 (1H, dd, J = 5.2, 11.0 Hz), 6.5
2-6.56 (1H, m), 6.78 (1H, d, J =
8.2 Hz), 7.27 (1H, s), 7.32 (1
H, d, J = 8.2 Hz), 7.35-7.39 (1
H, m), 7.58-7.63 (2H, m), 7.89.
−7.92 (1H, m) FAB-MS (m / e): 467 [M + H] ⁺

Example 1429 (R¹: H; R^Two: H;
R^Three: (3-Pyridyl) CH_TwoR ^Four: H; Z: P
h; R: 3-Me-4-n-PrNHCOCH_TwoOP
h)¹ HNMR (CDCl_Three) Δ: 0.93 (3H, t, J =
7.4-4), 1.54-1.68 (2H, m), 2.
27 (3H, s), 2.62 (1H, dd, J = 11.
0, 14.4 Hz), 3.17 (1H, dd, J = 4.
7, 14.4 Hz), 3.33 (2H, q, J = 6.7)
Hz), 4.90 (1H, dd, J = 4.5, 10.9)
Hz), 6.64-6.68 (1H, m), 6.82
(1H, d, J = 8.3 Hz), 7.14 (1H, d,
J = 1.8 Hz), 7.26-7.36 (3H, m),
7.56-7.64 (2H, m), 7.72-7.75
(2H, m), 7.84-7.87 (1H, m) FAB-MS (m / e): 486 [M + H]⁺

Example 1430 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Pr
_{NHCOCH 2 O-3-CH 2} = CH-Ph) 1 HNMR (CDCl 3) δ: 0.92 (3H, d, J =
6.5 Hz), 0.95 (3H, t, J = 7.3H)
z), 1.12 (3H, d, J = 6.5 Hz), 1.2
3-1.35 (1H, m), 1.50-1.67 (2
H, m), 3.33 (2H, q, J = 6.8 Hz),
4.21 (1H, d, J = 9.9 Hz), 4.53 (2
H, s), 5.40 (1H, d, J = 11.2 Hz),
5.76 (1H, d, J = 17.7 Hz), 6.44−
6.48 (1H, m), 6.85 (1H, d, J = 8.
8 Hz), 6.96 (1H, dd, J = 11.2, 1)
7.7 Hz), 7.27-7.40 (3H, m), 7.
59-7.61 (2H, m), 7.90-7.93 (1
H, m) FAB-MS (m / e): 449 [M + H] ⁺

Example 1431 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Pr
NHCOCH ₂ O-3- (2-Pyridyl) -P
h) ¹ H NMR (CDCl ₃ ) δ: 0.82 (3H, t, J =
7.4 Hz), 0.98 (3H, d, J = 6.6H)
z), 1.14 (3H, d, J = 6.6 Hz), 1.4
3-1.55 (2H, m), 1.65-1.77 (1
H, m), 3.25 (2H, q, J = 6.5 Hz),
4.23 (1H, d, J = 9.9 Hz), 4.62 (2
H, d, J = 14.9 Hz), 7.05 (1H, d, J)
= 8.7 Hz), 7.32-7.40 (2H, m),
7.50-7.63 (5H, m), 7.81-7.86
(1H, m), 7.90-7.92 (1H, m), 8.
195-8.197 (1H, m) FAB-MS (m / e): 500 [M + H] ⁺

Example 1432 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Pr
NHCOCH ₂ O-3- (3-Pyridyl) -P
h) ¹ H NMR (CDCl ₃ ) δ: 0.80 (3H, t, J =
7.4 Hz), 0.99 (3H, d, J = 6.6H)
z), 1.15 (3H, d, J = 6.6 Hz), 1.3
7-1.42 (2H, m), 1.65-1.75 (1
H, m), 3.18 (2H, q, J = 6.7 Hz),
4.24 (1H, d, J = 9.9 Hz), 4.50 (2
H, d, J = 14.2 Hz), 6.10-6.12 (1
H, m), 6.99 (1H, d, J = 8.7 Hz),
7.37-7.42 (2H, m), 7.44 (1H,
d, J = 2.4 Hz), 7.56-7.65 (3H,
m), 7.77 (1H, dd, J = 1.8, 7.8H
z), 7.91-7.94 (1H, m), 8.63-
8.72 (2H, m) FAB-MS (m / e): 500 [M + H] ⁺

Example 1433 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Pr
NHCOCH ₂ O-3- (4-Pyridyl) -P
h) ¹ H NMR (CDCl ₃ ) δ: 0.82 (3H, t, J =
7.4 Hz), 0.98 (3H, d, J = 6.6H)
z), 1.15 (3H, d, J = 6.6 Hz), 1.3
8-1.48 (2H, m), 1.64-1.74 (1
H, m), 3.19 (2H, q, J = 6.4 Hz),
4.24 (1H, d, J = 9.9 Hz), 4.52 (2
H, d, J = 14.2 Hz), 6.14-6.16 (1
H, m), 6.99 (1H, d, J = 8.6 Hz),
7.36-7.44 (3H, m), 7.47 (1H,
d, J = 2.4 Hz), 7.54-7.65 (3H,
m), 7.91-7.94 (1H, m), 8.69-
8.76 (2H, m) FAB-MS (m / e): 500 [M + H] ⁺

Example 1434 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Ph-4
_{-N-PrNHCOCH 2 O-Ph)} 1 HNMR (CDCl 3) δ: 0.79 (3H, t, J =
7.4 Hz), 0.99 (3H, d, J = 6.6H)
z), 1.15 (3H, d, J = 6.6 Hz), 1.2
6-1.40 (2H, m), 1.65-1.76 (1
H, m), 3.14 (2H, q, J = 7.1 Hz),
4.23 (1H, d, J = 9.9 Hz), 4.48 (2
H, d, J = 14.3 Hz), 6.25 (1H, s),
6.94 (1H, d, J = 8.6 Hz), 7.37-
7.45 (7H, m), 7.51 (1H, dd, J =
2.5, 8.6 Hz), 7.57-7.62 (2H,
m), 7.89-7.92 (1H, m) FAB-MS (m / e): 499 [M + H] ⁺

Example 1435 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Et-4
-N-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, t, J =
7.4 Hz), 0.94 (3H, d, J = 6.6H)
z), 1.11 (3H, d, J = 6.6 Hz), 1.2
1 (3H, t, J = 7.5 Hz), 1.53-1.68
(3H, m), 2.61-2.73 (2H, m), 3.
33 (2H, q, J = 6.6 Hz), 4.20 (1H,
d, J = 9.9 Hz), 4.50 (2H, s), 6.4
8-6.49 (1H, m), 6.80 (1H, d, J =
8.6 Hz), 7.28 (1H, d, J = 2.2H)
z), 7.34 (1H, dd, J = 2.2, 8.6H
z), 7.341-7.347 (1H, m), 7.58
-7.62 (2H, m), 7.90-7.93 (1H,
m) FAB-MS (m / e): 451 [M + H] ⁺

Example 1436 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-n-Bu
-4-n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.92 (3H, t, J =
7.3 Hz), 0.93 (3H, t, J = 7.3H)
z), 1.11 (3H, d, J = 6.8 Hz), 1.2
4-1.42 (6H, m), 1.28 (3H, d, J =
6.8 Hz), 1.53-1.64 (1H, m), 2.
51-2.71 (2H, m), 3.33 (2H, q, J
= 6.6 Hz), 4.20 (1H, d, J = 9.9H)
z), 4.49 (2H, s), 6.47-6.49 (1
H, m), 6.79 (1H, d, J = 8.4 Hz),
7.25 (1H, d, J = 2.4 Hz), 7.33 (1
H, dd, J = 2.4, 8.4 Hz), 7.33-7.
36 (1H, m), 7.56-7.61 (2H, m),
7.90-7.92 (1H, m) FAB-MS (m / e): 479 [M + H] ⁺

Example 1437 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-MeO-
6-Me-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.84 (3H, d, J =
6.2 Hz), 1.11 (3H, d, J = 6.2H)
z), 1.61-1.68 (1H, m), 1.73 (3
H, s), 3.86 (3H, s), 4.23 (1H,
d, J = 9.6 Hz), 6.82 (1H, dd, J =
2.1, 8.2 Hz), 6.99 (1H, d, J = 8.
2Hz), 7.30-7.31 (1H, m), 7.46
(1H, d, J = 2.1 Hz), 7.60-7.61
(2H, m), 7.92-7.95 (1H, m) FAB-MS (m / e): 352 [M + H] ⁺

Example 1438 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-HO-6
-Me-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.84 (3H, d, J =
6.6 Hz), 1.10 (3H, d, J = 6.6H)
z), 1.62-1.67 (1H, m), 1.71 (3
H, s), 4.24 (1H, d, J = 9.5 Hz),
5.72-5.73 (1H, m), 6.81 (1H, d
d, J = 2.3, 8.0 Hz), 6.94 (1H, d,
J = 8.0 Hz), 7.28-7.31 (1H, m),
7.42 (1H, d, J = 2.3 Hz), 7.59-
7.64 (2H, m), 7.93-7.96 (1H,
m) FAB-MS (m / e): 338 [M + H] ⁺

Example 1439 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 6-Me-3
-N-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.82 (3H, d, J =
6.7 Hz), 0.98 (3H, t, J = 7.4H)
z), 1.12 (3H, d, J = 6.7 Hz), 1.5
8-1.72 (3H, m), 1.75 (3H, s),
3.37 (2H, q, J = 6.7 Hz), 4.26 (1
H, d, J = 9.4 Hz), 4.51-4.52 (2
H, m), 6.70-6.71 (1H, m), 6.81
(1H, dd, J = 2.7, 8.3 Hz), 7.04
(1H, d, J = 8.3 Hz), 7.27-7.28
(1H, m), 7.30 (1H, d, J = 2.7H
z), 7.54-7.65 (2H, m), 7.94-
7.96 (1H, m) FAB-MS (m / e): 437 [M + H] ⁺

Example 2002 3- (1-methylethyl) -9b-phenyl-1H-i
Midazo [2,1-a] isoindole-2,5 (3H,
9bH) -dione (in the general formula [I-2], R ¹ :
^{H; R 2: H; R} 3: i-Pr; R 4: H; R 5: H; Z:
Ph; compound of R: Ph) Nt-butoxycarbonyl-D-valine 106 mg
(0.49 mmol) in a solution of N, N-dimethylformamide (1 ml) at room temperature was added with 100 mg (0.73 mmol) of 1-hydroxybenzotriazole hydrate,
113 mg (0.58 mmol) of (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 28
Aqueous ammonia solution (3 ml) was added, and the reaction solution was stirred at room temperature for 12 hours. Water and ethyl acetate were added to the reaction solution, and the organic layer was dried and concentrated under reduced pressure. The obtained residue was purified by flash silica gel column chromatography to obtain amide (80 mg, yield: 76%). The obtained amide (80 mg, 0.37 mmol) was dissolved in 4N hydrochloric acid in 1,4-dioxane (2 ml) at room temperature, and the reaction solution was stirred at room temperature for 1 hour and concentrated under reduced pressure. The obtained residue and 2-benzoylbenzoic acid 83m
g (0.37 mmol) in a dimethylformamide solution (2 ml) at room temperature was added with 60 mg (0.63 mmol) of 1-hydroxybenzotriazole hydrate and 1- (3-
85 mg (0.44 mmol) of dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 0.12 ml (0.85 mmol) of triethylamine were sequentially added, and the reaction solution was stirred at room temperature for 12 hours. Water and ethyl acetate were added to the reaction solution at room temperature, and the organic layer was dried and concentrated under reduced pressure. The obtained residue was purified by flash silica gel column chromatography to obtain the condensed compound 13
0 mg (yield: 99%) was obtained. Obtained condensation compound 1
3 mg (0.040 mmol) of a toluene solution (2 m
To l), p-toluenesulfonic acid (10 mg) was added at room temperature, and the reaction solution was stirred for 4 hours while heating under reflux. The reaction solution is concentrated under reduced pressure, and the obtained residue is azeotropically distilled with toluene.
Repeated times and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give the title compound (2.0 m).
g (Yield: 16%) as a colorless oil.

¹ H NMR (CDCl ₃ ) δ: 0.81 (3
H, d, J = 6.6 Hz), 1.14 (3H, d, J =
6.6 Hz), 1.70-1.83 (1H, m), 4.
15 (1H, d, J = 8.6 Hz), 7.30-7.3
5 (5H, m), 7.50-7.54 (2H, m),
7.89-7.93 (1H, m), 8.09 (1H, b
rs) FAB-MS (m / e): 307 [M + H] ⁺

In the same manner as in Example 2002, Examples 2011, 2050, 2074, and 246 corresponding to the compound numbers of the compounds of the general formula [I-2] in the above compound list.
7, 2471, 2472 and 2474 were obtained.
The physical constants are shown below.

[0476]

Embedded image

Example 2011 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 5: H; Z: Ph; R: 4
—MeO—Ph) ¹ H NMR (CDCl ₃ ) δ: 0.86 (3H, d, J =
6.8 Hz), 1.19 (3H, d, J = 6.8H)
z), 1.77-1.85 (1H, m), 3.79 (3
H, s), 4.16 (1H, d, J = 8.6 Hz),
6.84 (2H, d, J = 8.9 Hz), 7.22-
7.88 (6H, m), 9.55 (1H, brs) ESI-MS (m / e): 337 [M + H] ⁺

Example 2050 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 5: H; Z: Ph; R: 3
_{-NH 2 -4-Cl-Ph)} 1 HNMR (CDCl 3) δ: 0.89 (3H, d, J =
6.7 Hz), 1.17 (3H, d, J = 6.7H)
z), 1.77-1.88 (1H, m), 4.13 (1
H, d, J = 8.7 Hz), 6.67 (1H, dd, J)
= 2.2, 8.3 Hz), 6.77 (1H, d, J =
2.2Hz), 7.19 (1H, d, J = 8.3H)
z), 7.21-7.88 (4H, m), 9.02 (1
H, s) ESI-MS (m / e): 356 [M + H] ⁺

Example 2074 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 5: H; Z: Ph; R: 3
-I-4-n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.86 (3H, d, J =
6.7 Hz), 0.98 (3H, t, J = 7.4H)
z), 1.17 (3H, d, J = 6.7 Hz), 1.5
5-1.78 (3H, m), 3.35 (2H, q, J =
7.0 Hz), 4.16 (1H, d, J = 8.8H)
z), 4.50 (2H, s), 6.73 (1H, d, J
= 8.6 Hz), 6.92 (1H, brs), 7.16
-7.93 (6H, m), 8.98 (1H, brs) FAB-MS (m / e): 548 [M + H] ⁺

Example 2467 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 5: H; Z: Ph; R: 4
_{-N-PrNHCOCH 2 O-pyrimidin-} 5
-Yl) FAB-MS (m / e): 424 [M + H] ⁺

Example 2471 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 5: Me; Z: Ph; R:
4-n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.76 (3H, d, J =
6.6 Hz), 0.91 (3H, d, J = 7.4H)
z), 1.17 (3H, d, J = 6.6 Hz), 1.5
2-1.68 (3H, m), 3.13 (3H, s),
3.31 (2H, dt, J = 6.6,7.3 Hz),
4.03 (1H, d, J = 10.0 Hz), 4.48
(2H, s), 6.53 (1H, brs), 6.85-
8.00 (8H, m) FAB-MS (m / e): 436 [M + H] ⁺

Example 2472 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; R ⁵ : n-PrNHCOC
H ₂ ; Z: Ph; R: 4-n-PrNHCOCH ₂ O-P
h) ¹ H NMR (CDCl ₃ ) δ: 0.61 (3H, t, J =
7.4 Hz), 0.81 (3H, d, J = 6.5H)
z), 0.93 (3H, t, J = 7.4 Hz), 1.0
1-1.11 (2H, m), 1.20 (3H, d, J =
6.5 Hz), 1.51-1.68 (3H, m), 2.
83-2.97 (2H, m), 3.32 (2H, t, J
= 7.3 Hz), 4.17 (1H, d, J = 10.5H)
z), 4.33 (2H, d, J = 16.2 Hz);
50 (2H, s), 5.69 (1H, brs), 6.5
2 (1H, brs), 6.87-8.00 (8H, m) FAB-MS (m / e): 521 [M + H] ⁺

Example 2474 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; R ⁵ : MeSO ₂ NHCOCH
₂ ; Z: Ph; R: 4-n-PrNHCOCH ₂ O-P
h) FAB-MS (m / e): 557 [M + H] ⁺

Example 3011 9b- (4-Methoxyphenyl) -3- (1-methyle
Tyl) -1H-pyrrolo [2,1-a] isoindole-
2,5 (3H, 9bH) -dione (in the general formula [I-3], R ¹ : H; R ² : H; R ³ : i-Pr; R ⁴ : H;
^{R 6: H; Z: Ph} ; R: Compound of 4-MeO-Ph)

To a solution of 25 g (120 mmol) of Nt-butoxycarbonyl-D-valine in 500 ml of tetrahydrofuran was added 55 ml of triethylamine (390 ml).
mol), 13 ml of chloroformic acid ethyl ester (140
mmol) at −40 ° C., and the reaction solution is added at −40 ° C. for 2 hours.
After stirring for 24 hours, 23 g (230 mmol) of N, O-dimethylhydroxylamine hydrochloride was added at -40 ° C, and after stirring at 0 ° C for 1 hour, aqueous ammonium chloride solution was added. After extraction with ethyl acetate, the organic layer was washed with a saturated saline solution, dried, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 7: 3) to obtain 18 g of amide (yield: 61%). 3. The resulting amide
To a solution of 9 g (18.9 mmol) in tetrahydrofuran (100 ml) at -70 ° C was added 19.0 m of a solution of methylmagnesium bromide (3.0 M) in diethyl ether.
1 (56.6 mmol) was added dropwise, and the reaction solution was stirred at room temperature for 2 hours, and then aqueous ammonium chloride was added to the reaction solution. The mixture was extracted with ethyl acetate, and the organic layer was washed with a saturated saline solution, dried, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 8: 1) to give ketone 2.
0 g (yield: 50%) was obtained.

The obtained ketone (2.0 g, 0.22 mmol)
l) at room temperature in 4N hydrochloric acid in 1,4-dioxane (20
ml), and the reaction solution was stirred at room temperature for 1 hour and concentrated under reduced pressure to obtain 1.4 g (yield: 99%) of amine hydrochloride. Amine hydrochloride (510 mg, 3.4 mmol) was dissolved in methylene chloride (32 ml), and 1-
590 mg of hydroxybenzotriazole hydrate (4.
4 mmol), 860 mg (3.4 mmol) of 2- (4-methoxybenzoyl) benzoic acid, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride 8
40 mg (4.4 mmol) and triethylamine 1.
8 ml (13.5 mmol) was sequentially added, and after stirring the reaction solution at room temperature for 12 hours, water was added to the reaction solution. After extraction with ethyl acetate, the organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, dried, and concentrated under reduced pressure. The obtained residue is subjected to silica gel column chromatography (hexane: ethyl acetate = 3:
2), and 990 mg of the condensation product (yield: 83
%). 890 mg of the obtained condensed compound (2.5 m
mol) in methylene chloride (50 ml) solution, triethylamine 2.1 ml (15 mmol) and trifluoromethanesulfonic acid trimethylsilyl ester 2.7 ml (1
5 mmol), and the reaction solution was stirred at room temperature for 2 hours. Then, 6.4 ml (50 mmol) of boron trifluoride diethyl ether complex was added at -70 ° C, and the reaction solution was stirred at room temperature for 12 hours. Water was added to the reaction solution. After extraction with chloroform, the organic layer was washed with a saturated aqueous solution of ammonium chloride and a saturated aqueous solution of sodium chloride, dried, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1) to give 94 mg of diastereomer A of the title compound (yield:
11%) as colorless oil, diastereomer B30
6 mg (yield: 36%) was obtained as a colorless oil.

Diastereomer A ¹ HNMR (CDCl ₃ ) δ: 0.86 (3H, d, J =
7.0Hz), 1.19 (3H, d, J = 7.0H)
z), 2.59 (1H, d, J = 15.9 Hz);
44 (1H, d, J = 15.9 Hz), 3.63-3.
71 (1H, m), 3.76 (3H, s), 3.78
(1H, d, J = 3.2 Hz), 6.83 (2H, d,
J = 8.9 Hz), 7.23-7.28 (1H, m),
7.35-7.37 (1H, m), 7.43-7.54
(2H, m), 7.87-7.90 (1H, m) ESI-MS (m / e): 336 [M + H] ⁺

Diastereomer B ¹ HNMR (CDCl ₃ ) δ: 0.85 (3H, d, J =
6.7 Hz), 1.09 (3H, d, J = 6.7H)
z), 1.50-1.70 (1H, m), 2.53 (1
H, d, J = 17.4 Hz), 3.60 (1H, d, J)
= 17.4 Hz), 3.79 (3H, s), 4.01
(1H, d, J = 9.6 Hz), 6.84 (2H, d,
J = 9.0 Hz), 7.14-7.24 (1H, m),
7.21 (2H, d, J = 9.0 Hz), 7.45-
7.54 (2H, m), 7.90-7.93 (1H,
m) ESI-MS (m / e): 336 [M + H] ⁺

In the same manner as in Example 3011, the compound of the general formula [I-3a] and the compound of the general formula [I-
3b], Examples 3001, 3002, 3007, 3014, 3015 corresponding to the compound numbers of the compound of the general formula [I-3c] or the compound of the general formula [I-3d],
3020, 3023, 3024, 3033, 3039,
3047, 3050, 3051, 3056, 3057,
3058, 3061, 3063, 3065, 3072,
3073, 3074, 3082, 3092, 3093,
3094, 3095, 3096, 3103, 3104,
3107, 3112, 3115, 3117, 3126,
3129, 3134, 3226, 3241, 3246,
3258, 3266, 3296, 3307, 3319,
3412, 3418, 3464, 3472, 3473,
3474, 3475, 3476, 3377, 3478,
3479, 3480, 3481, 3482, 3485,
3486, 3487, 3488, 3489, 3492,
3499, 3500, 3501, 3509, 3510,
Compounds 3511, 3515 and 3516 were obtained. The physical constants are shown below.

[0490]

Embedded image

Example 3001 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 2
-MeO-Ph) diastereomer-A ¹ H NMR (CDCl ₃ ) δ: 0.85 (3H, d, J =
7.0 Hz), 1.21 (3H, d, J = 7.0H)
z), 2.61 (1H, d, J = 16.7 Hz);
67-3.78 (1H, m), 3.86 (1H, d, J
= 16.7 Hz), 3.87 (1H, d, J = 3.2H)
z), 4.01 (3H, s), 6.87 (1H, t, J
= 7.4 Hz), 6.94 (1H, d, J = 8.0H)
z), 7.22-7.28 (2H, m), 7.41-
7.50 (2H, m), 7.83 (1H, dd, J =
1.6, 7.4 Hz), 7.90 (1H, d, J = 6.
3 Hz) ESI-MS (m / e): 336 [M + H] ⁺

Diastereomer B ¹ HNMR (CDCl ₃ ) δ: 1.13 (6H, d, J =
6.6 Hz), 1.69-1.74 (1H, m), 2.
64 (1H, d, J = 18.1 Hz), 3.89 (3
H, brs), 3.97 (1H, d, J = 18.1H)
z), 4.00 (1H, d, J = 10.3 Hz), 6.
88 (1H, t, J = 7.6 Hz), 6.94 (1H,
d, J = 8.2 Hz), 7.30 (1H, t, J = 8.
2Hz), 7.41-7.50 (3H, m), 7.61
(1H, brs), 7.86 (1H, d, J = 6.5H)
z) ESI-MS (m / e): 336 [M + H] ⁺

Example 3002 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: P
h) ¹ H NMR (CDCl ₃ ) δ: 0.87 (3H, d, J =
6.7 Hz), 1.09 (3H, d, J = 6.6H)
z), 1.49-1.70 (1H, m), 2.58 (1
H, d, J = 17.6 Hz), 3.66 (1H, d, J)
= 17.6 Hz), 4.03 (1H, d, J = 9.6H)
z), 7.12-7.21 (1H, m), 7.25-
7.39 (5H, m), 7.42-7.56 (2H,
m), 7.89-7.97 (1H, m) FAB-MS (m / e): 306 [M + H] ⁺

Example 3007 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
-HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.84 (3H, d, J =
6.7 Hz), 1.09 (3H, d, J = 6.7H)
z), 1.51-1.64 (1H, m), 2.52 (1
H, d, J = 17.3 Hz), 3.59 (1H, d, J)
= 17.3 Hz), 4.01 (1H, d, J = 9.5H)
z), 5.17 (1H, brs), 6.79 (2H,
d, J = 8.8 Hz), 7.15-7.19 (1H,
m), 7.16 (2H, d, J = 8.8 Hz), 7.4
6-7.54 (2H, m), 7.90-7.93 (1
H, m) ESI-MS (m / e): 322 [M + H] ⁺

Example 3014 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
_{-T-BuO 2 CCH 2 O-} Ph) 1 HNMR (CDCl 3) δ: 0.83 (3H, d, J =
6.6 Hz), 1.08 (3H, d, J = 6.6H)
z), 1.45-1.46 (9H, m), 1.49-
1.67 (1H, m), 2.53 (1H, d, J = 1
7.3 Hz), 3.59 (1H, d, J = 17.3H)
z), 4.01 (1H, d, J = 9.6 Hz), 4.4
8-4.49 (2H, m), 6.83 (2H, d, J =
8.9 Hz), 7.15-7.24 (1H, m), 7.
20 (2H, d, J = 8.9 Hz), 7.45-7.5
5 (2H, m), 7.90-7.93 (1H, m) FAB-MS (m / e): 436 [M + H] ⁺

Example 3015 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
-HO ₂ CCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.83 (3H, d, J =
6.6 Hz), 1.08 (3H, d, J = 6.6H)
z), 1.47-1.59 (1H, m), 2.56 (1
H, d, J = 17.2 Hz), 3.61 (1H, d, J)
= 17.2 Hz), 4.02 (1H, d, J = 9.6H)
z), 4.67 (2H, s), 6.87 (2H, d, J
= 8.9 Hz), 7.17 (1H, dd, J = 1.4,
6.2 Hz), 7.22 (2H, d, J = 8.9H)
z), 7.46-7.56 (2H, m), 7.93 (1
H, dd, J = 1.8, 6.2 Hz), 8.65 (1
H, brs) FAB-MS (m / e): 380 [M + H] ⁺

Example 3020 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
_{-HOC (Me) 2 (CH 2} ) 2 O-Ph) 1 HNMR (CDCl 3) δ: 0.87 (3H, d, J =
6.6 Hz), 1.12 (3H, d, J = 6.6H)
z), 1.32 (6H, s), 1.50-1.62 (1
H, m), 1.99 (2H, t, J = 6.3 Hz),
2.55 (1H, d, J = 16.0 Hz), 3.62
(1H, d, J = 16.0 Hz), 4.02 (1H, d, J = 16.0 Hz)
d, J = 9.5 Hz), 4.17 (2H, t, J = 6.
3 Hz), 6.86 (1H, d, J = 8.8 Hz),
7.18-7.92 (6H, m) FAB-MS (m / e): 408 [M + H] ⁺

Example 3023 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
-EtNHCOCH ₂ O-Ph) FAB-MS (m / e): 407 [M + H] ⁺

Example 3024 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
_{-N-PrNHCOCH 2 O-Ph)} 1 HNMR (CDCl 3) δ: 0.84 (3H, d, J =
6.6 Hz), 0.90 (3H, t, J = 7.4H)
z), 1.09 (3H, d, J = 6.6 Hz), 1.4
9-1.61 (3H, m), 2.55 (1H, d, J =
17.4 Hz), 3.30 (2H, q, J = 6.8H)
z), 3.60 (1H, d, J = 17.4 Hz), 4.
02 (1H, d, J = 9.5 Hz), 4.47 (2H,
s), 6.53 (1H, brs), 6.88 (2H,
d, J = 9.0 Hz), 7.16 (1H, dd, J =
2.2, 5.7 Hz), 7.27 (2H, d, J = 9.
0 Hz), 7.46-7.55 (2H, m), 7.92
(1H, dd, J = 2.0, 5.1 Hz) FAB-MS (m / e): 421 [M + H] ⁺

Example 3033 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
-N-PrNHCOCH = CH-Ph) FAB-MS (m / e): 417 [M + H] ⁺

Example 3039 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
_{-HO 2 COCH 2 O-Ph)} FAB-MS (m / e): 380 [M + H] +

Example 3047 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
_{-Cl-3-NO 2 -Ph)} FAB-MS (m / e): 385 [M + H] +

Example 3050 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
_{-NH 2 -4-Cl-Ph)} FAB-MS (m / e): 355 [M + H] +

Example 3051 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-Cl-4-MeO-Ph) FAB-MS (m / e): 370 [M + H] ⁺

Example 3056 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-F-4-Me-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.90 (3H, d, J =
6.7 Hz), 1.10 (3H, d, J = 6.7H)
z), 1.53-1.65 (1H, m), 2.24 (3
H, s), 2.57 (1H, d, J = 17.5 Hz),
3.56 (1H, d, J = 17.5 Hz), 4.02
(1H, d, J = 9.7 Hz), 6.95 (1H, d
d, J = 1.9, 10.7 Hz), 7.02 (1H, d
d, J = 1.9, 7.9 Hz), 7.14 (1H, d,
J = 7.9 Hz), 7.17-7.20 (1H, m),
7.47-7.55 (2H, m), 7.90-7.93
(1H, m) ESI-MS (m / e): 338 [M + H] ⁺

Example 3057 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-Br-4-HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.88 (3H, d, J =
6.6 Hz), 1.11 (3H, d, J = 6.6H)
z), 1.53-1.70 (1H, m), 2.55 (1
H, d, J = 17.4 Hz), 3.55 (1H, d, J)
= 17.4 Hz), 4.02 (1H, d, J = 9.6H)
z), 5.81 (1H, brs), 6.98 (1H,
d, J = 8.5 Hz), 7.15-7.20 (2H,
m), 7.42 (1H, d, J = 2.3 Hz), 7.4
8-7.57 (2H, m), 7.91-7.94 (1
H, m) FAB-MS (m / e): 400/402 [M + H] ⁺

Example 3058 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-Br-4-MeO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.89 (3H, d, J =
6.6 Hz), 1.11 (3H, d, J = 6.6H)
z), 1.51-1.65 (1H, m), 2.55 (1
H, d, J = 17.4 Hz), 3.56 (1H, d, J)
= 17.4 Hz), 3.88 (3H, s), 4.02
(1H, d, J = 9.6 Hz), 6.84 (1H, d,
J = 8.6 Hz), 7.17-7.25 (2H, m),
7.47-7.56 (3H, m), 7.91-7.94
(1H, m) FAB-MS (m / e): 414/416 [M + H] ⁺

Example 3061 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
-HO-3-I-Ph) FAB-MS (m / e): 448 [M + H] ⁺

Example 3063 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-I-4-MeO-Ph) ¹ H NMR (CDCl ₃ ) δ: 1.11 (3H, d, J =
6.6 Hz), 1.27 (3H, d, J = 6.6H)
z), 1.53-1.60 (1H, m), 2.55 (1
H, d, J = 16.7 Hz), 3.56 (1H, d, J)
= 16.7 Hz), 3.86 (3H, s), 4.02
(1H, d, J = 9.7 Hz), 6.75 (1H, d,
J = 8.6 Hz), 7.17-7.94 (6H, m) FAB-MS (m / e): 462 [M + H] ⁺

Example 3065 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
-MeO-3-Me-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.88 (3H, d, J =
6.7 Hz), 1.09 (3H, d, J = 6.7H)
z), 1.39-1.62 (1H, m), 2.15 (3
H, s), 2.51 (1H, d, J = 17.3 Hz),
3.60 (1H, d, J = 17.3 Hz), 3.80
(3H, s), 4.00 (1H, d, J = 9.7H)
z), 6.74 (1H, d, J = 8.6 Hz), 7.0
1 (1H, d, J = 2.6 Hz), 7.10-7.21
(2H, m), 7.44-7.53 (2H, m), 7.
90-7.93 (1H, m) FAB-MS (m / e): 350 [M + H] ⁺

Example 3072 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-I-4-MeNHCOCH ₂ O-Ph) FAB-MS (m / e): 519 [M + H] ⁺

Example 3073 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
_{-EtNHCOCH 2 O-3-I-} Ph) FAB-MS (m / e): 533 [M + H] +

Example 3074 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-I-4-n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.90 (3H, d, J =
6.6 Hz), 0.96 (3H, t, J = 7.4H)
z), 1.11 (3H, d, J = 6.6 Hz), 1.5
3-1.67 (3H, m), 2.57 (1H, d, J =
16.7 Hz), 3.35 (2H, q, J = 6.6H)
z), 3.55 (1H, d, J = 16.7 Hz), 4.
03 (1H, d, J = 9.5 Hz), 4.49 (2H,
s), 6.73 (1H, d, J = 8.6 Hz), 6.8
8-6.93 (1H, m), 7.16-7.19 (1
H, m), 7.33 (1H, dd, J = 2.3, 8.6)
Hz), 7.48-7.57 (2H, m), 7.73
(1H, d, J = 2.3 Hz), 7.92-7.95
(1H, m) FAB-MS (m / e): 547 [M + H] ⁺

Example 3082 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
_{-CycloPrNHCOCH 2 O-3-I-} Ph) FAB-MS (m / e): 545 [M + H] +

Example 3092 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
_{-Cl-4-n-PrNHCOCH 2} O-Ph) 1 HNMR (CDCl 3) δ: 0.88 (3H, d, J =
6.6 Hz), 0.94 (3H, t, J = 7.4H)
z), 1.11 (3H, d, J = 6.6 Hz), 1.5
2-1.93 (3H, m), 2.58 (1H, d, J =
16.0 Hz), 3.32 (2H, q, J = 6.7H)
z), 3.56 (1H, d, J = 16.0 Hz), 4.
03 (1H, d, J = 9.6 Hz), 4.51 (2H,
s), 6.74-6.79 (1H, m), 6.87 (1
H, d, J = 8.6 Hz), 7.16-7.19 (1
H, m), 7.24 (1H, dd, J = 2.4, 8.6)
Hz), 7.36 (1H, d, J = 2.4 Hz), 7.
48-7.57 (2H, m), 7.92-7.96 (1
H, m) FAB-MS (m / e): 455/457 [M + H] ⁺

Example 3093 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
_{-Br-4-n-PrNHCOCH 2} O-Ph) 1 HNMR (CDCl 3) δ: 0.89 (3H, d, J =
6.6 Hz), 0.95 (3H, t, J = 7.4H)
z), 1.11 (3H, d, J = 6.6 Hz), 1.5
2-1.65 (3H, m), 2.58 (1H, d, J =
17.0 Hz), 3.33 (2H, q, J = 6.6H)
z), 3.56 (1H, d, J = 17.0 Hz), 4.
03 (1H, d, J = 9.6 Hz), 4.50 (2H,
s), 6.82-6.85 (1H, m), 6.83 (1
H, d, J = 8.6 Hz), 7.16-7.19 (1
H, m), 7.29-7.31 (1H, m), 7.48
−7.57 (3H, m), 7.88−7.94 (1H,
m) FAB-MS (m / e): 499/501 [M + H] ⁺

Example 3094 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-F-4-n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.88 (3H, d, J =
6.6 Hz), 0.92 (3H, t, J = 7.4H)
z), 1.11 (3H, d, J = 6.6 Hz), 1.5
1-1.64 (3H, m), 2.58 (1H, d, J =
17.5 Hz), 3.30 (2H, q, J = 6.8H)
z), 3.55 (1H, d, J = 17.5 Hz), 4.
03 (1H, d, J = 9.5 Hz), 4.51 (2H,
s), 6.61-6.64 (1H, m), 6.92 (1
H, t, J = 8.5 Hz), 7.04 (1H, d, J =
11.9 Hz), 7.07-7.18 (2H, m),
7.48-7.57 (2H, m), 7.91-7.98
(1H, m) FAB-MS (m / e): 439 [M + H] ⁺

Example 3095 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
_{-Me-4-n-PrNHCOCH 2} O-Ph) 1 HNMR (CDCl 3) δ: 0.87 (3H, d, J =
6.7 Hz), 0.92 (3H, t, J = 7.4H)
z), 1.09 (3H, d, J = 6.7 Hz), 1.4
9-1.59 (3H, m), 2.23 (3H, s),
2.54 (1H, d, J = 17.3 Hz), 3.21
(2H, q, J = 6.7 Hz), 3.58 (1H, d,
J = 17.3 Hz), 4.01 (1H, d, J = 9.6)
Hz), 4.47 (2H, s), 6.49-6.51
(1H, m), 6.73 (1H, d, J = 8.6H
z), 7.08 (1H, d, J = 2.0 Hz), 7.1
4-7.18 (2H, m), 7.46-7.54 (2
H, m), 7.90-7.93 (1H, m) FAB-MS (m / e): 435 [M + H] ⁺

Example 3096 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
_{-EtNHCOCH 2 O-3-F-} Ph) FAB-MS (m / e): 425 [M + H] +

Example 3103 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-F-4-HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.87 (3H, d, J =
6.7 Hz), 1.11 (3H, d, J = 6.7H)
z), 1.54-1.66 (1H, m), 2.55 (1
H, d, J = 17.3 Hz), 3.54 (1H, d, J)
= 17.3 Hz), 4.02 (1H, d, J = 9.6H)
z), 5.38-5.41 (1H, m), 6.94-
7.05 (3H, m), 7.16-7.19 (1H,
m), 7.47-7.57 (2H, m), 7.91-
7.94 (1H, m) FAB-MS (m / e): 340 [M + H] ⁺

Example 3104 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-F-4-MeO-Ph) diastereomer A ¹ HNMR (CDCl ₃ ) δ: 0.85 (3H, d, J =
6.9 Hz), 1.19 (3H, d, J = 6.9H)
z), 2.60 (1H, d, J = 16.0 Hz), 3.
40 (1H, d, J = 16.0 Hz), 3.63-3.
69 (1H, m), 3.78 (1H, d, J = 3.2H)
z), 3.84 (3H, s), 6.89 (1H, dd,
J = 7.3, 8.5 Hz), 7.02 (1H, d, J =
2.3 Hz), 7.09 (1H, dd, J = 2.3,
7.3 Hz), 7.36 (1H, dd, J = 1.1,
6.2 Hz), 7.37-7.56 (2H, m), 7.
89 (1H, dd, J = 1.9, 6.9 Hz) FAB-MS (m / e): 354 [M + H] ⁺

Diastereomer B ¹ HNMR (CDCl ₃ ) δ: 0.87 (3H, d, J =
6.6 Hz), 1.11 (3H, d, J = 6.6H)
z), 1.55-1.63 (1H, m), 2.55 (1
H, d, J = 17.4 Hz), 3.55 (1H, d, J)
= 17.4 Hz), 3.87 (3H, s), 4.02
(1H, d, J = 9.6 Hz), 6.91 (1H, t,
J = 8.5 Hz), 6.98 (1H, dd, J = 2.
3, 12.2 Hz), 7.07 (1H, ddd, J =
1.1, 2.3, 8.5 Hz), 7.16-7.19
(1H, m), 7.48-7.56 (2H, m), 7.
91-7.94 (1H, m) FAB-MS (m / e): 354 [M + H] ⁺

Example 3107 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R:
_{3,4-Cl 2 -Ph) FAB-} MS (m / e): 375 [M + H] +

Example 3112 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R:
_{3,5-Me 2 -Ph) FAB-} MS (m / e): 334 [M + H] +

Example 3115 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R:
3,5-I ₂ -4-MeO-Ph) FAB-MS (m / e): 588 [M + H] ⁺

Example 3117 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R:
_{2,4,6-Me 3 -Ph) FAB-} MS (m / e): 348 [M + H] +

Example 3126 (R ¹ : 6-F; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: P
h) FAB-MS (m / e): 324 [M + H] ⁺

Example 3129 (R ¹ : 9-F; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: P
h) FAB-MS (m / e): 324 [M + H] ⁺

Example 3134 (R ¹ : 7-NO ₂ ; R ² :
^{H; R 3: i-Pr} ; R 4: H; R 6: H; Z: Ph;
R: Ph) FAB-MS (m / e): 351 [M + H] ⁺

Example 3226 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
-N-PrNHCOCH ₂ CH ₂ O-Ph) FAB-MS (m / e): 435 [M + H] ⁺

Example 3246 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
_{-F-4-i-PrNHCOCH 2} CH 2 O-Ph) FAB-MS (m / e): 453 [M + H] +

Example 3258 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
_{-Cl-4-EtNHCOCH 2 CH 2} O-Ph) FAB-MS (m / e): 455 [M + H] +

Example 3266 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
_{-Me-4-n-BuNHCOCH 2} CH 2 O-Ph) FAB-MS (m / e): 463 [M + H] +

Example 3296 (R ¹ : H; R ² : H;
^{R 3: Bu; R 4:} H; R 6: H; Z: Ph; R: 3-M
e-4-MeNHCOCH ₂ O-Ph) FAB-MS (m / e): 421 [M + H] ⁺

Example 3307 (R ¹ : H; R ² : H;
^{R 3: t-Bu; R} 4: H; R 6: H; Z: Ph; R: 3
_{-Me-4-n-PrNHCOCH 2} O-Ph) FAB-MS (m / e): 449 [M + H] +

Example 3319 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: Me; R 6: H; Z: Ph; R:
3-Cl-4-cycloPrNHCOCH ₂ O-P
h) FAB-MS (m / e): 467 [M + H] ⁺

Example 3324 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: 2,3-Py
Ridyl; R: 3-Me-4-MeNHCOCH ₂ O
-Ph) FAB-MS (m / e): 408 [M + H] ⁺

Example 3331 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: 3,4-Py
Ridyl; R: 3-Cl-4-EtNHCOCH ₂ O
-Ph) FAB-MS (m / e): 442 [M + H] ⁺

Example 3337 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
_{-EtNHCOCH 2 O-3-F- (} 2-Pyridy
l)) FAB-MS (m / e): 446 [M + H] ⁺

Example 3344 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 6
_{-EtNHCOCH 2 O-5-I- (} 3-Pyridy
l)) FAB-MS (m / e): 534 [M + H] ⁺

Example 3351 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
-EtNHCOCH ₂ O-3-NO ₂ -Ph) FAB-MS (m / e): 452 [M + H] ⁺

Example 3412 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: Me; Z: Ph; R:
3-Cl-4-EtNHCOCH ₂ O-Ph) FAB-MS (m / e): 455 [M + H] ⁺

Example 3418 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: Et; Z: Ph; R:
4-EtNHCOCH ₂ O-3-Me-Ph) FAB-MS (m / e): 449 [M + H] ⁺

Example 3464 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: pyrimi
din-4,5-yl; R: 4-n-BuNHCOCH
₂ O-Ph) FAB-MS (m / e): 437 [M + H] ⁺

Example 3472 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-Cl-4-HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.88 (3H, d, J =
6.7 Hz), 1.11 (3H, d, J = 6.7H)
z), 1.53-1.65 (1H, m), 2.55 (1
H, d, J = 17.5 Hz), 3.54 (1H, d, J)
= 17.5 Hz), 4.01 (1H, d, J = 9.5H)
z), 6.98 (1H, d, J = 8.6 Hz), 7.1
0-7.20 (1H, m), 7.13 (1H, dd, J
= 2.3, 8.6 Hz), 7.27 (1H, d, J =
2.3 Hz), 7.47-7.57 (2H, m), 7.
91-7.94 (1H, m) FAB-MS (m / e): 356 [M + H] ⁺

Example 3473 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
-HO-3-Me-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.86 (3H, d, J =
6.6 Hz), 1.08 (3H, d, J = 6.6H)
z), 1.53-1.61 (3H, m), 2.20 (3
H, s), 2.50 (1H, d, J = 17.3 Hz),
3.60 (1H, d, J = 17.3 Hz), 4.00
(1H, d, J = 9.7 Hz), 5.98 (1H,
s), 6.76 (1H, d, J = 8.2 Hz), 6.9
9 (1H, d, J = 8.2 Hz), 7.01 (1H,
s), 7.18 (1H, dd, J = 1.5, 6.4H
z), 7.44-7.54 (2H, m), 7.91 (1
H, dd, J = 1.5, 6.2 Hz) FAB-MS (m / e): 336 [M + H] ⁺

Example 3474 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
_{-HO 2 CCH 2 O-3-} Me-Ph) 1 HNMR (CDCl 3) δ: 0.86 (3H, d, J =
6.6 Hz), 1.07 (3H, d, J = 6.6H)
z), 1.47-1.59 (1H, m), 2.19 (3
H, s), 2.52 (1H, d, J = 17.3 Hz),
3.58 (1H, d, J = 17.3 Hz), 4.00
(1H, d, J = 9.8 Hz), 4.60 (2H,
s), 5.99-6.13 (1H, m), 6.63 (1
H, d, J = 8.3 Hz), 7.05-7.17 (3
H, m), 7.44-7.52 (2H, m), 7.90
−7.93 (1H, m) FAB-MS (m / e): 394 [M + H] ⁺

Example 3475 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R:
_{3,5-Cl 2 -4-n-} PrNHCOCH 2 O-Ph) 1 HNMR (CDCl 3) δ: 0.94 (3H, d, J =
6.4 Hz), 0.98 (3H, t, J = 7.5H)
z), 1.13 (3H, d, J = 6.4 Hz), 1.5
4-1.68 (3H, m), 2.63 (1H, d, J =
16.1 Hz), 3.35 (2H, q, J = 6.6H)
z), 3.50 (1H, d, J = 16.1 Hz), 4.
04 (1H, d, J = 9.7 Hz), 4.51 (2H,
s), 6.93-6.94 (1H, m), 7.22-
7.25 (1H, m), 7.33 (2H, s), 7.5
1-7.61 (2H, m), 7.92-7.95 (1
H, m) FAB-MS (m / e): 489/491 [M + H] ⁺

Example 3476 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 3
-Me-4-n-PrNHCSCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.87 (3H, d, J =
6.6 Hz), 0.95 (3H, t, J = 7.5H)
z), 1.09 (3H, d, J = 6.6 Hz), 1.5
1-1.75 (3H, m), 2.23 (3H, s),
2.54 (1H, d, J = 17.4 Hz), 3.59
(1H, d, J = 17.4 Hz), 3.71 (2H,
q, J = 6.6 Hz), 4.01 (1H, d, J = 9.
8Hz), 4.88 (2H, s), 6.74 (1H,
d, J = 8.2 Hz), 7.09 (1H, d, J = 2.
2 Hz), 7.14-7.17 (2H, m), 7.46
−7.54 (2H, m), 7.91-7.93 (1H,
m), 8.19-8.21 (1H, m) FAB-MS (m / e): 451 [M + H] ⁺

Example 3377 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R:
_{3,5-Cl 2 -4-n-} PrNHCSCH 2 O-Ph) 1 HNMR (CDCl 3) δ: 0.93 (3H, d, J =
6.8 Hz), 1.04 (3H, t, J = 7.4H)
z), 1.13 (3H, d, J = 6.8 Hz), 1.3
2-1.41 (1H, m), 1.72-1.81 (2
H, m), 2.62 (1H, d, J = 17.7 Hz),
3.51 (1H, d, J = 17.7 Hz), 3.75
(2H, q, J = 6.6 Hz), 4.04 (1H, d,
J = 9.7 Hz), 4.89 (2H, s), 7.22
(1H, d, J = 7.9 Hz), 7.33 (2H,
s), 7.52-7.69 (2H, m), 7.93-
7.95 (1H, m), 8.69-8.71 (1H,
m) FAB-MS (m / e): 505/507 [M + H] ⁺

Example 3478 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R: 4
_{-N-Pentyl-NHCOCH 2 O-} Ph) 1 HNMR (CDCl 3) δ: 0.83-0.96 (3
H, m), 0.87 (3H, d, J = 6.7 Hz),
1.10 (3H, d, J = 6.7 Hz), 1.14
1.70 (7H, m), 2.56 (1H, d, J = 1
7.2 Hz), 3.32 (2H, q, J = 6.6H)
z), 3.60 (1H, d, J = 17.2 Hz), 4.
02 (1H, d, J = 9.6 Hz), 4.46 (2H,
s), 6.49 (1H, s), 6.87 (2H, d, J
= 9.0 Hz), 7.15-7.20 (1H, m),
7.25-7.34 (2H, m), 7.48-7.54
(2H, m), 7.91-7.92 (1H, m) FAB-MS (m / e): 449 [M + H] ⁺

Example 3479 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: Me; Z: Ph; R:
4-MeO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.69 (3H, d, J =
7.5 Hz), 0.91 (3H, d, J = 6.7H)
z), 1.11 (3H, d, J = 6.7 Hz), 1.4
8-1.73 (1H, m), 3.51 (1H, q, J =
7.5 Hz), 3.77 (3H, s), 4.02 (1
H, d, J = 9.6 Hz), 6.83 (2H, d, J =
8.9 Hz), 7.10-7.13 (1H, m), 7.
24 (2H, d, J = 8.9 Hz), 7.46-7.5
1 (2H, m), 7.89-7.99 (1H, m) FAB-MS (m / e): 350 [M + H] ⁺

Example 3480 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: Me; Z: Ph; R:
4-HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.68 (3H, d, J =
7.5 Hz), 0.89 (3H, d, J = 6.6H)
z), 1.10 (3H, d, J = 6.6 Hz), 1.4
8-1.69 (1H, m), 3.52 (1H, q, J =
7.5 Hz), 4.02 (1H, dd, J = 1.0,
9.5 Hz), 5.63 (1H, s), 6.79 (2
H, d, J = 8.8 Hz), 7.11-7.15 (1
H, m), 7.18 (2H, d, J = 8.8 Hz),
7.44-7.54 (2H, m), 7.90-7.92
(1H, m) FAB-MS (m / e): 336 [M + H] ⁺

Example 3481 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: Me; Z: Ph; R:
4-n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.70 (3H, d, J =
7.6 Hz), 0.90 (3H, d, J = 7.4H)
z), 0.90 (3H, d, J = 6.6 Hz), 1.1
1 (3H, d, J = 6.6 Hz), 1.48-1.66
(3H, m), 3.30 (2H, q, J = 6.8H
z), 3.50 (1H, q, J = 7.5 Hz), 4.0
4 (1H, dd, J = 1.0, 9.5 Hz), 4.46
(2H, s), 6.50-6.51 (1H, m), 6.
86 (2H, d, J = 8.9 Hz), 7.09-7.1
2 (1H, m), 7.29 (2H, d, J = 8.9H
z), 7.46-7.52 (2H, m), 7.91-
7.94 (1H, m) FAB-MS (m / e): 435 [M + H] ⁺

Example 3482 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: Br; Z: Ph; R:
4-n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.90 (3H, d, J =
6.6 Hz), 0.99 (3H, t, J = 6.6H)
z), 1.17 (3H, d, J = 6.6 Hz), 1.5
1-1.74 (3H, m), 3.30 (2H, q, J =
6.7 Hz), 4.36 (1H, d, J = 9.5H)
z), 4.47 (2H, s), 5.14 (1H, s),
6.47-6.50 (1H, m), 6.91 (2H,
d, J = 8.9 Hz), 7.16-7.19 (1H,
m), 7.34 (2H, d, J = 8.9 Hz), 7.5
0-7.57 (2H, m), 7.91-7.94 (1
H, m) FAB-MS (m / e): 499/501 [M + H] ⁺

Example 3485 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; R ⁶ : MeSO ₂ NHCH ₂ C
H ₂ ; Z: Ph; R: 4-n-PrNHCOCH ₂ O-P
h) FAB-MS (m / e): 542 [M + H] ⁺

Example 3486 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; R ⁶ : MeO ₂ CCH ₂ ; Z:
Ph; R: 4-n-PrNHCOCH ₂ O-Ph) FAB-MS (m / e): 493 [M + H] ⁺

Example 3487 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; R ⁶ : HOCH ₂ CH ₂ ; Z:
Ph; R: 4-n-PrNHCOCH ₂ O-Ph) FAB-MS (m / e): 465 [M + H] ⁺

[0559]

Embedded image

Example 3488 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R:
_{3,5-Cl 2 -4-n-} PrNHCOCH 2 O-Ph) 1 HNMR (CDCl 3) δ: 0.98 (3H, t, J =
7.4 Hz), 1.03 (3H, d, J = 6.6H)
z), 1.15 (3H, d, J = 6.6 Hz), 1.5
2-1.67 (3H, m), 2.61 (1H, d, J =
18.0 Hz), 3.35 (2H, q, J = 6.6H)
z), 3.55 (1H, d, J = 18.0 Hz), 4.
51 (2H, s), 4.57 (1H, d, J = 10.4
Hz), 6.89-6.93 (1H, m), 7.53-
7.61 (2H, m), 8.12-8.15 (1H,
m) FAB-MS (m / e): 505/507 [M + H] ⁺

Example 3489 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: Ph; R:
3,5-Cl ₂ -4-n-PrNHCSCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 1.02 (3H, d, J =
6.3 Hz), 1.04 (3H, t, J = 7.4H)
z), 1.14 (3H, d, J = 6.3 Hz), 1.5
2-1.59 (1H, m), 1.71-1.83 (2
H, m), 2.61 (1H, d, J = 17.5 Hz),
3.56 (1H, d, J = 17.5 Hz), 3.75
(2H, q, J = 6.6 Hz), 4.56 (1H, d,
J = 10.3 Hz), 4.90 (2H, s), 7.17
-7.20 (1H, m), 7.23 (2H, s), 7.
53-7.60 (2H, m), 8.12-8.15 (1
H, m) FAB-MS (m / e): 521/523/525 [M
+ H] ⁺

Example 3492 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: H; Z: pyrimi
din-4,5-yl; R: 4-n-BuNHCOCH
₂ O-Ph) FAB-MS (m / e): 453 [M + H] ⁺

[0563]

Embedded image

Example 3499 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 5: MeO; R 6: H; Z:
Ph; R: 3-Me-4-n-PrNHCOCH ₂ O-
Ph) Geometric isomer A ¹ HNMR (CDCl ₃ ) δ: 0.92 (3H, t, J =
7.5 Hz), 0.93 (3H, d, J = 6.6H)
z), 1.06 (3H, d, J = 6.6 Hz), 1.4
6-1.71 (3H, m), 2.22 (3H, s),
2.63 (1H, d, J = 18.1 Hz), 3.31
(2H, q, J = 6.7 Hz), 3.88 (3H,
s), 3.93 (1H, dd, J = 1.0, 18.1H)
z), 4.38 (1H, d, J = 9.9 Hz), 4.4
7 (2H, s), 6.50-6.52 (1H, m),
6.72 (1H, d, J = 8.5 Hz), 7.11 (1
H, d, J = 2.4 Hz), 7.11-7.13 (1
H, m), 7.21 (1H, dd, J = 2.4, 8.5).
Hz), 7.39-7.49 (2H, m), 7.81-
7.84 (1H, m) FAB-MS (m / e): 464 [M + H] ⁺

Geometric isomer B ¹ HNMR (CDCl ₃ ) δ: 0.59 (3H, d, J =
6.8 Hz), 0.92 (3H, t, J = 7.4H)
z), 0.97 (3H, d, J = 6.8 Hz), 1.5
2-1.61 (2H, m), 2.04-2.12 (1
H, m), 2.23 (3H, s), 2.90 (1H,
d, J = 17.3 Hz), 3.29 (2H, q, J =
6.7 Hz), 3.71 (1H, dd, J = 1.5, 1)
7.3 Hz), 3.79 (3H, s), 4.46 (2
H, s), 4.91 (1H, dd, J = 1.2, 7.6).
Hz), 6.50-6.51 (1H, m), 6.73
(1H, d, J = 8.5 Hz), 7.11-7.13
(1H, m), 7.14 (1H, d, J = 2.4H
z), 7.23 (1H, dd, J = 2.4, 8.5H
z), 7.37-7.50 (2H, m), 7.79-
7.82 (1H, m) FAB-MS (m / e): 464 [M + H] ⁺

Example 3500 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 5: HO; R 6: H; Z: P
h; R: 3-Cl-4-n-PrNHCOCH ₂ O-P
h) FAB-MS (m / e): 470 [M + H] ⁺

Example 3501 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 5: Me; R 6: H; Z: P
h; R: 4-n-PrNHCOCH ₂ O-Ph) FAB-MS (m / e): 434 [M + H] ⁺

[0568]

Embedded image

Example 3509 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: Me; R 7: Me; Z:
Ph; R: 4-MeO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.52 (3H, s),
1.01 (3H, d, J = 6.6 Hz), 1.29 (3
H, d, J = 6.6 Hz), 1.44 (3H, s),
1.85-1.99 (1H, m), 3.77 (3H,
s), 4.01 (1H, d, J = 10.3 Hz), 6.
78 (2H, d, J = 9.1 Hz), 7.14 (2H, d, J = 9.1 Hz)
d, J = 9.1 Hz), 7.47-7.66 (3H,
m), 7.92-7.95 (1H, m) FAB-MS (m / e): 364 [M + H] ⁺

Example 3510 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: Me; R 7: Me; Z:
Ph; R: 4-HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.50 (3H, s),
0.97 (3H, d, J = 6.6 Hz), 1.28 (3
H, d, J = 6.6 Hz), 1.44 (3H, s),
1.83-1.91 (1H, m), 4.01 (1H,
d, J = 10.3 Hz), 5.91-5.92 (1H,
m), 6.74 (2H, d, J = 8.9 Hz), 7.0
4 (2H, d, J = 8.9 Hz), 7.47 (1H,
d, J = 7.5 Hz), 7.93 (1H, d, J = 7.
5 Hz) FAB-MS (m / e): 350 [M + H] ⁺

Example 3511 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: Me; R 7: Me; Z:
Ph; R: 4-n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.50 (3H, s),
0.90 (3H, t, J = 7.4 Hz), 1.02 (3
H, d, J = 6.5 Hz), 1.30 (3H, d, J =
6.5 Hz), 1.43 (3H, s), 1.51-1.
58 (2H, m), 1.85-1.89 (1H, m),
3.29 (2H, q, J = 6.8 Hz), 4.02 (1
H, d, J = 10.4 Hz), 4.45 (2H, s),
6.49-6.50 (1H, m), 6.82 (2H,
d, J = 9.0 Hz), 7.20 (2H, d, J = 9.
0 Hz), 7.47-7.67 (3H, m), 7.93
−7.95 (1H, m) FAB-MS (m / e): 449 [M + H] ⁺

Example 3515 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; R 6: MeCOCH 2; R 7:
Me; Z: Ph; R: 4-n-PrNHCOCH ₂ O-
Ph) FAB-MS (m / e): 491 [M + H] ⁺

Example 3516 (R ¹ : H; R ² : H;
R ³ : i-Pr; R ⁴ : H; R ⁶ : MeO ₂ CCH ₂ ; R ⁷ :
Me; Z: Ph; R: 4-n-PrNHCOCH ₂ O-
Ph) FAB-MS (m / e): 507 [M + H] ⁺

Example 4002 3- (1-Methylethyl) -9b-phenyl [1,3]
Thiazolo [2,3-a] isoindole-2,5 (3
H, 9bH) -dione (in the general formula [I-4], R
^{1: H; R 2: H} ; R 3: i-Pr; R 4: H; Z: Ph;
R: Compound of Ph) 2-benzoylbenzoic acid 5.0 g (22.1 mmol)
l), 4.1 g of D-valine methyl ester hydrochloride (2
4.3 mmol) and 9.2 ml of triethylamine (6
6.3 mmol) in 250 ml of methylene chloride solution under ice cooling with 1-hydroxybenzotriazole hydrate 3.6.
g (26.5 mmol) and 5.1 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride
(26.5 mmol) was added and the reaction solution was stirred at room temperature for 3 hours. A saturated aqueous ammonium chloride solution was added to the reaction solution, and after extraction with chloroform, the organic layer was washed with a saturated aqueous sodium chloride solution, dried, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain 4.9 g (yield: 65%) of a condensation product. Sodium hydrosulfide n-hydrate 140 was added to a tetrahydrofuran solution (4.5 ml) of 212 mg (0.62 mmol) of the obtained condensation product.
mg (2.50 mmol) was added, and the reaction solution was heated at room temperature for 1 hour.
After stirring for 2 hours, a 1N aqueous hydrochloric acid solution was added to the reaction solution at room temperature. The mixture was extracted with ethyl acetate, the organic layer was dried, and concentrated under reduced pressure. The obtained crude thiocarboxylic acid was dissolved in 2.5 ml of methylene chloride. 2.5 ml of trifluoroacetic acid was added to the reaction solution at room temperature, and the mixture was stirred at room temperature for 30 minutes, and then concentrated under reduced pressure. The obtained residue was azeotropically repeated three times with toluene, and concentrated under reduced pressure. The obtained residue is subjected to silica gel column chromatography (hexane:
Purification by acetic acid ethyl ester = 2: 1) yielded 43.0 mg of diastereomer A of the title compound (yield: 21%).
As a colorless oil, 7.0 mg of diastereomer B
(Yield: 4%) was obtained as a colorless oil.

Diastereomer A ¹ HNMR (CDCl ₃ ) δ: 1.14 (3H, d, J =
6.7 Hz), 1.31 (3H, d, J = 6.7H)
z), 3.61-3.71 (1H, m), 3.81 (1
H, dd, J = 0.7, 4.6 Hz), 7.31-7.
60 (8H, m), 7.91 (1H, dd, J = 2.
7,7.9 Hz) FAB-MS (m / e): 324 [M + H] ⁺

Diastereomer B ¹ HNMR (CDCl ₃ ) δ: 0.85 (3H, d, J =
6.6 Hz), 1.05 (3H, d, J = 6.6H)
z), 1.51-1.62 (1H, m), 4.53 (1
H, d, J = 10.3 Hz), 7.14-7.17 (1
H, m), 7.30-7.98 (8H, m) FAB-MS (m / e): 324 [M + H] ⁺

In the same manner as in Example 4002, Examples 4007, 4011, 4024 and 406 corresponding to the compound numbers of the compounds of the general formula [I-4] in the above compound list
1, 4063, 4073, 4074, 4079, 408
7, 7092, 4113, 4410, 4419 and 44
24 compounds were obtained. The physical constants are shown below.

Embedded image

Example 4007 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO-P
h) ¹ H NMR (CDCl ₃ ) δ: 0.85 (3H, d, J =
6.6 Hz), 1.07 (3H, d, J = 6.7H)
z), 1.52-1.64 (1H, m), 4.50 (1
H, d, J = 10.4 Hz), 5.11 (1H, br)
s), 6.79 (2H, d, J = 8.8 Hz), 7.1
5-7.17 (1H, m), 7.32 (2H, d, J =
8.8 Hz), 7.51-7.57 (2H, m), 7.
94-7.97 (1H, m) FAB-MS (m / e): 340 [M + H] ⁺

Example 4011 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-MeO-
Ph) ¹ H NMR (CDCl ₃ ) δ: 0.85 (3H, d, J =
6.1 Hz), 1.07 (3H, d, J = 6.7H)
z), 1.52-1.64 (1H, m), 3.81 (3
H, s), 4.50 (1H, d, J = 10.4 Hz),
6.85 (2H, d, J = 9.0 Hz), 7.14-
7.17 (1H, m), 7.36 (2H, d, J = 9.
0 Hz), 7.51-7.57 (2H, m), 7.94.
−7.97 (1H, m) FAB-MS (m / e): 354 [M + H] ⁺

Example 4024 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Pr
NHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.84 (3H, d, J =
6.6 Hz), 0.91 (3H, t, J = 7.4H)
z), 1.07 (3H, d, J = 6.7 Hz), 1.5
0-1.62 (3H, m), 3.31 (2H, q, J =
7.0 Hz), 4.48 (2H, s), 4.51 (1
H, d, J = 10.4 Hz), 6.54 (1H, br)
s), 6.89 (2H, d, J = 9.0 Hz), 7.1
3-7.16 (1H, m), 7.41 (2H, d, J =
9.0 Hz), 7.52-7.59 (2H, m), 7.
95-7.98 (1H, m) FAB-MS (m / e): 439 [M + H] ⁺

Example 4061 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO-3
-I-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.89 (3H, d, J =
6.6 Hz), 1.08 (3H, d, J = 6.8H)
z), 1.52-1.64 (1H, m), 4.50 (1
H, d, J = 10.4 Hz), 5.70 (1H, br)
s), 6.94 (1H, d, J = 8.6 Hz), 7.1
4-7.19 (1H, m), 7.30 (1H, dd, J
= 2.4, 8.6 Hz), 7.53-7.62 (2H,
m), 7.77 (1H, d, J = 2.4 Hz), 7.9
5-7.98 (1H, m) FAB-MS (m / e): 466 [M + H] ⁺

Example 4063 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
MeO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.89 (3H, d, J =
6.6 Hz), 1.08 (3H, d, J = 6.9H)
z), 1.52-1.64 (1H, m), 3.88 (3
H, s), 4.51 (1H, d, J = 10.4 Hz),
6.76 (1H, d, J = 8.6 Hz), 7.16-
7.18 (1H, m), 7.43 (1H, dd, J =
2.5, 8.6 Hz), 7.55-7.59 (2H,
m), 7.81 (1H, d, J = 2.5 Hz), 7.9
5-7.98 (1H, m) FAB-MS (m / e): 480 [M + H] ⁺

Example 4073 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-EtNH
COCH ₂ O-3-I-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.89 (3H, d, J =
6.6 Hz), 1.08 (3H, d, J = 6.6H)
z), 1.23 (3H, t, J = 7.2 Hz), 1.5
0-1.58 (1H, m), 3.38-3.47 (2
H, m), 4.45 (2H, s), 4.52 (1H,
d, J = 10.7 Hz), 6.73 (1H, d, J =
8.5 Hz), 6.86 (1H, brs), 7.14-
7.26 (1H, m), 7.47 (1H, dd, J =
2.2, 8.5 Hz), 7.56-7.59 (2H,
m), 7.84 (1H, d, J = 2.2 Hz), 7.9
6-7.99 (1H, m) FAB-MS (m / e): 551 [M + H] ⁺

Example 4074 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-I-4-
n-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.89 (3H, d, J =
6.6 Hz), 0.98 (3H, t, J = 7.4H)
z), 1.08 (3H, d, J = 6.6 Hz), 1.5
0-1.65 (3H, m), 3.36 (2H, q, J =
7.0 Hz), 4.51 (2H, s), 4.52 (1
H, d, J = 10.4 Hz), 6.74 (1H, d, J)
= 8.6 Hz), 6.91 (1H, brs), 7.14
−7.17 (1H, m), 7.48 (1H, dd, J =
2.4, 8.6 Hz), 7.56-7.60 (2H,
m), 7.85 (1H, d, J = 2.4 Hz), 7.9
6-7.99 (1H, m) FAB-MS (m / e): 565 [M + H] ⁺

Example 4079 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-t-Bu
O ₂ CCH ₂ O-3-I-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.88 (3H, d, J =
6.6 Hz), 1.07 (3H, d, J = 6.6H)
z), 1.46 (9H, s), 1.52-1.64 (1
H, m), 4.50 (1H, d, J = 10.5 Hz),
4.57 (2H, s), 6.62 (1H, d, J = 8.
7 Hz), 7.15-7.18 (1H, m), 7.40
(1H, dd, J = 2.4, 8.7 Hz), 7.55-
7.59 (2H, m), 7.84 (1H, d, J = 2.
4Hz), 7.95-7.98 (1H, m) FAB-MS (m / e): 580 [M + H] ⁺

Example 4087 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-HO 2 C
_{CH 2 O-3-I-} Ph) 1 HNMR (CDCl 3) δ: 0.88 (3H, d, J =
6.0 Hz), 1.07 (3H, d, J = 6.6H)
z), 1.50-1.58 (1H, m), 4.51 (1
H, d, J = 10.6 Hz), 4.73 (2H, s),
5.93 (1H, brs), 6.69 (1H, d, J =
8.5Hz), 7.16-7.19 (1H, m), 7.
42 (1H, dd, J = 2.2, 8.5 Hz), 7.5
4-7.61 (2H, m), 7.85 (1H, d, J =
2.2 Hz), 7.96-7.99 (1 H, m) FAB-MS (m / e): 524 [M + H] ⁺

Example 4092 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Cl-4
-N-PrNHCOCH ₂ O-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.88 (3H, d, J =
6.6 Hz), 0.95 (3H, t, J = 7.4H)
z), 1.08 (3H, d, J = 6.7 Hz), 1.5
0-1.65 (3H, m), 3.34 (2H, q, J =
6.9 Hz), 4.52 (1H, d, J = 10.3H)
z), 4.53 (2H, s), 6.78 (1H, br)
s), 6.88 (1H, d, J = 8.6 Hz), 7.1
4-7.17 (1H, m), 7.39 (1H, dd, J
= 2.4, 8.6 Hz), 7.50 (1H, d, J =
2.4 Hz), 7.56-7.62 (2H, m), 7.
96-7.99 (1H, m) FAB-MS (m / e): 473 [M + H] ⁺

Example 4113 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3,5-I 2
-4-HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.93 (3H, d, J =
6.6 Hz), 1.10 (3H, d, J = 6.6H)
z), 1.52-1.64 (1H, m), 4.51 (1
H, d, J = 10.6 Hz), 7.18-7.21 (1
H, m), 7.57-7.62 (2H, m), 7.75
(2H, s), 7.96-7.99 (1H, m) FAB-MS (m / e): 592 [M + H] ⁺

Example 4410 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: 4,5-pyridaz
inyl; R: 4-n-PrNHCOCH ₂ O-Ph) FAB-MS (m / e): 441 [M + H] ⁺

Example 4419 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 4-n-Pr
NHCOCH ₂ O-pyrazin-2-yl) FAB-MS (m / e): 441 [M + H] ⁺

Example 4424 (R ¹ : H; R ² : H;
^{R 3: i-Pr; R} 4: H; Z: Ph; R: 3-Cl-4
-HO-Ph) ¹ H NMR (CDCl ₃ ) δ: 0.88 (3H, d, J =
6.6 Hz), 1.08 (3H, d, J = 6.6H)
z), 1.52-1.64 (1H, m), 4.51 (1
H, d, J = 10.3 Hz), 5.72 (1H, br)
s), 6.98 (1H, d, J = 8.6 Hz), 7.1
6-7.19 (1H, m), 7.24 (1H, dd, J
= 2.2, 8.6 Hz), 7.47 (1H, d, J =
2.2Hz), 7.56-7.59 (2H, m), 7.
95-7.98 (1H, m) FAB-MS (m / e): 374 [M + H] ⁺

[0592]

According to the present invention, since the compound of the present invention has an activity of exhibiting a high blood GLP-1 concentration, it is useful for treating diabetes, preventing chronic complications of diabetes or treating obesity. Useful.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07D 491/147 C07D 491/147 498/04 103 498/04 103 498/14 498/14 513/04 325 513 / 04 325 513/14 513/14 // A61K 31/4188 A61K 31/4188 31/424 31/424 31/429 31/429 31/437 31/437 31/4439 31/4439 31/4985 31/4985 31 / 5025 31/5025 31/5377 31/5377 (72) Inventor Teruyuki Nishimura 3 Okubo Tsukuba, Ibaraki Pref.Manyu Pharmaceutical Co., Ltd.Tsukuba Research Laboratories (72) Inventor Junichi Nagaki 3 Okubo 3 Tsukuba Ibaraki Pref. Tsukuba Research Laboratories, a pharmaceutical company

Claims (6)

[Claims] 1. A compound of the general formula [I][Wherein, R represents an azide group, an amino group, a carbamoyl group,
Carbamoylamino group, carbamoyloxy group, carbo
Xyl, cyano, sulfamoyl, sulfo,
Toro, halogen, hydroxy, formyl, e
Lumylamino group, cyclic saturated C_Three-C₉Aliphatic group, cyclic
Unsaturated C_Three-C₉Aliphatic group, aralkyl group, N-aralkyl
Amino group, N, N-diaralkylamino group, aralkyl
Ruoxy group, aralkylcarbonyl group, N-aralkyl
Carbamoyl group, aryl group, N-arylamino group,
N, N-diarylamino group, aryloxy group, ant
Arylsulfonyl group, arylsulfonyloxy group, N-
Arylsulfonylamino group, N-arylsulfonyl
Amino C₁-C_TenAlkylamino group, N-arylsul
Honylamino C₁-C_TenAlkylcarbamoyl group, N-
Arylsulfonylamino C₁-C₆Alkoxycarboni
Group, arylsulfamoyl group, arylsulfamo
Yloxy group, N-arylsulfamoyl C₁-C_Ten
Alkylcarbamoyl group, arylsulfamoyl C₁
-C₆Alkoxycarbonyl group, N-arylcarbamo
Yl, aroyl, alloxy, N- (N-alloy
Ruamino) C₁-C_TenAlkylcarbamoyl group, NA
Roylamino C₁-C_TenAlkoxycarbonyl group, C_Two−
C₆Alkanoyl group, NC_Two-C₆Alkanoylamino
Group, N, N-di-C_Two-C₆Alkanoylamino group, N-
C₁-C₆Alkylamino group, N, N-di-C₁-C₆Al
Killamino group, N-C₁-C_TenAlkyl carbamoyl
Group, NC₁-C_TenAlkylthiocarbamoyl group, N,
N-di-C₁-C_TenAlkylcarbamoyl group, N, N-
Di-C₁-C_TenAlkylthiocarbamoyl group, NC_Two−
C₆Alkenylcarbamoyl group, N, N-di-C_Two-C₆
Alkenylcarbamoyl group, N-amino C₁-C_TenAl
Kill carbamoyl group, NC₁-C₆Alkoxy C₁-C
_TenAlkylcarbamoyl group, NC₁-C₆Alkoxyka
Rubonil C₁-C _TenAlkylcarbamoyl group, NC₁−
C₆Alkoxycarbonylamino C₁-C_{1 0}Alkyl cal
Bamoyl group, NC₁-C₆Alkoxycarbonylamino
C₁-C₆Alkoxycarbonyl group, C₁-C₆Alkyl
O group, NC₁-C₆Alkylsulfamoyl group, N, N
-Di-C₁-C₆Alkylsulfamoyl group, C₁-C₆A
Rukylsulfinyl group, C₁-C₆Alkylsulfonyl
Group, NC₁-C₆Alkylsulfonylamino group, C₁−
C₆Alkoxy group, C₁-C₆An alkoxycarbonyl group,
Amino C₁-C₆Alkoxycarbonyl group, N-C_Three-C₆
Cycloalkylamino group, N, N-di-C_Three-C₆Cyclo
Alkylamino group, C_Three-C₆Cycloalkyloxy group,
N-C_Three-C₆Cycloalkylcarbamoyl group and N, N
-Di-C_Three-C₆Consists of a cycloalkylcarbamoyl group
Substituents selected from the group, isoxazolyl groups,
Azolyl, imidazolyl, oxazolyl, oxa
Diazolyl group, thiazolyl group, thiadiazolyl group, thie
Nyl, triazinyl, triazolyl, pyridyl
Group, pyrazinyl group, pyrimidinyl group, pyridazinyl group,
Pyrazolyl, pyrrolyl, pyranyl, furyl,
Lazanyl group, imidazolidinyl group, imidazolinyl group,
Tetrahydrofuranyl group, pyrazolidinyl group, pyrazoly
Nil, piperazinyl, piperidinyl, pyrrolidini
Selected from the group consisting of chloro, pyrrolinyl and morpholino groups
A selected 5- or 6-membered heterocyclic group, an acridinyl group,
Soquinolyl group, isoindolyl group, indazolyl group,
Group, indolizinyl group, ethylenedioxyphene
Nil group, carbazolyl group, quinazolinyl group, quinoxali
Nil group, quinolizinyl group, quinolyl group, coumalonyl group,
Chromenyl group, phenanthridinyl group, phenanthroli
Nyl group, dibenzofuranyl group, dibenzothiophenyl
Group, cinnolinyl group, thionaphthenyl group, naphthyridini
Group, phenazinyl group, phenaxazinyl group, phenothi
Azinyl group, phthalazinyl group, pteridinyl group, purini
Group, benzimidazolyl group, benzoxazolyl group,
Benzothiazolyl group, benzotriazolyl group, benzofu
A group consisting of a ranyl group and a methylenedioxyphenyl group
Consisting of selected nitrogen, oxygen and sulfur atoms
1 to 5 hetero atoms per ring system selected from the group
Having 1 to 3 cyclic heteroaromatic groups and the heterocycle
N-C substituted by a group or the heteroaromatic group₁-C_TenAl
Kill carbamoyl group, NC₁-C_TenAlkylthiocal
From bamoyl, thiocarbonyl and carbonyl groups
And a substituent selected from the group consisting of
A linear saturated C₁-C₉Aliphatic group, straight chain
Saturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic
Group, branched, unsaturated C₁-C₉Aliphatic group, C₁-C₆Al
Coxy group, C₁-C₆Alkylthio group and N-C₁-C₆A
A substituent selected from the group consisting of
Having one or more substituents selected from the group
, Aryl group, acenaphthylenyl group, adamanti
Group, anthryl group, indenyl group, norbornyl group and
1 to 1 selected from the group consisting of
Tricyclic C₇-C_FifteenCarbon aromatic ring group or isoxazolyl
Group, isothiazolyl group, imidazolyl group, oxazolyl
Group, oxadiazolyl group, thiazolyl group, thiadiazoli
Group, thienyl group, triazinyl group, triazolyl group,
Pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazi
Nil, pyrazolyl, pyrrolyl, pyranyl, free
Group, furazanyl group, imidazolidinyl group, imidazolyl
Nil group, tetrahydrofuranyl group, pyrazolidinyl group,
Pyrazolinyl, piperazinyl, piperidinyl,
Consists of loridinyl, pyrrolinyl and morpholino groups
A 5- or 6-membered heterocyclic group selected from the group
Lysinyl group, isoquinolyl group, isoindolyl group,
Dazolyl group, indolyl group, indolizinyl group, ethylene
Dioxyphenyl group, carbazolyl group, quinazolinyl
Group, quinoxalinyl group, quinolizinyl group, quinolyl group,
Coumaronyl group, chromenyl group, phenanthridinyl group,
Phenanthrolinyl group, dibenzofuranyl group, dibenzo
Thiophenyl group, cinnolinyl group, thionaphthenyl group,
Naphthyridinyl group, phenazinyl group, phenaxazinyl
Group, phenothiazinyl group, phthalazinyl group, pteridini
Group, purinyl group, benzimidazolyl group, benzooxy
Sazolyl group, benzothiazolyl group, benzotriazolyl group
Group, benzofuranyl group and methylenedioxyphenyl group
Nitrogen, oxygen and sulfur selected from the group consisting of
Heteroatoms selected from the group consisting of atoms per ring system
A mono- to tricyclic heteroaromatic group having 1 to 5 R
¹And R^TwoAre the same or different and are a hydrogen atom, an azide group,
Amino group, carbamoyl group, carbamoylamino group,
Rubamoyloxy group, carboxyl group, cyano group, sulf
Famoyl group, sulfo group, nitro group, halogen atom,
Droxy, formyl, formylamino, cyclic
Sum C_Three-C₉Aliphatic group, cyclic unsaturated C_Three-C₉Aliphatic groups,
Aralkyl group, N-aralkylamino group, aralkyl group
Xy group, aralkylcarbonyl group, aryl group, NA
Reel amino group, aryloxy group, aryl sulfoni
Group, N-arylsulfonylamino group, N-aryl
Sulfonylamino C₁-C_TenAlkylamino group, NA
Reel sulfonylamino C₁-C_TenAlkyl carbamoy
Group, N-arylsulfonylamino C₁-C₆Alkoki
Cicarbonyl group, C_Two-C₆Alkanoyl group, NC_Two−
C₆Alkanoylamino group, aroyl group, N-aroyl
Amino group, N-aroyl C₁-C_TenAlkylamino group,
N-aroyl C₁-C_TenAlkylcarbamoyl group, N-
C₁-C₆Alkylamino group, N, N-di-C₁-C₆Al
Killamino group, N-C₁-C_TenAlkyl carbamoyl
Group, N, N-di-C₁-C_TenAlkylcarbamoyl group,
N-C₁-C₆Alkylsulfamoyl group, C₁-C₆Al
Killsulfinyl group, C₁-C₆Alkylsulfonyl group,
N-C₁-C₆Alkylsulfonylamino group, C₁-C₆A
Alkylthio group, C₁-C₆Alkoxy group, C₁-C₆Arco
Xycarbonyl group, N-C_Three-C₆Cycloalkylamino
Group, C_Three-C₆Cycloalkyloxy group and N-C_Three-C₆
Selected from the group consisting of cycloalkylcarbamoyl groups
Or a linear group which may be substituted with the substituent
Saturated C ₁-C₉Aliphatic group, linear unsaturated C₁-C₉Aliphatic
Group, branched chain saturated C₁-C₉Aliphatic groups, branched unsaturated
C₁-C₉Aliphatic group, N-C₁-C₆Alkylamino group, C
₁-C₆Alkylthio group or C₁-C₆An alkoxy group,
R^ThreeAnd R^FourAre the same or different and represent a hydrogen atom, an azide
Group, amidino group, amino group, carbamoyl group, carbamo
Ylamino group, carbamoyloxy group, carboxyl
Group, guanidino group, cyano group, sulfamoyl group, sulfo group
E group, nitro group, halogen atom, hydroxy group, holmi
Group, formylamino group, cyclic saturated C_Three-C₉Aliphatic
Group, cyclic unsaturated C_Three-C₉Aliphatic group, C_Two-C₆Alkano
Il group, N-C_Two-C₆Alkanoylamino group, NC₁
-C₆Alkylamino group, N, N-di-C₁-C₆Archi
Ruamino group, NC₁-C_TenAlkylcarbamoyl group,
N, N-di-C₁-C_TenAlkylcarbamoyl group, C₁
-C₆Alkylthio group, N-C₁-C₆Alkyl sulfa
Moyl group, C₁-C₆Alkylsulfinyl group, C₁-C₆
Alkylsulfonyl group, NC₁-C₆Alkylsulfoni
Ruamino group, C₁-C₆Alkoxy group, C₁-C₆Alkoki
Cicarbonyl group, N-C_Three-C₆Cycloalkylamino
Group, C_Three-C₆Cycloalkyloxy group and N-C_Three-C₆
Selected from the group consisting of cycloalkylcarbamoyl groups
Substituents, straight-chain saturated
Sum C₁-C₉Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups,
Branched saturated C₁-C₉Aliphatic groups and branched unsaturated C
₁-C₉A substituent selected from the group consisting of aliphatic groups,
Group, amino group, carbamoyl group, carbamoylamino
Group, carbamoyloxy group, carboxyl group, cyano
Group, sulfamoyl group, sulfo group, nitro group, halogen
Atom, hydroxy group, formyl group, formylamino group,
Cyclic saturated C_Three-C₉Aliphatic group, cyclic unsaturated C_Three-C₉Fat
Aliphatic group, aralkyl group, N-aralkylamino group, N,
N-diaaralkylamino group, aralkyloxy group, ara
Alkylcarbonyl group, N-aralkylcarbamoyl group,
Aryl group, N-arylamino group, N, N-diary
Amino group, aryloxy group, arylsulfonyl
Group, arylsulfonyloxy group, N-arylsulfo
Nylamino group, N-arylsulfonylamino C₁-C
_TenAlkylamino group, N-arylsulfonylamino C
₁-C_TenAlkylcarbamoyl group, N-arylsulfo
Nilamino C₁-C₆Alkoxycarbonyl group, aryl
A sulfamoyl group, an arylsulfamoyloxy group,
N-arylsulfamoyl C₁-C_TenAlkyl carba
Moyl group, arylsulfamoyl C₁-C₆Alkoxy
Carbonyl group, N-arylcarbamoyl group, aroyl
Group, alloxy group, N- (N-aroylamino) C₁-C
_TenAlkylcarbamoyl group, N-aroylamino C₁−
C_TenAlkoxycarbonyl group, C_Two-C₆Alkanoyl
Group, NC_Two-C₆Alkanoylamino group, N, N-di
-C_Two-C₆Alkanoylamino group, NC₁-C₆Archi
Ruamino group, N, N-di-C₁-C₆Alkylamino group,
N-C₁-C_TenAlkylcarbamoyl group, NC₁-C_Ten
Alkylthiocarbamoyl group, N, N-di-C₁-C_Ten
Alkylcarbamoyl group, N, N-di-C₁-C_TenAl
Kirthiocarbamoyl group, NC_Two-C₆Alkenylcal
Bamoyl group, N, N-di-C_Two-C₆Alkenyl carbamo
Yl group, N-amino C₁-C_TenAlkyl carbamoyl
Group, NC₁-C₆Alkoxy C₁-C_TenAlkyl carba
Moyl group, NC₁-C₆Alkoxycarbonyl C₁-C
_TenAlkylcarbamoyl group, NC₁-C₆Alkoxyka
Rubonylamino C₁-C_TenAlkylcarbamoyl group, N
-C₁-C₆Alkoxycarbonylamino C₁-C₆Arco
Xycarbonyl group, C₁-C₆Alkylthio group, N-C₁
-C₆Alkylsulfamoyl group, N, N-di-C₁-C
₆Alkylsulfamoyl group, C₁-C₆Alkylsulf
Inyl group, C₁-C₆Alkylsulfonyl group, NC₁−
C₆Alkylsulfonylamino group, C₁-C₆Alkoxy
Group, C₁-C₆Alkoxycarbonyl group, amino C₁-C
₆Alkoxycarbonyl group, N-C_Three-C₆Cycloalkyl
Ruamino group, N, N-di-C_Three-C₆Cycloalkylamide
No group, C_Three-C₆Cycloalkyloxy group, N-C_Three-C
₆Cycloalkylcarbamoyl group and N, N-di-C_Three−
C₆Select from the group consisting of cycloalkylcarbamoyl groups
Substituent, isoxazolyl group, isothiazolyl
Group, imidazolyl group, oxazolyl group, oxadiazoli
Group, thiazolyl group, thiadiazolyl group, thienyl group,
Triazinyl group, triazolyl group, pyridyl group, pyrazi
Nil group, pyrimidinyl group, pyridazinyl group, pyrazolyl
Group, pyrrolyl group, pyranyl group, furyl group, furazanyl
Group, imidazolidinyl group, imidazolinyl group, tetrahi
Drofuranyl group, pyrazolidinyl group, pyrazolinyl group,
Piperazinyl, piperidinyl, pyrrolidinyl,
Selected from the group consisting of a lorinyl group and a morpholino group
5- or 6-membered heterocyclic group, acridinyl group, isoquinolyl
, Isoindolyl, indazolyl, indolyl
Group, indolizinyl group, ethylenedioxyphenyl group,
Carbazolyl group, quinazolinyl group, quinoxalinyl group,
Quinolizinyl, quinolyl, coumalonyl, chromeni
Phenanthridinyl group, phenanthrolinyl group,
Dibenzofuranyl group, dibenzothiophenyl group, Shinno
Linyl, thionaphthenyl, naphthyridinyl,
Nadinyl group, phenaxazinyl group, phenothiazinyl
Group, phthalazinyl group, pteridinyl group, purinyl group,
Benzoimidazolyl group, benzoxazolyl group, benzothi
Azolyl group, benzotriazolyl group, benzofuranyl group
And methylenedioxyphenyl groups
Selected from the group consisting of nitrogen, oxygen and sulfur atoms
1 to 5 heteroatoms per ring system
To a tricyclic heteroaromatic ring group and the heterocyclic group or the
N-C substituted with a heteroaromatic group₁-C_TenAlkyl cal
Bamoyl group, NC₁-C_TenAlkylthiocarbamoyl
Group consisting of a carbonyl group, a thiocarbonyl group and a carbonyl group
Substituents selected from the above, and even if
Good, straight-chain saturated C₁-C₉Aliphatic group, linear unsaturated C₁
-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic groups, branched
Chain unsaturated C₁-C₉Aliphatic group, C₁-C₆Alkoxy
Group, C₁-C₆Alkylthio group and N-C₁-C₆Alkyl
A group consisting of substituents selected from the group consisting of amino groups
May have one or more substituents selected
, Aryl group, acenaphthylenyl group, adamantyl
Group, anthryl group, indenyl group, norbornyl group and
1 to 3 selected from the group consisting of phenanthryl groups
Cyclic C₇-C_FifteenCarbon aromatic ring group or isoxazolyl
Group, isothiazolyl group, imidazolyl group, oxazolyl
Group, oxadiazolyl group, thiazolyl group, thiadiazoli
Group, thienyl group, triazinyl group, triazolyl group,
Pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazi
Nil, pyrazolyl, pyrrolyl, pyranyl, free
Group, furazanyl group, imidazolidinyl group, imidazolyl
Nil group, tetrahydrofuranyl group, pyrazolidinyl group,
Pyrazolinyl, piperazinyl, piperidinyl,
Consists of loridinyl, pyrrolinyl and morpholino groups
A 5- or 6-membered heterocyclic group selected from the group
Lysinyl group, isoquinolyl group, isoindolyl group,
Dazolyl group, indolyl group, indolizinyl group, ethylene
Dioxyphenyl group, carbazolyl group, quinazolinyl
Group, quinoxalinyl group, quinolizinyl group, quinolyl group,
Coumaronyl group, chromenyl group, phenanthridinyl group,
Phenanthrolinyl group, dibenzofuranyl group, dibenzo
Thiophenyl group, cinnolinyl group, thionaphthenyl group,
Naphthyridinyl group, phenazinyl group, phenaxazinyl
Group, phenothiazinyl group, phthalazinyl group, pteridini
Group, purinyl group, benzimidazolyl group, benzooxy
Sazolyl group, benzothiazolyl group, benzotriazolyl group
Group, benzofuranyl group and methylenedioxyphenyl group
Nitrogen, oxygen and sulfur selected from the group consisting of
Heteroatoms selected from the group consisting of atoms per ring system
1 to 5 monocyclic to 3 cyclic heteroaromatic ring groups or
The aryl group, the carbon aromatic ring group, the heterocyclic group or
Straight-chain saturated C which may be substituted with the heteroaromatic group
₁-C₉Aliphatic group, linear unsaturated C ₁-C₉Aliphatic groups, branched
Chain saturation C₁-C₉Aliphatic or branched unsaturated C
₁-C₉Represents an aliphatic group, or R^ThreeAnd R^FourAre together
The linear saturated C₁-C ₉Aliphatic group, linear unsaturated C₁
-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group
Is a branched unsaturated C₁-C₉Aliphatic group or 5 or 6
Membered carbocyclic group or 5- or 6-membered unsaturated carbon
Forming a ring, X₁Is an oxygen atom, a sulfur atom or a group: N
R^Five(Where R^FiveIs a hydrogen atom, a halogen atom,
Hydroxy group, N-C₁-C₆Alkylsulfonylamino
Group, C₁-C₆Alkoxy group, C₁-C₆Alkoxycarbo
Nyl group, C_Two-C₆Alkanoyl group, carbamoyl group and
N-C ₁-C_TenFrom the group consisting of alkylcarbamoyl groups
A substituent selected or may be substituted with the substituent
Straight-chain saturated C₁-C₉Aliphatic group, linear unsaturated C₁−
C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group or
Branched unsaturated C₁-C₉An aliphatic group), X_TwoIs
An oxygen atom or a sulfur atom, Y is an oxygen atom, a sulfur atom or
Group: NR^FiveOr group: CR⁶R⁷(Where R
⁶Represents a hydrogen atom, a halogen atom, a hydroxy group, N-C₁
-C₆Alkylsulfonylamino group, C₁-C₆Alkoki
Si group, C₁-C₆Alkoxycarbonyl group, C_Two-C₆Al
Canoyl group, carbamoyl group and NC₁-C_TenArchi
A substituent selected from the group consisting of a rucarbamoyl group or
Linear saturated C which may be substituted with the substituent₁-C₉
Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups, branched chains
Sum C₁-C₉Aliphatic or branched unsaturated C₁-C₉
Aliphatic group, R⁷Is a hydrogen atom or C₁-C₆An alkyl group
And R^FiveHas the meaning described above), and Z is a fused ant
Group, acenaphthylenyl group, adamantyl group, anse
Ryl group, indanyl group, indenyl group, C₆-C₈Cyclo
Alkanyl group, C₆-C₈Cycloalkadienyl group, C₆
-C₈Cycloalkenyl group, norbornyl group, phenane
Selected from the group consisting of a thrill group and a fluorenyl group
Bicyclic or tricyclic saturated or unsaturated C₆-C_FifteenCondensation
Carbocyclic or isoquinolyl, isoindolyl, in
Dazolyl group, indolyl group, indolizinyl group, ethylene
Dioxyphenyl, quinazolinyl, quinoxalini
Group, quinolidinyl group, quinolyl group, coumalonyl group,
Romenyl, thionaphthenyl, naphthyridinyl,
Lysyl, pyrazinyl, pyrimidinyl, pyridazini
Group, pyranyl group, phthalazyl group, benzimidazolyl
Group, benzoxazolyl group, benzothiazolyl group, ben
Zotriazolyl, benzofuranyl and methylenedi
6-membered hetero selected from the group consisting of xylphenyl groups
Consists of ring groups or nitrogen, oxygen and sulfur atoms
1 to 5 hetero atoms per ring system selected from the group
Represents a bicyclic or tricyclic fused heteroaromatic group having
Or a pharmaceutically acceptable salt thereof. 2. A compound of the general formula [Ia][Wherein, R^aRepresents an amino group, a carbamoyl group, a carbamo
Ylamino group, carbamoyloxy group, carboxyl
Group, nitro group, halogen atom, hydroxy group, cyclic
Sum C_Three-C₉Aliphatic group, cyclic unsaturated C_Three-C₉Aliphatic groups,
Aralkyl group, N-aralkylamino group, aralkyl group
Xy group, aralkylcarbonyl group, N-aralkylcal
Bamoyl group, aryl group, N-arylamino group, ant
Oxy, arylsulfonyl, arylsulfo
Nyloxy group, N-arylsulfonylamino group, N-
Arylsulfonylamino C₁-C_TenAlkylamino
Group, N-arylsulfonylamino C₁-C_TenAlkyl
Carbamoyl group, N-arylsulfonylamino C₁−
C₆Alkoxycarbonyl group, arylsulfamoyl
Group, arylsulfamoyloxy group, N-aryls
Rufamoyl C₁-C_TenAlkyl carbamoyl group, ant
Rusulfamoyl C₁-C₆An alkoxycarbonyl group,
N-arylcarbamoyl group, aroyl group, alloxy
Group, N- (N-aroylamino) C₁-C_TenAlkylka
Rubamoyl group, N-aroylamino C₁-C_TenAlkoki
Cicarbonyl group, C_Two-C₆Alkanoyl group, NC_Two−
C₆Alkanoylamino group, NC₁-C₆Alkylam
No group, N, N-di-C₁-C₆Alkylamino group, N-C
₁-C_TenAlkylcarbamoyl group, NC₁-C_TenArchi
Luthiocarbamoyl group, N, N-di-C₁-C_TenArchi
Rucarbamoyl group, N, N-di-C₁-C_TenAlkyl
Ocarbamoyl group, NC_Two-C₆Alkenylcarbamoy
Group, N, N-di-C_Two-C₆Alkenylcarbamoyl
Group, N-amino C₁-C_TenAlkylcarbamoyl group, N
-C₁-C₆Alkoxy C₁-C_TenAlkyl carbamoyl
Group, NC₁-C₆Alkoxycarbonyl C₁-C_TenAl
Kill carbamoyl group, NC₁-C₆Alkoxycarboni
Lumino C₁-C_TenAlkylcarbamoyl group, NC₁−
C₆Alkoxycarbonylamino C₁-C₆Alkoxyka
Rubonyl group, C₁-C₆Alkylthio group, C₁-C₆Archi
Rusulfinyl group, C₁-C₆Alkylsulfonyl group, N
-C₁-C₆Alkylsulfonylamino group, C₁-C₆Al
Coxy group, C₁-C₆Alkoxycarbonyl group, amino
C₁-C₆Alkoxycarbonyl group, N-C_Three-C₆Cyclo
Alkylamino group, N, N-di-C_Three-C₆Cycloalkyl
Ruamino group, C_Three-C₆Cycloalkyloxy group, N-
C_Three-C₆Cycloalkylcarbamoyl group and N, N-di
-C_Three-C₆Group consisting of cycloalkylcarbamoyl groups
Selected substituent, isoxazolyl group, isothiazo
Ryl group, imidazolyl group, oxazolyl group, oxadia
Zolyl, thiazolyl, thiadiazolyl, thienyl
Group, triazolyl group, pyridyl group, pyrazinyl group, pyriyl group
Midinyl group, pyridazinyl group, pyrazolyl group, pyrrolyl
Group, pyranyl group, furyl group, imidazolidinyl group, imi
Dazolinyl group, tetrahydrofuranyl group, pyrazolidini
, Pyrazolinyl, piperazinyl, piperidinyl
Group, pyrrolidinyl group, pyrrolinyl group and morpholino group
A 5- or 6-membered heterocyclic group selected from the group consisting of
Quinolyl group, isoindolyl group, indazolyl group,
Drill group, ethylenedioxyphenyl group, carbazolyl
Group, quinazolinyl group, quinoxalinyl group, quinolizinyl
Group, quinolyl group, cumaronyl group, chromenyl group, phena
Suridinyl group, phenanthrolinyl group, dibenzofura
Nil group, dibenzothiophenyl group, cinnolinyl group,
Onaphthenyl group, naphthyridinyl group, phenazinyl group,
Phenaxazinyl, benzimidazolyl, benzoo
Xazolyl group, benzothiazolyl group, benzotriazolyl group
Group, benzofuranyl group and methylenedioxyphenyl
Nitrogen, oxygen and sulfur selected from the group consisting of
A heteroatom selected from the group consisting of yellow atoms
1 to 3 cyclic heteroaromatic ring groups having 1 to 5
And the heterocyclic group or the heteroaromatic ring group is substituted with N-
C₁-C_TenAlkylcarbamoyl group, NC₁-C_TenAl
Quilthiocarbamoyl, thiocarbonyl, and car
A substituent selected from the group consisting of a bonyl group;
Straight-chain saturated C which may be substituted with₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic group, branched unsaturated C₁-C₉Aliphatic groups,
C₁-C₆Alkoxy group and C₁-C₆From the alkylthio group
Selected from the group consisting of substituents selected from the group consisting of
Aryl which may have one or more substituents
Group, adamantyl group, anthryl group, indenyl group,
Select from the group consisting of rubornyl group and phenanthryl group
1- to 3-cyclic C₇-C_FifteenA carbon aromatic ring group or a
Soxazolyl group, isothiazolyl group, imidazolyl
Group, oxazolyl group, oxadiazolyl group, thiazolyl
Group, thiadiazolyl group, thienyl group, triazolyl group,
Pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazi
Nil, pyrazolyl, pyrrolyl, pyranyl, free
Group, imidazolidinyl group, imidazolinyl group, tetra
Hydrofuranyl group, pyrazolidinyl group, pyrazolinyl
Group, piperazinyl group, piperidinyl group, pyrrolidinyl
Selected from the group consisting of a group, a pyrrolinyl group and a morpholino group
5- or 6-membered heterocyclic group or isoquinolyl
Group, isoindolyl group, indazolyl group, indolyl group
Group, ethylenedioxyphenyl group, carbazolyl group,
Nazolinyl group, quinoxalinyl group, quinolizinyl group,
Noryl group, coumalonyl group, chromenyl group, phenanthry
Dinyl group, phenanthrolinyl group, dibenzofuranyl
Group, dibenzothiophenyl group, cinnolinyl group, thiona
Phenyl, naphthyridinyl, phenazinyl,
Naxazinyl group, benzimidazolyl group, benzoxa
Zolyl, benzothiazolyl, benzotriazolyl
Group, benzofuranyl group and methylenedioxyphenyl group
Nitrogen, oxygen and sulfur selected from the group consisting of
Heteroatoms selected from the group consisting of atoms per ring system
A mono- to tricyclic heteroaromatic group having 1 to 5 R
^1aAnd R^2aIs the same or different and is a hydrogen atom, amino
Group, carboxyl group, cyano group, sulfamoyl group,
Ruho, nitro, halogen, hydroxy, phor
Mill group, cyclic saturated C_Three-C₉Aliphatic group, cyclic unsaturated C
_Three-C₉Aliphatic group, aralkyl group, aryl group, N-ali
Amino group, aryloxy group, C_Two-C₆Arcanoy
Group, N-C_Two-C₆Alkanoylamino group, aroyl
Group, NC₁-C₆Alkylamino group, N, N-di-C₁
-C₆Alkylamino group, N-C₁-C_TenAlkyl carba
Moyl group, NC₁-C₆Alkylsulfamoyl group, C
₁-C₆Alkylsulfinyl group, C₁-C₆Alkylsul
Honyl group, N-C₁-C₆Alkylsulfonylamino group,
C₁-C₆Alkoxy group, C₁-C₆Alkoxycarbonyl
Group, NC_Three-C₆Cycloalkylamino group, C_Three-C₆Shi
Chloroalkyloxy group and N-C_Three-C₆Cycloalkyl
A substituent selected from the group consisting of a carbamoyl group or
Straight-chain saturated C which may be substituted with a substituent₁-C₉Fat
Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups, branched chain saturation
C₁-C₉Aliphatic group, branched unsaturated C₁-C₉Aliphatic group
Or C ₁-C₆Alkoxy group, R^3aAnd R^4aAre the same
Or differently, a hydrogen atom, an azide group, an amidino group,
Group, carbamoyl group, carbamoylamino group, carb
Moyloxy group, carboxyl group, guanidino group, shea
, Sulfamoyl, sulfo, nitro, halogen
Atom, hydroxy group, formyl group, formylamino
Group, cyclic saturated C_Three-C₉Aliphatic group, cyclic unsaturated C_Three−
C₉Aliphatic group, C_Two-C₆Alkanoyl group, NC₁-C₆
Alkylamino group, N-C₁-C_TenAlkyl carbamoy
Group, C₁-C₆Alkylthio group, N-C₁-C₆Alkyl
Sulfamoyl group, C₁-C₆Alkylsulfinyl group,
C₁-C₆Alkylsulfonyl group, NC₁-C₆Alkyl
Sulfonylamino group, C₁-C₆Alkoxy group, C₁-C₆
Alkoxycarbonyl group and N-C_Three-C₆Cycloalkyl
A substituent selected from the group consisting of
Linear saturated C which may be substituted with₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic groups and branched unsaturated C₁-C₉Aliphatic group
A substituent amino group selected from the group consisting of: carbamoy
Carbamoylamino group, carbamoyloxy group,
Carboxyl group, nitro group, halogen atom, hydroxy
Group, cyclic saturated C_Three-C₉Aliphatic group, cyclic unsaturated C _Three−
C₉Aliphatic group, aralkyl group, N-aralkylamino
Group, aralkyloxy group, aralkylcarbonyl group, N
-Aralkylcarbamoyl group, aryl group, N-aryl
Amino group, aryloxy group, arylsulfonyl
Group, arylsulfonyloxy group, N-arylsulfo
Nylamino group, N-arylsulfonylamino C₁-C
_TenAlkylamino group, N-arylsulfonylamino C
₁-C_TenAlkylcarbamoyl group, N-arylsulfo
Nilamino C₁-C₆Alkoxycarbonyl group, aryl
A sulfamoyl group, an arylsulfamoyloxy group,
N-arylsulfamoyl C₁-C_TenAlkyl carba
Moyl group, arylsulfamoyl C₁-C₆Alkoxy
Carbonyl group, N-arylcarbamoyl group, aroyl
Group, alloxy group, N- (N-aroylamino) C₁-C
_TenAlkylcarbamoyl group, N-aroylamino C₁−
C_TenAlkoxycarbonyl group, C_Two-C₆Alkanoyl
Group, NC_Two-C₆Alkanoylamino group, NC₁-C₆
Alkylamino group, N, N-di-C₁-C₆Alkylam
No group, NC₁-C_TenAlkylcarbamoyl group, NC₁
-C_TenAlkylthiocarbamoyl group, N, N-di-C₁
-C_TenAlkylcarbamoyl group, N, N-di-C₁-C
_TenAlkylthiocarbamoyl group, NC_Two-C₆Alkene
Rucarbamoyl group, N, N-di-C_Two-C₆Alkenylka
Rubamoyl group, N-amino C₁-C_TenAlkyl carbamo
Il group, N-C₁-C₆Alkoxy C₁-C_TenAlkylka
Rubamoyl group, NC₁-C₆Alkoxycarbonyl C₁
-C _TenAlkylcarbamoyl group, NC₁-C₆Alkoki
Cicarbonylamino C₁-C_{1 0}Alkyl carbamoyl
Group, NC₁-C₆Alkoxycarbonylamino C₁-C₆
Alkoxycarbonyl group, C₁-C₆Alkylthio group, C
₁-C₆Alkylsulfinyl group, C₁-C₆Alkylsul
Honyl group, N-C₁-C₆Alkylsulfonylamino group,
C₁-C₆Alkoxy group, C₁-C₆Alkoxycarbonyl
Group, amino C₁-C₆Alkoxycarbonyl group, N-C_Three
-C₆Cycloalkylamino group, N, N-di-C_Three-C₆
Cycloalkylamino group, C_Three-C₆Cycloalkyl
Xy group, N-C_Three-C₆Cycloalkylcarbamoyl group and
And N, N-di-C_Three-C₆Cycloalkylcarbamoyl group
Isoxazolyl, a substituent selected from the group consisting of
Group, isothiazolyl group, imidazolyl group, oxazolyl
Group, oxadiazolyl group, thiazolyl group, thiadiazoli
Group, thienyl group, triazolyl group, pyridyl group, pyra
Dinyl group, pyrimidinyl group, pyridazinyl group, pyrazoly
, Pyrrolyl, pyranyl, furyl, imidazolyl
Dinyl group, imidazolinyl group, tetrahydrofuranyl
Group, pyrazolidinyl group, pyrazolinyl group, piperazinyl
Group, piperidinyl group, pyrrolidinyl group, pyrrolidinyl group and
And a 5- or 6-membered member selected from the group consisting of
Heterocyclic group, isoquinolyl group, isoindolyl group,
Dazolyl group, indolyl group, ethylenedioxyphenyl
Group, carbazolyl group, quinazolinyl group, quinoxalinyl
Group, quinolidinyl group, quinolyl group, coumalonyl group,
Menyl group, phenanthridinyl group, phenanthrolinyl
Group, dibenzofuranyl group, dibenzothiophenyl group,
Nonolinyl group, thionaphthenyl group, naphthyridinyl group,
Phenazinyl group, phenaxazinyl group, benzimidazo
Ryl group, benzoxazolyl group, benzothiazolyl group,
Benzotriazolyl group, benzofuranyl group and methylene
Nitrogen source selected from the group consisting of dioxyphenyl groups
Selected from the group consisting of oxygen, oxygen and sulfur
1 to 3 rings having 1 to 5 ring atoms per ring system
Heteroaromatic ring group and the heterocyclic group or the heteroaromatic ring
N—C substituted with a group₁-C_TenAlkyl carbamoyl
Group, NC₁-C_TenAlkylthiocarbamoyl group, thio
Selected from the group consisting of carbonyl groups and carbonyl groups
Substituents which may be substituted with the substituents,
Chain saturation C₁-C₉Aliphatic group, linear unsaturated C₁-C₉fat
Group, branched saturated C₁-C₉Aliphatic groups, branched chain unsaturation
C ₁-C₉Aliphatic group, C₁-C₆Alkoxy group and C₁−
C₆A substituent selected from the group consisting of alkylthio groups
Having one or more substituents selected from the group consisting of
Aryl, adamantyl, anthryl
Group, indenyl group, norbornyl group and phenanthryl
Mono- to tricyclic C selected from the group consisting of ₇-C
_FifteenCarbon aromatic ring group or isoxazolyl group, isothiazolyl
Group, imidazolyl group, oxazolyl group, oxadiazo
Ryl, thiazolyl, thiadiazolyl, thienyl
Group, triazolyl group, pyridyl group, pyrazinyl group, pyriyl group
Midinyl group, pyridazinyl group, pyrazolyl group, pyrrolyl
Group, pyranyl group, furyl group, imidazolidinyl group, imi
Dazolinyl group, tetrahydrofuranyl group, pyrazolidini
, Pyrazolinyl, piperazinyl, piperidinyl
Group, pyrrolidinyl group, pyrrolinyl group and morpholino group
A 5- or 6-membered heterocyclic group selected from the group consisting of
Is isoquinolyl, isoindolyl, indazolyl
Group, indolyl group, ethylenedioxyphenyl group,
Bazolyl group, quinazolinyl group, quinoxalinyl group, quino
Lysinyl group, quinolyl group, coumalonyl group, chromenyl
Group, phenanthridinyl group, phenanthrolinyl group,
Benzofuranyl group, dibenzothiophenyl group, Shinnori
Nyl, thionaphthenyl, naphthyridinyl, phena
Dinyl group, phenaxazinyl group, benzimidazolyl
Group, benzoxazolyl group, benzothiazolyl group, ben
Zotriazolyl, benzofuranyl and methylenedi
Nitrogen atom or acid selected from the group consisting of xylphenyl groups
Heteroatoms selected from the group consisting of elemental atoms and sulfur atoms
From 1 to 3 rings having 1 to 5 rings per ring system
An aromatic ring group or the aryl group, the carbon aromatic ring group,
Or a heterocyclic group.
Straight-chain saturated C₁-C₉Aliphatic group, linear unsaturated C₁−
C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group or
Branched unsaturated C₁-C ₉Represents an aliphatic group, or R^3a
And R^4aTogether form a linear saturated C₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic or branched unsaturated C₁-C₉fat
Group or 5- or 6-membered saturated carbocyclic group or 5 or less
Or a 6-membered unsaturated carbocyclic ring, X_1aIs an oxygen source
Child, sulfur atom or group: NR^5a(Where R^5aIs
Hydrogen atom, halogen atom, hydroxy group, N-C₁-C₆
Alkylsulfonylamino group, C₁-C₆An alkoxy group,
C₁-C₆Alkoxycarbonyl group, C_Two-C₆Arcanoy
Carbamoyl group and N-C ₁-C_TenAlkyl cal
A substituent selected from the group consisting of a bamoyl group or the substituent
Straight-chain saturated C which may be substituted with₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic or branched unsaturated C₁-C₉fat
Represents a group), X_2aIs an oxygen or sulfur atom, Y
_aIs an oxygen atom, a sulfur atom or a group: NR^5aOr group:
CR^6aR^7a(Where R^6aIs a hydrogen atom, halogen
Atom, hydroxy group, N-C₁-C₆Alkylsulfoni
Ruamino group, C₁-C₆Alkoxy group, C₁-C₆Alkoki
Cicarbonyl group, C_Two-C₆Alkanoyl group, carbamoy
And N-C₁-C_TenAlkyl carbamoyl group
Or a substituent selected from the group consisting of
A linear saturated C₁-C₉Aliphatic group, linear unsaturated
C₁-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group
Or branched, unsaturated C₁-C₉Aliphatic group, R^7aIs hydrogen
Atom or C₁-C₆Represents an alkyl group;^5aMeans the above
Taste), Z_aIs a fused aryl group, adamantyl
Group, anthryl group, indanyl group, indenyl group, C₆
-C₈Cycloalkanyl group, C₆-C₈Cycloalkadie
Nyl group, C₆-C₈Cycloalkenyl group, norbornyl group
2 selected from the group consisting of and phenanthryl groups
Tricyclic saturated or unsaturated C₆-C_FifteenFused carbocycle
Group or ethylenedioxyphenyl group, pyridyl group, pyra
Dinyl, pyrimidinyl, pyridazinyl, benzoy
Midazolyl group, benzoxazolyl group, benzothiazoly
Group, benzotriazolyl group, benzofuranyl group and
6 selected from the group consisting of tylenedioxyphenyl groups
Membered heterocyclic group or nitrogen atom, oxygen atom and sulfur atom
One heteroatom selected from the group consisting of
And 5 to 5 bicyclic or 3-cyclic fused heteroaromatic groups
Or a pharmaceutical thereof.
Acceptable salt. 3. A compound of the general formula [Ib][Wherein, R^bRepresents an amino group, a carbamoyl group,
Sil group, nitro group, halogen atom, hydroxy group, ara
Alkylcarbonyl group, N-aralkylcarbamoyl group,
Aryl group, aroyl group, C_Two-C₆Alkanoyl group, N
-C₁-C₆Alkylamino group, N-C₁-C_TenAlkyl
Carbamoyl group, NC₁-C_TenAlkylthiocarbamo
Yl group, N, N-di-C₁-C_TenAlkyl carbamoyl
Group, N, N-di-C₁-C_TenAlkylthiocarbamoyl
Group, NC_Two-C₆Alkenylcarbamoyl group, N, N-
Di-C_Two-C₆Alkenylcarbamoyl group, N-amino C
₁-C_{1 0}Alkylcarbamoyl group, NC₁-C₆Arco
Kishi C₁-C_TenAlkylcarbamoyl group, NC₁-C₆
Alkoxycarbonyl C₁-C_TenAlkyl carbamoyl
Group, C₁-C₆Alkoxy group, amino C₁-C₆Alkoki
Cicarbonyl group, N-C_Three-C₆Cycloalkylamino
Group, N, N-di-C_Three-C₆Cycloalkylamino group, C
_Three-C₆Cycloalkyloxy group, N-C_Three-C₆Cycloa
Alkylcarbamoyl group and N, N-di-C_Three-C₆Cyclo
Substitution selected from the group consisting of alkylcarbamoyl groups
Group, thienyl group, pyridyl group, pyrazinyl group, pyrimidi
Nyl, furyl, tetrahydrofuranyl and morpho
5- or 6-membered heterocycle selected from the group consisting of lino groups
Group, ethylenedioxyphenyl group, dibenzofuranyl
Group, dibenzothiophenyl group and methylenedioxyphene
A nitrogen atom, an oxygen atom and a nitrogen atom selected from the group consisting of
A heteroatom selected from the group consisting of
1 to 5 mono- to 3-cyclic heteroaromatic rings per 1 to 5
Group and the heterocyclic group or the heteroaromatic ring group is substituted,
N-C₁-C_TenAlkylcarbamoyl group, NC₁-C _Ten
Alkylthiocarbamoyl group, thiocarbonyl group and
A substituent selected from the group consisting of a carbonyl group;
Straight-chain saturated C which may be substituted with a substituent ₁-C₉Fat
Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups, branched chain saturation
C₁-C₉Aliphatic group, branched unsaturated C₁-C₉Aliphatic group
And C₁-C₆A position selected from the group consisting of alkoxy groups
One or more substituents selected from the group consisting of
Aryl group, anthryl group and
Mono- to tricyclic selected from the group consisting of nanthryl groups
C₇-C_FifteenCarbon aromatic ring group or thienyl group, pyridyl
Group, pyrazinyl group, pyrimidinyl group, furyl group, tetra
Select from the group consisting of hydrofuranyl and morpholino groups
5- or 6-membered heterocyclic group or ethylene dioxy
Cyphenyl group, dibenzofuranyl group, dibenzothiophene
From the group consisting of a nyl group and a methylenedioxyphenyl group
The group consisting of selected nitrogen, oxygen and sulfur atoms
1 to 5 hetero atoms per ring system
A mono- to tricyclic heteroaromatic group, R^1bAnd R^2bIs
Same or different, hydrogen atom, amino group, nitro group,
Logen atom, hydroxy group, aryl group, N-aryl
Amino group, N-C₁-C₆Alkylamino group, N, N-di
-C₁-C₆Alkylamino group, N-C₁-C_TenAlkyl
Carbamoyl group, C₁-C₆Alkoxy group, C₁-C₆Al
Coxycarbonyl group and N-C_Three-C₆Cycloalkylua
A substituent selected from the group consisting of a mino group or
Optionally substituted straight-chain saturated C₁-C₉Aliphatic groups,
Linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉
Aliphatic group, branched unsaturated C₁-C₉Aliphatic group or
C₁-C₆Alkoxy group, R^3bAnd R^4bAre the same or different
Are hydrogen, azide, amidino, amino,
Rubamoyl group, carboxyl group, guanidino group, cyano
Group, sulfamoyl group, sulfo group, nitro group, halogen
Atom, hydroxy group, formyl group, cyclic saturated C_Three-C₉
Aliphatic group, cyclic unsaturated C_Three-C₉Aliphatic group, N-C₁−
C₆Alkylamino group, N-C₁-C_TenAlkyl carbamo
Il group, C₁-C₆Alkylthio group, C₁-C₆Alkoxy
Group and C₁-C₆From the group consisting of alkoxycarbonyl groups
Selected substituents, which may be substituted with the substituents,
Linear saturated C₁-C₉Aliphatic group, linear unsaturated C₁-C₉Fat
Aliphatic group, branched saturated C₁-C₉Aliphatic groups and branched chains
Saturated C₁-C₉Substitution selected from the group consisting of aliphatic groups
Group, amino group, carbamoyl group, carboxyl group, nitro
B group, halogen atom, hydroxy group, aralkyl carb
A nyl group, an N-aralkylcarbamoyl group, an aryl group,
Aroyl group, C_Two-C₆Alkanoyl group, NC₁-C₆A
Alkylamino group, N-C₁-C_TenAlkyl carbamoyl
Group, NC₁-C_TenAlkylthiocarbamoyl group, N,
N-di-C₁-C_TenAlkylcarbamoyl group, N, N-
Di-C₁-C_TenAlkylthiocarbamoyl group, NC_Two−
C₆Alkenylcarbamoyl group, N, N-di-C_Two-C₆
Alkenylcarbamoyl group, N-amino C₁-C_TenAl
Kill carbamoyl group, NC₁-C₆Alkoxy C₁-C
_TenAlkylcarbamoyl group, NC₁-C₆Alkoxyka
Rubonil C₁-C _TenAlkylcarbamoyl group, C₁-C₆
Alkoxy group, amino C₁-C₆Alkoxycarbonyl
Group, NC_Three-C₆Cycloalkylamino group, N, N-di
-C_Three-C₆Cycloalkylamino group, C_Three-C₆Cyclo
Alkyloxy group, N-C_Three-C₆Cycloalkyl carb
Moyl group and N, N-di-C_Three-C₆Cycloalkylcal
Thienyl, a substituent selected from the group consisting of a bamoyl group
Group, pyridyl group, pyrazinyl group, pyrimidinyl group, free
Group, tetrahydrofuranyl group and morpholino group.
A 5- or 6-membered heterocyclic group selected from the group consisting of
Dioxyphenyl group, dibenzofuranyl group, dibenzothi
Consists of an ophenyl group and a methylenedioxyphenyl group
From nitrogen, oxygen and sulfur selected from the group
A heteroatom selected from the group consisting of 1 to
5- to 5-cyclic heteroaromatic ring groups and
N-C substituted with a heterocyclic group or the heteroaromatic group₁-C_Ten
Alkylcarbamoyl group, NC₁-C_TenAlkylthio
Carbamoyl group, thiocarbonyl group and carbonyl group
And a substituent selected from the group consisting of
Straight-chain saturated C₁-C₉Aliphatic group, straight chain
Of unsaturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉fat
Group, branched chain unsaturated C₁-C₉Aliphatic group and C₁-C₆
Consisting of a substituent selected from the group consisting of alkoxy groups
Even if it has one or more substituents selected from the group
Good aryl, anthryl and phenanthryl groups
1- to 3-cyclic C selected from the group consisting of₇-C_Fifteen
Carbon aromatic ring group or thienyl group, pyridyl group, pyrazinyl
Group, pyrimidinyl group, furyl group, tetrahydrofuranyl
Or 6 selected from the group consisting of a group and a morpholino group
Membered heterocyclic group or ethylenedioxyphenyl group,
Dibenzofuranyl, dibenzothiophenyl and methyl
Nitrogen selected from the group consisting of rangeoxyphenyl groups
Atoms selected from the group consisting of atoms, oxygen atoms and sulfur atoms
1 to 3 having 1 to 5 telo atoms per ring system
Cyclic heteroaromatic ring group or the aryl group, the carbon aromatic ring
Substituted with the group, the heterocyclic group or the heteroaromatic group
A linear saturated C₁-C₉Aliphatic group, straight-chain unsaturated
Sum C₁-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group
Or branched unsaturated C₁-C₉Indicates an aliphatic group, or
Is R^3bAnd R^4bTogether form a linear unsaturated C₁−
C₉Forming an aliphatic group or a 5- or 6-membered saturated carbocyclic group
Then X_1bIs an oxygen atom or group: NR^5b(put it here,
R^5bIs a hydrogen atom, a hydroxy group, C₁-C₆Alkoxy
Group, C₁-C₆Alkoxycarbonyl group and N-C₁-C
_TenA position selected from the group consisting of alkylcarbamoyl groups
Linear group, which may be substituted or may be substituted with the substituent.
C₁-C₉Aliphatic group, linear unsaturated C₁-C₉Aliphatic group, minute
Branched saturated C₁-C₉Aliphatic or branched unsaturated
C₁-C₉An aliphatic group), X_2bIs an oxygen atom or sulfur
Atom, Y_bRepresents an oxygen atom, a sulfur atom or a group: CR^6bR^7b
(Where R^6bIs a hydrogen atom, a hydroxy group, C
₁-C₆Alkoxy group, C₁-C₆Alkoxycarbonyl group
And N-C₁-C_TenGroup consisting of alkylcarbamoyl groups
Or a substituent selected from the group consisting of
Good, straight-chain saturated C₁-C₉Aliphatic group, linear unsaturated C₁
-C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group
Is a branched unsaturated C₁-C ₉Aliphatic group, R^7bIs a hydrogen source
Child or C₁-C₆An alkyl group), Z_bIs the condensation ant
Group, anthryl group, C₆-C₈Cycloalkanyl group,
C₆-C₈Cycloalkadienyl group and C₆-C₈Cycloa
Bicyclic to tricyclic selected from the group consisting of alkenyl groups
Saturated or unsaturated C₆-C_FifteenFused carbocyclic group or ethyl
Rangeoxyphenyl group, pyridyl group, pyrazinyl group,
Pyrimidinyl group, pyridazinyl group and methylenedioxy
6-membered heterocyclic group selected from the group consisting of phenyl groups
Or a group consisting of nitrogen, oxygen and sulfur
1 to 5 heteroatoms per ring system
A bicyclic or tricyclic fused heteroaromatic group.
3. The compound according to claim 1 or 2 or a pharmaceutically acceptable compound thereof.
Salt to be carried. 4. A compound of the general formula [Ic][Wherein, R^cIs an aryl which may have a substituent
Group, 1 to 3 cyclic C₇-C_FifteenCarbon aromatic ring group (however,
Excludes aryl groups. ) Or 5- or 6-membered heterocyclic group
Or a group consisting of nitrogen, oxygen and sulfur
1 to 5 heteroatoms per ring system
A 1 to 3 ring heteroaromatic group (provided that the group is a 5- or 6-membered heteroaromatic group)
Excludes heterocyclic groups. ), R^1cAnd R^2cAre the same or different
Represents a hydrogen atom, an azide group, an amino group, carbamoyl
Group, carbamoylamino group, carbamoyloxy group,
Ruboxyl group, cyano group, sulfamoyl group, sulfo
Group, nitro group, halogen atom, hydroxy group, formyl
Group, formylamino group, cyclic saturated or unsaturated C
_Three-C₉Aliphatic group, aralkyl group, N-aralkylamino
Group, aralkyloxy group, aralkylcarbonyl group,
Reel group, N-arylamino group, aryloxy group,
Arylsulfonyl group, N-arylsulfonylamino
Group, N-arylsulfonylamino C₁-C₆Alkyria
Mino group, N-arylsulfonylamino C₁-C_TenAl
Kilcarbamoyl group, arylsulfonylamino C₁−
C₆Alkoxycarbonyl group, C_Two-C₆Alkanoyl
Group, NC_Two-C₆Alkanoylamino group, aroyl group,
N-aroylamino group, N-aroyl C₁-C₆Alkyl
Amino group, N-aroyl C₁-C_TenAlkyl carbamoy
Group, N-C ₁-C₆Alkylamino group, N, N-di-C
₁-C₆Alkylamino group, N-C₁-C_TenAlkyl cal
Bamoyl group, N, N-di-C₁-C_TenAlkyl carbamo
Il group, N-C₁-C₆Alkylsulfamoyl group, C₁
-C₆Alkylsulfinyl group, C₁-C₆Alkylsul
Honyl group, C₁-C₆Alkylthio group, C₁-C₆Alkoki
Si group, C₁-C₆Alkoxycarbonyl group, N-C_Three-C₆
Cycloalkylamino group, C_Three-C₆Cycloalkyloxy
Si group and NC_Three-C₆Is it a cycloalkylcarbamoyl group
Or a substituent selected from the group consisting of
Straight or branched chain saturated or unsaturated
Sum C₁-C₉Aliphatic group, N-C₁-C₆Alkylamino
Group, C₁-C₆Alkylthio group or C₁-C₆Alkoki
Si group, R^3cAnd R^4cAre the same or different and are a hydrogen atom,
Azide, amidino, amino, carbamoyl,
Rubamoylamino group, carbamoyloxy group, carboxy
A sil group, a guanidino group, a cyano group, a sulfamoyl group,
Sulfo group, nitro group, halogen atom, hydroxy group,
Lumyl group, formylamino group, cyclic saturated or unsaturated
Sum C_Three-C₉Aliphatic group, C_Two-C₆Alkanoyl group, N-
C_Two-C₆Alkanoylamino group, NC₁-C₆Alkyl
Amino group, N, N-di-C₁-C₆Alkylamino group, N
-C₁-C_TenAlkylcarbamoyl group, N, N-di-C
₁-C_TenAlkylcarbamoyl group, C₁-C₆Alkyl
O group, NC₁-C₆Alkylsulfamoyl group, C₁−
C₆Alkylsulfinyl group, C₁-C₆Alkylsulfo
Nyl group, C₁-C₆Alkoxy group, C₁-C₆Alkoxyka
Rubonyl group, N-C_Three-C₆Cycloalkylamino group, C
_Three-C₆Cycloalkyloxy group and N-C_Three-C₆Cyclo
Substitution selected from the group consisting of alkylcarbamoyl groups
Group, which may be substituted with the substituent, linear or branched
Branched or unsaturated C₁-C₉Aliphatic group, substituent
An aryl group, mono- to tricyclic C
₇-C_FifteenA carbon aromatic ring group (excluding an aryl group),
5- or 6-membered heterocyclic group or nitrogen atom, oxygen atom
1 heteroatom selected from the group consisting of
1 to 3 heterocyclic heteroaromatics having 1 to 5 ring systems
Aromatic ring group (excluding 5- or 6-membered heterocyclic group) or
The aryl group, the carbon aromatic ring group, the heterocyclic group or
Linear or linear, which may be substituted with the heteroaromatic group;
Branched or unsaturated C₁-C₉Indicates an aliphatic group
Or R^3cAnd R^4cAre together, linear or
Branched unsaturated C₁-C₉Aliphatic group or 5 or 6 members
Forms a saturated or unsaturated carbocyclic ring of_1cAnd X_2c
Are the same or different and are an oxygen atom or a sulfur atom, Y
_cIs an oxygen atom, a sulfur atom or a group: CHR^5cOr
Group: NR^5c(Where R^5cIs hydrogen atom, halogen
Atom, hydroxy group, C₁-C₆Alkoxy group, C_Two-C₆
Alkanoyl group, carbamoyl group and N-C₁-C_TenA
Substituents selected from the group consisting of alkylcarbamoyl groups
Or linear or branched, which may be substituted with the substituent.
Branched or unsaturated C₁-C₉Indicates an aliphatic group
S), Z_cIs a fused aryl group, bicyclic or tricyclic saturated
Or unsaturated C₆-C_FifteenCondensed carbocyclic group (however,
Excludes aryl groups. ) Or 6-membered heterocyclic group or nitrogen
Selected from the group consisting of elementary atoms, oxygen atoms and sulfur atoms
2 to 2 having 1 to 5 hetero atoms per ring system
Tricyclic fused heteroaromatic group (provided that a 6-membered heterocyclic group is
except. The compound according to claim 1, which is represented by:
Is a pharmaceutically acceptable salt thereof. 5. A compound of the general formula [II][Wherein, R⁰Represents an azide group, an optionally protected amino group.
Group, carbamoyl group, carbamoylamino group, carb
Moyloxy group, carboxyl which may be protected
Group, cyano group, sulfamoyl group, sulfo group, nitro
Group, halogen atom, hydroxy which may be protected
Group, formyl group, formylamino group, cyclic saturated C_Three−
C₉Aliphatic group, cyclic unsaturated C_Three-C₉Aliphatic group, aral
Kill group, N-aralkylamino group, N, N-diaralkyl
Ruamino group, aralkyloxy group, aralkyl carbonyl
Group, N-aralkylcarbamoyl group, aryl group, N
-Arylamino group, N, N-diarylamino group,
Reeloxy, arylsulfonyl, arylsul
Honyloxy group, N-arylsulfonylamino group, N
-Arylsulfonylamino C₁-C_TenAlkylamino
Group, N-arylsulfonylamino C₁-C_TenAlkyl
Carbamoyl group, N-arylsulfonylamino C₁−
C ₆Alkoxycarbonyl group, arylsulfamoyl
Group, arylsulfamoyloxy group, N-aryls
Rufamoyl C₁-C_TenAlkyl carbamoyl group, ant
Rusulfamoyl C₁-C₆An alkoxycarbonyl group,
N-arylcarbamoyl group, aroyl group, alloxy
Group, N- (N-aroylamino) C₁-C_TenAlkylka
Rubamoyl group, N-aroylamino C₁-C_TenAlkoki
Cicarbonyl group, C_Two-C₆Alkanoyl group, NC_Two−
C₆Alkanoylamino group, N, N-di-C_Two-C₆Al
Canoylamino group, NC₁-C₆Alkylamino group,
N, N-di-C₁-C₆Alkylamino group, N-C₁-C
_TenAlkylcarbamoyl group, NC₁-C_TenAlkyl
Ocarbamoyl group, N, N-di-C₁-C_TenAlkylka
Rubamoyl group, N, N-di-C₁-C_TenAlkylthioca
Rubamoyl group, NC_Two-C₆Alkenylcarbamoyl
Group, N, N-di-C_Two-C₆Alkenylcarbamoyl group,
Optionally protected N-amino C₁-C_TenAlkylka
Rubamoyl group, NC₁-C₆Alkoxy C₁-C_TenAl
Kill carbamoyl group, NC₁-C₆Alkoxycarboni
Le C₁-C_TenAlkylcarbamoyl group, NC₁-C₆A
Lucoxycarbonylamino C₁-C_TenAlkyl carbamo
Il group, N-C₁-C₆Alkoxycarbonylamino C₁
-C₆Alkoxycarbonyl group, C₁-C₆Alkylthio
Group, NC₁-C₆Alkylsulfamoyl group, N, N-
Di-C₁-C₆Alkylsulfamoyl group, C₁-C₆Al
Killsulfinyl group, C₁-C₆Alkylsulfonyl group,
N-C₁-C₆Alkylsulfonylamino group, C₁-C₆A
Lucoxy group, C₁-C₆Alkoxycarbonyl group, protection
Amino C which may be₁-C₆Alkoxycarbonyl
Group, NC_Three-C₆Cycloalkylamino group, N, N-di
-C_Three-C₆Cycloalkylamino group, C_Three-C₆Cycloa
Alkyloxy group, N-C_Three-C₆Cycloalkylcarbamo
Yl group and N, N-di-C_Three-C₆Cycloalkyl carb
A substituent selected from the group consisting of moyl groups,
Zolyl, isothiazolyl, imidazolyl, oxa
Zolyl group, oxadiazolyl group, thiazolyl group, thiazi
Azolyl, thienyl, triazinyl, triazolyl
Group, pyridyl group, pyrazinyl group, pyrimidinyl group,
Ridazinyl group, pyrazolyl group, pyrrolyl group, pyranyl
Group, furyl group, furazanyl group, imidazolidinyl group, i
Midazolinyl group, tetrahydrofuranyl group, pyrazolidi
Nil, pyrazolinyl, piperazinyl, piperidini
Group, pyrrolidinyl group, pyrrolinyl group and morpholino group
A 5- or 6-membered heterocyclic group selected from the group consisting of
Clidinyl group, isoquinolyl group, isoindolyl group, i
Ndazolyl group, indolyl group, indolizinyl group, ethyl
Rangeoxyphenyl group, carbazolyl group, quinazolini
Group, quinoxalinyl group, quinolizinyl group, quinolyl
Group, coumalonyl group, chromenyl group, phenanthridinyl
Group, phenanthrolinyl group, dibenzofuranyl group,
Benzothiophenyl group, cinnolinyl group, thionaphthenyl
Group, naphthyridinyl group, phenazinyl group, phenaxazi
Nil, phenothiazinyl, phthalazinyl, pteri
Dinyl, prenyl, benzimidazolyl, benzo
Oxazolyl group, benzothiazolyl group, benzotriazo
Ryl, benzofuranyl and methylenedioxyphenyl
Nitrogen atom, oxygen atom selected from the group consisting of
A heteroatom selected from the group consisting of sulfur
1 to 5 cyclic aromatic heterocyclic groups having 1 to 5
And N substituted with the heterocyclic group or the heteroaromatic group.
-C₁-C_TenAlkylcarbamoyl group, NC₁-C_TenA
Alkylthiocarbamoyl, thiocarbonyl and
A substituent selected from the group consisting of a rubonyl group;
Straight-chain saturated C which may be substituted with a substituent₁-C₉fat
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C
₁-C₉Aliphatic group, branched unsaturated C₁-C₉Aliphatic groups,
C₁-C₆Alkoxy group, C₁-C₆Alkylthio group and N
-C₁-C₆Selected from the group consisting of alkylamino groups
One or more substituents selected from the group consisting of
Aryl group, acenaphthylenyl which may have
Group, adamantyl group, anthryl group, indenyl group,
Select from the group consisting of rubornyl group and phenanthryl group
1- to 3-cyclic C₇-C_FifteenA carbon aromatic ring group or a
Soxazolyl group, isothiazolyl group, imidazolyl
Group, oxazolyl group, oxadiazolyl group, thiazolyl
Group, thiadiazolyl group, thienyl group, triazinyl group,
Triazolyl group, pyridyl group, pyrazinyl group, pyrimidi
Nil group, pyridazinyl group, pyrazolyl group, pyrrolyl group,
Pyranyl group, furyl group, furazanyl group, imidazolidini
Group, imidazolinyl group, tetrahydrofuranyl group,
Lazolidinyl, pyrazolinyl, piperazinyl,
Peridinyl group, pyrrolidinyl group, pyrrolinyl group and mol
5- or 6-membered hetero selected from the group consisting of holino groups
Ring group or acridinyl group, isoquinolyl group, isoyl
Indolyl, indazolyl, indolyl, indole
Dinyl group, ethylenedioxyphenyl group, carbazolyl
Group, quinazolinyl group, quinoxalinyl group, quinolizinyl
Group, quinolyl group, cumaronyl group, chromenyl group, phena
Suridinyl group, phenanthrolinyl group, dibenzofura
Nil group, dibenzothiophenyl group, cinnolinyl group,
Onaphthenyl group, naphthyridinyl group, phenazinyl group,
Phenaxazinyl, phenothiazinyl, phthalazinyl
Group, pteridinyl group, purinyl group, benzimidazoly
Group, benzoxazolyl group, benzothiazolyl group,
Benzotriazolyl, benzofuranyl and methylenedi
A nitrogen atom selected from the group consisting of an oxyphenyl group,
Heteroatoms selected from the group consisting of oxygen and sulfur atoms
1 to 3 ring groups having 1 to 5 rings per ring system
Heteroaromatic group, R^TenAnd R²⁰Are the same or different,
Atom, azide group, amino group which may be protected,
Rubamoyl group, carbamoylamino group, carbamoylo
Xy group, carboxyl group which may be protected, cyano
Group, sulfamoyl group, sulfo group, nitro group, halogen
Atom, hydroxy group which may be protected, formyl
Group, formylamino group, cyclic saturated C_Three-C₉Aliphatic groups,
Cyclic unsaturated C_Three-C₉Aliphatic group, aralkyl group, NA
Aralkylamino, aralkyloxy, aralkyl
Rubonyl group, aryl group, N-arylamino group, ant
Oxy group, arylsulfonyl group, N-aryls
Ruphonylamino group, N-arylsulfonylamino C₁
-C_TenAlkylamino group, N-arylsulfonylamido
No C₁-C_TenAlkylcarbamoyl group, N-aryls
Ruphonylamino C₁-C₆Alkoxycarbonyl group, C_Two
-C₆Alkanoyl group, NC_Two-C₆Alkanoylami
Group, aroyl group, N-aroylamino group, N-alloy
Le C₁-C_TenAlkylamino group, N-aroyl C₁-C_Ten
Alkylcarbamoyl group, NC₁-C₆Alkylamino
Group, N, N-di-C₁-C₆Alkylamino group, N-C₁
-C_TenAlkylcarbamoyl group, N, N-di-C₁-C
_TenAlkylcarbamoyl group, NC₁-C₆Alkylsul
Famoyl group, C₁-C₆Alkylsulfinyl group, C₁
-C₆Alkylsulfonyl group, NC₁-C₆Alkyls
Rufonylamino group, C₁-C₆Alkylthio group, C₁-C₆
Alkoxy group, C₁-C₆Alkoxycarbonyl group, N-
C_Three-C₆Cycloalkylamino group, C_Three-C₆Cycloal
Killoxy group and N-C_Three-C₆Cycloalkylcarbamo
Or a substituent selected from the group consisting of
Optionally substituted straight-chain saturated C₁-C₉Aliphatic groups,
Linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁-C₉
Aliphatic group, branched unsaturated C₁-C₉Aliphatic group, N-C
₁-C₆Alkylamino group, C₁-C₆Alkylthio group
Kuha C₁-C₆X represents an alkoxy group;_TwoAnd Z are
Carboxylic acid or thiocarbo represented by the formula:
Acid and general formula [III][Where Y_TenIs an oxygen atom or group: NR⁵⁰Or group:
CR⁶⁰R⁷(Where R⁵⁰Is a hydrogen atom, amino
Group protecting group, halogen atom, hydrid which may be protected
Roxy group, N-C₁-C₆Alkylsulfonylamino group,
C₁-C₆Alkoxy group, C₁-C₆Alkoxycarbonyl
Group, C_Two-C₆Alkanoyl group, carbamoyl group and N-
C₁-C_TenSelect from the group consisting of alkylcarbamoyl groups
Or a substituent which may be substituted with the substituent,
Chain saturation C₁-C₉Aliphatic group, linear unsaturated C₁-C₉fat
Group, branched saturated C₁-C₉Aliphatic or branched
Unsaturated C₁-C₉Aliphatic group, R⁶⁰Is a hydrogen atom, halogen
Atom, an optionally protected hydroxy group, N-C₁
-C₆Alkylsulfonylamino group, C₁-C₆Alkoki
Si group, C₁-C₆Alkoxycarbonyl group, C_Two-C₆Al
Canoyl group, carbamoyl group and NC₁-C_TenArchi
A substituent selected from the group consisting of a rucarbamoyl group or
Linear saturated C which may be substituted with the substituent₁-C₉
Aliphatic group, linear unsaturated C₁-C₉Aliphatic groups, branched chains
Sum C₁-C₉Aliphatic or branched unsaturated C₁-C₉
An aliphatic group;⁷Has the meaning described above), R³⁰
And R⁴⁰Are the same or different and are a hydrogen atom, an azide group,
Amidino group, optionally protected amino group, carbamo
Yl group, carbamoylamino group, carbamoyloxy
Group, carboxyl group which may be protected, guanidino
Group, cyano group, sulfamoyl group, sulfo group, nitro
Group, halogen atom, hydroxy which may be protected
Group, formyl group, formylamino group, cyclic saturated C_Three−
C₉Aliphatic group, cyclic unsaturated C _Three-C₉Aliphatic group, C_Two-C
₆Alkanoyl group, NC_Two-C₆Alkanoylamino
Group, NC₁-C₆Alkylamino group, N, N-di-C₁
-C₆Alkylamino group, N-C₁-C_TenAlkyl carba
Moyl group, N, N-di-C₁-C_TenAlkyl carbamoy
Group, C₁-C₆Alkylthio group, N-C₁-C₆Alkyl
Sulfamoyl group, C ₁-C₆Alkylsulfinyl group,
C₁-C₆Alkylsulfonyl group, NC₁-C₆Alkyl
Sulfonylamino group, C₁-C₆Alkoxy group, C₁-C₆
Alkoxycarbonyl group, N-C_Three-C₆Cycloalkyl
Amino group, C_Three-C₆Cycloalkyloxy group and N-C
_Three-C₆Selected from the group consisting of cycloalkylcarbamoyl groups
Selected substituents, which may be substituted with the substituents,
Chain saturation C₁-C₉Aliphatic group, linear unsaturated C₁-C₉fat
Group, branched saturated C₁-C₉Unsaturation of aliphatic groups and branches
Sum C₁-C₉Substitution selected from the group consisting of aliphatic groups
Group, azide group, optionally protected amino group, carb
Moyl group, carbamoylamino group, carbamoyloxy
Group, carboxyl group which may be protected, cyano group,
Sulfamoyl group, sulfo group, nitro group, halogen source
, An optionally protected hydroxy group, a formyl group,
Formylamino group, cyclic saturated C_Three-C₉Aliphatic group, cyclic
Of unsaturated C_Three-C₉Aliphatic group, aralkyl group, N-aral
Killamino group, N, N-diaralkylamino group, arral
Killoxy group, aralkylcarbonyl group, N-aralkyl
Rucarbamoyl group, aryl group, N-arylamino
Group, N, N-diarylamino group, aryloxy group,
Arylsulfonyl group, arylsulfonyloxy group,
N-arylsulfonylamino group, N-arylsulfo
Nilamino C₁-C_TenAlkylamino group, N-aryl
Sulfonylamino C₁-C_TenAlkylcarbamoyl group,
N-arylsulfonylamino C₁-C₆Alkoxycal
Bonyl group, aryl sulfamoyl group, aryl sulf
Amoyloxy group, N-arylsulfamoyl C₁−
C_TenAlkyl carbamoyl group, aryl sulfamoyl
C₁-C₆Alkoxycarbonyl group, N-arylcarba
Moyl group, aroyl group, alloxy group, N- (N-aro
Ilamino) C₁-C_TenAlkylcarbamoyl group, N-
Aroylamino C₁-C_TenAlkoxycarbonyl group, C_Two
-C₆Alkanoyl group, NC_Two-C₆Alkanoylami
Group, N, N-di-C_Two-C₆Alkanoylamino group,
N-C₁-C₆Alkylamino group, N, N-di-C₁-C₆
Alkylamino group, N-C₁-C _TenAlkyl carbamoy
Group, N-C₁-C_TenAlkylthiocarbamoyl group,
N, N-di-C₁-C_TenAlkylcarbamoyl group, N,
N-di-C₁-C_TenAlkylthiocarbamoyl group, N-
C_Two-C₆Alkenylcarbamoyl group, N, N-di-C_Two
-C₆Alkenylcarbamoyl group, protected
N-amino C₁-C_TenAlkylcarbamoyl group, N-
C₁-C₆Alkoxy C₁-C_TenAlkyl carbamoyl
Group, NC₁-C₆Alkoxycarbonyl C₁-C_TenAl
Kill carbamoyl group, NC₁-C₆Alkoxycarboni
Lumino C₁-C_TenAlkylcarbamoyl group, NC₁−
C₆Alkoxycarbonylamino C₁-C₆Alkoxyka
Rubonyl group, C ₁-C₆Alkylthio group, N-C₁-C₆A
Rukylsulfamoyl group, N, N-di-C₁-C₆Archi
Rusulfamoyl group, C₁-C₆Alkylsulfinyl
Group, C₁-C₆Alkylsulfonyl group, NC₁-C₆Al
Killsulfonylamino group, C₁-C ₆Alkoxy group, C₁
-C₆Alkoxycarbonyl group, which may be protected
Amino C₁-C₆Alkoxycarbonyl group, N-C_Three-C₆
Cycloalkylamino group, N, N-di-C_Three-C₆Cyclo
Alkylamino group, C_Three-C₆Cycloalkyloxy
Group, NC_Three-C₆A cycloalkylcarbamoyl group and
N, N-di-C_Three-C₆Is it a cycloalkylcarbamoyl group
A substituent selected from the group consisting of, an isoxazolyl group,
Isothiazolyl group, imidazolyl group, oxazolyl group,
Oxadiazolyl group, thiazolyl group, thiadiazolyl
Group, thienyl group, triazinyl group, triazolyl group,
Lysyl, pyrazinyl, pyrimidinyl, pyridazini
Group, pyrazolyl group, pyrrolyl group, pyranyl group, furyl
Group, furazanyl group, imidazolidinyl group, imidazolini
Group, tetrahydrofuranyl group, pyrazolidinyl group,
Lazolinyl group, piperazinyl group, piperidinyl group, pyro
Group consisting of lysinyl, pyrrolinyl and morpholino groups
Acridinyl, a 5- or 6-membered heterocyclic group selected from
Group, isoquinolyl group, isoindolyl group, indazolyl group
Group, indolyl group, indolizinyl group, ethylene dioxy group
Cyphenyl group, carbazolyl group, quinazolinyl group, quino
Xalinyl group, quinolizinyl group, quinolyl group, cumaroni
Group, chromenyl group, phenanthridinyl group, phenane
Slurolinyl group, dibenzofuranyl group, dibenzothiophene
Nil group, cinnolinyl group, thionaphthenyl group, naphthyl
Dinyl group, phenazinyl group, phenaxazinyl group,
Notiazinyl, phthalazinyl, pteridinyl,
Linyl group, benzimidazolyl group, benzoxazolyl
Group, benzothiazolyl group, benzotriazolyl group, ben
Consists of zofuranyl and methylenedioxyphenyl groups
From nitrogen, oxygen and sulfur selected from the group
A heteroatom selected from the group consisting of 1 to
5- to 5-cyclic heteroaromatic ring groups and
N-C substituted with a heterocyclic group or the heteroaromatic group₁-C_Ten
Alkylcarbamoyl group, NC₁-C_TenAlkylthio
Carbamoyl group, thiocarbonyl group and carbonyl group
And a substituent selected from the group consisting of
Straight-chain saturated C₁-C₉Aliphatic group, straight chain
Of unsaturated C ₁-C₉Aliphatic groups, branched saturated C₁-C₉fat
Group, branched chain unsaturated C₁-C₉Aliphatic group, C₁-C₆A
Lucoxy group, C₁-C₆Alkylthio group and N-C₁-C₆
From substituents selected from the group consisting of alkylamino groups
Having one or more substituents selected from the group consisting of
May be an aryl group, an acenaphthylenyl group, an adaman
Chill, anthryl, indenyl, norbornyl
And at least one selected from the group consisting of phenanthryl groups
Tricyclic C₇-C_FifteenCarbon aromatic ring group or isoxazoly
Group, isothiazolyl group, imidazolyl group, oxazolyl group
Group, oxadiazolyl group, thiazolyl group, thiadiazo
Ryl, thienyl, triazinyl, triazolyl
Group, pyridyl group, pyrazinyl group, pyrimidinyl group, pyri
Dazinyl group, pyrazolyl group, pyrrolyl group, pyranyl group,
Furyl, furazanyl, imidazolidinyl, imida
Zolinyl group, tetrahydrofuranyl group, pyrazolidinyl
Group, pyrazolinyl group, piperazinyl group, piperidinyl
Group, pyrrolidinyl group, pyrrolinyl group and morpholino group
A 5- or 6-membered heterocyclic group selected from the group consisting of
Is acridinyl group, isoquinolyl group, isoindolyl
Group, indazolyl group, indolyl group, indolizinyl
Group, ethylenedioxyphenyl group, carbazolyl group,
Nazolinyl group, quinoxalinyl group, quinolizinyl group,
Noryl group, coumalonyl group, chromenyl group, phenanthry
Dinyl group, phenanthrolinyl group, dibenzofuranyl
Group, dibenzothiophenyl group, cinnolinyl group, thiona
Phenyl, naphthyridinyl, phenazinyl,
Naxazinyl group, phenothiazinyl group, phthalazinyl
Group, pteridinyl group, purinyl group, benzimidazolyl
Group, benzoxazolyl group, benzothiazolyl group, ben
Zotriazolyl, benzofuranyl and methylenedi
Nitrogen atom or acid selected from the group consisting of xylphenyl groups
Heteroatoms selected from the group consisting of elemental atoms and sulfur atoms
From 1 to 3 rings having 1 to 5 rings per ring system
An aromatic ring group or the aryl group, the carbon aromatic ring group,
Or a heterocyclic group.
Straight-chain saturated C₁-C₉Aliphatic group, linear unsaturated C₁−
C₉Aliphatic groups, branched saturated C₁-C₉Aliphatic group or
Branched unsaturated C₁-C₉Represents an aliphatic group, or R³⁰
And R⁴⁰Together form a linear saturated C₁-C₉Aliphatic
Group, linear unsaturated C₁-C₉Aliphatic groups, branched saturated C₁
-C₉Aliphatic or branched unsaturated C₁-C₉fat
Group or 5- or 6-membered saturated carbocyclic group or 5 or less
Or a 6-membered unsaturated carbocyclic ring,₁Is a hydrogen source
Protecting group for carboxyl group or protecting group for amino group
Or carboxyl groups in solid-phase synthesis of peptides or
Is an amino group resin carrier, X_TenIs an oxygen atom, a sulfur atom or
Is a group: NR⁵⁰(Where R⁵⁰Has the above meaning
) Is reacted with an amine derivative represented by
Amino-protecting group, hydroxy-protecting group or carboxy
By removing the protecting group of the general formula [I
V '][Where Y₁Is an oxygen atom or group: NR^FiveOr group: C
R⁶R⁷(Where R^Five, R⁶And R⁷Means the above
Having a taste), R⁰, R^Ten, R²⁰, R³⁰, R ⁴⁰,
L₁, X_Two, X_TenAnd Z have the meaning given above.
And a compound represented by the general formula [V ']:[Wherein, R⁰, R^Ten, R²⁰, R³⁰, R⁴⁰, L₁, X_Two, X
_Ten, Y₁And Z have the meaning described above.
Mixture and then equilibrate the inactive mixture
Reaction with an acid in a neutral organic solvent to give a compound of the general formula [VII
I '][Wherein, R⁰, R^Ten, R²⁰, R³⁰, R⁴⁰, X_Two, X_Ten, Y
₁And Z have the above-mentioned meaning];
Wherein the protecting group is removed as appropriate.[Wherein, R, R¹, R^Two, R^Three, R^Four, X₁, X_Two, Y₁as well as
Z has the meaning described above] or a compound represented by the formula
A method for producing a pharmaceutically acceptable salt. 6. A compound of the general formula [IV ″] [Wherein, Y ₂ represents an oxygen atom, L ₂ represents a hydrogen atom,
⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , X ₂ , X ₁₀ and Z have the above-mentioned meanings] and a compound represented by the general formula [V ″] [Wherein, R ⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , L ₂ , X ₂ , X
₁₀ , Y ₂ and Z have the same meanings as defined above], and the equilibrium mixture is reacted with a sulfurizing agent to give a compound of the general formula [VI ″] [Wherein, Y ₃ represents a sulfur atom, and R ⁰ , R ¹⁰ , R ²⁰ ,
R ³⁰ , R ⁴⁰ , L ₂ , X ₂ , X ₁₀ and Z have the above-mentioned meanings] and a compound represented by the general formula [VII ″]: [Wherein, R ⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , L ₂ , X ₂ , X
₁₀ , Y ₃ and Z have the above-mentioned meaning], and then reacted with an acid to give a compound of the general formula [VIII ″] [Wherein R ⁰ , R ¹⁰ , R ²⁰ , R ³⁰ , R ⁴⁰ , X ₂ , X ₁₀ , Y
Wherein ₃ and Z have the same meanings as described above, and the protecting group is removed as appropriate. [Wherein R, R ¹ , R ² , R ³ , R ⁴ , X ₁ , X ₂ , Y ₃ and Z have the above-mentioned meanings] or a pharmaceutically acceptable salt thereof. Manufacturing method.