JP2002167382A - Amino alcohol derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an amino alcohol or its pharmaceutically acceptable salts, esters, and other derivatives having low toxicity and an immunosuppressive activity. SOLUTION: The amino alcohol derivative is represented by formula (1) [wherein, R1 and R2 are a hydrogen atom or a protecting group of an amino group; R3 is a hydrogen atom or a protecting group of a hydroxy group; R4 is a lower alkyl group; n is an integer of 1-6; X is an ethylene group; Y is a C1-C10 alkylene group; R5 is an aryl group or a substituted aryl group; R6 and R7 are hydrogen atoms; where if R5 is a hydrogen atom, Y is a group other than a single bonded normal chain C1-C10 alkylene group]. Its pharmaceutically acceptable salts, esters, and other derivatives are also provided.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an amino alcohol derivative having excellent immunosuppressive activity, a pharmaceutically acceptable salt thereof, an ester or other derivative thereof, a pharmaceutical composition containing them as an active ingredient, The present invention relates to a method for preventing or treating an autoimmune disease or the like, which comprises using the same for producing a pharmaceutical composition, or administering a pharmacologically effective amount thereof to a warm-blooded animal.

Further, the present invention provides a novel optically active amino alcohol compound, particularly an optically active 4,4 compound, which is useful as an intermediate for the synthesis of pharmaceuticals such as the above-mentioned amino alcohol derivatives.
-Disubstituted oxazolidin-2-one compounds.

Further, the present invention relates to an optically active 2-substituted-2-amino-1,3-propanediol which is important as a synthetic intermediate for the above-mentioned optically active amino alcohol compound.
The present invention relates to a novel and highly selective process for producing a monoester derivative.

[0004]

2. Description of the Related Art Conventionally, in the treatment of immune-related diseases such as rheumatism and other autoimmune diseases, anti-inflammatory drugs such as steroids have been used for inflammatory reactions caused by abnormal immune reactions. However, these are symptomatic treatments, not radical treatments.

It has been reported that abnormalities in the immune system are also involved in the development of diabetes and nephritis [Kidney
International, 51, 94 (1997); Journal of Immunol
ogy, 157, 4691 (1996)], and no drug has been developed to improve the abnormality.

On the other hand, the development of a method for suppressing the immune response
It is also very important in preventing rejection in organ and cell transplantation and in treating and preventing various autoimmune diseases. However, conventionally known immunosuppressants such as cyclosporin A (CsA) and tacrolimus (TRL) are known to be toxic to the kidney and liver, and in order to reduce such side effects, Although treatments such as combined use of steroids have been widely used, at present, they have not always exerted a sufficient immunosuppressive effect without showing any side effects.

[0007] Under such circumstances, attempts have been made to find compounds having low toxicity and excellent immunosuppressive activity.

[0008] As immunosuppressants, for example, the following compounds are known. (1) WO94 / 08943 (EP627406) In this publication, the following general formula (a)

[0009]

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[In the above compound (a), R is a linear or branched carbon chain which may have a substituent.] In the chain, a double bond, a triple bond, oxygen, sulfur, -N ( R ⁶ ) −
(Wherein R ⁶ is hydrogen), an arylene which may have a substituent, or a heteroarylene which may have a substituent. And aryl which may have a substituent, cycloalkyl which may have a substituent, and heteroaryl which may have a substituent. 、 And R ² ,
R ³ , R ⁴ and R ⁵ are the same or different and are hydrogen or alkyl. ] Are disclosed as immunosuppressants.

The compound (a) of the prior art has two oxymethyl groups (—CH ₂ O) as essential substituents.
R ⁴ and —CH ₂ OR ⁵ ), but the compound of the present invention is different from the above-mentioned compound (a) in having a —CH ₂ OR ³ group and a lower alkyl group as corresponding groups.

This publication does not specifically disclose any compound having a structure similar to that of the compound (I) of the present invention, and most closely resembles the structure of the compound (I) of the present invention. Even if the compound is selected, at most, only the following compounds are disclosed.

[0013]

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(2) WO96 / 06068 This publication discloses the following general formula (b)

[0015]

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[In the above compound (b), R ¹ , R ² and R ³ are a hydrogen atom, W is a hydrogen atom, an alkyl group, etc., Z is a single bond or an alkylene group,
X represents a hydrogen atom or an alkoxy group, and Y represents a hydrogen atom, an alkyl, an alkoxy, an acyl, an acyloxy, an amino, an acylamino group or the like. Is a compound having
It is disclosed as an immunosuppressant.

The compound (b) essentially requires a phenyl group in the basic skeleton, but the compound (I) of the present invention differs from the compound (b) in that the corresponding group is a thiophene group which is a heterocyclic ring. Is different from

Further, this publication does not specifically disclose any compound having a structure similar to the structure of the compound (I) of the present invention, and most specifically discloses the structure of the compound (I) of the present invention. Even if similar compounds are selected, at most only the following compounds are disclosed.

[0019]

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(3) WO98 / 45249 In this publication, the following general formula (c)

[0021]

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[In the above compound (c), R ¹ , R ² ,
R ³ and R ⁴ are the same or different and are hydrogen or an acyl group. ] Are disclosed as immunosuppressants. The compound (c) has two oxymethyl groups (—CH ₂ OR ³ and —CH ₂ OR ⁴ ) as essential substituents, but the compound of the present invention has —CH
_It differs from the above compound (c) in having a ₂ OR ³ group and a lower alkyl group. The compound (c) has a phenyl group as an essential group between the — (CH ₂ ) ₂ — group and the —CO— (CH ₂ ) ₄ — group in the basic skeleton. ) Is also different from compound (c) above in that the corresponding group is a thiophene group which is a heterocycle.

The compound (c) is a compound of the formula -CO- (C
Although it has a phenyl group at the chain end as an essential substituent of the H ₂ ) ₄ — group, the compound (I) of the present invention is different in that it may have a cycloalkyl group or a heterocyclic group as a corresponding group.

Further, this publication does not specifically disclose any compound having a structure similar to the structure of the compound (I) of the present invention, Even if similar compounds are selected, at most only the following compounds are disclosed.

[0025]

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On the other hand, optically active substituted amino acids and substituted amino alcohol derivatives (particularly α-substituted amino acids and α-substituted amino acids)
-Substituted amino alcohol derivatives) are often important compounds such as those having physiological activity per se, partial components of natural products and pharmaceuticals, and synthetic intermediates.

For example, α-methyl-α-vinyl amino acid is an amino acid decarboxylase inhibitor, and α-ethynyl-α-methyl amino acid is glutamic acid decarboxylas.
It is a useful compound as an inhibitor of e and is involved in the regulation of immune response by ISP-1 (Myriocin) and T cells isolated from metabolites of Cordyceps sinensis (Isalia sinclairii) having immunosuppressive activity Cona is known
α-Substituted amino acids and amino alcohol derivatives, which are optically active even as a partial constituent of a biologically active natural product such as genin, are of great interest in biochemistry and organic synthetic chemistry.

Since these α-substituted amino acids and amino alcohol derivatives have an asymmetric carbon, a means for efficiently synthesizing one of the enantiomers has been desired.

Process for producing optically active substituted amino acids and amino alcohol derivatives, and optically active 4,4-disubstituted oxazolidines useful as synthetic intermediates for pharmaceuticals such as the optically active substituted amino acids and amino alcohol derivatives
Syntheses of optically active amino alcohol compounds such as -2-one compounds are extremely few.
Many methods are known, as summarized in "e α-Amino Acids" (Pergamon Press), and are roughly classified into two methods.

First, a method using diastereoselective alkylation using an asymmetric auxiliary group, a typical method of which is described by Seebach et al. In Helv. Chim. Acta., 71, 224 (198)
8), or by Nagao and Sano et al. In Tetrahedron Lett., 36, 2097 (1995) and Tetrahe
High diastereoselective aldol utilizing chiral bislactam ether carboxylic acid ester and Mg (II) and Sn (II) Lewis acids as reported in dron Lett., 36, 4101 (1995) Synthesis of α-substituted serine derivatives by reaction is known.

Second, Chemistry by Nagao and Tamai et al.
Lett., 239 (1989) and Chemistry Lett., 2381 (1994). There is a method using an enantioselective enzymatic hydrolysis reaction of a novel α-substituted-α-protected aminomalonic acid diester.

Each of the production methods classified into the first method has many steps, and requires the use of a stoichiometric amount of an asymmetric source. In addition, the second method has a drawback such that there is a limitation in the case where there is a substituent which is unstable under reducing conditions because of the reduction step.

As described above, there are many reports, but very few practical methods. In general, a method of optically resolving a racemate to obtain one of the optical isomers is common, and in that case, there is a problem that a decrease in the total yield is inevitable.

[0034]

The present inventors have conducted intensive studies on derivatives having an immunosuppressive action, and as a result,
The amino alcohol derivative (I) of the present invention has low toxicity and excellent immunosuppressive activity, and has systemic lupus erythematosus,
Rheumatoid arthritis, polymyositis, dermatomyositis, scleroderma, Behcet's disease, Chron's disease, ulcerative colitis, autoimmune hepatitis, aplastic anemia, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia , Multiple sclerosis, autoimmune bullous disease,
Psoriasis vulgaris, vasculitis group, Wegener's granuloma, uveitis, idiopathic interstitial pneumonia, Goodpasture syndrome, sarcoidosis, allergic granulomatous vasculitis, bronchial asthma,
Myocarditis, cardiomyopathy, aortitis syndrome, post-myocardial infarction syndrome,
Primary pulmonary hypertension, minimal change nephrosis, membranous nephropathy,
Membranous proliferative nephritis, focal glomerulosclerosis, crescentic nephritis, myasthenia gravis, inflammatory neuropathy, atopic dermatitis, chronic actinic dermatitis, acute polyarthritis, Syd
enham chorea, systemic sclerosis, adult-onset diabetes, insulin-dependent diabetes, juvenile diabetes, atherosclerosis, glomerulonephritis, tubular interstitial nephritis, primary biliary cirrhosis, primary sclerosing bile duct Inflammation, fulminant hepatitis, viral hepatitis, GVHD, rejection in various organ transplants, contact dermatitis,
The present invention has been found to be useful for autoimmune diseases such as sepsis or other immune-related diseases, and has completed the present invention.

Accordingly, an object of the present invention is to provide an amino alcohol derivative, a pharmacologically acceptable salt, an ester or other derivative thereof having a low toxicity and excellent immunosuppressive activity.

Another object of the present invention is to provide the above-mentioned amino alcohol
, A pharmaceutical composition containing a pharmaceutically acceptable salt thereof, an ester or other derivative thereof as an active ingredient, their use for producing the above pharmaceutical composition, or a pharmaceutically effective amount thereof. To prevent or treat the above-mentioned diseases such as autoimmune diseases, which are administered to warm-blooded animals.

The present inventors have conducted intensive studies to solve the above-mentioned problems with respect to a method for producing an optically active amino alcohol compound and an intermediate thereof.
New optically active amino alcohol compounds (La) and (Lb), especially optically active 4,4-disubstituted oxazolidin-2-one derivatives, can be produced by a simpler method than conventional methods. In addition, it has been found that the derivative is useful as an intermediate for the production of pharmaceuticals such as optically active substituted amino acids and substituted amino alcohol derivatives.

Furthermore, the present inventors have conducted intensive studies on a method for selectively producing the above optically active amino alcohol compounds (La) and (Lb). As a result, an optically active 2-substituted compound was obtained as a synthetic intermediate thereof. 2-amino-1,3-propanediol monoester derivatives (XLIVa) or (XLIVb) are preferred, and the compounds (XLIVa) and (XLIVb) are 2-substituted-2-amino-1,3-
By using a propanediol derivative (XLII) as a raw material and using a vinyl carboxylate derivative (XLIII) in the presence of a lipase, the selective acylation of only one of the hydroxyl groups enables easy, convenient, and high yield. They found that they could be manufactured and completed the present invention.

[0039]

Means for Solving the Problems (1) The amino alcohol derivative of the present invention has the following general formula (I).

[0040]

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Wherein R ¹ and R ² are the same or different and each represent a hydrogen atom or an amino-protecting group, R ³ represents a hydrogen atom or a hydroxy-protecting group, and R ⁴ represents a lower group. An alkyl group; n represents an integer of 1 to 6;
Is an ethylene group, a vinylene group, an ethynylene group, a formula -D-
A group having CH ₂ — (where D is a carbonyl group,
A group having CH (OH)-, an oxygen atom, a sulfur atom or a nitrogen atom. ), An aryl group or an aryl group substituted with 1 to 3 aryl groups or a group selected from substituent group a;
Represents a single bond, C ₁ -C ₁₀ alkylene group, C ₁ -C ₁₀ for 1 to are three substituted with a group selected from Substituent group a and b
An alkylene group, a C ₁ -C ₁₀ alkylene group having an oxygen atom or a sulfur atom in a carbon chain or at a chain end, or a carbon chain substituted with 1 to 3 groups selected from substituent groups a and b, or A C ₁ -C ₁₀ alkylene group having an oxygen atom or a sulfur atom at a chain end, wherein R ⁵ is selected from a hydrogen atom, a cycloalkyl group, an aryl group, a heterocyclic group, and substituent groups a and b A cycloalkyl group substituted by 1 to 3 groups, an aryl group substituted by 1 to 3 groups selected from substituent groups a and b, or a group selected from substituent groups a and b 1 to 3 substituted heterocyclic groups are shown, and R ⁶ and R ⁷ are the same or different and represent a hydrogen atom or a group selected from substituent group a.

However, when R ⁵ is a hydrogen atom, Y represents a group other than a single bond or a linear C ₁ -C ₁₀ alkylene group. ], A pharmacologically acceptable salt thereof, an ester thereof, or another derivative thereof. <Substituent group a> halogen atom, lower alkyl group, halogeno lower alkyl group, lower alkoxy group, lower alkylthio group, carboxyl group, lower alkoxycarbonyl group,
Hydroxy group, lower aliphatic acyl group, amino group, mono-
Lower alkylamino group, di-lower alkylamino group, lower aliphatic acylamino group, cyano group and nitro group <Substituent group b> selected from cycloalkyl group, aryl group, heterocyclic group and substituent group a A cycloalkyl group substituted by 1 to 3 groups, 1 group selected from substituent group a
An aryl group substituted with 1 to 3 substituents, and a heterocyclic group substituted with 1 to 3 substituent (s) selected from Substituent Group a.

In the above compound (1), preferred compounds are as follows. (2) In (1), the formula (Ia)

[0044]

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A compound having the formula (Ib), a pharmaceutically acceptable salt thereof, an ester or other derivative thereof;

[0046]

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(4) In any one selected from (1) to (3), R ¹ and R ² are the same Or differently, a hydrogen atom,
A compound or a pharmacologically acceptable salt thereof, which is a lower alkoxycarbonyl group, an aralkyloxycarbonyl group or an aralkyloxycarbonyl group substituted by 1 to 3 groups selected from a substituent group a, or a pharmacologically acceptable salt thereof; In any one selected from (3), a compound in which R ¹ and R ² are hydrogen atoms or a pharmaceutically acceptable salt thereof, (6) any one selected from (1) to (5) In the above item 1, the compound wherein R ³ is a hydrogen atom, a lower alkyl group, a lower aliphatic acyl group, an aromatic acyl group or an aromatic acyl group substituted by 1 to 3 groups selected from substituent group a. Or a pharmacologically acceptable salt thereof. (7) In any one selected from (1) to (5), a compound wherein R ³ is a hydrogen atom or a pharmacologically acceptable salt thereof, (8) (1) to (7) In any one of the al selected, R ⁴ is, C ₁ -C ₄ compound is an alkyl group or a pharmacologically acceptable salt thereof, any one selected from (9) (1) to (7) 1 in terms, R ⁴ is C ₁ -C ₂ alkyl group compound or a pharmacologically acceptable salt thereof, in any one selected from (10) (1) to (7), R ⁴ is, A compound which is a methyl group or a pharmacologically acceptable salt thereof, (11) any one selected from (1) to (10)
In the above item, n is 2 or 3, or a pharmacologically acceptable salt thereof, (12) any one selected from (1) to (10).
In the above item, n is 2 or a pharmacologically acceptable salt thereof, (13) any one selected from (1) to (12).
In the above item, X is an ethylene group, an ethynylene group, an aryl group or an aryl group substituted by 1 to 3 groups selected from substituent group a, or a pharmacologically acceptable salt thereof, (14) ) Any one selected from (1) to (12)
In the above item, a compound wherein X is an ethylene group or a pharmaceutically acceptable salt thereof, (15) any one selected from (1) to (12),
In the above item, the compound wherein X is an ethynylene group or a pharmaceutically acceptable salt thereof, (16) any one selected from (1) to (12),
In terms, X is the formula -D-CH ₂ - group, compound or a pharmacologically acceptable salt thereof having, any one selected from (17) (1) to (12) 1
In terms, X is the formula -D-CH ₂ - group (wherein, D is a carbonyl group or the formula -CH (OH) - groups are shown having a.) With the compounds wherein or a pharmacologically acceptable Salt, (18) any one selected from (1) to (17)
In the above item, Y is a C ₁ -C ₁₀ alkylene group or a C ₁ -C 3 substituted with one or three groups selected from substituent groups a and b.
₁ -C ₁₀ compound or a pharmacologically acceptable salt thereof is an alkylene group, any one selected from (19) (1) to (17) 1
In terms, C ₁ to Y were 1 to 3 substituted with a group selected from C ₁ -C ₆ alkylene group or a substituent group a and b
A compound which is a —C ₆ alkylene group or a pharmacologically acceptable salt thereof, (20) any one selected from (1) to (17)
In the above item, Y is an ethylene, trimethylene or tetramethylene group, which is an ethylene group, a trimethylene group, a tetramethylene group, or a group selected from the substituent groups a and b, and is substituted by 1 to 3 groups, or a pharmacological compound thereof. (21) Any one selected from (1) to (17)
In the above item, Y is an ethylene group, a trimethylene group or a tetramethylene group, or a pharmaceutically acceptable salt thereof; (22) any one selected from (1) to (17);
In the above item, Y is an ethylene group or a trimethylene group, or a pharmaceutically acceptable salt thereof; (23) any one selected from (1) to (17);
In the above item, carbon is a group in which 1 to 3 Y are substituted with a C ₁ -C ₁₀ alkylene group having an oxygen atom or a sulfur atom in a carbon chain or at a chain end, or a group selected from substituent groups a and b. A compound which is a C ₁ -C ₁₀ alkylene group having an oxygen atom or a sulfur atom in the chain or at the chain end, or a pharmaceutically acceptable salt thereof, (24) any one selected from (1) to (17)
In the above item, Y is a C ₁ -C ₁₀ alkylene group having an oxygen atom or a sulfur atom in a carbon chain or at a chain end, or a pharmacologically acceptable salt thereof, (25) From (1) to (17), Any one selected
In the above items, Y is a C ₁ -C ₁₀ alkylene group having an oxygen atom in a carbon chain or at a chain end, or a pharmacologically acceptable salt thereof, (26) selected from (1) to (17). Any one
In the above item, Y is a C ₁ -C ₆ alkylene group having an oxygen atom in a carbon chain or at a chain end, or a pharmaceutically acceptable salt thereof, (27) selected from (1) to (17). Any one
In the above, Y represents —O—CH ₂ —, —O— (CH ₂ ) _{2
-, - O- (CH 2)} 3 -, - CH 2 -O -, - (CH 2)
₂ -O- or - (CH _{2) 3} is a group having a -O- compound or a pharmacologically acceptable salt thereof, any one selected from (28) (1) to (17) 1
In terms, Y is a group, compound or a pharmacologically acceptable salt thereof having a -CH ₂ -O-, any selected from (29) (1) to (17) 1
In terms, Y is, -O- (CH _{2) 2} - or - (C
(30) any one selected from (1) to (29), a compound which is a group having H ₂ ) ₂ —O— or a pharmacologically acceptable salt thereof
In the above item, R ⁵ is a hydrogen atom or a pharmacologically acceptable salt thereof, (31) any one selected from (1) to (29).
In the above, R ⁵ is a cycloalkyl group, a heterocyclic group, a cycloalkyl group substituted by 1 to 3 groups selected from substituent groups a and b, or a group selected from substituent groups a and b. A compound which is a substituted heterocyclic group having 1 to 3 or a pharmacologically acceptable salt thereof, (32) any one selected from (1) to (29)
In the above item, R ⁵ is a cycloalkyl group or a substituent group a
And a compound which is a cycloalkyl group substituted by 1 to 3 groups selected from and b, or a pharmacologically acceptable salt thereof, (33) any one selected from (1) to (29)
In the above item, R ⁵ is a cycloalkyl group or a pharmaceutically acceptable salt thereof, (34) any one selected from (1) to (29).
In the above item, R ⁵ is a cyclohexyl group, or a pharmaceutically acceptable salt thereof; (35) any one selected from (1) to (29);
In the above item, R ⁵ is an aryl group or a substituent group a and b
Or a pharmacologically acceptable salt thereof, wherein the compound is an aryl group substituted by 1 to 3 groups selected from: (36) any one selected from (1) to (29)
In the above item, R ⁵ is an aryl group or an aryl group having 1 to 3 substituents (the substituent is a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group,
It is a group selected from the group consisting of a lower alkylthio group and a lower aliphatic acyl group. Or a pharmacologically acceptable salt thereof, (37) any one selected from (1) to (29)
In the above item, R ⁵ is an aryl group or an aryl group having 1 to 3 substituents (the substituent is a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group or a lower aliphatic acyl group). Or a pharmacologically acceptable salt thereof, or (38) any one selected from (1) to (29).
In the above item, R ⁵ is a phenyl group or a phenyl group having 1 to 3 substituents (the substituent is a group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower aliphatic acyl group). Or a pharmacologically acceptable salt thereof, (39) any one selected from (1) to (29).
In the above item, R ⁵ is a phenyl group or a phenyl group having 1 to 3 substituents (the substituent is a group selected from the group consisting of a fluorine atom, a chlorine atom, methyl, trifluoromethyl, methoxy and acetyl group). (40) Any one selected from the group consisting of (40) (1) to (29)
In the above, R ⁵ represents phenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl,
3,5-dichlorophenyl, 3-methylphenyl, 4-
Methylphenyl, 3,4-dimethylphenyl, 3,5-
Dimethylphenyl, 3-trifluoromethylphenyl,
4-trifluoromethylphenyl, 3,4-ditrifluoromethylphenyl, 3,5-ditrifluoromethylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, A compound which is a 4,4,5-trimethoxyphenyl, 3-acetylphenyl or 4-acetylphenyl group or a pharmaceutically acceptable salt thereof, (41) any one selected from (1) to (40)
Wherein R ⁶ and R ⁷ are the same or different and are a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group or a lower alkylthio group, or a pharmaceutically acceptable salt thereof; 42) Any one selected from (1) to (40)
In the above item, the compound wherein R ⁶ and R ⁷ are a hydrogen atom or a pharmaceutically acceptable salt thereof, (43) In (1), any one compound selected from the following, or a pharmaceutically acceptable salt thereof: , Its esters or other derivatives.

2-amino-2-methyl-4- [5- (6-cyclohexylhexyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5- Cyclohexylpentyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4
-[5- (4-cyclohexylbutyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (6-cyclohexylhex-1-ynyl) thiophen-2- Yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexylpent-1-ynyl) thiophen-2-yl] butan-1-ol, 2-
Amino-2-methyl-4- [5- (4-cyclohexylbut-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-
Methyl-4- [5- (6-cyclohexylhexanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5-
(5-cyclohexylpentanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-cyclohexylbutanoyl) thiophen-2-yl] butan-1-ol , 2-amino-2-ethyl-4- [5- (6-cyclohexylhexyl) thiophen-2-yl] butan-1-ol, 2-amino-2-
Ethyl-4- [5- (5-cyclohexylpentyl) thiophene-2
-Yl] butan-1-ol, 2-amino-2-ethyl-4- [5- (4-
Cyclohexylbutyl) thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4- [5- (6-cyclohexylhex-1-ynyl) thiophen-2-yl] butan-1-ol , 2-
Amino-2-ethyl-4- [5- (5-cyclohexylpent-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2
-Ethyl-4- [5- (4-cyclohexylbut-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4-
[5- (6-cyclohexylhexanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4- [5- (5-cyclohexylpentanoyl) thiophen-2-yl] butane- 1-
All, 2-amino-2-ethyl-4- [5- (4-cyclohexylbutanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (6- Phenylhexyl) thiophen-2-
Yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-phenylpentyl) thiophen-2-yl] butan-1-ol,
2-amino-2-methyl-4- [5- (4-phenylbutyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5-
(6-phenylhex-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-phenylpent-1-ynyl) thiophen-2-yl] Butan-1-ol, 2
-Amino-2-methyl-4- [5- (4-phenylbut-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl
-4- [5- (6-phenylhexanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-phenylpentanoyl) thiophen-2-yl ] Butan-1-ol, 2-
Amino-2-methyl-4- [5- (4-phenylbutanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4-
[5- (5-cyclohexyloxypent-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5-
(4-cyclohexyloxybut-1-ynyl) thiophen-2-
Yl] butan-1-ol, 2-amino-2-methyl-4- [5- (3-cyclohexyloxypropynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexyloxypentyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-cyclohexyloxybutyl) thiophen-2-yl] butane- 1-ol, 2-amino-2-methyl-4- [5- (3-cyclohexyloxypropyl)
Thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexyloxypentanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2 -Methyl-4-
[5- (4-cyclohexyloxybutanoyl) thiophen-2-
Yl] butan-1-ol, 2-amino-2-methyl-4- [5- (3-cyclohexyloxypropanoyl) thiophen-2-yl]
Butan-1-ol, 2-amino-2-methyl-4- [5- (5-phenoxypent-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4 -[5- (4-phenoxybut-1-
Inyl) thiophen-2-yl] butan-1-ol, 2-amino
-2-methyl-4- [5- (3-phenoxypropynyl) thiophene-
2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-
Phenoxypentyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-phenoxybutyl) thiophen-2-yl] butan-1-ol, 2-amino- 2-methyl
-4- [5- (3-phenoxypropyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-phenoxypentanoyl) thiophen-2-yl] Butan-1-ol, 2-
Amino-2-methyl-4- [5- (4-phenoxybutanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4
-[5- (3-phenoxypropanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-benzyloxyphenyl) thiophen-2-yl] butane -1-ol,
2-amino-2-methyl-4- [5- (4-cyclohexylmethoxyphenyl) thiophen-2-yl] butan-1-ol, 2-amino
-2-methyl-4- [5- (4-cyclohexylethoxyphenyl)
Thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-cyclohexylmethoxypropynyl) thiophen-2-yl] butan-1-ol, 2-amino-2- Methyl-4-
[5- (4-cyclohexylmethoxypropyl) thiophen-2-
Yl] butan-1-ol and 2-amino-2-methyl-4- [5-
(4-cyclohexylmethoxypropanoyl) thiophene-2
-Yl] butan-1-ol, (44) In (1), any one compound selected from the following, a pharmaceutically acceptable salt thereof, an ester or other derivative thereof: 2-amino-2-methyl -4- [5- (4-cyclohexylbutyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexylpentyl) thiophen-2-yl] butane -1-ol, 2-amino-2-
Methyl-4- [5- (5-phenylpentyl) thiophen-2-yl]
Butan-1-ol, 2-amino-2-methyl-4- [5- (4-cyclohexyloxybutyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5 -[4- (4-Fluorophenoxy) butyl] thiophen-2-yl] butan-1-ol, 2-
Amino-2-methyl-4- [5- [4- (4-methoxyphenoxy) butyl] thiophen-2-yl] butan-1-ol, 2-amino-2-
Methyl-4- [5- (4-benzyloxybutyl) thiophen-2-
Yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-cyclohexylbut-1-ynyl) thiophen-2-yl] butane
-1-ol, 2-amino-2-methyl-4- [5- (4-phenylbut-
1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexylpent-1-ynyl)
Thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-phenylpent-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino -2-methyl-4- [5- [5- (4-
Fluorophenyl) pent-1-ynyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [5- (4-
Methoxyphenyl) pent-1-ynyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [3- (4-
Methylcyclohexyloxy) propynyl] thiophene-2
-Yl] butan-1-ol, 2-amino-2-methyl-4- [5- [3-
(4-methylphenoxy) propynyl] thiophen-2-yl]
Butan-1-ol, 2-amino-2-methyl-4- [5- [3- (4-ethylphenoxy) propynyl] thiophen-2-yl] butane-1
-Ol, 2-amino-2-methyl-4- [5- [3- (4-methylthiophenoxy) propynyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [ 5- (4-cyclohexyloxybut-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [4- (4-fluorophenoxy) but-1 -Inyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [4- (4-methylphenoxy)
But-1-ynyl] thiophen-2-yl] butan-1-ol, 2
-Amino-2-methyl-4- [5- (3-cyclohexylmethoxypropynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-phenylmethoxybut (-1-ynyl)
Thiophene-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-cyclohexylbutanoyl) thiophen-2-
Yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-phenylbutanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexylpentanoyl) thiophen-2-yl] butan-1-ol, 2-amino
-2-methyl-4- [5- (5-phenylpentanoyl) thiophene-
2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [5-
(4-Fluorophenyl) pentanoyl] thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4- [5- (5-cyclohexylpentyl) thiophen-2-yl] butan-1-ol , 2-amino-2-ethyl-4- [5- (5-cyclohexylpent)
-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4- [5- (5-cyclohexylpentanoyl)
Thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [3- (4-chlorophenoxy) propynyl] thiophen-2-yl] butan-1-ol, 2- Amino-2-methyl-4- [5-
[3- (3-methylphenoxy) propynyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [3- (3,4
-Dimethylphenoxy) propynyl] thiophen-2-yl]
Butan-1-ol, 2-amino-2-methyl-4- [5- [3- (3-methoxyphenoxy) propynyl] thiophen-2-yl] butane
-1-ol, 2-amino-2-methyl-4- [5- [3- (3,4-dimethoxyphenoxy) propynyl] thiophen-2-yl] butane-1
-All, 2-amino-2-methyl-4- [5- [3- (3,5-dimethoxyphenoxy) propynyl] thiophen-2-yl] butane-1-
All, 2-amino-2-methyl-4- [5- [3- (3-acetylphenoxy) propynyl] thiophen-2-yl] butan-1-ol, and 2-amino-2-methyl-4- [ 5- [3- (4-acetylphenoxy) propynyl] thiophen-2-yl] butan-1-ol.

In the above compound (I), (2) or (3); (4) or (5); (6) or (7);
(10); (11) or (12); (13) to (17); (18) to (29); (30) to (4).
0); and a compound obtained by arbitrarily combining any one selected from the group consisting of (41) and (42) is also preferable. (45) The optically active amino alcohol compound of the present invention has the following general formula (La) or (Lb).

[0050]

Embedded image

[Wherein, R¹And R^TwoAre the same or different
Represents a protecting group for a hydrogen atom or an amino group;^3aIs the water
Represents a protecting group for a hydrogen atom or a hydroxy group, or
R¹Is a hydrogen atom, and R^TwoAnd R^3aBut together
Represents a group of the formula (-(C = O)-),^4aIs C₁-C
₂₀Alkyl group, heteroatom intervening C_Two-C₂₀Archi
Substituted with an aryl group, an aryl group or an aromatic heterocyclic group
C₁-C₂₀Alkyl group, C_Two-C ₂₀Alkynyl group, hetero
C atom intervening_Three-C₂₀Alkynyl group, aryl group
Or C substituted with an aromatic heterocyclic group_Two-C₂₀Alkini
Group, C_Two-C₂₀Alkenyl group, with intervening heteroatoms
C_Three-C₂₀Alkenyl group, aryl group or aromatic compound
C substituted with a ring group_Two-C₂₀Alkenyl group, aryl
Or a heteroatom substituted with an aromatic heterocyclic group
C that exists_Two-C₂₀Alkyl group or cycloalkyl group
And m represents an integer of 0 to 4, and Ar represents an aryl.
Group, aromatic heterocyclic group, group selected from substituent group a
1 to 5 substituted aryl groups, selected from substituent group a
Represents an aromatic heterocyclic group substituted by 1 to 5 substituents
You. However, when Ar is an aryl group, R¹Is hydrogen field
Does not show a child and R^TwoAnd / or R^3aDoes not represent a hydrogen atom
No. ] The compound represented by these. <Substituent group a> Halogen atom, lower alkyl group, halogen
Lower alkyl group, lower alkoxy group, lower alkyl group
O group, carboxyl group, lower alkoxycarbonyl group,
Hydroxy group, lower aliphatic acyl group, amino group, mono-
Lower alkylamino group, di-lower alkylamino group, lower
Lower aliphatic acylamino, cyano and nitro groups
In the compound (La) or (Lb), a suitable compound is
It can be mentioned in the note. (46) In (45), a compound having the general formula (La)
Compound (47) In (45) or (46), R¹But hydrogen
A compound that is an atom, (48) any one selected from (45) to (47)
In one term, R^TwoAnd R^3aBut together, the formula (-
(C = O)-) a compound which is a group, (49) any one selected from (45) to (47)
In one term, R^3aIs a compound selected from the group consisting of: (50), (45) to (49),
In one term, R^4aBut C₁-C_TenAlkyl group, hetero
C atom intervening_Two-C_TenAlkyl group, aryl group or
C substituted with an aromatic heterocyclic group₁-C_TenAlkyl group, C_Two
-C_TenAlkynyl group, heteroatom-intervening C_Three-C_Ten
Substituted with an alkynyl group, an aryl group or an aromatic heterocyclic group
C_Two-C_TenAlkynyl group, C_Two-C_TenAlkenyl group,
C with heteroatom_Three-C_TenAlkenyl group, ally
Substituted with a phenyl group or an aromatic heterocyclic group_Two-C_TenArche
Substituted with a phenyl group, an aryl group or an aromatic heterocyclic group.
C with a terrorist atom_Two-C_TenAn alkyl group or C_Five−
C_TenA compound which is a cycloalkyl group, (51) any one selected from (45) to (49)
In one term, R^4aBut C₁-C_TenAlkyl group, hetero
C atom intervening_Two-C_TenAlkyl group, aryl group or
C substituted with an aromatic heterocyclic group₁-C_TenAlkyl group, C_Two
-C_TenAlkynyl group, C_Two-C_TenAn alkenyl group, or
C_Five-C_TenA compound which is a cycloalkyl group, (52) any one selected from (45) to (49)
In one term, R^4aBut C₁-C_TenConversion to an alkyl group
Compound, any one selected from (53), (45) to (49)
In one term, R^4aBut C₁-C₆Compounds that are alkyl groups
Object, any one selected from (54), (45) to (49)
In one term, R^4aIs a methyl or ethyl group
Object, any one selected from (55), (45) to (54)
In one aspect, Ar is phenyl, furyl, thienyl,
Benzothienyl group or a group selected from the above-mentioned substituent group a
1 to 4 phenyl, furyl, thienyl,
Or a compound which is a benzothienyl group, (56) any one selected from (45) to (54)
In one embodiment, Ar is a thienyl group or the substituent group a
A thienyl group substituted by 1 to 4 groups with a group selected from
A compound, (57) any one selected from (45) to (54)
In one embodiment, Ar is a benzothienyl group or the above substituted
Benzo substituted with 1 to 4 groups selected from group a
A compound which is a thienyl group, (58) any one selected from (45) to (57)
In one embodiment, a compound wherein m is 0, (59) any one selected from (45) to (57)
In one embodiment, the substituent group a is a halogen atom, a hydroxyl group,
Lower alkyl group, halogeno lower alkyl group, lower alcohol
Xy group, carboxy group, lower aliphatic acyl group, lower fat
Aromatic acylamino, amino, cyano and nitro groups
Some compounds. (60) Further, the present invention provides a compound represented by the following general formula (XLIVa):
Or a method for producing a compound having (XLIVb).
You. That is, the general formula (XLII)

[0052]

Embedded image

[Wherein, R¹And R^TwoAre the same or different
Represents a protecting group for a hydrogen atom or an amino group;^4aIs C
₁-C₂₀Alkyl group, heteroatom intervening C_Two-C₂₀A
Substituted with an alkyl group, aryl group or aromatic heterocyclic group
C₁-C₂₀Alkyl group, C_Two-C ₂₀Alkynyl group, f
C with a terrorist atom_Three-C₂₀Alkynyl group, aryl
Substituted by a group or an aromatic heterocyclic group_Two-C₂₀Al
Quinyl group, C_Two-C₂₀Alkenyl group, heteroatom interposed
C_Three-C₂₀Alkenyl group, aryl group or aromatic
Substituted with a heterocyclic group_Two-C₂₀Alkenyl group, ant
Atom substituted by a thiol group or an aromatic heterocyclic group
Intervening C_Two-C₂₀Alkyl group or cycloalkyl
Represents a hydroxyl group. 2-substituted-2-amino-1, represented by the formula:
Only one hydroxy group of the 3-propanediol derivative
With the formula (XLIII) R in the presence of lipase¹¹COOCH = CH_Two (XLIII) A carboxylic acid vinyl ester derivative having the formula:¹¹
Is R^4aAnd the same groups as in the definition of )
Wherein the compound has the general formula (X)
2-substituted-represented by LIVa) or (XLIVb)
2-amino-1,3-propanediol monoester
Derivative

[0054]

Embedded image

Wherein R ¹ , R ² , R ^4a and R ¹¹ have the same meaning as described above. ] Manufacturing method.

In the above, preferably, in (61) and (60), a production method wherein ^one of R ¹ and R ² is a hydrogen atom and the other is a protecting group for an amino group, (62) (60) or (60) 61) wherein R ^4a is C ₁
-C ₁₀ alkyl group, C ₂ -C ₁₀ alkyl group which heteroatom is interposed, an aryl group or an aromatic heterocyclic C ₁ -C ₁₀ alkyl group substituted with a group, C ₂ -C ₁₀ alkynyl group, a hetero atom intervening C ₃ -C ₁₀ alkynyl group, C ₃ an aryl group or an aromatic heterocyclic C ₂ -C ₁₀ alkynyl group substituted with a group, C ₂ -C ₁₀ alkenyl group, a hetero atom-mediated
-C ₁₀ alkenyl, C ₂ an aryl group or an aromatic heterocyclic C ₂ -C ₁₀ alkenyl group substituted with a group, a hetero atom substituted by an aryl group or an aromatic heterocyclic group interposed -
C ₁₀ alkyl group, or a method for producing a C ₅ -C ₁₀ cycloalkyl group, in (62) (60) or (61), R ^4a is, C ₁
-C ₁₀ alkyl group, C ₂ -C ₁₀ alkyl group which heteroatoms are mediated, C ₁ -C ₁₀ alkyl group substituted with an aryl group or an aromatic heterocyclic group, C ₂ -C ₁₀ alkynyl group, C ₂ -
C ₁₀ alkenyl group, or a method for producing a C ₅ -C ₁₀ cycloalkyl group, in any one selected from (63) (60) to (62), R ¹¹ is, C ₁ -C ₂₀ An alkyl group, or
C ₁ -C substituted with an aryl group or a heteroaryl group
_A production method in which the compound is a ₂₀ alkyl group can be mentioned.

In the above formula, X, R ⁵ , Ar and substituent group b
"Aryl group", "aryl group substituted by 1 to 3 groups selected from substituent group a" in definition, and "1 to 3 groups selected from substituent groups a and b" The aryl part of the "substituted aryl group" and the "aryl group substituted by 1 to 5 groups selected from the substituent group a" includes, for example, phenyl, indenyl and naphthyl. Carbon number 6
There may be mentioned up to 10 aromatic hydrocarbon groups, preferably a phenyl or naphthyl group, most preferably a phenyl group.

In the above formula, “C ₁ -C ₁₀ ” in the definition of Y
The C ₁ -C ₁₀ alkylene part of the “alkylene group” and the “C ₁ -C ₁₀ alkylene group substituted by 1 to 3 groups selected from the substituent groups a and b” is methylene, methylmethylene, ethylene, propylene. , Trimethylene, 1-methylethylene, tetramethylene, 1-methyltrimethylene,
2-methyltrimethylene, 3-methyltrimethylene, 1
-Methylpropylene, 1,1-dimethylethylene, pentamethylene, 1-methyltetramethylene, 2-methyltetramethylene, 3-methyltetramethylene, 4-methyltetramethylene, 1,1-dimethyltrimethylene, 2,
2-dimethyltrimethylene, 3,3-dimethyltrimethylene, hexamethylene, 1-methylpentamethylene, 2
-Methylpentamethylene, 3-methylpentamethylene,
4-methylpentamethylene, 5-methylpentamethylene, 1,1-dimethyltetramethylene, 2,2-dimethyltetramethylene, 3,3-dimethyltetramethylene,
4,4-dimethyltetramethylene, heptamethylene, 1
-Methylhexamethylene, 2-methylhexamethylene,
5-methylhexamethylene, 3-ethylpentamethylene, octamethylene, 2-methylheptamethylene, 5-
Methylheptamethylene, 2-ethylhexamethylene, 2
-Ethyl-3-methylpentamethylene, 3-ethyl-2
Such as -methylpentamethylene, nonamethylene, 2-methyloctamethylene, 7-methyloctamethylene, 4-ethylheptamethylene, 3-ethyl-2-methylhexamethylene, 2-ethyl-1-methylhexamethylene, and decamethylene It is a linear or branched alkylene group having 1 to 10 carbon atoms, preferably a C ₁ -C ₆ alkylene group, more preferably a C ₁ -C ₅ alkylene group, more preferably, It is an ethylene, trimethylene or tetramethylene group, most preferably an ethylene or trimethylene group.

In the above formula, "C _1- having an oxygen atom or a sulfur atom in a carbon chain or at a chain end in the definition of Y"
A "C ₁₀ alkylene group" and a "C ₁ -C ₁₀ alkylene group having an oxygen atom or a sulfur atom in a carbon chain or at a chain end substituted with 1 to 3 groups selected from substituent groups a and b". , part "C ₁ -C ₁₀ alkylene having oxygen atom or sulfur atom in the carbon chain during or chain ends" has an oxygen atom or a sulfur atom in the chain end or chain of the "C ₁ -C ₁₀ alkylene group" Group, for example,-
_{O-CH 2 -, - O-} (CH 2) 2 -, - O- (CH 2) 3
_{-, - O- (CH 2)} 4 -, - O- (CH 2) 5 -, - O-
_{(CH 2) 6 -, -} O- (CH 2) 7 -, - O- (CH 2) 8
_{-, - O- (CH 2)} 9 -, - O- (CH 2) 10 -, - C
H ₂ —O—CH ₂ —, —CH ₂ —O— (CH ₂ ) ₂ —, —C
H ₂ —O— (CH ₂ ) ₃ —, —CH ₂ —O— (CH ₂ ) ₄ —,
— (CH ₂ ) ₂ —O—CH ₂ —, — (CH ₂ ) ₂ —O— (C
_{H 2) 2 -, - (} CH 2) 2 -O- (CH 2) 3 -, - (CH
_{2) 2 -O- (CH 2)} 4 -, - (CH 2) 3 -O-CH
_{2 -, - (CH 2)} 3 -O- (CH 2) 2 -, - (CH 2) 3
_{-O- (CH 2) 3 -,} - (CH 2) 4 -O-CH 2 -, -
_{(CH 2) 4 -O- (CH} 2) 2 -, - (CH 2) 5 -O-C
_{H 2 -, - CH 2 -O} -, - (CH 2) 2 -O -, - (CH
_{2) 3 -O -, - (} CH 2) 4 -O -, - (CH 2) 5 -O
_{-, - (CH 2) 6} -O -, - (CH 2) 7 -O -, - (C
_{H 2) 8 -O -, -} (CH 2) 9 -O -, - (CH 2) 10 -
_{O -, - S-CH 2} -, - S- (CH 2) 2 -, - S-
_{(CH 2) 3 -, -} S- (CH 2) 4 -, - S- (CH 2) 5
_{-, - S- (CH 2)} 6 -, - S- (CH 2) 7 -, - S-
_{(CH 2) 8 -, -} S- (CH 2) 9 -, - S- (CH 2)
_{10 -, - CH 2 -S-} CH 2 -, - CH 2 -S- (CH 2)
_{2 -, - CH 2 -S- (} CH 2) 3 -, - CH 2 -S- (C
_{H 2) 4 -, - (} CH 2) 2 -S-CH 2 -, - (CH 2) 2
_{-S- (CH 2) 2 -,} - (CH 2) 2 -S- (CH 2)
_{3 -, - (CH 2)} 2 -S- (CH 2) 4 -, - (CH 2) 3
_{-S-CH 2 -, - (} CH 2) 3 -S- (CH 2) 2 -, -
_{(CH 2) 3 -S- (CH} 2) 3 -, - (CH 2) 4 -S-C
_{H 2 -, - (CH 2} ) 4 -S- (CH 2) 2 -, - (CH 2)
_{5 -S-CH 2 -, -} CH 2 -S -, - (CH 2) 2 -S
_{-, - (CH 2) 3} -S -, - (CH 2) 4 -S -, - (C
_{H 2) 5 -S -, -} (CH 2) 6 -S -, - (CH 2) 7 -S
_{-, - (CH 2) 8} -S -, - (CH 2) 9 -S -, - (C
H ₂₎ is a group having ₁₀ -S-, preferably a C ₁ -C ₆ alkylene group having an oxygen atom in the carbon chain or the chain ends, more preferably, -O-CH ₂ -, -O- (C
_{H 2) 2 -, - O-} (CH 2) 3 -, - CH 2 -O -, -
A group having (CH ₂ ) ₂ —O— or — (CH ₂ ) ₃ —O—, most preferably —CH ₂ —O—, —O— (CH ₂ )
₂ - or - (CH ₂₎ a group having ₂ -O-.

In the above formula, “cycloalkyl group”, “substituent group a” in the definition of R ^4a , R ⁵ , R ¹¹ and substituent group b
A cycloalkyl group substituted by 1 to 3 groups with a group selected from and a cycloalkyl group substituted by 1 to 3 groups with a group selected from a substituent group a and b are, for example, A saturated carbocyclic group having 3 to 10 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, adamantyl, and indanyl; and a condensed ring with another cyclic group such as a benzene ring. You may have. As the cycloalkyl group in the definition of R ⁵ and the substituent group b,
Preferably a C ₅ -C ₆ cycloalkyl group, most preferably a cyclohexyl group. On the other hand, the cycloalkyl group in the definition of R ^4a and R ¹¹ is preferably C ₅ -C
_{It is a 10} cycloalkyl group.

In the above formula, 1 to 5 of the groups selected from the “aromatic heterocyclic group” and the “substituent group a” in the definition of Ar
The “substituted aromatic heterocyclic group” refers to a 5- to 7-membered heterocyclic group containing 1 to 3 sulfur atoms, oxygen atoms, and / or nitrogen atoms, and examples thereof include furyl, thienyl, pyrrolyl, azepinyl, and pyrazolyl. , Imidazolyl, oxazolyl,
Isoxazolyl, thiazolyl, isothiazolyl, 1,
Examples thereof include aromatic heterocyclic groups such as 2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, and pyrazinyl.

The above "aromatic heterocyclic group" may be condensed with another cyclic group. Isoindolyl, indolyl, indazolyl, purinyl, quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl,
Groups such as quinoxalinyl, quinazolinyl, carbazolyl, carbolinyl, acridinyl, isoindolinyl can be mentioned. Preferably, such "aromatic heterocyclic group" is a phenyl, furyl, thienyl, benzothienyl group, most preferably a thienyl or benzothienyl group.

In the above formula, “heterocyclic group” in the definition of R ⁵ and the substituent group b, and “1 is a group selected from the substituent group a.
To 3 substituted heterocyclic groups "and" substituent groups a and b
The heterocyclic group portion of the "heterocyclic group substituted by 1 to 3 groups selected from" represents a 5- to 7-membered heterocyclic group containing 1 to 3 sulfur atoms, oxygen atoms and / or nitrogen atoms, For example, the above "aromatic heterocyclic group", and tetrahydropyranyl, morpholinyl, thiomorpholinyl, pyrrolidinyl,
Partially or completely reduced saturated heterocyclic groups corresponding to these groups such as pyrrolinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl and pyrazolidinyl can be mentioned. Such a heterocyclic group is preferably a 5- or 6-membered aromatic heterocyclic group, most preferably a morpholinyl, thiomorpholinyl or piperidinyl group.

In the above formula, the “halogen atom” in the definition of the substituent group “a” is a fluorine, chlorine, bromine or iodine atom.
Preferably it is a fluorine atom or a chlorine atom, most preferably a fluorine atom.

In the above formula, the “lower alkyl group” in the definition of R ⁴ and the substituent group a is, for example, methyl, ethyl,
Propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl,
3,3-dimethylbutyl, 2,2-dimethylbutyl,
1,1-dimethylbutyl, 1,2-dimethylbutyl,
1,3-dimethylbutyl, 2,3-dimethylbutyl, 1
1-carbon group such as ethylbutyl and 2-ethylbutyl groups
From 6 to 6 linear or branched alkyl groups, preferably C ₁ -C ₄ alkyl groups, more preferably C ₁ -C ₂ alkyl groups, most preferably methyl group .

In the above formula, the “halogeno lower alkyl group” in the definition of the substituent group “a” refers to a group in which the above “lower alkyl group” is substituted by a halogen atom. Dichloromethyl, dibromomethyl, fluoromethyl, 2,
2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2-iodoethyl, 3-chloropropyl, 4-fluorobutyl, 6-io- Dohexyl, 2,2
A halogeno C ₁ -C ₆ alkyl group, such as a dibromoethyl group, preferably a halogeno C ₁ -C ₄ alkyl group, more preferably a halogeno C ₁ -C ₂ alkyl group;
Most preferably, it is a trifluoromethyl group.

In the above formula, the “lower alkoxy group” in the definition of the substituent group “a” indicates a group in which the above “lower alkyl group” is bonded to an oxygen atom, for example, methoxy, ethoxy,
Propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, pentoxy, isopentoxy, 2-methylbutoxy, 1-ethylpropoxy, 2-ethylpropoxy, neopentoxy, hexyloxy, 4-methylpentoxy, 3-methyl Pentoxy, 2-methylpentoxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,3-dimethylbutoxy 1 carbon such as a group
From 6 to 6 linear or branched alkoxy groups, preferably C ₁ -C ₄ alkoxy groups, more preferably C ₁ -C ₂ alkoxy groups.
An alkoxy group, most preferably a methoxy group.

In the above formula, the “lower alkylthio group” in the definition of the substituent group “a” indicates a group in which the above “lower alkyl group” is bonded to a sulfur atom, such as methylthio, ethylthio, propylthio, isopropylthio, butylthio,
Isobutylthio, s-butylthio, t-butylthio, pentylthio, isopentylthio, 2-methylbutylthio, neopentylthio, hexylthio, 4-methylpentylthio, 3-methylpentylthio, 2-methylpentylthio, 3,3 -Dimethylbutylthio, 2,2-dimethylbutylthio, 1,1-dimethylbutylthio, 1,2-
Dimethylbutylthio, 1,3-dimethylbutylthio,
1 to 6 carbon atoms such as 2,3-dimethylbutylthio group
Linear or branched alkylthio groups, preferably
An ₁ -C ₄ alkylthio group, more preferably a C ₁ -C ₂ alkylthio group, most preferably a methylthio group.

In the above formula, the “lower alkoxycarbonyl group” in the definition of the substituent group “a” indicates a group in which the above “lower alkoxy group” is bonded to a carbonyl group, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, Propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, s-butoxycarbonyl, t-butoxycarbonyl, pentoxycarbonyl,
Isopentoxycarbonyl, 2-methylbutoxycarbonyl, neopentoxycarbonyl, hexyloxycarbonyl, 4-methylpentoxycarbonyl, 3-methylpentoxycarbonyl, 2-methylpentoxycarbonyl, 3,3-dimethylbutoxycarbonyl, 2 , 2-dimethylbutoxycarbonyl, 1,1-dimethylbutoxycarbonyl, 1,2-dimethylbutoxycarbonyl,
A linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms such as 1,3-dimethylbutoxycarbonyl, 2,3-dimethylbutoxycarbonyl,
Suitable a C ₁ -C ₄ alkoxycarbonyl group, a still more preferably C ₁ -C ₂ alkoxycarbonyl group, most preferably a methoxycarbonyl group.

In the above formula, the “lower aliphatic acyl group” in the definition of the substituent group “a” represents a group in which a hydrogen atom or a saturated or unsaturated chain hydrocarbon group is bonded to a carbonyl group. Acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, acryloyl, methacryloyl,
It is a linear or branched lower aliphatic acyl group having 1 to 7 carbon atoms such as a crotonoyl group, preferably a C ₁ -C ₄ lower aliphatic acyl group, more preferably an acetyl or propionyl group. And most preferably an acetyl group.

In the above formula, the “mono-lower alkylamino group” in the definition of the substituent group “a” has the same meaning as described above in which one “lower alkyl group” is bonded to an amino group. Amino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, s-butylamino, t-butylamino, pentylamino, isopentylamino, 2-methylbutylamino, neopentylamino, 1-ethylpropylamino, Hexylamino, isohexylamino, 4-methylpentylamino, 3-methylpentylamino, 2-methylpentylamino, 1-methylpentylamino, 3,3
-Dimethylbutylamino, 2,2-dimethylbutylamino, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,3
A mono-C ₁ -C ₆ alkylamino group, such as -dimethylbutylamino or 2-ethylbutylamino group, preferably a mono-C ₁ -C ₄ alkylamino group, and more preferably a mono-C ₁ -C ₄ alkylamino group. an ₁ -C ₂ alkylamino group, and most preferably a methylamino group.

In the above formula, the “di-lower alkylamino group” in the definition of the substituent group “a” is the above “lower alkyl group”
Represents a group bonded to two amino groups, for example, di-C ₁ -C such as dimethylamino, diethylamino, N-ethyl-N-methylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino group. ₆ alkylamino group, preferably a di -C ₁ -C ₄ alkylamino group, more preferably a di -C ₁ -C ₂ alkylamino group, most preferably a dimethylamino group.

In the above formula, the “lower aliphatic acylamino group” in the definition of the substituent group “a” refers to a group in which the above “lower aliphatic acyl group” is bonded to an amino group, for example, formylamino, acetylamino, propionyl C1-C7 linear or branched lower fatty acids such as amino, butyrylamino, isobutyrylamino, valerylamino, isovalerylamino, pivaloylamino, hexanoylamino, acryloylamino, methacryloylamino, crotonoylamino groups Group, preferably an acetylamino or propionylamino group, most preferably an acetylamino group.

In the above formula, the term “amino-protecting group” in the definition of R ¹ and R ² means an amino-protecting group generally used in the field of synthetic organic chemistry. A lower alkyl group ";a" lower aliphatic acyl group ", a halogeno lower aliphatic acyl group such as chloroacetyl, dichloroacetyl, trichloroacetyl, and trifluoroacetyl; and a lower aliphatic group substituted with a lower alkoxy group such as methoxyacetyl. “Aliphatic acyls” such as an acyl group; aromatic acyl groups such as benzoyl, 1-indancarbonyl, 2-indancarbonyl, 1- or 2-naphthoyl, 4-chlorobenzoyl, 4-fluorobenzoyl, 2,4 , 6-trimethylbenzoyl, 4-
Toluoyl, 4-anisoyl 4-nitrobenzoyl, 2
"Aromatic acyls" such as aromatic acyl groups substituted by 1 to 3 groups selected from the above-mentioned substituent group a, such as -nitrobenzoyl, 2- (methoxycarbonyl) benzoyl, 4-phenylbenzoyl; The aforementioned “lower alkoxycarbonyl group”, “alkoxycarbonyls” such as a lower alkoxycarbonyl group substituted with halogen such as 2,2,2-trichloroethoxycarbonyl, 2-trimethylsilylethoxycarbonyl or tri-lower-alkylsilyl; vinyloxy “Alkenyloxycarbonyls” such as carbonyl, allyloxycarbonyl;
Aralkyloxycarbonyl groups such as benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl,
An aralkyloxycarbonyl group substituted by 1 to 3 groups selected from the above-mentioned substituent group a, such as 3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, and 4-nitrobenzyloxycarbonyl; Aralkyloxycarbonyls "; tri-lower alkylsilyl groups such as trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-t-butylsilyl, triisopropylsilyl, diphenylmethylsilyl, diphenylbutylsilyl "Silyls" such as a silyl group tri-substituted with aryl or aryl and lower alkyl such as diphenylisopropylsilyl, phenyldiisopropylsilyl; benzyl,
Lower substituted with 1 to 3 aryl groups such as phenethyl, 3-phenylpropyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, 9-anthrylmethyl Alkyl group, 4-methylbenzyl, 2,4,6-
Trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, -Cyanobenzyldiphenylmethyl,
"Aralkyls" such as lower alkyl groups substituted with one to three aryl groups in which the aryl ring is substituted with lower alkyl such as bis (2-nitrophenyl) methyl and piperonyl, lower alkoxy, nitro, halo or cyano ";
And N, N-dimethylaminomethylene, benzylidene, 4-methoxybenzylidene, 4-nitrobenzylidene, salicylidene, 5-chlorosalicylidene, diphenylmethylene, (5-chloro-2-hydroxyphenyl)
"Substituted methylene groups which form a Schiff base" such as phenylmethylene are included, and are preferably substituted by 1 to 3 groups with a lower alkoxycarbonyl group, an aralkyloxycarbonyl group or a group selected from substituent group a. Aralkyloxycarbonyl group.

The “protecting group for hydroxy group” in the definition of R ³ and R ^3a includes hydrogenolysis, hydrolysis, electrolysis,
It indicates "a general protecting group in a reaction" that can be cleaved by a chemical method such as photolysis, and "a protecting group that can be cleaved by a biological method such as hydrolysis in a living body".

Such a “common protecting group in the reaction”
For example, the above “lower alkyl group”; the above “aliphatic acyls”; the above “aromatic acyls”; tetrahydropyran-2-yl, 3-bromotetrahydropyran-2
-Yl, 4-methoxytetrahydropyran-4-yl,
"Tetrahydropyranyl or tetrahydrothiopyranyls" such as tetrahydrothiopyran-2-yl and 4-methoxytetrahydrothiopyran-4-yl; tetrahydrofuran-2-yl, tetrahydrothiofuran-2-
“Tetrahydrofuranyl or tetrahydrothiofuranyl” such as il; the aforementioned “silyl”; methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, t-methyl A lower alkoxymethyl group such as butoxymethyl, a lower alkoxylated lower alkoxymethyl group such as 2-methoxyethoxymethyl, 2,2,2-
Trichloroethoxymethyl, bis (2-chloroethoxy)
“Alkoxymethyl group” such as halogeno lower alkoxymethyl such as methyl; 1-ethoxyethyl, 1- (
"Substituted ethyls" such as lower alkoxylated ethyl groups such as isopropoxyethyl and halogenated ethyl groups such as 2,2,2-trichloroethyl; the above "aralkyls"; the above "alkoxycarbonyls";“Alkenyloxycarbonyls”; the above-mentioned “aralkyloxycarbonyl groups” can be mentioned.

On the other hand, examples of the “protecting group that can be cleaved in vivo by a biological method such as hydrolysis” include, for example, ethylcarbonyloxymethyl, pivaloyloxymethyl, dimethylaminoacetyloxymethyl, 1-acetoxy Acyloxyalkyls such as ethyl; 1- (methoxycarbonyloxy) ethyl, 1- (ethoxycarbonyloxy) ethyl, ethoxycarbonyloxymethyl, 1- (isopropoxycarbonyloxy) ethyl,
1- (t-butoxycarbonyloxy) ethyl, 1-
1- such as (ethoxycarbonyloxy) propyl, 1- (cyclohexyloxycarbonyloxy) ethyl
(Alkoxycarbonyloxy) alkyls; phthalidyl group; 4-methyl-oxodioxorenylmethyl, 4-
"Carbonyloxyalkyls" such as oxodioxorenylmethyl groups such as phenyl-oxodioxorenylmethyl and oxodioxorenylmethyl; "aliphatic acyls";"aromaticacyls";"Half ester salt residue of succinic acid";"phosphateresidue";"ester forming residue of amino acid"; carbamoyl group; aralkylidene group such as benzylidene; alkoxyethylidene group such as methoxyethylidene and ethoxyethylidene. Oxomethylene; "two protecting groups for hydroxy group" such as thioxomethylene; and "carbonyloxyalkyloxycarbonyl group" such as pivaloyloxymethyloxycarbonyl, and derivatives thereof. Or not by intravenous injection into experimental animals such as rats and mice. And, it examines the body fluids of the subsequent animal,
It can be determined by detecting the original compound or a pharmacologically acceptable salt thereof. As the protecting group for such a hydroxy group, preferably, an aromatic acyl group substituted by 1 to 3 groups selected from a lower alkyl group, a lower aliphatic acyl group, an aromatic acyl group or a substituent group a It is.

In the above, specific examples of “cycloalkyl group substituted by 1 to 3 groups selected from substituent groups a and b” in the definition of R ⁵ include, for example, 2-fluorocyclopropyl, 2-fluorocyclopropyl, -Chlorocyclopropyl, 2
-Or 3-fluorocyclopentyl, 2- or 3-chlorocyclopentyl, 2-, 3- or 4-fluorocyclohexyl, 2-, 3- or 4-chlorocyclohexyl, 2-, 3- or 4-bromocyclohexyl, 2- , 3- or 4-iodocyclohexyl, 2-methylcyclopropyl, 2-ethylcyclopropyl, 2- or 3-methylcyclopentyl, 2- or 3-ethylcyclopentyl, 2-, 3- or 4-methylcyclohexyl, 2-, 3- or 4-ethylcyclohexyl, 2-trifluoromethylcyclopropyl, 2- or 3-trifluoromethylcyclobutyl, 2- or 3-trifluoromethylcyclopentyl, 2-, 3- or 4-trifluoro Methylcyclohexyl, 2- Toxycyclopropyl, 2- or 3-methoxycyclobutyl, 2- or 3-methoxycyclopentyl, 2-, 3- or 4-methoxycyclohexyl, 2-, 3- or 4-ethoxycyclohexyl, 2-, 3- or 4 -Propoxycyclohexyl, 2-, 3- or 4-isopropoxycyclohexyl, 2-, 3- or 4- (1-ethylpropoxy) cyclohexyl, 2-, 3- or 4- (2-
Ethylpropoxy) cyclohexyl, 2-carboxylcyclopropyl, 2- or 3-carboxylcyclopentyl, 2-, 3- or 4-carboxylcyclohexyl, 2-methoxycarbonylcyclopropyl, 2
-Or 3-methoxycarbonylcyclopentyl, 2
-, 3- or 4-methoxycarbonylcyclohexyl, 2-hydroxycyclopropyl, 2- or 3-
Hydroxycyclopentyl, 2-, 3- or 4-hydroxycyclohexyl, 2-formylcyclopropyl, 2- or 3-formylcyclopentyl, 2-,
3- or 4-formylcyclohexyl, 2-acetylcyclopropyl, 2- or 3-acetylcyclopentyl, 2-, 3- or 4-acetylcyclohexyl, 2-aminocyclopropyl, 2- or 3-aminocyclopentyl, 2-, 3- or 4-aminocyclohexyl, 2-methylaminocyclopropyl, 2- or 3-methylaminocyclobutyl, 2- or 3
-Methylaminocyclopentyl, 2-, 3- or 4
-Methylaminocyclohexyl, 2-dimethylaminocyclopropyl, 2- or 3-dimethylaminocyclobutyl, 2- or 3-dimethylaminocyclopentyl, 2-, 3- or 4-dimethylaminocyclohexyl, 2-cyanocyclopropyl, 2 -Or 3-cyanocyclopentyl, 2-, 3- or 4-cyanocyclohexyl, 2- or 3-cyclohexylcyclopentyl, 2-, 3- or 4-cyclohexylcyclohexyl, 2-phenylcyclopropyl, 2- or 3-phenylcyclopentyl , 2-, 3- or 4
-Phenylcyclohexyl, 3,4-difluorocyclohexyl, 3,4-dichlorocyclohexyl, 2,3-
Dimethoxycyclohexyl, 3,4-dimethoxycyclohexyl, 3,5-dimethoxycyclohexyl, 3,
A 4,5-trimethoxycyclohexyl group, preferably a cycloalkyl group substituted with 1 to 3 substituents (the substituent may be a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, , A lower alkylthio group and a lower aliphatic acyl group), more preferably a cycloalkyl group substituted with 1 to 3 substituents (the substituent is a halogen atom, a lower An alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower aliphatic acyl group), and more preferably a cyclohexyl group substituted with 1 to 3 substituents (the substituent Is a group selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower aliphatic acyl group.) Most preferably, 1 to 3 substituted cyclohexyl groups, wherein said substituents are groups selected from the group consisting of fluorine, chlorine, methyl, trifluoromethyl, methoxy and acetyl. is there.

In the above, specific examples of “aryl group substituted by 1 to 3 groups selected from substituent groups a and b” in the definition of R ⁵ include, for example, 2-, 3- or 4-fluorophenyl, 2-, 3- or 4-
Chlorophenyl, 2-, 3- or 4-bromophenyl, 2-, 3- or 4-iodophenyl, 2-, 3
-Or 4-methylphenyl, 2-, 3- or 4
-Ethylphenyl, 2-, 3- or 4-propylphenyl, 2-, 3- or 4-butylphenyl, 2
-, 3- or 4-pentylphenyl, 2-, 3- or 4-trifluoromethylphenyl, 2-, 3- or 4-methoxyphenyl, 2-, 3- or 4-
Ethoxyphenyl, 2-, 3- or 4-propoxyphenyl, 2-, 3- or 4-isopropoxyphenyl, 2-, 3- or 4-butoxyphenyl, 2
-, 3- or 4- (1-ethylpropoxy) phenyl, 2-, 3- or 4- (2-ethylpropoxy)
Phenyl, 2-, 3- or 4-methylthiophenyl, 2-, 3- or 4-ethylthiophenyl, 2
-, 3- or 4-carboxylphenyl, 2-, 3
-Or 4-methoxycarbonylphenyl, 2-, 3
-Or 4-ethoxycarbonylphenyl, 2-, 3
-Or 4-hydroxyphenyl, 2-, 3- or 4-formylphenyl, 2-, 3- or 4-acetylphenyl, 2-, 3- or 4-aminophenyl, 2-, 3- or 4-methylamino Phenyl, 2
-, 3- or 4-dimethylaminophenyl, 2-,
3- or 4-cyanophenyl, 2-, 3- or 4-cyclopentylphenyl, 2-, 3- or 4-
Cyclohexylphenyl, 2-, 3- or 4-biphenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2,4-
Dichlorophenyl, 3,4-dichlorophenyl, 3,5
-Dichlorophenyl, 3,4-dibromophenyl, 2,
3-dimethylphenyl, 3,4-dimethylphenyl,
3,5-dimethylphenyl, 2,3-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 3-fluoro-4-methoxyphenyl, 4-methyl -2-methoxyphenyl, 6-fluoro-4-methyl-2-methoxyphenyl, 5-fluoroinden-3-yl, 5-fluoroinden-3-yl, 5-methylinden-3-
Yl, 5-methoxyinden-3-yl, 5-fluoroinden-2-yl, 5-chloroinden-2-yl,
5-methylinden-2-yl, 5-methoxyinden-2-yl, 5-hydroxyinden-3-yl, 5-
Nitroinden-3-yl, 5-cyclohexylinden-3-yl, 5-phenylinden-3-yl, 5-
Phenoxyinden-3-yl, 5-benzyloxyinden-3-yl, 5-phenylthioinden-3-yl, 5-hydroxyinden-2-yl, 5-nitroinden-2-yl, 5-cyclohexylindene- 2-
Yl, 5-phenylinden-2-yl, 5-fluoronaphthalen-2-yl, 5-fluoronaphthalen-2-
Yl, 5-methylnaphthalen-2-yl, 5-methoxynaphthalen-2-yl, 5-fluoronaphthalen-1-
Yl, 5-fluoronaphthalen-1-yl, 5-methylnaphthalen-1-yl, 5-methoxynaphthalene-1-
Yl, 5-hydroxynaphthalen-2-yl, 5-nitronaphthalen-2-yl, 5-cyclohexylnaphthalen-2-yl, 5-phenylnaphthalen-2-yl,
-Phenoxynaphthalen-2-yl, 5-benzyloxynaphthalen-2-yl, 5-phenylthionaphthalen-2-yl, 5-hydroxynaphthalen-1-yl,
-Nitronaphthalen-1-yl, 5-cyclohexylnaphthalen-1-yl and 5-phenylnaphthalen-1-yl groups, preferably 1 to 3 substituted aryl groups (the substituents being A halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, a lower alkylthio group and a lower aliphatic acyl group.), And more preferably 1 to 3 substituents Aryl group (the substituent is a group selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower aliphatic acyl group), which is more preferable. Is a phenyl group substituted with 1 to 3 substituents (the substituents include a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower aliphatic acyl group) And more preferably still more preferably 1 to 3 substituted phenyl groups, wherein said substituents are fluorine, chlorine, methyl, trifluoromethyl, methoxy and Acetyl group), most preferably 3-fluorophenyl, 4-fluorophenyl,
3,4-difluorophenyl, 3,5-difluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,
4-dichlorophenyl, 3,5-dichlorophenyl, 3
-Methylphenyl, 4-methylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,4-ditrifluoromethylphenyl, 3,5-
Ditrifluoromethylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 3-acetylphenyl or 4-acetylphenyl is there.

In the above, specific examples of “heterocyclic group substituted by 1 to 3 groups selected from substituent groups a and b” in the definition of R ⁵ include, for example, 3-, 4- or 5 -Methylfuran-2-yl, 2-, 4- or 5-methylfuran-3-yl, 3-, 4- or 5-
Fluorothiophen-2-yl, 2-, 4- or 5
-Fluorofuran-3-yl, 3-, 4- or 5-
Bromothiophen-2-yl, 2-, 4- or 5-
Bromofuran-3-yl, 3-, 4- or 5-methylthiophen-2-yl, 2-, 4- or 5-methylthiophen-3-yl, 3-, 4- or 5-ethylthiophen-2-yl 2-, 4- or 5-ethylthiophen-3-yl, 3-, 4- or 5-methoxythiophen-2-yl, 2-, 4- or 5-methoxythiophen-3-yl, 3- or 4 -Methylthiazol-5-yl, 3-, 4- or 5-fluorobenzothiophen-2-yl, 3-, 4- or 5
-Bromobenzothiophen-2-yl, 3-, 4- or 5-methylbenzothiophen-2-yl, 3-, 4
-Or 5-methoxybenzothiophen-2-yl,
2-, 4- or 5-fluorobenzothiophene-3
-Yl, 2-, 4- or 5-bromobenzothiophen-3-yl, 2-, 4- or 5-methylbenzothiophen-3-yl, 2-, 4- or 5-methoxybenzothiophen-3-yl , 4-, 5-, 6- or 7-methylbenzothiophen-2-yl, 3-, 4-
Or 5-hydroxyfuran-2-yl, 2-, 4-
Or 5-hydroxyfuran-3-yl, 3-, 4-
Or 5-hydroxythiophen-2-yl, 3-,
4- or 5-nitrothiophen-2-yl, 3-,
4- or 5-phenylthiophen-2-yl, 2
-, 4- or 5-hydroxythiophen-3-yl, 2-, 4- or 5-cyanothiophen-3-yl, 1-, 2- or 3-hydroxypyridine-4-
Yl, 1-, 2- or 3-cyanopyridin-4-yl, 1-, 2- or 3-phenylpyridin-4-yl, preferably 3-, 4- or 5-fluorothiophene- 2-yl or 2-, 4- or 5-fluorofuran-3-yl group.

In the above, the “C ₁ -C ₂₀ alkyl group” in the definition of R ^4a and R ¹¹ is, for example, the above “lower alkyl group”, heptyl, 1-methylhexyl, 2-methylhexyl, 3-methyl Hexyl, 4-methylhexyl, 5-methylhexyl, 1-propylbutyl, 4,4
-Dimethylpentyl, octyl, 1-methylheptyl,
2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl, 6-methylheptyl,
1-propylpentyl, 2-ethylhexyl, 5,5-
Dimethylhexyl, nonyl, 3-methyloctyl, 4-
Methyloctyl, 5-methyloctyl, 6-methyloctyl, 1-propylhexyl, 2-ethylheptyl,
6,6-dimethylheptyl, decyl, 1-methylnonyl, 3-methylnonyl, 8-methylnonyl, 3-ethyloctyl, 3,7-dimethyloctyl, 7,7-dimethyloctyl, undecyl, 4,8-dimethylnonyl, dodecyl , Tridecyl, tetradecyl, pentadecyl,
3,7,11-trimethyldodecyl, hexadecyl,
4,8,12-trimethyltridecyl, 1-methylpentadecyl, 14-methylpentadecyl, 13,13-dimethyltetradecyl, heptadecyl, 15-methylhexadecyl, octadecyl, 1-methylheptadecyl, nonadecyl, eicosyl, And straight-chain or branched-chain alkyl groups having 1 to 20 carbon atoms such as 3,7,11,15-tetramethylhexadecyl group, and preferably a C ₁ -C ₁₀ alkyl group. And more preferably C ₁ -C ₆
An alkyl group, most preferably a methyl or ethyl group.

[0082] In the above, the "C ₂ -C _{2 0} alkyl group having a heteroatom-mediated" in the definition of R ^4a and R ^11, the "number 2 to carbon atoms of the" C ₁ -C ₂₀ alkyl group ""20 alkyl groups" are the same or different and represent one or two groups intervened by a sulfur atom, an oxygen atom, or a nitrogen atom, for example, methylthiomethyl, 1-methylthioethyl, 2- Methylthioethyl, ethylthiomethyl, 1-methylthiopropyl, 2-methylthiopropyl, 3-methylthiopropyl, 2-ethylthioethyl,
2-methyl-2-methylthioethyl, 1-methylthiobutyl, 2-methylthiobutyl, 3-methylthiobutyl,
2-ethylthiopropyl, 3-methyl-3-methylthiopropyl, 4-methylthiopentyl, 3-methylthiopentyl, 2-methylthiopentyl, 1-methylthiopentyl, 3,3-dimethylthiobutyl, 2,2-dimethylthiobutyl 1,1-dimethylthiobutyl, 1-methyl-2-methylthiobutyl, 1,3-dimethylthiobutyl, 2,3-dimethylthiobutyl, 2-ethylthiobutyl, 1-methylthiohexyl, 2-methylthiohexyl, 3-methylthiohexyl, 4-methylthiohexyl, 5-methylthiohexyl, 1-propylthiobutyl, 4-methyl-4-methylthiopentyl, 1-methylthioheptyl, 2-methylthioheptyl, 3-methylthioheptyl, 4-methylthioheptyl, 5-methylthioheptyl, 6-methylthio Heptyl, 1-propyl thio-pentyl, 2-ethyl-thio-hexyl, 5-methyl-5-
Methylthiohexyl, 3-methylthiooctyl, 4-methylthiooctyl, 5-methylthiooctyl, 6-methylthiooctyl, 1-propylthiohexyl, 2-ethylthioheptyl, 6-methyl-6-methylthioheptyl, 1-methylthiononyl, 3 -Methylthiononyl, 8
-Methylthiononyl, 3-ethylthiooctyl, 3-methyl-7-methylthiooctyl, 7,7-dimethylthiooctyl, 4-methyl-8-methylthiononyl, 3,7
-Dimethyl-11-methylthiododecyl, 4,8-dimethyl-12-methylthiotridecyl, 1-methylthiopentadecyl, 14-methylthiopentadecyl, 13-methyl-13-methylthiotetradecyl, 15-methylthiohexadecyl, 1- Methylthioheptadecyl, and
Alkyloxy having 2 to 20 carbon atoms interposed by one or two sulfur atoms such as 3,7,11-trimethyl-15-methylthiohexadecyl; methyloxymethyl,
1-methyloxyethyl, 2-methyloxyethyl, ethyloxymethyl, 1-methyloxypropyl, 2-methyloxypropyl, 3-methyloxypropyl, 2-
Ethyloxyethyl, 2-methyl-2-methyloxyethyl, 1-methyloxybutyl, 2-methyloxybutyl, 3-methyloxybutyl, 2-ethyloxypropyl, 3-methyl-3-methyloxypropyl, 4-methyl Oxypentyl, 3-methyloxypentyl, 2-methyloxypentyl, 1-methyloxypentyl, 3,
3-dimethyloxybutyl, 2,2-dimethyloxybutyl, 1,1-dimethyloxybutyl, 1-methyl-2
-Methyloxybutyl, 1,3-dimethyloxybutyl, 2,3-dimethyloxybutyl, 2-ethyloxybutyl, 1-methyloxyhexyl, 2-methyloxyhexyl, 3-methyloxyhexyl, 4-methyloxyhexyl , 5-methyloxyhexyl, 1-propyloxybutyl, 4-methyl-4-methyloxypentyl, 1-methyloxyheptyl, 2-methyloxyheptyl, 3-methyloxyheptyl, 4-methyloxyheptyl, 5-methyl Oxyheptyl, 6-methyloxyheptyl, 1-propyloxypentyl, 2-ethyloxyhexyl, 5-methyl-5-methyloxyhexyl, 3-methyloxyoctyl, 4-methyloxyoctyl, 5-methyloxyoctyl, 6 -Methyloxyoctyl, 1-propylo Shihekishiru, 2-ethyl-oxy-heptyl, 6-methyl-6-methyloxy-heptyl,
1-methyloxynonyl, 3-methyloxynonyl, 8
-Methyloxynonyl, 3-ethyloxyoctyl, 3
-Methyl-7-methyloxyoctyl, 7,7-dimethyloxyoctyl, 4-methyl-8-methyloxynonyl, 3,7-dimethyl-11-methyloxidedecyl,
4,8-dimethyl-12-methyloxytridecyl, 1
-Methyloxypentadecyl, 14-methyloxypentadecyl, 13-methyl-13-methyloxytetradecyl, 15-methyloxyhexadecyl, 1-methyloxyheptadecyl, and 3,7,11-trimethyl-
An alkyl group having 2 to 20 carbon atoms interposed by one or two oxygen atoms such as 15-methyloxyhexadecyl; N-methylaminomethyl, 1- (N-methylamino) ethyl, 2- ( N-methylamino) ethyl, N-ethylaminomethyl, 1- (N-methylamino) propyl, 2- (N-methylamino) propyl, 3- (N-methylamino) propyl, 2- (N-ethylamino ) Ethyl, 2- (N, N-dimethylamino) ethyl, 1- (N
-Methylamino) butyl, 2- (N-methylamino) butyl, 3- (N-methylamino) butyl, 2- (N-ethylamino) propyl, 3- (N, N-dimethylamino) propyl, 4- (N-methylamino) pentyl, 3
-(N-methylamino) pentyl, 2- (N-methylamino) pentyl, 1- (N-methylamino) pentyl,
3- (N, N-dimethylamino) butyl, 2- (N, N
-Dimethylamino) butyl, 1- (N, N-dimethylamino) butyl, 1-methyl-2- (N-methylamino)
Butyl, 1,3-di (N-methylamino) butyl, 2,
3-di (N-methylamino) butyl, 2- (N-ethylamino) butyl, 1- (N-methylamino) hexyl,
2- (N-methylamino) hexyl, 3- (N-methylamino) hexyl, 4- (N-methylamino) hexyl, 5- (N-methylamino) hexyl, 1- (N-propylamino) butyl, 4-methyl-4- (N-methylamino) pentyl, 1- (N-methylamino) heptyl, 2- (N-methylamino) heptyl, 3- (N-methylamino) heptyl, 4- (N-methyl Amino) heptyl, 5- (N-methylamino) heptyl, 6- (N-
Methylamino) heptyl, 1- (N-propylamino)
Pentyl, 2- (N-ethylamino) hexyl, 5-methyl-5- (N-methylamino) hexyl, 3- (N-
Methylamino) octyl, 4- (N-methylamino) octyl, 5- (N-methylamino) octyl, 6- (N
-Methylamino) octyl, 1- (N-propylamino) hexyl, 2- (N-ethylamino) heptyl, 6
-Methyl-6- (N-methylamino) heptyl, 1-
(N-methylamino) nonyl, 3- (N-methylamino) nonyl, 8- (N-methylamino) nonyl, 3-
(N-ethylamino) octyl, 3-methyl-7- (N
-Methylamino) octyl, 7,7-di (N-methylamino) octyl, 4-methyl-8- (N-methylamino) nonyl, 3,7-dimethyl-11- (N-methylamino) dodecyl, , 8-dimethyl-12- (N-methylamino) tridecyl, 1- (N-methylamino) pentadecyl, 14- (N-methylamino) pentadecyl,
13-methyl-13- (N-methylamino) tetradecyl, 15- (N-methylamino) hexadecyl, 1-
(N-methylamino) heptadecyl and 3,7,1
Examples thereof include an alkyl group having 2 to 20 carbon atoms interposed by one or two nitrogen atoms, such as 1-trimethyl-15- (N-methylamino) hexadecyl. a C ₂ -C ₁₀ alkyl group interposed.

In the above, “C _1- substituted with an aryl group or an aromatic heterocyclic group” in the definition of R ^4a and R ¹¹ is used.
The “C ₂₀ alkyl group” refers to the aforementioned “C ₁ -C ₂₀ alkyl group”
Is the same or different and is a group substituted with one or three of the above “aryl group” or the above “aromatic heterocyclic group”.

In the above, the “C ₂ -C ₂₀ alkynyl group” in the definition of R ^4a and R ¹¹ includes, for example, ethynyl, 2-propynyl, 1-methyl-2-propynyl,
-Methyl-2-propynyl, 2-ethyl-2-propynyl, 2-butynyl, 1-methyl-2-butynyl, 2-methyl-2-butynyl, 1-ethyl-2-butynyl, 3-
Butynyl, 1-methyl-3-butynyl, 2-methyl-3
-Butynyl, 1-ethyl-3-butynyl, 2-pentynyl, 1-methyl-2-pentynyl, 2-methyl-2-pentynyl, 3-pentynyl, 1-methyl-3-pentynyl, 2-methyl-3-pentynyl , 4-pentynyl, 1
-Methyl-4-pentynyl, 2-methyl-4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, heptynyl, 1-methylhexynyl, 2-methylhexynyl, 3-methylhexynyl, 4
-Methylhexynyl, 5-methylhexynyl, 1-propylbutynyl, 4,4-dimethylpentynyl, octynyl, 1-methylheptynyl, 2-methylheptynyl, 3
-Methylheptynyl, 4-methylheptynyl, 5-methylheptynyl, 6-methylheptynyl, 1-propylpentynyl, 2-ethylhexynyl, 5,5-dimethylhexynyl, noninyl, 3-methyloctynyl, 4-methyloctynyl, 5-methyl Octynyl, 6-methyloctynyl, 1-propylhexynyl, 2-ethylheptynyl, 6,6-dimethylheptynyl, decynyl, 1-methylnoninyl, 3-methylnoninyl, 8-methylnoninyl, 3-ethyloctynyl, 3,7- Dimethyloctynyl, 7,7-dimethyloctynyl, undecinyl, 4,
8-dimethylnoninyl, dodecynyl, tridecynyl, tetradecynyl, pentadecynyl, 3,7,11-trimethyldodecynyl, hexadecynyl, 4,8,12-trimethyltridecynyl, 1-methylpentadecynyl, 14
-Methylpentadecynyl, 13,13-dimethyltetradecynyl, heptadecynyl, 15-methylhexadecynyl, octadecynyl, 1-methylheptadecynyl, nonadecinyl, eicosinyl, and 3,7,11,15-
2 to 2 carbon atoms such as tetramethylhexadecynyl group
0 straight-chain or branched-chain alkynyl groups;
Preferably, it is a C ₂ -C ₁₀ alkynyl group.

[0085] In the above, R ^4a and the "C ₃ -C _{2 0} alkynyl group having a heteroatom-mediated" in the definition of R ^11, the "carbon number 3 of the" C ₂ -C ₂₀ alkynyl group "
-20 alkynyl groups "are the same or different
Or two groups interposed by a sulfur atom, an oxygen atom, or a nitrogen atom, for example, 1-methylthioethynyl, 2-methylthioethynyl, 1-methylthiopropynyl, 2-methylthiopropynyl, 3-methylthiopropynyl 2-ethylthioethynyl, 2-methyl-2-methylthioethynyl, 1-methylthiobutynyl, 2-methylthiobutynyl, 3-methylthiobutynyl, 2-ethylthiopropynyl, 3-methyl-3-methylthiopropynyl, 4-methylthiobutynyl Methylthiopentynyl, 3-methylthiopentynyl, 2-methylthiopentynyl, 1-methylthiopentynyl, 3,3-dimethylthiobutynyl, 2,2-dimethylthiobutynyl, 1,1-dimethylthiobutynyl, 1
-Methyl-2-methylthiobutynyl, 1,3-dimethylthiobutynyl, 2,3-dimethylthiobutynyl, 2-ethylthiobutynyl, 1-methylthiohexynyl, 2-methylthiohexynyl, 3-methylthiohexynyl Cynyl, 4-
Methylthiohexynyl, 5-methylthiohexynyl, 1
-Propylthiobutynyl, 4-methyl-4-methylthiopentynyl, 1-methylthioheptynyl, 2-methylthioheptynyl, 3-methylthioheptynyl, 4-methylthioheptynyl, 5-methylthioheptynyl , 6-methylthioheptynyl, 1-propylthiopentynyl, 2-
Ethylthiohexynyl, 5-methyl-5-methylthiohexynyl, 3-methylthiooctynyl, 4-methylthiooctynyl, 5-methylthiooctynyl, 6-methylthiooctynyl, 1-propylthiohexynyl, 2-ethylthio Heptynyl, 6-methyl-6-methylthioheptinyl, 1-methylthiononinyl, 3-methylthiononinyl, 8-methylthiononinyl, 3-ethylthiooctynyl, 3-methyl-7-methylthiooctynyl, 7,7-
Dimethylthiooctynyl, 4-methyl-8-methylthiononinyl, 3,7-dimethyl-11-methylthiododecynyl, 4,8-dimethyl-12-methylthiotridecinyl, 1-methylthiopentadecynyl, 14-methylthio 1 or such as pentadecynyl, 13-methyl-13-methylthiotetradecynyl, 15-methylthiohexadecynyl, 1-methylthioheptadecynyl and 3,7,11-trimethyl-15-methylthiohexadecynyl An alkynyl group having 3 to 20 carbon atoms interposed by two sulfur atoms; 1-methyloxyethynyl, 2-methyloxyethynyl, 1-methyloxypropynyl, 2-methyloxypropynyl, 3-methyloxypropynyl,
2-ethyloxyethynyl, 2-methyl-2-methyloxyethynyl, 1-methyloxybutynyl, 2-methyloxybutynyl, 3-methyloxybutynyl, 2-ethyloxypropynyl, 3-methyl-3-methyloxy Propynyl, 4-methyloxypentynyl, 3-methyloxypentynyl, 2-methyloxypentynyl, 1-methyloxypentynyl, 3,3-dimethyloxybutynyl, 2,2-dimethyloxybutynyl, 1, 1-dimethyloxybutynyl, 1-methyl-2-methyloxybutynyl, 1,3-dimethyloxybutynyl, 2,3-dimethyloxybutynyl, 2-ethyloxybutynyl, 1-
Methyloxyhexynyl, 2-methyloxyhexynyl, 3-methyloxyhexynyl, 4-methyloxyhexynyl, 5-methyloxyhexynyl, 1-propyloxybutynyl, 4-methyl-4-methyloxypentynyl , 1-methyloxyheptynyl, 2-methyloxyheptynyl, 3-methyloxyheptynyl, 4-methyloxyheptynyl, 5-methyloxyheptynyl, 6-
Methyloxyheptynyl, 1-propyloxypentynyl, 2-ethyloxyhexynyl, 5-methyl-5-methyloxyhexynyl, 3-methyloxyoctynyl,
4-methyloxyoctynyl, 5-methyloxyoctynyl, 6-methyloxyoctynyl, 1-propyloxyhexynyl, 2-ethyloxyheptynyl, 6-methyl-6-methyloxyheptynyl, 1- Methyloxynoninyl, 3-methyloxynoninyl, 8-methyloxynoninyl, 3-ethyloxyoctynyl, 3-methyl-
7-methyloxyoctynyl, 7,7-dimethyloxyoctynyl, 4-methyl-8-methyloxynoninyl,
3,7-dimethyl-11-methyloxidedecinyl,
4,8-dimethyl-12-methyloxytridecynyl,
1-methyloxypentadecynyl, 14-methyloxypentadecynyl, 13-methyl-13-methyloxytetradecynyl, 15-methyloxyhexadecynyl, 1
-Methyloxyheptadecynyl and 3,7,11-
An alkynyl group having 3 to 20 carbon atoms interposed by one or two oxygen atoms such as trimethyl-15-methyloxyhexadecynyl; 1- (N-methylamino) ethynyl, 2- (N-methyl Amino) ethynyl, 1- (N-
Methylamino) propynyl, 2- (N-methylamino)
Propynyl, 3- (N-methylamino) propynyl, 2
-(N-ethylamino) ethynyl, 2- (N, N-dimethylamino) ethynyl, 1- (N-methylamino) butynyl, 2- (N-methylamino) butynyl, 3- (N-
Methylamino) butynyl, 2- (N-ethylamino) propynyl, 3- (N, N-dimethylamino) propynyl, 4- (N-methylamino) pentynyl, 3- (N-
Methylamino) pentynyl, 2- (N-methylamino)
Pentynyl, 1- (N-methylamino) pentynyl, 3
-(N, N-dimethylamino) butynyl, 2- (N, N
-Dimethylamino) butynyl, 1- (N, N-dimethylamino) butynyl, 1-methyl-2- (N-methylamino) butynyl, 1,3-di (N-methylamino) butynyl, 2,3-di (N-methylamino) butynyl, 2-
(N-ethylamino) butynyl, 1- (N-methylamino) hexynyl, 2- (N-methylamino) hexynyl, 3- (N-methylamino) hexynyl, 4- (N-
Methylamino) hexynyl, 5- (N-methylamino)
Hexynyl, 1- (N-propylamino) butynyl, 4
-Methyl-4- (N-methylamino) pentynyl, 1-
(N-methylamino) heptynyl, 2- (N-methylamino) heptynyl, 3- (N-methylamino) heptynyl, 4- (N-methylamino) heptynyl, 5- (N-
Methylamino) heptynyl, 6- (N-methylamino)
Heptynyl, 1- (N-propylamino) pentynyl,
2- (N-ethylamino) hexynyl, 5-methyl-5
-(N-methylamino) hexynyl, 3- (N-methylamino) octynyl, 4- (N-methylamino) octynyl, 5- (N-methylamino) octynyl, 6- (N
-Methylamino) octynyl, 1- (N-propylamino) hexynyl, 2- (N-ethylamino) heptynyl, 6-methyl-6- (N-methylamino) heptynyl, 1- (N-methylamino) noninyl, 3- (N-methylamino) noninyl, 8- (N-methylamino) noninyl, 3- (N-ethylamino) octynyl, 3-methyl-7- (N-methylamino) octynyl, 7,7-di ( N-methylamino) octynyl, 4-methyl-8-
(N-methylamino) noninyl, 3,7-dimethyl-1
1- (N-methylamino) dodecinyl, 4,8-dimethyl-12- (N-methylamino) tridecinyl, 1-
(N-methylamino) pentadecynyl, 14- (N-methylamino) pentadecynyl, 13-methyl-13
Such as (N-methylamino) tetradecynyl, 15- (N-methylamino) hexadecynyl, 1- (N-methylamino) heptadecynyl, and 3,7,11-trimethyl-15- (N-methylamino) hexadecinyl 3 or 2 carbon atoms interposed by one or two nitrogen atoms
It can be exemplified 0 of alkynyl groups, preferably a C ₃ -C ₁₀ alkynyl group heteroatoms are interposed.

In the above, “C _2- substituted with an aryl group or an aromatic heterocyclic group” in the definition of R ^4a and R ¹¹ is used.
The “C ₂₀ alkynyl group” is a group in which the “C ₂ -C ₂₀ alkynyl group” is the same or different and is substituted with one or three “aryl groups” or “aromatic heterocyclic groups”. Is shown.

In the above, “C ₂ -C ₂₀ alkenyl group” in the definition of R ^4a and R ¹¹ includes, for example, ethenyl, 2-propenyl, 1-methyl-2-propenyl,
-Methyl-2-propenyl, 2-ethyl-2-propenyl, 2-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 1-ethyl-2-butenyl, 3-
Butenyl, 1-methyl-3-butenyl, 2-methyl-3
-Butenyl, 1-ethyl-3-butenyl, 2-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl , 4-pentenyl, 1
-Methyl-4-pentenyl, 2-methyl-4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, heptenyl, 1-methylhexenyl, 2-methylhexenyl, 3-methylhexenyl, 4
-Methylhexenyl, 5-methylhexenyl, 1-propylbutenyl, 4,4-dimethylpentenyl, octenyl, 1-methylheptenyl, 2-methylheptenyl, 3
-Methylheptenyl, 4-methylheptenyl, 5-methylheptenyl, 6-methylheptenyl, 1-propylpentenyl, 2-ethylhexenyl, 5,5-dimethylhexenyl, nonenyl, 3-methyloctenyl, 4-methyloctenyl, 5-methyloctenyl Thenyl, 6-methyloctenyl, 1-propylhexenyl, 2-ethylheptenyl, 6,6-dimethylheptenyl, decenyl, 1-methylnonenyl, 3-methylnonenyl, 8-methylnonenyl, 3-ethyloctenyl, 3,7-dimethyloctenyl , 7,7-dimethyloctenyl, undecenyl, 4,
8-dimethylnonenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, 3,7,11-trimethyldodecenyl, hexadecenyl, 4,8,12-trimethyltridecenyl, 1-methylpentadecenyl, 14
-Methylpentadecenyl, 13,13-dimethyltetradecenyl, heptadecenyl, 15-methylhexadecenyl, octadecenyl, 1-methylheptadecenyl, nonadecenyl, eicosenyl and 3,7,11,15 −
2 to 2 carbon atoms such as tetramethylhexadecenyl group
0 straight-chain or branched-chain alkenyl groups;
Preferably, it is a C ₂ -C ₁₀ alkenyl group.

[0088] In the above, R ^4a and the "C ₃ -C _{2 0} alkenyl group having a heteroatom-mediated" in the definition of R ^11, the "carbon number 3 of the" C ₂ -C ₂₀ alkenyl group "
To 20 alkenyl groups "are the same or different
Or two groups that are interposed with a sulfur atom, an oxygen atom, or a nitrogen atom, for example, 1-methylthioethenyl, 2-methylthioethenyl, 1-methylthiopropenyl, 2-methylthiopropenyl, 3- Methylthiopropenyl, 2-ethylthioethenyl, 2-methyl-2-methylthioethenyl, 1-methylthiobutenyl, 2-methylthiobutenyl, 3-methylthiobutenyl, 2-ethylthiopropenyl, 3-methyl-3-methylthio Propenyl, 4-methylthiopentenyl, 3-methylthiopentenyl, 2-methylthiopentenyl, 1-methylthiopentenyl, 3,3-dimethylthiobutenyl, 2,2-dimethylthiobutenyl, 1,1-dimethylthiobutenyl, 1
-Methyl-2-methylthiobutenyl, 1,3-dimethylthiobutenyl, 2,3-dimethylthiobutenyl, 2-ethylthiobutenyl, 1-methylthiohexenyl, 2-methylthiohexenyl, 3-methylthiohexenyl, −
Methylthiohexenyl, 5-methylthiohexenyl, 1
-Propylthiobutenyl, 4-methyl-4-methylthiopentenyl, 1-methylthioheptenyl, 2-methylthioheptenyl, 3-methylthioheptenyl, 4-methylthioheptenyl, 5-methylthioheptenyl, 6-methylthioheptenyl , 1-propylthiopentenyl, 2-
Ethylthiohexenyl, 5-methyl-5-methylthiohexenyl, 3-methylthiooctenyl, 4-methylthiooctenyl, 5-methylthiooctenyl, 6-methylthiooctenyl, 1-propylthiohexenyl, 2-ethylthioheptenyl, 6-methyl-6-methylthioheptenyl, 1-methylthiononenyl, 3-methylthiononenyl, 8-methylthiononenyl, 3-ethylthiooctenyl, 3-methyl-7-methylthiooctenyl, 7,7-
Dimethylthiooctenyl, 4-methyl-8-methylthiononenyl, 3,7-dimethyl-11-methylthiododecenyl, 4,8-dimethyl-12-methylthiotridecenyl, 1-methylthiopentadecenyl, 14-methylthiopentadecenyl, 13-methyl-13-methylthiotetradecenyl, 15-methylthiohexadecenyl, 1-methylthioheptadecenyl and 3,7,11-trimethyl-15-methylthiohexa An alkenyl group having 3 to 20 carbon atoms and interposed by 1 or 2 sulfur atoms such as decenyl; 1-methyloxyethenyl, 2-methyloxyethenyl, 1-methyloxypropenyl, Methyloxypropenyl, 3-methyloxypropenyl,
2-ethyloxyethenyl, 2-methyl-2-methyloxyethenyl, 1-methyloxybutenyl, 2-methyloxybutenyl, 3-methyloxybutenyl, 2-ethyloxypropenyl, 3-methyl-3- Methyloxypropenyl, 4-methyloxypentenyl, 3-methyloxypentenyl, 2-methyloxypentenyl, 1-methyloxypentenyl, 3,3-dimethyloxybutenyl, 2,2-dimethyloxybutenyl, 1,1- Dimethyloxybutenyl, 1-methyl-2-methyloxybutenyl, 1,3-dimethyloxybutenyl, 2,3-dimethyloxybutenyl, 2-ethyloxybutenyl, 1-
Methyloxyhexenyl, 2-methyloxyhexenyl, 3-methyloxyhexenyl, 4-methyloxyhexenyl, 5-methyloxyhexenyl, 1-propyloxybutenyl, 4-methyl-4-methyloxypentenyl, 1-methyloxyheptenyl Tenyl, 2-methyloxyheptenyl, 3-methyloxyheptenyl, 4-methyloxyheptenyl, 5-methyloxyheptenyl, 6-
Methyloxyheptenyl, 1-propyloxypentenyl, 2-ethyloxyhexenyl, 5-methyl-5-methyloxyhexenyl, 3-methyloxyoctenyl,
4-methyloxyoctenyl, 5-methyloxyoctenyl, 6-methyloxyoctenyl, 1-propyloxyhexenyl, 2-ethyloxyheptenyl, 6-methyl-6-methyloxyheptenyl, 1-methyloxynone Nyl, 3-methyloxynonenyl, 8-methyloxynonenyl, 3-ethyloxyoctenyl, 3-methyl-
7-methyloxyoctenyl, 7,7-dimethyloxyoctenyl, 4-methyl-8-methyloxynonenyl,
3,7-dimethyl-11-methyloxidedecenyl,
4,8-dimethyl-12-methyloxytridecenyl,
1-methyloxypentadecenyl, 14-methyloxypentadecenyl, 13-methyl-13-methyloxytetradecenyl, 15-methyloxyhexadecenyl, 1
-Methyloxyheptadecenyl and 3,7,11-
An alkenyl group having 3 to 20 carbon atoms and interposed by one or two oxygen atoms such as trimethyl-15-methyloxyhexadecenyl; 1- (N-methylamino) ethenyl, 2- (N- Methylamino) ethenyl, 1- (N-
Methylamino) propenyl, 2- (N-methylamino)
Propenyl, 3- (N-methylamino) propenyl, 2
-(N-ethylamino) ethenyl, 2- (N, N-dimethylamino) ethenyl, 1- (N-methylamino) butenyl, 2- (N-methylamino) butenyl, 3- (N-
Methylamino) butenyl, 2- (N-ethylamino) propenyl, 3- (N, N-dimethylamino) propenyl, 4- (N-methylamino) pentenyl, 3- (N-
Methylamino) pentenyl, 2- (N-methylamino)
Pentenyl, 1- (N-methylamino) pentenyl, 3
-(N, N-dimethylamino) butenyl, 2- (N, N
-Dimethylamino) butenyl, 1- (N, N-dimethylamino) butenyl, 1-methyl-2- (N-methylamino) butenyl, 1,3-di (N-methylamino) butenyl, 2,3-di (N-methylamino) butenyl, 2-
(N-ethylamino) butenyl, 1- (N-methylamino) hexenyl, 2- (N-methylamino) hexenyl, 3- (N-methylamino) hexenyl, 4- (N-
Methylamino) hexenyl, 5- (N-methylamino)
Hexenyl, 1- (N-propylamino) butenyl, 4
-Methyl-4- (N-methylamino) pentenyl, 1-
(N-methylamino) heptenyl, 2- (N-methylamino) heptenyl, 3- (N-methylamino) heptenyl, 4- (N-methylamino) heptenyl, 5- (N-
Methylamino) heptenyl, 6- (N-methylamino)
Heptenyl, 1- (N-propylamino) pentenyl,
2- (N-ethylamino) hexenyl, 5-methyl-5
-(N-methylamino) hexenyl, 3- (N-methylamino) octenyl, 4- (N-methylamino) octenyl, 5- (N-methylamino) octenyl, 6- (N
-Methylamino) octenyl, 1- (N-propylamino) hexenyl, 2- (N-ethylamino) heptenyl, 6-methyl-6- (N-methylamino) heptenyl, 1- (N-methylamino) nonenyl, 3- (N-methylamino) nonenyl, 8- (N-methylamino) nonenyl, 3- (N-ethylamino) octenyl, 3-methyl-7- (N-methylamino) octenyl, 7,7-di ( N-methylamino) octenyl, 4-methyl-8-
(N-methylamino) nonenyl, 3,7-dimethyl-1
1- (N-methylamino) dodecenyl, 4,8-dimethyl-12- (N-methylamino) tridecenyl,
(N-methylamino) pentadecenyl, 14- (N-methylamino) pentadecenyl, 13-methyl-13
Such as (N-methylamino) tetradecenyl, 15- (N-methylamino) hexadecenyl, 1- (N-methylamino) heptadecenyl, and 3,7,11-trimethyl-15- (N-methylamino) hexadecenyl 3 or 2 carbon atoms interposed by one or two nitrogen atoms
It can be exemplified 0 alkenyl group, preferably a C ₃ -C ₁₀ alkenyl group which heteroatoms are interposed.

In the above, “C _2- substituted with an aryl group or an aromatic heterocyclic group” in the definition of R ^4a and R ¹¹ is used.
The “C ₂₀ alkenyl group” is a group in which the above “C ₂ -C ₂₀ alkenyl group” is the same or different and is substituted with one or three of the above “aryl group” or the above “aromatic heterocyclic group”. Is shown.

In the above, in the definition of R ^4a and R ¹¹ , the “C ₂ -C ₂₀ alkyl group in which a hetero atom substituted with an aryl group or an aromatic heterocyclic group is present” refers to the above “C ₂ -C ₂₀ alkyl group in which a hetero atom is present. “C ₂ -C ₂₀ alkyl group” is the same or different and represents one or three groups substituted with the above “aryl group” or the above “aromatic heterocyclic group”.

The "lipase" used in the present invention is not particularly limited, and the optimum one varies depending on the type of the starting compound.
orescens, Pseudomonas cepacia, Chromobacterium vis
cosum, Aspergillus niger, Aspergillus oryzae, Cand
ida antarctica, Candida cylindracea, Candida lipol
ytica, Candida rugosa, Candida utilis, Penicillium
roqueforti, Rhizopus arrhizus, Rhizopus delemar,
Rhizopus javanicus, Rhizomucor miehei, Rhizopus ni
veus, Humicola lanuginosa, Mucor javanicus, Mucor m
iehei, Thermusaquaticus, Thermus flavus, Thermus ther
mophilus etc., human pancreas, hog pancreas, porcine
It is a lipase derived from pancreas and wheat germ. The enzyme can be used not only partially or completely after purification, but also in an immobilized form. Most preferably, Pseudomonas sp. Immobilized (for example, immobilized lipase from Pseudomonas sp. (TOYOB
O))).

The carboxylic acid vinyl ester derivative having the formula (XLIII) (R ¹¹ COOC) used in the present invention
As H ＝ CH ₂ ), the most suitable one varies depending on the type of the raw material compound, but generally preferred are n-hexanoic acid vinyl ester, n-heptanoic acid vinyl ester, and n-hexanoic acid vinyl ester.
It is a linear aliphatic carboxylic acid vinyl ester such as vinyl pentanoate or vinyl acetate, and most preferably vinyl n-hexanoate.

"Pharmacologically acceptable salt thereof" means that the compound having the general formula (I) of the present invention is reacted with an acid when the compound has a basic group such as an amino group.
When the compound has an acidic group such as a carboxyl group, it can be converted to a salt by reacting with a base.

As the salt based on a basic group, preferably,
Inorganic acid salts such as hydrohalides such as hydrofluoride, hydrochloride, hydrobromide and hydroiodide, nitrates, perchlorates, sulfates and phosphates; methanesulfonic acid Salts, lower alkane sulfonates such as trifluoromethane sulfonate, ethane sulfonate, benzene sulfonate,
aryl sulfonates such as p-toluene sulfonate, acetate, malate, fumarate, succinate,
Organic acid salts such as citrate, ascorbate, tartrate, oxalate, and maleate; and amino acid salts such as glycine, lysine, arginine, ornithine, glutamate, and aspartate. And most preferably an organic acid salt.

On the other hand, the salt based on an acidic group is preferably an alkali metal salt such as a sodium salt, a potassium salt or a lithium salt; an alkaline earth metal salt such as a calcium salt or a magnesium salt; an aluminum salt; Metal salts such as salts; inorganic salts such as ammonium salts, t-octylamine salts, dibenzylamine salts, morpholine salts, glucosamine salts, phenylglycine alkyl ester salts, ethylenediamine salts, N-methylglucamine salts, guanidine salts,
Diethylamine salt, triethylamine salt, dicyclohexylamine salt, N, N′-dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzylphenethylamine salt, piperazine salt, tetramethylammonium salt, tris (hydroxymethyl A) amine salts such as organic salts such as aminomethane salts; and amino acid salts such as glycine salts, lysine salts, arginine salts, ornithine salts, glutamates and aspartates.

The compound of the present invention having the general formula (I), its pharmacologically acceptable salt, its ester or other derivative absorbs moisture by being left in the air or recrystallized. However, in some cases, hydrates are formed with adsorbed water, and such hydrates are also included in the salts of the present invention.

The compound of the present invention having the general formula (I), a pharmaceutically acceptable salt thereof, an ester or other derivative thereof has an asymmetric carbon atom in the molecule, and therefore has an optical isomer. In the compounds of the present invention, optical isomers and mixtures of optical isomers are all represented by a single formula, that is, general formula (I). Therefore, the present invention includes all optical isomers and mixtures of optical isomers in any ratio. For example, the compound of the present invention having the general formula (I), a pharmacologically acceptable salt thereof, an ester or other derivative thereof is represented by the following formula:

[0098]

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Has the following.

In the above formula, the —NR ¹ R ² group is substituted by an asymmetric carbon atom, and a compound having an absolute configuration of R is particularly preferable.

The term "ester" as used herein means the compound (I) of the present invention, which can be converted into an ester. Such esters include "esters of hydroxy group" and "esters of carboxy group". And an ester in which each ester residue is a "general protecting group in a reaction" or a "protecting group that can be cleaved in vivo by a biological method such as hydrolysis".

The “general protecting group in the reaction” refers to a protecting group that can be cleaved by a chemical method such as hydrogenolysis, hydrolysis, electrolysis, or photolysis.

The “general protecting group in the reaction” and the “protecting group that can be cleaved in vivo by a biological method such as hydrolysis” as the “ester of a hydroxy group” include:
The consent is shown with the above "hydroxyl protecting group".

As the “general protecting group in the reaction” for the “ester of a carboxy group”, preferably the above “lower alkyl group”; ethenyl, 1-propenyl, 2-
Propenyl, 1-methyl-2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-
Methyl-2-propenyl, 2-ethyl-2-propenyl, 1-butenyl, 2-butenyl, 1-methyl-2-butenyl, 1-methyl-1-butenyl, 3-methyl-2-
Butenyl, 1-ethyl-2-butenyl, 3-butenyl,
1-methyl-3-butenyl, 2-methyl-3-butenyl, 1-ethyl-3-butenyl, 1-pentenyl, 2-
Pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-
Pentenyl, 2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-
Lower alkenyl groups such as pentenyl 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl; ethynyl, 2-propynyl, 1-methyl-2-propynyl, 2-methyl-2-propynyl, 2 −
Ethyl-2-propynyl, 2-butynyl, 1-methyl-
2-butynyl, 2-methyl-2-butynyl, 1-ethyl-2-butynyl, 3-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-ethyl-3-butynyl, 2- Pentynyl, 1-methyl-2-pentynyl, 2-methyl-2-pentynyl, 3-pentynyl, 1
-Methyl-3-pentynyl, 2-methyl-3-pentynyl, 4-pentynyl, 1-methyl-4-pentynyl, 2
Lower alkynyl groups such as -methyl-4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl and 5-hexynyl; the above-mentioned "halogeno lower alkyl"; 2-hydroxyethyl, 2,3-dihydroxypropyl, 3-
Hydroxypropyl, 3,4-dihydroxybutyl, 4
A hydroxy "lower alkyl group" such as hydroxybutyl; a "lower aliphatic acyl" such as acetylmethyl
"Lower alkyl group";"aralkylgroup";"silylgroup";

The “protecting group that can be cleaved in vivo by a biological method such as hydrolysis” means that it is cleaved in a human body by a biological method such as hydrolysis to produce a free acid or a salt thereof. It refers to a protecting group, and whether such a derivative is administered by intravenous injection to experimental animals such as rats and mice,
Subsequent examination of the body fluids of the animals allows the determination of the ability to detect the original compound or a pharmacologically acceptable salt thereof. Protecting group that can be cleaved by the method "
Preferably, methoxyethyl, 1-ethoxyethyl, 1-methyl-1-methoxyethyl, 1- (isopropoxy) ethyl, 2-methoxyethyl, 2-ethoxyethyl, 1,1-dimethyl-1- Methoxyethyl, ethoxymethyl, n-propoxymethyl, isopropoxymethyl, n-butoxymethyl, lower alkoxy lower alkyl groups such as t-butoxymethyl, lower alkoxylated lower alkoxy lower alkyl groups such as 2-methoxyethoxymethyl, “Alkoxyalkyl groups” such as “aryl” oxy “lower alkyl groups” such as phenoxymethyl, and halogenated lower alkoxy lower alkyl groups such as 2,2,2-trichloroethoxymethyl and bis (2-chloroethoxy) methyl A lower alcohol such as methoxycarbonylmethyl Shi "carbonyl" lower alkyl group ""; cyanomethyl, 2-"cyano" lower alkyl groups such as cyanoethyl "; methylthiomethyl, such as ethylthiomethyl,""loweralkyl" thiomethyl group ";
"" Aryl "thiomethyl group" such as phenylthiomethyl and naphthylthiomethyl; "" lower alkyl "which may be substituted by halogen" such as 2-methanesulfonylethyl and 2-trifluoromethanesulfonylethyl "sulfonyl" lower alkyl "Group"";" aryl "sulfonyl" lower alkyl group "such as 2-benzenesulfonylethyl and 2-toluenesulfonylethyl;" 1- (acyloxy) "lower alkyl group"";" phthalidyl group "; The "aryl group"; the "lower alkyl group"; the "carboxyalkyl group" such as carboxymethyl; and the "amide-forming residue of amino acid" such as phenylalanine.

The "other derivatives" are defined as the above-mentioned "pharmacologically acceptable salts" and "the esters thereof" when the compound having the general formula (I) of the present invention has an amino group and / or a carboxy group. The derivative is shown because it can be a derivative other than. Such derivatives include, for example, amide derivatives such as acyl groups.

As specific examples of the compound having the general formula (I) of the present invention, there can be mentioned, for example, the compounds shown in Tables 1 and 2 below. Specific examples of the compound having 1) include, for example, compounds described in Tables 3 and 4 below, but the present invention is not limited to these compounds.

The abbreviations in the table are as follows. Ac: acetyl group Boc: t-butoxycarbonyl group Bpyrr: benzopyrrolyl group Bu: butyl group iBu: isobutyl group Bz: benzyl group Bzt: benzothienyl group Et: ethyl group Fur: furyl group cHx: methyl group: cHx: methyl 1): naphthalen-1-yl group Np (2): naphthalen-2-yl group Ph: phenyl group cPn: cyclopentyl group Pr: propyl group iPr: isopropyl group. Pyr: pyridyl group TBDMS: t-butyldimethylsilyl group The: thienyl group

[0109]

[Table 1]

[0110]

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Compd. R¹ R^Two R^Three R^Four n -X-Y-R^Five R⁶ R⁷  1-1 H H H Me 1-(CH_Two)_Five-cHx H H 1-2 H H H Me 1-(CH_Two)₆-cHx H H 1-3 H H H Me 1 -CH = CH- (CH_Two)_Three-cHx H H 1-4 H H H Me 1 -CH = CH- (CH_Two)_Four-cHx H H 1-5 H H H Me 1 -C≡C- (CH_Two)_Three-cHx H H 1-6 H H H Me 1 -C≡C- (CH_Two)_Four-cHx H H 1-7 H H H Me 1 -CO- (CH_Two)_Four-cHx H H 1-8 H H H Me 1 -CO- (CH_Two)_Five-cHx H H 1-9 H H H Me 1 -CH (OH)-(CH_Two)_Four-cHx H H 1-10 H H H Me 1 -CH (OH)-(CH_Two)_Five-cHx H H 1-11 H H H Me 1 -4- (cHx-CH_TwoO) Ph H H 1-12 H H H Me 1-(4-BzO-Ph) H H 1-13 H H H Me 1 -C≡C-CH_TwoO-cPn H H 1-14 H H H Me 1 -C≡C- (CH_Two)_TwoO-cPn H H 1-15 H H H Me 1 -C≡C-CH_TwoO-cHx H H 1-16 H H H Me 1 -C≡C- (CH_Two)_TwoO-cHx H H 1-17 H H H Me 1 -C≡C-CH_TwoO-Ph H H 1-18 H H H Me 1 -C≡C- (CH_Two)_TwoO-Ph H H 1-19 H H H Me 2-(CH_Two)_Two-cHx H H 1-20 H H Me Me 2-(CH_Two)_Two-cHx H H 1-21 Me H H Me 2-(CH_Two)_Two-cHx H H 1-22 CO_TwoMe H H Me 2-(CH_Two)_Two-cHx H H 1-23 H H H Me 2-(CH_Two)_Two-(4-F-cHx) H H 1-24 H H H Me 2-(CH_Two)_Two-(4-Me-cHx) H H 1-25 H H H Me 2-(CH_Two)_Two-(4-Et-cHx) H H 1-26 H H H Me 2-(CH_Two)_Two-(4-CF_Three-cHx) H H 1-27 H H H Me 2-(CH_Two)_Two-(4-MeO-cHx) H H 1-28 H H H Me 2-(CH_Two)_Two-(4-EtO-cHx) H H 1-29 H H H Me 2-(CH_Two)_Two-(4-MeS-cHx) H H 1-30 H H H Me 2-(CH_Two)_Two-(4-cHx-cHx) H H 1-31 H H H Me 2-(CH_Two)_Two-(4-Ph-cHx) H H 1-32 H H H Me 2-(CH_Two)_Two-Ph H H 1-33 H H Me Me 2-(CH_Two)_Two-Ph H H 1-34 Me H H Me 2-(CH_Two)_Two-Ph H H 1-35 CO_TwoMe H H Me 2-(CH_Two)_Two-Ph H H 1-36 H H H Me 2-(CH_Two)_Two-(4-F-Ph) H H 1-37 H H H Me 2-(CH_Two)_Two-(4-Me-Ph) H H 1-38 H H H Me 2-(CH_Two)_Two-(4-Et-Ph) H H 1-39 H H H Me 2-(CH_Two)_Two-(4-CF_Three-Ph) H H 1-40 H H H Me 2-(CH_Two)_Two-(4-MeO-Ph) H H 1-41 H H H Me 2-(CH_Two)_Two-(4-EtO-Ph) H H 1-42 H H H Me 2-(CH_Two)_Two-(4-MeS-Ph) H H 1-43 H H H Me 2-(CH_Two)_Two-(4-cHx-Ph) H H 1-44 H H H Me 2-(CH_Two)_Two-(4-Ph-Ph) H H 1-45 H H H Me 2-(CH_Two)_Three-cHx H H 1-46 H H Me Me 2-(CH_Two)_Three-cHx H H 1-47 Me H H Me 2-(CH_Two)_Three-cHx H H 1-48 CO_TwoMe H H Me 2-(CH_Two)_Three-cHx H H 1-49 H H H Me 2-(CH_Two)_Three-(4-F-cHx) H H 1-50 H H H Me 2-(CH_Two)_Three-(4-Me-cHx) H H 1-51 H H H Me 2-(CH_Two)_Three-(4-Et-cHx) H H 1-52 H H H Me 2-(CH_Two)_Three-(4-CF_Three-cHx) H H 1 -53 H H H Me 2-(CH_Two)_Three-(4-MeO-cHx) H H 1-54 H H H Me 2-(CH_Two)_Three-(4-EtO-cHx) H H 1-55 H H H Me 2-(CH_Two)_Three-(4-MeS-cHx) H H 1-56 H H H Me 2-(CH_Two)_Three-(4-cHx-cHx) H H 1-57 H H H Me 2-(CH_Two)_Three-(4-Ph-cHx) H H 1-58 H H H Me 2-(CH_Two)_Three-Ph H H 1-59 H H Me Me 2-(CH_Two)_Three-Ph H H 1-60 Me H H Me 2-(CH_Two)_Three-Ph H H 1-61 CO_TwoMe H H Me 2-(CH_Two)_Three-Ph H H 1-62 H H H Me 2-(CH_Two)_Three-(4-F-Ph) H H 1-63 H H H Me 2-(CH_Two)_Three-(4-Me-Ph) H H 1-64 H H H Me 2-(CH_Two)_Three-(4-Et-Ph) H H 1-65 H H H Me 2-(CH_Two)_Three-(4-CF_Three-Ph) H H 1-66 H H H Me 2-(CH_Two)_Three-(4-MeO-Ph) H H 1-67 H H H Me 2-(CH_Two)_Three-(4-EtO-Ph) H H 1-68 H H H Me 2-(CH_Two)_Three-(4-MeS-Ph) H H 1-69 H H H Me 2-(CH_Two)_Three-(4-cHx-Ph) H H 1-70 H H H Me 2-(CH_Two)_Three-(4-Ph-Ph) H H 1-71 H H H Me 2-(CH_Two)_Four-cHx H H 1-72 H H Me Me 2-(CH_Two)_Four-cHx H H 1-73 Me H H Me 2-(CH_Two)_Four-cHx H H 1-74 CO_TwoMe H H Me 2-(CH_Two)_Four-cHx H H 1-75 H H H Me 2-(CH_Two)_Four-(4-F-cHx) H H 1-76 H H H Me 2-(CH_Two)_Four-(4-Me-cHx) H H 1-77 H H H Me 2-(CH_Two)_Four-(4-Et-cHx) H H 1-78 H H H Me 2-(CH_Two)_Four-(4-CF_Three-cHx) H H 1 -79 H H H Me 2-(CH_Two)_Four-(4-MeO-cHx) H H 1-80 H H H Me 2-(CH_Two)_Four-(4-EtO-cHx) H H 1-81 H H H Me 2-(CH_Two)_Four-(4-MeS-cHx) H H 1-82 H H H Me 2-(CH_Two)_Four-(4-cHx-cHx) H H 1-83 H H H Me 2-(CH_Two)_Four-(4-Ph-cHx) H H 1-84 H H H Me 2-(CH_Two)_Four-Ph H H 1-85 H H Me Me 2-(CH_Two)_Four-Ph H H 1-86 Me H H Me 2-(CH_Two)_Four-Ph H H 1-87 CO_TwoMe H H Me 2-(CH_Two)_Four-Ph H H 1-88 H H H Me 2-(CH_Two)_Four-(4-F-Ph) H H 1-89 H H H Me 2-(CH_Two)_Four-(4-Me-Ph) H H 1-90 H H H Me 2-(CH_Two)_Four-(4-Et-Ph) H H 1-91 H H H Me 2-(CH_Two)_Four-(4-CF_Three-Ph) H H 1-92 H H H Me 2-(CH_Two)_Four-(4-MeO-Ph) H H 1-93 H H H Me 2-(CH_Two)_Four-(4-EtO-Ph) H H 1-94 H H H Me 2-(CH_Two)_Four-(4-MeS-Ph) H H 1-95 H H H Me 2-(CH_Two)_Four-(4-cHx-Ph) H H 1-96 H H H Me 2-(CH_Two)_Four-(4-Ph-Ph) H H 1-97 H H H Me 2-(CH_Two)_Five-cPn H H 1-98 H H H Me 2-(CH_Two)_Five-cHx H H 1-99 H H H Me 2-(CH_Two)_Five-cHx Me H 1-100 H H H Me 2-(CH_Two)_Five-cHx H Me 1-101 H H H Me 2-(CH_Two)_Five-cHx F H 1-102 H H H Me 2-(CH_Two)_Five-cHx H F 1-103 H H Me Me 2-(CH_Two)_Five-cHx H H 1-104 Me H H Me 2-(CH_Two)_Five-cHx H H 1-105 CO_TwoMe H H Me 2-(CH_Two)_Five-cHx H H 1-106 H H H Me 2-(CH_Two)_Five-(3-F-cHx) H H 1-107 H H H Me 2-(CH_Two)_Five-(4-F-cHx) H H 1-108 H H H Me 2-(CH_Two)_Five-(4-Cl-cHx) H H 1-109 H H H Me 2-(CH_Two)_Five-(4-Br-cHx) H H 1-110 H H H Me 2-(CH_Two)_Five-(3-Me-cHx) H H 1-111 H H H Me 2-(CH_Two)_Five-(4-Me-cHx) H H 1-112 H H H Me 2-(CH_Two)_Five-(3-Et-cHx) H H 1-113 H H H Me 2-(CH_Two)_Five-(4-Et-cHx) H H 1-114 H H H Me 2-(CH_Two)_Five-(3-Pr-cHx) H H 1-115 H H H Me 2-(CH_Two)_Five-(4-Pr-cHx) H H 1-116 H H H Me 2-(CH_Two)_Five-(4-iPr-cHx) H H 1-117 H H H Me 2-(CH_Two)_Five-(3-Bu-cHx) H H 1-118 H H H Me 2-(CH_Two)_Five-(4-Bu-cHx) H H 1-119 H H H Me 2-(CH_Two)_Five-(3-CF_Three-cHx) H H 1-120 H H H Me 2-(CH_Two)_Five-(4-CF_Three-cHx) H H 1-121 H H H Me 2-(CH_Two)_Five-(3-MeO-cHx) H H 1-122 H H H Me 2-(CH_Two)_Five-(4-MeO-cHx) H H 1-123 H H H Me 2-(CH_Two)_Five-(3-EtO-cHx) H H 1-124 H H H Me 2-(CH_Two)_Five-(4-EtO-cHx) H H 1-125 H H H Me 2-(CH_Two)_Five-(3-PrO-cHx) H H 1-126 H H H Me 2-(CH_Two)_Five-(4-PrO-cHx) H H 1-127 H H H Me 2-(CH_Two)_Five-(3-iPrO-cHx) H H 1-128 H H H Me 2-(CH_Two)_Five-(4-iPrO-cHx) H H 1-129 H H H Me 2-(CH_Two)_Five-[3- (2-Et-PrO) -cHx] H H 1-130 H H H Me 2-(CH_Two)_Five-[4- (2-Et-PrO) -cHx] H H 1-131 H H H Me 2-(CH_Two)_Five-(3-iBuO-cHx) H H 1-132 H H H Me 2-(CH_Two)_Five-(4-iBuO-cHx) H H 1-133 H H H Me 2-(CH_Two)_Five-(3-MeS-cHx) H H 1-134 H H H Me 2-(CH_Two)_Five-(4-MeS-cHx) H H 1-135 H H H Me 2-(CH_Two)_Five-(3-EtS-cHx) H H 1-136 H H H Me 2-(CH_Two)_Five-(4-EtS-cHx) H H 1-137 H H H Me 2-(CH_Two)_Five-(3-PrS-cHx) H H 1-138 H H H Me 2-(CH_Two)_Five-(4-PrS-cHx) H H 1-139 H H H Me 2-(CH_Two)_Five-(3-iPrS-cHx) H H 1-140 H H H Me 2-(CH_Two)_Five-(4-iPrS-cHx) H H 1-141 H H H Me 2-(CH_Two)_Five-[3- (2-Et-PrS) -cHx] H H 1-142 H H H Me 2-(CH_Two)_Five-[4- (2-Et-PrS) -cHx] H H 1-143 H H H Me 2-(CH_Two)_Five-(3-iBuS-cHx) H H 1-144 H H H Me 2-(CH_Two)_Five-(4-iBuS-cHx) H H 1-145 H H H Me 2-(CH_Two)_Five-(3-cHx-cHx) H H 1-146 H H H Me 2-(CH_Two)_Five-(4-cHx-cHx) H H 1-147 H H H Me 2-(CH_Two)_Five-(3-Ph-cHx) H H 1-148 H H H Me 2-(CH_Two)_Five-(4-Ph-cHx) H H 1-149 H H H Me 2-(CH_Two)_Five-(2,4-diMe-cHx) H H 1-150 H H H Me 2-(CH_Two)_Five-(3,4-diMe-cHx) H H 1-151 H H H Me 2-(CH_Two)_Five-(3,5-diMe-cHx) H H 1-152 H H H Me 2-(CH_Two)_Five-Ph H H 1-153 H H H Me 2-(CH_Two)_Five-Ph Me H 1-154 H H H Me 2-(CH_Two)_Five-Ph H Me 1-155 H H H Me 2-(CH_Two)_Five-Ph F H 1-156 H H H Me 2-(CH_Two)_Five-Ph H F 1-157 H H Me Me 2-(CH_Two)_Five-Ph H H 1-158 Me H H Me 2-(C
H₂)₅-Ph H H 1-159 CO₂MeHHMe2- (C
H₂)₅-PhHH1-160HHHMe2- (C
H₂)₅-(3-F-Ph) HH1-161HHHMe2- (C
H₂)₅-(4-F-Ph) HH1-162HHHMe2- (C
H₂)₅-(4-Cl-Ph) HH1-163HHHMe2- (C
H₂)₅-(4-Br-Ph) HH1-164HHHMe2- (C
H₂)₅-(3-Me-Ph) HH1-165HHHMe2- (C
H₂)₅-(4-Me-Ph) HH1-166HHHMe2- (C
H₂)₅-(3-Et-Ph) HH1-167HHHMe2- (C
H₂)₅-(4-Et-Ph) HH1-168HHHMe2- (C
H₂)₅-(3-Pr-Ph) HH1-169HHHMe2- (C
H₂)₅-(4-Pr-Ph) HH1-170HHHMe2- (C
H₂)₅-(3-iPr-Ph) HH1-171HHHMe2- (C
H₂)₅-(4-iPr-Ph) HH1-172HHHMe2- (C
H₂)₅-(3-Bu-Ph) HH1-173HHHMe2- (C
H₂)₅-(4-Bu-Ph) HH1-174HHHMe2- (C
H₂)₅− (3-CF₃-Ph) HH1-175HHHMe2- (C
H₂)₅− (4-CF₃-Ph) HH1-176HHHMe2- (C
H₂)₅-(3-MeO-Ph) HH1-177HHHMe2- (C
H₂)₅-(4-MeO-Ph) HH1-178HHHMe2- (C
H₂)₅-(3-EtO-Ph) HH1-179HHHMe2- (C
H₂)₅-(4-EtO-Ph) HH1-180HHHMe2- (C
H₂)₅-(3-PrO-Ph) HH1-181HHHMe2- (C
H₂)₅-(4-PrO-Ph) HH1-182HHHMe2- (C
H₂)₅-(3-iPrO-Ph) HH1-183HHHMe2- (C
H₂)₅-(4-iPrO-Ph) HH1-184HHHMe2- (C
H₂)₅-[3- (2-Et-PrO) -Ph] HH1-185HHHMe2- (C
H₂)₅-[4- (2-Et-PrO) -Ph] H H 1-187 H H H Me 2-(CH_Two)_Five-(4-iBuO-Ph) H H 1-188 H H H Me 2-(CH_Two)_Five-(3-MeS-Ph) H H 1-189 H H H Me 2-(CH_Two)_Five-(4-MeS-Ph) H H 1-190 H H H Me 2-(CH_Two)_Five-(3-EtS-Ph) H H 1-191 H H H Me 2-(CH_Two)_Five-(4-EtS-Ph) H H 1-192 H H H Me 2-(CH_Two)_Five-(3-PrS-Ph) H H 1-193 H H H Me 2-(CH_Two)_Five-(4-PrS-Ph) H H 1-194 H H H Me 2-(CH_Two)_Five-(3-iPrS-Ph) H H 1-195 H H H Me 2-(CH_Two)_Five-(4-iPrS-Ph) H H 1-196 H H H Me 2-(CH_Two)_Five-[3- (2-Et-PrS) -Ph] H H 1-197 H H H Me 2-(CH_Two)_Five-[4- (2-Et-PrS) -Ph] H H 1-198 H H H Me 2-(CH_Two)_Five-(3-iBuS-Ph) H H 1-199 H H H Me 2-(CH_Two)_Five-(4-iBuS-Ph) H H 1-200 H H H Me 2-(CH_Two)_Five-(3-cHx-Ph) H H 1-201 H H H Me 2-(CH_Two)_Five-(4-cHx-Ph) H H 1-202 H H H Me 2-(CH_Two)_Five-(3-Ph-Ph) H H 1-203 H H H Me 2-(CH_Two)_Five-(4-Ph-Ph) H H 1-204 H H H Me 2-(CH_Two)_Five-(2,4-diMe-Ph) H H 1-205 H H H Me 2-(CH_Two)_Five-(3,4-diMe-Ph) H H 1-206 H H H Me 2-(CH_Two)_Five-(3,5-diMe-Ph) H H 1-207 H H H Me 2-(CH_Two)_Five-Np (1) H H 1-208 H H H Me 2-(CH_Two)_Five-Np (2) H H 1-209 H H H Me 2-(CH_Two)₆-cPn H H 1-210 H H H Me 2-(CH_Two)₆-cHx H H 1-211 H H H Me 2-(CH_Two)₆-cHx Me H 1-212 H H H Me 2-(CH_Two)₆-cHx H Me 1-213 H H H Me 2-(CH_Two)₆-cHx F H 1-214 H H H Me 2-(CH_Two)₆-cHx H F 1-215 H H Me Me 2-(CH_Two)₆-cHxHH1-216MeHHMe2- (C
H₂)₆-CHxHH1-217CO₂MeHHMe2- (C
H₂)₆-CHxHH1-218HHHMe2- (C
H₂)₆-(3-F-cHx) HH1-219HHHMe2- (C
H₂)₆-(4-F-cHx) HH1-220HHHMe2- (C
H₂)₆-(4-Cl-cHx) HH1-221 HHHMe2- (C
H₂)₆-(4-Br-cHx) HH1-222HHHMe2- (C
H₂)₆-(3-Me-cHx) HH1-223HHHMe2- (C
H₂)₆-(4-Me-cHx) HH1-224HHHMe2- (C
H₂)₆-(3-Et-cHx) HH1-225HHHMe2- (C
H₂)₆-(4-Et-cHx) HH1-226HHHMe2- (C
H₂)₆-(3-Pr-cHx) HH1-227HHHMe2- (C
H₂)₆-(4-Pr-cHx) HH1-228HHHMe2- (C
H₂)₆-(4-iPr-cHx) HH1-229HHHMe2- (C
H₂)₆-(3-Bu-cHx) HH1-230HHHMe2- (C
H₂)₆-(4-Bu-cHx) HH1-231HHHMe2- (C
H₂)₆− (3-CF₃-CHx) HH1-232HHHMe2- (C
H₂)₆− (4-CF₃-CHx) H H 1-233 H H H Me 2-(C
H₂)₆-(3-MeO-cHx) HH1-234HHHMe2- (C
H₂)₆-(4-MeO-cHx) HH1-235HHHMe2- (C
H₂)₆-(3-EtO-cHx) HH1-236HHHMe2- (C
H₂)₆-(4-EtO-cHx) HH1-237HHHMe2- (C
H₂)₆-(3-PrO-cHx) HH1-238HHHMe2- (C
H₂)₆-(4-PrO-cHx) HH1-239HHHMe2- (C
H₂)₆-(3-iPrO-cHx) HH1-240HHHMe2- (C
H₂)₆-(4-iPrO-cHx) HH1-241HHHMe2- (C
H₂)₆-[3- (2-Et-PrO) -cHx] HH1-242HHHMe2- (C
H₂)₆-[4- (2-Et-PrO) -cHx] HH1-243HHHMe2- (C
H₂)₆-(3-iBuO-cHx) H H 1-245 H H H Me 2-(CH_Two)₆-(3-MeS-cHx) H H 1-246 H H H Me 2-(CH_Two)₆-(4-MeS-cHx) H H 1-247 H H H Me 2-(CH_Two)₆-(3-EtS-cHx) H H 1-248 H H H Me 2-(CH_Two)₆-(4-EtS-cHx) H H 1-249 H H H Me 2-(CH_Two)₆-(3-PrS-cHx) H H 1-250 H H H Me 2-(CH_Two)₆-(4-PrS-cHx) H H 1-251 H H H Me 2-(CH_Two)₆-(3-iPrS-cHx) H H 1-252 H H H Me 2-(CH_Two)₆-(4-iPrS-cHx) H H 1-253 H H H Me 2-(CH_Two)₆-[3- (2-Et-PrS) -cHx] H H 1-254 H H H Me 2-(CH_Two)₆-[4- (2-Et-PrS) -cHx] H H 1-255 H H H Me 2-(CH_Two)₆-(3-iBuS-cHx) H H 1-256 H H H Me 2-(CH_Two)₆-(4-iBuS-cHx) H H 1-257 H H H Me 2-(CH_Two)₆-(3-cHx-cHx) H H 1-258 H H H Me 2-(CH_Two)₆-(4-cHx-cHx) H H 1-259 H H H Me 2-(CH_Two)₆-(3-Ph-cHx) H H 1-260 H H H Me 2-(CH_Two)₆-(4-Ph-cHx) H H 1-261 H H H Me 2-(CH_Two)₆-(2,4-diMe-cHx) H H 1-262 H H H Me 2-(CH_Two)₆-(3,4-diMe-cHx) H H 1-263 H H H Me 2-(CH_Two)₆-(3,5-diMe-cHx) H H 1-264 H H H Me 2-(CH_Two)₆-Ph H H 1-265 H H H Me 2-(CH_Two)₆-Ph Me H 1-266 H H H Me 2-(CH_Two)₆-Ph H Me 1-267 H H H Me 2-(CH_Two)₆-Ph F H 1-268 H H H Me 2-(CH_Two)₆-Ph H F 1-269 H H Me Me 2-(CH_Two)₆-Ph H H 1-270 Me H H Me 2-(CH_Two)₆-Ph H H 1-271 CO_TwoMe H H Me 2-(CH_Two)₆-Ph H H 1-272 H H H Me 2-(CH_Two)₆-(3-F-Ph) H H 1-273 H H H Me 2-(CH_Two)₆-(4-F-Ph) H H 1-274 H H H Me 2-(CH_Two)₆-(4-Cl-Ph) H H 1-275 H H H Me 2-(CH_Two)₆-(4-Br-Ph) H H 1-276 H H H Me 2-(CH_Two)₆-(3-Me-Ph) H H 1-277 H H H Me 2-(CH_Two)₆-(4-Me-Ph) H H 1-278 H H H Me 2-(CH_Two)₆-(3-Et-Ph) H H 1-279 H H H Me 2-(CH_Two)₆-(4-Et-Ph) H H 1-280 H H H Me 2-(CH_Two)₆-(3-Pr-Ph) H H 1-281 H H H Me 2-(CH_Two)₆-(4-Pr-Ph) H H 1-282 H H H Me 2-(CH_Two)₆-(3-iPr-Ph) H H 1-283 H H H Me 2-(CH_Two)₆-(4-iPr-Ph) H H 1-284 H H H Me 2-(CH_Two)₆-(3-Bu-Ph) H H 1-285 H H H Me 2-(CH_Two)₆-(4-Bu-Ph) H H 1-286 H H H Me 2-(CH_Two)₆-(3-CF_Three-Ph) H H 1-287 H H H Me 2-(CH_Two)₆-(4-CF_Three-Ph) H H 1-288 H H H Me 2-(CH_Two)₆-(3-MeO-Ph) H H 1-289 H H H Me 2-(CH_Two)₆-(4-MeO-Ph) H H 1-290 H H H Me 2-(CH_Two)₆-(3-EtO-Ph) H H 1-291 H H H Me 2-(CH_Two)₆-(4-EtO-Ph) H H 1-292 H H H Me 2-(CH_Two)₆-(3-PrO-Ph) H H 1-293 H H H Me 2-(CH_Two)₆-(4-PrO-Ph) H H 1-294 H H H Me 2-(CH_Two)₆-(3-iPrO-Ph) H H 1-295 H H H Me 2-(CH_Two)₆-(4-iPrO-Ph) H H 1-296 H H H Me 2-(CH_Two)₆-[3- (2-Et-PrO) -Ph] H H 1-297 H H H Me 2-(CH_Two)₆-[4- (2-Et-PrO) -Ph] H H 1-298 H H H Me 2-(CH_Two)₆-(3-iBuO-Ph) H H 1-299 H H H Me 2-(CH_Two)₆-(4-iBuO-Ph) H H 1-300 H H H Me 2-(CH_Two)₆-(3-MeS-Ph) H H 1-301 H H H Me 2-(CH_Two)₆-(4-MeS-Ph) H H 1-302 H H H Me 2-(CH_Two)₆-(3-EtS-Ph) H H 1-303 H H H Me 2-(CH_Two)₆-(4-EtS-Ph) H H 1-304 H H H Me 2-(CH_Two)₆-(3-PrS-Ph) H H 1-305 H H H Me 2-(CH_Two)₆-(4-PrS-Ph) H H 1-306 H H H Me 2-(CH_Two)₆-(3-iPrS-Ph) H H 1-307 H H H Me 2-(CH_Two)₆-(4-iPrS-Ph) H H 1-308 H H H Me 2-(CH_Two)₆-[3- (2-Et-PrS) -Ph] H H 1-309 H H H Me 2-(CH_Two)₆-[4- (2-Et-PrS) -Ph] H H 1-310 H H H Me 2-(CH_Two)₆-(3-iBuS-Ph) H H 1-311 H H H Me 2-(CH_Two)₆-(4-iBuS-Ph) H H 1-312 H H H Me 2-(CH_Two)₆-(3-cHx-Ph) H H 1-313 H H H Me 2-(CH_Two)₆-(4-cHx-Ph) H H 1-314 H H H Me 2-(CH_Two)₆-(3-Ph-Ph) H H 1-315 H H H Me 2-(CH_Two)₆-(4-Ph-Ph) H H 1-316 H H H Me 2-(CH_Two)₆-(2,4-diMe-Ph) H H 1-317 H H H Me 2-(CH_Two)₆-(3,4-diMe-Ph) H H 1-318 H H H Me 2-(CH_Two)₆-(3,5-diMe-Ph) H H 1-319 H H H Me 2-(CH_Two)₆-Np (1) H H 1-320 H H H Me 2-(CH_Two)₆-Np (2) H H 1-321 H H H Me 2-(CH_Two)₇-cHx H H 1-322 H H Me Me 2-(CH_Two)₇-cHx H H 1-323 Me H H Me 2-(CH_Two)₇-cHx H H 1-324 CO_TwoMe H H Me 2-(CH_Two)₇-cHx H H 1-325 H H H Me 2-(CH_Two)₇-(4-F-cHx) H H 1-326 H H H Me 2-(CH_Two)₇-(4-Me-cHx) H H 1-327 H H H Me 2-(CH_Two)₇-(4-Et-cHx) H H 1-328 H H H Me 2-(CH_Two)₇-(4-CF_Three-cHx) H H 1-329 H H H Me 2-(CH_Two)₇-(4-MeO-cHx) H H 1-330 H H H Me 2-(CH_Two)₇-(4-EtO-cHx) H H 1-331 H H H Me 2-(CH_Two)₇-(4-MeS-cHx) H H 1-332 H H H Me 2-(CH_Two)₇-(4-cHx-cHx) H H 1-333 H H H Me 2-(CH_Two)₇-(4-Ph-cHx) H H 1-334 H H H Me 2-(CH_Two)₇-Ph H H 1-335 H H Me Me 2-(CH_Two)₇-Ph H H 1-336 Me H H Me 2-(CH_Two)₇-Ph H H 1-337 CO_TwoMe H H Me 2-(CH_Two)₇-Ph H H 1-338 H H H Me 2-(CH_Two)₇-(4-F-Ph) H H 1-339 H H H Me 2-(CH_Two)₇-(4-Me-Ph) H H 1-340 H H H Me 2-(CH_Two)₇-(4-Et-Ph) H H 1-341 H H H Me 2-(CH_Two)₇-(4-CF_Three-Ph) H H 1-342 H H H Me 2-(CH_Two)₇-(4-MeO-Ph) H H 1-343 H H H Me 2-(CH_Two)₇-(4-EtO-Ph) H H 1-344 H H H Me 2-(CH_Two)₇-(4-MeS-Ph) H H 1-345 H H H Me 2-(CH_Two)₇-(4-cHx-Ph) H H 1-346 H H H Me 2-(CH_Two)₇-(4-Ph-Ph) H H 1-347 H H H Me 2-(CH_Two)₈-cHx H H 1-348 H H Me Me 2-(CH_Two)₈-cHx H H 1-349 Me H H Me 2-(CH_Two)₈-cHx H H 1-350 CO_TwoMe H H Me 2-(CH_Two)₈-cHx H H 1-351 H H H Me 2-(CH_Two)₈-(4-F-cHx) H H 1-352 H H H Me 2-(CH_Two)₈-(4-Me-cHx) H H 1-353 H H H Me 2-(CH_Two)₈-(4-Et-cHx) H H 1-354 H H H Me 2-(CH_Two)₈-(4-CF_Three-cHx) H H 1-355 H H H Me 2-(CH_Two)₈-(4-MeO-cHx) H H 1-356 H H H Me 2-(CH_Two)₈-(4-EtO-cHx) H H 1-357 H H H Me 2-(CH_Two)₈-(4-MeS-cHx) H H 1-358 H H H Me 2-(CH_Two)₈-(4-cHx-cHx) H H 1-359 H H H Me 2-(CH_Two)₈-(4-Ph-cHx) H H 1-360 H H H Me 2-(CH_Two)₈-Ph H H 1-361 H H Me Me 2-(CH_Two)₈-Ph H H 1-362 Me H H Me 2-(CH_Two)₈-Ph H H 1-363 CO_TwoMe H H Me 2-(CH_Two)₈-Ph H H 1-364 H H H Me 2-(CH_Two)₈-(4-F-Ph) H H 1-365 H H H Me 2-(CH_Two)₈-(4-Me-Ph) H H 1-366 H H H Me 2-(CH_Two)₈-(4-Et-Ph) H H 1-367 H H H Me 2-(CH_Two)₈-(4-CF_Three-Ph) H H 1-368 H H H Me 2-(CH_Two)₈-(4-MeO-Ph) H H 1-369 H H H Me 2-(CH_Two)₈-(4-EtO-Ph) H H 1-370 H H H Me 2-(CH_Two)₈-(4-MeS-Ph) H H 1-371 H H H Me 2-(CH_Two)₈-(4-cHx-Ph) H H 1-372 H H H Me 2-(CH_Two)₈-(4-Ph-Ph) H H 1-373 H H H Me 2-(CH_Two)_Three-O-cHx H H 1-374 H H Me Me 2-(CH_Two)_Three-O-cHx H H 1-375 Me H H Me 2-(CH_Two)_Three-O-cHx H H 1-376 CO_TwoMe H H Me 2-(CH_Two)_Three-O-cHx H H 1-377 H H H Me 2-(CH_Two)_Three-O- (4-F-cHx) H H 1-378 H H H Me 2-(CH_Two)_Three-O- (4-Me-cHx) H H 1-379 H H H Me 2-(CH_Two)_Three-O- (4-Et-cHx) H H 1-380 H H H Me 2-(CH_Two)_Three-O- (4-CF_Three-cHx) H H 1-381 H H H Me 2-(CH_Two)_Three-O- (4-MeO-cHx) H H 1-382 H H H Me 2-(CH_Two)_Three-O- (4-EtO-cHx) H H 1-383 H H H Me 2-(CH_Two)_Three-O- (4-MeS-cHx) H H 1-384 H H H Me 2-(CH_Two)_Three-O- (4-cHx-cHx) H H 1-385 H H H Me 2-(CH_Two)_Three-O- (4-Ph-cHx) H H 1-386 H H H Me 2-(CH_Two)_Three-O-Ph H H 1-387 H H Me Me 2-(CH_Two)_Three-O-Ph H H 1-388 Me H H Me 2-(CH_Two)_Three-O-Ph H H 1-389 CO_TwoMe H H Me 2-(CH_Two)_Three-O-Ph H H 1-390 H H H Me 2-(CH_Two)_Three-O- (4-F-Ph) H H 1-391 H H H Me 2-(CH_Two)_Three-O- (4-Me-Ph) H H 1-392 H H H Me 2-(CH_Two)_Three-O- (4-Et-Ph) H H 1-393 H H H Me 2-(CH_Two)_Three-O- (4-CF_Three-Ph) H H 1-394 H H H Me 2-(CH_Two)_Three-O- (4-MeO-Ph) H H 1-395 H H H Me 2-(CH_Two)_Three-O- (4-EtO-Ph) H H 1-396 H H H Me 2-(CH_Two)_Three-O- (4-MeS-Ph) H H 1-397 H H H Me 2-(CH_Two)_Three-O- (4-cHx-Ph) H H 1-398 H H H Me 2-(CH_Two)_Three-O- (4-Ph-Ph) H H 1-399 H H H Me 2-(CH_Two)_Four-O-cPn H H 1-400 H H H Me 2-(CH_Two)_Four-O-cHx H H 1-401 H H H Me 2-(CH_Two)_Four-O-cHx Me H 1-402 H H H Me 2-(CH_Two)_Four-O-cHx H Me 1-403 H H H Me 2-(CH_Two)_Four-O-cHx F H 1-404 H H H Me 2-(CH_Two)_Four-O-cHx H F 1-405 H H Me Me 2-(CH_Two)_Four-O-cHx H H 1-406 Me H H Me 2-(CH_Two)_Four-O-cHx H H 1-407 CO_TwoMe H H Me 2-(CH_Two)_Four-O-cHx H H 1-408 H H H Me 2-(CH_Two)_Four-O- (3-F-cHx) H H 1-409 H H H Me 2-(CH_Two)_Four-O- (4-F-cHx) H H 1-410 H H H Me 2-(CH_Two)_Four-O- (4-Cl-cHx) H H 1-411 H H H Me 2-(CH_Two)_Four-O- (4-Br-cHx) H H 1-412 H H H Me 2-(CH_Two)_Four-O- (3-Me-cHx) H H 1-413 H H H Me 2-(CH_Two)_Four-O- (4-Me-cHx) H H 1-414 H H H Me 2-(CH_Two)_Four-O- (3-Et-cHx) H H 1-415 H H H Me 2-(CH_Two)_Four-O- (4-Et-cHx) H H 1-416 H H H Me 2-(CH_Two)_Four-O- (3-Pr-cHx) H H 1-417 H H H Me 2-(CH_Two)_Four-O- (4-Pr-cHx) H H 1-418 H H H Me 2-(CH_Two)_Four-O- (4-iPr-cHx) H H 1-419 H H H Me 2-(CH_Two)_Four-O- (3-Bu-cHx) H H 1-420 H H H Me 2-(CH_Two)_Four-O- (4-Bu-cHx) H H 1-421 H H H Me 2-(CH_Two)_Four-O- (3-CF_Three-cHx) H H 1-422 H H H Me 2-(CH_Two)_Four-O- (4-CF_Three-cHx) H H 1-423 H H H Me 2-(CH_Two)_Four-O- (3-MeO-cHx) H H 1-424 H H H Me 2-(CH_Two)_Four-O- (4-MeO-cHx) H H 1-425 H H H Me 2-(CH_Two)_Four-O- (3-EtO-cHx) H H 1-426 H H H Me 2-(CH_Two)_Four-O- (4-EtO-cHx) H H 1-427 H H H Me 2-(CH_Two)_Four-O- (3-PrO-cHx) H H 1-428 H H H Me 2-(CH_Two)_Four-O- (4-PrO-cHx) H H 1-429 H H H Me 2-(CH_Two)_Four-O- (3-iPrO-cHx) H H 1-430 H H H Me 2-(CH_Two)_Four-O- (4-iPrO-cHx) H H 1-431 H H H Me 2-(CH_Two)_Four-O- [3- (2-Et-PrO) -cHx] H H 1-432 H H H Me 2-(CH_Two)_Four-O- [4- (2-Et-PrO) -cHx] H H 1-433 H H H Me 2-(CH_Two)_Four-O- (3-iBuO-cHx) H H 1-434 H H H Me 2-(CH_Two)_Four-O- (4-iBuO-cHx) H H 1-435 H H H Me 2-(CH_Two)_Four-O- (3-MeS-cHx) H H 1-436 H H H Me 2-(CH_Two)_Four-O- (4-MeS-cHx) H H 1-437 H H H Me 2-(CH_Two)_Four-O- (3-EtS-cHx) H H 1-438 H H H Me 2-(CH_Two)_Four-O- (4-EtS-cHx) H H 1-439 H H H Me 2-(CH_Two)_Four-O- (3-PrS-cHx) H H 1-440 H H H Me 2-(CH_Two)_Four-O- (4-PrS-cHx) H H 1-441 H H H Me 2-(CH_Two)_Four-O- (3-iPrS-cHx) H H 1-442 H H H Me 2-(CH_Two)_Four-O- (4-iPrS-cHx) H H 1-443 H H H Me 2-(CH_Two)_Four-O- [3- (2-Et-PrS) -cHx] H H 1-444 H H H Me 2-(CH_Two)_Four-O- [4- (2-Et-PrS) -cHx] H H 1-445 H H H Me 2-(CH_Two)_Four-O- (3-iBuS-cHx) H H 1-446 H H H Me 2-(CH_Two)_Four-O- (4-iBuS-cHx) H H 1-447 H H H Me 2-(CH_Two)_Four-O- (3-cHx-cHx) H H 1-448 H H H Me 2-(CH_Two)_Four-O- (4-cHx-cHx) H H 1-449 H H H Me 2-(CH_Two)_Four-O- (3-Ph-cHx) H H 1-450 H H H Me 2-(CH_Two)_Four-O- (4-Ph-cHx) H H 1-451 H H H Me 2-(CH_Two)_Four-O- (2,4-diMe-cHx) H H 1-452 H H H Me 2-(CH_Two)_Four-O- (3,4-diMe-cHx) H H 1-453 H H H Me 2-(CH_Two)_Four-O- (3,5-diMe-cHx) H H 1-454 H H H Me 2-(CH_Two)_Four-O-Ph H H 1-455 H H H Me 2-(CH_Two)_Four-O-Ph Me H 1-456 H H H Me 2-(CH_Two)_Four-O-Ph H Me 1-457 H H H Me 2-(CH_Two)_Four-O-Ph F H 1-458 H H H Me 2-(CH_Two)_Four-O-Ph H F 1-459 H H Me Me 2-(CH_Two)_Four-O-Ph H H 1-460 Me H H Me 2-(CH_Two)_Four-O-Ph H H 1-461 CO_TwoMe H H Me 2-(CH_Two)_Four-O-Ph H H 1-462 H H H Me 2-(CH_Two)_Four-O- (3-F-Ph) H H 1-463 H H H Me 2-(CH_Two)_Four-O- (4-F-Ph) H H 1-464 H H H Me 2-(CH_Two)_Four-O- (4-Cl-Ph) H H 1-465 H H H Me 2-(CH_Two)_Four-O- (4-Br-Ph) H H 1-466 H H H Me 2-(CH_Two)_Four-O- (3-Me-Ph) H H 1-467 H H H Me 2-(CH_Two)_Four-O- (4-Me-Ph) H H 1-468 H H H Me 2-(CH_Two)_Four-O- (3-Et-Ph) H H 1-469 H H H Me 2-(CH_Two)_Four-O- (4-Et-Ph) H H 1-470 H H H Me 2-(CH_Two)_Four-O- (3-Pr-Ph) H H 1-471 H H H Me 2-(CH_Two)_Four-O- (4-Pr-Ph) H H 1-472 H H H Me 2-(CH_Two)_Four-O- (3-iPr-Ph) H H 1-473 H H H Me 2-(CH_Two)_Four-O- (4-iPr-Ph) H H 1-474 H H H Me 2-(CH_Two)_Four-O- (3-Bu-Ph) H H 1-475 H H H Me 2-(CH_Two)_Four-O- (4-Bu-Ph) H H 1-476 H H H Me 2-(CH_Two)_Four-O- (3-CF_Three-Ph) H H 1-477 H H H Me 2-(CH_Two)_Four-O- (4-CF_Three-Ph) H H 1-478 H H H Me 2-(CH_Two)_Four-O- (3-MeO-Ph) H H 1-479 H H H Me 2-(CH_Two)_Four-O- (4-MeO-Ph) H H 1-480 H H H Me 2-(CH_Two)_Four-O- (3-EtO-Ph) H H 1-481 H H H Me 2-(CH_Two)_Four-O- (4-EtO-Ph) H H 1-482 H H H Me 2-(CH_Two)_Four-O- (3-PrO-Ph) H H 1-483 H H H Me 2-(CH_Two)_Four-O- (4-PrO-Ph) H H 1-484 H H H Me 2-(CH_Two)_Four-O- (3-iPrO-Ph) H H 1-485 H H H Me 2-(CH_Two)_Four-O- (4-iPrO-Ph) H H 1-486 H H H Me 2-(CH_Two)_Four-O- [3- (2-Et-PrO) -Ph] H H 1-487 H H H Me 2-(CH_Two)_Four-O- [4- (2-Et-PrO) -Ph] H H 1-488 H H H Me 2-(CH_Two)_Four-O- (3-iBuO-Ph) H H 1-489 H H H Me 2-(CH_Two)_Four-O- (4-iBuO-Ph) H H 1-490 H H H Me 2-(CH_Two)_Four-O- (3-MeS-Ph) H H 1-491 H H H Me 2-(CH_Two)_Four-O- (4-MeS-Ph) H H 1-492 H H H Me 2-(CH_Two)_Four-O- (3-EtS-Ph) H H 1-493 H H H Me 2-(CH_Two)_Four-O- (4-EtS-Ph) H H 1-494 H H H Me 2-(CH_Two)_Four-O- (3-PrS-Ph) H H 1-495 H H H Me 2-(CH_Two)_Four-O- (4-PrS-Ph) H H 1-496 H H H Me 2-(CH_Two)_Four-O- (3-iPrS-Ph) H H 1-497 H H H Me 2-(CH_Two)_Four-O- (4-iPrS-Ph) H H 1-498 H H H Me 2-(CH_Two)_Four-O- [3- (2-Et-PrS) -Ph] H H 1-499 H H H Me 2-(CH_Two)_Four-O- [4- (2-Et-PrS) -Ph] H H 1-500 H H H Me 2-(CH_Two)_Four-O- (3-iBuS-Ph) H H 1 -501 H H H Me 2-(CH_Two)_Four-O- (4-iBuS-Ph) H H 1 -502 H H H Me 2-(CH_Two)_Four-O- (3-cHx-Ph) H H 1 -503 H H H Me 2-(CH_Two)_Four-O- (4-cHx-Ph) H H 1 -504 H H H Me 2-(CH_Two)_Four-O- (3-Ph-Ph) H H 1 -505 H H H Me 2-(CH_Two)_Four-O- (4-Ph-Ph) H H 1-506 H H H Me 2-(CH_Two)_Four-O- (2,4-diMe-Ph) H H 1-507 H H H Me 2-(CH_Two)_Four-O- (3,4-diMe-Ph) H H 1 -508 H H H Me 2-(CH_Two)_Four-O- (3,5-diMe-Ph) H H 1-509 H H H Me 2-(CH_Two)_Five-O-cHx H H 1-510 H H H Me 2-(CH_Two)_Five-O-Ph H H 1 -511 H H H Me 2-(CH_Two)₆-O-cHx H H 1 -512 H H H Me 2-(CH_Two)₆-O-Ph H H 1-513 H H H Me 2-(CH_Two)_Three-OCH_Two-cHx H H 1 -514 H H Me Me 2-(CH_Two)_Three-OCH_Two-cHx H H 1 -515 Me H H Me 2-(CH_Two)_Three-OCH_Two-cHx H H 1 -516 CO_TwoMe H H Me 2-(CH_Two)_Three-OCH_Two-cHx H H 1 -517 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-F-cHx) H H 1-518 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-Me-cHx) H H 1-519 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-Et-cHx) H H 1-520 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-CF_Three-cHx) H H 1 -521 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-MeO-cHx) H H 1-522 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-EtO-cHx) H H 1-523 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-MeS-cHx) H H 1-524 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-cHx-cHx) H H 1-525 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-Ph-cHx) H H 1-526 H H H Me 2-(CH_Two)_Three-OCH_Two-Ph H H 1 -527 H H Me Me 2-(CH_Two)_Three-OCH_Two-Ph H H 1 -528 Me H H Me 2-(CH_Two)_Three-OCH_Two-Ph H H 1-529 CO_TwoMe H H Me 2-(CH_Two)_Three-OCH_Two-Ph H H 1-530 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-F-Ph) H H 1-531 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-Me-Ph) H H 1-532 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-Et-Ph) H H 1 -533 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-CF_Three-Ph) H H 1 -534 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-MeO-Ph) H H 1-535 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-EtO-Ph) H H 1-536 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-MeS-Ph) H H 1-537 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-cHx-Ph) H H 1-538 H H H Me 2-(CH_Two)_Three-OCH_Two-(4-Ph-Ph) H H 1-539 H H H Me 2-(CH_Two)_Four-OCH_Two-cPn H H 1 -540 H H H Me 2-(CH_Two)_Four-OCH_Two-cHx H H 1 -541 H H H Me 2-(CH_Two)_Four-OCH_Two-cHx Me H 1-542 H H H Me 2-(CH_Two)_Four-OCH_Two-cHx H Me 1 -543 H H H Me 2-(CH_Two)_Four-OCH_Two-cHx F H 1-544 H H H Me 2-(CH_Two)_Four-OCH_Two-cHx H F 1 -545 H H Me Me 2-(CH_Two)_Four-OCH_Two-cHx H H 1 -546 Me H H Me 2-(CH_Two)_Four-OCH_Two-cHx H H 1-547 CO_TwoMe H H Me 2-(CH_Two)_Four-OCH_Two-cHx H H 1 -548 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-F-cHx) H H 1-549 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-F-cHx) H H 1-550 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Cl-cHx) H H 1-551 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Br-cHx) H H 1-552 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-Me-cHx) H H 1-553 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Me-cHx) H H 1-554 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-Et-cHx) H H 1-555 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Et-cHx) H H 1-556 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-Pr-cHx) H H 1-557 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Pr-cHx) H H 1 -558 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-iPr-cHx) H H 1-559 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-Bu-cHx) H H 1-560 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Bu-cHx) H H 1-561 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-CF_Three-cHx) H H 1 -562 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-CF_Three-cHx) H H 1 -563 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-MeO-cHx) H H 1-564 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-MeO-cHx) H H 1 -565 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-EtO-cHx) H H 1 -566 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-EtO-cHx) H H 1-567 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-PrO-cHx) H H 1 -568 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-PrO-cHx) H H 1 -569 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-iPrO-cHx) H H 1-570 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-iPrO-cHx) H H 1 -571 H H H Me 2-(CH_Two)_Four-OCH_Two-[3- (2-Et-PrO) -cHx] H H 1 -572 H H H Me 2-(CH_Two)_Four-OCH_Two-[4- (2-Et-PrO) -cHx] H H 1-573 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-iBuO-cHx) H H 1 -574 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-iBuO-cHx) H H 1 -575 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-MeS-cHx) H H 1-576 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-MeS-cHx) H H 1-577 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-EtS-cHx) H H 1-578 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-EtS-cHx) H H 1-579 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-PrS-cHx) H H 1 -580 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-PrS-cHx) H H 1 -581 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-iPrS-cHx) H H 1-582 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-iPrS-cHx) H H 1-583 H H H Me 2-(CH_Two)_Four-OCH_Two-[3- (2-Et-PrS) -cHx] H H 1-584 H H H Me 2-(CH_Two)_Four-OCH_Two-[4- (2-Et-PrS) -cHx] H H 1-585 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-iBuS-cHx) H H 1-586 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-iBuS-cHx) H H 1-587 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-cHx-cHx) H H 1 -588 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-cHx-cHx) H H 1-589 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-Ph-cHx) H H 1 -590 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Ph-cHx) H H 1-591 H H H Me 2-(CH_Two)_Four-OCH_Two-(2,4-diMe-cHx) H H 1-592 H H H Me 2-(CH_Two)_Four-OCH_Two-(3,4-diMe-cHx) H H 1-593 H H H Me 2-(CH_Two)_Four-OCH_Two-(3,5-diMe-cHx) H H 1-594 H H H Me 2-(CH_Two)_Four-OCH_Two-Ph H H 1-595 H H H Me 2-(CH_Two)_Four-OCH_Two-Ph Me H 1-596 H H H Me 2-(CH_Two)_Four-OCH_Two-Ph H Me 1-597 H H H Me 2-(CH_Two)_Four-OCH_Two-Ph F H 1-598 H H H Me 2-(CH_Two)_Four-OCH_Two-Ph H F 1-599 H H Me Me 2-(CH_Two)_Four-OCH_Two-Ph H H 1-600 Me H H Me 2-(CH_Two)_Four-OCH_Two-Ph H H 1 -601 CO_TwoMe H H Me 2-(CH_Two)_Four-OCH_Two-Ph H H 1 -602 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-F-Ph) H H 1-603 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-F-Ph) H H 1-604 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Cl-Ph) H H 1-605 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Br-Ph) H H 1-606 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-Me-Ph) H H 1-607 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Me-Ph) H H 1-608 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-Et-Ph) H H 1-609 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Et-Ph) H H 1 -610 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-Pr-Ph) H H 1-611 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Pr-Ph) H H 1-612 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-iPr-Ph) H H 1-613 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-iPr-Ph) H H 1-614 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-Bu-Ph) H H 1-615 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Bu-Ph) H H 1-616 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-CF_Three-Ph) H H 1-617 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-CF_Three-Ph) H H 1 -618 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-MeO-Ph) H H 1-619 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-MeO-Ph) H H 1-620 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-EtO-Ph) H H 1-621 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-EtO-Ph) H H 1-622 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-PrO-Ph) H H 1-623 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-PrO-Ph) H H 1-624 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-iPrO-Ph) H H 1-625 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-iPrO-Ph) H H 1-626 H H H Me 2-(CH_Two)_Four-OCH_Two-[3- (2-Et-PrO) -Ph] H H 1-627 H H H Me 2-(CH_Two)_Four-OCH_Two-[4- (2-Et-PrO) -Ph] H H 1-628 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-iBuO-Ph) H H 1-629 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-iBuO-Ph) H H 1-630 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-MeS-Ph) H H 1-631 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-MeS-Ph) H H 1-632 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-EtS-Ph) H H 1-633 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-EtS-Ph) H H 1-634 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-PrS-Ph) H H 1-635 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-PrS-Ph) H H 1-636 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-iPrS-Ph) H H 1-637 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-iPrS-Ph) H H 1-638 H H H Me 2-(CH_Two)_Four-OCH_Two-[3- (2-Et-PrS) -Ph] H H 1-639 H H H Me 2-(CH_Two)_Four-OCH_Two-[4- (2-Et-PrS) -Ph] H H 1-640 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-iBuS-Ph) H H 1-641 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-iBuS-Ph) H H 1-642 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-cHx-Ph) H H 1-643 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-cHx-Ph) H H 1-644 H H H Me 2-(CH_Two)_Four-OCH_Two-(3-Ph-Ph) H H 1-645 H H H Me 2-(CH_Two)_Four-OCH_Two-(4-Ph-Ph) H H 1-646 H H H Me 2-(CH_Two)_Four-OCH_Two-(2,4-diMe-Ph) H H 1-647 H H H Me 2-(CH_Two)_Four-OCH_Two-(3,4-diMe-Ph) H H 1-648 H H H Me 2-(CH_Two)_Four-OCH_Two-(3,5-diMe-Ph) H H 1-649 H H H Me 2-(CH_Two)_Five-OCH_Two-cHx H H 1 -650 H H H Me 2-(CH_Two)_Five-OCH_Two-Ph H H 1-651 H H H Me 2-(CH_Two)₆-OCH_Two-cHx H H 1 -652 H H H Me 2-(CH_Two)₆-OCH_Two-Ph H H 1-653 H H H Me 2 -CH = CH-cHx H H 1-654 H H H Me 2 -CH = CH-Ph H H 1-655 H H H Me 2 -CH = CH- (CH_Two)_Two-cHx H H 1-656 H H H Me 2 -CH = CH- (CH_Two)_Two-Ph H H 1-657 H H H Me 2 -CH = CH- (CH_Two)_Three-cHx H H 1-658 H H Me Me 2 -CH = CH- (CH_Two)_Three-cHx H H 1-659 Me H H Me 2 -CH = CH- (CH_Two)_Three-cHx H H 1-660 CO_TwoMe H H Me 2 -CH = CH- (CH_Two)_Three-cHx H H 1 -661 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-F-cHx) H H 1-662 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-Me-cHx) H H 1-663 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-Et-cHx) H H 1-664 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-CF_Three-cHx) H H 1 -665 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-MeO-cHx) H H 1-666 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-EtO-cHx) H H 1-667 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-MeS-cHx) H H 1-668 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-cHx-cHx) H H 1-669 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-Ph-cHx) H H 1-670 H H H Me 2 -CH = CH- (CH_Two)_Three-Ph H H 1-671 H H Me Me 2 -CH = CH- (CH_Two)_Three-Ph H H 1-672 Me H H Me 2 -CH = CH- (CH_Two)_Three-Ph H H 1-673 CO_TwoMe H H Me 2 -CH = CH- (CH_Two)_Three-Ph H H 1-674 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-F-Ph) H H 1-675 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-Me-Ph) H H 1-676 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-Et-Ph) H H 1-677 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-CF_Three-Ph) H H 1 -678 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-MeO-Ph) H H 1-679 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-EtO-Ph) H H 1-680 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-MeS-Ph) H H 1-681 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-cHx-Ph) H H 1-682 H H H Me 2 -CH = CH- (CH_Two)_Three-(4-Ph-Ph) H H 1-683 H H H Me 2 -CH = CH- (CH_Two)_Four-cHx H H 1 -684 H H Me Me 2 -CH = CH- (CH_Two)_Four-cHx H H 1-685 Me H H Me 2 -CH = CH- (CH_Two)_Four-cHx H H 1-686 CO_TwoMe H H Me 2 -CH = CH- (CH_Two)_Four-cHx H H 1-687 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-F-cHx) H H 1-688 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-Me-cHx) H H 1-689 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-Et-cHx) H H 1-690 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-CF_Three-cHx) H H 1-691 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-MeO-cHx) H H 1-692 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-EtO-cHx) H H 1-693 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-MeS-cHx) H H 1-694 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-cHx-cHx) H H 1-695 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-Ph-cHx) H H 1-696 H H H Me 2 -CH = CH- (CH_Two)_Four-Ph H H 1-697 H H Me Me 2 -CH = CH- (CH_Two)_Four-Ph H H 1-698 Me H H Me 2 -CH = CH- (CH_Two)_Four-Ph H H 1 -699 CO_TwoMe H H Me 2 -CH = CH- (CH_Two)_Four-Ph H H 1-700 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-F-Ph) H H 1-701 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-Me-Ph) H H 1-702 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-Et-Ph) H H 1-703 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-CF_Three-Ph) H H 1-704 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-MeO-Ph) H H 1-705 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-EtO-Ph) H H 1-706 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-MeS-Ph) H H 1-707 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-cHx-Ph) H H 1-708 H H H Me 2 -CH = CH- (CH_Two)_Four-(4-Ph-Ph) H H 1-709 H H H Me 2 -CH = CH- (CH_Two)_Five-cHx H H 1-710 H H H Me 2 -CH = CH- (CH_Two)_Five-Ph H H 1-711 H H H Me 2 -CH = CH- (CH_Two)₆-cHx H H 1-712 H H H Me 2 -CH = CH- (CH_Two)₆-Ph H H 1 -713 H H H Me 2 -C = C-CH_TwoO-cHx H H 1 -714 H H H Me 2 -C = C-CH_TwoO-Ph H H 1-715 H H H Me 2 -C = C- (CH_Two)_TwoO-cHx H H 1-716 H H H Me 2 -C = C- (CH_Two)_TwoO-Ph H H 1-717 H H H Me 2 -C≡C-cHx H H 1-718 H H Me Me 2 -C≡C-cHx H H 1-719 Me H H Me 2 -C≡C-cHx H H 1-720 CO_TwoMe HH Me 2 -C≡C-cHx HH 1-721 HHH Me 2 -C≡C- (4-F-cHx) HH 1-722 HHH Me 2 -C≡C- (4-Me-cHx) HH 1 -723 HHH Me 2 -C≡C- (4-Et-cHx) HH 1-724 HHH Me 2 -C≡C- (4-CF_Three-cHx) HH 1-725 HHH Me 2 -C≡C- (4-MeO-cHx) HH 1-726 HHH Me 2 -C≡C- (4-EtO-cHx) HH 1-727 HHH Me 2 -C ≡C- (4-MeS-cHx) HH 1-728 HHH Me 2 -C≡C- (4-cHx-cHx) HH 1-729 HHH Me 2 -C≡C- (4-Ph-cHx) HH 1 -730 HHH Me 2 -C≡C-Ph HH 1-731 HH Me Me 2 -C≡C-Ph HH 1-732 Me HH Me 2 -C≡C-Ph HH 1-733 CO_TwoMe HH Me 2 -C≡C-Ph HH 1-734 HHH Me 2 -C≡C- (4-F-Ph) HH 1-735 HHH Me 2 -C≡C- (4-Me-Ph) HH 1 -736 HHH Me 2 -C≡C- (4-Pr-Ph) HH 1-737 HHH Me 2 -C≡C- (4-Bu-Ph) HH 1-738 HHH Me 2 -C≡C- (4 -MeO-Ph) HH 1-739 HHH Me 2 -C≡C- (4-EtO-Ph) HH 1-740 HHH Me 2 -C≡C- (4-PrO-Ph) HH 1-741 HHH Me 2 -C≡C- (4-cHx-Ph) HH 1-742 HHH Me 2 -C≡C- (4-Ph-Ph) HH 1-743 HHH Me 2 -C≡C- (CH_Two)_Two-cHx H H 1 -744 H H Me Me 2 -C≡C- (CH_Two)_Two-cHx H H 1-745 Me H H Me 2 -C≡C- (CH_Two)_Two-cHx H H 1-746 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_Two-cHx H H 1 -747 H H H Me 2 -C≡C- (CH_Two)_Two-(4-F-cHx) H H 1-748 H H H Me 2 -C≡C- (CH_Two)_Two-(4-Me-cHx) H H 1-749 H H H Me 2 -C≡C- (CH_Two)_Two-(4-Et-cHx) H H 1-750 H H H Me 2 -C≡C- (CH_Two)_Two-(4-CF_Three-cHx) H H 1-751 H H H Me 2 -C≡C- (CH_Two)_Two-(4-MeO-cHx) H H 1-752 H H H Me 2 -C≡C- (CH_Two)_Two-(4-EtO-cHx) H H 1-753 H H H Me 2 -C≡C- (CH_Two)_Two-(4-MeS-cHx) H H 1-754 H H H Me 2 -C≡C- (CH_Two)_Two-(4-cHx-cHx) H H 1-755 H H H Me 2 -C≡C- (CH_Two)_Two-(4-Ph-cHx) H H 1-756 H H H Me 2 -C≡C- (CH_Two)_Two-Ph H H 1-757 H H Me Me 2 -C≡C- (CH_Two)_Two-Ph H H 1-758 Me H H Me 2 -C≡C- (CH_Two)_Two-Ph H H 1-759 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_Two-Ph H H 1 -760 H H H Me 2 -C≡C- (CH_Two)_Two-(4-F-Ph) H H 1-761 H H H Me 2 -C≡C- (CH_Two)_Two-(4-Me-Ph) H H 1-762 H H H Me 2 -C≡C- (CH_Two)_Two-(4-Et-Ph) H H 1-763 H H H Me 2 -C≡C- (CH_Two)_Two-(4-CF_Three-Ph) H H 1-764 H H H Me 2 -C≡C- (CH_Two)_Two-(4-MeO-Ph) H H 1-765 H H H Me 2 -C≡C- (CH_Two)_Two-(4-EtO-Ph) H H 1-766 H H H Me 2 -C≡C- (CH_Two)_Two-(4-MeS-Ph) H H 1-767 H H H Me 2 -C≡C- (CH_Two)_Two-(4-cHx-Ph) H H 1-768 H H H Me 2 -C≡C- (CH_Two)_Two-(4-Ph-Ph) H H 1-769 H H H Me 2 -C≡C- (CH_Two)_Three-cPn H H 1 -770 H H H Me 2 -C≡C- (CH_Two)_Three-cHx H H 1-771 H H H Me 2 -C≡C- (CH_Two)_Three-cHx Me H 1-772 H H H Me 2 -C≡C- (CH_Two)_Three-cHx H Me 1 -773 H H H Me 2 -C≡C- (CH_Two)_Three-cHx F H 1 -774 H H H Me 2 -C≡C- (CH_Two)_Three-cHx H F 1-775 H H Me Me 2 -C≡C- (CH_Two)_Three-cHx H H 1-776 Me H H Me 2 -C≡C- (CH_Two)_Three-cHx H H 1-777 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_Three-cHx H H 1 -778 H H H Me 2 -C≡C- (CH_Two)_Three-(3-F-cHx) H H 1-779 H H H Me 2 -C≡C- (CH_Two)_Three-(4-F-cHx) H H 1-780 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Cl-cHx) H H 1-781 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Br-cHx) H H 1-782 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Me-cHx) H H 1-783 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Me-cHx) H H 1-784 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Et-cHx) H H 1-785 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Et-cHx) H H 1-786 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Pr-cHx) H H 1-787 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Pr-cHx) H H 1-788 H H H Me 2 -C≡C- (CH_Two)_Three-(4-iPr-cHx) H H 1-789 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Bu-cHx) H H 1-790 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Bu-cHx) H H 1-791 H H H Me 2 -C≡C- (CH_Two)_Three-(3-CF_Three-cHx) H H 1 -792 H H H Me 2 -C≡C- (CH_Two)_Three-(4-CF_Three-cHx) H H 1 -793 H H H Me 2 -C≡C- (CH_Two)_Three-(3-MeO-cHx) H H 1-794 H H H Me 2 -C≡C- (CH_Two)_Three-(4-MeO-cHx) H H 1-795 H H H Me 2 -C≡C- (CH_Two)_Three-(3-EtO-cHx) H H 1-796 H H H Me 2 -C≡C- (CH_Two)_Three-(4-EtO-cHx) H H 1-797 H H H Me 2 -C≡C- (CH_Two)_Three-(3-PrO-cHx) H H 1-798 H H H Me 2 -C≡C- (CH_Two)_Three-(4-PrO-cHx) H H 1-799 H H H Me 2 -C≡C- (CH_Two)_Three-(3-iPrO-cHx) H H 1 -800 H H H Me 2 -C≡C- (CH_Two)_Three-(4-iPrO-cHx) H H 1-801 H H H Me 2 -C≡C- (CH_Two)_Three-[3- (2-Et-PrO) -cHx] H H 1-802 H H H Me 2 -C≡C- (CH_Two)_Three-[4- (2-Et-PrO) -cHx] H H 1-803 H H H Me 2 -C≡C- (CH_Two)_Three-(3-iBuO-cHx) H H 1-804 H H H Me 2 -C≡C- (CH_Two)_Three-(4-iBuO-cHx) H H 1-805 H H H Me 2 -C≡C- (CH_Two)_Three-(3-MeS-cHx) H H 1-806 H H H Me 2 -C≡C- (CH_Two)_Three-(4-MeS-cHx) H H 1-807 H H H Me 2 -C≡C- (CH_Two)_Three-(3-EtS-cHx) H H 1-808 H H H Me 2 -C≡C- (CH_Two)_Three-(4-EtS-cHx) H H 1-809 H H H Me 2 -C≡C- (CH_Two)_Three-(3-PrS-cHx) H H 1-810 H H H Me 2 -C≡C- (CH_Two)_Three-(4-PrS-cHx) H H 1-811 H H H Me 2 -C≡C- (CH_Two)_Three-(3-iPrS-cHx) H H 1-812 H H H Me 2 -C≡C- (CH_Two)_Three-(4-iPrS-cHx) H H 1-813 H H H Me 2 -C≡C- (CH_Two)_Three-[3- (2-Et-PrS) -cHx] H H 1-814 H H H Me 2 -C≡C- (CH_Two)_Three-[4- (2-Et-PrS) -cHx] H H 1-815 H H H Me 2 -C≡C- (CH_Two)_Three-(3-iBuS-cHx) H H 1-816 H H H Me 2 -C≡C- (CH_Two)_Three-(4-iBuS-cHx) H H 1-817 H H H Me 2 -C≡C- (CH_Two)_Three-(3-cHx-cHx) H H 1-818 H H H Me 2 -C≡C- (CH_Two)_Three-(4-cHx-cHx) H H 1-819 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Ph-cHx) H H 1-820 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Ph-cHx) H H 1-821 H H H Me 2 -C≡C- (CH_Two)_Three-(2,4-diMe-cHx) H H 1-822 H H H Me 2 -C≡C- (CH_Two)_Three-(3,4-diMe-cHx) H H 1-823 H H H Me 2 -C≡C- (CH_Two)_Three-(3,5-diMe-cHx) H H 1-824 H H H Me 2 -C≡C- (CH_Two)_Three-Ph H H 1-825 H H H Me 2 -C≡C- (CH_Two)_Three-Ph Me H 1-826 H H H Me 2 -C≡C- (CH_Two)_Three-Ph H Me 1-827 H H H Me 2 -C≡C- (CH_Two)_Three-Ph F H 1-828 H H H Me 2 -C≡C- (CH_Two)_Three-Ph H F 1 -829 H H Me Me 2 -C≡C- (CH_Two)_Three-Ph H H 1-830 Me H H Me 2 -C≡C- (CH_Two)_Three-Ph H H 1-831 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_Three-Ph H H 1-832 H H H Me 2 -C≡C- (CH_Two)_Three-(3-F-Ph) H H 1-833 H H H Me 2 -C≡C- (CH_Two)_Three-(4-F-Ph) H H 1-834 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Cl-Ph) H H 1-835 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Br-Ph) H H 1-836 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Me-Ph) H H 1-837 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Me-Ph) H H 1-838 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Et-Ph) H H 1-839 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Et-Ph) H H 1-840 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Pr-Ph) H H 1-841 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Pr-Ph) H H 1-842 H H H Me 2 -C≡C- (CH_Two)_Three-(3-iPr-Ph) H H 1-843 H H H Me 2 -C≡C- (CH_Two)_Three-(4-iPr-Ph) H H 1-844 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Bu-Ph) H H 1-845 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Bu-Ph) H H 1-846 H H H Me 2 -C≡C- (CH_Two)_Three-(3-CF_Three-Ph) H H 1 -847 H H H Me 2 -C≡C- (CH_Two)_Three-(4-CF_Three-Ph) H H 1 -848 H H H Me 2 -C≡C- (CH_Two)_Three-(3-MeO-Ph) H H 1-849 H H H Me 2 -C≡C- (CH_Two)_Three-(4-MeO-Ph) H H 1-850 H H H Me 2 -C≡C- (CH_Two)_Three-(3-EtO-Ph) H H 1-851 H H H Me 2 -C≡C- (CH_Two)_Three-(4-EtO-Ph) H H 1-852 H H H Me 2 -C≡C- (CH_Two)_Three-(3-PrO-Ph) H H 1-853 H H H Me 2 -C≡C- (CH_Two)_Three-(4-PrO-Ph) H H 1-854 H H H Me 2 -C≡C- (CH_Two)_Three-(3-iPrO-Ph) H H 1-855 H H H Me 2 -C≡C- (CH_Two)_Three-(4-iPrO-Ph) H H 1-856 H H H Me 2 -C≡C- (CH_Two)_Three-[3- (2-Et-PrO) -Ph] H H 1-857 H H H Me 2 -C≡C- (CH_Two)_Three-[4- (2-Et-PrO) -Ph] H H 1-858 H H H Me 2 -C≡C- (CH_Two)_Three-(3-iBuO-Ph) H H 1-859 H H H Me 2 -C≡C- (CH_Two)_Three-(4-iBuO-Ph) H H 1-860 H H H Me 2 -C≡C- (CH_Two)_Three-(3-MeS-Ph) H H 1-861 H H H Me 2 -C≡C- (CH_Two)_Three-(4-MeS-Ph) H H 1-862 H H H Me 2 -C≡C- (CH_Two)_Three-(3-EtS-Ph) H H 1-863 H H H Me 2 -C≡C- (CH_Two)_Three-(4-EtS-Ph) H H 1 -864 H H H Me 2 -C≡C- (CH_Two)_Three-(3-PrS-Ph) H H 1-865 H H H Me 2 -C≡C- (CH_Two)_Three-(4-PrS-Ph) H H 1-866 H H H Me 2 -C≡C- (CH_Two)_Three-(3-iPrS-Ph) H H 1-867 H H H Me 2 -C≡C- (CH_Two)_Three-(4-iPrS-Ph) H H 1 -868 H H H Me 2 -C≡C- (CH_Two)_Three-[3- (2-Et-PrS) -Ph] H H 1-869 H H H Me 2 -C≡C- (CH_Two)_Three-[4- (2-Et-PrS) -Ph] H H 1-870 H H H Me 2 -C≡C- (CH_Two)_Three-(3-iBuS-Ph) H H 1-871 H H H Me 2 -C≡C- (CH_Two)_Three-(4-iBuS-Ph) H H 1-872 H H H Me 2 -C≡C- (CH_Two)_Three-(3-cHx-Ph) H H 1-873 H H H Me 2 -C≡C- (CH_Two)_Three-(4-cHx-Ph) H H 1-874 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Ph-Ph) H H 1-875 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Ph-Ph) H H 1-876 H H H Me 2 -C≡C- (CH_Two)_Three-(2,4-diMe-Ph) H H 1-877 H H H Me 2 -C≡C- (CH_Two)_Three-(3,4-diMe-Ph) H H 1-878 H H H Me 2 -C≡C- (CH_Two)_Three-(3,5-diMe-Ph) H H 1-879 H H H Me 2 -C≡C- (CH_Two)_Three-Np (1) H H 1 -880 H H H Me 2 -C≡C- (CH_Two)_Three-Np (2) H H 1-881 H H H Me 2 -C≡C- (CH_Two)_Four-cPn H H 1 -882 H H H Me 2 -C≡C- (CH_Two)_Four-cHx H H 1 -883 H H H Me 2 -C≡C- (CH_Two)_Four-cHx Me H 1-884 H H H Me 2 -C≡C- (CH_Two)_Four-cHx H Me 1-885 H H H Me 2 -C≡C- (CH_Two)_Four-cHx F H 1-886 H H H Me 2 -C≡C- (CH_Two)_Four-cHx H F 1-887 H H Me Me 2 -C≡C- (CH_Two)_Four-cHx H H 1 -888 Me H H Me 2 -C≡C- (CH_Two)_Four-cHx H H 1-889 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_Four-cHx H H 1-890 H H H Me 2 -C≡C- (CH_Two)_Four-(3-F-cHx) H H 1-891 H H H Me 2 -C≡C- (CH_Two)_Four-(4-F-cHx) H H 1-892 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Cl-cHx) H H 1-893 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Br-cHx) H H 1-894 H H H Me 2 -C≡C- (CH_Two)_Four-(3-Me-cHx) H H 1-895 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Me-cHx) H H 1-896 H H H Me 2 -C≡C- (CH_Two)_Four-(3-Et-cHx) H H 1-897 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Et-cHx) H H 1-898 H H H Me 2 -C≡C- (CH_Two)_Four-(3-Pr-cHx) H H 1-899 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Pr-cHx) H H 1-900 H H H Me 2 -C≡C- (CH_Two)_Four-(4-iPr-cHx) H H 1-901 H H H Me 2 -C≡C- (CH_Two)_Four-(3-Bu-cHx) H H 1-902 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Bu-cHx) H H 1-903 H H H Me 2 -C≡C- (CH_Two)_Four-(3-CF_Three-cHx) H H 1 -904 H H H Me 2 -C≡C- (CH_Two)_Four-(4-CF_Three-cHx) H H 1-905 H H H Me 2 -C≡C- (CH_Two)_Four-(3-MeO-cHx) H H 1-906 H H H Me 2 -C≡C- (CH_Two)_Four-(4-MeO-cHx) H H 1-907 H H H Me 2 -C≡C- (CH_Two)_Four-(3-EtO-cHx) H H 1-908 H H H Me 2 -C≡C- (CH_Two)_Four-(4-EtO-cHx) H H 1-909 H H H Me 2 -C≡C- (CH_Two)_Four-(3-PrO-cHx) H H 1-910 H H H Me 2 -C≡C- (CH_Two)_Four-(4-PrO-cHx) H H 1-911 H H H Me 2 -C≡C- (CH_Two)_Four-(3-iPrO-cHx) H H 1-912 H H H Me 2 -C≡C- (CH_Two)_Four-(4-iPrO-cHx) H H 1-913 H H H Me 2 -C≡C- (CH_Two)_Four-[3- (2-Et-PrO) -cHx] H H 1-914 H H H Me 2 -C≡C- (CH_Two)_Four-[4- (2-Et-PrO) -cHx] H H 1-915 H H H Me 2 -C≡C- (CH_Two)_Four-(3-iBuO-cHx) H H 1-916 H H H Me 2 -C≡C- (CH_Two)_Four-(4-iBuO-cHx) H H 1-917 H H H Me 2 -C≡C- (CH_Two)_Four-(3-MeS-cHx) H H 1-918 H H H Me 2 -C≡C- (CH_Two)_Four-(4-MeS-cHx) H H 1-919 H H H Me 2 -C≡C- (CH_Two)_Four-(3-EtS-cHx) H H 1-920 H H H Me 2 -C≡C- (CH_Two)_Four-(4-EtS-cHx) H H 1-921 H H H Me 2 -C≡C- (CH_Two)_Four-(3-PrS-cHx) H H 1-922 H H H Me 2 -C≡C- (CH_Two)_Four-(4-PrS-cHx) H H 1-923 H H H Me 2 -C≡C- (CH_Two)_Four-(3-iPrS-cHx) H H 1-924 H H H Me 2 -C≡C- (CH_Two)_Four-(4-iPrS-cHx) H H 1-925 H H H Me 2 -C≡C- (CH_Two)_Four-[3- (2-Et-PrS) -cHx] H H 1-926 H H H Me 2 -C≡C- (CH_Two)_Four-[4- (2-Et-PrS) -cHx] H H 1-927 H H H Me 2 -C≡C- (CH_Two)_Four-(3-iBuS-cHx) H H 1-928 H H H Me 2 -C≡C- (CH_Two)_Four-(4-iBuS-cHx) H H 1-929 H H H Me 2 -C≡C- (CH_Two)_Four-(3-cHx-cHx) H H 1-930 H H H Me 2 -C≡C- (CH_Two)_Four-(4-cHx-cHx) H H 1-931 H H H Me 2 -C≡C- (CH_Two)_Four-(3-Ph-cHx) H H 1-932 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Ph-cHx) H H 1-933 H H H Me 2 -C≡C- (CH_Two)_Four-(2,4-diMe-cHx) H H 1-934 H H H Me 2 -C≡C- (CH_Two)_Four-(3,4-diMe-cHx) H H 1-935 H H H Me 2 -C≡C- (CH_Two)_Four-(3,5-diMe-cHx) H H 1-936 H H H Me 2 -C≡C- (CH_Two)_Four-Ph H H 1-937 H H H Me 2 -C≡C- (CH_Two)_Four-Ph Me H 1-938 H H H Me 2 -C≡C- (CH_Two)_Four-Ph H Me 1-939 H H H Me 2 -C≡C- (CH_Two)_Four-Ph F H 1-940 H H H Me 2 -C≡C- (CH_Two)_Four-Ph H F 1-941 H H Me Me 2 -C≡C- (CH_Two)_Four-Ph H H 1-942 Me H H Me 2 -C≡C- (CH_Two)_Four-Ph H H 1-943 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_Four-Ph H H 1-944 H H H Me 2 -C≡C- (CH_Two)_Four-(3-F-Ph) H H 1-945 H H H Me 2 -C≡C- (CH_Two)_Four-(4-F-Ph) H H 1-946 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Cl-Ph) H H 1-947 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Br-Ph) H H 1-948 H H H Me 2 -C≡C- (CH_Two)_Four-(3-Me-Ph) H H 1-949 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Me-Ph) H H 1-950 H H H Me 2 -C≡C- (CH_Two)_Four-(3-Et-Ph) H H 1-951 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Et-Ph) H H 1-952 H H H Me 2 -C≡C- (CH_Two)_Four-(3-Pr-Ph) H H 1-953 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Pr-Ph) H H 1-954 H H H Me 2 -C≡C- (CH_Two)_Four-(3-iPr-Ph) H H 1-955 H H H Me 2 -C≡C- (CH_Two)_Four-(4-iPr-Ph) H H 1-956 H H H Me 2 -C≡C- (CH_Two)_Four-(3-Bu-Ph) H H 1-957 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Bu-Ph) H H 1-958 H H H Me 2 -C≡C- (CH_Two)_Four-(3-CF_Three-Ph) H H 1-959 H H H Me 2 -C≡C- (CH_Two)_Four-(4-CF_Three-Ph) H H 1-960 H H H Me 2 -C≡C- (CH_Two)_Four-(3-MeO-Ph) H H 1-961 H H H Me 2 -C≡C- (CH_Two)_Four-(4-MeO-Ph) H H 1-962 H H H Me 2 -C≡C- (CH_Two)_Four-(3-EtO-Ph) H H 1-963 H H H Me 2 -C≡C- (CH_Two)_Four-(4-EtO-Ph) H H 1-964 H H H Me 2 -C≡C- (CH_Two)_Four-(3-PrO-Ph) H H 1-965 H H H Me 2 -C≡C- (CH_Two)_Four-(4-PrO-Ph) H H 1-966 H H H Me 2 -C≡C- (CH_Two)_Four-(3-iPrO-Ph) H H 1-967 H H H Me 2 -C≡C- (CH_Two)_Four-(4-iPrO-Ph) H H 1-968 H H H Me 2 -C≡C- (CH_Two)_Four-[3- (2-Et-PrO) -Ph] H H 1-969 H H H Me 2 -C≡C- (CH_Two)_Four-[4- (2-Et-PrO) -Ph] H H 1-970 H H H Me 2 -C≡C- (CH_Two)_Four-(3-iBuO-Ph) H H 1-971 H H H Me 2 -C≡C- (CH_Two)_Four-(4-iBuO-Ph) H H 1-972 H H H Me 2 -C≡C- (CH_Two)_Four-(3-MeS-Ph) H H 1-973 H H H Me 2 -C≡C- (CH_Two)_Four-(4-MeS-Ph) H H 1-974 H H H Me 2 -C≡C- (CH_Two)_Four-(3-EtS-Ph) H H 1-975 H H H Me 2 -C≡C- (CH_Two)_Four-(4-EtS-Ph) H H 1-976 H H H Me 2 -C≡C- (CH_Two)_Four-(3-PrS-Ph) H H 1-977 H H H Me 2 -C≡C- (CH_Two)_Four-(4-PrS-Ph) H H 1-978 H H H Me 2 -C≡C- (CH_Two)_Four-(3-iPrS-Ph) H H 1-979 H H H Me 2 -C≡C- (CH_Two)_Four-(4-iPrS-Ph) H H 1-980 H H H Me 2 -C≡C- (CH_Two)_Four-[3- (2-Et-PrS) -Ph] H H 1-981 H H H Me 2 -C≡C- (CH_Two)_Four-[4- (2-Et-PrS) -Ph] H H 1-982 H H H Me 2 -C≡C- (CH_Two)_Four-(3-iBuS-Ph) H H 1-983 H H H Me 2 -C≡C- (CH_Two)_Four-(4-iBuS-Ph) H H 1-984 H H H Me 2 -C≡C- (CH_Two)_Four-(3-cHx-Ph) H H 1-985 H H H Me 2 -C≡C- (CH_Two)_Four-(4-cHx-Ph) H H 1-986 H H H Me 2 -C≡C- (CH_Two)_Four-(3-Ph-Ph) H H 1-987 H H H Me 2 -C≡C- (CH_Two)_Four-(4-Ph-Ph) H H 1-988 H H H Me 2 -C≡C- (CH_Two)_Four-(2,4-diMe-Ph) H H 1-989 H H H Me 2 -C≡C- (CH_Two)_Four-(3,4-diMe-Ph) H H 1-990 H H H Me 2 -C≡C- (CH_Two)_Four-(3,5-diMe-Ph) H H 1-991 H H H Me 2 -C≡C- (CH_Two)_Four-Np (1) H H 1-992 H H H Me 2 -C≡C- (CH_Two)_Four-Np (2) H H 1-993 H H H Me 2 -C≡C- (CH_Two)_Five-cHx H H 1-994 H H Me Me 2 -C≡C- (CH_Two)_Five-cHx H H 1-995 Me H H Me 2 -C≡C- (CH_Two)_Five-cHx H H 1-996 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_Five-cHx H H 1-997 H H H Me 2 -C≡C- (CH_Two)_Five-(4-F-cHx) H H 1-998 H H H Me 2 -C≡C- (CH_Two)_Five-(4-Me-cHx) H H 1-999 H H H Me 2 -C≡C- (CH_Two)_Five-(4-Et-cHx) H H 1-1000 H H H Me 2 -C≡C- (CH_Two)_Five-(4-CF_Three-cHx) H H 1-1001 H H H Me 2 -C≡C- (CH_Two)_Five-(4-MeO-cHx) H H 1-1002 H H H Me 2 -C≡C- (CH_Two)_Five-(4-EtO-cHx) H H 1-1003 H H H Me 2 -C≡C- (CH_Two)_Five-(4-MeS-cHx) H H 1-1004 H H H Me 2 -C≡C- (CH_Two)_Five-(4-cHx-cHx) H H 1-1005 H H H Me 2 -C≡C- (CH_Two)_Five-(4-Ph-cHx) H H 1-1006 H H H Me 2 -C≡C- (CH_Two)_Five-Ph H H 1-1007 H H Me Me 2 -C≡C- (CH_Two)_Five-Ph H H 1-1008 Me H H Me 2 -C≡C- (CH_Two)_Five-Ph H H 1-1009 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_Five-Ph H H 1-1010 H H H Me 2 -C≡C- (CH_Two)_Five-(4-F-Ph) H H 1-1011 H H H Me 2 -C≡C- (CH_Two)_Five-(4-Me-Ph) H H 1-1012 H H H Me 2 -C≡C- (CH_Two)_Five-(4-Et-Ph) H H 1-1013 H H H Me 2 -C≡C- (CH_Two)_Five-(4-CF_Three-Ph) H H 1-1014 H H H Me 2 -C≡C- (CH_Two)_Five-(4-MeO-Ph) H H 1-1015 H H H Me 2 -C≡C- (CH_Two)_Five-(4-EtO-Ph) H H 1-1016 H H H Me 2 -C≡C- (CH_Two)_Five-(4-MeS-Ph) H H 1-1017 H H H Me 2 -C≡C- (CH_Two)_Five-(4-cHx-Ph) H H 1-1018 H H H Me 2 -C≡C- (CH_Two)_Five-(4-Ph-Ph) H H 1-1019 H H H Me 2 -C≡C- (CH_Two)₆-cHx H H 1-1020 H H Me Me 2 -C≡C- (CH_Two)₆-cHx H H 1-1021 Me H H Me 2 -C≡C- (CH_Two)₆-cHx H H 1-1022 CO_TwoMe H H Me 2 -C≡C- (CH_Two)₆-cHx H H 1-1023 H H H Me 2 -C≡C- (CH_Two)₆-(4-F-cHx) H H 1-1024 H H H Me 2 -C≡C- (CH_Two)₆-(4-Me-cHx) H H 1-1025 H H H Me 2 -C≡C- (CH_Two)₆-(4-Et-cHx) H H 1-1026 H H H Me 2 -C≡C- (CH_Two)₆-(4-CF_Three-cHx) H H 1-1027 H H H Me 2 -C≡C- (CH_Two)₆-(4-MeO-cHx) H H 1-1028 H H H Me 2 -C≡C- (CH_Two)₆-(4-EtO-cHx) H H 1-1029 H H H Me 2 -C≡C- (CH_Two)₆-(4-MeS-cHx) H H 1-1030 H H H Me 2 -C≡C- (CH_Two)₆-(4-cHx-cHx) H H 1-1031 H H H Me 2 -C≡C- (CH_Two)₆-(4-Ph-cHx) H H 1-1032 H H H Me 2 -C≡C- (CH_Two)₆-Ph H H 1-1033 H H Me Me 2 -C≡C- (CH_Two)₆-Ph H H 1-1034 Me H H Me 2 -C≡C- (CH_Two)₆-Ph H H 1-1035 CO_TwoMe H H Me 2 -C≡C- (CH_Two)₆-Ph H H 1-1036 H H H Me 2 -C≡C- (CH_Two)₆-(4-F-Ph) H H 1-1037 H H H Me 2 -C≡C- (CH_Two)₆-(4-Me-Ph) H H 1-1038 H H H Me 2 -C≡C- (CH_Two)₆-(4-Et-Ph) H H 1-1039 H H H Me 2 -C≡C- (CH_Two)₆-(4-CF_Three-Ph) H H 1-1040 H H H Me 2 -C≡C- (CH_Two)₆-(4-MeO-Ph) H H 1-1041 H H H Me 2 -C≡C- (CH_Two)₆-(4-EtO-Ph) H H 1-1042 H H H Me 2 -C≡C- (CH_Two)₆-(4-MeS-Ph) H H 1-1043 H H H Me 2 -C≡C- (CH_Two)₆-(4-cHx-Ph) H H 1-1044 H H H Me 2 -C≡C- (CH_Two)₆-(4-Ph-Ph) H H 1-1045 H H H Me 2 -C≡C-CH_Two-O-cHx H H 1-1046 H H Me Me 2 -C≡C-CH_Two-O-cHx H H 1-1047 Me H H Me 2 -C≡C-CH_Two-O-cHx H H 1-1048 CO_TwoMe H H Me 2 -C≡C-CH_Two-O-cHx H H 1-1049 H H H Me 2 -C≡C-CH_Two-O- (4-F-cHx) H H 1-1050 H H H Me 2 -C≡C-CH_Two-O- (4-Me-cHx) H H 1-1051 H H H Me 2 -C≡C-CH_Two-O- (4-Et-cHx) H H 1-1052 H H H Me 2 -C≡C-CH_Two-O- (4-CF_Three-cHx) H H 1-1053 H H H Me 2 -C≡C-CH_Two-O- (4-MeO-cHx) H H 1-1054 H H H Me 2 -C≡C-CH_Two-O- (4-EtO-cHx) H H 1-1055 H H H Me 2 -C≡C-CH_Two-O- (4-MeS-cHx) H H 1-1056 H H H Me 2 -C≡C-CH_Two-O- (4-cHx-cHx) H H 1-1057 H H H Me 2 -C≡C-CH_Two-O- (4-Ph-cHx) H H 1-1058 H H H Me 2 -C≡C-CH_Two-O-Ph H H 1-1059 H H Me Me 2 -C≡C-CH_Two-O-Ph H H 1-1060 Me H H Me 2 -C≡C-CH_Two-O-Ph H H 1-1061 CO_TwoMe H H Me 2 -C≡C-CH_Two-O-Ph H H 1-1062 H H H Me 2 -C≡C-CH_Two-O- (4-F-Ph) H H 1-1063 H H H Me 2 -C≡C-CH_Two-O- (4-Me-Ph) H H 1-1064 H H H Me 2 -C≡C-CH_Two-O- (4-Et-Ph) H H 1-1065 H H H Me 2 -C≡C-CH_Two-O- (4-CF_Three-Ph) H H 1-1066 H H H Me 2 -C≡C-CH_Two-O- (4-MeO-Ph) H H 1-1067 H H H Me 2 -C≡C-CH_Two-O- (4-EtO-Ph) H H 1-1068 H H H Me 2 -C≡C-CH_Two-O- (4-MeS-Ph) H H 1-1069 H H H Me 2 -C≡C-CH_Two-O- (4-cHx-Ph) H H 1-1070 H H H Me 2 -C≡C-CH_Two-O- (4-Ph-Ph) H H 1-1071 H H H Me 2 -C≡C- (CH_Two)_TwoO-cPn H H 1-1072 H H H Me 2 -C≡C- (CH_Two)_TwoO-cHx H H 1-1073 H H H Me 2 -C≡C- (CH_Two)_TwoO-cHx Me H 1-1074 H H H Me 2 -C≡C- (CH_Two)_TwoO-cHx H Me 1-1075 H H H Me 2 -C≡C- (CH_Two)_TwoO-cHx F H 1-1076 H H H Me 2 -C≡C- (CH_Two)_TwoO-cHx H F 1-1077 H H Me Me 2 -C≡C- (CH_Two)_TwoO-cHx H H 1-1078 Me H H Me 2 -C≡C- (CH_Two)_TwoO-cHx H H 1-1079 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_TwoO-cHx H H 1-1080 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-F-cHx) H H 1-1081 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-F-cHx) H H 1-1082 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Cl-cHx) H H 1-1083 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Br-cHx) H H 1-1084 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-Me-cHx) H H 1-1085 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Me-cHx) H H 1-1086 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-Et-cHx) H H 1-1087 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Et-cHx) H H 1-1088 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-Pr-cHx) H H 1-1089 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Pr-cHx) H H 1-1090 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-iPr-cHx) H H 1-1091 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-Bu-cHx) H H 1-1092 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Bu-cHx) H H 1-1093 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-CF_Three-cHx) H H 1-1094 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-CF_Three-cHx) H H 1-1095 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-MeO-cHx) H H 1-1096 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-MeO-cHx) H H 1-1097 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-EtO-cHx) H H 1-1098 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-EtO-cHx) H H 1-1099 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-PrO-cHx) H H 1-1100 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-PrO-cHx) H H 1-1101 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-iPrO-cHx) H H 1-1102 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-iPrO-cHx) H H 1-1103 H H H Me 2 -C≡C- (CH_Two)_TwoO- [3- (2-Et-PrO) -cHx] H H 1-1104 H H H Me 2 -C≡C- (CH_Two)_TwoO- [4- (2-Et-PrO) -cHx] H H 1-1105 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-iBuO-cHx) H H 1-1106 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-iBuO-cHx) H H 1-1107 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-MeS-cHx) H H 1-1108 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-MeS-cHx) H H 1-1109 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-EtS-cHx) H H 1-1110 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-EtS-cHx) H H 1-1111 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-PrS-cHx) H H 1-1112 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-PrS-cHx) H H 1-1113 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-iPrS-cHx) H H 1-1114 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-iPrS-cHx) H H 1-1115 H H H Me 2 -C≡C- (CH_Two)_TwoO- [3- (2-Et-PrS) -cHx] H H 1-1116 H H H Me 2 -C≡C- (CH_Two)_TwoO- [4- (2-Et-PrS) -cHx] H H 1-1117 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-iBuS-cHx) H H 1-1118 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-iBuS-cHx) H H 1-1119 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-cHx-cHx) H H 1-1120 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-cHx-cHx) H H 1-1121 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-Ph-cHx) H H 1-1122 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Ph-cHx) H H 1-1123 H H H Me 2 -C≡C- (CH_Two)_TwoO- (2,4-diMe-cHx) H H 1-1124 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3,4-diMe-cHx) H H 1-1125 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3,5-diMe-cHx) H H 1-1126 H H H Me 2 -C≡C- (CH_Two)_TwoO-Ph H H 1-1127 H H H Me 2 -C≡C- (CH_Two)_TwoO-Ph Me H 1-1128 H H H Me 2 -C≡C- (CH_Two)_TwoO-Ph H Me 1-1129 H H H Me 2 -C≡C- (CH_Two)_TwoO-Ph F H 1-1130 H H H Me 2 -C≡C- (CH_Two)_TwoO-Ph H F 1-1131 H H Me Me 2 -C≡C- (CH_Two)_TwoO-Ph H H 1-1132 Me H H Me 2 -C≡C- (CH_Two)_TwoO-Ph H H 1-1133 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_TwoO-Ph H H 1-1134 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-F-Ph) H H 1-1135 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-F-Ph) H H 1-1136 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Cl-Ph) H H 1-1137 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Br-Ph) H H 1-1138 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-Me-Ph) H H 1-1139 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Me-Ph) H H 1-1140 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-Et-Ph) H H 1-1141 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Et-Ph) H H 1-1142 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-Pr-Ph) H H 1-1143 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Pr-Ph) H H 1-1144 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-iPr-Ph) H H 1-1145 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-iPr-Ph) H H 1-1146 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-Bu-Ph) H H 1-1147 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Bu-Ph) H H 1-1148 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-CF_Three-Ph) H H 1-1149 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-CF_Three-Ph) H H 1-1150 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-MeO-Ph) H H 1-1151 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-MeO-Ph) H H 1-1152 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-EtO-Ph) H H 1-1153 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-EtO-Ph) H H 1-1154 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-PrO-Ph) H H 1-1155 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-PrO-Ph) H H 1-1156 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-iPrO-Ph) H H 1-1157 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-iPrO-Ph) H H 1-1158 H H H Me 2 -C≡C- (CH_Two)_TwoO- [3- (2-Et-PrO) -Ph] H H 1-1159 H H H Me 2 -C≡C- (CH_Two)_TwoO- [4- (2-Et-PrO) -Ph] H H 1-1160 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-iBuO-Ph) H H 1-1161 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-iBuO-Ph) H H 1-1162 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-MeS-Ph) H H 1-1163 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-MeS-Ph) H H 1-1164 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-EtS-Ph) H H 1-1165 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-EtS-Ph) H H 1-1166 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-PrS-Ph) H H 1-1167 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-PrS-Ph) H H 1-1168 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-iPrS-Ph) H H 1-1169 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-iPrS-Ph) H H 1-1170 H H H Me 2 -C≡C- (CH_Two)_TwoO- [3- (2-Et-PrS) -Ph] H H 1-1171 H H H Me 2 -C≡C- (CH_Two)_TwoO- [4- (2-Et-PrS) -Ph] H H 1-1172 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-iBuS-Ph) H H 1-1173 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-iBuS-Ph) H H 1-1174 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-cHx-Ph) H H 1-1175 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-cHx-Ph) H H 1-1176 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3-Ph-Ph) H H 1-1177 H H H Me 2 -C≡C- (CH_Two)_TwoO- (4-Ph-Ph) H H 1-1178 H H H Me 2 -C≡C- (CH_Two)_TwoO- (2,4-diMe-Ph) H H 1-1179 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3,4-diMe-Ph) H H 1-1180 H H H Me 2 -C≡C- (CH_Two)_TwoO- (3,5-diMe-Ph) H H 1-1181 H H H Me 2 -C≡C- (CH_Two)_ThreeO-cHx H H 1-1182 H H H Me 2 -C≡C- (CH_Two)_ThreeO-Ph H H 1-1183 H H H Me 2 -C≡C- (CH_Two)_FourO-cHx H H 1-1184 H H H Me 2 -C≡C- (CH_Two)_FourO-Ph H H 1-1185 H H H Me 2 -C≡C-CH_Two-OCH_Two-cHx H H 1-1186 H H Me Me 2 -C≡C-CH_Two-OCH_Two-cHx H H 1-1187 Me H H Me 2 -C≡C-CH_Two-OCH_Two-cHx H H 1-1188 CO_TwoMe H H Me 2 -C≡C-CH_Two-OCH_Two-cHx H H 1-1189 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-F-cHx) H H 1-1190 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-Me-cHx) H H 1-1191 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-Et-cHx) H H 1-1192 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-CF_Three-cHx) H H 1-1193 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-MeO-cHx) H H 1-1194 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-EtO-cHx) H H 1-1195 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-MeS-cHx) H H 1-1196 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-cHx-cHx) H H 1-1197 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-Ph-cHx) H H 1-1198 H H H Me 2 -C≡C-CH_Two-OCH_Two-Ph H H 1-1199 H H Me Me 2 -C≡C-CH_Two-OCH_Two-Ph H H 1-1200 Me H H Me 2 -C≡C-CH_Two-OCH_Two-Ph H H 1-1201 CO_TwoMe H H Me 2 -C≡C-CH_Two-OCH_Two-Ph H H 1-1202 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-F-Ph) H H 1-1203 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-Me-Ph) H H 1-1204 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-Et-Ph) H H 1-1205 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-CF_Three-Ph) H H 1-1206 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-MeO-Ph) H H 1-1207 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-EtO-Ph) H H 1-1208 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-MeS-Ph) H H 1-1209 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-cHx-Ph) H H 1-1210 H H H Me 2 -C≡C-CH_Two-OCH_Two-(4-Ph-Ph) H H 1-1211 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-cPn H H 1-1212 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-cHx H H 1-1213 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-cHx Me H 1-1214 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-cHx H Me 1-1215 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-cHx F H 1-1216 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-cHx H F 1-1217 H H Me Me 2 --C≡C- (CH_Two)_Two-OCH_Two-CH_Two-cHx H H 1-1218 Me H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-cHx H H 1-1219 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-cHx H H 1-1220 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-F-cHx) H H 1-1221 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-F-cHx) H H 1-1222 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Cl-cHx) H H 1-1223 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Br-cHx) H H 1-1224 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-Me-cHx) H H 1-1225 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Me-cHx) H H 1-1226 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-Et-cHx) H H 1-1227 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Et-cHx) H H 1-1228 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-Pr-cHx) H H 1-1229 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Pr-cHx) H H 1-1230 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-iPr-cHx) H H 1-1231 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-Bu-cHx) H H 1-1232 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Bu-cHx) H H 1-1233 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-CF_Three-cHx) H H 1-1234 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-CF_Three-cHx) H H 1-1235 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-MeO-cHx) H H 1-1236 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-MeO-cHx) H H 1-1237 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-EtO-cHx) H H 1-1238 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-EtO-cHx) H H 1-1239 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-PrO-cHx) H H 1-1240 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-PrO-cHx) H H 1-1241 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-iPrO-cHx) H H 1-1242 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-iPrO-cHx) H H 1-1243 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-[3- (2-Et-PrO) cHx] H H 1-1244 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-[4- (2-Et-PrO) cHx] H H 1-1245 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-iBuO-cHx) H H 1-1246 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-iBuO-cHx) H H 1-1247 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-MeS-cHx) H H 1-1248 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-MeS-cHx) H H 1-1249 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-EtS-cHx) H H 1-1250 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-EtS-cHx) H H 1-1251 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-PrS-cHx) H H 1-1252 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-PrS-cHx) H H 1-1253 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-iPrS-cHx) H H 1-1254 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-iPrS-cHx) H H 1-1255 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-[3- (2-Et-PrS) cHx] H H 1-1256 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-[4- (2-Et-PrS) cHx] H H 1-1257 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-iBuS-cHx) H H 1-1258 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-iBuS-cHx) H H 1-1259 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-cHx-cHx) H H 1-1260 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-cHx-cHx) H H 1-1261 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-Ph-cHx) H H 1-1262 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Ph-cHx) H H 1-1263 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(2,4-diMe-cHx) H H 1-1264 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3,4-diMe-cHx) H H 1-1265 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3,5-diMe-cHx) H H 1-1266 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-Ph H H 1-1267 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-Ph Me H 1-1268 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-Ph H Me 1-1269 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-Ph F H 1-1270 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-Ph H F 1-1271 H H Me Me 2 -C≡C- (CH_Two)_Two-OCH_Two-CH_Two-Ph H H 1-1272 Me H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-Ph H H 1-1273 CO_TwoMe H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-Ph H H 1-1274 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-F-Ph) H H 1-1275 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-F-Ph) H H 1-1276 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Cl-Ph) H H 1-1277 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Br-Ph) H H 1-1278 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-Me-Ph) H H 1-1279 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Me-Ph) H H 1-1280 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-Et-Ph) H H 1-1281 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Et-Ph) H H 1-1282 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-Pr-Ph) H H 1-1283 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Pr-Ph) H H 1-1284 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-iPr-Ph) H H 1-1285 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-iPr-Ph) H H 1-1286 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-Bu-Ph) H H 1-1287 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Bu-Ph) H H 1-1288 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-CF_Three-Ph) H H 1-1289 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-CF_Three-Ph) H H 1-1290 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-MeO-Ph) H H 1-1291 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-MeO-Ph) H H 1-1292 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-EtO-Ph) H H 1-1293 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-EtO-Ph) H H 1-1294 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-PrO-Ph) H H 1-1295 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-PrO-Ph) H H 1-1296 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-iPrO-Ph) H H 1-1297 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-iPrO-Ph) H H 1-1298 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-[3- (2-Et-PrO) Ph] H H 1-1299 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-[4- (2-Et-PrO) Ph] H H 1-1300 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-iBuO-Ph) H H 1-1301 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-iBuO-Ph) H H 1-1302 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-MeS-Ph) H H 1-1303 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-MeS-Ph) H H 1-1304 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-EtS-Ph) H H 1-1305 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-EtS-Ph) H H 1-1306 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-PrS-Ph) H H 1-1307 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-PrS-Ph) H H 1-1308 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-iPrS-Ph) H H 1-1309 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-iPrS-Ph) H H 1-1310 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-[3- (2-Et-PrS) Ph] H H 1-1311 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-[4- (2-Et-PrS) Ph] H H 1-1312 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-iBuS-Ph) H H 1-1313 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-iBuS-Ph) H H 1-1314 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-cHx-Ph) H H 1-1315 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-cHx-Ph) H H 1-1316 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3-Ph-Ph) H H 1-1317 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(4-Ph-Ph) H H 1-1318 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(2,4-diMe-Ph) H H 1-1319 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3,4-diMe-Ph) H H 1-1320 H H H Me 2 -C≡C- (CH_Two)_Two-OCH_Two-(3,5-diMe-Ph) H H 1-1321 H H H Me 2 -C≡C- (CH_Two)_Three-OCH_Two-cHx H H 1-1322 H H H Me 2 -C≡C- (CH_Two)_Three-OCH_Two-Ph H H 1-1323 H H H Me 2 -C≡C- (CH_Two)_Four-OCH_Two-cHx H H 1-1324 H H H Me 2 -C≡C- (CH_Two)_Four-OCH_Two-Ph H H 1-1325 H H H Me 2 -CO-CH_Two-(4-cHx-Ph) H H 1-1326 H H H Me 2 -CO-CH_Two-(4-Ph-Ph) H H 1-1327 H H H Me 2 -CO- (CH_Two)_Two-cHx H H 1-1328 H H H Me 2 -CO- (CH_Two)_Two-Ph H H 1-1329 H H H Me 2 -CO- (CH_Two)_Three-cHx H H 1-1330 H H H Me 2 -CO- (CH_Two)_Three-Ph H H 1-1331 H H H Me 2 -CO- (CH_Two)_Four-cHx H H 1-1332 H H Me Me 2 -CO- (CH_Two)_Four-cHx H H 1-1333 Me H H Me 2 -CO- (CH_Two)_Four-cHx H H 1-1334 CO_TwoMe H H Me 2 -CO- (CH_Two)_Four-cHx H H 1-1335 H H H Me 2 -CO- (CH_Two)_Four-(4-F-cHx) H H 1-1336 H H H Me 2 -CO- (CH_Two)_Four-(4-Me-cHx) H H 1-1337 H H H Me 2 -CO- (CH_Two)_Four-(4-Et-cHx) H H 1-1338 H H H Me 2 -CO- (CH_Two)_Four-(4-CF_Three-cHx) H H 1-1339 H H H Me 2 -CO- (CH_Two)_Four-(4-MeO-cHx) H H 1-1340 H H H Me 2 -CO- (CH_Two)_Four-(4-EtO-cHx) H H 1-1341 H H H Me 2 -CO- (CH_Two)_Four-(4-MeS-cHx) H H 1-1342 H H H Me 2 -CO- (CH_Two)_Four-(4-cHx-cHx) H H 1-1343 H H H Me 2 -CO- (CH_Two)_Four-(4-Ph-cHx) H H 1-1344 H H H Me 2 -CO- (CH_Two)_Four-Ph H H 1-1345 H H Me Me 2 -CO- (CH_Two)_Four-Ph H H 1-1346 Me H H Me 2 -CO- (CH_Two)_Four-Ph H H 1-1347 CO_TwoMe H H Me 2 -CO- (CH_Two)_Four-Ph H H 1-1348 H H H Me 2 -CO- (CH_Two)_Four-(4-F-Ph) H H 1-1349 H H H Me 2 -CO- (CH_Two)_Four-(4-Me-Ph) H H 1-1350 H H H Me 2 -CO- (CH_Two)_Four-(4-Et-Ph) H H 1-1351 H H H Me 2 -CO- (CH_Two)_Four-(4-CF_Three-Ph) H H 1-1352 H H H Me 2 -CO- (CH_Two)_Four-(4-MeO-Ph) H H 1-1353 H H H Me 2 -CO- (CH_Two)_Four-(4-EtO-Ph) H H 1-1354 H H H Me 2 -CO- (CH_Two)_Four-(4-MeS-Ph) H H 1-1355 H H H Me 2 -CO- (CH_Two)_Four-(4-cHx-Ph) H H 1-1356 H H H Me 2 -CO- (CH_Two)_Four-(4-Ph-Ph) H H 1-1357 H H H Me 2 -CO- (CH_Two)_Five-cHx H H 1-1358 H H Me Me 2 -CO- (CH_Two)_Five-cHx H H 1-1359 Me H H Me 2 -CO- (CH_Two)_Five-cHx H H 1-1360 CO_TwoMe H H Me 2 -CO- (CH_Two)_Five-cHx H H 1-1361 H H H Me 2 -CO- (CH_Two)_Five-(4-F-cHx) H H 1-1362 H H H Me 2 -CO- (CH_Two)_Five-(4-Me-cHx) H H 1-1363 H H H Me 2 -CO- (CH_Two)_Five-(4-Et-cHx) H H 1-1364 H H H Me 2 -CO- (CH_Two)_Five-(4-CF_Three-cHx) H H 1-1365 H H H Me 2 -CO- (CH_Two)_Five-(4-MeO-cHx) H H 1-1366 H H H Me 2 -CO- (CH_Two)_Five-(4-EtO-cHx) H H 1-1367 H H H Me 2 -CO- (CH_Two)_Five-(4-MeS-cHx) H H 1-1368 H H H Me 2 -CO- (CH_Two)_Five-(4-cHx-cHx) H H 1-1369 H H H Me 2 -CO- (CH_Two)_Five-(4-Ph-cHx) H H 1-1370 H H H Me 2 -CO- (CH_Two)_Five-Ph H H 1-1371 H H Me Me 2 -CO- (CH_Two)_Five-Ph H H 1-1372 Me H H Me 2 -CO- (CH_Two)_Five-Ph H H 1-1373 CO_TwoMe H H Me 2 -CO- (CH_Two)_Five-Ph H H 1-1374 H H H Me 2 -CO- (CH_Two)_Five-(4-F-Ph) H H 1-1375 H H H Me 2 -CO- (CH_Two)_Five-(4-Me-Ph) H H 1-1376 H H H Me 2 -CO- (CH_Two)_Five-(4-Et-Ph) H H 1-1377 H H H Me 2 -CO- (CH_Two)_Five-(4-CF_Three-Ph) H H 1-1378 H H H Me 2 -CO- (CH_Two)_Five-(4-MeO-Ph) H H 1-1379 H H H Me 2 -CO- (CH_Two)_Five-(4-EtO-Ph) H H 1-1380 H H H Me 2 -CO- (CH_Two)_Five-(4-MeS-Ph) H H 1-1381 H H H Me 2 -CO- (CH_Two)_Five-(4-cHx-Ph) H H 1-1382 H H H Me 2 -CO- (CH_Two)_Five-(4-Ph-Ph) H H 1-1383 H H H Me 2 -CO- (CH_Two)₆-cHx H H 1-1384 H H H Me 2 -CO- (CH_Two)₆-Ph H H 1-1385 H H H Me 2 -CO- (CH_Two)₇-cHx H H 1-1386 H H H Me 2 -CO- (CH_Two)₇-Ph H H 1-1387 H H H Me 2 -CO- (CH_Two)_Two-O-cHx H H 1-1388 H H Me Me 2 -CO- (CH_Two)_Two-O-cHx H H 1-1389 Me H H Me 2 -CO- (CH_Two)_Two-O-cHx H H 1-1390 CO_TwoMe H H Me 2 -CO- (CH_Two)_Two-O-cHx H H 1-1391 H H H Me 2 -CO- (CH_Two)_Two-O- (4-F-cHx) H H 1-1392 H H H Me 2 -CO- (CH_Two)_Two-O- (4-Me-cHx) H H 1-1393 H H H Me 2 -CO- (CH_Two)_Two-O- (4-Et-cHx) H H 1-1394 H H H Me 2 -CO- (CH_Two)_Two-O- (4-CF_Three-cHx) H H 1-1395 H H H Me 2 -CO- (CH_Two)_Two-O- (4-MeO-cHx) H H 1-1396 H H H Me 2 -CO- (CH_Two)_Two-O- (4-EtO-cHx) H H 1-1397 H H H Me 2 -CO- (CH_Two)_Two-O- (4-MeS-cHx) H H 1-1398 H H H Me 2 -CO- (CH_Two)_Two-O- (4-cHx-cHx) H H 1-1399 H H H Me 2 -CO- (CH_Two)_Two-O- (4-Ph-cHx) H H 1-1400 H H H Me 2 -CO- (CH_Two)_Two-O-Ph H H 1-1401 H H Me Me 2 -CO- (CH_Two)_Two-O-Ph H H 1-1402 Me H H Me 2 -CO- (CH_Two)_Two-O-Ph H H 1-1403 CO_TwoMe H H Me 2 -CO- (CH_Two)_Two-O-Ph H H 1-1404 H H H Me 2 -CO- (CH_Two)_Two-O- (4-F-Ph) H H 1-1405 H H H Me 2 -CO- (CH_Two)_Two-O- (4-Me-Ph) H H 1-1406 H H H Me 2 -CO- (CH_Two)_Two-O- (4-Et-Ph) H H 1-1407 H H H Me 2 -CO- (CH_Two)_Two-O- (4-CF_Three-Ph) H H 1-1408 H H H Me 2 -CO- (CH_Two)_Two-O- (4-MeO-Ph) H H 1-1409 H H H Me 2 -CO- (CH_Two)_Two-O- (4-EtO-Ph) H H 1-1410 H H H Me 2 -CO- (CH_Two)_Two-O- (4-MeS-Ph) H H 1-1411 H H H Me 2 -CO- (CH_Two)_Two-O- (4-cHx-Ph) H H 1-1412 H H H Me 2 -CO- (CH_Two)_Two-O- (4-Ph-Ph) H H 1-1413 H H H Me 2 -CO- (CH_Two)_Three-O-cPn H H 1-1414 H H H Me 2 -CO- (CH_Two)_Three-O-cHx H H 1-1415 H H H Me 2 -CO- (CH_Two)_Three-O-cHx Me H 1-1416 H H H Me 2 -CO- (CH_Two)_Three-O-cHx H Me 1-1417 H H H Me 2 -CO- (CH_Two)_Three-O-cHx F H 1-1418 H H H Me 2 -CO- (CH_Two)_Three-O-cHx H F 1-1419 H H Me Me 2 -CO- (CH_Two)_Three-O-cHx H H 1-1420 Me H H Me 2 -CO- (CH_Two)_Three-O-cHx H H 1-1421 CO_TwoMe H H Me 2 -CO- (CH_Two)_Three-O-cHx H H 1-1422 H H H Me 2 -CO- (CH_Two)_Three-O- (3-F-cHx) H H 1-1423 H H H Me 2 -CO- (CH_Two)_Three-O- (4-F-cHx) H H 1-1424 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Cl-cHx) H H 1-1425 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Br-cHx) H H 1-1426 H H H Me 2 -CO- (CH_Two)_Three-O- (3-Me-cHx) H H 1-1427 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Me-cHx) H H 1-1428 H H H Me 2 -CO- (CH_Two)_Three-O- (3-Et-cHx) H H 1-1429 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Et-cHx) H H 1-1430 H H H Me 2 -CO- (CH_Two)_Three-O- (3-Pr-cHx) H H 1-1431 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Pr-cHx) H H 1-1432 H H H Me 2 -CO- (CH_Two)_Three-O- (4-iPr-cHx) H H 1-1433 H H H Me 2 -CO- (CH_Two)_Three-O- (3-Bu-cHx) H H 1-1434 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Bu-cHx) H H 1-1435 H H H Me 2 -CO- (CH_Two)_Three-O- (3-CF_Three-cHx) H H 1-1436 H H H Me 2 -CO- (CH_Two)_Three-O- (4-CF_Three-cHx) H H 1-1437 H H H Me 2 -CO- (CH_Two)_Three-O- (3-MeO-cHx) H H 1-1438 H H H Me 2 -CO- (CH_Two)_Three-O- (4-MeO-cHx) H H 1-1439 H H H Me 2 -CO- (CH_Two)_Three-O- (3-EtO-cHx) H H 1-1440 H H H Me 2 -CO- (CH_Two)_Three-O- (4-EtO-cHx) H H 1-1441 H H H Me 2 -CO- (CH_Two)_Three-O- (3-PrO-cHx) H H 1-1442 H H H Me 2 -CO- (CH_Two)_Three-O- (4-PrO-cHx) H H 1-1443 H H H Me 2 -CO- (CH_Two)_Three-O- (3-iPrO-cHx) H H 1-1444 H H H Me 2 -CO- (CH_Two)_Three-O- (4-iPrO-cHx) H H 1-1445 H H H Me 2 -CO- (CH_Two)_Three-O- [3- (2-Et-PrO) cHx] H H 1-1446 H H H Me 2 -CO- (CH_Two)_Three-O- [4- (2-Et-PrO) cHx] H H 1-1447 H H H Me 2 -CO- (CH_Two)_Three-O- (3-iBuO-cHx) H H 1-1448 H H H Me 2 -CO- (CH_Two)_Three-O- (4-iBuO-cHx) H H 1-1449 H H H Me 2 -CO- (CH_Two)_Three-O- (3-MeS-cHx) H H 1-1450 H H H Me 2 -CO- (CH_Two)_Three-O- (4-MeS-cHx) H H 1-1451 H H H Me 2 -CO- (CH_Two)_Three-O- (3-EtS-cHx) H H 1-1452 H H H Me 2 -CO- (CH_Two)_Three-O- (4-EtS-cHx) H H 1-1453 H H H Me 2 -CO- (CH_Two)_Three-O- (3-PrS-cHx) H H 1-1454 H H H Me 2 -CO- (CH_Two)_Three-O- (4-PrS-cHx) H H 1-1455 H H H Me 2 -CO- (CH_Two)_Three-O- (3-iPrS-cHx) H H 1-1456 H H H Me 2 -CO- (CH_Two)_Three-O- (4-iPrS-cHx) H H 1-1457 H H H Me 2 -CO- (CH_Two)_Three-O- [3- (2-Et-PrS) cHx] H H 1-1458 H H H Me 2 -CO- (CH_Two)_Three-O- [4- (2-Et-PrS) cHx] H H 1-1459 H H H Me 2 -CO- (CH_Two)_Three-O- (3-iBuS-cHx) H H 1-1460 H H H Me 2 -CO- (CH_Two)_Three-O- (4-iBuS-cHx) H H 1-1461 H H H Me 2 -CO- (CH_Two)_Three-O- (3-cHx-cHx) H H 1-1462 H H H Me 2 -CO- (CH_Two)_Three-O- (4-cHx-cHx) H H 1-1463 H H H Me 2 -CO- (CH_Two)_Three-O- (3-Ph-cHx) H H 1-1464 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Ph-cHx) H H 1-1465 H H H Me 2 -CO- (CH_Two)_Three-O- (2,4-diMe-cHx) H H 1-1466 H H H Me 2 -CO- (CH_Two)_Three-O- (3,4-diMe-cHx) H H 1-1467 H H H Me 2 -CO- (CH_Two)_Three-O- (3,5-diMe-cHx) H H 1-1468 H H H Me 2 -CO- (CH_Two)_Three-O-Ph H H 1-1469 H H H Me 2 -CO- (CH_Two)_Three-O-Ph Me H 1-1470 H H H Me 2 -CO- (CH_Two)_Three-O-Ph H Me 1-1471 H H H Me 2 -CO- (CH_Two)_Three-O-Ph F H 1-1472 H H H Me 2 -CO- (CH_Two)_Three-O-Ph H F 1-1473 H H Me Me 2 -CO- (CH_Two)_Three-O-Ph H H 1-1474 Me H H Me 2 -CO- (CH_Two)_Three-O-Ph H H 1-1475 CO_TwoMe H H Me 2 -CO- (CH_Two)_Three-O-Ph H H 1-1476 H H H Me 2 -CO- (CH_Two)_Three-O- (3-F-Ph) H H 1-1477 H H H Me 2 -CO- (CH_Two)_Three-O- (4-F-Ph) H H 1-1478 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Cl-Ph) H H 1-1479 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Br-Ph) H H 1-1480 H H H Me 2 -CO- (CH_Two)_Three-O- (3-Me-Ph) H H 1-1481 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Me-Ph) H H 1-1482 H H H Me 2 -CO- (CH_Two)_Three-O- (3-Et-Ph) H H 1-1483 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Et-Ph) H H 1-1484 H H H Me 2 -CO- (CH_Two)_Three-O- (3-Pr-Ph) H H 1-1485 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Pr-Ph) H H 1-1486 H H H Me 2 -CO- (CH_Two)_Three-O- (3-iPr-Ph) H H 1-1487 H H H Me 2 -CO- (CH_Two)_Three-O- (4-iPr-Ph) H H 1-1488 H H H Me 2 -CO- (CH_Two)_Three-O- (3-Bu-Ph) H H 1-1489 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Bu-Ph) H H 1-1490 H H H Me 2 -CO- (CH_Two)_Three-O- (3-CF_Three-Ph) H H 1-1491 H H H Me 2 -CO- (CH_Two)_Three-O- (4-CF_Three-Ph) H H 1-1492 H H H Me 2 -CO- (CH_Two)_Three-O- (3-MeO-Ph) H H 1-1493 H H H Me 2 -CO- (CH_Two)_Three-O- (4-MeO-Ph) H H 1-1494 H H H Me 2 -CO- (CH_Two)_Three-O- (3-EtO-Ph) H H 1-1495 H H H Me 2 -CO- (CH_Two)_Three-O- (4-EtO-Ph) H H 1-1496 H H H Me 2 -CO- (CH_Two)_Three-O- (3-PrO-Ph) H H 1-1497 H H H Me 2 -CO- (CH_Two)_Three-O- (4-PrO-Ph) H H 1-1498 H H H Me 2 -CO- (CH_Two)_Three-O- (3-iPrO-Ph) H H 1-1499 H H H Me 2 -CO- (CH_Two)_Three-O- (4-iPrO-Ph) H H 1-1500 H H H Me 2 -CO- (CH_Two)_Three-O- [3- (2-Et-PrO) -Ph] H H 1-1501 H H H Me 2 -CO- (CH_Two)_Three-O- [4- (2-Et-PrO) -Ph] H H 1-1502 H H H Me 2 -CO- (CH_Two)_Three-O- (3-iBuO-Ph) H H 1-1503 H H H Me 2 -CO- (CH_Two)_Three-O- (4-iBuO-Ph) H H 1-1504 H H H Me 2 -CO- (CH_Two)_Three-O- (3-MeS-Ph) H H 1-1505 H H H Me 2 -CO- (CH_Two)_Three-O- (4-MeS-Ph) H H 1-1506 H H H Me 2 -CO- (CH_Two)_Three-O- (3-EtS-Ph) H H 1-1507 H H H Me 2 -CO- (CH_Two)_Three-O- (4-EtS-Ph) H H 1-1508 H H H Me 2 -CO- (CH_Two)_Three-O- (3-PrS-Ph) H H 1-1509 H H H Me 2 -CO- (CH_Two)_Three-O- (4-PrS-Ph) H H 1-1510 H H H Me 2 -CO- (CH_Two)_Three-O- (3-iPrS-Ph) H H 1-1511 H H H Me 2 -CO- (CH_Two)_Three-O- (4-iPrS-Ph) H H 1-1512 H H H Me 2 -CO- (CH_Two)_Three-O- [3- (2-Et-PrS) -Ph] H H 1-1513 H H H Me 2 -CO- (CH_Two)_Three-O- [4- (2-Et-PrS) -Ph] H H 1-1514 H H H Me 2 -CO- (CH_Two)_Three-O- (3-iBuS-Ph) H H 1-1515 H H H Me 2 -CO- (CH_Two)_Three-O- (4-iBuS-Ph) H H 1-1516 H H H Me 2 -CO- (CH_Two)_Three-O- (3-cHx-Ph) H H 1-1517 H H H Me 2 -CO- (CH_Two)_Three-O- (4-cHx-Ph) H H 1-1518 H H H Me 2 -CO- (CH_Two)_Three-O- (3-Ph-Ph) H H 1-1519 H H H Me 2 -CO- (CH_Two)_Three-O- (4-Ph-Ph) H H 1-1520 H H H Me 2 -CO- (CH_Two)_Three-O- (2,4-diMe-Ph) H H 1-1521 H H H Me 2 -CO- (CH_Two)_Three-O- (3,4-diMe-Ph) H H 1-1522 H H H Me 2 -CO- (CH_Two)_Three-O- (3,5-diMe-Ph) H H 1-1523 H H H Me 2 -CO- (CH_Two)_Four-O-cHx H H 1-1524 H H H Me 2 -CO- (CH_Two)_Four-O-Ph H H 1-1525 H H H Me 2 -CO- (CH_Two)_Five-O-cHx H H 1-1526 H H H Me 2 -CO- (CH_Two)_Five-O-Ph H H 1-1527 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-cHx H H 1-1528 H H Me Me 2 -CO- (CH_Two)_Two-OCH_Two-cHx H H 1-1529 Me H H Me 2 -CO- (CH_Two)_Two-OCH_Two-cHx H H 1-1530 CO_TwoMe H H Me 2 -CO- (CH_Two)_Two-OCH_Two-cHx H H 1-1531 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-F-cHx) H H 1-1532 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-Me-cHx) H H 1-1533 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-Et-cHx) H H 1-1534 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-CF_Three-cHx) H H 1-1535 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-MeO-cHx) H H 1-1536 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-EtO-cHx) H H 1-1537 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-MeS-cHx) H H 1-1538 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-cHx-cHx) H H 1-1539 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-Ph-cHx) H H 1-1540 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-Ph H H 1-1541 H H Me Me 2 -CO- (CH_Two)_Two-OCH_Two-Ph H H 1-1542 Me H H Me 2 -CO- (CH_Two)_Two-OCH_Two-Ph H H 1-1543 CO_TwoMe H H Me 2 -CO- (CH_Two)_Two-OCH_Two-Ph H H 1-1544 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-F-Ph) H H 1-1545 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-Me-Ph) H H 1-1546 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-Et-Ph) H H 1-1547 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-CF_Three-Ph) H H 1-1548 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-MeO-Ph) H H 1-1549 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-EtO-Ph) H H 1-1550 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-MeS-Ph) H H 1-1551 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-cHx-Ph) H H 1-1552 H H H Me 2 -CO- (CH_Two)_Two-OCH_Two-(4-Ph-Ph) H H 1-1553 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-CH_Two-cPn H H 1-1554 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-cHx H H 1-1555 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-cHx Me H 1-1556 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-cHx H Me 1-1557 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-cHx F H 1-1558 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-cHx H F 1-1559 H H Me Me 2 -CO- (CH_Two)_Three-OCH_Two-cHx H H 1-1560 Me H H Me 2 -CO- (CH_Two)_Three-OCH_Two-cHx H H 1-1561 CO_TwoMe H H Me 2 -CO- (CH_Two)_Three-OCH_Two-cHx H H 1-1562 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-F-cHx) H H 1-1563 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-F-cHx) H H 1-1564 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Cl-cHx) H H 1-1565 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Br-cHx) H H 1-1566 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-Me-cHx) H H 1-1567 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Me-cHx) H H 1-1568 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-Et-cHx) H H 1-1569 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Et-cHx) H H 1-1570 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-Pr-cHx) H H 1-1571 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Pr-cHx) H H 1-1572 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-iPr-cHx) H H 1-1573 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-Bu-cHx) H H 1-1574 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Bu-cHx) H H 1-1575 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-CF_Three-cHx) H H 1-1576 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-CF_Three-cHx) H H 1-1577 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-MeO-cHx) H H 1-1578 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-MeO-cHx) H H 1-1579 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-EtO-cHx) H H 1-1580 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-EtO-cHx) H H 1-1581 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-PrO-cHx) H H 1-1582 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-PrO-cHx) H H 1-1583 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-iPrO-cHx) H H 1-1584 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-iPrO-cHx) H H 1-1585 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-[3- (2-Et-PrO) cHx] H H 1-1586 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-[4- (2-Et-PrO) cHx] H H 1-1587 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-iBuO-cHx) H H 1-1588 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-iBuO-cHx) H H 1-1589 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-MeS-cHx) H H 1-1590 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-MeS-cHx) H H 1-1591 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-EtS-cHx) H H 1-1592 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-EtS-cHx) H H 1-1593 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-PrS-cHx) H H 1-1594 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-PrS-cHx) H H 1-1595 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-iPrS-cHx) H H 1-1596 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-iPrS-cHx) H H 1-1597 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-[3- (2-Et-PrS) cHx] H H 1-1598 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-[4- (2-Et-PrS) cHx] H H 1-1599 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-iBuS-cHx) H H 1-1600 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-iBuS-cHx) H H 1-1601 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-cHx-cHx) H H 1-1602 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-cHx-cHx) H H 1-1603 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-Ph-cHx) H H 1-1604 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Ph-cHx) H H 1-1605 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(2,4-diMe-cHx) H H 1-1606 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3,4-diMe-cHx) H H 1-1607 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3,5-diMe-cHx) H H 1-1608 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-Ph H H 1-1609 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-Ph Me H 1-1610 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-Ph H Me 1-1611 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-Ph F H 1-1612 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-Ph H F 1-1613 H H Me Me 2 -CO- (CH_Two)_Three-OCH_Two-Ph H H 1-1614 Me H H Me 2 -CO- (CH_Two)_Three-OCH_Two-Ph H H 1-1615 CO_TwoMe H H Me 2 -CO- (CH_Two)_Three-OCH_Two-Ph H H 1-1616 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-F-Ph) H H 1-1617 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-F-Ph) H H 1-1618 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Cl-Ph) H H 1-1619 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Br-Ph) H H 1-1620 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-Me-Ph) H H 1-1621 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Me-Ph) H H 1-1622 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-Et-Ph) H H 1-1623 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Et-Ph) H H 1-1624 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-Pr-Ph) H H 1-1625 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Pr-Ph) H H 1-1626 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-iPr-Ph) H H 1-1627 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-iPr-Ph) H H 1-1628 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-Bu-Ph) H H 1-1629 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Bu-Ph) H H 1-1630 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-CF_Three-Ph) H H 1-1631 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-CF_Three-Ph) H H 1-1632 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-MeO-Ph) H H 1-1633 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-MeO-Ph) H H 1-1634 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-EtO-Ph) H H 1-1635 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-EtO-Ph) H H 1-1636 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-PrO-Ph) H H 1-1637 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-PrO-Ph) H H 1-1638 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-iPrO-Ph) H H 1-1639 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-iPrO-Ph) H H 1-1640 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-[3- (2-Et-PrO) Ph] H H 1-1641 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-[4- (2-Et-PrO) Ph] H H 1-1642 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-iBuO-Ph) H H 1-1643 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-iBuO-Ph) H H 1-1644 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-MeS-Ph) H H 1-1645 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-MeS-Ph) H H 1-1646 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-EtS-Ph) H H 1-1647 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-EtS-Ph) H H 1-1648 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-PrS-Ph) H H 1-1649 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-PrS-Ph) H H 1-1650 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-iPrS-Ph) H H 1-1651 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-iPrS-Ph) H H 1-1652 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-[3- (2-Et-PrS) Ph] H H 1-1653 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-[4- (2-Et-PrS) Ph] H H 1-1654 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-iBuS-Ph) H H 1-1655 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-iBuS-Ph) H H 1-1656 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-cHx-Ph) H H 1-1657 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-cHx-Ph) H H 1-1658 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3-Ph-Ph) H H 1-1659 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(4-Ph-Ph) H H 1-1660 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(2,4-diMe-Ph) H H 1-1661 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3,4-diMe-Ph) H H 1-1662 H H H Me 2 -CO- (CH_Two)_Three-OCH_Two-(3,5-diMe-Ph) H H 1-1663 H H H Me 2 -CO- (CH_Two)_Four-OCH_Two-cHx H H 1-1664 H H H Me 2 -CO- (CH_Two)_Four-OCH_Two-Ph H H 1-1665 H H H Me 2 -CO- (CH_Two)_Five-OCH_Two-cHx H H 1-1666 H H H Me 2 -CO- (CH_Two)_Five-OCH_Two-Ph H H 1-1667 H H H Me 2 -CH (OH) -CH_Two-cHx H H 1-1668 H H H Me 2 -CH (OH) -CH_Two-Ph H H 1-1669 H H H Me 2 -CH (OH)-(CH_Two)_Two-cHx H H 1-1670 H H H Me 2 -CH (OH)-(CH_Two)_Two-Ph H H 1-1671 H H H Me 2 -CH (OH)-(CH_Two)_Three-cHx H H 1-1672 H H H Me 2 -CH (OH)-(CH_Two)_Three-Ph H H 1-1673 H H H Me 2 -CH (OH)-(CH_Two)_Four-cHx H H 1-1674 H H Me Me 2 -CH (OH)-(CH_Two)_Four-cHx H H 1-1675 Me H H Me 2 -CH (OH)-(CH_Two)_Four-cHx H H 1-1676 CO_TwoMe H H Me 2 -CH (OH)-(CH_Two)_Four-cHx H H 1-1677 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-F-cHx) H H 1-1678 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-Me-cHx) H H 1-1679 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-Et-cHx) H H 1-1680 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-CF_Three-cHx) H H 1-1681 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-MeO-cHx) H H 1-1682 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-EtO-cHx) H H 1-1683 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-MeS-cHx) H H 1-1684 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-cHx-cHx) H H 1-1685 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-Ph-cHx) H H 1-1686 H H H Me 2 -CH (OH)-(CH_Two)_Four-Ph H H 1-1687 H H Me Me 2 -CH (OH)-(CH_Two)_Four-Ph H H 1-1688 Me H H Me 2 -CH (OH)-(CH_Two)_Four-Ph H H 1-1689 CO_TwoMe H H Me 2 -CH (OH)-(CH_Two)_Four-Ph H H 1-1690 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-F-Ph) H H 1-1691 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-Me-Ph) H H 1-1692 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-Et-Ph) H H 1-1693 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-CF_Three-Ph) H H 1-1694 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-MeO-Ph) H H 1-1695 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-EtO-Ph) H H 1-1696 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-MeS-Ph) H H 1-1697 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-cHx-Ph) H H 1-1698 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-Ph-Ph) H H 1-1699 H H H Me 2 -CH (OH)-(CH_Two)_Five-cHx H H 1-1700 H H Me Me 2 -CH (OH)-(CH_Two)_Five-cHx H H 1-1701 Me H H Me 2 -CH (OH)-(CH_Two)_Five-cHx H H 1-1702 CO_TwoMe H H Me 2 -CH (OH)-(CH_Two)_Five-cHx H H 1-1703 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-F-cHx) H H 1-1704 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-Me-cHx) H H 1-1705 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-Et-cHx) H H 1-1706 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-CF_Three-cHx) H H 1-1707 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-MeO-cHx) H H 1-1708 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-EtO-cHx) H H 1-1709 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-MeS-cHx) H H 1-1710 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-cHx-cHx) H H 1-1711 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-Ph-cHx) H H 1-1712 H H H Me 2 -CH (OH)-(CH_Two)_Five-Ph H H 1-1713 H H Me Me 2 -CH (OH)-(CH_Two)_Five-Ph H H 1-1714 Me H H Me 2 -CH (OH)-(CH_Two)_Five-Ph H H 1-1715 CO_TwoMe H H Me 2 -CH (OH)-(CH_Two)_Five-Ph H H 1-1716 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-F-Ph) H H 1-1717 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-Me-Ph) H H 1-1718 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-Et-Ph) H H 1-1719 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-CF_Three-Ph) H H 1-1720 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-MeO-Ph) H H 1-1721 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-EtO-Ph) H H 1-1722 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-MeS-Ph) H H 1-1723 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-cHx-Ph) H H 1-1724 H H H Me 2 -CH (OH)-(CH_Two)_Five-(4-Ph-Ph) H H 1-1725 H H H Me 2 -CH (OH)-(CH_Two)₆-cHx H H 1-1726 H H H Me 2 -CH (OH)-(CH_Two)₆-Ph H H 1-1727 H H H Me 2 -CH (OH)-(CH_Two)₇-cHx H H 1-1728 H H H Me 2 -CH (OH)-(CH_Two)₇-Ph H H 1-1729 H H H Me 2 -4- (cHx-CH_TwoO) Ph H H 1-1730 H H Me Me 2 -4- (cHx-CH_TwoO) Ph H H 1-1731 Me H H Me 2 -4- (cHx-CH_TwoO) Ph H H 1-1732 CO_TwoMe H H Me 2 -4- (cHx-CH_TwoO) Ph H H 1-1733 H H H Me 2 -4- (cHx-CH_TwoO) -2-F-Ph H H 1-1734 H H H Me 2 -4- (cHx-CH_TwoO) -3-F-Ph H H 1-1735 H H H Me 2 -4- (cHx-CH_TwoO) -2,3-diF-Ph H H 1-1736 H H H Me 2 -4- (cHx-CH_TwoO) -2-Cl-Ph H H 1-1737 H H H Me 2 -4- (cHx-CH_TwoO) -3-Cl-Ph H H 1-1738 H H H Me 2 -4- (cHx-CH_TwoO) -2,3-diCl-Ph H H 1-1739 H H H Me 2 -4- (cHx-CH_TwoO) -2-Me-Ph H H 1-1740 H H H Me 2 -4- (cHx-CH_TwoO) -3-Me-Ph H H 1-1741 H H H Me 2 -4- (cHx-CH_TwoO) -2,3-diMe-Ph H H 1-1742 H H H Me 2 -4- [cHx- (CH_Two)_TwoO] Ph H H 1-1743 H H H Me 2 -4- [cHx- (CH_Two)_ThreeO] Ph HH 1-1744 HHH Me 2-(4-BzO-Ph) HH 1-1745 HH Me Me 2-(4-BzO-Ph) HH 1-1746 Me HH Me 2-(4-BzO-Ph) HH 1-1747 CO_TwoMe HH Me 2-(4-BzO-Ph) HH 1-1748 HHH Me 2-(4-BzO-2-F-Ph) HH 1-1749 HHH Me 2-(4-BzO-3-F-Ph) HH 1-1750 HHH Me 2-(4-BzO-2,3-diF-Ph) HH 1-1751 HHH Me 2-(4-BzO-2-Cl-Ph) HH 1-1752 HHH Me 2-(4 -BzO-3-Cl-Ph) HH 1-1753 HHH Me 2-(4-BzO-2,3-diCl-Ph) HH 1-1754 HHH Me 2-(4-BzO-2-Me-Ph) HH 1-1755 HHH Me 2-(4-BzO-3-Me-Ph) HH 1-1756 HHH Me 2-(4-BzO-2,3-diMe-Ph) HH 1-1757 HHH Me 2 -4- [ Ph- (CH_Two)_TwoO] -Ph H H 1-1758 H H H Me 2 -4- [Ph- (CH_Two)_ThreeO] -Ph H H 1-1759 H H H Et 2-(CH_Two)_Three-cHx H H 1-1760 H H H Et 2-(CH_Two)_Three-Ph H H 1-1761 H H H Et 2-(CH_Two)_Four-cHx H H 1-1762 H H H Et 2-(CH_Two)_Four-Ph H H 1-1763 H H H Et 2-(CH_Two)_Five-cPn H H 1-1764 H H H Et 2-(CH_Two)_Five-cHx H H 1-1765 H H H Et 2-(CH_Two)_Five-cHx Me H 1-1766 H H H Et 2-(CH_Two)_Five-cHx H Me 1-1767 H H H Et 2-(CH_Two)_Five-cHx F H 1-1768 H H H Et 2-(CH_Two)_Five-cHx H F 1-1769 H H Me Et 2-(CH_Two)_Five-cHx H H 1-1770 Me H H Et 2-(CH_Two)_Five-cHx H H 1-1771 CO_TwoMe H H Et 2-(CH_Two)_Five-cHx H H 1-1772 H H H Et 2-(CH_Two)_Five-(4-F-cHx) H H 1-1773 H H H Et 2-(CH_Two)_Five-(4-Cl-cHx) H H 1-1774 H H H Et 2-(CH_Two)_Five-(4-Br-cHx) H H 1-1775 H H H Et 2-(CH_Two)_Five-(4-Me-cHx) H H 1-1776 H H H Et 2-(CH_Two)_Five-(4-Et-cHx) H H 1-1777 H H H Et 2-(CH_Two)_Five-(4-Pr-cHx) H H 1-1778 H H H Et 2-(CH_Two)_Five-(4-iPr-cHx) H H 1-1779 H H H Et 2-(CH_Two)_Five-(4-CF_Three-cHx) H H 1-1780 H H H Et 2-(CH_Two)_Five-(4-MeO-cHx) H H 1-1781 H H H Et 2-(CH_Two)_Five-(4-EtO-cHx) H H 1-1782 H H H Et 2-(CH_Two)_Five-(4-PrO-cHx) H H 1-1783 H H H Et 2-(CH_Two)_Five-(4-iPrO-cHx) H H 1-1784 H H H Et 2-(CH_Two)_Five-(3-MeS-cHx) H H 1-1785 H H H Et 2-(CH_Two)_Five-(4-MeS-cHx) H H 1-1786 H H H Et 2-(CH_Two)_Five-(2,4-diMe-cHx) H H 1-1787 H H H Et 2-(CH_Two)_Five-(3,4-diMe-cHx) H H 1-1788 H H H Et 2-(CH_Two)_Five-(3,5-diMe-cHx) H H 1-1789 H H H Et 2-(CH_Two)_Five-Ph H H 1-1790 H H H Et 2-(CH_Two)_Five-Ph Me H 1-1791 H H H Et 2-(CH_Two)_Five-Ph H Me 1-1792 H H H Et 2-(CH_Two)_Five-Ph F H 1-1793 H H H Et 2-(CH_Two)_Five-Ph H F 1-1794 H H Me Et 2-(CH_Two)_Five-Ph H H 1-1795 Me H H Et 2-(CH_Two)_Five-Ph H H 1-1796 CO_TwoMe H H Et 2-(CH_Two)_Five-Ph H H 1-1797 H H H Et 2-(CH_Two)_Five-(4-F-Ph) H H 1-1798 H H H Et 2-(CH_Two)_Five-(4-Cl-Ph) H H 1-1799 H H H Et 2-(CH_Two)_Five-(4-Br-Ph) H H 1-1800 H H H Et 2-(CH_Two)_Five-(4-Me-Ph) H H 1-1801 H H H Et 2-(CH_Two)_Five-(4-Et-Ph) H H 1-1802 H H H Et 2-(CH_Two)_Five-(4-Pr-Ph) H H 1-1803 H H H Et 2-(CH_Two)_Five-(4-iPr-Ph) H H 1-1804 H H H Et 2-(CH_Two)_Five-(4-Bu-Ph) H H 1-1805 H H H Et 2-(CH_Two)_Five-(4-CF_Three-Ph) H H 1-1806 H H H Et 2-(CH_Two)_Five-(4-MeO-Ph) H H 1-1807 H H H Et 2-(CH_Two)_Five-(4-EtO-Ph) H H 1-1808 H H H Et 2-(CH_Two)_Five-(4-PrO-Ph) H H 1-1809 H H H Et 2-(CH_Two)_Five-(4-iPrO-Ph) H H 1-1810 H H H Et 2-(CH_Two)_Five-(3-MeS-Ph) H H 1-1811 H H H Et 2-(CH_Two)_Five-(4-MeS-Ph) H H 1-1812 H H H Et 2-(CH_Two)_Five-(2,4-diMe-Ph) H H 1-1813 H H H Et 2-(CH_Two)_Five-(3,4-diMe-Ph) H H 1-1814 H H H Et 2-(CH_Two)_Five-(3,5-diMe-Ph) H H 1-1815 H H H Et 2-(CH_Two)₆-cPn H H 1-1816 H H H Et 2-(CH_Two)₆-cHx H H 1-1817 H H H Et 2-(CH_Two)₆-cHx Me H 1-1818 H H H Et 2-(CH_Two)₆-cHx H Me 1-1819 H H H Et 2-(CH_Two)₆-cHx F H 1-1820 H H H Et 2-(CH_Two)₆-cHx H F 1-1821 H H Me Et 2-(CH_Two)₆-cHx H H 1-1822 Me H H Et 2-(CH_Two)₆-cHx H H 1-1823 CO_TwoMe H H Et 2-(CH_Two)₆-cHx H H 1-1824 H H H Et 2-(CH_Two)₆-(4-F-cHx) H H 1-1825 H H H Et 2-(CH_Two)₆-(4-Cl-cHx) H H 1-1826 H H H Et 2-(CH_Two)₆-(4-Br-cHx) H H 1-1827 H H H Et 2-(CH_Two)₆-(4-Me-cHx) H H 1-1828 H H H Et 2-(CH_Two)₆-(4-Et-cHx) H H 1-1829 H H H Et 2-(CH_Two)₆-(4-Pr-cHx) H H 1-1830 H H H Et 2-(CH_Two)₆-(4-iPr-cHx) H H 1-1831 H H H Et 2-(CH_Two)₆-(4-Bu-cHx) H H 1-1832 H H H Et 2-(CH_Two)₆-(4-CF_Three-cHx) H H 1-1833 H H H Et 2-(CH_Two)₆-(4-MeO-cHx) H H 1-1834 H H H Et 2-(CH_Two)₆-(4-EtO-cHx) H H 1-1835 H H H Et 2-(CH_Two)₆-(4-PrO-cHx) H H 1-1836 H H H Et 2-(CH_Two)₆-(4-iPrO-cHx) H H 1-1837 H H H Et 2-(CH_Two)₆-(3-MeS-cHx) H H 1-1838 H H H Et 2-(CH_Two)₆-(4-MeS-cHx) H H 1-1839 H H H Et 2-(CH_Two)₆-(2,4-diMe-cHx) H H 1-1840 H H H Et 2-(CH_Two)₆-(3,4-diMe-cHx) H H 1-1841 H H H Et 2-(CH_Two)₆-(3,5-diMe-cHx) H H 1-1842 H H H Et 2-(CH_Two)₆-Ph H H 1-1843 H H H Et 2-(CH_Two)₆-Ph Me H 1-1844 H H H Et 2-(CH_Two)₆-Ph H Me 1-1845 H H H Et 2-(CH_Two)₆-Ph F H 1-1846 H H H Et 2-(CH_Two)₆-Ph H F 1-1847 H H Me Et 2-(CH_Two)₆-Ph H H 1-1848 Me H H Et 2-(CH_Two)₆-Ph H H 1-1849 CO_TwoMe H H Et 2-(CH_Two)₆-Ph H H 1-1850 H H H Et 2-(CH_Two)₆-(4-F-Ph) H H 1-1851 H H H Et 2-(CH_Two)₆-(4-Cl-Ph) H H 1-1852 H H H Et 2-(CH_Two)₆-(4-Br-Ph) H H 1-1853 H H H Et 2-(CH_Two)₆-(4-Me-Ph) H H 1-1854 H H H Et 2-(CH_Two)₆-(4-Et-Ph) H H 1-1855 H H H Et 2-(CH_Two)₆-(4-Pr-Ph) H H 1-1856 H H H Et 2-(CH_Two)₆-(4-iPr-Ph) H H 1-1857 H H H Et 2-(CH_Two)₆-(4-Bu-Ph) H H 1-1858 H H H Et 2-(CH_Two)₆-(4-CF_Three-Ph) H H 1-1859 H H H Et 2-(CH_Two)₆-(4-MeO-Ph) H H 1-1860 H H H Et 2-(CH_Two)₆-(4-EtO-Ph) H H 1-1861 H H H Et 2-(CH_Two)₆-(4-PrO-Ph) H H 1-1862 H H H Et 2-(CH_Two)₆-(4-iPrO-Ph) H H 1-1863 H H H Et 2-(CH_Two)₆-(3-MeS-Ph) H H 1-1864 H H H Et 2-(CH_Two)₆-(4-MeS-Ph) H H 1-1865 H H H Et 2-(CH_Two)₆-(2,4-diMe-Ph) H H 1-1866 H H H Et 2-(CH_Two)₆-(3,4-diMe-Ph) H H 1-1867 H H H Et 2-(CH_Two)₆-(3,5-diMe-Ph) H H 1-1868 H H H Et 2-(CH_Two)₇-cHx H H 1-1869 H H H Et 2-(CH_Two)₇-Ph H H 1-1870 H H H Et 2 -CH = CH-cHx H H 1-1871 H H H Et 2 -CH = CH-Ph H H 1-1872 H H H Et 2 -CH = CH- (CH_Two)_Three-cHx H H 1-1873 H H Me Et 2 -CH = CH- (CH_Two)_Three-cHx H H 1-1874 Me H H Et 2 -CH = CH- (CH_Two)_Three-cHx H H 1-1875 CO_TwoMe H H Et 2 -CH = CH- (CH_Two)_Three-cHx H H 1-1876 H H H Et 2 -CH = CH- (CH_Two)_Three-Ph H H 1-1877 H H Me Et 2 -CH = CH- (CH_Two)_Three-Ph H H 1-1878 Me H H Et 2 -CH = CH- (CH_Two)_Three-Ph H H 1-1879 CO_TwoMe H H Et 2 -CH = CH- (CH_Two)_Three-Ph H H 1-1880 H H H Et 2 -CH = CH- (CH_Two)_Four-cHx H H 1-1881 H H Me Et 2 -CH = CH- (CH_Two)_Four-cHx H H 1-1882 Me H H Et 2 -CH = CH- (CH_Two)_Four-cHx H H 1-1883 CO_TwoMe H H Et 2 -CH = CH- (CH_Two)_Four-cHx H H 1-1884 H H H Et 2 -CH = CH- (CH_Two)_Four-Ph H H 1-1885 H H Me Et 2 -CH = CH- (CH_Two)_Four-Ph H H 1-1886 Me H H Et 2 -CH = CH- (CH_Two)_Four-Ph H H 1-1887 CO_TwoMe H H Et 2 -CH = CH- (CH_Two)_Four-Ph H H 1-1888 H H H Et 2 -CH = CH-CH_TwoO-cHx H H 1-1889 H H H Et 2 -CH = CH-CH_TwoO-Ph H H 1-1890 H H H Et 2 -CH = CH- (CH_Two)_TwoO-cHx H H 1-1891 H H H Et 2 -CH = CH- (CH_Two)_TwoO-Ph H H 1-1892 H H H Et 2 -C≡C-CH_Two-cHx H H 1-1893 H H Me Et 2 -C≡C-CH_Two-cHx H H 1-1894 Me H H Et 2 -C≡C-CH_Two-cHx H H 1-1895 CO_TwoMe H H Et 2 -C≡C-CH_Two-cHx H H 1-1896 H H H Et 2 -C≡C-CH_Two-Ph H H 1-1897 H H Me Et 2 -C≡C-CH_Two-Ph H H 1-1898 Me H H Et 2 -C≡C-CH_Two-Ph H H 1-1899 CO_TwoMe H H Et 2 -C≡C-CH_Two-Ph H H 1-1900 H H H Et 2 -C≡C- (CH_Two)_Two-cHx H H 1-1901 H H Me Et 2 -C≡C- (CH_Two)_Two-cHx H H 1-1902 Me H H Et 2 -C≡C- (CH_Two)_Two-cHx H H 1-1903 CO_TwoMe H H Et 2 -C≡C- (CH_Two)_Two-cHx H H 1-1904 H H H Et 2 -C≡C- (CH_Two)_Two-Ph H H 1-1905 H H Me Et 2 -C≡C- (CH_Two)_Two-Ph H H 1-1906 Me H H Et 2 -C≡C- (CH_Two)_Two-Ph H H 1-1907 CO_TwoMe H H Et 2 -C≡C- (CH_Two)_Two-Ph H H 1-1908 H H H Et 2 -C≡C- (CH_Two)_Three-cPn H H 1-1909 H H H Et 2 -C≡C- (CH_Two)_Three-cHx H H 1-1910 H H H Et 2 -C≡C- (CH_Two)_Three-cHx Me H 1-1911 H H H Et 2 -C≡C- (CH_Two)_Three-cHx H Me 1-1912 H H H Et 2 -C≡C- (CH_Two)_Three-cHx F H 1-1913 H H H Et 2 -C≡C- (CH_Two)_Three-cHx H F 1-1914 H H Me Et 2 -C≡C- (CH_Two)_Three-cHx H H 1-1915 Me H H Et 2 -C≡C- (CH_Two)_Three-cHx H H 1-1916 CO_TwoMe H H Et 2 -C≡C- (CH_Two)_Three-cHx H H 1-1917 H H H Et 2 -C≡C- (CH_Two)_Three-(4-F-cHx) H H 1-1918 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Cl-cHx) H H 1-1919 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Br-cHx) H H 1-1920 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Me-cHx) H H 1-1921 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Et-cHx) H H 1-1922 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Pr-cHx) H H 1-1923 H H H Et 2 -C≡C- (CH_Two)_Three-(4-iPr-cHx) H H 1-1924 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Bu-cHx) H H 1-1925 H H H Et 2 -C≡C- (CH_Two)_Three-(4-CF_Three-cHx) H H 1-1926 H H H Et 2 -C≡C- (CH_Two)_Three-(4-MeO-cHx) H H 1-1927 H H H Et 2 -C≡C- (CH_Two)_Three-(4-EtO-cHx) H H 1-1928 H H H Et 2 -C≡C- (CH_Two)_Three-(4-PrO-cHx) H H 1-1929 H H H Et 2 -C≡C- (CH_Two)_Three-(4-iPrO-cHx) H H 1-1930 H H H Et 2 -C≡C- (CH_Two)_Three-(3-MeS-cHx) H H 1-1931 H H H Et 2 -C≡C- (CH_Two)_Three-(4-MeS-cHx) H H 1-1932 H H H Et 2 -C≡C- (CH_Two)_Three-(2,4-diMe-cHx) H H 1-1933 H H H Et 2 -C≡C- (CH_Two)_Three-(3,4-diMe-cHx) H H 1-1934 H H H Et 2 -C≡C- (CH_Two)_Three-(3,5-diMe-cHx) H H 1-1935 H H H Et 2 -C≡C- (CH_Two)_Three-Ph H H 1-1936 H H H Et 2 -C≡C- (CH_Two)_Three-Ph Me H 1-1937 H H H Et 2 -C≡C- (CH_Two)_Three-Ph H Me 1-1938 H H H Et 2 -C≡C- (CH_Two)_Three-Ph F H 1-1939 H H H Et 2 -C≡C- (CH_Two)_Three-Ph H F 1-1940 H H Me Et 2 -C≡C- (CH_Two)_Three-Ph H H 1-1941 Me H H Et 2 -C≡C- (CH_Two)_Three-Ph H H 1-1942 CO_TwoMe H H Et 2 -C≡C- (CH_Two)_Three-Ph H H 1-1943 H H H Et 2 -C≡C- (CH_Two)_Three-(4-F-Ph) H H 1-1944 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Cl-Ph) H H 1-1945 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Br-Ph) H H 1-1946 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Me-Ph) H H 1-1947 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Et-Ph) H H 1-1948 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Pr-Ph) H H 1-1949 H H H Et 2 -C≡C- (CH_Two)_Three-(4-iPr-Ph) H H 1-1950 H H H Et 2 -C≡C- (CH_Two)_Three-(4-Bu-Ph) H H 1-1951 H H H Et 2 -C≡C- (CH_Two)_Three-(4-CF_Three-Ph) H H 1-1952 H H H Et 2 -C≡C- (CH_Two)_Three-(4-MeO-Ph) H H 1-1953 H H H Et 2 -C≡C- (CH_Two)_Three-(4-EtO-Ph) H H 1-1954 H H H Et 2 -C≡C- (CH_Two)_Three-(4-PrO-Ph) H H 1-1955 H H H Et 2 -C≡C- (CH_Two)_Three-(4-iPrO-Ph) H H 1-1956 H H H Et 2 -C≡C- (CH_Two)_Three-(3-MeS-Ph) H H 1-1957 H H H Et 2 -C≡C- (CH_Two)_Three-(4-MeS-Ph) H H 1-1958 H H H Et 2 -C≡C- (CH_Two)_Three-(2,4-diMe-Ph) H H 1-1959 H H H Et 2 -C≡C- (CH_Two)_Three-(3,4-diMe-Ph) H H 1-1960 H H H Et 2 -C≡C- (CH_Two)_Three-(3,5-diMe-Ph) H H 1-1961 H H H Et 2 -C≡C- (CH_Two)_Four-cPn H H 1-1962 H H H Et 2 -C≡C- (CH_Two)_Four-cHx H H 1-1963 H H H Et 2 -C≡C- (CH_Two)_Four-cHx Me H 1-1964 H H H Et 2 -C≡C- (CH_Two)_Four-cHx H Me 1-1965 H H H Et 2 -C≡C- (CH_Two)_Four-cHx F H 1-1966 H H H Et 2 -C≡C- (CH_Two)_Four-cHx H F 1-1967 H H Me Et 2 -C≡C- (CH_Two)_Four-cHx H H 1-1968 Me H H Et 2 -C≡C- (CH_Two)_Four-cHx H H 1-1969 CO_TwoMe H H Et 2 -C≡C- (CH_Two)_Four-cHx H H 1-1970 H H H Et 2 -C≡C- (CH_Two)_Four-(4-F-cHx) H H 1-1971 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Cl-cHx) H H 1-1972 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Br-cHx) H H 1-1973 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Me-cHx) H H 1-1974 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Et-cHx) H H 1-1975 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Pr-cHx) H H 1-1976 H H H Et 2 -C≡C- (CH_Two)_Four-(4-iPr-cHx) H H 1-1977 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Bu-cHx) H H 1-1978 H H H Et 2 -C≡C- (CH_Two)_Four-(4-CF_Three-cHx) H H 1 -1979 H H H Et 2 -C≡C- (CH_Two)_Four-(4-MeO-cHx) H H 1-1980 H H H Et 2 -C≡C- (CH_Two)_Four-(4-EtO-cHx) H H 1-1981 H H H Et 2 -C≡C- (CH_Two)_Four-(4-PrO-cHx) H H 1-1982 H H H Et 2 -C≡C- (CH_Two)_Four-(4-iPrO-cHx) H H 1 -1983 H H H Et 2 -C≡C- (CH_Two)_Four-(4-MeS-cHx) H H 1-1984 H H H Et 2 -C≡C- (CH_Two)_Four-(2,4-diMe-cHx) H H 1-1985 H H H Et 2 -C≡C- (CH_Two)_Four-(3,4-diMe-cHx) H H 1-1986 H H H Et 2 -C≡C- (CH_Two)_Four-(3,5-diMe-cHx) H H 1-1987 H H H Et 2 -C≡C- (CH_Two)_Four-Ph H H 1-1988 H H H Et 2 -C≡C- (CH_Two)_Four-Ph Me H 1-1989 H H H Et 2 -C≡C- (CH_Two)_Four-Ph H Me 1-1990 H H H Et 2 -C≡C- (CH_Two)_Four-Ph F H 1-1991 H H H Et 2 -C≡C- (CH_Two)_Four-Ph H F 1-1992 H H Me Et 2 -C≡C- (CH_Two)_Four-Ph H H 1-1993 Me H H Et 2 -C≡C- (CH_Two)_Four-Ph H H 1-1994 CO_TwoMe H H Et 2 -C≡C- (CH_Two)_Four-Ph H H 1-1995 H H H Et 2 -C≡C- (CH_Two)_Four-(4-F-Ph) H H 1-1996 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Cl-Ph) H H 1-1997 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Br-Ph) H H 1-1998 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Me-Ph) H H 1-1999 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Et-Ph) H H 1-2000 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Pr-Ph) H H 1-2001 H H H Et 2 -C≡C- (CH_Two)_Four-(4-iPr-Ph) H H 1-2002 H H H Et 2 -C≡C- (CH_Two)_Four-(4-Bu-Ph) H H 1-2003 H H H Et 2 -C≡C- (CH_Two)_Four-(4-CF_Three-Ph) H H 1 -2004 H H H Et 2 -C≡C- (CH_Two)_Four-(4-MeO-Ph) H H 1-2005 H H H Et 2 -C≡C- (CH_Two)_Four-(4-EtO-Ph) H H 1-2006 H H H Et 2 -C≡C- (CH_Two)_Four-(4-PrO-Ph) H H 1-2007 H H H Et 2 -C≡C- (CH_Two)_Four-(4-iPrO-Ph) H H 1-2008 H H H Et 2 -C≡C- (CH_Two)_Four-(3-MeS-Ph) H H 1-2009 H H H Et 2 -C≡C- (CH_Two)_Four-(4-MeS-Ph) H H 1-2010 H H H Et 2 -C≡C- (CH_Two)_Four-(2,4-diMe-Ph) H H 1-2011 H H H Et 2 -C≡C- (CH_Two)_Four-(3,4-diMe-Ph) H H 1-2012 H H H Et 2 -C≡C- (CH_Two)_Four-(3,5-diMe-Ph) H H 1-2013 H H H Et 2 -C≡C- (CH_Two)_Five-cHx H H 1-2014 H H Me Et 2 -C≡C- (CH_Two)_Five-cHx H H 1-2015 Me H H Et 2 -C≡C- (CH_Two)_Five-cHx H H 1 -2016 CO_TwoMe H H Et 2 -C≡C- (CH_Two)_Five-cHx H H 1-2017 H H H Et 2 -C≡C- (CH_Two)_Five-Ph H H 1-2018 H H Me Et 2 -C≡C- (CH_Two)_Five-Ph H H 1-2019 Me H H Et 2 -C≡C- (CH_Two)_Five-Ph H H 1-2020 CO_TwoMe H H Et 2 -C≡C- (CH_Two)_Five-Ph H H 1-2021 H H H Et 2 -C≡C- (CH_Two)₆-cHx H H 1-2022 H H Me Et 2 -C≡C- (CH_Two)₆-cHx H H 1-2023 Me H H Et 2 -C≡C- (CH_Two)₆-cHx H H 1-2024 CO_TwoMe H H Et 2 -C≡C- (CH_Two)₆-cHx H H 1-2025 H H H Et 2 -C≡C- (CH_Two)₆-Ph H H 1-2026 H H Me Et 2 -C≡C- (CH_Two)₆-Ph H H 1-2027 Me H H Et 2 -C≡C- (CH_Two)₆-Ph H H 1-2028 CO_TwoMe H H Et 2 -C≡C- (CH_Two)₆-Ph H H 1-2029 H H H Et 2 -C≡C-CH_TwoO-cHx H H 1-2030 H H Me Et 2 -C≡C-CH_TwoO-cHx H H 1-2031 Me H H Et 2 -C≡C-CH_TwoO-cHx H H 1-2032 CO_TwoMe H H Et 2 -C≡C-CH_TwoO-cHx H H 1-2033 H H H Et 2 -C≡C-CH_TwoO-Ph H H 1-2034 H H Me Et 2 -C≡C-CH_TwoO-Ph H H 1-2035 Me H H Et 2 -C≡C-CH_TwoO-Ph H H 1-2036 CO_TwoMe H H Et 2 -C≡C-CH_TwoO-Ph H H 1-2037 H H H Et 2 -C≡C- (CH_Two)_TwoO-cPn H H 1-2038 H H H Et 2 -C≡C- (CH_Two)_TwoO-cHx H H 1-2039 H H H Et 2 -C≡C- (CH_Two)_TwoO-cHx Me H 1-2040 H H H Et 2 -C≡C- (CH_Two)_TwoO-cHx H Me 1-2041 H H H Et 2 -C≡C- (CH_Two)_TwoO-cHx F H 1-2042 H H H Et 2 -C≡C- (CH_Two)_TwoO-cHx H F 1-2043 H H Me Et 2 -C≡C- (CH_Two)_TwoO-cHx H H 1-2044 Me H H Et 2 -C≡C- (CH_Two)_TwoO-cHx H H 1-2045 CO_TwoMe H H Et 2 -C≡C- (CH_Two)_TwoO-cHx H H 1-2046 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-F-cHx) H H 1-2047 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Cl-cHx) H H 1-2048 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Br-cHx) H H 1-2049 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Me-cHx) H H 1-2050 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Et-cHx) H H 1-2051 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Pr-cHx) H H 1-2052 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-iPr-cHx) H H 1-2053 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Bu-cHx) H H 1-2054 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-CF_Three-cHx) H H 1-2055 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-MeO-cHx) H H 1-2056 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-EtO-cHx) H H 1-2057 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-PrO-cHx) H H 1-2058 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-iPrO-cHx) H H 1-2059 H H H Et 2 -C≡C- (CH_Two)_TwoO- (3-MeS-cHx) H H 1-2060 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-MeS-cHx) H H 1-2061 H H H Et 2 -C≡C- (CH_Two)_TwoO- (2,4-diMe-cHx) H H 1-2062 H H H Et 2 -C≡C- (CH_Two)_TwoO- (3,4-diMe-cHx) H H 1-2063 H H H Et 2 -C≡C- (CH_Two)_TwoO- (3,5-diMe-cHx) H H 1-2064 H H H Et 2 -C≡C- (CH_Two)_TwoO-Ph H H 1-2065 H H H Et 2 -C≡C- (CH_Two)_TwoO-Ph Me H 1-2066 H H H Et 2 -C≡C- (CH_Two)_TwoO-Ph H Me 1-2067 H H H Et 2 -C≡C- (CH_Two)_TwoO-Ph F H 1-2068 H H H Et 2 -C≡C- (CH_Two)_TwoO-Ph H F 1-2069 H H Me Et 2 -C≡C- (CH_Two)_Two-OCH_Two-Ph H H 1-2070 Me H H Et 2 -C≡C- (CH_Two)_TwoO-Ph H H 1-2071 CO_TwoMe H H Et 2 -C≡C- (CH_Two)_TwoO-Ph H H 1-2072 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-F-Ph) H H 1-2073 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Cl-Ph) H H 1-2074 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Br-Ph) H H 1-2075 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Me-Ph) H H 1-2076 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Et-Ph) H H 1-2077 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Pr-Ph) H H 1-2078 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-iPr-Ph) H H 1-2079 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-Bu-Ph) H H 1-2080 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-CF_Three-Ph) H H 1-2081 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-MeO-Ph) H H 1-2082 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-EtO-Ph) H H 1-2083 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-PrO-Ph) H H 1-2084 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-iPrO-Ph) H H 1-2085 H H H Et 2 -C≡C- (CH_Two)_TwoO- (4-MeS-Ph) H H 1-2086 H H H Et 2 -C≡C- (CH_Two)_TwoO- (2,4-diMe-Ph) H H 1-2087 H H H Et 2 -C≡C- (CH_Two)_TwoO- (3,4-diMe-Ph) H H 1-2088 H H H Et 2 -C≡C- (CH_Two)_TwoO- (3,5-diMe-Ph) H H 1-2089 H H H Et 2 -CO- (CH_Two)_Three-cHx H H 1-2090 H H Me Et 2 -CO- (CH_Two)_Three-cHx H H 1-2091 Me H H Et 2 -CO- (CH_Two)_Three-cHx H H 1-2092 CO_TwoMe H H Et 2 -CO- (CH_Two)_Three-cHx H H 1-2093 H H H Et 2 -CO- (CH_Two)_Three-Ph H H 1-2094 H H Me Et 2 -CO- (CH_Two)_Three-Ph H H 1-2095 Me H H Et 2 -CO- (CH_Two)_Three-Ph H H 1-2096 CO_TwoMe H H Et 2 -CO- (CH_Two)_Three-Ph H H 1-2097 H H H Et 2 -CO- (CH_Two)_Four-cHx H H 1-2098 H H Me Et 2 -CO- (CH_Two)_Four-cHx H H 1-2099 Me H H Et 2 -CO- (CH_Two)_Four-cHx H H 1-2100 CO_TwoMe H H Et 2 -CO- (CH_Two)_Four-cHx H H 1-2101 H H H Et 2 -CO- (CH_Two)_Four-Ph H H 1-2102 H H Me Et 2 -CO- (CH_Two)_Four-Ph H H 1-2103 Me H H Et 2 -CO- (CH_Two)_Four-Ph H H 1-2104 CO_TwoMe H H Et 2 -CO- (CH_Two)_Four-Ph H H 1-2105 H H H Et 2 -CO- (CH_Two)_Five-cHx H H 1-2106 H H Me Et 2 -CO- (CH_Two)_Five-cHx H H 1-2107 Me H H Et 2 -CO- (CH_Two)_Five-cHx H H 1-2108 CO_TwoMe H H Et 2 -CO- (CH_Two)_Five-cHx H H 1-2109 H H H Et 2 -CO- (CH_Two)_Five-Ph H H 1-2110 H H Me Et 2 -CO- (CH_Two)_Five-Ph H H 1-2111 Me H H Et 2 -CO- (CH_Two)_Five-Ph H H 1-2112 CO_TwoMe H H Et 2 -CO- (CH_Two)_Five-Ph H H 1-2113 H H H Et 2 -CH (OH)-(CH_Two)_Four-cHx H H 1-2114 H H Me Et 2 -CH (OH)-(CH_Two)_Four-cHx H H 1-2115 Me H H Et 2 -CH (OH)-(CH_Two)_Four-cHx H H 1-2116 CO_TwoMe H H Et 2 -CH (OH)-(CH_Two)_Four-cHx H H 1-2117 H H H Et 2 -CH (OH)-(CH_Two)_Four-Ph H H 1-2118 H H Me Et 2 -CH (OH)-(CH_Two)_Four-Ph H H 1-2119 Me H H Et 2 -CH (OH)-(CH_Two)_Four-Ph H H 1-2120 CO_TwoMe H H Et 2 -CH (OH)-(CH_Two)_Four-Ph H H 1-2121 H H H Et 2 -CH (OH)-(CH_Two)_Five-cHx H H 1-2122 H H Me Et 2 -CH (OH)-(CH_Two)_Five-cHx H H 1-2123 Me H H Et 2 -CH (OH)-(CH_Two)_Five-cHx H H 1-2124 CO_TwoMe H H Et 2 -CH (OH)-(CH_Two)_Five-cHx H H 1-2125 H H H Et 2 -CH (OH)-(CH_Two)_Five-Ph H H 1-2126 H H Me Et 2 -CH (OH)-(CH_Two)_Five-Ph H H 1-2127 Me H H Et 2 -CH (OH)-(CH_Two)_Five-Ph H H 1-2128 CO_TwoMe H H Et 2 -CH (OH)-(CH_Two)_Five-Ph H H 1-2129 H H H Et 2 -4- (cHx-CH_TwoO) Ph H H 1-2130 H H Me Et 2 -4- (cHx-CH_TwoO) Ph H H 1-2131 Me H H Et 2 -4- (cHx-CH_TwoO) Ph H H 1-2132 CO_TwoMe H H Et 2 -4- (cHx-CH_TwoO) Ph H H 1-2133 H H H Et 2 -4- [cHx- (CH_Two)_TwoO] Ph H H 1-2134 H H H Et 2 -4- [cHx- (CH_Two)_ThreeO] Ph HH 1-2135 HHH Et 2-(4-BzO-Ph) HH 1-2136 HH Me Et 2-(4-BzO-Ph) HH 1-2137 Me HH Et 2-(4-BzO-Ph) HH 1-2138 CO_TwoMe HH Et 2-(4-BzO-Ph) HH 1-2139 HHH Et 2-(4-BzO-2-F-Ph) HH 1-2140 HHH Et 2-(4-BzO-3-F-Ph) HH 1-2141 HHH Et 2-(4-BzO-2,3-diF-Ph) HH 1-2142 HHH Et 2-(4-BzO-2-Cl-Ph) HH 1-2143 HHH Et 2-(4 -BzO-3-Cl-Ph) HH 1-2144 HHH Et 2-(4-BzO-2,3-diCl-Ph) HH 1-2145 HHH Et 2-(4-BzO-2-Me-Ph) HH 1-2146 HHH Et 2-(4-BzO-3-Me-Ph) HH 1-2147 HHH Et 2-(4-BzO-2,3-diMe-Ph) HH 1-2148 HHH Et 2 -4- [ Ph- (CH_Two)_TwoO] -Ph H H 1-2149 H H H Et 2 -4- [Ph- (CH_Two)_ThreeO] -Ph H H 1-2 150 H H H Pr 2-(CH_Two)_Five-cHx H H 1-2151 H H H Pr 2-(CH_Two)_Five-Ph H H 1-2152 H H H Pr 2-(CH_Two)₆-cHx H H 1-2153 H H H Pr 2-(CH_Two)₆-Ph H H 1-2154 H H H Pr 2 -C≡C-CH_Two-cHx H H 1-2155 H H H Pr 2 -C≡C- (CH_Two)_Three-cHx H H 1-2156 H H H Pr 2 -C≡C- (CH_Two)_Three-Ph H H 1-2157 H H H Pr 2 -C≡C- (CH_Two)_Four-cHx H H 1-2158 H H H Pr 2 -C≡C- (CH_Two)_Four-Ph H H 1-2159 Me H H Pr 2 -C≡C-CH_TwoO-Ph H H 1-2160 CO_TwoMe H H Pr 2 -C≡C-CH_TwoO-Ph H H 1-2161 H H H Pr 2 -C≡C- (CH_Two)_TwoO-cHx H H 1-2162 H H H Pr 2 -C≡C- (CH_Two)_TwoO-Ph H H 1-2163 H H H Pr 2 -4- (cHx-CH_TwoO) Ph H H 1-2164 H H H Pr 2-(4-BzO-Ph) H H 1-2165 H H H Me 3-(CH_Two)_Five-cHx H H 1-2166 H H H Me 3-(CH_Two)₆-cHx H H 1-2167 H H H Me 3 -CH = CH- (CH_Two)_Three-cHx H H 1-2168 H H H Me 3 -CH = CH- (CH_Two)_Four-cHx H H 1-2169 H H H Me 3 -C≡C- (CH_Two)_Three-cHx H H 1-2170 H H H Me 3 -C≡C- (CH_Two)_Four-cHx H H 1-2171 H H H Me 3 -CO- (CH_Two)_Four-cHx H H 1-2172 H H H Me 3 -CO- (CH_Two)_Five-cHx H H 1-2173 H H H Me 3 -CO- (CH_Two)_Four-Ph H H 1-2174 H H H Me 3 -CO- (CH_Two)_Five-Ph H H 1-2175 H H H Me 3 -CH (OH)-(CH_Two)_Four-cHx H H 1-2176 H H H Me 3 -CH (OH)-(CH_Two)_Five-cHx H H 1-2177 H H H Me 3 -4- (cHx-CH_TwoO) Ph H H 1-2178 H H H Me 3-(4-BzO-Ph) H H 1-2179 H H H Me 3 -C≡C-CH_TwoO-cPn H H 1-2180 H H H Me 3 -C≡C- (CH_Two)_TwoO-cPn H H 1-2181 H H H Me 3 -C≡C-CH_TwoO-cHx H H 1-2182 H H H Me 3 -C≡C- (CH_Two)_TwoO-cHx H H 1-2183 H H H Me 3 -C≡C-CH_TwoO-Ph H H 1-2184 H H H Me 3 -C≡C- (CH_Two)_TwoO-Ph H H 1-2185 H H H Me 2-(CH_Two)_Four-(3-F-Ph) H H 1-2186 H H H Me 2-(CH_Two)_Four-(3,4-diF-Ph) H H 1-2187 H H H Me 2-(CH_Two)_Four-(3,5-diF-Ph) H H 1-2188 H H H Me 2-(CH_Two)_Four-(3-Cl-Ph) H H 1-2189 H H H Me 2-(CH_Two)_Four-(4-Cl-Ph) H H 1-2190 H H H Me 2-(CH_Two)_Four-(3,4-diCl-Ph) H H 1-2191 H H H Me 2-(CH_Two)_Four-(3,5-diCl-Ph) H H 1-2192 H H H Me 2-(CH_Two)_Four-(3-Me-Ph) H H 1-2193 H H H Me 2-(CH_Two)_Four-(3,4-diMe-Ph) H H 1-2194 H H H Me 2-(CH_Two)_Four-(3,5-diMe-Ph) H H 1-2195 H H H Me 2-(CH_Two)_Four-(3-CF_Three-Ph) H H 1-2196 H H H Me 2-(CH_Two)_Four-(3,4-diCF_Three-Ph) H H 1-2197 H H H Me 2-(CH_Two)_Four-(3,5-diCF_Three-Ph) H H 1-2198 H H H Me 2-(CH_Two)_Four-(3-MeO-Ph) H H 1-2199 H H H Me 2-(CH_Two)_Four-(3,4-diMeO-Ph) H H 1-2200 H H H Me 2-(CH_Two)_Four-(3,5-diMeO-Ph) H H 1-2201 H H H Me 2-(CH_Two)_Four-(3,4,5-triMeO-Ph) H H 1-2202 H H H Me 2-(CH_Two)_Four-(3-Ac-Ph) H H 1-2203 H H H Me 2-(CH_Two)_Four-(4-Ac-Ph) H H 1-2204 H H H Me 2-(CH_Two)_Five-(3,4-diF-Ph) H H 1-2205 H H H Me 2-(CH_Two)_Five-(3,5-diF-Ph) H H 1-2206 H H H Me 2-(CH_Two)_Five-(3-Cl-Ph) H H 1-2207 H H H Me 2-(CH_Two)_Five-(3,4-diCl-Ph) H H 1-2208 H H H Me 2-(CH_Two)_Five-(3,5-diCl-Ph) H H 1-2209 H H H Me 2-(CH_Two)_Five-(3,4-diCF_Three-Ph) H H 1-2210 H H H Me 2-(CH_Two)_Five-(3,5-diCF_Three-Ph) H H 1-2211 H H H Me 2-(CH_Two)_Five-(3,4-diMeO-Ph) H H 1-2212 H H H Me 2-(CH_Two)_Five-(3,5-diMeO-Ph) H H 1-2213 H H H Me 2-(CH_Two)_Five-(3,4,5-triMeO-Ph) H H 1-2214 H H H Me 2-(CH_Two)_Five-(3-Ac-Ph) H H 1-2215 H H H Me 2-(CH_Two)_Five-(4-Ac-Ph) H H 1-2216 H H H Me 2-(CH_Two)_Three-O- (3-F-Ph) H H 1-2217 H H H Me 2-(CH_Two)_Three-O- (3,4-diF-Ph) H H 1-2218 H H H Me 2-(CH_Two)_Three-O- (3,5-diF-Ph) H H 1-2219 H H H Me 2-(CH_Two)_Three-O- (3-Me-Ph) H H 1-2220 H H H Me 2-(CH_Two)_Three-O- (3,4-diMe-Ph) H H 1-2221 H H H Me 2-(CH_Two)_Three-O- (3,5-diMe-Ph) H H 1-2222 H H H Me 2-(CH_Two)_Three-O- (3-CF_Three-Ph) H H 1-2223 H H H Me 2-(CH_Two)_Three-O- (3,4-diCF_Three-Ph) H H 1-2224 H H H Me 2-(CH_Two)_Three-O- (3,5-diCF_Three-Ph) H H 1-2225 H H H Me 2-(CH_Two)_Three-O- (3-MeO-Ph) H H 1-2226 H H H Me 2-(CH_Two)_Three-O- (3,4-diMeO-Ph) H H 1-2227 H H H Me 2-(CH_Two)_Three-O- (3,5-diMeO-Ph) H H 1-2228 H H H Me 2-(CH_Two)_Three-O- (3,4,5-triMeO-Ph) H H 1-2229 H H H Me 2-(CH_Two)_Three-O- (3-Ac-Ph) H H 1-2 230 H H H Me 2-(CH_Two)_Three-O- (4-Ac-Ph) H H 1-2231 H H H Me 2-(CH_Two)_Four-O- (3,4-diF-Ph) H H 1-2232 H H H Me 2-(CH_Two)_Four-O- (3,5-diF-Ph) H H 1-2233 H H H Me 2-(CH_Two)_Four-O- (3,4-diMeO-Ph) H H 1-2234 H H H Me 2-(CH_Two)_Four-O- (3,5-diMeO-Ph) H H 1-2235 H H H Me 2-(CH_Two)_Four-O- (3,4,5-triMeO-Ph) H H 1-2236 H H H Me 2-(CH_Two)_Four-O- (3-Ac-Ph) H H 1-2237 H H H Me 2-(CH_Two)_Four-O- (4-Ac-Ph) H H 1-2238 H H H Me 2 -C≡C- (CH_Two)_Two-(3-F-Ph) H H 1-2239 H H H Me 2 -C≡C- (CH_Two)_Two-(3,4-diF-Ph) H H 1-2240 H H H Me 2 -C≡C- (CH_Two)_Two-(3,5-diF-Ph) H H 1-2241 H H H Me 2 -C≡C- (CH_Two)_Two-(3-Cl-Ph) H H 1-2242 H H H Me 2 -C≡C- (CH_Two)_Two-(4-Cl-Ph) H H 1-2243 H H H Me 2 -C≡C- (CH_Two)_Two-(3,4-diCl-Ph) H H 1-2244 H H H Me 2 -C≡C- (CH_Two)_Two-(3,5-diCl-Ph) H H 1-2245 H H H Me 2 -C≡C- (CH_Two)_Two-(3-Me-Ph) H H 1-2246 H H H Me 2 -C≡C- (CH_Two)_Two-(3,4-diMe-Ph) H H 1-2247 H H H Me 2 -C≡C- (CH_Two)_Two-(3,5-diMe-Ph) H H 1-2248 H H H Me 2 -C≡C- (CH_Two)_Two-(3-CF_Three-Ph) H H 1-2249 H H H Me 2 -C≡C- (CH_Two)_Two-(3,4-diCF_Three-Ph) H H 1-2 250 H H H Me 2 -C≡C- (CH_Two)_Two-(3,5-diCF_Three-Ph) H H 1-2251 H H H Me 2 -C≡C- (CH_Two)_Two-(3-MeO-Ph) H H 1-2252 H H H Me 2 -C≡C- (CH_Two)_Two-(3,4-diMeO-Ph) H H 1-2253 H H H Me 2 -C≡C- (CH_Two)_Two-(3,5-diMeO-Ph) H H 1-2254 H H H Me 2 -C≡C- (CH_Two)_Two-(3,4,5-triMeO-Ph) H H 1-2255 H H H Me 2 -C≡C- (CH_Two)_Two-(3-Ac-Ph) H H 1-2 256 H H H Me 2 -C≡C- (CH_Two)_Two-(4-Ac-Ph) H H 1-2257 H H H Me 2 -C≡C- (CH_Two)_Three-(3,4-diF-Ph) H H 1-2258 H H H Me 2 -C≡C- (CH_Two)_Three-(3,5-diF-Ph) H H 1-2259 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Cl-Ph) H H 1-2260 H H H Me 2 -C≡C- (CH_Two)_Three-(3,4-diCl-Ph) H H 1-2261 H H H Me 2 -C≡C- (CH_Two)_Three-(3,5-diCl-Ph) H H 1-2262 H H H Me 2 -C≡C- (CH_Two)_Three-(3,4-diCF_Three-Ph) H H 1-2263 H H H Me 2 -C≡C- (CH_Two)_Three-(3,5-diCF_Three-Ph) H H 1-2264 H H H Me 2 -C≡C- (CH_Two)_Three-(3,4-diMeO-Ph) H H 1-2265 H H H Me 2 -C≡C- (CH_Two)_Three-(3,5-diMeO-Ph) H H 1-2266 H H H Me 2 -C≡C- (CH_Two)_Three-(3,4,5-triMeO-Ph) H H 1-2267 H H H Me 2 -C≡C- (CH_Two)_Three-(3-Ac-Ph) H H 1-2268 H H H Me 2 -C≡C- (CH_Two)_Three-(4-Ac-Ph) H H 1-2269 H H H Me 2 -C≡C-CH_Two-O- (3-F-Ph) H H 1-2270 H H H Me 2 -C≡C-CH_Two-O- (3,4-diF-Ph) H H 1-2271 H H H Me 2 -C≡C-CH_Two-O- (3,5-diF-Ph) H H 1-2272 H H H Me 2 -C≡C-CH_Two-O- (3-Cl-Ph) H H 1-2273 H H H Me 2 -C≡C-CH_Two-O- (4-Cl-Ph) H H 1-2274 H H H Me 2 -C≡C-CH_Two-O- (3,4-diCl-Ph) H H 1-2275 H H H Me 2 -C≡C-CH_Two-O- (3,5-diCl-Ph) H H 1-2276 H H H Me 2 -C≡C-CH_Two-O- (3-Me-Ph) H H 1-2277 H H H Me 2 -C≡C-CH_Two-O- (2,4-diMe-Ph) H H 1-2278 H H H Me 2 -C≡C-CH_Two-O- (3,4-diMe-Ph) H H 1-2279 H H H Me 2 -C≡C-CH_Two-O- (3,5-diMe-Ph) H H 1-2280 H H H Me 2 -C≡C-CH_Two-O- (3-CF_Three-Ph) H H 1-2281 H H H Me 2 -C≡C-CH_Two-O- (3,4-diCF_Three-Ph) H H 1-2282 H H H Me 2 -C≡C-CH_Two-O- (3,5-diCF_Three-Ph) H H 1-2283 H H H Me 2 -C≡C-CH_Two-O- (3-MeO-Ph) H H 1-2284 H H H Me 2 -C≡C-CH_Two-O- (3,4-diMeO-Ph) H H 1-2285 H H H Me 2 -C≡C-CH_Two-O- (3,5-diMeO-Ph) H H 1-2286 H H H Me 2 -C≡C-CH_Two-O- (3,4,5-triMeO-Ph) H H 1-2287 H H H Me 2 -C≡C-CH_Two-O- (3-Ac-Ph) H H 1-2288 H H H Me 2 -C≡C-CH_Two-O- (4-Ac-Ph) H H 1-2289 H H H Me 2 -C≡C-CH_Two-O- (4-CO_TwoH-Ph) H H 1-2290 H H H Me 2 -C≡C- (CH_Two)_Two-O- (3,4-diF-Ph) H H 1-2291 H H H Me 2 -C≡C- (CH_Two)_Two-O- (3,5-diF-Ph) H H 1-2292 H H H Me 2 -C≡C- (CH_Two)_Two-O- (3-Cl-Ph) H H 1-2293 H H H Me 2 -C≡C- (CH_Two)_Two-O- (3,4-diCl-Ph) H H 1-2294 H H H Me 2 -C≡C- (CH_Two)_Two-O- (3,5-diCl-Ph) H H 1-2295 H H H Me 2 -C≡C- (CH_Two)_Two-O- (3,4-diCF_Three-Ph) H H 1-2296 H H H Me 2 -C≡C- (CH_Two)_Two-O- (3,5-diCF_Three-Ph) H H 1-2297 H H H Me 2 -C≡C- (CH_Two)_Two-O- (3,4-diMeO-Ph) H H 1-2298 H H H Me 2 -C≡C- (CH_Two)_Two-O- (3,5-diMeO-Ph) H H 1-2299 H H H Me 2 -C≡C- (CH_Two)_Two-O- (3,4,5-triMeO-Ph) H H 1-2300 H H H Me 2 -C≡C- (CH_Two)_Two-O- (3-Ac-Ph) H H 1-2301 H H H Me 2 -C≡C- (CH_Two)_Two-O- (4-Ac-Ph) H H 1-2302 H H H Me 2 -CO- (CH_Two)_Three-(3-F-Ph) H H 1-2303 H H H Me 2 -CO- (CH_Two)_Three-(4-F-Ph) H H 1-2304 H H H Me 2 -CO- (CH_Two)_Three-(3,4-diF-Ph) H H 1-2305 H H H Me 2 -CO- (CH_Two)_Three-(3,5-diF-Ph) H H 1-2306 H H H Me 2 -CO- (CH_Two)_Three-(3-Cl-Ph) H H 1-2307 H H H Me 2 -CO- (CH_Two)_Three-(4-Cl-Ph) H H 1-2308 H H H Me 2 -CO- (CH_Two)_Three-(3,4-diCl-Ph) H H 1-2309 H H H Me 2 -CO- (CH_Two)_Three-(3,5-diCl-Ph) H H 1-2310 H H H Me 2 -CO- (CH_Two)_Three-(3-Me-Ph) H H 1-2311 H H H Me 2 -CO- (CH_Two)_Three-(4-Me-Ph) H H 1-2312 H H H Me 2 -CO- (CH_Two)_Three-(3,4-diMe-Ph) H H 1-2313 H H H Me 2 -CO- (CH_Two)_Three-(3,5-diMe-Ph) H H 1-2314 H H H Me 2 -CO- (CH_Two)_Three-(3-Et-Ph) H H 1-2315 H H H Me 2 -CO- (CH_Two)_Three-(4-Et-Ph) H H 1-2316 H H H Me 2 -CO- (CH_Two)_Three-(3-CF_Three-Ph) H H 1-2317 H H H Me 2 -CO- (CH_Two)_Three-(4-CF_Three-Ph) H H 1-2318 H H H Me 2 -CO- (CH_Two)_Three-(3,4-diCF_Three-Ph) H H 1-2319 H H H Me 2 -CO- (CH_Two)_Three-(3,5-diCF_Three-Ph) H H 1-2320 H H H Me 2 -CO- (CH_Two)_Three-(3-MeO-Ph) H H 1-2321 H H H Me 2 -CO- (CH_Two)_Three-(4-MeO-Ph) H H 1-2322 H H H Me 2 -CO- (CH_Two)_Three-(3,4-diMeO-Ph) H H 1-2323 H H H Me 2 -CO- (CH_Two)_Three-(3,5-diMeO-Ph) H H 1-2324 H H H Me 2 -CO- (CH_Two)_Three-(3,4,5-triMeO-Ph) H H 1-2325 H H H Me 2 -CO- (CH_Two)_Three-(4-MeS-Ph) H H 1-2326 H H H Me 2 -CO- (CH_Two)_Three-(3-Ac-Ph) H H 1-2327 H H H Me 2 -CO- (CH_Two)_Three-(4-Ac-Ph) H H 1-2328 H H H Me 2 -CO- (CH_Two)_Four-(3-F-Ph) H H 1-2329 H H H Me 2 -CO- (CH_Two)_Four-(3,4-diF-Ph) H H 1-2330 H H H Me 2 -CO- (CH_Two)_Four-(3,5-diF-Ph) H H 1-2331 H H H Me 2 -CO- (CH_Two)_Four-(3-Cl-Ph) H H 1-2332 H H H Me 2 -CO- (CH_Two)_Four-(4-Cl-Ph) H H 1-2333 H H H Me 2 -CO- (CH_Two)_Four-(3,4-diCl-Ph) H H 1-2334 H H H Me 2 -CO- (CH_Two)_Four-(3,5-diCl-Ph) H H 1-2335 H H H Me 2 -CO- (CH_Two)_Four-(3-Me-Ph) H H 1-2336 H H H Me 2 -CO- (CH_Two)_Four-(3,4-diMe-Ph) H H 1-2337 H H H Me 2 -CO- (CH_Two)_Four-(3,5-diMe-Ph) H H 1-2338 H H H Me 2 -CO- (CH_Two)_Four-(3-CF_Three-Ph) H H 1-2339 H H H Me 2 -CO- (CH_Two)_Four-(3,4-diCF_Three-Ph) H H 1-2340 H H H Me 2 -CO- (CH_Two)_Four-(3,5-diCF_Three-Ph) H H 1-2341 H H H Me 2 -CO- (CH_Two)_Four-(3-MeO-Ph) H H 1-2342 H H H Me 2 -CO- (CH_Two)_Four-(3,4-diMeO-Ph) H H 1-2343 H H H Me 2 -CO- (CH_Two)_Four-(3,5-diMeO-Ph) H H 1-2344 H H H Me 2 -CO- (CH_Two)_Four-(3,4,5-triMeO-Ph) H H 1-2345 H H H Me 2 -CO- (CH_Two)_Four-(3-Ac-Ph) H H 1-2346 H H H Me 2 -CO- (CH_Two)_Four-(4-Ac-Ph) H H 1-2347 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3-F-Ph) H H 1-2348 H H H Me 2 -CH (OH)-(CH_Two)_Three-(4-F-Ph) H H 1-2349 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3,4-diF-Ph) H H 1-2 350 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3,5-diF-Ph) H H 1-2351 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3-Cl-Ph) H H 1-2352 H H H Me 2 -CH (OH)-(CH_Two)_Three-(4-Cl-Ph) H H 1-2353 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3,4-diCl-Ph) H H 1-2354 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3,5-diCl-Ph) H H 1-2355 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3-Me-Ph) H H 1-2356 H H H Me 2 -CH (OH)-(CH_Two)_Three-(4-Me-Ph) H H 1-2357 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3,4-diMe-Ph) H H 1-2358 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3,5-diMe-Ph) H H 1-2359 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3-Et-Ph) H H 1-2360 H H H Me 2 -CH (OH)-(CH_Two)_Three-(4-Et-Ph) H H 1-2361 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3-CF_Three-Ph) H H 1-2362 H H H Me 2 -CH (OH)-(CH_Two)_Three-(4-CF_Three-Ph) H H 1-2363 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3,4-diCF_Three-Ph) H H 1-2364 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3,5-diCF_Three-Ph) H H 1-2365 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3-MeO-Ph) H H 1-2366 H H H Me 2 -CH (OH)-(CH_Two)_Three-(4-MeO-Ph) H H 1-2367 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3,4-diMeO-Ph) H H 1-2368 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3,5-diMeO-Ph) H H 1-2369 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3,4,5-triMeO-Ph) H H 1-2370 H H H Me 2 -CH (OH)-(CH_Two)_Three-(4-MeS-Ph) H H 1-2371 H H H Me 2 -CH (OH)-(CH_Two)_Three-(3-Ac-Ph) H H 1-2372 H H H Me 2 -CH (OH)-(CH_Two)_Three-(4-Ac-Ph) H H 1-2373 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3-F-Ph) H H 1-2374 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3,4-diF-Ph) H H 1-2375 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3,5-diF-Ph) H H 1-2376 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3-Cl-Ph) H H 1-2377 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-Cl-Ph) H H 1-2378 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3,4-diCl-Ph) H H 1-2379 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3,5-diCl-Ph) H H 1-2380 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3-Me-Ph) H H 1-2381 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3,4-diMe-Ph) H H 1-2382 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3,5-diMe-Ph) H H 1-2383 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3-CF_Three-Ph) H H 1-2384 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3,4-diCF_Three-Ph) H H 1-2385 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3,5-diCF_Three-Ph) H H 1-2386 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3-MeO-Ph) H H 1-2387 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3,4-diMeO-Ph) H H 1-2388 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3,5-diMeO-Ph) H H 1-2389 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3,4,5-triMeO-Ph) H H 1-2390 H H H Me 2 -CH (OH)-(CH_Two)_Four-(3-Ac-Ph) H H 1-2391 H H H Me 2 -CH (OH)-(CH_Two)_Four-(4-Ac-Ph) H H 1-2392 H H H Me 2 -O- (CH_Two)_Three-cHx H H 1-2393 H H H Me 2 -O- (CH_Two)_Four-cHx H H 1-2394 H H H Me 2 -O- (CH_Two)_Five-cHx H H 1-2395 H H H Me 2 -O- (CH_Two)_Three-Ph H H 1-2396 H H H Me 2 -O- (CH_Two)_Four-Ph H H 1-2397 H H H Me 2 -O- (CH_Two)_Five-Ph H H  .

[0112]

[Table 2]

[0113]

Embedded image

Compd. R ¹ R ² R ³ R ⁴ n -XYR ⁵ R ⁶ R ⁷ 2-1 HHH Me 1-(CH ₂ ) ₅ -cHx HH 2-2 HHH Me 1-(CH ₂ ) ₆ -cHx HH 2-3 HHH Me 1 -C≡C- (CH ₂ ) ₃ -cHx HH 2 -4 HHH Me 1 -C≡C- (CH ₂ ) ₄ -cHx HH 2-5 HHH Me 1 -4- (cHx-CH ₂ O) Ph HH 2-6 HHH Me 1-(4-BzO-Ph) HH 2-7 HHH Me 1 -C≡C- (CH ₂ ) ₂ O-cHx HH 2-8 HHH Me 1 -C≡C- (CH ₂ ) ₂ O-Ph HH 2-9 HHH Me 2-(CH ₂ ) ₃ -cHx HH 2-10 HHH Me 2-(CH ₂ ) ₃ -Ph HH 2-11 HHH Me 2-(CH ₂ ) ₄ -cHx HH 2-12 HHH Me 2-(CH ₂ ) ₄ -Ph HH 2-13 HHH Me 2-(CH ₂ ) ₅ -cPn HH 2-14 HHH Me 2-(CH ₂ ) ₅ -cHx HH 2-15 HHH Me 2-(CH ₂ ) ₅ -cHx Me H 2-16 HHH Me 2-(CH ₂ ) ₅ -cHx H Me 2-17 HHH Me 2-(CH ₂ ) ₅ -cHx FH 2-18 HHH Me 2-(CH ₂ ) ₅ -cHx HF 2-19 HH Me Me 2 -(CH ₂ ) ₅ -cHx HH 2-20 Me HH Me 2-(CH ₂ ) ₅ -cHx HH 2-21 CO ₂ Me HH Me 2-(CH ₂ ) ₅ -cHx HH 2-22 HHH Me 2- (CH ₂ ) _5- (4-F-cHx) HH 2-23 HHH Me 2-(CH ₂ ) _5- (4-Cl-cHx) HH 2-24 HHH Me 2-(CH ₂ ) _5- (4 -Br-cHx) HH 2-25 HHH Me 2-(CH ₂ ) _5- (4-Me-cHx) HH 2-26 HHH Me 2-(CH ₂ ) _5- (4-Et-cHx) HH 2- 27 HHH Me 2-(CH ₂ ) _5- (4-Pr-cHx) HH 2-28 HHH Me 2-(CH ₂ ) _5- (4-iPr-cHx) HH 2-29 HHH Me 2-(CH ₂ ) _5- (4-CF ₃ -cHx) HH 2-30 HHH Me 2-(CH ₂ ) _5- (4-MeO-cHx) HH 2-31 HHH Me 2- (CH ₂ ) _5- (4-EtO-cHx) HH 2-32 HHH Me 2-(CH ₂ ) _5- (4-PrO-cHx) HH 2-33 HHH Me 2-(CH ₂ ) _5- (4 -iPrO-cHx) HH 2-34 HHH Me 2-(CH ₂ ) _5- (3-MeS-cHx) HH 2-35 HHH Me 2-(CH ₂ ) _5- (4-MeS-cHx) HH 2- 36 HHH Me 2-(CH ₂ ) _5- (2,4-diMe-cHx) HH 2-37 HHH Me 2-(CH ₂ ) _5- (3,4-diMe-cHx) HH 2-38 HHH Me 2 -(CH ₂ ) _5- (3,5-diMe-cHx) HH 2-39 HHH Me 2-(CH ₂ ) ₅ -Ph HH 2-40 HHH Me 2-(CH ₂ ) ₅ -Ph Me H 2- 41 HHH Me 2-(CH ₂ ) ₅ -Ph H Me 2-42 HHH Me 2-(CH ₂ ) ₅ -Ph FH 2-43 HHH Me 2-(CH ₂ ) ₅ -Ph HF 2-44 HH Me Me 2-(CH ₂ ) ₅ -Ph HH 2-45 Me HH Me 2-(CH ₂ ) ₅ -Ph HH 2-46 CO ₂ Me HH Me 2-(CH ₂ ) ₅ -Ph HH 2-47 HHH Me 2 -(CH ₂ ) _5- (4-F-Ph) HH 2-48 HHH Me 2-(CH ₂ ) _5- (4-Cl-Ph) HH 2-49 HHH Me 2-(CH ₂ ) _5- ( 4-Br-Ph) HH 2-50 HHH Me 2-(CH ₂ ) _5- (4-Me-Ph) HH 2-51 HHH Me 2-(CH ₂ ) _5- (4-Et-Ph) HH 2 -52 HHH Me 2-(CH ₂ ) _5- (4-Pr-Ph) HH 2-53 HHH Me 2-(CH ₂ ) _5- (4-iPr-Ph) HH 2-54 HHH Me 2-(CH ₂ ) _5- (4-Bu-Ph ) HH 2-55 HHH Me 2-(CH ₂ ) _5- (4-CF ₃ -Ph) HH 2-56 HHH Me 2-(CH ₂ ) _5- (4-MeO-Ph) HH 2-57 HHH Me 2-(CH ₂ ) _5- (4-EtO-Ph) HH 2-58 HHH Me 2-(CH ₂ ) _5- (4-PrO-Ph) HH 2-59 HHH Me 2-(CH ₂ ) _5- (4-iPrO-Ph) HH 2-60 HHH Me 2-(CH ₂ ) _5- (3-MeS-Ph) HH 2-61 HHH Me 2-(CH ₂ ) _5- (4-MeS-Ph) HH 2-62 HHH Me 2-(CH ₂ ) _5- (2,4-diMe-Ph) HH 2-63 HHH Me 2-(CH ₂ ) _5- (3,4-diMe-Ph) HH 2-64 HHH Me 2-(CH ₂ ) _5- (3,5-diMe-Ph) HH 2-65 HHH Me 2-(CH ₂ ) ₆ -cPn HH 2-66 HHH Me 2-(CH ₂ ) ₆ -cHx HH 2 -67 HHH Me 2-(CH ₂ ) ₆ -cHx Me H 2-68 HHH Me 2-(CH ₂ ) ₆ -cHx H Me 2-69 HHH Me 2-(CH ₂ ) ₆ -cHx FH 2-70 HHH Me 2-(CH ₂ ) ₆ -cHx HF 2-71 HH Me Me 2-(CH ₂ ) ₆ -cHx HH 2-72 Me HH Me 2-(CH ₂ ) ₆ -cHx HH 2-73 CO ₂ Me HH Me 2-(CH ₂ ) ₆ -cHx HH 2-74 HHH Me 2-(CH ₂ ) _6- (4-F-cHx) HH 2-75 HHH Me 2-(CH ₂ ) _6- (4-Cl- cHx) HH 2-76 HHH Me 2-(CH ₂ ) _6- (4-Br-cHx) HH 2-77 HHH Me 2-(CH ₂ ) _6- (4-Me-cHx) HH 2-78 HHH Me 2-(CH ₂ ) _6- (4-Et-cHx) HH 2-79 HHH Me 2-(CH ₂ ) _6- (4-Pr-cHx) HH 2-80 HHH Me 2-(CH ₂ ) _6- (4-iPr -cHx) HH 2-81 HHH Me 2-(CH ₂ ) _6- (4-Bu-cHx) HH 2-82 HHH Me 2-(CH ₂ ) _6- (4-CF ₃ -cHx) HH 2-83 HHH Me 2-(CH ₂ ) _6- (4-MeO-cHx) HH 2-84 HHH Me 2-(CH ₂ ) _6- (4-EtO-cHx) HH 2-85 HHH Me 2-(CH ₂ ) _6- (4-PrO-cHx) HH 2-86 HHH Me 2-(CH ₂ ) _6- (4-iPrO-cHx) HH 2-87 HHH Me 2-(CH ₂ ) _6- (3-MeS-cHx ) HH 2-88 HHH Me 2-(CH ₂ ) _6- (4-MeS-cHx) HH 2-89 HHH Me 2-(CH ₂ ) _6- (2,4-diMe-cHx) HH 2-90 HHH Me 2-(CH ₂ ) _6- (3,4-diMe-cHx) HH 2-91 HHH Me 2-(CH ₂ ) _6- (3,5-diMe-cHx) HH 2-92 HHH Me 2-( CH ₂ ) ₆ -Ph HH 2-93 HHH Me 2-(CH ₂ ) ₆ -Ph Me H 2-94 HHH Me 2-(CH ₂ ) ₆ -Ph H Me 2-95 HHH Me 2-(CH ₂ ) ₆ -Ph FH 2-96 HHH Me 2-(CH ₂ ) ₆ -Ph HF 2-97 HH Me Me 2-(CH ₂ ) ₆ -Ph HH 2-98 Me HH Me 2-(CH ₂ ) ₆ -Ph HH 2-99 CO ₂ Me HH Me 2-(CH ₂ ) ₆ -Ph HH 2-100 HHH Me 2-(CH ₂ ) _6- (4-F-Ph) HH 2-101 HHH Me 2-(CH _{2 ) 6 - (4-Cl-} Ph) HH 2-102 HHH Me 2 - (CH 2) 6 - (4-Br-Ph) HH 2-103 HHH Me 2 - (CH 2) 6 - (4-Me- Ph) HH 2-104 HHH Me 2-(CH ₂ ) _6- (4-Et-Ph) HH 2-105 HHH Me 2-(CH ₂ ) _6- (4-Pr-Ph) HH 2-106 HHH Me 2-(CH ₂ ) _6- (4-iPr-Ph) HH 2-107 HHH Me 2-(CH ₂ ) _6- (4-Bu-Ph) HH 2-108 HHH Me 2-(CH ₂ ) _6- (4-CF ₃ -Ph) HH 2-109 HHH Me 2-(CH ₂ ) _6- (4-MeO-Ph) HH 2-110 HHH Me 2-(CH ₂ ) _6- (4-EtO-Ph) HH 2-111 HHH Me 2-(CH ₂ ) _6- (4-PrO-Ph) HH 2-112 HHH Me 2-(CH ₂ ) _6- (4-iPrO-Ph) HH 2-113 HHH Me 2-(CH ₂ ) _6- (3-MeS-Ph) HH 2-114 HHH Me 2-(CH ₂ ) _6- (4-MeS-Ph) HH 2-115 HHH Me 2-(CH ₂ ) _6- (2,4-diMe -Ph) HH 2-116 HHH Me 2-(CH ₂ ) _6- (3,4-diMe-Ph) HH 2-117 HHH Me 2-(CH ₂ ) _6- (3,5-diMe-Ph) HH 2-118 HHH Me 2-(CH ₂ ) ₇ -cHx HH 2-119 HHH Me 2-(CH ₂ ) ₇ -Ph HH 2-120 HHH Me 2-(CH ₂ ) ₈ -cHx HH 2-121 HHH Me 2-(CH ₂ ) ₈ -Ph HH 2-122 HHH Me 2 -CH = CH- (CH ₂ ) ₃ -cHx HH 2-123 HH Me Me 2 -CH = CH- (CH ₂ ) ₃ -cHx HH 2 -124 Me HH Me 2 -CH = CH- (CH ₂ ) ₃ -cHx HH 2-125 CO ₂ Me HH Me 2 -CH = CH- (CH ₂ ) ₃ -cHx HH 2-126 HHH Me 2 -CH = CH- (CH ₂ ) ₃ -Ph HH 2-127 HH Me Me 2 -CH = CH- (CH ₂ ) ₃ -Ph HH 2-128 Me HH Me 2 -CH = CH- (CH ₂ ) ₃ -Ph HH 2-129 CO ₂ Me HH Me 2 -CH = CH- (CH ₂ ) ₃ -Ph HH 2-130 HHH Me 2 -CH = CH- (CH ₂ ) ₄ -cHx HH 2-13 1 HH Me Me 2 -CH = CH- (CH ₂ ) ₄ -cHx HH 2-132 Me HH Me 2 -CH = CH- (CH ₂ ) ₄ -cHx HH 2-133 CO ₂ Me HH Me 2 -CH = CH- (CH ₂ ) ₄ -cHx HH 2-134 HHH Me 2 -CH = CH- (CH ₂ ) ₄ -Ph HH 2-135 HH Me Me 2 -CH = CH- (CH ₂ ) ₄ -Ph HH 2 -136 Me HH Me 2 -CH = CH- (CH ₂ ) ₄ -Ph HH 2-137 CO ₂ Me HH Me 2 -CH = CH- (CH ₂ ) ₄ -Ph HH 2-138 HHH Me 2 -C = C-CH ₂ O-cHx HH 2-139 HHH Me 2 -C = C-CH ₂ O-Ph HH 2-140 HHH Me 2 -C = C- (CH ₂ ) ₂ O-cHx HH 2-141 HHH Me 2 -C = C- (CH ₂ ) ₂ O-Ph HH 2-142 HHH Me 2 -C≡C-CH ₂ -cHx HH 2-143 HH Me Me 2 -C≡C-CH ₂ -cHx HH 2- 144 Me HH Me 2 -C≡C-CH ₂ -cHx HH 2-145 CO ₂ Me HH Me 2 -C≡C-CH ₂ -cHx HH 2-146 HHH Me 2 -C≡C-CH ₂ -Ph HH 2-147 HH Me Me 2 -C≡C-CH ₂ -Ph HH 2-148 Me HH Me 2 -C≡C-CH ₂ -Ph HH 2-149 CO ₂ Me HH Me 2 -C≡C-CH ₂ -Ph HH 2-150 HHH Me 2 -C≡C- (CH ₂ ) ₂ -cHx HH 2-151 HH Me Me 2 -C≡C- (CH ₂ ) ₂ -cHx HH 2-152 Me HH Me 2- C≡C- (CH ₂ ) ₂ -cHx HH 2-153 CO ₂ Me HH Me 2 -C≡C- (CH ₂ ) ₂ -cHx HH 2-154 HHH Me 2 -C≡C- (CH ₂ ) ₂ -Ph HH 2-155 HH Me Me 2 -C≡C- (CH ₂ ) ₂ -Ph HH 2-156 Me HH M e 2 -C≡C- (CH ₂ ) ₂ -Ph HH 2-157 CO ₂ Me HH Me 2 -C≡C- (CH ₂ ) ₂ -Ph HH 2-158 HHH Me 2 -C≡C- (CH ₂ ) ₃ -cPn HH 2-159 HHH Me 2 -C≡C- (CH ₂ ) ₃ -cHx HH 2-160 HHH Me 2 -C≡C- (CH ₂ ) ₃ -cHx Me H 2-161 HHH Me 2 -C≡C- (CH ₂ ) ₃ -cHx H Me 2-162 HHH Me 2 -C≡C- (CH ₂ ) ₃ -cHx FH 2-163 HHH Me 2 -C≡C- (CH ₂ ) ₃ -cHx HF 2-164 HH Me Me 2 -C≡C- (CH ₂ ) ₃ -cHx HH 2-165 Me HH Me 2 -C≡C- (CH ₂ ) ₃ -cHx HH 2-166 CO ₂ Me HH Me 2 -C≡C- (CH ₂ ) ₃ -cHx HH 2-167 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-F-cHx) HH 2-168 HHH Me 2 -C≡C -(CH ₂ ) _3- (4-Cl-cHx) HH 2-169 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-Br-cHx) HH 2-170 HHH Me 2 -C≡C -(CH ₂ ) _3- (4-Me-cHx) HH 2-171 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-Et-cHx) HH 2-172 HHH Me 2 -C≡C -(CH ₂ ) _3- (4-Pr-cHx) HH 2-173 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-iPr-cHx) HH 2-174 HHH Me 2 -C≡C -(CH ₂ ) _3- (4-Bu-cHx) HH 2-175 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-CF ₃ -cHx) HH 2-176 HHH Me 2 -C≡ C- (CH ₂ ) _3- (4-MeO-cHx) HH 2-177 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-EtO-cHx) HH 2-178 HHH Me 2 -C≡ C- (CH ₂ ) _3- (4-PrO-cHx) HH 2-179 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-iPrO-cHx) HH 2-180 HHH Me 2 -C≡C- (CH ₂ ) _3- (3-MeS-cHx) HH 2-181 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-MeS-cHx) HH 2-182 HHH Me 2 -C≡C- (CH ₂ ) _3- (2,4-diMe-cHx) HH 2-183 HHH Me 2 -C≡C- (CH ₂ ) _3- (3,4-diMe-cHx) HH 2-184 HHH Me 2 -C≡C- (CH ₂ ) _3- (3,5-diMe-cHx) HH 2-185 HHH Me 2 -C≡C- (CH ₂ ) ₃ -Ph HH 2-186 HHH Me 2 -C≡C- (CH ₂ ) ₃ -Ph Me H 2-187 HHH Me 2 -C≡C- (CH ₂ ) ₃ -Ph H Me 2-188 HHH Me 2 -C≡C- (CH ₂ ) ₃ -Ph FH 2-189 HHH Me 2 -C≡C- (CH ₂ ) ₃ -Ph HF 2-190 HH Me Me 2 -C≡C- (CH ₂ ) ₃ -Ph HH 2-191 Me HH Me 2 -C≡C- (CH ₂ ) ₃ -Ph HH 2-192 CO ₂ Me HH Me 2 -C≡C- (CH ₂ ) ₃ -Ph HH 2-193 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-F-Ph) HH 2-194 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-Cl-Ph) HH 2-195 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-Br-Ph) HH 2-196 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-Me-Ph) HH 2-197 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-Et-Ph) HH 2-198 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-Pr-Ph) HH 2-199 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-iPr-Ph) HH 2-200 HHH Me 2 -C≡C- (CH ₂ ) _3- ( 4-Bu-Ph) HH 2-201 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-CF ₃ -Ph) HH 2-202 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-MeO-Ph) HH 2-203 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-EtO-Ph) HH 2-204 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-PrO-Ph) HH 2-205 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-iPrO-Ph) HH 2-206 HHH Me 2 -C≡C- (CH ₂ ) _3- (3-MeS-Ph) HH 2-207 HHH Me 2 -C≡C- (CH ₂ ) _3- (4-MeS-Ph) HH 2-208 HHH Me 2 -C≡C- (CH ₂ ) _3- (2,4-diMe-Ph) HH 2-209 HHH Me 2 -C≡C- (CH ₂ ) _3- (3,4-diMe-Ph) HH 2-210 HHH Me 2 -C≡C- (CH _{2) 3 - (3,5-diMe} -Ph) HH 2-211 HHH Me 2 -C≡C- (CH 2) 4 -cPn HH 2-212 HHH Me 2 -C≡C- (CH 2) 4 - cHx HH 2-213 HHH Me 2 -C≡C- (CH ₂ ) ₄ -cHx Me H 2-214 HHH Me 2 -C≡C- (CH ₂ ) ₄ -cHx H Me 2-215 HHH Me 2 -C ≡C- (CH ₂ ) ₄ -cHx FH 2-216 HHH Me 2 -C≡C- (CH ₂ ) ₄ -cHx HF 2-217 HH Me Me 2 -C≡C- (CH ₂ ) ₄ -cHx HH 2-218 Me HH Me 2 -C≡C- (CH ₂ ) ₄ -cHx HH 2-219 CO ₂ Me HH Me 2 -C≡C- (CH ₂ ) ₄ -cHx HH 2-220 HHH Me 2 -C _{≡C- (CH 2) 4 - (} 4-F-cHx) HH 2-221 HHH Me 2 -C≡C- (CH 2) 4 - (4-Cl-cHx) HH 2-222 HHH Me 2 -C _{≡C- (CH 2) 4 - (} 4-Br -cHx) HH 2-223 HHH Me 2 -C≡C- (CH 2) 4 - (4-Me-cHx) HH 2-224 HHH Me 2 -C≡C- (CH 2) 4 - (4-Et -cHx) HH 2-225 HHH Me 2 -C≡C- (CH 2) 4 - (4-Pr-cHx) HH 2-226 HHH Me 2 -C≡C- (CH 2) 4 - (4-iPr -cHx) HH 2-227 HHH Me 2 -C≡C- (CH 2) 4 - (4-Bu-cHx) HH 2-228 HHH Me 2 -C≡C- (CH 2) 4 - (4-CF _{3 -cHx) HH 2-229 HHH Me 2} -C≡C- (CH 2) 4 - (4-MeO-cHx) HH 2-230 HHH Me 2 -C≡C- (CH 2) 4 - (4- EtO-cHx) HH 2-231 HHH Me 2 -C≡C- (CH 2) 4 - (4-PrO-cHx) HH 2-232 HHH Me 2 -C≡C- (CH 2) 4 - (4- iPrO-cHx) HH 2-233 HHH Me 2 -C≡C- (CH 2) 4 - (4-MeS-cHx) HH 2-234 HHH Me 2 -C≡C- (CH 2) 4 - (2, 4-diMe-cHx) HH 2-235 HHH Me 2 -C≡C- (CH 2) 4 - (3,4-diMe-cHx) HH 2-236 HHH Me 2 -C≡C- (CH 2) 4 -(3,5-diMe-cHx) HH 2-237 HHH Me 2 -C≡C- (CH ₂ ) ₄ -Ph HH 2-238 HHH Me 2 -C≡C- (CH ₂ ) ₄ -Ph Me H 2-239 HHH Me 2 -C≡C- (CH ₂ ) ₄ -Ph H Me 2-240 HHH Me 2 -C≡C- (CH ₂ ) ₄ -Ph FH 2-241 HHH Me 2 -C≡C- (CH ₂ ) ₄ -Ph HF 2-242 HH Me Me 2 -C≡C- (CH ₂ ) ₄ -Ph HH 2-243 Me HH Me 2 -C≡C- (CH ₂ ) ₄ -Ph HH 2- 244 CO ₂ Me HH Me 2 -C≡C- ( _{CH 2) 4 -Ph HH 2-245 HHH} Me 2 -C≡C- (CH 2) 4 - (4-F-Ph) HH 2-246 HHH Me 2 -C≡C- (CH 2) 4 - ( 4-Cl-Ph) HH 2-247 HHH Me 2 -C≡C- (CH 2) 4 - (4-Br-Ph) HH 2-248 HHH Me 2 -C≡C- (CH 2) 4 - ( 4-Me-Ph) HH 2-249 HHH Me 2 -C≡C- (CH 2) 4 - (4-Et-Ph) HH 2-250 HHH Me 2 -C≡C- (CH 2) 4 - ( 4-Pr-Ph) HH 2-251 HHH Me 2 -C≡C- (CH 2) 4 - (4-iPr-Ph) HH 2-252 HHH Me 2 -C≡C- (CH 2) 4 - ( 4-Bu-Ph) HH 2-253 HHH Me 2 -C≡C- (CH 2) 4 - (4-CF 3 -Ph) HH 2-254 HHH Me 2 -C≡C- (CH 2) 4 - (4-MeO-Ph) HH 2-255 HHH Me 2 -C≡C- (CH 2) 4 - (4-EtO-Ph) HH 2-256 HHH Me 2 -C≡C- (CH 2) 4 - (4-PrO-Ph) HH 2-257 HHH Me 2 -C≡C- (CH 2) 4 - (4-iPrO-Ph) HH 2-258 HHH Me 2 -C≡C- (CH 2) 4 - (3-MeS-Ph) HH 2-259 HHH Me 2 -C≡C- (CH 2) 4 - (4-MeS-Ph) HH 2-260 HHH Me 2 -C≡C- (CH 2) 4 - (2,4-diMe-Ph) HH 2-261 HHH Me 2 -C≡C- (CH 2) 4 - (3,4-diMe-Ph) HH 2-262 HHH Me 2 -C≡C- (CH _{2) 4 - (3,5-diMe} -Ph) HH 2-263 HHH Me 2 -C≡C- (CH 2) 5 -cHx HH 2-264 HH Me Me 2 -C≡C- (CH 2) 5 -cHx HH 2-265 Me HH Me 2 -C≡C- (CH ₂ ) ₅ -cHx HH 2-266 CO ₂ Me HH Me 2 -C≡C- (CH ₂ ) ₅ -cHx HH 2-267 HHH Me 2 -C≡C- (CH ₂ ) ₅ -Ph HH 2-268 HH Me Me 2 -C≡C- (CH ₂ ) ₅ -Ph HH 2-269 Me HH Me 2 -C≡C- (CH ₂ ) ₅ -Ph HH 2-270 CO ₂ Me HH Me 2 -C≡C- (CH ₂ ) ₅ -Ph HH 2- 271 HHH Me 2 -C≡C- (CH ₂ ) ₆ -cHx HH 2-272 HH Me Me 2 -C≡C- (CH ₂ ) ₆ -cHx HH 2-273 Me HH Me 2 -C≡C- ( CH ₂ ) ₆ -cHx HH 2-274 CO ₂ Me HH Me 2 -C≡C- (CH ₂ ) ₆ -cHx HH 2-275 HHH Me 2 -C≡C- (CH ₂ ) ₆ -Ph HH 2- 276 HH Me Me 2 -C≡C- (CH ₂ ) ₆ -Ph HH 2-277 Me HH Me 2 -C≡C- (CH ₂ ) ₆ -Ph HH 2-278 CO ₂ Me HH Me 2 -C≡ C- (CH ₂ ) ₆ -Ph HH 2-279 HHH Me 2 -C≡C-CH ₂ O-cHx HH 2-280 HH Me Me 2 -C≡C-CH ₂ O-cHx HH 2-281 Me HH Me 2 -C≡C-CH ₂ O-cHx HH 2-282 CO ₂ Me HH Me 2 -C≡C-CH ₂ O-cHx HH 2-283 HHH Me 2 -C≡C-CH ₂ O-Ph HH 2-284 HH Me Me 2 -C≡C-CH ₂ O-Ph HH 2-285 Me HH Me 2 -C≡C-CH ₂ O-Ph HH 2-286 CO ₂ Me HH Me 2 -C≡C- CH ₂ O-Ph HH 2-287 HHH Me 2 -C≡C- (CH ₂ ) ₂ O-cPn HH 2-288 HHH Me 2 -C≡C- (CH ₂ ) ₂ O-cHx HH 2-289 HHH Me 2 -C≡C- (CH ₂ ) ₂ O-cHx Me H 2-290 HHH Me 2 -C≡C- (CH ₂ ) ₂ O-cHx H Me 2-291 HHH Me 2 -C≡C- (CH ₂ ) ₂ O-cHx FH 2-292 HHH Me 2 -C≡C- (CH ₂ ) ₂ O-cHx HF 2-293 HH Me Me 2 -C≡C- (CH ₂ ) ₂ -OCH ₂ -cHx HH 2-294 Me HH Me 2 -C≡C- (CH ₂ ) ₂ O-cHx HH 2-295 CO ₂ Me HH Me 2 -C≡C- (CH ₂ ) ₂ O-cHx HH 2-296 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-F-cHx) HH 2-297 HHH Me 2 -C≡C -(CH ₂ ) ₂ O- (4-Cl-cHx) HH 2-298 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-Br-cHx) HH 2-299 HHH Me 2 -C ≡C- (CH ₂ ) ₂ O- (4-Me-cHx) HH 2-300 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-Et-cHx) HH 2-301 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-Pr-cHx) HH 2-302 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-iPr-cHx) HH 2-303 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-Bu-cHx) HH 2-304 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-CF ₃ -cHx) HH 2 -305 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-MeO-cHx) HH 2-306 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-EtO-cHx) HH 2-307 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-PrO-cHx) HH 2-308 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-iPrO- cHx) HH 2-309 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (3-MeS-cHx) HH 2-310 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4- MeS-cHx) HH 2-311 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (2,4-diMe-cHx) HH 2-312 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (3,4-diMe-cHx) HH 2-313 HHH Me 2 -C≡C -(CH ₂ ) ₂ O- (3,5-diMe-cHx) HH 2-314 HHH Me 2 -C≡C- (CH ₂ ) ₂ O-Ph HH 2-315 HHH Me 2 -C≡C- ( CH ₂ ) ₂ O-Ph Me H 2-316 HHH Me 2 -C≡C- (CH ₂ ) ₂ O-Ph H Me 2-317 HHH Me 2 -C≡C- (CH ₂ ) ₂ O-Ph FH 2-318 HHH Me 2 -C≡C- (CH ₂ ) ₂ O-Ph HF 2-319 HH Me Me 2 -C≡C- (CH ₂ ) ₂ -OCH ₂ -Ph HH 2-320 Me HH Me 2 -C≡C- (CH ₂ ) ₂ O-Ph HH 2-321 CO ₂ Me HH Me 2 -C≡C- (CH ₂ ) ₂ O-Ph HH 2-322 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-F-Ph) HH 2-323 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-Cl-Ph) HH 2-324 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-Br-Ph) HH 2-325 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-Me-Ph) HH 2-326 HHH Me 2 -C≡ C- (CH ₂ ) ₂ O- (4-Et-Ph) HH 2-327 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-Pr-Ph) HH 2-328 HHH Me 2- C≡C- (CH ₂ ) ₂ O- (4-iPr-Ph) HH 2-329 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-Bu-Ph) HH 2-330 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-CF ₃ -Ph) HH 2-331 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-MeO-Ph) HH 2- 332 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-EtO-Ph) HH 2-333 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-PrO-Ph) HH 2-334 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-iPrO-Ph) HH 2-335 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (4-MeS-Ph) HH 2-336 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (2,4-diMe-Ph) HH 2-337 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (3,4-diMe-Ph) HH 2-338 HHH Me 2 -C≡C- (CH ₂ ) ₂ O- (3, 5-diMe-Ph) HH 2-339 HHH Me 2 -CO- (CH ₂ ) ₄ -cHx HH 2-340 HH Me Me 2 -CO- (CH ₂ ) ₄ -cHx HH 2-341 Me HH Me 2- CO- (CH ₂ ) ₄ -cHx HH 2-342 CO ₂ Me HH Me 2 -CO- (CH ₂ ) ₄ -cHx HH 2-343 HHH Me 2 -CO- (CH ₂ ) ₄ -Ph HH 2-344 HH Me Me 2 -CO- (CH ₂ ) ₄ -Ph HH 2-345 Me HH Me 2 -CO- (CH ₂ ) ₄ -Ph HH 2-346 CO ₂ Me HH Me 2 -CO- (CH ₂ ) ₄ -Ph HH 2-347 HHH Me 2 -CO- (CH ₂ ) ₅ -cHx HH 2-348 HH Me Me 2 -CO- (CH ₂ ) ₅ -cHx HH 2-349 Me HH Me 2 -CO- (CH ₂ ) ₅ -cHx HH 2-350 CO ₂ Me HH Me 2 -CO- (CH ₂ ) ₅ -cHx HH 2-351 HHH Me 2 -CO- (CH ₂ ) ₅ -Ph HH 2-352 HH Me Me 2 -CO- (CH ₂ ) ₅ -Ph HH 2-353 Me HH Me 2 -CO- (CH ₂ ) ₅ -Ph HH 2-354 CO ₂ Me HH Me 2 -CO- (CH ₂ ) ₅ -Ph HH 2 -355 HHH Me 2 -CH (OH)-(CH ₂ ) ₄ -cHx HH 2-356 HH Me Me 2 -CH (OH)-(CH ₂ ) ₄ -cHx HH 2-3 57 Me HH Me 2 -CH (OH)-(CH ₂ ) ₄ -cHx HH 2-358 CO ₂ Me HH Me 2 -CH (OH)-(CH ₂ ) ₄ -cHx HH 2-359 HHH Me 2 -CH (OH)-(CH ₂ ) ₄ -Ph HH 2-360 HH Me Me 2 -CH (OH)-(CH ₂ ) ₄ -Ph HH 2-361 Me HH Me 2 -CH (OH)-(CH ₂ ) ₄ -Ph HH 2-362 CO ₂ Me HH Me 2 -CH (OH)-(CH ₂ ) ₄ -Ph HH 2-363 HHH Me 2 -CH (OH)-(CH ₂ ) ₅ -cHx HH 2-364 HH Me Me 2 -CH (OH)-(CH ₂ ) ₅ -cHx HH 2-365 Me HH Me 2 -CH (OH)-(CH ₂ ) ₅ -cHx HH 2-366 CO ₂ Me HH Me 2 -CH (OH)-(CH ₂ ) ₅ -cHx HH 2-367 HHH Me 2 -CH (OH)-(CH ₂ ) ₅ -Ph HH 2-368 HH Me Me 2 -CH (OH)-(CH ₂ ) ₅ -Ph HH 2-369 Me HH Me 2 -CH (OH)-(CH ₂ ) ₅ -Ph HH 2-370 CO ₂ Me HH Me 2 -CH (OH)-(CH ₂ ) ₅ -Ph HH 2-371 HHH Me 2 -4- (cHx-CH ₂ O) Ph HH 2-372 HH Me Me 2 -4- (cHx-CH ₂ O) Ph HH 2-373 Me HH Me 2 -4- (cHx-CH ₂ O ) Ph HH 2-374 CO ₂ Me HH Me 2 -4- (cHx-CH ₂ O) Ph HH 2-375 HHH Me 2 -4- [cHx- (CH ₂ ) ₂ O] Ph HH 2-376 HHH Me 2 -4- [cHx- (CH ₂ ) ₃ O] Ph HH 2-377 HHH Me 2-(4-BzO-Ph) HH 2-378 HH Me Me 2-(4-BzO-Ph) HH 2-379 Me HH Me 2-(4-BzO-Ph) HH 2-380 CO ₂ Me HH Me 2-(4-BzO-Ph) HH 2-381 HHH Me 2-(4-BzO-2-F- Ph) HH 2-382 HHH Me 2-(4-BzO-3-F-Ph) HH 2-383 HHH Me 2-(4-BzO-2,3-diF-Ph) HH 2-384 HHH Me 2- (4-BzO-2-Cl-Ph) HH 2-385 HHH Me 2-(4-BzO-3-Cl-Ph) HH 2-386 HHH Me 2-(4-BzO-2,3-diCl-Ph ) HH 2-387 HHH Me 2-(4-BzO-2-Me-Ph) HH 2-388 HHH Me 2-(4-BzO-3-Me-Ph) HH 2-389 HHH Me 2-(4- BzO-2,3-diMe-Ph) HH 2-390 HHH Me 2 -4- [Ph- (CH ₂ ) ₂ O] -Ph HH 2-391 HHH Me 2 -4- [Ph- (CH ₂ ) ₃ O] -Ph HH 2-392 HHH Et 2-(CH ₂ ) ₅ -cHx HH 2-393 HHH Et 2-(CH ₂ ) ₆ -cHx HH 2-394 HHH Et 2 -C≡C- (CH ₂ ) ₃ -cHx HH 2-395 HHH Et 2 -C≡C- (CH ₂ ) ₄ -cHx HH 2-396 HHH Et 2 -4- (cHx-CH ₂ O) Ph HH 2-397 HHH Et 2-(4 -BzO-Ph) HH 2-398 HHH Et 2 -C≡C- (CH ₂ ) ₂ O-cHx HH 2-399 HHH Et 2 -C≡C- (CH ₂ ) ₂ O-Ph HH 2-400 HHH Pr 2-(CH ₂ ) ₅ -cHx HH 2-401 HHH Pr 2-(CH ₂ ) ₆ -cHx HH 2-402 HHH Pr 2 -C≡C- (CH ₂ ) ₃ -cHx HH 2-403 HHH Pr 2 -C≡C- (CH ₂ ) ₄ -cHx HH 2-404 HHH Pr 2 -4- (cHx-CH ₂ O) Ph HH 2-405 HHH Pr 2-(4-BzO-Ph) HH 2-406 HHH Pr 2 -C≡C- (CH ₂ ) ₂ O-cHx HH 2-407 HHH Pr 2 -C≡C- (CH ₂ ) ₂ O-Ph HH 2-408 HHH Me 3-(CH ₂ ) _5- cHx HH 2-409 HHH Me 3-(CH ₂ ) ₆ -cHx HH 2-410 HHH Me 3 -C≡C- (CH ₂ ) ₃ -cHx HH 2-411 HHH Me 3 -C≡C- (CH ₂ ) ₄ -cHx HH 2-412 HHH Me 3 -4- (cHx-CH ₂ O) Ph HH 2-413 HHH Me 3-(4-BzO-Ph) HH 2-414 HHH Me 3 -C≡C- (CH ₂ ) ₂ O-cHx HH 2-415 HHH Me 3 -C≡C- (CH ₂ ) ₂ O-Ph HH .

In the above Tables 1 and 2, the compounds of the present invention
Preferred as (I) are exemplified compound numbers: 1-19, 1-23 to 1-32, 1-36 to 1-45, 1-49
~ 1-58, 1-62 ~ 1-71, 1-75 ~ 1-84, 1-88 ~ 1-102, 1-106
~ 1-156, 1-160 ~ 1-214, 1-218 ~ 1-268, 1-272 ~ 1-322,
1-325 ~ 1-334, 1-338 ~ 1-347, 1-351 ~ 1-360, 1-364 ~
1-373, 1-377 ~ 1-386, 1-390 ~ 1-404, 1-408 ~ 1-458, 1
-462〜1-513, 1-517〜1-526, 1-530〜1-544, 1-548〜1-
598, 1-602 to 1-657, 1-670, 1-674 to 1-683, 1-696, 1-7
00 ~ 1-717,1-721 ~ 1-730, 1-734 ~ 1-743, 1-747 ~ 1-75
6, 1-760〜1-774, 1-778〜1-828, 1-832〜1-886, 1-890
〜1-940, 1-944〜1-993, 1-997〜1-1006, 1-1010〜1-10
19,1-1045, 1-1049 ~ 1-1058, 1-1062 ~ 1-1076, 1-1080
~ 1-1130, 1-1134 ~ 1-1185, 1-1189 ~ 1-1198, 1-1202 ~ 1
-1208, 1-1212 to 1-1216, 1-1220 to 1-1270, 1-1274 to 1-1
331, 1-1335-1-1344, 1-1348-1-1357, 1-1361-1-137
0, 1-1374 to 1-1387, 1-1391 to 1-1400, 1-1404 to 1-1418,
1-1422 to 1-1472, 1-1476 to 1-1527, 1-1531 to 1-1540, 1-
1544 to 1-1558, 1-1562 to 1-1612, 1-1616 to 1-1673, 1-16
77-1-1686, 1-1690-1-1699, 1-1703-1-1712, 1-1716
~ 1-1729, 1-1733 ~ 1-1744, 1-1748 ~ 1-1767, 1-1772 ~
1-1793, 1-1797 to 1-1818, 1-1824 to 1-1846, 1-1850 to 1-
1869,1-1872, 1-1876, 1-1880, 1-1884, 1-1888-1-189
2, 1-1896, 1-1900, 1-1908-1-1913, 1-1917-1-1939,
1-1943〜1-1966, 1-1970〜1-1991, 1-1995〜1-2013,1-
2017, 1- 2021, 1-2025, 1-2029, 1-2033, 1-2037-1-2
042, 1-2045 ~ 1-2068, 1-2072 ~ 1-2089, 1-2093, 1-209
7, 1-2101, 1-2105, 1-2109, 1-2113, 1-2117,1-2121,
1-2125, 1-2129, 1-2133, 1-2135, 1-2139〜1-2158, 1-
2161 to 1-2164, 1-2184 to 1-2346, 2-9 to 2-18, 2-22 to 2-43,
2-47 to 2-70, 2-74 to 2-96, 2-100 to 2-119, 2-142, 2-14
6, 2-150, 2-154, 2-158 to 2-163, 2-167 to 2-183, 2-185
~ 2-189, 2-193 ~ 2-216,2-220 ~ 2-241, 2-245 ~ 2-263,
2-267, 2-271, 2-275, 2-279, 2-283, 2-287 to 2-292, 2
-296 ~ 2-318, 2-322 ~ 2-338, 2-343, 2-347, 2-351, 2-
371, 2-375 ~ 2-377, 2-381 ~ 2-407
And more preferably, 1-19, 1-32, 1-36 to 1-45, 1-57, 1-
62 ~ 1-71, 1-84, 1-88, 1-97 ~ 1-100, 1-152 ~ 1-154, 1
-160 to 1-214, 1-218 to 1-227, 1-264 to 1-268, 1-272 to 1-
322, 1-334,1-347, 1-360, 1-373, 1-386, 1-390-1-40
2, 1-454〜1-458, 1-462〜1-513, 1-526, 1-530〜1-54
2, 1-594〜1-598, 1-602〜1-653, 1-743, 1-756, 1-760
~ 1-768, 1-770 ~ 1-774, 1-778 ~ 1-828, 1-832 ~ 1-886,
1-890〜1-940, 1-944〜1-993,1-1045, 1-1058, 1-1062
~ 1-1074, 1-1126 ~ 1-1130, 1-1134 ~ 1-1185, 1-1198,1
-1202 to 1-1208, 1-1212, 1-1213, 1-1214, 1-1266 to 1-1
270, 1-1274 to 1-1331, 1-1344, 1-1348 to 1-1357, 1-137
0, 1-1374 ~ 1-1387, 1-1400, 1-1404 ~ 1-1416, 1-1468 ~
1-1472, 1-1476 to 1-1527, 1-1540, 1-1544 to 1-1556, 1-
1608-1-1612,1-1616-1-1666, 1-1729, 1-1742, 1-174
4, 1-1759 to 1-1767, 1-1789 to 1-1793, 1-1797 to 1-1818,
1-1842 to 1-1846, 1-1900, 1-1908 to 1-1913, 1-1935 to 1-
1939,1-1943〜1-1966, 1-1987〜1-1991, 1-2013, 1-201
7, 1-2029, 1-2033, 1-2037 ~ 1-2042, 1-2064 ~ 1-2068,
1-2072〜1-2089, 1-2093, 1-2097, 1-2101, 1-2105, 1
-2109, 1-2129, 1-2133, 1-2135, 1-2184〜1-2346,2-11
~ 2-18, 2-39 ~ 2-43, 2-47 ~ 2-70, 2-185 ~ 2-189, 2-19
3-2-216, 2-287-2-292, 2-338, 2-343, 2-347, 2-35
1, and more preferably 1-45, 1-71, 1-
84, 1-88, 1-97 to 1-100, 1-152 to 1-154, 1-160 to 1-206,
1-209-1-212, 1-264-1-266, 1-334, 1-373, 1-386,
1-390 ~ 1-402, 1-454 ~ 1-458, 1-462 ~ 1-485, 1-509, 1
-510, 1-513, 1-526, 1-530 to 1-542, 1-594 to 1-598, 1-
602 ~ 1-613, 1-649, 1-650, 1-743, 1-756, 1-760 ~ 1-7
68, 1-770 to 1-772, 1-824 to 1-828, 1-832 to 1-884, 1-93
6, 1-1045, 1-1058, 1-1062 to 1-1074, 1-1126 to 1-1130,
1-1134 to 1-1145, 1-1148 to 1-1151, 1-1162, 1-1163, 1
-1179 to 1-1182, 1-1185, 1-1198, 1-1202 to 1-1208, 1-1
212, 1-1213, 1-1214, 1-1266-1-1270, 1-1274-1-128
5, 1-1288-1-1291, 1-1319-1-1322, 1-1329-1-1331,
1-1344, 1-1348 to 1-1357, 1-1370, 1-1387, 1-1400, 1
-1404 to 1-1416, 1-1468 to 1-1472, 1-1476 to 1-1487, 1-1
490-1-1493, 1-1504, 1-1505, 1-1521-1-1524, 1-152
7, 1-1540, 1-1544 to 1-1556, 1-1608 to 1-1612, 1-1616
~ 1-1627, 1-1663, 1-1664, 1-1729, 1-1742, 1-1744,
1-1761 to 1-1766, 1-1789 to 1-11791, 1-1815 to 1-1818, 1-
1900, 1-1909, 1-1962, 1-2064 to 1-2066, 1-2089, 1-20
93, 1-2097, 1-2105, 1-2133, 1-2216-1-2288, 1-2290
To 1-2346, and even more suitable compounds
For example, Exemplified Compound No. 1-71: 2-amino-2-methyl-4- [5- (4-cycle
Rohexylbutyl) thiophen-2-yl] butan-1-o
Compound No. 1-84: 2-amino-2-methyl-4- [5- (4-phenyl
N-butyl) thiophen-2-yl] butan-1-ol, Exemplified Compound No. 1-98: 2-amino-2-methyl-4- [5- (5-cyclyl)
Rohexylpentyl) thiophen-2-yl] butan-1-o
Exemplified Compound No. 1-152: 2-amino-2-methyl-4- [5- (5-f
Enylpentyl) thiophen-2-yl] butan-1-ol, Exemplified Compound No. 1-210: 2-amino-2-methyl-4- [5- (6-cy
Clohexylhexyl) thiophen-2-yl] butan-1-o
Compound No. 1-264: 2-amino-2-methyl-4- [5- (6-phenyl)
Enylhexyl) thiophen-2-yl] butan-1-ol, Exemplified Compound No. 1-373: 2-amino-2-methyl-4- [5- (3-cy
Clohexyloxypropyl) thiophen-2-yl] buta
1-386: 2-amino-2-methyl-4- [5- (3-f
Enoxypropyl) thiophen-2-yl] butan-1-o
Compound No. 1-400: 2-amino-2-methyl-4- [5- (4-cy
Clohexyloxybutyl) thiophen-2-yl] butane-
1-ol, Exemplified Compound No. 1-454: 2-amino-2-methyl-4- [5- (4-f
Phenoxybutyl) thiophen-2-yl] butan-1-ol, Exemplified Compound No. 1-509: 2-amino-2-methyl-4- [5- (5-si
Clohexyloxypentyl) thiophen-2-yl] pig
1-510: 2-amino-2-methyl-4- [5- (5-f
Enoxypentyl) thiophen-2-yl] butan-1-o
Example Compound No. 1-513: 2-amino-2-methyl-4- [5- (4-
Clohexylmethoxypropyl) thiophen-2-yl]
Tan-1-ol, Exemplified Compound No. 1-743: 2-amino-2-methyl-4- [5- (4-si
Chlohexylbut-1-ynyl) thiophen-2-yl] butane
-1-ol, Exemplified Compound No. 1-756: 2-amino-2-methyl-4- [5- (4-f
Enylbut-1-ynyl) thiophen-2-yl] butane-1-o
Exemplified Compound No. 1-770: 2-amino-2-methyl-4- [5- (5-series
Clohexylpent-1-ynyl) thiophen-2-yl] buta
1-824, Exemplified Compound No. 1-824: 2-amino-2-methyl-4- [5- (5-f
Enylpent-1-ynyl) thiophen-2-yl] butane-1-
All, Exemplified Compound No. 1-882: 2-amino-2-methyl-4- [5- (6-si
Clohexylhex-1-ynyl) thiophen-2-yl] buta
1-936: 2-amino-2-methyl-4- [5- (6-f
Enylhex-1-ynyl) thiophen-2-yl] butane-1-
All, Exemplified Compound No. 1-1045: 2-amino-2-methyl-4- [5- (3-si
Clohexyloxypropynyl) thiophen-2-yl] B
Tan-1-ol, Exemplified Compound No. 1-1058: 2-amino-2-methyl-4- [5- (3-f
Enoxypropynyl) thiophen-2-yl] butan-1-o
Compound No. 1-1072: 2-amino-2-methyl-4- [5- (4-cy
Clohexyloxybut-1-ynyl) thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1126: 2-amino-2-methyl-4- [5- (4-f
Enoxybut-1-ynyl) thiophen-2-yl] butane-1-
All, Exemplified Compound No. 1-1181: 2-amino-2-methyl-4- [5- (5-cy
Clohexyloxypent-1-ynyl) thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1182: 2-amino-2-methyl-4- [5- (5-f
Enoxypent-1-ynyl) thiophen-2-yl] butane-1
-All, Exemplified Compound No. 1-1185: 2-amino-2-methyl-4- [5- (3-si
Clohexylmethoxypropynyl) thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1329: 2-amino-2-methyl-4- [5- (4-si
Clohexylbutanoyl) thiophen-2-yl] butane-1-
All, Exemplified Compound No. 1-1330: 2-amino-2-methyl-4- [5- (4-f
Enylbutanoyl) thiophen-2-yl] butan-1-o
Compound No. 1-1331: 2-amino-2-methyl-4- [5- (5-
Clohexylpentanoyl) thiophen-2-yl] butane-
1-ol, Exemplified Compound No. 1-1344: 2-amino-2-methyl-4- [5- (5-f
Enylpentanoyl) thiophen-2-yl] butan-1-o
Compound No. 1-1357: 2-amino-2-methyl-4- [5- (6-s
Clohexylhexanoyl) thiophen-2-yl] butane-
1-ol, Exemplified Compound No. 1-1370: 2-amino-2-methyl-4- [5- (6-f
Enylhexanoyl) thiophen-2-yl] butan-1-o
Compound No. 1-1387: 2-amino-2-methyl-4- [5- (3-s
Clohexyloxypropanoyl) thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1400: 2-amino-2-methyl-4- [5- (3-f
Enoxypropanoyl) thiophen-2-yl] butane-1-o
Illustrative Compound No. 1-1414: 2-amino-2-methyl-4- [5- (4-series
Chlohexyloxybutanoyl) thiophen-2-yl] B
Tan-1-ol, Exemplified Compound No. 1-1468: 2-amino-2-methyl-4- [5- (4-f
Enoxybutanoyl) thiophen-2-yl] butan-1-o
Compound No. 1-1523: 2-amino-2-methyl-4- [5- (5-
Clohexyloxypentanoyl) thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1524: 2-amino-2-methyl-4- [5- (5-f
Enoxypentanoyl) thiophen-2-yl] butane-1-o
Compound No. 1-1527: 2-amino-2-methyl-4- [5- (4-series
Clohexylmethoxypropanoyl) thiophen-2-i
L] butan-1-ol, Exemplified Compound No. 1-1729: 2-amino-2-methyl-4- [5- (4-si
Clohexylmethoxyphenyl) thiophen-2-yl]
Tan-1-ol, Exemplified Compound No. 1-1742: 2-amino-2-methyl-4- [5- (4-si
Chlohexylethoxyphenyl) thiophen-2-yl] B
Tan-1-ol, Exemplified Compound No. 1-1744: 2-amino-2-methyl-4- [5- (4-
Ndyloxyphenyl) thiophen-2-yl] butan-1-o
Compound No. 1-1761: 2-amino-2-ethyl-4- [5- (4-series
Clohexylbutyl) thiophen-2-yl] butan-1-o
, Exemplified Compound No. 1-1764: 2-amino-2-ethyl-4- [5- (5-
Clohexylpentyl) thiophen-2-yl] butan-1-o
Illustrative Compound No. 1-1816: 2-amino-2-ethyl-4- [5- (6-series
Clohexylhexyl) thiophen-2-yl] butan-1-o
Illustrative Compound No. 1-1900: 2-amino-2-ethyl-4- [5- (4-series
Chlohexylbut-1-ynyl) thiophen-2-yl] butane
-1-ol, Exemplified Compound No. 1-1909: 2-amino-2-ethyl-4- [5- (5-si
Clohexylpent-1-ynyl) thiophen-2-yl] buta
-1-ol, Exemplified Compound No. 1-1962: 2-amino-2-ethyl-4- [5- (6-si
Clohexylhex-1-ynyl) thiophen-2-yl] buta
-1-ol, Exemplified Compound No. 1-2089: 2-amino-2-ethyl-4- [5- (4-si
Clohexylbutanoyl) thiophen-2-yl] butane-1-
All, Exemplified Compound No. 1-2097: 2-amino-2-ethyl-4- [5- (5-
Clohexylpentanoyl) thiophen-2-yl] butane-
1-ol, and Exemplified Compound No. 1-2105: 2-amino-2-ethyl-4- [5- (6-si
Clohexylhexanoyl) thiophen-2-yl] butane-
1-ol, and Exemplified Compound No. 1-463: 2-amino-2-methyl-4- [5- [4- (4-
Fluorophenoxy) butyl] thiophen-2-yl] butane
-1-ol, Exemplified Compound No. 1-479: 2-amino-2-methyl-4- [5- [4- (4-
Methoxyphenoxy) butyl] thiophen-2-yl] butane
-1-ol, Exemplified Compound No. 1-594: 2-amino-2-methyl-4- [5- (4-
Ndyloxybutyl) thiophen-2-yl] butan-1-o
Compound No. 1-760: 2-amino-2-methyl-4- [5- [4
-(4-Fluorophenyl) but-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-761: 2-amino-2-methyl-4- [5- [4- (4-
Methylphenyl) but-1-ynyl] thiophen-2-yl] but
Tan-1-ol, Exemplified Compound No. 1-762: 2-amino-2-methyl-4- [5- [4- (4-
Ethylphenyl) but-1-ynyl] thiophen-2-yl] but
Tan-1-ol, Exemplified Compound No. 1-763: 2-amino-2-methyl-4- [5- [4- (4-
Trifluoromethylphenyl) but-1-ynyl] thiofe
N-2-yl] butan-1-ol, Exemplified Compound No. 1-764: 2-amino-2-methyl-4- [5- [4- (4-
Methoxyphenyl) but-1-ynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-765: 2-amino-2-methyl-4- [5- [4- (4-
Ethoxyphenyl) but-1-ynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-766: 2-amino-2-methyl-4- [5- [4- (4-
Methylthiophenyl) but-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-832: 2-amino-2-methyl-4- [5- [5- (3-
Fluorophenyl) pent-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-833: 2-amino-2-methyl-4- [5- [5- (4-
Fluorophenyl) pent-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-834: 2-amino-2-methyl-4- [5- [5- (4-
Chlorophenyl) pent-1-ynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-836: 2-amino-2-methyl-4- [5- [5- (3-
Methylphenyl) pent-1-ynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-837: 2-amino-2-methyl-4- [5- [5- (4-
Methylphenyl) pent-1-ynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-846: 2-amino-2-methyl-4- [5- [5- (3-
Trifluoromethylphenyl) pent-1-ynyl] thiof
En-2-yl] butan-1-ol, Exemplified Compound No. 1-847: 2-amino-2-methyl-4- [5- [5- (4-
Trifluorophenyl) pent-1-ynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-848: 2-amino-2-methyl-4- [5- [5- (3-
Methoxyphenyl) pent-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-849: 2-amino-2-methyl-4- [5- [5- (4-
Methoxyphenyl) pent-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-860: 2-amino-2-methyl-4- [5- [5- (3-
Methylthiophenyl) pent-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-861: 2-amino-2-methyl-4- [5- [5- (4-
Methylphenyl) pent-1-ynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-877: 2-amino-2-methyl-4- [5- [5- (3,
4-dimethylphenyl) pent-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-878: 2-amino-2-methyl-4- [5- [5- (3,
5-dimethylphenyl) pent-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1050: 2-amino-2-methyl-4- [5- [3- (4
-Methylcyclohexyloxy) propynyl] thiophene-
2-yl] butan-1-ol, Exemplified Compound No. 1-1062: 2-amino-2-methyl-4- [5- [3- (4
-Fluorophenoxy) propynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1063: 2-amino-2-methyl-4- [5- [3- (4
-Methylphenoxy) propynyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-1064: 2-amino-2-methyl-4- [5- [3- (4
-Ethylphenoxy) propynyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-1065: 2-amino-2-methyl-4- [5- [3- (4
-Trifluoromethylphenoxy) propynyl] thiofe
N-2-yl] butan-1-ol, Exemplified Compound No. 1-1066: 2-amino-2-methyl-4- [5- [3- (4
-Methoxyphenoxy) propynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1067: 2-amino-2-methyl-4- [5- [3- (4
-Ethoxyphenoxy) propynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1068: 2-amino-2-methyl-4- [5- [3- (4
-Methylthiophenoxy) propynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1134: 2-amino-2-methyl-4- [5- [4- (3
-Fluorophenoxy) but-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1135: 2-amino-2-methyl-4- [5- [4- (4
-Fluorophenoxy) but-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1136: 2-amino-2-methyl-4- [5- [4- (4
-Chlorophenoxy) but-1-ynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1138: 2-amino-2-methyl-4- [5- [4- (3
-Methylphenoxy) but-1-ynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1139: 2-amino-2-methyl-4- [5- [4- (4
-Methylphenoxy) but-1-ynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1148: 2-amino-2-methyl-4- [5- [4- (3
-Trifluoromethylphenoxy) but-1-ynyl] thiof
En-2-yl] butan-1-ol, Exemplified Compound No. 1-1149: 2-amino-2-methyl-4- [5- [4- (4
-Trifluoromethylphenoxy) but-1-ynyl] thiof
En-2-yl] butan-1-ol, Exemplified Compound No. 1-1150: 2-amino-2-methyl-4- [5- [4- (3
-Methoxyphenoxy) but-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1151: 2-amino-2-methyl-4- [5- [4- (4
-Methoxyphenoxy) but-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1162: 2-amino-2-methyl-4- [5- [4- (3
-Methylthiophenoxy) but-1-ynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-1163: 2-amino-2-methyl-4- [5- [4- (4
-Methylthiophenoxy) but-1-ynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-1179: 2-amino-2-methyl-4- [5- [4-
(3,4-Dimethylphenoxy) but-1-ynyl] thiophene-2
-Yl] butan-1-ol, Exemplified Compound No. 1-1180: 2-amino-2-methyl-4- [5- [4-
(3,5-Dimethylphenoxy) but-1-ynyl] thiophene-2
-Yl] butan-1-ol, Exemplified Compound No. 1-1198: 2-amino-2-methyl-4- [5- (3-f
Enylmethoxypropynyl) thiophen-2-yl] butane-
1-ol, Exemplified Compound No. 1-1202: 2-amino-2-methyl-4- [5- [3- (4
-Fluorophenyl) methoxypropynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-1203: 2-amino-2-methyl-4- [5- [3- (4
-Methylphenyl) methoxypropynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1204: 2-amino-2-methyl-4- [5- [3- (4
-Ethylphenyl) methoxypropynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1205: 2-amino-2-methyl-4- [5- [3- (4
-Trifluoromethylphenyl) methoxypropynyl] thio
Offen-2-yl] butan-1-ol, Exemplified Compound No. 1-1206: 2-amino-2-methyl-4- [5- [3- (4
-Methoxyphenyl) methoxypropynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-1207: 2-amino-2-methyl-4- [5- [3- (4
-Ethoxyphenyl) methoxypropynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-1208: 2-amino-2-methyl-4- [5- [3- (4
-Methylthiophenyl) methoxypropynyl] thiophene-
2-yl] butan-1-ol, Exemplified Compound No. 1-1212: 2-amino-2-methyl-4- [5- (4-si
Clohexylmethoxybut-1-ynyl) thiophen-2-i
L] butan-1-ol, Exemplified Compound No. 1-1266: 2-amino-2-methyl-4- [5- (4-f
Enylmethoxybut-1-ynyl) thiophen-2-yl] buta
-1-ol, Exemplified Compound No. 1-1274: 2-amino-2-methyl-4- [5- [4- (3
-Fluorophenyl) methoxybut-1-ynyl] thiophene
2-yl] butan-1-ol, Exemplified Compound No. 1-1275: 2-amino-2-methyl-4- [5- [4- (4
-Fluorophenyl) methoxybut-1-ynyl] thiophene
2-yl] butan-1-ol, Exemplified Compound No. 1-1276: 2-amino-2-methyl-4- [5- [4- (4
-Chlorophenyl) methoxybut-1-ynyl] thiophene-2
-Yl] butan-1-ol, Exemplified Compound No. 1-1278: 2-amino-2-methyl-4- [5- [4- (3
-Methylphenyl) methoxybut-1-ynyl] thiophene-2
-Yl] butan-1-ol, Exemplified Compound No. 1-1279: 2-amino-2-methyl-4- [5- [4- (4
-Methylphenyl) methoxybut-1-ynyl] thiophene-2
-Yl] butan-1-ol, Exemplified Compound No. 1-1288: 2-amino-2-methyl-4- [5- [4- (3
-Trifluoromethylphenyl) methoxybut-1-ynyl]
Thiophen-2-yl] butan-1-ol, Exemplified Compound No. 1-1289: 2-amino-2-methyl-4- [5- [4- (4
-Trifluoromethylphenyl) methoxybut-1-ynyl]
Thiophen-2-yl] butan-1-ol, Exemplified Compound No. 1-1290: 2-amino-2-methyl-4- [5- [4- (3
-Methoxyphenyl) methoxybut-1-ynyl] thiophene
2-yl] butan-1-ol, Exemplified Compound No. 1-1291: 2-amino-2-methyl-4- [5- [4- (4
-Methoxyphenyl) methoxybut-1-ynyl] thiophene
2-yl] butan-1-ol, Exemplified Compound No. 1-1319: 2-amino-2-methyl-4- [5- [4-
(3,4-dimethylphenyl) methoxybut-1-ynyl] thiof
En-2-yl] butan-1-ol, Exemplified Compound No. 1-1320: 2-amino-2-methyl-4- [5- [4-
(3,5-dimethylphenyl) methoxybut-1-ynyl] thiof
En-2-yl] butan-1-ol, Exemplified Compound No. 1-1348: 2-amino-2-methyl-4- [5- [5- (4
-Fluorophenyl) pentanoyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1349: 2-amino-2-methyl-4- [5- [5- (4
-Methylphenyl) pentanoyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-1350: 2-amino-2-methyl-4- [5- [5- (4
-Ethylphenyl) pentanoyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-1351: 2-amino-2-methyl-4- [5- [5- (4
-Trifluoromethylphenyl) pentanoyl] thiofe
N-2-yl] butan-1-ol, Exemplified Compound No. 1-1352: 2-amino-2-methyl-4- [5- [5- (4
-Methoxyphenyl) pentanoyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1353: 2-amino-2-methyl-4- [5- [5- (4
-Ethoxyphenyl) pentanoyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1354: 2-amino-2-methyl-4- [5- [5- (4
-Methylthiophenyl) pentanoyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1476: 2-amino-2-methyl-4- [5- [4- (3
-Fluorophenoxy) butanoyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1477: 2-amino-2-methyl-4- [5- [4- (4
-Fluorophenoxy) butanoyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1478: 2-amino-2-methyl-4- [5- [4- (4
-Chlorophenoxy) butanoyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-1480: 2-amino-2-methyl-4- [5- [4- (3
-Methylphenoxy) butanoyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-1481: 2-amino-2-methyl-4- [5- [4- (4
-Methylphenoxy) butanoyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-1490: 2-amino-2-methyl-4- [5- [4- (3
-Trifluoromethylphenoxy) butanoyl] thiofe
N-2-yl] butan-1-ol, Exemplified Compound No. 1-1491: 2-amino-2-methyl-4- [5- [4- (4
-Trifluoromethylphenoxy) butanoyl] thiofe
2-N-yl] butan-1-ol, Exemplified Compound No. 1-1492: 2-amino-2-methyl-4- [5- [4- (3
-Methoxyphenoxy) butanoyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1493: 2-amino-2-methyl-4- [5- [4- (4
-Methoxyphenoxy) butanoyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1504: 2-amino-2-methyl-4- [5- [4- (3
-Methylthiophenoxy) butanoyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1505: 2-amino-2-methyl-4- [5- [4- (4
-Methylthiophenoxy) butanoyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1521: 2-amino-2-methyl-4- [5- [4-
(3,4-Dimethylphenoxy) butanoyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1522: 2-amino-2-methyl-4- [5- [4-
(3,5-Dimethylphenoxy) butanoyl] thiophen-2-i
L] butan-1-ol, Exemplified Compound No. 1-2093: 2-amino-ethyl-4- [5- (4-f
Enylbutanoyl) thiophen-2-yl] butan-1-o
Compound No. 1-2101: 2-amino-ethyl-4- [5- (5-f
Enylpentanoyl) thiophen-2-yl] butan-1-o
Compound No. 1-2109: 2-amino-ethyl-4- [5- (6-f
Enylhexanoyl) thiophen-2-yl] butan-1-o
Compound No. 1-2257: 2-amino-2-methyl-4- [5- [5-
(3,4-Difluorophenyl) pent-1-ynyl] thiophene
2-yl] butan-1-ol, Exemplified Compound No. 1-2258: 2-amino-2-methyl-4- [5- [5-
(3,5-Difluorophenyl) pent-1-ynyl] thiophene
2-yl] butan-1-ol, Exemplified Compound No. 1-2259: 2-amino-2-methyl-4- [5- [5- (3
-Chlorophenyl) pent-1-ynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-2260: 2-amino-2-methyl-4- [5- [5-
(3,4-dichlorophenyl) pent-1-ynyl] thiophene-2
-Yl] butan-1-ol, Exemplified Compound No. 1-2261: 2-amino-2-methyl-4- [5- [5-
(3,5-dichlorophenyl) pent-1-ynyl] thiophene-2
-Yl] butan-1-ol, Exemplified Compound No. 1-2262: 2-amino-2-methyl-4- [5- [5-
(3,4-ditrifluoromethylphenyl) pent-1-ynyl]
Thiophen-2-yl] butan-1-ol, Exemplified Compound No. 1-2263: 2-amino-2-methyl-4- [5- [5-
(3,5-ditrifluoromethylphenyl) pent-1-ynyl]
Thiophen-2-yl] butan-1-ol, Exemplified Compound No. 1-2264: 2-amino-2-methyl-4- [5- [5-
(3,4-Dimethoxyphenyl) pent-1-ynyl] thiophene
2-yl] butan-1-ol, Exemplified Compound No. 1-2265: 2-amino-2-methyl-4- [5- [5-
(3,5-Dimethoxyphenyl) pent-1-ynyl] thiophene
-2-yl] butan-1-ol, Exemplified Compound No. 1-2266: 2-amino-2-methyl-4- [5- [5-
(3,4,5-trimethoxyphenyl) pent-1-ynyl] thiof
En-2-yl] butan-1-ol, Exemplified Compound No. 1-2267: 2-amino-2-methyl-4- [5- [5- (3
-Acetylphenyl) pent-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2268: 2-amino-2-methyl-4- [5- [5- (4
-Acetylphenyl) pent-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2269: 2-amino-2-methyl-4- [5- [3- (3
-Fluorophenoxy) propynyl] thiophen-2-yl]
Butan-1-ol, exemplified compound number 1-2270: 2-amino-2-methyl-4- [5- [3-
(3,4-Difluorophenoxy) propynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-2271: 2-amino-2-methyl-4- [5- [3-
(3,5-difluorophenoxy) propynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-2272: 2-amino-2-methyl-4- [5- [3- (3
-Chlorophenoxy) propynyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-2273: 2-amino-2-methyl-4- [5- [3- (4
-Chlorophenoxy) propynyl] thiophen-2-yl] butyl
Tan-1-ol, exemplified compound number 1-2274: 2-amino-2-methyl-4- [5- [3-
(3,4-Dichlorophenoxy) propynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2275: 2-amino-2-methyl-4- [5- [3-
(3,5-Dichlorophenoxy) propynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2276: 2-amino-2-methyl-4- [5- [3- (3
-Methylphenoxy) propynyl] thiophen-2-yl] butyl
Tan-1-ol, exemplified compound number 1-2278: 2-amino-2-methyl-4- [5- [3-
(3,4-Dimethylphenoxy) propynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2279: 2-amino-2-methyl-4- [5- [3-
(3,5-Dimethylphenoxy) propynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2280: 2-amino-2-methyl-4- [5- [3- (3
-Trifluoromethylphenoxy) propynyl] thiofe
N-2-yl] butan-1-ol, Exemplified Compound No. 1-2281: 2-amino-2-methyl-4- [5- [3-
(3,4-Ditrifluoromethylphenoxy) propynyl] thio
Offen-2-yl] butan-1-ol, Exemplified Compound No. 1-2282: 2-amino-2-methyl-4- [5- [3-
(3,5-Ditrifluoromethylphenoxy) propynyl] thio
Offen-2-yl] butan-1-ol, Exemplified Compound No. 1-2283: 2-amino-2-methyl-4- [5- [3- (3
-Methoxyphenoxy) propynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-2284: 2-amino-2-methyl-4- [5- [3-
(3,4-Dimethoxyphenoxy) propynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-2285: 2-amino-2-methyl-4- [5- [3-
(3,5-Dimethoxyphenoxy) propynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-2286: 2-amino-2-methyl-4- [5- [3-
(3,4,5-trimethoxyphenoxy) propynyl] thiofe
2-Nyl] butan-1-ol, Exemplified Compound No. 1-2287: 2-amino-2-methyl-4- [5- [3- (3
-Acetylphenoxy) propynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-2288: 2-amino-2-methyl-4- [5- [3- (4
-Acetylphenoxy) propynyl] thiophen-2-yl]
Butan-1-ol, exemplified compound number 1-2290: 2-amino-2-methyl-4- [5- [4-
(3,4-Difluorophenoxy) but-1-ynyl] thiophene
2-yl] butan-1-ol, Exemplified Compound No. 1-2291: 2-amino-2-methyl-4- [5- [4-
(3,5-difluorophenoxy) but-1-ynyl] thiophene
2-yl] butan-1-ol, Exemplified Compound No. 1-2292: 2-amino-2-methyl-4- [5- [4- (3
-Chlorophenoxy) but-1-ynyl] thiophen-2-yl]
Butan-1-ol, exemplified compound number 1-2293: 2-amino-2-methyl-4- [5- [4-
(3,4-Dichlorophenoxy) but-1-ynyl] thiophene-2
-Yl] butan-1-ol, Exemplified Compound No. 1-2294: 2-amino-2-methyl-4- [5- [4-
(3,5-dichlorophenoxy) but-1-ynyl] thiophene-2
-Yl] butan-1-ol, Exemplified Compound No. 1-2295: 2-amino-2-methyl-4- [5- [4-
(3,4-Ditrifluoromethylphenoxy) but-1-ynyl]
Thiophen-2-yl] butan-1-ol, Exemplified Compound No. 1-2296: 2-amino-2-methyl-4- [5- [4-
(3,5-ditrifluoromethylphenoxy) but-1-ynyl]
Thiophen-2-yl] butan-1-ol, Exemplified Compound No. 1-2297: 2-amino-2-methyl-4- [5- [4-
(3,4-Dimethoxyphenoxy) but-1-ynyl] thiophene
2-yl] butan-1-ol, Exemplified Compound No. 1-2298: 2-amino-2-methyl-4- [5- [4-
(3,5-dimethoxyphenoxy) but-1-ynyl] thiophene
2-yl] butan-1-ol, Exemplified Compound No. 1-2299: 2-amino-2-methyl-4- [5- [4-
(3,4,5-trimethoxyphenoxy) but-1-ynyl] thiof
En-2-yl] butan-1-ol, Exemplified Compound No. 1-2300: 2-amino-2-methyl-4- [5- [4- (3
-Acetylphenoxy) but-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2301: 2-amino-2-methyl-4- [5- [4- (4
-Acetylphenoxy) but-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2328: 2-amino-2-methyl-4- [5- [5- (3
-Fluorophenyl) pentanoyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-2329: 2-amino-2-methyl-4- [5- [5-
(3,4-Difluorophenyl) pentanoyl] thiophene-2
-Yl] butan-1-ol, Exemplified Compound No. 1-2330: 2-amino-2-methyl-4- [5- [5-
(3,5-difluorophenyl) pentanoyl] thiophene-2
-Yl] butan-1-ol, Exemplified Compound No. 1-2331: 2-amino-2-methyl-4- [5- [5- (3
-Chlorophenyl) pentanoyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-2332: 2-amino-2-methyl-4- [5- [5- (4
-Chlorophenyl) pentanoyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-2333: 2-amino-2-methyl-4- [5- [5-
(3,4-Dichlorophenyl) pentanoyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2334: 2-amino-2-methyl-4- [5- [5-
(3,5-dichlorophenyl) pentanoyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2335: 2-amino-2-methyl-4- [5- [5- (3
-Methylphenyl) pentanoyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-2336: 2-amino-2-methyl-4- [5- [5-
(3,4-Dimethylphenyl) pentanoyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2337: 2-amino-2-methyl-4- [5- [5-
(3,5-Dimethylphenyl) pentanoyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2338: 2-amino-2-methyl-4- [5- [5- (3
-Trifluoromethylphenyl) pentanoyl] thiofe
N-2-yl] butan-1-ol, Exemplified Compound No. 1-2339: 2-amino-2-methyl-4- [5- [5-
(3,4-ditrifluoromethylphenyl) pentanoyl] thio
Offen-2-yl] butan-1-ol, Exemplified Compound No. 1-2340: 2-amino-2-methyl-4- [5- [5-
(3,5-Ditrifluoromethylphenyl) pentanoyl] thio
Offen-2-yl] butan-1-ol, Exemplified Compound No. 1-2341: 2-amino-2-methyl-4- [5- [5- (3
-Methoxyphenyl) pentanoyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-2342: 2-amino-2-methyl-4- [5- [5-
(3,4-dimethoxyphenyl) pentanoyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-2343: 2-amino-2-methyl-4- [5- [5-
(3,5-dimethoxyphenyl) pentanoyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-2344: 2-amino-2-methyl-4- [5- [5-
(3,4,5-trimethoxyphenyl) pentanoyl] thiof
En-2-yl] butan-1-ol, Exemplified Compound No. 1-2345: 2-amino-2-methyl-4- [5- [5- (3
-Acetylphenyl) pentanoyl] thiophen-2-yl]
Butan-1-ol, and Exemplified Compound No. 1-2346: 2-amino-2-methyl-4- [5- [5- (4
-Acetylphenyl) pentanoyl] thiophen-2-yl]
Butan-1-ol, and most preferably, Exemplified Compound No. 1-71: 2-amino-2-methyl-4- [5- (4-cyclyl)
Rohexylbutyl) thiophen-2-yl] butan-1-o
Compound No. 1-98: 2-amino-2-methyl-4- [5- (5-cyclyl)
Rohexylpentyl) thiophen-2-yl] butan-1-o
Exemplified Compound No. 1-152: 2-amino-2-methyl-4- [5- (5-f
Enylpentyl) thiophen-2-yl] butan-1-ol, Exemplified Compound No. 1-400: 2-amino-2-methyl-4- [5- (4-cy
Clohexyloxybutyl) thiophen-2-yl] butane-
1-ol, Exemplified Compound No. 1-463: 2-amino-2-methyl-4- [5- [4- (4-
Fluorophenoxy) butyl] thiophen-2-yl] butane
-1-ol, Exemplified Compound No. 1-479: 2-amino-2-methyl-4- [5- [4- (4-
Methoxyphenoxy) butyl] thiophen-2-yl] butane
-1-ol, Exemplified Compound No. 1-594: 2-amino-2-methyl-4- [5- (4-
Ndyloxybutyl) thiophen-2-yl] butan-1-o
Compound number 1-743: 2-amino-2-methyl-4- [5- (4-
Chlohexylbut-1-ynyl) thiophen-2-yl] butane
-1-ol, Exemplified Compound No. 1-756: 2-amino-2-methyl-4- [5- (4-f
Enylbut-1-ynyl) thiophen-2-yl] butane-1-o
Exemplified Compound No. 1-770: 2-amino-2-methyl-4- [5- (5-series
Clohexylpent-1-ynyl) thiophen-2-yl] buta
1-824, Exemplified Compound No. 1-824: 2-amino-2-methyl-4- [5- (5-f
Enylpent-1-ynyl) thiophen-2-yl] butane-1-
All, Exemplified Compound No. 1-833: 2-amino-2-methyl-4- [5- [5- (4-
Fluorophenyl) pent-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-849: 2-amino-2-methyl-4- [5- [5- (4-
Methoxyphenyl) pent-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1050: 2-amino-2-methyl-4- [5- [3- (4
-Methylcyclohexyloxy) propynyl] thiophene-
2-yl] butan-1-ol, Exemplified Compound No. 1-1063: 2-amino-2-methyl-4- [5- [3- (4
-Methylphenoxy) propynyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-1064: 2-amino-2-methyl-4- [5- [3- (4
-Ethylphenoxy) propynyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-1068: 2-amino-2-methyl-4- [5- [3- (4
-Methylthiophenoxy) propynyl] thiophen-2-i
L] butan-1-ol, Exemplified Compound No. 1-1072: 2-amino-2-methyl-4- [5- (4-si
Clohexyloxybut-1-ynyl) thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1135: 2-amino-2-methyl-4- [5- [4- (4
-Fluorophenoxy) but-1-ynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-1139: 2-amino-2-methyl-4- [5- [4- (4
-Methylphenoxy) but-1-ynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1185: 2-amino-2-methyl-4- [5- (3-si
Clohexylmethoxypropynyl) thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1266: 2-amino-2-methyl-4- [5- (4-f
Enylmethoxybut-1-ynyl) thiophen-2-yl] buta
-1-ol, Exemplified Compound No. 1-1329: 2-amino-2-methyl-4- [5- (4-si
Clohexylbutanoyl) thiophen-2-yl] butane-1-
All, Exemplified Compound No. 1-1330: 2-amino-2-methyl-4- [5- (4-f
Enylbutanoyl) thiophen-2-yl] butan-1-o
Compound No. 1-1331: 2-amino-2-methyl-4- [5- (5-
Clohexylpentanoyl) thiophen-2-yl] butane-
1-ol, Exemplified Compound No. 1-1344: 2-amino-2-methyl-4- [5- (5-f
Enylpentanoyl) thiophen-2-yl] butan-1-o
Compound No. 1-1348: 2-amino-2-methyl-4- [5- [5- (4
-Fluorophenyl) pentanoyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-1764: 2-amino-2-ethyl-4- [5- (5-cy
Clohexylpentyl) thiophen-2-yl] butan-1-o
Illustrative Compound No. 1-1909: 2-amino-2-ethyl-4- [5- (5-series
Clohexylpent-1-ynyl) thiophen-2-yl] buta
-1-ol, Exemplified Compound No. 1-2097: 2-amino-2-ethyl-4- [5- (5-cy
Clohexylpentanoyl) thiophen-2-yl] butane-
1-ol, Exemplified Compound No. 1-2273: 2-amino-2-methyl-4- [5- [3- (4
-Chlorophenoxy) propynyl] thiophen-2-yl] butyl
Tan-1-ol, Exemplified Compound No. 1-2276: 2-amino-2-methyl-4- [5- [3- (3
-Methylphenoxy) propynyl] thiophen-2-yl] butyl
Tan-1-ol, exemplified compound number 1-2278: 2-amino-2-methyl-4- [5- [3-
(3,4-Dimethylphenoxy) propynyl] thiophen-2-i
Ru] butan-1-ol, Exemplified Compound No. 1-2283: 2-amino-2-methyl-4- [5- [3- (3
-Methoxyphenoxy) propynyl] thiophen-2-yl]
Butan-1-ol, Exemplified Compound No. 1-2284: 2-amino-2-methyl-4- [5- [3-
(3,4-Dimethoxyphenoxy) propynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-2285: 2-amino-2-methyl-4- [5- [3-
(3,5-Dimethoxyphenoxy) propynyl] thiophen-2-
Il] butan-1-ol, Exemplified Compound No. 1-2287: 2-amino-2-methyl-4- [5- [3- (3
-Acetylphenoxy) propynyl] thiophen-2-yl]
Butan-1-ol, and Exemplified Compound No. 1-2288: 2-amino-2-methyl-4- [5- [3- (4
-Acetylphenoxy) propynyl] thiophen-2-yl]
Butan-1-ol can be mentioned.

[0116]

[Table 3]

[0117]

Embedded image

[0118]

[0119]

[Table 4]

[0120]

Embedded image

[0121] In the above Tables 3 and 4, preferably, 3-5, 3-6, 3-7, 3-
8, 3-11, 3-12, 4-4, 4-5, 4-6, 4-7, 4-8, 4-9, 4-10,
4-11, 4-12, 4-13, 4-17, 4-23, 4-24, 4-27, 4-28, 4
-31 and 4-32, the most preferable ones being exemplified compound No. 4-4: 4-methyl-4-[(thiophen-yl) ethyl] oxazolidin-one, exemplified compound No. 4-5: 4 -Methyl-4-[(thiophen-3-yl)
Ethyl] oxazolidin-one, Exemplified Compound No. 4-8: 4-methyl-4-[(5-bromothiophene
-Yl) ethyl] oxazolidin-one and Exemplified Compound No. 4-9: 4-methyl-4-[(5-bromothiophene
-3-yl) ethyl] oxazolidin-one.

[0122]

BEST MODE FOR CARRYING OUT THE INVENTION Compounds (I) and (XLI) of the present invention
Va), (XLIVb), (La) and (Lb) can be produced according to the method described below.

In the method A, in the compound (I) and the compound (I), R ¹ is a hydrogen atom, and R ² is a group selected from a lower alkoxycarbonyl group, an aralkyloxycarbonyl group and a substituent group a. The method is for producing a compound (Ic) which is an aralkyloxycarbonyl group substituted by 1 to 3 groups.

[0124]

Embedded image

In the above formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ ,
R ⁶ , R ⁷ , X, Y and n have the same meaning as described above, R ⁸ represents a formyl group, a carboxyl group or a lower alkoxycarbonyl group, and R ⁹ and R ^9a are the same or different. , A hydrogen atom or a lower alkyl group;
¹⁰ is a lower alkyl group, an aralkyl group or an aralkyl group substituted by 1 to 3 groups selected from the substituent group a, wherein R ^5a , R ^6a and R ^7a are R ⁵ , R ⁶ and R ^The amino, hydroxy and / or carboxyl group contained as a substituent in the group ⁷ is an amino, hydroxy and / or carboxyl group which may be protected, and other groups in the definition of R ⁵ , R ⁶ and R ⁷ groups. Shows similar groups.

In the above, the "protecting group" of the "optionally protected amino group" in the definition of R ^5a , R ^6a and R ^7a
Is not particularly limited as long as it is a protecting group for an amino group used in the field of synthetic organic chemistry. -Butoxycarbonyl group.

In the above, the “protecting group” of the “optionally protected hydroxy group” in the definition of R ^5a , R ^6a and R ^7a is a protecting group for a hydroxy group used in the field of synthetic organic chemistry. Although not particularly limited, for example, it has the same meaning as the above-mentioned "general protective group in the reaction for the ester of a hydroxy group", and is preferably a lower aliphatic acyl group, an aromatic acyl group, a lower alkoxycarbonyl group or It is a (lower alkoxy) methyl group, more preferably a lower aliphatic acyl group or a (lower alkoxy) methyl group, most preferably an acetyl group or a methoxymethyl group.

In the above, the “protecting group” of the “optionally protected carboxyl group” in the definition of R ^5a , R ^6a and R ^7a is a carboxyl protecting group used in the field of synthetic organic chemistry. Although not particularly limited, for example, it has the same meaning as the above “general protective group in the reaction for the ester of a carboxy group”, preferably a lower alkyl group, and most preferably a methyl group.

The step A1 is a step for producing a compound having the general formula (III). (In the presence), by reaction with a reducing agent.

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. For example, aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; benzene , Toluene, xylene; aromatic hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, carbon tetrachloride; acetic acid, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, carbonic acid Esters such as diethyl; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol
, Isopropanol, n-butanol, isobutanol
Alcohols such as toluene, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve; amides such as formamide, dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide Water; or water or a mixture of the above solvents; preferably ethers (most preferably tetrahydrofuran)
It is.

The reducing agent used in the above reaction is, for example,
Alkali metal borohydrides, such as sodium borohydride, lithium borohydride, sodium cyanoborohydride; aluminum hydride compounds, such as diisobutylaluminum hydride, lithium aluminum hydride, lithium triethoxyaluminum hydride; Yes,
Preferably they are alkali metal borohydrides (most preferably sodium borohydride).

The reaction temperature varies depending on the starting compound, the reducing agent used, the type of the solvent and the like, but is usually from -50 ° C to 100 ° C (preferably from 0 ° C to 50 ° C).

The reaction time varies depending on the starting compound, the reducing agent used, the solvent, the reaction temperature and the like, but is usually 15 minutes to 150 hours (preferably 1 hour to 100 hours).

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

Step A2 is a step of preparing a compound having the general formula (IV), in which a hydroxy group of the compound (III) is converted into a leaving group in an inert solvent in the presence of a base, and then iodine is added. The reaction is carried out by reacting with an agent to iodate the leaving group.

As the reagent for forming a leaving group, for example,
Sulfonyl halides such as methanesulfonyl chloride and P-toluenesulfonyl chloride; thionyl halides such as thionyl chloride, thionyl bromide and thionyl iodide; sulfuryl halides such as sulfuryl chloride, sulfuryl bromide and sulfuryl iodide; phosphorus trichloride Phosphorus trihalides such as phosphorus tribromide and phosphorus triiodide; phosphorus pentahalides such as phosphorus pentachloride, phosphorus pentabromide and phosphorus pentaiodide; phosphorus oxychloride, phosphorus oxybromide, A halogenating agent such as phosphorus oxyhalide such as phosphorus oxyiodide; a rhenium reagent such as methyltrioxorhenium (VII); and sulfonyl halide is preferable.

The base used for converting the hydroxy group to a leaving group includes, for example, alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate; lithium hydrogen carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate. Alkali metal bicarbonates such as; alkali metal hydrides such as lithium hydride, sodium hydride and potassium hydride; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide;
Alkali metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide, potassium t-butoxide; triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N-dimethylamino) pyridine , N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo [5.
4.0] -7-undecene (DBU); preferably organic amines (most preferably triethylamine).

The inert solvent used for converting the hydroxy group to the leaving group is not particularly limited as long as it is inert to the reaction. For example, hexane, heptane,
Aliphatic hydrocarbons such as ligroin and petroleum ether;
Aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol Ethers such as dimethyl ether; ketones such as acetone and 2-butanone; formamide;
Amides such as dimethylformamide, dimethylacetamide, and hexamethylphosphoric triamide; sulfoxides such as dimethylsulfoxide; sulfolane; and preferably halogenated hydrocarbons (most preferably,
Dichloromethane).

The reaction temperature for converting the hydroxy group to a leaving group varies depending on the starting compound, the reagent used, the type of solvent and the like, but is usually -50 ° C to 200 ° C (preferably -10 ° C to 150 ° C.).

The reaction time for converting the hydroxy group to a leaving group varies depending on the starting compound, the reagent used, the solvent, the reaction temperature and the like, but is usually 15 minutes to 24 hours (preferably 30 minutes to 12 hours). Time).

The iodinating agent used in the above reaction is, for example, phosphorus pentaiodide, phosphorus oxyiodide, sodium iodide, potassium iodide, and preferably sodium iodide.

The reaction temperature for the iodination of the leaving group varies depending on the starting compound, the reagent used, the type of solvent and the like, but is usually from 0 ° C. to 200 ° C. (preferably from 10 ° C. to 15 ° C.).
0 ° C).

The reaction time for iodination of the leaving group varies depending on the starting compound, the reagent used, the solvent, the reaction temperature and the like, but is usually 15 minutes to 24 hours (preferably 30 minutes to 12 hours). It is.

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

Step A3 is a step for producing a compound having the general formula (VI), and the compound (I) is prepared in an inert solvent.
V) is reacted with a compound having the general formula (V) in the presence of a base.

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction, and examples thereof include diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether. Ethers: methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; formamide, dimethylformamide, dimethylacetamide;
Amides such as hexamethylphosphoric triamide; water;
Or water or a mixed solvent of the above solvents; preferably alcohols or amides (most preferably dimethylformamide).

As the base used in the above reaction, for example, those similar to the bases used for converting a hydroxy group into a leaving group in the above-mentioned Method A, Step A2 can be mentioned. , Alkali metal hydrides or alkali metal alkoxides (most preferably sodium hydride).

The reaction temperature varies depending on the type of the starting compound, base, solvent and the like, but is usually from -78 ° C to 100 ° C.
(Preferably 0 ° C. to 50 ° C.).

The reaction time varies depending on the starting compound, base, solvent, reaction temperature and the like, but is usually 15 minutes to 48 hours (preferably 30 minutes to 12 hours).

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

Step A4 is a step for producing a compound having the general formula (VII), which is carried out by reacting compound (VI) with a base in an inert solvent and hydrolyzing an ester group to a carboxy group. Is

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; benzene , Toluene, xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol
Alcohols such as toluene, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve Or water or a mixed solvent of the above solvents; preferably alcohols (most preferably ethanol-
Le).

Examples of the base used in the above reaction include the same bases as those used for converting the hydroxy group to the leaving group in the above-mentioned Method A, Step A2. And alkali metal hydroxides (most preferably potassium hydroxide).

The reaction temperature varies depending on the type of the starting compound, base, solvent and the like, but is usually from -20 ° C to 200 ° C.
(Preferably 0 ° C. to 50 ° C.).

The reaction time varies depending on the starting compound, base, solvent, reaction temperature and the like, but is usually 30 minutes to 120 hours (preferably 1 hour to 80 hours).

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

Step A5 is a step of producing a compound having the general formula (IX), wherein the carboxyl group of the compound (VII) is subjected to a Curtius rearrangement reaction to convert the compound into a carbamate. Is reacted with a diarylphosphate azide derivative such as diphenylphosphate azide in an inert solvent in the presence of a base.
The reaction is carried out by heating with a compound having III).

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; benzene , Toluene, xylene; aromatic hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, carbon tetrachloride; halogenated hydrocarbons such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether Ethers; or water or a mixed solvent of the above solvents;
And preferably aromatic hydrocarbons (most preferably benzene).

Examples of the base used in the above reaction include the same bases as those used when converting the hydroxy group to the leaving group in the above-mentioned Method A, Step A2. And organic amines (most preferably, triethylamine).

The reaction temperature when reacting compound (VII) with a diarylphosphoric acid azide derivative and compound (VII)
The reaction temperature for the reaction with I) varies depending on the type of the starting compound, the base, the solvent, and the like.
00 ° C (preferably 20 ° C to 150 ° C).

The reaction temperature when reacting the compound (VII) with a diarylphosphoric acid azide derivative and the compound (VII)
The reaction temperature for the reaction with I) depends on the starting compound, base, solvent, reaction temperature and the like, but is usually 15 minutes to 24 hours (preferably 30 minutes to 12 hours).

When compound (VII) is reacted with a diarylphosphoric acid azide derivative, compounds (VIII) which are hardly directly reacted with the diarylphosphoric acid azide derivative are reacted together, so that the carboxyl group can be formed at a stroke. Can be converted to

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

Step A6 is a step for producing a compound having the general formula (X), which is carried out by reducing the ester of compound (IX), and converting compound (IX) into a reducing agent in an inert solvent. The reaction is carried out by reacting

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; benzene , Toluene, xylene; aromatic hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, carbon tetrachloride; halogenated hydrocarbons such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether Ethers such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol,
Alcohols such as diethylene glycol, glycerin, octanol, cyclohexanol, methyl cellosolve
And a mixed solvent of the above solvents, preferably a mixed solvent of alcohols and ethers (most preferably a mixed solvent of ethanol and tetrahydrofuran).

Examples of the reducing agent used in the above reaction include those similar to those used in the above-mentioned Method A, Step A1. Preferably, alkali metal borohydrides (most preferably) Is sodium borohydride or lithium borohydride).

The reaction temperature varies depending on the starting compound, the kind of the solvent and the like, but is usually from -78 ° C to 150 ° C (preferably from -20 ° C to 50 ° C).

The reaction time varies depending on the starting compound, solvent, reaction temperature and the like, but is usually 5 minutes to 48 hours (preferably 30 minutes to 24 hours).

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

Step A7 is a step for producing a compound having the general formula (XI), which is carried out by reacting compound (X) with a base to close the ring to an oxazolidine ring.

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction, and examples thereof include diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether. Ethers: methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; formamide, dimethylformamide, dimethylacetamide;
Amides such as hexamethylphosphoric triamide; water;
Or water or a mixed solvent of the above solvents; preferably alcohols or amides (most preferably dimethylformamide).

As the base used in the above reaction, for example, those similar to the bases used for converting a hydroxy group to a leaving group in the above-mentioned Method A, Step A2 can be mentioned. And alkali metal alkoxides (most preferably potassium t-butoxide).

The reaction temperature varies depending on the type of the starting compound, base, solvent and the like, but is usually from -78 ° C to 100 ° C.
(Preferably −50 ° C. to 50 ° C.).

The reaction time varies depending on the starting compound, base, solvent, reaction temperature and the like, but is usually 15 minutes to 48 hours (preferably 30 minutes to 12 hours).

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

Step A8 is a step for producing a compound having the general formula (I), and the compound (X) is prepared in an inert solvent.
After reacting I) with a base and hydrolyzing, optionally amino at R ¹ , R ² , R ³ , R ^5a , R ^6a and R ^7a ,
It is performed by removing the protecting group of the hydroxy and / or carboxyl group, protecting the amino group in R ¹ and / or R ^2, and / or protecting the hydroxy group in R ³ .

The inert solvent used when reacting compound (XI) with a base is not particularly limited as long as it is inert to the reaction. For example, hexane, heptane,
Aliphatic hydrocarbons such as ligroin and petroleum ether;
Aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol Ethers such as dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol;
Alcohols such as alcohol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve; water; or a mixed solvent of the above solvents, preferably a mixed solvent of alcohols and ethers (Most preferably, a mixed solvent of methanol and tetrahydrofuran).

The base used for reacting compound (XI) with a base is, for example, the same as the one used for converting a hydroxy group to a leaving group in the above-mentioned step A2, method A. And preferably alkali metal hydrides (most preferably potassium hydroxide).

The reaction temperature varies depending on the type of the starting compound, base, solvent and the like, but is usually from -20 ° C to 200 ° C.
(Preferably 0 ° C. to 100 ° C.).

The reaction time varies depending on the starting compound, the base, the type of the solvent, the reaction temperature and the like.
8 hours (preferably 1 hour to 24 hours).

The removal of the protecting groups for the amino, hydroxy and carboxyl groups depends on the type of the protecting group.
n, (Protective Groups in Organic Synthesis), John
Wiley & Sons: JFWMcOmis, (Protective Groups in
Organic Chemistry), Plenum Press.

When the amino-protecting group is a silyl, a compound which generates a fluorine anion, such as tetrabutylammonium fluoride, hydrofluoric acid, hydrofluoric acid-pyridine and potassium fluoride, is usually used. And removed by treating with.

The solvent used in the above reaction is not particularly limited as long as it does not inhibit the reaction. Examples of the solvent include ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether. Is preferred.

The reaction temperature and reaction time are not particularly limited, but the reaction is usually carried out at 0 ° C. to 50 ° C. for 10 minutes to 18 hours.

When the protecting group for the amino group is an aliphatic acyl, an aromatic acyl, an alkoxycarbonyl or a substituted methylene group forming a Schiff base, an acid or a base is added in the presence of an aqueous solvent. Can be removed.

The acid used in the above reaction is not particularly limited as long as it is a commonly used acid and does not inhibit the reaction. Examples thereof include hydrobromic acid, hydrochloric acid, sulfuric acid, and the like.
Inorganic acids such as perchloric acid, phosphoric acid and nitric acid, preferably hydrochloric acid.

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

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

The reaction temperature and the reaction time vary depending on the starting compound, the solvent and the acid or base to be used, and are not particularly limited. Let react for ~ 10 hours.

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

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

The catalyst used for the removal by catalytic reduction is not particularly limited as long as it is usually used for the catalytic reduction reaction.
Carbon, Raney-nickel, platinum oxide, platinum black, rhodium-
Aluminum oxide, triphenylphosphine-rhodium chloride, palladium-barium sulfate are used.

Although the pressure is not particularly limited, it is usually 1 to 1
Performed at 0 atm.

The reaction temperature and reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually from 0 ° C. to 100 ° C.
For 5 minutes to 24 hours.

The solvent used in the removal by oxidation is not particularly limited as long as it does not participate in the present reaction, but is preferably a water-containing organic solvent.

Examples of such organic solvents include halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; nitriles such as acetonitrile, diethyl ether, diisopropyl ether, tetrahydrofuran, and the like. Ethers such as dioxane, dimethoxyethane and diethylene glycol dimethyl ether; ketones such as acetone; amides such as formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide; and sulfoxides such as dimethylsulfoxide; And preferably halogenated hydrocarbons, ethers or sulfoxides (most preferably halogenated hydrocarbons or sulfoxides).

The oxidizing agent to be used is not particularly limited as long as it is a compound used for oxidation. Preferably, potassium persulfate, sodium persulfate, ammonium cerium nitrate (CAN), 2,3- Dichloro-5,6-
Dicyano-p-benzoquinone (DDQ) is used.

The reaction temperature and reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually 0 ° C. to 150 ° C.
For 10 minutes to 24 hours.

When the protecting group for the amino group is an aralkyl, the protecting group can be removed using an acid.

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

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

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

The reaction time depends on the starting compound, the acid used,
The time is usually from 15 minutes to 48 hours (preferably from 30 minutes to 20 hours), although it depends on the solvent, the reaction temperature and the like.

When the amino-protecting group is an alkenyloxycarbonyl, the amino-protecting group is usually the above-mentioned aliphatic acyl, aromatic acyl, alkoxycarbonyl or a substituted methylene group forming a Schiff base. It is carried out by treating with a base in the same manner as the conditions for the removal reaction in the case of a group.

In the case of an allyloxycarbonyl group,
In particular, the removal method using palladium and triphenylphosphine or nickel tetracarbonyl is simple and can be carried out with few side reactions.

When a silyl is used as the protecting group for the hydroxy group, a fluorine anion such as tetrabutylammonium fluoride, hydrofluoric acid, hydrofluoric acid-pyridine, or potassium fluoride is usually formed. Treated with compounds or
Or an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, phosphoric acid or acetic acid, formic acid, oxalic acid, methanesulfonic acid, p
-It can be removed by treatment with an organic acid such as toluenesulfonic acid, camphorsulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid.

In the case of removal by fluorine anion,
The reaction may be accelerated by adding organic acids such as formic acid, acetic acid, propionic acid.

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Preferably, diethyl ether or diisopropyl ether is used.
Ethers such as ter, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; nitriles such as acetonitrile and isobutyronitrile; organic acids such as acetic acid; water;

The reaction temperature and reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually from 0 ° C. to 100 ° C.
(Preferably 10 ° C. to 50 ° C.) for 1 hour to 24 hours.

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

The solvent used for the removal by catalytic reduction is not particularly limited as long as it does not participate in the present reaction. Aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; toluene, benzene , Xylene and the like; aromatic hydrocarbons such as xylene; esters such as ethyl acetate and propyl acetate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; methanol; Ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol,
Alcohols such as diethylene glycol, glycerin, octanol, cyclohexanol, methyl cellosolve
Amides such as formamide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone and hexamethylphosphoric triamide; fatty acids such as formic acid and acetic acid; water; a mixed solvent of the above solvents; Preferably they are alcohols (most preferably methanol).

As the catalyst used for the removal by the catalytic reduction, if it is usually used for the catalytic reduction reaction,
Although not particularly limited, for example, palladium-carbon, palladium-black, Raney-nickel, platinum oxide, platinum black, rhodium-aluminum oxide, triphenylphosphine-rhodium chloride, palladium-barium sulfate, and preferably palladium- Carbon.

The pressure is not particularly limited, but is usually 1 to 1
Performed at 0 atm.

The reaction temperature and reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually from 0 ° C. to 100 ° C.
(Preferably 20 ° C. to 70 ° C.) for 5 minutes to 48 hours (preferably 1 hour to 24 hours).

The solvent used in the removal by oxidation is not particularly limited as long as it does not participate in the present reaction, but is preferably a water-containing organic solvent.

Preferred as such organic solvents are ketones such as acetone; halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride; nitriles such as acetonitrile; diethyl ether, tetrahydrofuran; Ethers such as dioxane; amides such as dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; and sulfoxides such as dimethylsulfoxide.

The oxidizing agent to be used is not particularly limited as long as it is a compound used for oxidation. Preferably, potassium persulfate, sodium persulfate, ammonium cerium nitrate (CAN), 2,3- Dichloro-5,6-
Dicyano-p-benzoquinone (DDQ) is used.

The reaction temperature and reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually 0 ° C. to 150 ° C.
For 10 minutes to 24 hours.

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

Further, it can be removed by using an alkylsilyl halide such as aluminum chloride-sodium iodide or trimethylsilyl iodide in a solvent.

The solvent to be used is not particularly limited as long as it does not participate in the reaction. Preferably, the solvent is a halogenated hydrocarbon such as methylene chloride, chloroform or carbon tetrachloride; or a solvent such as acetonitrile. Nitriles;
A mixed solvent of the above solvents is exemplified. The reaction temperature and the reaction time vary depending on the starting compound, the solvent, and the like.
C. to 50.degree. C. for 5 minutes to 72 hours.

In the case where the reaction substrate has a sulfur atom,
Preferably, aluminum chloride-sodium iodide is used.

When the protecting group for the hydroxy group is an aliphatic acyl, an aromatic acyl or an alkoxycarbonyl group, it is removed by treating with a base in a solvent.

The base used in the above reaction is not particularly limited as long as it does not affect the other parts of the compound, and examples thereof include alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate. Alkali metal bicarbonates such as lithium bicarbonate, sodium bicarbonate and potassium bicarbonate; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; lithium methoxide, sodium methoxide; Metal alkoxides such as sodium ethoxide and potassium t-butoxide; ammonia such as aqueous ammonia and concentrated ammonia-methanol; preferably alkali metal hydroxides, metal alkoxides or ammonia (Most preferably alkali metal hydroxides or metal alkoxides) It is the earth).

The solvent to be used is not particularly limited as long as it is used in a usual hydrolysis reaction, and examples thereof include diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether. Ethers; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve; water; mixed solvents of the above solvents are preferred.

The reaction temperature and reaction time vary depending on the starting compound, the base used, the solvent and the like, and are not particularly limited.
In order to suppress side reactions, usually -20 ° C to 150 ° C
For 1 to 10 hours.

When the protecting group for the hydroxy group is an alkoxymethyl, a tetrahydropyranyl, a tetrahydrothiopyranyl, a tetrahydrofuranyl, a tetrahydrothiofuranyl or a substituted ethyl, it is usually used in a solvent. , By treatment with an acid.

The acid used is not particularly limited as long as it is usually used as a Bronsted acid or a Lewis acid, and is preferably hydrogen chloride; an inorganic acid such as hydrochloric acid, sulfuric acid or nitric acid; or Bronsted acids such as acetic acid, trifluoroacetic acid, methanesulfonic acid, and organic acids such as p-toluenesulfonic acid: Lewis acids such as boron trifluoride, but strongly acidic cations such as Dowex 50W Exchange resins can also be used.

The solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction.
Aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene,
Halogenated hydrocarbons such as dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate, and diethyl carbonate; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether Such ethers; methanol, ethanol
Alcohols such as n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve Ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; water; a mixed solvent of the above solvents; preferably ethers (most preferably tetrahydrofuran) or alcohols ( Most preferably, methanol).

The reaction temperature and the reaction time vary depending on the starting compound, the acid used, the solvent and the like, but are usually -10 ° C to 200 ° C (preferably 0 ° C to 150 ° C) for 5 minutes to 48 hours. (Preferably 30 minutes to 10 hours).

When the protecting group for the hydroxy group is an alkenyloxycarbonyl, the conditions for the removal reaction when the protecting group for the hydroxy group is the above-mentioned aliphatic acyls, aromatic acyls or alkoxycarbonyls are usually used. In the same manner as in the above, it is achieved by treating with a base.

In the case of an allyloxycarbonyl group,
In particular, the removal method using palladium and triphenylphosphine, or bis (methyldiphenylphosphine) (1,5-cyclooctadiene) iridium (I) hexafluorophosphate is simple and is carried out with few side reactions. Can be.

[0233] protecting groups for a carboxyl group, C ₁ -C ₆ alkyl group or a C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, nitro, three 1 may be substituted by halogen or cyano C ₆ In the case of a C ₁ -C ₆ alkyl group substituted with —C ₁₀ aryl, the removal reaction is usually performed when the protecting group of the hydroxy group is the above-mentioned aliphatic acyl, aromatic acyl or alkoxycarbonyl. As with the conditions,
Achieved by treatment with a base.

The removal of the protecting group for the amino, hydroxy and / or carboxyl groups can be carried out in any order and the desired removal reaction can be carried out sequentially.

The method of protecting the amino and hydroxy groups depends on the type of the protecting group, but can be generally carried out as follows by a method well known in the art of synthetic organic chemistry.

The method for protecting the amino group is described in Compound (I).
Wherein the compound in which R ¹ and R ² are hydrogen atoms is reacted in an inert solvent (preferably ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; Methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, methyl cellosolve And the bases (organic amines such as triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine) in the presence or absence of the following compounds R ^1a -Z. (XII) [in the above formula, R ^1a is amino Shows the protective group (showing a consent Yi as described above.), Z is a halogen atom. ]
With 0 ° C. to 50 ° C. (preferably around room temperature) for 30 minutes to 10 hours (preferably 1 hour to 5 hours).

The method for protecting the hydroxy group is as follows. In the compound (I), the compound in which R ³ is a hydrogen atom is treated in an inert solvent (preferably, chloroform, dichloromethane,
Halogenated hydrocarbons such as 1,2-dichloroethane and carbon tetrachloride; formamide, dimethylformamide,
Amides such as dimethylacetamide and hexamethylphosphoric triamide; sulfoxides such as dimethylsulfoxide) in the presence of a base (preferably alkali metal hydride such as lithium hydride, sodium hydride and potassium hydride) And organic amines such as triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine and pyridine), and the following compounds R ^3a -Z (XIII) wherein R ^3a is a hydroxyl-protecting group Z indicates the consent as described above. ] At 0 ° C to 50 ° C (preferably around room temperature).
The reaction is carried out for a period of from minutes to 24 hours (preferably from 1 hour to 24 hours).

The removal of the protecting group for the amino, hydroxy and / or carboxyl groups, and the reaction for protecting the amino and / or hydroxy groups can be carried out in any order and in any order.

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

Step A9 is a step of producing a compound having the general formula (I) from the compound (X).
Removing, if desired, protecting groups for amino, hydroxy and / or carboxyl groups on R ¹ , R ² , R ³ , R ^5a , R ^6a and R ^7a , protecting amino groups on R ¹ and / or R ² And / or by protecting the hydroxy group in R ³ , and this step is performed in the same manner as in the above-mentioned Method A, Step A8.

Step A10 produces compound (Ic).
In which the ester of compound (IX) is reduced.
Later, if desired, R¹, R^Two, R^Three, R^5a, R^6aAnd R^7aTo
Amino, hydroxy and / or carboxyl in
Removing the protecting group of the group R ¹And / or R^TwoIn
And / or R^ThreeIn
By protecting the hydroxy group in the
In the method for reducing the ester of (IX), this step comprises
This is performed in the same manner as in the method step A6.

In the method B, the compound (I) in which X is an ethynylene group, the compound (Ie) in which X is a vinylene group, and the compound (I) in which X is an ethylene group
f), X is -CO-CH ₂ - compound is a group having a (Ig), X is -CO-CH ₂ - is a radical having, R ¹
Compounds There is a ^{_{-CO 2 R 10 (Ig-1}} ), X is -CH
Compound (Ih), which is a group having (OH) —CH ₂ —,
Compound (Ii) in which X is an aryl group or an aryl group substituted by 1 to 3 groups selected from substituent group a and compound (Ij) in which X is an oxygen atom or a nitrogen atom Is the way.

[0243]

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[0244]

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[0245]

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In the above formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R
^5a , R ⁶ , R ^6a , R ⁷ , R ^7a , R ¹⁰ , Y and n are as defined above, X _a is an oxygen atom or a sulfur atom, and Ya is C ₁ -C ₁₀ C ₁ to 1 are three substituted with a group selected from an alkylene group, or a substituent group a and b
A -C ₁₀ alkylene group, ring A, 1 or have been three substituted with a group selected from aryl group or a substituent group a ants - indicates Le group, W is represented by the following general formula

[0247]

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[Wherein R ⁴ and R ¹⁰ have the same meanings as described above, and R ′ and R ″ are the same or different and are selected from a lower alkyl group, an aryl group and a substituent group a. Represents an aryl group substituted by 1 to 3 groups. ] Is shown.

Step B1 is a step for producing a compound having the general formula (XVI). The compound having the general formula (XIV) is prepared by reacting the compound having the general formula (XIV) in an inert solvent in the presence of a base and a palladium catalyst. ) And Sonogashira
This is performed by causing a coupling reaction.

The solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction.
Aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene,
Halogenated hydrocarbons such as dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate and diethyl carbonate; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether Ethers; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; nitriles such as acetonitrile, isobutyl bitrile; formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide Amides; sulfoxides such as dimethyl sulfoxide and sulfolane;
Preferably, they are ethers, amides or sulfoxides (most preferably amides or ethers). Further, the addition of a small amount of water to the reaction solvent may accelerate the progress of the reaction.

As the base used in the above reaction, for example, those similar to the bases used for converting a hydroxy group into a leaving group in the above-mentioned Method A, Step A2 can be mentioned. , Organic amines (most preferably, triethylamine).

The palladium catalyst used in the above reaction is not particularly limited as long as it is used in a usual Sonogashira coupling reaction. Palladium salt complexes such as bistriphenylphosphine chloride palladium complex forming a complex with the ligand can be mentioned.

By using cuprous iodide and benzyltriethylammonium chloride as additives,
The yield can be improved.

The reaction temperature varies depending on the type of the starting compound, the base, the solvent and the like, but is usually from -20 ° C to 200 ° C.
(Preferably 0 ° C. to 120 ° C.).

The reaction time varies depending on the starting compound, base, solvent, reaction temperature and the like, but is usually 5 minutes to 48 hours (preferably 15 minutes to 24 hours).

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

Step B2 is a step of producing a compound having the general formula (Id). When W of the compound (XVI) is a (W-1) group, the above-mentioned Method A step A7 and A
It can be produced by reacting in 8 steps or in the same manner as in the above-mentioned Method A, Step A9. Compound (XVI)
When W is a (W-2) or (W-3) group, the reaction is carried out in the same manner as in the above-mentioned Method A, Step A8 to obtain a compound of the general formula (Id)
Can be produced.

Step B3 is a step of producing a compound having the general formula (XVII). After reacting compound (XV) with catecholborane, compound (XIV) and Suzu
This is performed by performing a kicoupling reaction.

The reaction temperature at which the compound (XV) is reacted with catechol borane varies depending on the type of the starting compound, base, solvent and the like, but is usually from 0 ° C. to 150 ° C. (preferably from 10 ° C. to 100 ° C.). is there.

The reaction time for reacting compound (XV) with catecholborane varies depending on the starting compound, base, solvent, reaction temperature and the like, but is usually 15 minutes to 24 hours (preferably 30 minutes to 12 hours). It is.

Thereafter, the Suzuki coupling reaction is carried out in the same manner as in the Sonogashira coupling reaction in the B1 step B method.

As the solvent used in the above reaction, the same solvents as those used in the above-mentioned Method B, Step B1 can be mentioned. Preferably, aromatic hydrocarbons (most preferably toluene) are used. It is.

Examples of the base used in the above reaction include the same bases as those used when converting the hydroxy group to the leaving group in the above-mentioned Method A, Step A2. And alkali metal alkoxides (most preferably, sodium ethoxide).

Examples of the palladium catalyst used in the above reaction include the same palladium catalysts as those used in the above-mentioned Method B, Step B1, and are preferably palladium salt complexes (most preferably bistrichloride). Phenylphosphine palladium). Step B4 is a step of producing a compound having the general formula (Ie), and the step of preparing the compound (XVII)
When W is a (W-1) group, it can be produced by reacting in the same manner as in Method A, Steps A7 and A8, or Method A, Step A9. Further, the compound (X
When W in (VII) is a (W-2) or (W-3) group, the compound having the general formula (Ie) can be produced by reacting in the same manner as in the above-mentioned Method A, Step A8.

Step B5 is a step for producing a compound having the general formula (XVIII), in which the compound (XVI) is reduced in an inert solvent (preferably catalytic reduction at room temperature under a catalyst). It is performed by

The solvent used for removal by catalytic reduction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; Aromatic hydrocarbons such as toluene, benzene, xylene; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, halogenated hydrocarbons such as dichlorobenzene; methyl acetate, ethyl acetate, propyl acetate, butyl acetate; Esters such as diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methano-
, Ethanol, n-propanol, isopropanol
, N-butanol, isobutanol, t-butanol
Alcohols such as alcohol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; organic acids such as acetic acid and hydrochloric acid; water; a mixed solvent of the above solvent and water; Include alcohols or ethers (most preferably,
Methanol).

The catalyst used for the removal by the catalytic reduction is not particularly limited as long as it is usually used for the catalytic reduction reaction.
Carbon, Raney-nickel, platinum oxide, platinum black, rhodium-
Aluminum oxide, triphenylphosphine-rhodium chloride, palladium-barium sulfate are used.

The reaction temperature varies depending on the type of the starting compound, base, solvent and the like, but is usually from -20 ° C to 200 ° C.
(Preferably 0 ° C. to 100 ° C.).

The reaction time varies depending on the starting compound, base, solvent, reaction temperature and the like, but is usually 5 minutes to 96 hours (preferably 15 minutes to 72 hours).

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

Step B6 is a step of producing a compound having the general formula (If), and is performed by reacting the compound (XVIII) with W
Is a (W-1) group, it can be produced by reacting in the same manner as in Method A, Steps A7 and A8, or Method A, Step A9. In addition, the compound (XVI
When W in II) is a (W-2) or (W-3) group, the compound having the general formula (If) can be produced by reacting in the same manner as in the above-mentioned Method A, Step A8.

Step B7 is a step of producing a compound having the general formula (XIX). When W of the compound (XVI) is a (W-1) group, the method A step A and the step A
It can be produced by reacting in 8 steps or in the same manner as in the above-mentioned Method A, Step A9. Compound (XVI)
Is a group (W-2) or (W-3), the reaction is carried out in the same manner as in the above-mentioned Method A, Step A8 to obtain a compound of the general formula (XI)
The compound having X) can be produced.

Step B8 is a step of reacting a compound having the general formula (Ig)
A step of producing a compound, wherein the compound (XIX) is inactivated
Addition of water using an acid catalyst or mercury oxide
To the method via the oximeration reaction used
And optionally R ¹, R^Two, R^Three, R^5a, R^6a
And R^7aAmino, hydroxy and / or mosquito
Removing the protecting group of the ruboxyl group;¹And / or young
Kuha R^TwoProtecting the amino group in and / or
Is R^ThreeBy protecting the hydroxy group in
Is

The solvent used in the above reaction is not particularly limited as long as it is inert to this reaction.
Aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene,
Halogenated hydrocarbons such as dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate, and diethyl carbonate; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether Such ethers; methanol, ethanol
Alcohols such as toluene, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve Ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; water; a mixed solvent of the above solvents; and preferably alcohols (most preferably methanol).

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

The reaction temperature varies depending on the type of the starting compound, base, solvent and the like, but is usually from -20 ° C to 200 ° C.
(Preferably 0 ° C. to 100 ° C.).

The reaction time varies depending on the starting compound, base, solvent, reaction temperature and the like, but is usually 5 minutes to 96 hours (preferably 15 minutes to 72 hours).

R ¹ , R ² , R ³ , R
A method for removing the protecting group of amino, hydroxy and / or carboxyl group in ^5a , R ^6a and R ^7a , protecting the amino group in R ¹ and / or R ^2, and / or protecting the hydroxy group in R ³ The method is performed in the same manner as in the above-mentioned Method A, Step A8.

Step B9 is a step for producing a compound having the general formula (Ig-1),
Is carried out in an inert solvent by a method via a water addition reaction using an acid catalyst or an oximeration reaction using mercury oxide, and if desired, R ¹ , R ² , R ³ , R ³
This step is carried out by removing the protecting group for the amino, hydroxy and / or carboxyl group in ^5a , R ^6a and R ^7a and / or protecting the hydroxy group in R ³ . It is performed in the same manner as the process.

Step B10 is a step for producing a compound having the general formula (XX). The compound (XIX) is prepared by adding water in an inert solvent using an acid catalyst or oxidizing the compound using mercuric oxide. This is carried out by a method via a mercury reaction, and if desired, R ¹ , R ² , R ³ , R ^5a , R ⁵
Removing amino, hydroxy and / or carboxyl protecting groups on ^6a and R ^7a , protecting amino groups on R ¹ and / or R ^2, and / or
Alternatively, this step is performed by protecting the hydroxy group in R ³ , and this step is performed in the same manner as in the above-mentioned Method B, Step B8.

Step B11 is a step for producing a compound having the general formula (Ih). After reducing the compound (XX) in an inert solvent, if desired, R ¹ , R ² , R ³ , R ^3
5a, amino in R ^{6 a} and R ^7a, removing the protecting group of the hydroxyl and / or carboxyl groups, protecting the amino group in R ¹ and / or R ^2, and / or, a hydroxy group in R ³ It is done by protecting.

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; benzene , Toluene, xylene; aromatic hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, and carbon tetrachloride; halogenated hydrocarbons such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether Ethers such as: methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol,
Alcohols such as diethylene glycol, glycerin, octanol, cyclohexanol, methyl cellosolve
Or a mixed solvent of the above solvents, preferably ethers or alcohols (most preferably methanol or ethanol).

Examples of the reducing agent used in the above reaction include alkali metal borohydrides such as sodium borohydride, lithium borohydride and sodium cyanoborohydride; diisobutylaluminum hydride;
Aluminum hydride compounds such as lithium aluminum hydride, lithium triethoxyaluminum hydride;
And preferably alkali metal borohydrides (sodium cyanoborohydride).

The reaction temperature varies depending on the type of the starting compound, base, solvent and the like, but is usually from -10 ° C to 100 ° C.
(Preferably −20 ° C. to 20 ° C.).

The reaction time varies depending on the starting compound, base, solvent, reaction temperature and the like, but is usually from 10 minutes to 48 hours (preferably from 30 minutes to 12 hours).

R ¹ , R ² , R ³ , R
A method for removing the protecting group of amino, hydroxy and / or carboxyl group in ^5a , R ^6a and R ^7a , protecting the amino group in R ¹ and / or R ^2, and / or protecting the hydroxy group in R ³ The method is performed in the same manner as in the above-mentioned Method A, Step A8.

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

Step B12 is a step of preparing a compound having the general formula (XXII), which is carried out by subjecting compound (XXI) to a Suzuki coupling reaction with compound (XIV). Sonoga of B3 process
It is performed in the same way as the shira coupling reaction part.

Step B13 is a step for producing a compound having the general formula (Ii),
Is a (W-1) group, it can be produced by reacting in the same manner as in Method A, Steps A7 and A8, or Method A, Step A9. Compound (XXI)
When W in I) is a (W-2) or (W-3) group, the above-mentioned A
By reacting in the same manner as in step A8 of the method, the compound represented by the general formula (I)
Compounds having i) can be prepared.

Step B14 is a step for producing a compound having the general formula (XXIV). The compound having the general formula (XXIV) is prepared by reacting the compound having the general formula (XIV) without a solvent or in an inert solvent with a copper catalyst. ) With an alkali metal salt of a compound having the formula: In this step, for example, a method as described in J. Heterocyclic. Chem., 20, 1557 (1983) can be used.

The solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. For example, diethyl ether, dioxane, tetrahydrofuran,
Ethers such as dimethoxyethane and diethylene glycol dimethyl ether; and pyridines such as pyridine, picoline, lutidine and collidine; and preferably without solvent. Examples of the copper catalyst used in the above reaction include cuprous iodide, cuprous bromide, cuprous oxide, and cupric oxide, and preferably cuprous oxide.

The compound (XXII) used in the above reaction
The alkali metal salt of I) is prepared from the general formula (XXIII) and an alkali metal or an alkali metal compound. As the alkali metal, for example, lithium, sodium,
Potassium is exemplified, and examples of the alkali metal compound include alkali metal hydrides such as lithium hydride, sodium hydride and potassium hydride. It is preferably adjusted using metallic sodium. Further, by using potassium iodide as an additive, the yield can be improved.

The reaction temperature varies depending on the type of the starting compound, the catalyst and the solvent, but is usually from room temperature to 150 ° C. (preferably from 60 ° C. to 120 ° C.).

The reaction time varies depending on the type of the starting compound, the catalyst and the solvent, but is usually 1 hour to 7 days (preferably 3 hours to 72 hours).

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

Step B15 is a step for producing a compound having the general formula (Ij),
Is a (W-1) group, it can be produced by reacting in the same manner as in Method A, Steps A7 and A8, or Method A, Step A9. Compound (XXI)
V) wherein W is a (W-2) or (W-3) group,
By reacting in the same manner as in step A8 of the method, the compound represented by the general formula (I)
The compound having j) can be produced.

Step B16 is a step for producing a compound having the general formula (XXVI), which is carried out by reacting a compound having the general formula (XIV) with a compound having the general formula (XXV). Is performed in the same manner as in the B method, step B1.

In step B17, compound (XVI) wherein Y is a group having the formula -Ya-OR ^5a
This is a step of producing VIb), which is carried out by condensing compound (XXVI) with a compound having the general formula (XXVII) by an Mitsunobu reaction in an inert solvent.

The reagent used in the Mitsunobu reaction is not particularly limited as long as it can be used in the Mitsunobu reaction, but is preferably a di-lower such as diethyl azodicarboxylate or diisopropyl azodicarboxylate. Azo compounds such as alkylazodicarboxylates or azodicarbonyls such as 1,1 '-(azodicarbonyl) dipiperidine and triarylphosphines such as triphenylphosphine or tris such as tri-n-butylphosphine. It is a combination with a phosphine such as a lower alkyl phosphine, and more preferably a combination of a di-lower alkyl azodicarboxylate and a triaryl phosphine.

The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent, but is preferably an aromatic hydrocarbon such as benzene, toluene and xylene; Methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene,
Halogenated hydrocarbons such as dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether : Nitriles such as acetonitrile, isobutyronitrile, formamide, N, N-
Dimethylformamide, N, N-dimethylacetamide, N-
Amides such as methyl-2-pyrrolidone, N-methylpyrrolidinone, and hexamethylphosphorotriamide; sulphoxides such as dimethylsulfoxide and sulfolane; and preferred are aromatic hydrocarbons and ethers. is there.

The reaction is carried out at a temperature from -20 ° C to 100 ° C, preferably from 0 ° C to 50 ° C.

The reaction time depends mainly on the reaction temperature, the starting compound, the reaction reagent and the type of the solvent used, but is usually from 10 minutes to 3 days, preferably from 30 minutes to 30 days.
Minutes to 12 hours.

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

Further, separately from the present method, compound (XI)
After hydrolyzing the W group of V), compounds (XV), (X
Compounds (Id) to (Ij) can also be produced by reacting with (XI), (XXIII) or (XXV).

Starting compounds (II), (V) and (VII)
I), (XII), (XIII), (XIV), (X
V), (XXI), (XXIII), (XXV) and (XXVII) are known or are easily prepared according to known methods or methods analogous thereto.

The starting compounds (II) and (XIV) can also be produced by the following method.

In the method C, the compound (XIV) and the compound (XIV) have a bromine atom as a substituent at the 2-position of the thiophene group, and have-(CH ₂ ) n at the 5-position of the thiophene group.
This is a method for producing a compound (XIVa) having a group having —W.

[0308]

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[0309]

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In the above formula, R ⁴ , R ^6a , R ^7a , R ⁸ , R ⁹ ,
R ^9a , R ¹⁰ , n and W indicate agreement with those described above.

Step C1 is a step for producing a compound having the general formula (XXIX),
The reaction is carried out by reacting the compound having I) with a reducing agent in an inert solvent in the presence or absence (preferably in the presence) of a base. This step is the same as the above-mentioned Method A step A1. Done in

Step C2 is a step of preparing a compound having the general formula (XXX). The step of converting the hydroxy group of the compound (XXIX) to a leaving group in an inert solvent in the presence of a base is followed by iodine This step is performed in the same manner as the above-mentioned Method A, Step A2.

Step C3 is a step for producing a compound having the general formula (XXXI), which is carried out by reacting compound (XXX) with compound (V) in an inert solvent in the presence of a base. This step is performed in the same manner as in the above-mentioned Method A, Step A3.

Step C4 is a step for producing a compound having the general formula (XXXII), which is carried out by reacting the compound (XXXI) with a base in an inert solvent and hydrolyzing the compound. It is performed in the same manner as in the above-mentioned Method A, Step A4.

Step C5 is a step for producing a compound having the general formula (XXXIII), and the compound (XXXI)
A method of subjecting a carboxyl group of I) to a Curtius rearrangement reaction to convert the carboxyl group into a carbamate, wherein the compound (XXXI)
The reaction is carried out by reacting I) with a diarylphosphoric acid azide derivative such as diphenylphosphoric acid azide in an inert solvent in the presence of a base, and then reacting with compound (VIII). This is performed in the same manner as in the step A5.

Step C6 is a step of producing compound (XIV), which is carried out by reducing the ester of compound (XXXIII).
It is performed in the same manner as the process.

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

Step C7 is a step for producing a compound having the general formula (XXXV),
Is carried out in an inert solvent in the presence or absence (preferably in the presence) of a base with a reducing agent. This step is carried out in the same manner as in the above-mentioned Method A, Step A1. Will be

Step C8 is a step for producing a compound having the general formula (XXXVI), wherein the hydroxy group of the compound (XXXV) is converted into a leaving group in an inert solvent in the presence of a base, and then the iodine is added. This step is performed in the same manner as the above-mentioned Method A, Step A2.

Step C9 is a step of producing a compound having the general formula (XXXVII), which is carried out by reacting compound (XXXVI) with compound (V) in an inert solvent in the presence of a base. In this step, the method A
It is performed in the same manner as the three steps.

Step C10 is a step represented by the general formula (XXXVII)
A step of producing a compound having I), which is carried out by reacting the compound (XXXVII) with a base in an inert solvent and hydrolyzing the same. This step is carried out in the same manner as the above-mentioned Method A, Step A4. .

Step C11 is a step for producing a compound having the general formula (XXXIX).
III), wherein the carboxyl group is subjected to a Curtius rearrangement reaction to convert the carboxyl group into a carbamate.
XVIII) is reacted with a diarylphosphate azide derivative such as diphenylphosphate azide in an inert solvent in the presence of a base, and then reacted with compound (VIII). This is performed in the same manner as in the step A5.

Step C12 is a step of producing a compound having the general formula (XL), which is carried out by reducing the ester of compound (XXXIX). This step is carried out in the same manner as in the above-mentioned Method A, Step A6. Done.

Step C13 is a step of producing compound (XIVa), which is carried out by reacting compound (XL) with a brominating agent in an inert solvent.

The solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction.
Halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; Amides, such as formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide; preferably amides (most preferably dimethylformamide).

As the brominating agent used in the above reaction,
Although not particularly limited, for example, “Comprehensive Organic
Transformations "(Larock, VCH, p316-317).
N-bromosuccinimide or bromine.

The reaction temperature varies depending on the type of the starting compound, the brominating agent, the solvent and the like, but is usually from -78 ° C to 150 ° C.
° C (preferably -20 ° C to 100 ° C).

The reaction time varies depending on the starting compound, the brominating agent, the solvent, the reaction temperature and the like, but is usually from 5 minutes to 48 minutes.
Time (preferably 30 minutes to 24 hours).

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

In the method D, compound (II) wherein X is an ethynylene group, compound (IIb) where X is an ethylene group, compound (IIc) where X is a vinylene group, and X is -CO -CH ₂ - groups with a compound (IId), X is -CH (OH) -CH ₂ - a group compound is a group having a (IIe), X is selected from an aryl group or a substituent group a 1 to 3 substituted ants
This is a method for producing a compound (IIf) in which X is an oxygen atom or a sulfur atom.

[0331]

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[0332]

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In the above formula, R ^5a , R ^6a , R ^7a , R ⁸ , n,
X _a , Y, Ya and ring A show consent as described above.

Step D1 is a step for producing a compound (IIa), and the compound (XXVIII) is prepared in an inert solvent.
Is reacted with a compound (XV) in the presence of a base and a palladium catalyst.
This step is carried out by a Sonogashira coupling reaction with a compound having the following formula: This step is carried out in the same manner as the above-mentioned Method B, Step B1.

Step D2 is a step of producing compound (IIb), which is carried out by reducing compound (IIa) in an inert solvent (preferably catalytic reduction at room temperature under a catalyst). This step is performed in the same manner as in the B method, step B5.

Step D3 is a step of producing compound (IIc). After reacting compound (XV) with catechol borane, compound (XXVIII) is reacted with Suzuki coupli.
This step is performed in the same manner as in the above-mentioned Method B, Step B3.

The step D4 is a step of producing the compound (IId). The compound (IIa) is prepared by subjecting the compound (IIa) to an addition reaction of water using an acid catalyst or an oximeration reaction using mercury oxide in an inert solvent. This step is performed in the same manner as in the B method, step B8.

Step D5 is a step of producing compound (IIe), which is carried out by reducing compound (IId) in an inert solvent. This step is carried out in the same manner as in the above-mentioned Method B, Step B11. .

Step D6 is a step for producing a compound (IIf), wherein the compound (XXI) is converted to a compound (XXVII).
This step is carried out by performing a Suzuki coupling reaction with I), and this step is carried out in the same manner as the above-mentioned Method B, Step B3.

Step D7 is a step of producing compound (IIg). Compound (XXVIII) is prepared by reacting compound (XXVIII) in the absence of a solvent or in the presence of a copper catalyst in an inert solvent.
This step is carried out by reacting with an alkali metal salt of I), and this step is carried out in the same manner as in the above-mentioned Method B, Step B14.

Step D8 is a step for producing a compound having the general formula (XLI), and is carried out using a compound (XXVIII)
Is reacted with compound (XXV), and this step is performed in the same manner as in the above-mentioned Method B, Step B1.

In step D9, compound (IIa-) wherein Y in compound (IIa) is a group having the formula -Ya-O-
This is a step of producing 1), which is carried out by reacting compound (XLI) with compound (XXVII). This step is carried out in the same manner as in the above-mentioned Method B, Step B17.

Method E can be carried out using compounds (XLIVa), (XLIVb) and (L) which are intermediates of compound (I) of the present invention.
a) and (Lb).

[0344]

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In the above formula, R ¹ , R ² , R ³ , R ^4a , R ¹¹ ,
Ar, m, and Z indicate consent as described above.

Step E1 is a step for producing a compound of the general formula (XLIVa) or (XLIVb).
Only one hydroxyl group of the compound having the formula (I) is converted to a compound represented by the general formula (XLII) in the presence or absence of a solvent and in the presence of a lipase.
It is carried out by selective acylation using a compound having I).

The solvent used in the present invention is not particularly limited, and may be the compound (XLIII) alone, or the most suitable one varies depending on the type of the starting compound, but various organic solvents and aqueous organic solvents may be used. And preferably, ethers such as diisopropyl ether, t-butyl methyl ether, diethyl ether, and tetrahydrofuran; aliphatic hydrocarbons such as n-hexane and n-pentane; aromatic hydrocarbons such as benzene and toluene. Hydrogens;
And halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane, more preferably ethers, and most preferably diisopropyl ether.

The reaction temperature is determined by using the starting compound, the solvent used, the lipase used, and the compound (XLIII)
The temperature is usually -50 to 50 ° C, preferably 0 to 40 ° C, although it depends on the type and the like.

The reaction time also depends on the starting compound, the solvent used, the lipase used, and the compound (XLIII).
The time is usually 15 minutes to 150 hours, preferably 30 minutes to 24 hours, although it varies depending on the type of the film.

After completion of the reaction, the desired compound (XLI)
Va) or (XLIVb) is collected from the reaction mixture according to a conventional method. For example, if insolubles are present, they are removed by filtration, and then concentrated or an immiscible organic solvent such as water and ethyl acetate is added. The organic layer containing the target compound is separated, and anhydrous sodium sulfate and anhydrous magnesium sulfate are removed. It is obtained by evaporating the solvent after drying with the above.

If necessary, the obtained target product can be separated and purified by a conventional method, for example, recrystallization, reprecipitation, or the like, or by eluting with a suitable eluent using chromatography.

Step E2 is a step of producing a compound having the general formula (XLV), which is carried out by oxidizing the alcohol moiety of the compound (XLIVa) to an aldehyde in an inert solvent in the presence of an oxidizing agent. .

The oxidation reaction used in this step is not particularly limited as long as it is an oxidation reaction for producing an aldehyde from a primary alcohol. For example, Collins oxidation carried out in methylene chloride using pyridine and chromic acid; PCC oxidation performed using pyridinium chromate chloride (PCC) in methylene chloride; PDC oxidation performed using pyridinium dichromate (PDC) in methylene chloride; electrophilic agent (eg, acetic anhydride, Trifluoroacetic anhydride, thionyl chloride, sulfuryl chloride, oxalyl chloride,
Dicyclohexylcarbodiimide, diphenylketene-p
-Tolylimine, N, N-diethylaminoacetylene, sulfur trioxide / pyridine complex, etc.) and dimethyl sulfoxide
(DMSO), DMSO oxidation, such as Swern oxidation; and methylene chloride or manganese dioxide oxidation using manganese dioxide in benzene, and the like, preferably in methylene chloride. Done, PC
C oxidation or Swern oxidation.

The reaction temperature varies depending on the type of the starting compound, the solvent, the oxidizing agent and the like, but is usually from -50 ° C to 50 ° C, preferably from -10 ° C to 30 ° C.

The reaction time varies depending on the starting compound, the solvent, the kind of the oxidizing agent, the reaction temperature and the like, but is usually from 10 minutes to 2 days, preferably from 30 minutes to 24 hours.

For example, the oxidizing agent is neutralized with aqueous sodium hydrogen sulfite, etc., and if there is any insoluble matter, it is removed by filtration and then concentrated or an immiscible organic solvent such as water and ethyl acetate is added thereto to obtain the desired compound. Is obtained by separating an organic layer containing, drying with anhydrous sodium sulfate, anhydrous magnesium sulfate and the like, and distilling off the solvent.

The obtained target compound can be separated and purified by a conventional method, for example, recrystallization, reprecipitation or the like, or elution with a suitable eluent, if necessary, by applying chromatography.

Step E3 is a step for producing a compound having the general formula (XLVII). The compound having the general formula (XLVI) is added to the aldehyde of the compound (XLV) in an inert solvent in the presence of a base. It is performed by reacting.

The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent, but is preferably an aromatic hydrocarbon such as benzene, toluene or xylene. Halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, dichlorobenzene;
Ethers such as diethyl ether, diisopropyl ether, t-butyl methyl ether, tetrahydrofuran; nitriles such as acetonitrile, isobutyronitrile; formamide, N, N-dimethylformamide, N,
Amides such as N-dimethylacetamide and hexamethylphosphorotriamide; sulfoxides such as dimethylsulfoxide and sulfolane; and ethers are more preferable.

The base to be used is not particularly limited as long as it is used as a base in a usual reaction, but preferably, alkali metal carbonates such as sodium carbonate, potassium carbonate and lithium carbonate; Alkali metal bicarbonates such as sodium bicarbonate, potassium bicarbonate and lithium bicarbonate; Alkali metal hydrides such as lithium hydride, sodium hydride and potassium hydride; sodium hydroxide, potassium hydroxide, and hydroxide Alkali metal hydroxides such as barium and lithium hydroxide; inorganic bases such as alkali metal fluorides such as sodium fluoride and potassium fluoride; sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxy Alkali metal such as potassium, potassium t-butoxide, lithium methoxide Alkoxides; N- methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N- methylpiperidine, 4- pyrrolidinopyridine, picoline, 4- (N, N- dimethylamino) pyridine, 2,
6-di (t-butyl) -4-methylpyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,4-diazabicyclo [4.
3.0] octane (DABCO), 1,8-diazabicyclo [5.4.0] -7-
Organic amines such as undecene (DBU), 1,5-diazabicyclo [4.3.0] -5-nonene (DBN); or butyllithium,
Examples thereof include organic metal bases such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and more preferred are alkali metal alkoxides, alkali metal hydrides, and organic metal bases.

The reaction temperature varies depending on the starting compound, solvent, type of phosphonium salt, type of base and the like.
The reaction is carried out at -80 ° C to 100 ° C, preferably -20 ° C.
C. to 50.degree.

The reaction time varies depending on the starting compound, solvent, type of phosphonium salt, type of base and the like.
0 minutes to 2 days, preferably 30 minutes to 12 days
Time.

For example, the reaction solution is neutralized with dilute hydrochloric acid or the like, and if there is any insoluble matter, it is removed by filtration, and then concentrated or an immiscible organic solvent such as water and ethyl acetate is added thereto. It is obtained by separating the layers, drying over anhydrous sodium sulfate, anhydrous magnesium sulfate, etc., and distilling off the solvent.

The obtained target product can be separated and purified, if necessary, by applying a conventional method, for example, recrystallization, reprecipitation or the like, or chromatography, and eluting with a suitable eluent.

Step E4 is a step for producing a compound having the general formula (XLVIII),
The reaction is carried out by hydrolyzing compound (XLVII) in the presence of a base.

The solvent to be used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. Preferably, alcohols such as methanol and ethanol, benzene, toluene and xylene are used. Aromatic hydrocarbons, such as methylene chloride, chloroform, halogenated hydrocarbons, such as carbon tetrachloride, dichloroethane,
Diethyl ether, tetrahydrofuran, dioxane,
Examples thereof include ethers such as dimethoxyethane and diethylene glycol dimethyl ether, or a mixed solvent of these solvents, or a mixed solvent of these solvents and water, and more preferably, alcohols and ethers.

The base to be used is not particularly limited as long as it is used as a base in a usual reaction, and preferably, sodium hydroxide, potassium hydroxide,
And alkali metal hydroxides such as lithium hydroxide and barium hydroxide.

The reaction temperature varies depending on the type of the starting compound, solvent, base and the like, but is usually from -20 ° C to 200 ° C, preferably from 0 ° C to 20 ° C.

The reaction time varies depending on the type of the starting compound, the reaction temperature, the solvent and the base, but is usually 30 minutes to 48 hours, preferably 1 hour to 24 hours.

For example, the reaction solution is neutralized with dilute hydrochloric acid or the like, and if there is any insoluble matter, it is removed by filtration, and then concentrated or an immiscible organic solvent such as water and ethyl acetate is added thereto to obtain an organic compound containing the target compound. It is obtained by separating the layers, drying over anhydrous sodium sulfate, anhydrous magnesium sulfate, etc., and distilling off the solvent.

The obtained target compound can be separated and purified, if necessary, by applying a conventional method, for example, recrystallization, reprecipitation or the like, or chromatography and eluting with a suitable eluent.

Step E5 is a step of producing a compound having the general formula (IL), and is a step of converting a compound (XLVIII) into a compound (IL) in an inert solvent in the presence of a base.

The solvent to be used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. Such ethers; N,
N-dimethylformamide, N, N-dimethylacetamide,
Amides such as N-methyl-2-pyrrolidone, N-methylpyrrolidinone, and hexamethylphosphorotriamide; aromatic hydrocarbons such as benzene, toluene, and xylene; more preferably, ethers and amides It is.

The base to be used is not particularly limited as long as it is used as a base in a usual reaction, but preferably, lithium hydride, sodium hydride,
Alkali metal hydrides such as potassium hydride; inorganic bases such as alkali metal fluorides such as sodium fluoride and potassium fluoride; sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, potassium alkali metal alkoxides such as t-butoxide, lithium methoxide; or butyllithium,
Organometallic bases such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide can be mentioned. More preferred are alkali metal alkoxides and alkali metal hydrides.

The reaction temperature varies depending on the type of the starting compound, solvent, base and the like, but is usually from -80 ° C to 100 ° C, preferably from 0 ° C to 50 ° C.

The reaction time varies depending on the type of the starting compound, the reaction temperature, the solvent and the type of the base, but is usually from 5 minutes to 4 minutes.
Eight hours, for example, the reaction solution is neutralized with dilute hydrochloric acid or the like, and if there is any insoluble matter, it is removed by filtration and then concentrated as it is or an immiscible organic solvent such as water and ethyl acetate is added to contain the target compound. The organic layer is separated, dried over anhydrous sodium sulfate, anhydrous magnesium sulfate, or the like, and then obtained by distilling off the solvent.

The obtained target product can be separated and purified by a conventional method, for example, recrystallization, reprecipitation or the like, or elution with an appropriate eluent, if necessary, by applying chromatography.

Step E6 is a step of reacting compound (La)
R ¹ is a hydrogen atom, and R ² and R ^3a are taken together to form a compound having a formula (— (C ＝ O) —) group (La-
This is a step of producing 1), in which the compound (IL) is converted to the target compound (La-1) in an inert solvent in the presence of a reducing agent.

The solvent to be used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent, but is preferably alcohols such as methanol, ethanol and isopropanol; diethyl ether Ethers such as benzene, diisopropyl ether, t-butyl methyl ether, tetrahydrofuran and dioxane; aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as hexane and cyclohexane; ethyl acetate and propyl acetate And more preferably, alcohols.

The reducing agent to be used is not particularly limited as long as it is generally used in a catalytic reduction reaction.
Preferably, palladium carbon, platinum oxide, platinum black, rhodium-aluminum oxide, triphenylphosphine-rhodium chloride (Wilkinson complex), palladium-barium sulfate, and Raney nickel are used. More preferably, it is palladium carbon.

Although the pressure is not particularly limited, it is usually 1 to 1
It is performed at 0 atm.

The reaction temperature varies depending on the type of the starting compound, solvent, base and the like, but is usually from 0 ° C. to 100 ° C.

The reaction time varies depending on the type of the starting compound, the reaction temperature, the solvent and the type of the base.
8 hours.

For example, after removing the catalyst by filtration, concentrating or adding an immiscible organic solvent such as water and ethyl acetate, separating the organic layer containing the target compound, drying the resultant with anhydrous sodium sulfate, anhydrous magnesium sulfate, etc. Obtained by distilling off the solvent.

The obtained target product can be separated and purified by a conventional method, for example, recrystallization, reprecipitation or the like, or elution with an appropriate eluent, if necessary, by chromatography.

Step E7 is a step of producing a compound having the general formula (LI), and is a step of converting the compound (XLVII) into a compound (LI) in an inert solvent in the presence of a reducing agent. This step can be performed according to the above-mentioned Method E, Step E6.

[0387] Step E8 is a step of reacting compound (La) with R
A step of producing a compound having a compound (La-2) wherein ^3a is a hydrogen atom, in an inert solvent in the presence of a base,
This is a step for producing a compound (La-2) by hydrolyzing the compound (LI), and this step can be carried out according to the above-mentioned Method E, Step E4.

Step E9 is a step of producing the compound (La-1), which is a step of producing the target compound (La-1) from the compound (La-2) in an inert solvent in the presence of a base. Yes, this step can be performed according to the above-mentioned Method E, Step E5.

In the step E10, in the compound (La), R ² and R ^3a are taken together to form a compound of the formula (— (C ＝ O) —)
A step of producing a compound (La-3) having no group, if necessary, by protecting the hydroxyl group of the compound (La-2). This step differs depending on the protecting group of the hydroxy group. The method to be performed, for example, Prot
ective Groups in Organic Synthesis (Third Edition, 1
999, issued by John Wiley & Sons, Inc.).

In addition, compound (XLIVb) was used in place of compound (XLIVa), and compound (XLIVb) was used.
By performing the step, compound (Lb) can be produced.

Method F is a method for producing compound (XLVI).

[0392]

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In the above formula, Ar and Z have the same meanings as described above.

Step F1 is a step for producing a compound (XLVI), which is carried out by reacting a compound having the general formula (LII) with triphenylphosphine in an inert solvent.

The inert solvent used in the above reaction is not particularly limited as long as it is inert to this reaction.
For example, aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether; aromatic hydrocarbons such as toluene, benzene, xylene; methylene chloride;
Halogenated hydrocarbons such as chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, and dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether, preferably aromatic Hydrocarbons (most preferably benzene).

The reaction temperature varies depending on the starting compound, the kind of the solvent and the like, but is usually from room temperature to 200 ° C., preferably 0 ° C. to 150 ° C. (most preferably 110 ° C.).

The reaction time mainly depends on the reaction temperature, starting compound,
Although it depends on the type of the solvent used, it is usually 5 minutes to 96 hours, preferably 15 minutes to 48 hours (most preferably 24 hours).

If necessary, the target compound in each step of the present Method F can be obtained by a conventional method, for example, recrystallization, reprecipitation, or a method usually used for separation and purification of an organic compound, for example, silica gel, alumina, magnesium, and the like. Adsorption column chromatography using a carrier such as musilica gel type Florisil; Sephadex LH-20 (Pharmacia), Amberlite XAD-11 (Rohm &
A method using a synthetic adsorbent such as distribution column chromatography using a carrier such as Haas Co., Ltd., Diaion HP-20 (manufactured by Mitsubishi Kasei), a method using ion exchange chromatography, or silica gel or alkylation. Separation and purification can be achieved by appropriately combining a normal phase / reverse phase column chromatography method with silica gel (preferably high performance liquid chromatography) and eluting with a suitable eluent.

When it is necessary to separate the isomers, the separation can be carried out by the above-described separation and purification means after the completion of the reaction in each of the above steps or at an appropriate time after the completion of the desired step.

Starting compounds (XXVIII) and (XXXI)
V), (XLII), (XLIII) and (LII)
Is readily produced according to known or known methods or methods analogous thereto.

The amino alcohol derivative having the general formula (I) of the present invention, its pharmacologically acceptable salt, its ester or other derivative has a low toxicity and excellent immunosuppressive activity. A pharmaceutical composition containing a compound having (I), a pharmacologically acceptable salt thereof, or an ester or other derivative thereof as an active ingredient,
Systemic lupus erythematosus, rheumatoid arthritis, polymyositis, dermatomyositis, scleroderma, Behcet's disease, Chron disease, ulcerative colitis, autoimmune hepatitis, aplastic anemia, idiopathic thrombocytopenic purpura, autoimmunity Hemolytic anemia, multiple sclerosis, autoimmune bullous disease, psoriasis vulgaris, vasculitis group, We
gener granulomas, uveitis, idiopathic interstitial pneumonia, Goodpas
ture syndrome, sarcoidosis, allergic granulomatous vasculitis, bronchial asthma, myocarditis, cardiomyopathy, aortitis syndrome, post-myocardial infarction syndrome, primary pulmonary hypertension, minimal change nephrosis, membranous nephropathy, membranous proliferation Nephritis, focal glomerulosclerosis, crescentic nephritis, myasthenia gravis, inflammatory neuropathy, atopic dermatitis, chronic actinic dermatitis, acute polyarthritis, Sydenham's chorea, systemic sclerosis, Adult-onset diabetes, insulin-dependent diabetes, juvenile diabetes, atherosclerosis, glomerulonephritis, tubular interstitial nephritis, primary biliary cirrhosis, primary sclerosing cholangitis, fulminant hepatitis, viral hepatitis , GVHD, rejection reactions in various organ transplants, contact dermatitis, autoimmune diseases such as sepsis, and other immunological-related diseases.

The novel optically active amino alcohol compounds (La) and (Lb) of the present invention are useful as intermediates for producing pharmaceuticals.

As an intermediate for synthesizing the optically active amino alcohol compounds (La) and (Lb), optically active 2-substituted-2-amino-1,3-propanediol is used.
Monoester derivative (XLIVa) or (XLIVb)
Is preferable, and such an optically active 2-substituted-2-amino-
1,3-propanediol monoester derivative (XL
IVa) and (XLIVb) are obtained by using a 2-substituted-2-amino-1,3-propanediol derivative (XLII) as a raw material and using a vinyl carboxylate derivative (XLIII) in the presence of a lipase. By selective acylation of only one of the hydroxyl groups, the compound can be easily and simply produced in a high yield.

When the compound having the general formula (I) of the present invention, its pharmaceutically acceptable salt or its ester is used as the above-mentioned therapeutic or prophylactic agent, it may be used as such or an appropriate pharmacologically. Mix with acceptable excipients, diluents, etc.
For example, it can be administered orally by tablets, capsules, granules, powders or syrups, or parenterally by injections or suppositories.

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

The amount of use varies depending on symptoms, age, etc., but in the case of oral administration, the lower limit is 0.05 m per day per dose.
g (preferably 5 mg), upper limit 200 mg (preferably,
In the case of intravenous administration, the lower limit is 0.01 mg (preferably 1 mg) and the upper limit is 100 mg per day.
(Preferably 10 mg) is desirably administered to an adult 1 to 6 times a day depending on the symptoms.

[0407]

The present invention will be described in more detail with reference to the following examples and test examples, but the scope of the present invention is not limited to these examples.

Example 1 (2R) -Amino -2-methyl-4- [5- (5-cyclohexylpent-
1-Inyl) thiophen-2-yl] butan-1-ol (Exemplary Compound No. 1-770) Example 1 (a) 2-methyl-2- (2-thienyl) ethylmalonic acid diethyles
Ether Sodium hydride (55%) 18.8 g (0.43 mol) was suspended in dimethylformamide (200 ml), under ice-cooling, methyl malonic acid diethyl ester 50.0 g (0.29 mol) 3
It was added slowly over 0 minutes and stirred for another 30 minutes. Next, a solution of 75.2 g (0.32 mol) of 2- (2-iodoethyl) thiophene dissolved in dimethylformamide (200 ml) was added over 15 minutes under a nitrogen atmosphere, and the mixture was further stirred at room temperature for 4 hours. The reaction mixture was poured into ice-cooled 10% hydrochloric acid (500 ml) and extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure, and the residue was purified by flash silica gel column chromatography (elution solvent: hexane: ethyl acetate = 10: 1 to 1).
Purification was performed in 5: 1) to give 53.1 g (65%) of the title compound as a colorless oil. Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 2986, 1726,
1271, 1252 Mass spectrum (FAB) m / z: 285 ((M + H) ^<+> ).

Example 1 (b) Monoethyl 2-methyl-2- (2-thienyl) ethylmalonate
Ester 52.7 g (0.19 mol) of 2-methyl-2- (2-thienyl) ethylmalonic acid diethyl ester obtained in Example 1 (a) was dissolved in ethanol (240 ml) and water (80 ml), Under ice-cooling, 11.4 g (0.20 mol) of potassium hydroxide was added, and the mixture was stirred for 2 hours.
In addition, 5.7 g (0.1 mol) of potassium hydroxide was added every 3 hours.
It was added repeatedly and stirred for a total of 6 hours. Water (300 ml) and ice cold 10
% Hydrochloric acid (500 ml) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure, and the residue was purified by flash silica gel column chromatography (eluent; hexane: ethyl acetate = 2: 1 to 0: 1) to give the title compound as a pale yellow oil (28.6 g, 60%). )Obtained. Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 2987, 1732,
1712, 1251, 1109 Mass spectrum (FAB) m / z: 257 ((M + H) ⁺ ).

Example 1 (c) 2-methoxycarbonylamino-2-methyl-4- (2-thienyl)
Butanoic acid ethyl ester 2-methyl-2- (2-thienyl) ethylmalonic acid monoethyl ester obtained in Example 1 (b) 19.0 g (74.3 mmol)
Was dissolved in benzene (450 ml) and triethylamine 11.4
ml (81.7 mmol) and diphenyl phosphate azide 17.6 m
l (81.7 mmol) was added, and the mixture was stirred at room temperature for 10 minutes, and further stirred at 80 ° C. for 1.5 hours. Then 60.3 ml of methanol
(1.49 mol) was slowly dropped at the same temperature over 30 minutes,
The mixture was further stirred for 8 hours. The reaction mixture was poured into water (500 ml) and extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure, and the residue was subjected to flash silica gel column chromatography (elution solvent: hexane: ethyl acetate = 8: 1 to 4:
Purification was performed in 1) to give the title compound as a colorless oil.
14.7 g (69%) were obtained. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.11
(1H, d, J = 5.1 Hz), 6.90 (1H, dd, J = 5.1, 3.5 H
z), 6.77 (1H, d, J = 3.5 Hz), 5.69 (1H, brs), 4.19
(2H, q.J = 7.3 Hz), 3.66 (3H, s), 2.84 (2H, dd, J
= 10.5, 10.5 Hz), 2.64 (2H, m), 2.20 (2H, dd, J =
10.5, 8.4 Hz), 1.61 (3H, s), 1.28 (3H, t, J = 7.3
Hz) Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 3417, 2987,
1719, 1503, 1453, 1081 Mass spectrum (FAB) m / z: 286 ((M + H) ⁺ ).

Example 1 (d) 2-methoxycarbonylamino-2-methyl-4- (2-thienyl)
Butan-1-ol 2-methoxycarbonylamino-2- obtained in Example 1 (c)
Methyl-4- (2-thienyl) butanoic acid ethyl ester 14.7
g (51.6 mmol) was dissolved in ethanol (150 ml) and tetrahydrofuran (100 ml), and sodium borohydride was dissolved.
5.07 g (0.13 mol) and lithium chloride 5.68 g (0.13 mol)
Was added, and the mixture was stirred overnight at room temperature under a nitrogen atmosphere. Next morning, in the same manner, sodium borohydride 5.07 g (0.13 mol)
And 5.68 g (0.13 mol) of lithium chloride were added, and the mixture was further stirred overnight at room temperature under a nitrogen atmosphere. The same operation was performed for another two days. The reaction mixture was ice-cooled 10% hydrochloric acid (500
ml) and extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure, and the residue was subjected to flash silica gel column chromatography (elution solvent: hexane: ethyl acetate =
Purification was performed in a ratio of 2: 1 to 1: 5) to obtain 11.7 g (93%) of the title compound as white crystals. Infrared absorption spectrum ν _max cm ^-1 (KBr): 3406, 3244, 1
687, 1562, 1264, 1089 Mass spectrum (FAB) m / z: 244
((M + H) ⁺ ) Elemental analysis; (% as C ₁₁ H ₁₇ NO ₃ S) Calculated: C: 54.30, H: 7.04, N: 5.76, S: 13.18 Found: C: 54.18, H: 6.98, N: 5.78, S: 13.34.

Example 1 (e) 2-methoxycarbonylamino-2-methyl-4- (5-bromothio
Offen-2-yl) butan-1-ol 2-methoxycarbonylamino-2- obtained in Example 1 (d)
Dissolve 11.7 g (48.0 mmol) of methyl-4- (2-thienyl) butan-1-ol in dimethylformamide (120 ml),
Under ice cooling, N-bromosuccinimide 10.8 g (60.8 mmol)
Was added and stirred at room temperature under a nitrogen atmosphere for 4 hours. The reaction mixture was poured into ice-cooled 10% hydrochloric acid (300 ml) and extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure, and the residue was purified by flash silica gel column chromatography (eluent: hexane: ethyl acetate = 4: 1 to 1: 3) to give the title compound as a pale yellow oil (12.4 g, 80%) )
Obtained. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 6.84
(1H, d, J = 3.7 Hz), 6.57 (1H, d, J = 3.7 Hz), 4.8
0 (1H, brs), 3.68 (2H, m), 3.64 (3H, s), 2.80 (2H,
m), 1.9-2.2 (2H, m), 1.24 (3H, s) infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 3627, 3436,
2956, 1722, 1711, 1513, 1259, 1087, 1048 Mass spectrum (FAB) m / z: 322 ((M + H) ⁺ ).

Example 1 (f) 4- [2- (5-bromothiophen-2-yl)] ethyl-4-methylo
Xazolidin-2-one 2-methoxycarbonylamino-2- obtained in Example 1 (e)
Methyl-4- (5-bromothiophen-2-yl) butan-1-ol 12.4 g (38.6 mmol) was added to dimethylformamide (125
ml), potassium t-butoxide (6.50 g, 57.9 mmol) was added under a nitrogen atmosphere under ice cooling, and the mixture was further stirred at the same temperature for 3 hours. The reaction mixture was ice-cooled with 10% hydrochloric acid (300 m
l) and extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure, and the residue was subjected to flash silica gel column chromatography (elution solvent: hexane: ethyl acetate = 4:
Purification was carried out according to 1-1: 2) to obtain 10.7 g (95%) of the title compound as white crystals. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 6.86
(1H, d, J = 3.7 Hz), 6.58 (1H, d, J = 3.7 Hz), 5.7
3 (1H, brs), 4.18 (1H, d, J = 8.6 Hz), 4.08 (1H,
d, J = 8.6 Hz), 2.84 (2H, m), 1.94 (2H, m), 1.41
(3H, s) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3211, 1749, 1
399, 1037, 798 Mass spectrum (FAB) m / z: 290 ((M + H) ⁺ ) Elemental analysis; (% as C ₁₀ H ₁₂ NO ₂ SBr) Calculated: C: 41.39, H: 4.17, N : 4.83, S: 11.05, B
r: 27.54 Observed value: C: 41.36, H: 4.04, N: 4.82, S: 11.08, B
r: 27.29.

Example 1 (g) (4R)-[2- (5-Bromothiophen-2-yl)] ethyl-4-methyl
Luoxazolidine-2-one and (4S)-[2- (5-bromothiophene
E emission-2-yl)] ethyl-4-methyl-oxazolidine-2-one Example 1 (obtained in f) 4- [2- (5- bromo-2-yl)] ethyl-4-methyl oxazolidine The 2-one was subjected to optical resolution on a preparative optically active HPLC column (ChiralCel OD, Daicel) (column, ChiralCel OD (2 cmφ × 25 cm);
Elution solvent, hexane: 2-propanol = 70: 30;
5 ml / min). The substance eluted first (55 min) was the 4S form, and the substance eluted later (77 min) was the 4R form. The absolute configuration was determined by X-ray crystal structure analysis. (4S) form; [α] _D ²⁴ -4.2 (c 1.03, methanol) (4R) form; [α] _D ²⁴ +4.2 (c 1.00, methanol).

Example 1 (h) (4R)-[2- [5- (5-Cyclohexylpent-1-ynyl) thiof
[En-2-yl]] ethyl-4-methyloxazolidin-2-one (4R)-[2- (5-bromothiophen-2-) obtained in Example 1 (g)
Yl)] ethyl-4-methyloxazolidine-2-one 450 mg
(1.55 mmol) was dissolved in 4.5 ml of dimethylformamide, and 1.40 g (4.65 mmol) of 5-cyclohexylpent-1-yne (50% xylene solution) and 2.16 ml of triethylamine were dissolved.
(15.5 mmol), copper (I) iodide 30 mg (0.16 mmol)
And 109 mg (0.16 mmol) of dichlorobis (triphenylphosphine) palladium were added at 80 ° C. under a nitrogen atmosphere.
Stirred for hours. The reaction solution was poured into water, extracted with ethyl acetate, and the ethyl acetate layer was washed with saturated saline. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue is subjected to silica gel chromatography (elution solvent;
Hexane: ethyl acetate = 4: 1-3: 2)
456 mg (82%) of the title compound were obtained. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 6.92
(1H, d, J = 3.6 Hz), 6.63 (1H, d, J = 3.6 Hz), 5.4
5 (1H, brs), 4.18 (1H, d, J = 8.6 Hz), 4.07 (1H, d,
J = 8.6 Hz), 2.78-2.90 (2H, m), 2.38 (2H, t, J =
7.2 Hz), 1.92-2.00 (2H, m), 1.55-1.75 (7H, m), 1.4
0 (3H, s), 1.10-1.35 (6H, m), 0.83-0.95 (2H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3450, 2926,
2852, 1758, 1382, 1046.

Example 1 (i) (2R) -Amino -2-methyl-4- [5- (5-cyclohexylpent-
1-Inyl) thiophen-2-yl] butan-1-ol (4R)-[2- [5- (5-cyclohexylpent-1-ynyl) thiophen-2-yl obtained in Example 1 (h) ]] Ethyl-4-methyloxazolidine-2-one (456 mg, 1.27 mmol) was dissolved in tetrahydrofuran (1 ml) and methanol (2 ml), and the mixture was dissolved under ice-cooling.
2 ml of a 5N aqueous potassium hydroxide solution was added, and the mixture was heated under reflux for 18 hours. Water was added to the reaction solution, which was extracted with methylene chloride. After the methylene chloride layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue is subjected to silica gel chromatography (elution solvent: methylene chloride: methanol = 20: 1 ~
Methylene chloride: methanol: aqueous ammonia = 10: 1: 0.
Purification according to 1) gave 353 mg (83%) of the title compound. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 6.92
(1H, d, J = 3.5 Hz), 6.62 (1H, d, J = 3.5 Hz), 3.3
7 (1H, d, J = 10.5 Hz), 3.32 (1H, d, J = 10.5 Hz),
2.75-2.90 (2H, m), 2.38 (2H, t, J = 7.1 Hz), 1.52
-1.79 (9H, m), 1.12-1.33 (6H, m), 1.11 (3H, s), 0.
81-0.96 (2H, m) Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 2925, 285
2, 1449, 1041 Mass spectrum (FAB) m / z: 334 ((M + H) ⁺ ) Elemental analysis; (% as C ₂₀ H ₃₁ NOS · 0.3H ₂ O) Calculated: C: 70.87, H: 9.40, N: 4.13, S: 9.46 Found: C: 70.83, H: 9.21, N: 4.22, S: 9.64 [α] _D ²⁴ -2.0 (c 0.60, methanol).

Example 2 (2R) -Amino -2-methyl-4- [5- (6-cyclohexylhexyl-
1-Inyl) thiophen-2-yl] butan-1-ol (Exemplary Compound No. 1-882) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 6.91
(1H, d, J = 3.6 Hz), 6.62 (1H, d, J = 3.6 Hz), 3.3
9 (1H, d, J = 10.7 Hz), 3.34 (1H, d, J = 10.7 Hz),
2.82 (2H, t, J = 8.5 Hz), 2.40 (2H, t, J = 6.9 H
z), 2.18-1.92 (4H, m), 1.88-1.51 (8H, m), 1.47-1.38
(2H, m), 1.28-1.07 (9H, m), 0.93-0.78 (2H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3327, 3275, 2
922, 2850, 1611, 1563, 1539, 1447, 1065, 1040, 803,
Example 521 2-Amino-2-methyl-4- [5- (5-phenylpent-1-ynyl)
Thiophen-2-yl] butan-1-ol (Exemplary Compound No. 1
-824) Racemic 4- [2- (5-bromothiophen-2-yl)] ethyl-
Using 4-methyloxazolidine-2-one as a starting material, the title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.32-
7.26 (2H, m), 7.25-7.16 (3H, m), 6.94 (1H, d, J =
3.6 Hz), 6.93 (1H, d, J = 3.6 Hz), 3.37 (1H, d, J =
10.8 Hz), 3.31 (1H, d, J = 10.4 Hz), 2.83 (2H, t,
J = 8.4 Hz), 2.77 (2H, t, J = 7.6 Hz), 2.42 (2H,
t, J = 7.2 Hz), 1.96-1.85 (2H, m), 1.84-1.64 (2H,
m), 1.50 (3H, brs), 1.11 (3H, s) Infrared absorption spectrum ν _max cm ^-1 (liquid film): 293
1, 2859, 1748, 1602, 1584, 1538, 1496, 1455, 1191,
1053, 908, 804, 747, 700, 573.

Example 4 2-amino-2-methyl-4- [5- [5- (4-methoxyphenyl) pen
To-1-ynyl] thiophen-2-yl] butan-1-ol salt
Acid salt (Exemplified Compound No. 1-849) Racemic 4- [2- (5-bromothiophen-2-yl)] ethyl-
Using 4-methyloxazolidine-2-one as a starting material, the title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 8.07
(3H, brs), 7.10 (2H, d, J = 8.6 Hz), 6.89 (1H, d,
J = 3.5 Hz), 6.81 (2H, d, J = 8.6 Hz), 6.65 (1H, d,
J = 3.5 Hz), 4.72 (1H, brs), 3.77 (3H, s), 3.65
(2H, s), 2.78-2.97 (2H, m), 2.66 (2H, t, J = 7.5 H
z), 2.36 (2H, t, J = 7.1 Hz), 1.77-2.20 (4H, m),
1.36 (3H, s) infrared absorption spectrum ν _max cm ^-1 (KBr): 3370, 3009,
2932, 1589, 1511, 1245, 1070, 1036.

Example 5 2-amino-2-methyl-4- [5- [5- (4-fluorophenyl) pen
To-1-ynyl] thiophen-2-yl] butan-1-ol
Rain salt (Exemplified Compound No. 1-833) Racemic 4- [2- (5-bromothiophen-2-yl)] ethyl-
Using 4-methyloxazolidine-2-one as a starting material, the title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD) δppm: 7.18-
7.25 (2H, m), 6.95-7.03 (2H, m), 6.94 (1H, d, J =
3.6 Hz), 6.73 (1H, d, J = 3.6 Hz), 6.25 (2H, s), 3.
61 (1H, d, J = 11.6 Hz), 3.52 (1H, d, J = 11.6 H
z), 2.80-2.95 (2H, m), 2.74 (2H, t, J = 7.6 Hz),
2.40 (2H, t, J = 7.0 Hz), 1.80-2.10 (4H, m), 1.31
(3H, s) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3352, 2940,
1578, 1509, 1385, 1367, 1221, 1194.

Example 6 2-amino-2-methyl-4- [5- (biphenyl-4-yl) ethynyl
Thiophen-2-yl] butan-1-ol (Exemplary Compound No. 1
-742) Racemic 4- [2- (5-bromothiophen-2-yl)] ethyl-
Using 4-methyloxazolidine-2-one as a starting material, the title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.55-
7.65 (6H, m), 7.43-7.50 (2H, m), 7.33-7.40 (1H,
m), 7.11 (1H, d, J = 3.6 Hz), 6.72 (1H, d, J = 3.6
Hz), 3.39 (1H, d, J = 10.4 Hz), 3.34 (1H, d, J = 1
0.4 Hz), 2.80-2.95 (2H, m), 1.70-1.90 (2H, m), 1.1
3 (3H, s) infrared absorption spectrum ν _max cm ^-1 (KBr): 3335, 3075,
2924, 1485, 1463, 1051, 837, 809, 764, 698.

Example 7 2-amino-2-methyl-4- [5- (4-butylphenyl) ethynyl
Thiophen-2-yl] butan-1-ol (Exemplary Compound No. 1
-737) Racemic 4- [2- (5-bromothiophen-2-yl)] ethyl-
Using 4-methyloxazolidine-2-one as a starting material, the title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.42
(2H, d, J = 8.1 Hz), 7.36-7.15 (5H, m), 7.16 (2H,
d, J = 8.1 Hz), 7.07 (1H, d, J = 3.3 Hz), 6.70 (1
H, d, J = 3.3 Hz), 3.99 (2H, s), 3.36-3.24 (2H,
m), 2.92-2.81 (2H, m), 2.01-1.95 (2H, m), 2.65-2.2
6 (3H, m), 1.11 (3H, s) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3326, 3264, 2
926, 2904, 1603, 1541,1468, 1454, 1211, 1063, 103
3, 803, 701.

Example 8 2-Amino-2-methyl-4- [5- (4-cyclohexylphenyl)
Ethinylthiophen -2-yl] butan-1-ol (Exemplified Compound No. 1-741) Racemic 4- [2- (5-bromothiophen-2-yl)] ethyl-
Using 4-methyloxazolidine-2-one as a starting material, the title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum _{(400MHz, DMSO-d 6)} δppm: 7.42
(2H, d, J = 8.2 Hz), 7.26 (2H, d, J = 8.2 Hz), 7.2
0 (1H, d, J = 3.6 Hz), 6.83 (1H, d, J = 3.6 Hz), 3.
56-3.24 (5H, m), 2.88-2.70 (2H, m), 1.89-1.52 (7H,
m), 1.43-1.21 (6H, m), 0.97 (3H, s) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3326, 3279, 2
924, 2850, 1645, 1567,1539, 1448, 1385, 1055, 826,
547.

Example 9 2-amino-2-methyl-4- [5- (4-propylphenyl) ethini
Luthiophen-2-yl] butan-1-ol (Exemplified Compound No. 1-736) Racemic 4- [2- (5-bromothiophen-2-yl)] ethyl-
Using 4-methyloxazolidine-2-one as a starting material, the title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD) δppm: 7.36
(2H, d, J = 8.2 Hz), 7.18 (2H, d, J = 8.2 Hz), 7.06
(1H, d, J = 3.5 Hz), 6.76 (1H, d, J = 3.5 Hz), 3.
39 (1H, d, J = 10.7 Hz), 3.38 (1H, d, J = 10.7 H
z), 2.93-2.80 (2H, m), 2.69-2.58 (2H, m), 1.83-1.59
(4H, m), 1.10 (3H, s), 0.94 (3H, t, J = 7.3 Hz) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3323, 3267, 2
959, 2929, 2869, 1611,1540, 1510, 1468, 1213, 106
6, 1035, 816, 804, 510.

Example 10 2-amino-2-methyl-4- [5- (4-propyloxyphenyl)
Ethinylthiophen -2-yl] butan-1-ol (Exemplified Compound No. 1-740) Racemic 4- [2- (5-bromothiophen-2-yl)] ethyl-
Using 4-methyloxazolidine-2-one as a starting material, the title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD) δppm: 7.37
(2H, d, J = 8.9 Hz), 7.03 (1H, d, J = 3.6 Hz), 6.8
9 (2H, d, J = 8.9 Hz), 6.75 (1H, d, J = 3.6 Hz),
3.95 (2H, t, J = 6.3 Hz), 3.39 (1H, d, J = 10.7 H
z), 3.35 (1H, d, J = 10.7 Hz), 2.92-2.78 (2H, m),
1.86-1.72 (4H, m), 1.09 (3H, s), 1.04 (3H, t, J =
7.6 Hz) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3329, 3275, 2
964, 2936, 1604, 1509,1466, 1249, 1065, 975, 832,
807.

Example 11 (2R) -Amino -2-methyl-4- [5- (5-cyclohexylpentene)
Ru) thiophen-2-yl] butan-1-ol (Exemplary Compound No. 1-98) (2R) -amino-2-methyl-4- [5- (5-cyclohexylpent-1) obtained in Example 1 -Inyl) thiophen-2-yl] butane
175 mg (0.53 mmol) of 1-ol was dissolved in 9 ml of ethanol, 90 mg of 10% palladium-carbon was added, and the mixture was stirred under a hydrogen atmosphere for 2 days. After filtration of the palladium-carbon through celite, the filtrate was evaporated under reduced pressure to give 150 mg of the title compound (85 mg).
%). Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 6.58
(1H, d, J = 3.2 Hz), 6.55 (1H, d, J = 3.2 Hz), 3.36
(1H, d, J = 10.5 Hz), 3.31 (1H, d, J = 10.5Hz),
2.75-2.90 (2H, m), 2.73 (2H, t, J = 7.6 Hz), 1.59
-1.83 (9H, m), 1.12-1.32 (10H, m), 1.11 (3H, s), 0.
81-0.89 (2H, m) Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 2926, 2853,
1440, 1042 Mass spectrum (FAB) m / z: 338 ((M + H) ⁺ ) Elemental analysis; (% as C ₂₀ H ₃₅ NOS · H ₂ O) Calculated: C: 67.56, H: 10.49, N : 3.94, S: 9.01 Found: C: 67.11, H: 10.03, N: 3.93, S: 8.88 [α] _D ²⁴ -0.7 (c 3.03, methanol).

Example 12 (2R) -Amino -2-methyl-4- [5- (6-cyclohexylhexyl)
Ru) thiophen-2-yl] butan-1-ol (Exemplary Compound No. 1-210) (2R) -amino-2-methyl-4- [5- (6-cyclohexylhexyl-) obtained in Example 2 1-Inyl) thiophen-2-yl] butane
The title compound was obtained in the same manner as in Example 11 using 1-ol. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 6.58
(1H, d, J = 3.3 Hz), 6.55 (1H, d, J = 3.3 Hz), 3.3
7 (1H, d, J = 10.4 Hz), 3.32 (1H, d, J = 10.4 Hz),
2.68-2.93 (4H, m), 1.05-1.85 (24H, m), 0.77-0.93
(2H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3334, 3269,
3159, 2922, 2850, 1465, 1448, 1060 Mass spectrum (EI) m / z: 351 (M ⁺ ) Elemental analysis; (% as C ₂₁ H ₃₇ NOS) Calculated: C: 71.74, H: 10.61, N : 3.98, S: 9.12 Found: C: 71.47, H: 10.48, N: 3.98, S: 9.37 [α] _D ²⁴ -1.3 (c 1.15, methanol).

Example 13 2-Amino-2-methyl-4- [5- (5-phenylpentyl) thiol
2- en -2-yl] butan-1-ol (Exemplary Compound No. 1-152) 2-amino-2-methyl-4- [5- (5-phenylpent-1-ynyl) obtained in Example 3 The title compound was obtained in the same manner as in Example 11 using [thiophen-2-yl] butan-1-ol. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.31-
7.24 (2H, m), 7.20-7.14 (3H, m), 6.58 (1H, d, J =
2.8 Hz), 6.54 (1H, d, J = 3.6 Hz), 3.36 (1H, d, J =
10.8 Hz), 3.31 (1H, d, J = 10.4 Hz), 2.81 (2H, t,
J = 8.4 Hz), 2.74 (2H, t, J = 7.6 Hz), 2.61 (2H,
t, J = 7.6 Hz), 1.84-1.56 (6H, m), 1.52 (3H, brs),
1.46-1.37 (2H, m), 1.11 (3H, s) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3333, 3263,
2927, 2852, 1496, 1453, 1059, 969, 928, 798, 747,
699, 569.

[0428] Example 14 2-amino-2-methyl-4- [5- [5- (4-
Methoxyphenyl) pentyl] thiophen-2-yl] butane
-1-ol (exemplary compound number 1-177) 2-amino-2-methyl-4- [5- [5- (4-methoxyphenyl) pent-1-ynyl] thiophene-2 obtained in Example 4 The title compound was obtained in the same manner as in Example 11 using [-yl] butan-1-ol. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.08
(2H, d, J = 8.5 Hz), 6.82 (2H, d, J = 8.5 Hz), 6.5
8 (1H, d, J = 3.3 Hz), 6.54 (1H, d, J = 3.3 Hz), 3.
79 (3H, s), 3.36 (1H, d, J = 10.5 Hz), 3.31 (1H,
d, J = 10.5 Hz), 2.70-2.85 (4H, m), 2.55 (2H, t, J
= 7.7 Hz), 1.55-1.85 (6H, m), 1.35-1.45 (2H, m),
1.11 (3H, s) infrared absorption spectrum ν _max cm ^-1 (KBr): 3333, 3263,
3103, 2926, 2852, 1514, 1247, 1061, 1029.

Example 15 2-amino-2-methyl-4- [5- [5- (4-fluorophenyl) pen
[Tyl] thiophen-2-yl] butan-1-ol (Exemplary Compound No. 1-161) 2-amino-2-methyl-4- [5- [5- (4-fluorophenyl) obtained in Example 5 The title compound was obtained in the same manner as in Example 11, using pent-1-ynyl] thiophen-2-yl] butan-1-ol. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD) δppm: 7.12-
7.18 (2H, m), 6.92-6.98 (2H, m), 6.63 (1H, d, J =
3.5 Hz), 6.56 (1H, d, J = 3.5 Hz), 6.25 (2H, s), 3.
61 (1H, d, J = 11.6 Hz), 3.51 (1H, d, J = 11.6 H
z), 2.70-2.90 (4H, m), 2.58 (2H, t, J = 7.6 Hz),
1.88-2.03 (2H, m), 1.57-1.70 (4H, m), 1.28-1.42 (5
H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 2929, 2854,
1578, 1509, 1464, 1387, 1356, 1223.

Example 16 2-Amino-2-methyl-4- [5- [2- (biphenyl-4-yl) ethyl]
L] thiophen-2-yl] butan-1-ol (Exemplified Compound No. 1-44) 2-amino-2-methyl-4- [5- (biphenyl-4-yl) ethynylthiophene obtained in Example 6 The title compound was obtained in the same manner as in Example 11 using [-2-yl] butan-1-ol. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.25
7.65 (9H, m), 6.60 (1H, d, J = 3.5 Hz), 6.59 (1H,
d, J = 3.5 Hz), 3.37 (1H, d, J = 10.5 Hz), 3.32 (1
(H, d, J = 10.5 Hz), 3.06-3.15 (2H, m), 2.95-3.04
(2H, m), 2.75-2.90 (2H, m), 1.65-1.85 (2H, m), 1.1
2 (3H, s) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3333, 3265,
2924, 2852, 1598, 1486, 1448, 1059, 798, 695.

Example 17 (2R) -Amino -2-methyl-4- [5- (5-cyclohexylpentane)
Noyl ) thiophen-2-yl] butan-1-ol (Exemplified Compound No. 1-1331) (2R) -amino-2-methyl-4- [5- (5-cyclohexylpent-1) obtained in Example 1 -Inyl) thiophen-2-yl] butane
126 mg (0.41 mmol) of 1-ol was dissolved in 2 ml of methanol, 2 ml of 6N sulfuric acid was added, and the mixture was heated under reflux for 4 hours. The reaction solution was made alkaline with a 1N aqueous solution of sodium hydroxide and then extracted with methylene chloride. After drying the methylene chloride layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure.
130 mg (91%) of the title compound were obtained. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.54
(1H, d, J = 3.7 Hz), 6.84 (1H, d, J = 3.7 Hz), 3.3
9 (1H, d, J = 10.4 Hz), 3.34 (1H, d, J = 10.4 Hz),
2.78-2.98 (4H, m), 1.13 (3H, brs), 0.8-1.9 (19H,
m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3332, 3267,
3134, 2922, 2851, 1647, 1457, 1057 Mass spectrum (EI) m / z: 351 (M ⁺ ) Elemental analysis; (% as C ₂₀ H ₃₃ NO ₂ S) Calculated: C: 68.33, H: 9.46 , N: 3.98, S: 9.12 Found: C: 67.99, H: 9.48, N: 3.92, S: 9.11 [α] _D ²⁴ -2.1 (c 1.03, methanol).

Example 18 (2R) -Amino -2-methyl-4- [5- (6-cyclohexylhexa)
Noyl ) thiophen-2-yl] butan-1-ol (Exemplary Compound No. 1-1357) (2R) -amino-2-methyl-4- [5- (6-cyclohexylhexyl) obtained in Example 2 1-Inyl) thiophen-2-yl] butane
The title compound was obtained in the same manner as in Example 17 using 1-ol. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.53
(1H, d, J = 3.9 Hz), 6.63 (1H, d, J = 3.9 Hz), 3.3
9 (1H, d, J = 10.5 Hz), 3.34 (1H, d, J = 10.5 Hz),
2.80-2.95 (4H, m), 1.33 (3H, brs), 0.8-1.9 (21H,
m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3149, 2922, 2
851, 1654, 1460, 1059,922 Mass spectrum (EI) m / z: 365 (M ⁺ ) Elemental analysis; (% as C ₂₁ H ₃₅ NO ₂ S) Calculated: C: 69.00, H: 9.65, N : 3.83, S: 8.77 Found: C: 68.74, H: 9.50, N: 3.83, S: 8.85 [α] _D ²⁴ -1.3 (c 1.15, methanol).

Example 19 2-amino-2-methyl-4- [5- (5-phenylpentanoyl) thio
Offen-2-yl] butan-1-ol hydrochloride (Exemplary Compound No. 1-1344) 2-Amino-2-methyl-4- [5- (5-phenylpent-1-ynyl) obtained in Example 3 ) The title compound was obtained in the same manner as in Example 17 using [thiophen-2-yl] butan-1-ol. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD) δppm: 7.71
(1H, d, J = 4.0 Hz), 7.28-7.20 (2H, m), 7.20-7.10
(3H, m), 6.98 (1H, d, J = 3.6 Hz), 3.62 (1H, d, J =
7.6 Hz), 3.53 (1H, d, J = 12.0 Hz), 3.04-2.88 (4
H, m), 2.64 (2H, t, J = 7.2 Hz), 2.15-2.04 (1H, m),
2.04-1.92 (1H, m), 1.78-1.62 (4H, m), 1.32 (3H,
s) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3378, 2927,
1648, 1588, 1562, 1504, 1456, 1230, 1067, 827, 74
8, 698, 578.

Example 20 2-amino-2-methyl-4- [5- [5- (4-fluorophenyl) pen
Tanoyl] thiophen-2-yl] butan-1-ol (Exemplary Compound No. 1-1348) 2-amino-2-methyl-4- [5- [5- (4-fluorophenyl) obtained in Example 6 The title compound was obtained in the same manner as in Example 17 using pent-1-ynyl] thiophen-2-yl] butan-1-ol. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.51
(1H, d, J = 3.7 Hz), 7.08-7.17 (2H, m), 6.90-7.00
(2H, m), 6.83 (1H, d, J = 3.7 Hz), 3.39 (1H, d, J =
10.4 Hz), 3.33 (1H, d, J = 10.4 Hz), 2.80-2.98 (4
H, m), 2.62 (2H, t, J = 7.5 Hz), 1.60-1.90 (6H,
m), 1.12 (3H, s) infrared absorption spectrum ν _max cm ^-1 (KBr): 3178, 2935,
2858, 1645, 1455, 1218, 1058.

Example 21 2-amino-2-methyl-4- [5- (biphenyl-4-yl) acetyl
Thiophen-2-yl] butan-1-ol (Exemplary Compound No. 1
-1326) Using 2-amino-2-methyl-4- [5- (biphenyl-4-yl) ethynylthiophen-2-yl] butan-1-ol obtained in Example 6, the procedure of Example 17 was repeated. The title compound was obtained in the same manner. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.64
(1H, d, J = 3.7 Hz), 7.52-7.60 (4H, m), 7.30-7.47
(5H, m), 6.86 (1H, d, J = 3.7 Hz), 4.18 (2H, s), 3.
38 (1H, d, J = 10.3 Hz), 3.33 (1H, d, J = 10.3 H
z), 2.84-2.98 (2H, m), 1.70-1.87 (2H, m), 1.12 (3
H, s) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3420, 2927,
1654, 1488, 1455, 1234, 1058, 751.

Example 222-amino-2-methyl-4- [5- (5-phenylpent-1-enyl)
Thiophene-2-yl] butan-1-ol maleate
 Example Compound No. 1-670 Example 22 (a)4-methyl-4- [2- [5- (5-phenylpent-1-enyl) thiof
[En-2-yl]] ethyloxazolidin-2-one 0.38 ml (2.58 mmol) of 5-phenylpent-1-yne
Catechol borane 500 mg (1.72 mmol) was added at room temperature
Thereafter, the mixture was stirred at 60 ° C. for 3 hours. Cool the reaction to room temperature
After the reaction, 5.0 ml of toluene was added to the reaction solution, and the reaction was performed in Example 1 (f).
Synthesized 4- [2- (5-bromothiophen-2-yl)] ethyl-4-
Methyl oxazolidine-2-one 500 mg (1.72 mmol),
Bis (triphenylphosphine) palladium chloride 119 mg
 (0.17 mmol), 0.83 ml of sodium ethoxide (20%
(Ethanol solution) was added at room temperature. This at 60 ° C for 2 hours
Stirred. After cooling the reaction solution to room temperature, 1N sodium hydroxide
Um was added. This is extracted with ethyl acetate,
Washed with saline. The ethyl acetate layer was dried over anhydrous sodium sulfate.
After drying over, the solvent was distilled off under reduced pressure. Separation of residue
Chromatography (elution solvent; hexane: ethyl acetate =
1: 1) to give 378 mg (68%) of the title compound
Was.

Example 22 (b) 2-Amino-2-methyl-4- [5- (5-phenylpent-1-enyl)
Thiophene-2-yl] butan-1-ol maleate 4-methyl-4- [2- [5- (5-phenylpent-1-enyl) thiophen-2- obtained in Example 22 (a) Yl]] ethyloxazolidin-2-one 370 mg (1.15 mmol) was hydrolyzed in the same manner as in Example 1 (i) to give 2-amino-2-methyl-4- [5
205 mg (0.69 mmol) of-(5-phenylpent-1-enyl) thiophen-2-yl] butan-1-ol were obtained. This was subjected to a general procedure for preparing a maleate to obtain 160 mg (34%) of the title compound as a maleate. Nuclear magnetic resonance spectrum _{(400MHz, DMSO-d 6)} δppm: 7.83
-7.70 (2H, m), 7.38-7.12 (5H, m), 6.78 (1H, d, J =
3.5 Hz), 6.71 (1H, d, J = 3.5 Hz), 6.50 (1H, d, J
= 15.6 Hz), 6.02 (2H, s), 5.96-5.83 (1H, m), 5.52
(2H, brs), 5.36-5.10 (1H, m), 3.51-3.38 (2H, m),
2.83-2.58 (4H, m), 2.28-2.15 (2H, m), 1.88-1.63 (4
H, m), 1.18 (3H, s) infrared absorption spectrum ν _max cm ^-1 (KBr): 3026, 2932, 1
579, 1497, 1386, 1357,1194, 1075, 1012, 865, 699,
570.

Example 23 2-Amino-2-methyl-4- [5- (5-cyclohexylpent-1-)
Enyl ) thiophen-2-yl] butan-1-ol (Exemplified Compound No. 1-657) The title compound was obtained in the same manner as in Example 22. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 6.64
(1H, d, J = 3.5 Hz), 6.61 (1H, d, J = 3.5 Hz), 6.4
1 (1H, d, J = 15.7 Hz), 5.95-5.88 (1H, m), 3.36 (1
H, d, J = 10.5 Hz), 3.31 (1H, d, J = 10.5 Hz), 2.8
6-2.73 (2H, m), 2.29-2.08 (2H, m), 1.83-1.55 (8H, m
m), 1.52-1.33 (4H, m), 1.30-1.12 (6H, m), 1.11 (3
H, s), 0.92-0.79 (2H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3328, 3275, 2
921, 2850, 1610, 1447,1225, 1066, 1038, 957, 804,
504.

Example 24 2-Amino-2-methyl-4- [5- (6-cyclohexylhex-1-
Enyl) thiophen-2-yl] butan-1-ol malein
Acid salt (Exemplified Compound No. 1-683) The title compound was obtained in the same manner as in Example 22. Nuclear magnetic resonance spectrum _{(400MHz, DMSO-d 6)} δppm: 7.90
-7.69 (2H, m), 6.77 (1H, d, J = 3.4 Hz), 6.70 (1H,
d, J = 3.4 Hz), 6.47 (1H, d, J = 15.8 Hz), 6.04 (2
H, s), 5.92-5.84 (1H, m), 5.55 (1H, brs), 3.49-3.3
2 (2H, m), 2.85-2.71 (2H, m), 2.18-2.06 (2H, m),
1.96-1.53 (8H, m), 1.42-1.03 (14H, m), 0.93-0.78 (2
H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3042, 2924, 2
851, 1695, 1577, 1533,1493, 1477, 1387, 1362, 135
1, 1210, 1074, 866.

Example 25 2-amino-2-methyl-4- [4- (5-phenylpent-1-ynyl)
Thiophen-2-yl] butan-1-ol hydrochloride (Exemplified Compound No. 2-185) Example 25 (a) 4- (5-phenylpent-1-ynyl) thiophen-2-carbo
18.1 g (126 mmol) of aldehyde 5-phenylpent-1-yne was dissolved in 100 ml of tetrahydrofuran, and 18.7 g (98 mmol) of 4-bromothiophene-2-carbaldehyde dissolved in 200 ml of tetrahydrofuran, and triethylamine 1
50 ml (1.07 mol), 962 mg (5.05 mmol) of copper (I) iodide, 3.54 g (5.04 mmol) of dichlorobis (triphenylphosphine) palladium were added, and the mixture was heated to 50 ° C. under a nitrogen atmosphere.
For 4 hours. After filtering the reaction solution, the filtrate was distilled off under reduced pressure. Ether was added to the residue and washed with water and saturated saline. After the ether layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (elution solvent; hexane: ethyl acetate = 100: 1-10:
Purification according to 1) afforded 19.4 g (78%) of the title compound. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 9.88
(1H, s), 7.72 (1H, s), 7.71 (1H, s), 7.35-7.27 (2H,
m), 7.24-7.16 (3H, m), 2.78 (2H, t, J = 7.2 Hz),
2.41 (2H, t, J = 7.2 Hz), 1.98-1.88 (2H, m) Infrared absorption spectrum ν _max cm ^-1 (liquid film): 223
8, 1679, 1440, 1234, 1157, 858, 748, 700, 665, 620 Mass spectrum (FAB) m / z: 255 ((M + H) ⁺ ).

Example 25 (b) [4- (5-Phenylpent-1-ynyl) thiophen-2-yl] meth
Tanol 4- (5-phenylpent-1-ynyl) obtained in Example 25 (a)
Thiophene-2-carbaldehyde 15.0 g (59.0 mmol)
Was dissolved in 150 ml of methanol, and under ice-cooling, 2.29 g (60.5 mmol) of sodium borohydride was added. below freezing,
After stirring for 25 minutes, the solvent was distilled off under reduced pressure. Water was added to the residue, extracted with ethyl acetate, and the ethyl acetate layer was washed with saturated saline. After drying the ethyl acetate layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to give the title compound (15.2 g).
(99%). Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.34-
7.27 (3H, m), 7.24-7.17 (3H, m), 6.98 (1H, s), 4.7
8 (2H, d, J = 5.6 Hz), 2.77 (2H, t, J = 7.6 Hz), 2.
39 (2H, t, J = 7.2 Hz), 1.96-1.85 (2H, m), 1.77 (1
(H, t, J = 5.6 Hz) Infrared absorption spectrum ν _max cm ^-1 (liquid film): 334
6, 3026, 2940, 2861, 2235, 1602, 1496, 1455, 1355,
1182, 1141, 1013, 844, 748, 700, 626 Mass spectrum (FAB) m / z: 256 (M ⁺ ).

Example 25 (c) [4- (5-Phenylpent-1-ynyl) thiophen-2-yl] a
Cetonitrile 4.68 g (18.3 mmol) of [4- (5-phenylpent-1-ynyl) thiophen-2-yl] methanol synthesized in Example 25 (b) was dissolved in 70 ml of tetrahydrofuran, and triodore was added under ice cooling. 20 ml of tetrahydrofuran in which 0.69 ml (7.30 mmol) of phosphorus hydride was dissolved was added dropwise. After completion of the dropwise addition, the mixture was stirred under ice-cooling under a nitrogen atmosphere for 10 minutes. Ice water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and saturated saline. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was dissolved in acetonitrile (120 ml), tetraethylammonium cyanide (2.85 g, 18.3 mmol) was added under ice-cooling, and the mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. Reaction solution 5
% Aqueous sodium bicarbonate, extracted with ethyl acetate, and the ethyl acetate layer was washed with saturated saline. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (elution solvent; hexane: ethyl acetate = 20: 1 to 15: 1) to obtain 3.21 g (66%) of the title compound. Nuclear magnetic resonance spectrum (270MHz, CDCl ₃ ) δppm: 7.15-
7.35 (6H, m), 7.03 (1H, s), 3.86 (2H, s), 2.77 (2
H, t, J = 7.5 Hz), 2.39 (2H, t, J = 7.0 Hz), 1.83-
1.98 (2H, m) infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 3691, 294
6, 2236, 1603, 1497, 1454, 1416, 1361.

Example 25 (d) 2- [4- (5-Phenylpent-1-ynyl) thiophen-2-yl]
Ethanol 3.21 g (12.1 mmol) of [4- (5-phenylpent-1-ynyl) thiophen-2-yl] acetonitrile obtained in Example 25 (c) was dissolved in 15 ml of ethanol, and water was added under ice-cooling. 15 m
1.70 g (30.2 mmol) of potassium hydroxide dissolved in l were added, and the mixture was heated under reflux for 2 hours. The reaction solution was acidified with 1N hydrochloric acid and extracted with ethyl acetate. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 15 ml of tetrahydrofuran,
1.69 ml (12.1 mmol) of triethylamine were added. Thereafter, 1.21 ml of ethyl chloroformate (12.
(7 mmol) dissolved in tetrahydrofuran (15 ml) was added dropwise, and the mixture was stirred under ice-cooling under a nitrogen atmosphere for 30 minutes. After the reaction solution was filtered, the obtained filtrate was slowly added to an aqueous solution (10 ml) of 2.29 g (60.5 mmol) of sodium borohydride under ice-cooling, followed by stirring at room temperature for 3 days. After cooling the reaction mixture, the mixture was acidified with 1N hydrochloric acid and extracted with ethyl acetate.
The ethyl acetate layer was washed with a 1 N aqueous solution of sodium hydroxide and a saturated saline solution. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: hexane: ethyl acetate = 10: 1 to 4: 1) to give 2.74 g of the title compound (8
4%). Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.15-
7.30 (6H, m), 6.86 (1H, s), 3.85 (2H, t, J = 6.2 H
z), 3.02 (2H, t, J = 6.2 Hz), 2.77 (2H, t, J = 7.6
Hz), 2.39 (2H, t, J = 7.1 Hz), 1.85-1.95 (2H, m) Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 3620, 294
7, 1732, 1603, 1497, 1454, 1359, 1250, 1046.

Example 25 (e) 2- (2-Iodoethyl) -4- (5-phenylpent-1-ynyl) thio
Offen Using 2-69 g (9.95 mmol) of 2- [4- (5-phenylpent-1-ynyl) thiophen-2-yl] ethanol obtained in Example 25 (d), Example 1 (g) was used. Similarly, the title compound 3.4
5 g (91%) were obtained. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.15-
7.30 (6H, m), 6.84 (1H, s), 3.30-3.35 (4H, m), 2.7
7 (2H, t, J = 7.6 Hz), 2.39 (2H, t, J = 7.0Hz), 1.
85-1.95 (2H, m) Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 2946, 286
3, 1603, 1497, 1454, 1429, 1360, 1172.

Example 25 (f) 2-Methyl-2- [4- (5-phenylpent-1-ynyl) thiophene
2-ethyl] ethylmalonic acid monoethyl ester methylmalonic acid diethyl ester 1.57 g (9.02 mmol) was dissolved in dimethylformamide 30 ml, and the mixture was dissolved under ice-cooling.
0.38 g (9.47 mmol) of sodium hydride was added, followed by stirring at room temperature under a nitrogen atmosphere for 1 hour. Thereafter, the reaction solution was cooled with ice, and the 2- (2-iodoethyl)-obtained in Example 25 (e) was obtained.
30 ml of dimethylformamide in which 4- (5-phenylpent-1-ynyl) thiophene was dissolved was added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 4 hours. After cooling the reaction solution, the mixture was acidified with 1N hydrochloric acid, extracted with ethyl acetate, and the ethyl acetate layer was washed with a 1N aqueous sodium hydroxide solution and saturated saline. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (elution solvent: hexane: ethyl acetate = 50: 1-20:
Partial purification was performed according to 1). The resulting mixture is ethanol 9
dissolved in 1 ml of water and 1 ml of potassium hydroxide under ice cooling.
g (14.3 mmol) was added and the mixture was stirred at room temperature for 3 days. The reaction solution was acidified with 1N hydrochloric acid and extracted with ethyl acetate. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. Silica gel chromatography of the residue (elution solvent; methylene chloride: methanol = 50: 1)
To give 1.02 g (28%) of the title compound. Nuclear magnetic resonance spectrum (500MHz, CDCl ₃ ) δppm: 7.15-
7.30 (6H, m), 6.79 (1H, s), 4.23 (2H, q, J = 7.1 H
z), 2.60-2.85 (4H, m), 2.38 (2H, t, J = 7.0Hz), 2.
20-2.32 (2H, m), 1.86-1.94 (2H, m), 1.53 (3H, s),
1.29 (3H, t, J = 7.1 Hz) Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 3509, 294
4, 1732, 1713, 1455, 1377, 1254, 1181, 1113.

Example 25 (g) 2-methoxycarbonylamino-2-methyl-4- [4- (5-phenyl
Rupent-1-ynyl) thiophen-2-yl] butanoic acid
Using 2-methyl-2- [4- (5-phenylpent-1-ynyl) thiophen-2-yl] ethylmalonic acid monoethyl ester 0.99 g (2.48 mmol) obtained in Example 25 (f) Thus, in the same manner as in Example 1 (j), 0.85 g (80%) of the title compound was obtained. Nuclear magnetic resonance spectrum (500MHz, CDCl ₃ ) δppm: 7.15-
7.30 (5H, m), 7.13 (1H, s), 6.75 (1H, s), 5.69 (1
H, brs), 4.15-4.33 (2H, m), 3.66 (3H, s), 2.50-2.8
0 (5H, m), 2.38 (2H, t, J = 7.0 Hz), 2.15-2.23 (1
H, m), 1.87-1.93 (2H, m), 1.60 (3H, s), 1.25-1.30
(3H, m) Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 3417, 298
7, 2945, 1719, 1504, 1453, 1323, 1077.

Example 25 (h) 4-Methyl-4- [2- [4- (5-phenylpent-1-ynyl) thiol
[En-2-yl]] ethyloxazolidin-2-one 2-methoxycarbonylamino-2- obtained in Example 25 (g)
Methyl-4- [4- (5-phenylpent-1-ynyl) thiophene-
2-yl] butanoic acid ethyl ester 0.82 g (1.92 mmol) was dissolved in ethanol 15 ml and tetrahydrofuran 10 ml, and under ice-cooling, lithium chloride 0.24 g (5.75 mmol),
0.22 g (5.75 mmol) of sodium borohydride was added,
The mixture was stirred at 70 ° C. for 2 hours under a nitrogen atmosphere. After cooling the reaction mixture, the mixture was acidified with 1N hydrochloric acid and extracted with ethyl acetate.
The ethyl acetate layer was washed with saturated saline. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure.
The residue was purified by silica gel chromatography (elution solvent: hexane: ethyl acetate = 4: 1 to 1: 1) to obtain 0.65 g (96%) of the title compound. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.15-
7.35 (6H, m), 6.79 (1H, s), 5.38 (1H, brs), 4.18
(1H, d, J = 8.6 Hz), 4.08 (1H, d, J = 8.6 Hz), 2.8
0-2.90 (2H, m), 2.77 (2H, t, J = 7.6 Hz), 2.38 (2
H, t, J = 7.0 Hz), 1.85-2.00 (4H, m), 1.41 (3H, s) Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 3450, 297
8, 2945, 1757, 1497, 1401, 1382, 1249, 1046.

Example 25 (i) 2-Amino-2-methyl-4- [4- (5-phenylpent-1-ynyl)
Thiophen-2-yl] butan-1-ol hydrochloride 4-methyl-4- [2- [4- (5-phenylpent-1-ynyl) thiophen-2-yl obtained in Example 25 (h) ]] Ethyl oxazolidin-2-one (200 mg, 0.57 mmol) was dissolved in tetrahydrofuran (1 ml) and methanol (2 ml). Under ice-cooling, a 5 N aqueous potassium hydroxide solution (2 ml) was added, and the mixture was heated under reflux for 18 hours. Water was added to the reaction solution, which was extracted with methylene chloride. After the methylene chloride layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was dissolved in 2 ml of 1,4-dioxane,
Under ice cooling, a 4N hydrochloric acid dioxane solution was added and the solvent was distilled off. The obtained white solid was washed with ether and dried to obtain 165 mg (80%) of the title compound. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD) δppm: 7.15-
7.30 (6H, m), 6.84 (1H, s), 3.61 (1H, d, J = 11.5
Hz), 3.52 (1H, d, J = 11.5 Hz), 2.80-2.95 (2H, m),
2.75 (2H, t, J = 7.5 Hz), 2.35 (2H, t, J = 7.0 H
z), 1.82-2.10 (4H, m), 1.32 (3H, s) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3351, 3027,
2928, 1594, 1509, 1455, 1389, 1062.

Example 26 2-amino-2-methyl-4- [4- (5-phenylpentyl) thiol
E emission-2-yl] butan-1-ol hydrochloride (Compound No. 2-39) Example 26 (a) 4-Methyl-4- [2- [4- (5-phenyl-pentyl) thiophene-2
Yl]] ethyloxazolidin-2-one 4-methyl-4- [2- [4- (5-phenylpent-1-ynyl) thiophen-2-yl]] ethyloxazolidine obtained in Example 25 (h) 174 mg (0.49 mmol) of 2-one in 9 ml of ethanol
, And 90 mg of 5% palladium-carbon was added, followed by stirring under a hydrogen atmosphere for 4 hours. After filtering the catalyst through Celite,
The filtrate was evaporated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: hexane: ethyl acetate = 1: 1) to obtain 164 mg (93%) of the title compound. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.25
7.30 (2H, m), 7.15-7.20 (3H, m), 6.70 (1H, s), 6.6
3 (1H, s), 5.33 (1H, brs), 4.18 (1H, d, J = 8.6 H
z), 4.07 (1H, d, J = 8.6 Hz), 2.80-2.90 (2H, m),
2.61 (2H, t, J = 7.8 Hz), 2.53 (2H, t, J = 7.7 H
z), 1.93-2.02 (2H, m), 1.55-1.70 (4H, m), 1.35-1.45
(5H, m) Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 3451, 297
7, 2934, 2858, 1757, 1400, 1382, 1045.

Example 26 (b) 2-Amino-2-methyl-4- [4- (5-phenylpentyl) thiol
Hen-2-yl] butan-1-ol hydrochloride 4-methyl-4- [2- [4- (5-phenylpentyl) thiophen-2-yl]] ethyl obtained in Example 26 (a) Oxazolidine-2
In a similar manner to Example 25 (i), using 136 mg (0.38 mmol) of -one, 107 mg (76%) of the title compound was obtained. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.10-
7.30 (5H, m), 6.63 (1H, s), 6.61 (1H, s), 3.66 (2
H, s), 2.80-2.95 (2H, m), 2.58 (2H, t, J = 7.7 H
z), 2.47 (2H, t, J = 7.7 Hz), 2.00-2.18 (2H, m),
1.52-1.67 (4H, m), 1.25-1.45 (5H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3223, 2929, 2
887, 1606, 1525, 1455, 1400, 1054.

Example 27 2-Amino-2-methyl-4- [4- (5-phenylpentanoyl) thio
Thiophene-2-yl] butan-1-ol hydrochloride (Compound No. 2-343) obtained in Example 26 (i) 2-amino-2-methyl-4- [4- (5-phenyl-pent - 1-Inyl) thiophen-2-yl] butane-1-
All hydrochloride 178 mg (0.49 mmol) was added to methanol 2
Then, 2 ml of 6N sulfuric acid was added, and the mixture was heated under reflux for 4 hours. The reaction solution was made alkaline with a 1N aqueous solution of sodium hydroxide and then extracted with methylene chloride. After the methylene chloride layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was dissolved in 1,4-dioxane (2 ml), 4N hydrochloric acid in dioxane was added under ice-cooling, the solvent was distilled off, and the obtained white solid was washed with ether and dried to obtain 100 mg of the title compound. (53%). Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD) δppm: 8.14
(1H, s), 7.29 (1H, s), 7.10-7.27 (5H, m), 3.63 (1H,
d, J = 11.6 Hz), 3.53 (1H, d, J = 11.6 Hz), 2.85-
3.00 (4H, m), 2.64 (2H, t, J = 7.0 Hz), 1.92-2.13
(2H, m), 1.67-1.75 (4H, m), 1.33 (3H, s) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3361, 3026,
2939, 1666, 1591, 1456, 1154, 1072.

Embodiment 282-amino-2-ethyl-4- [5- (5-cyclohexylpent-1-
Inyl) thiophen-2-yl] butan-1-ol malein
Acid salt (Exemplified Compound No. 1-1909) Racemic 4- [2- (5-bromothiophen-2-yl)] ethyl-
Using 4-ethyloxazolidin-2-one as a starting material
The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 6.90
 (1H, d, J = 3.6 Hz), 6.72 (1H, d, J = 3.6 Hz), 6.2
5 (2H, s), 3.61 (1H, d, J = 11.7 Hz), 3.57 (1H, d,
J = 11.7 Hz), 2.75-2.90 (2H, m), 2.38 (2H, t, J =
(7.0 Hz), 1.88-2.06 (2H, m), 1.52-1.82 (9H, m), 1.1
2-1.37 (6H, m), 0.85-1.04 (5H, m) Infrared absorption spectrum
Le ν_max cm^-1 (KBr): 3191, 2922, 2851, 1576, 152
1, 1386, 1362, 1193, 1068 Example 292-amino-2-ethyl-4- [5- (5-cyclohexylpentyl)
Thiophene-2-yl] butan-1-ol maleate
 (Exemplified Compound No. 1-1764) 2-Amino-2-ethyl-4- [5- (5-cyclo) obtained in Example 28
Hexylpent-1-ynyl) thiophen-2-yl] butane-1
Using -ol, the title compound was prepared in the same manner as in Example 11.
Obtained. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 6.64
 (1H, d, J = 3.7 Hz), 6.57 (1H, d, J = 3.7 Hz), 6.2
5 (2H, s), 3.61 (1H, d, J = 11.8 Hz), 3.57 (1H, d,
J = 11.8 Hz), 2.70-2.87 (4H, m), 1.88-2.05 (2H,
m), 1.56-1.82 (9H, m), 1.10-1.38 (10H, m), 0.99 (3
(H, t, J = 7.5 Hz), 0.81-0.93 (2H, m) infrared absorption spectrum
Tor ν_max cm^-1 (KBr): 3196, 2923, 2852, 1581, 15
23, 1385, 1368, 1193, 1067, 1016 Example 302-amino-2-ethyl-4- [5- (5-cyclohexylpentanoy
L) thiophen-2-yl] butan-1-ol maleate
 (Exemplified Compound No. 1-2097) 2-amino-2-ethyl-4- [5- (5-cyclo-2-
Hexylpent-1-ynyl) thiophen-2-yl] butane-1
Using -ol, the title compound was obtained in the same manner as in Example 17.
Obtained. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 7.72
 (1H, d, J = 3.7 Hz), 6.99 (1H, d, J = 3.7 Hz), 6.2
5 (2H, s), 3.63 (1H, d, J = 11.6 Hz), 3.59 (1H, d,
J = 11.6 Hz), 2.85-3.02 (4H, m), 1.94-2.12 (2H,
m), 1.60-1.83 (9H, m), 1.10-1.42 (8H, m), 1.01 (3
(H, t, J = 7.5 Hz), 0.82-0.96 (2H, m) infrared absorption spectrum
Tor ν_max cm^-1 (KBr): 3395, 2922, 2851, 1654, 15
82, 1520, 1458, 1385, 1370, 1203, 1067 Example 31(2R) -amino-2-methyl-4- [5- (4-cyclohexyloxy
But-1-ynyl) thiophen-2-yl] butan-1-ol
Maleate (Exemplary Compound No. 1-1072) 4- [2- (5-bromothiophen-2-yl)] ethyl-4-methylo
Using xazolidin-2-one as a starting material, Example 1
The title compound was obtained in the same manner. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 6.93
 (1H, d, J = 3.6 Hz), 6.73 (1H, d, J = 3.6 Hz), 6.2
5 (2H, s), 3.57-3.67 (3H, m), 3.51 (1H, d, J = 11.6
 Hz), 3.32-3.42 (1H, m), 2.78-2.95 (2H, m), 2.63
(2H, t, J = 6.7Hz), 1.50-2.10 (7H, m), 1.17-1.37
(8H, m) Infrared absorption spectrum ν_max cm^-1 (KBr): 3394, 2932,
2858, 1583, 1506, 1386, 1367, 1194, 1104 Example 322-amino-2-methyl-4- [5- (4-cyclohexylmethoxy)
Enyl) thiophen-2-yl] butan-1-ol (Example compound
Product number 1-1729) 4- [2- (5-bromothiophen-2-yl)] ethyl-4-methylo
Using xazolidin-2-one as a starting material, Example 1
The title compound was obtained in the same manner. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 7.45
 (2H, d, J = 8.7 Hz), 7.02 (1H, d, J = 3.6 Hz), 6.8
8 (2H, d, J = 8.7 Hz), 6.76 (1H, d, J = 3.6Hz), 3.
77 (2H, d, J = 6.3 Hz), 3.40 (1H, d, J = 10.9 H
z), 3.36 (1H, d, J = 10.9 Hz), 2.91-2.79 (2H, m),
1.90-1.68 (8H, m), 1.41-1.08 (5H, m), 1.11 (3H, s) Example 332-amino-2-methyl-4- [5- (4-benzyloxyphenyl)
Thiophene-2-yl] butan-1-ol (Exemplary Compound No. 1
-1744) 4- [2- (5-bromothiophen-2-yl)] ethyl-4-methylo
Using xazolidin-2-one as a starting material, Example 1
The title compound was obtained in the same manner. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 7.51
-7.27 (7H, m), 7.07 (1H, d, J = 3.6 Hz), 6.98 (2H,
 d, J = 8.7 Hz), 6.76 (1H, d, J = 3.6 Hz), 5.06 (2
H, s), 3.44-3.38 (2H, m), 2.91-2.80 (2H, m), 1.86-
1.74 (2H, m), 1.11 (3H, s) Example 34(2R) -amino-2-methyl-4- {5- [3- (4
-Methylphenoxy) propynyl] thiophen-2-i
Libutan-1-ol maleate (Example compound number
No. 1-1063) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.31
(3H, s), 1.88-2.10 (2H, m), 2.27 (3H, s), 2.80-2.95
 (2H, m), 3.51 (1H, d, J = 11.6 Hz), 3.60 (1H, d, J = 1
1.6 Hz), 4.89 (2H, s), 6.25 (2H, s), 6.77 (1H, d,
J = 3.6 Hz), 6.88 (2H, d, J = 8.6 Hz), 7.05 (1H, d, J =
3.6 Hz), 7.09 (2H, d, J = 8.6 Hz) Infrared absorption spectrum ν_max cm^-1(KBr): 3338, 3211, 3
006, 2923, 2229, 1583,1511, 1372, 1228, 1018 Example 35(2R) -amino-2-methyl-4- {5- [3- (4
-Methylphenoxy) propyl] thiophen-2-i
Libutan-1-ol maleate (Example compound number
No. 1-391) (2R) -amino-2-methyl-4 obtained in Example 34
-{5- [3- (4-methylphenoxy) propynyl] thio
Ophen-2-yl dibutane-1-ol maleate
And the title compound was obtained in the same manner as in Example 11. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.31
(3H, s), 1.88-2.10 (4H, m), 2.25 (3H, s), 2.77-2.92
 (2H, m), 2.94 (2H, t, J = 7.5 Hz), 3.51 (1H, d, J = 1
1.6 Hz), 3.60 (1H, d, J = 11.6 Hz), 3.93 (2H, t, J =
6.2 Hz), 6.25 (2H, s), 6.62 (1H, d, J = 3.3 Hz), 6.6
5 (1H, d, J = 3.3 Hz), 6.77 (2H, d, J = 8.5Hz), 7.04
(2H, d, J = 8.5 Hz) Infrared absorption spectrum ν_max cm^-1(KBr): 3412, 3028, 2
947, 2926, 1577, 1513, 1387, 1357, 1239, 1055 Example 36(2R) -amino-2-methyl-4- {5- [3- (3
-Methylphenoxy) propynyl] thiophen-2-i
Libutan-1-ol oxalate (Example compound number
1-2276) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.31
(3H, s), 1.90-2.10 (2H, m), 2.31 (3H, s), 2.82-2.96
 (2H, m), 3.52 (1H, d, J = 11.7 Hz), 3.60 (1H, d, J = 1
1.7 Hz), 4.90 (2H, s), 6.73-6.85 (4H, m), 7.05 (1
(H, d, J = 3.6 Hz), 7.16 (1H, m) Infrared absorption spectrum ν_max cm^-1(KBr): 2923, 2575, 2
226, 1621, 1583, 1559, 1489, 1290, 1255, 1154, 1045 Example 37(2R) -amino-2-methyl-4- {5- [3- (4
-Ethylphenoxy) propynyl] thiophen-2-i
Libutan-1-ol maleate (Example compound number
No. 1-1064) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.20
(3H, t, J = 7.6 Hz), 1.31 (3H, s), 1.88-2.10 (2H, m),
 2.58 (2H, q, J = 7.6 Hz), 2.80-2.95 (2H, m), 3.51 (1
H, d, J = 11.5 Hz), 3.60 (1H, d, J = 11.5 Hz), 4.89 (2
H, s), 6.25 (2H, s), 6.77 (1H, d, J = 3.6 Hz), 6.90
(2H, d, J = 8.6 Hz), 7.05 (1H, d, J = 3.6Hz), 7.12 (2
(H, d, J = 8.6 Hz) Infrared absorption spectrum ν_max cm^-1(KBr): 3385, 2959, 2
928, 2226, 1581, 1510, 1384, 1232, 1020 Example 38(2R) -amino-2-methyl-4- {5- [3- (4
-Methylthiophenoxy) propynyl] thiophene-2
-Ill-butan-1-ol maleate (Example compound
Compound No. 1-1068) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.31
(3H, s), 1.88-2.10 (2H, m), 2.42 (3H, s), 2.81-2.96
 (2H, m), 3.51 (1H, d, J = 11.5 Hz), 3.60 (1H, d, J = 1
1.5 Hz), 4.92 (2H, s), 6.25 (2H, s), 6.78 (1H, d,
J = 3.6 Hz), 6.96 (2H, d, J = 8.9 Hz), 7.06 (1H, d, J =
3.6 Hz), 7.27 (2H, d, J = 8.9 Hz) Infrared absorption spectrum ν_max cm^-1(KBr): 3401, 2984, 2
918, 2227, 1575, 1492, 1376, 1237, 1011 Example 39(2R) -amino-2-methyl-4- {5- [3-
(3,5-dimethoxyphenoxy) propynyl] thiof
1-yl-2-butane-1-ol fumarate (Example
Compound No. 1-2285) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.31
(3H, s), 1.90-2.10 (2H, m), 2.82-2.96 (2H, m), 3.51
 (1H, d, J = 11.6 Hz), 3.61 (1H, d, J = 11.6 Hz), 3.75
 (6H, s), 4.89 (2H, s), 6.13 (1H, dd, J = 2.2, 2.2 H
z), 6.43 (2H, d, J = 2.2 Hz), 6.69 (2H, s), 6.78 (1H,
 d, J = 3.6 Hz), 7.07 (1H, d, J = 3.6 Hz)
Kutor ν_max cm^-1(KBr): 3382, 2936, 2222, 1682, 1
601, 1476, 1205, 1152, 1066 Example 40(2R) -amino-2-methyl-4- {5- [3-
(3,4-Dimethoxyphenoxy) propynyl] thiof
Hen-2-yldibutan-1-ol maleic acid salt
(Exemplified Compound No. 1-2284) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.31
(3H, s), 1.88-2.10 (2H, m), 2.81-2.95 (2H, m), 3.51
 (1H, d, J = 11.4 Hz), 3.61 (1H, d, J = 11.4 Hz), 3.78
 (3H, s), 3.81 (3H, s), 4.88 (2H, s), 6.25 (2H,
s), 6.54 (1H, dd, J = 8.7, 2.7 Hz), 6.66 (1H, d, J = 2.
7 Hz), 6.78 (1H, d, J = 3.6 Hz), 6.87 (1H, d, J = 8.7
Hz), 7.05 (1H, d, J = 3.6 Hz) Infrared absorption spectrum ν_max cm^-1(KBr): 3361, 2934, 2
221, 1581, 1512, 1385, 1369, 1228, 1196, 1023 Example 41(2R) -amino-2-methyl-4- {5- [3- (4
-Acetylphenoxy) propynyl] thiophen-2-
Illbutan-1-ol (Exemplified Compound No. 1-2288) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.07
(3H, s), 1.68-1.82 (2H, m), 2.56 (3H, s), 2.77-2.91
 (2H, m), 3.33 (1H, d, J = 11.0 Hz), 3.36 (1H, d, J = 1
1.0 Hz), 5.05 (2H, s), 6.73 (1H, d, J = 3.6 Hz), 7.0
4 (1H, d, J = 3.6Hz), 7.10 (2H, d, J = 9.0 Hz), 8.00
(2H, d, J = 9.0Hz) Infrared absorption spectrum ν_max cm^-1(KBr): 3351, 3315, 3
287, 2916, 2878, 2734,2229, 1673, 1599, 1376, 136
4, 1253, 1174 Example 42(2R) -amino-2-methyl-4- {5- [3- (4
-Carboxyphenoxy) propynyl] thiophene-2
-Illbutan-1-ol hydrochloride (Example compound number
1-2289) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.31
(3H, s), 1.90-2.10 (2H, m), 2.82-2.96 (2H, m), 3.51
 (1H, d, J = 11.5 Hz), 3.61 (1H, d, J = 11.5 Hz), 5.04
 (2H, s), 6.79 (1H, d, J = 3.7 Hz), 7.05-7.11 (3H,
m), 7.99 (2H, d, J = 8.8 Hz) Infrared absorption spectrum ν_max cm^-1(KBr): 3383, 3064, 2
226, 1699, 1604, 1508, 1379, 1233, 1170, 1002 Example 43(2R) -amino-2-methyl-4- [5- [3- (3-methoxy
Phenoxy) propynyl] thiophen-2-yl] butane-1
-All maleate (Exemplified Compound No. 1-2283) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.31
(3H, s), 1.88-2.10 (2H, m), 2.80-2.96 (2H, m), 3.51
 (1H, d, J = 11.6 Hz), 3.60 (1H, d, J = 11.6Hz), 3.77
(3H, s), 4.91 (2H, s), 6.25 (2H, s), 6.52-6.61 (3
H, m), 6.78 (1H, d, J = 3.6Hz), 7.06 (1H, d, J = 3.6H
z), 7.18 (1H, t, J = 8.4Hz) Infrared absorption spectrum ν_max cm^-1(KBr): 3005, 2940, 2
223, 1583, 1493, 1387,1362, 1284, 1191, 1153, 108
0, 1045, 1020, 866, 813, 758, 687, 565 Example 44(2R) -amino-2-methyl-4- [5- [4- (4-methylf
Enoxy) but-1-ynyl] thiophen-2-yl] butane-
1-ol maleate (Exemplary Compound No. 1-1139) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.31
(3H, s), 1.87-2.10 (2H, m), 2.26 (3H, s), 2.85 (2H,
 t, J = 6.8Hz), 2.78-2.95 (2H, m), 3.51 (1H, d, J = 1
1.61), 3.61 (1H, d, J = 11.6Hz), 4.09 (2H, t, J = 6.
8Hz), 6.25 (2H, s), 6.73 (1H, d, J = 3.6Hz), 6.82 (2
H, d, J = 8.4Hz), 6.96 (1H, d, J = 3.6Hz), 7.07 (2H, d,
 (J = 8.4Hz) Infrared absorption spectrum ν_max cm^-1(KBr): 3032, 2925, 2
596, 1578, 1513, 1388,1359, 1293, 1244, 1205, 117
6, 1079, 1039, 867, 812, 509 Example 45(2R) -amino-2-methyl-4- [5- [4- (4-fluoro
Phenoxy) but-1-ynyl] thiophen-2-yl] buta
N-1-all (Exemplified Compound No. 1-1135) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.15
(3H, s), 1.72-1.89 (2H, m), 2.22 (3H, brs), 2.88 (2
H, t, J = 6.8Hz), 2.76-2.93 (2H, m), 3.37 (1H, d, J = 1
0.8 Hz), 3.42 (1H, d, J = 10.8Hz), 4.11 (2H, t, J = 6.
8Hz), 6.64 (1H, d, J = 3.6Hz), 6.84-6.90 (2H, m), 6.9
3-7.03 (3H, m) Infrared absorption spectrum ν_max cm^-1(KBr): 3356, 3296, 3
090, 2971, 2950, 2916,2896, 2877, 2812, 2735, 158
9, 1506, 1465, 1389, 1289, 1245, 1219, 1203,1154,
1065, 1039, 974, 923, 831, 819, 742, 568, 523, 509 Example 46(2R) -amino-2-methyl-4- {5- [3-
(3,4-dimethylphenoxy) propynyl] thiofe
2-yl-butan-1-ol maleate (Example
Compound No. 1-2278) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.31
(3H, s), 1.90-2.09 (2H, m), 2.19 (3H, s), 2.23 (3H,
 s), 2.81-2.94 (2H, m), 3.31 (1H, s), 3.51 (1H, d,
 J = 11.6 Hz), 3.61 (1H, d, J = 11.6 Hz), 4.87 (2H,
s), 6.25 (2H, s), 6.70-6.78 (3H, m), 7.01-7.04 (2H,
 m) Infrared absorption spectrum ν_max cm^-1(Liquid Film): 3353,
 3022, 2971, 2923, 2226, 1579, 1500, 1385, 1368, 1
287, 1249, 1205, 1165, 1120, 1077, 1039, 930, 865,
 806, 713, 573, 446 Example 47(2R) -2-amino-2-methyl-4- [2- (3-
Phenylpropyloxy) thiophen-5-yl] buta
N-1-ol tartrate Example Compound No. 1-2395 Example 47 (a)(2R) -amino-2-methyl-4-thiophen-2-
Irbutan-1-ol 1 / 2D-(-)-tartrate 85% ee (4R) -methyl-4- [2 obtained in Example 56
-(Thiophen-2-yl)] ethyloxazolidine-
7.30 g (34.6 mmol) of 2-one in tetrahydrofuran
Dissolve in 35 ml and 70 ml of methanol and cool under ice-cooling, 5N
Add 70 ml of aqueous potassium hydroxide solution and stir at 80 ° C for 2 days.
Stirred. Methylene chloride was added to the reaction solution, which was washed with water.
The methylene chloride layer is dried over anhydrous magnesium sulfate,
Was distilled off under reduced pressure. 6.20 g of the obtained residue was ethanol 60
of D-(-)-tartaric acid in 5.19 g (34.6 mmol)
A 50 ml solution of ethanol was added, and the deposited precipitate was collected by filtration.
This gave 7.56 g of the crude title compound. The crude eye obtained
7.54 g of the target compound in 75 ml of ethanol and 50 ml of water
And recrystallized to give 5.89 g (98% ee) of the title compound.
Was. Again, 5.88 g of the obtained target compound was added to 60 ml of ethanol.
l and 54 ml of water to give the title compound 5.11.
g (57%, 99.7% ee). Infrared absorption spectrum ν_max cm^-1 (KBr): 3400, 3218, 31
26, 2937, 2596, 1599, 1530, 1400, 1124, 1077, 715 Elemental analysis;₉H_FifteenNOS ・ 0.5C_FourH_FourO₆%) Calculated value : C, 50.95; H, 6.61; N, 5.40; S, 12.36 Found: C, 50.68; H, 6.91; N, 5.38; S, 12.48 [α]_D ^{twenty four} -14 (c 1.00, H_TwoO) Example 47 (b)Acetic acid (2R) -acetylamino-2-methyl-4-
(Thiophen-2-yl) butyl (2R) -amino-2-methyl obtained in Example 47 (a)
-4-thiophen-2-ylbutan-1-ol 1 /
To 5.11 g (19.6 mmol) of 2D-(-)-tartrate, under ice-cooling
Add 30ml of 1N sodium hydroxide aqueous solution
And extracted with methylene chloride. Methylene chloride layer
After drying over anhydrous sodium sulfate, the solvent is distilled off under reduced pressure.
And (2R) -amino-2-methyl-4-thiol
3.55 g (98%) of ene-2-ylbutan-1-ol
Was. The resulting (2R) -amino-2-methyl-4- (H
Offen-2-yl) butan-1-ol 1.51 g (8.15
Mmol), and then add 30 ml of pyridine, and under ice-cooling,
Acetic anhydride 1.95 ml (20.7 mmol), 4- (dimethylamine)
200 mg (1.64 mmol) of mino) pyridine were added. Nitrification
The mixture was stirred at room temperature for 2.5 hours under a hydrogen atmosphere. Cool the reaction solution with ice
The mixture is poured into 150 ml of 1N hydrochloric acid and extracted with ethyl acetate.
The ethyl acetate layer was washed successively with 1N hydrochloric acid and saturated saline.
Was. After drying the ethyl acetate layer over anhydrous sodium sulfate, the pressure was reduced.
The lower solvent was distilled off. Silica gel chromatography of the residue
-(Elution solvent; hexane: ethyl acetate = 3: 1-1:
Purification according to 2) gave 2.15 g (98%) of the title compound. Nuclear magnetic resonance spectrum (400MHz, CDCl_Three): Δ 1.37 (3H,
 s), 1.93 (3H, s), 1.94-2.10 (1H, m), 2.10 (3H, s),
 2.24-2.38 (1H, m), 2.85 (2H, t, J = 8.0 Hz), 4.18 (1
H, d, J = 11.6 Hz), 4.32 (1H, d, J = 11.6 Hz), 5.39 (1
H, brs), 6.81 (1H, dd, J = 1.2, 3.6 Hz), 6.92 (1H, d
d, J = 3.6, 5.2 Hz), 7.12 (1H, dd, J = 1.2, 5.2 Hz) Infrared absorption spectrum ν_max cm^-1 (KBr): 3265, 3079, 29
33, 2862, 1735, 1638,1559, 1472, 1441, 1374, 1318,
 1241, 1179, 1039, 701, 616 Example 47 (c)Acetic acid (2R) -acetylamino-2-methyl-4-
(5-bromothiophen-2-yl) butyl Acetic acid (2R) -acetylamino obtained in Example 47 (b)
No-2-methyl-4- (thiophen-2-yl) butyl
1.81 g (6.70 mmol) in dimethylformamide 20 ml
And N-bromosuccinimide 1.27 g under ice-cooling
(7.11 mmol) and 10 minutes under ice-cooling under nitrogen atmosphere
The mixture was stirred overnight at room temperature. Pour the reaction mixture into water and add
The mixture was extracted with chill, and the ethyl acetate layer was washed with saturated saline.
After drying the ethyl acetate layer over anhydrous sodium sulfate, the solvent was reduced.
Distilled off under pressure. Silica gel chromatography of the residue
(Eluent solvent: hexane: ethyl acetate = 3: 1-1: 2)
Purification was performed to obtain 2.32 g (99%) of the title compound.
Was. Nuclear magnetic resonance spectrum (400MHz, CDCl_Three): Δ 1.35 (3H,
 s), 1.95 (3H, s), 1.95-2.08 (1H, m), 2.10 (3H, s),
 2.24-2.37 (1H, m), 2.76 (2H, t, J = 8.4 Hz), 4.15 (1
H, d, J = 11.2 Hz), 4.30 (1H, d, J = 11.2 Hz), 5.39 (1
H, brs), 6.57 (1H, d, J = 3.6 Hz), 6.84 (1H, d, J = 3.
6 Hz) Infrared absorption spectrum ν_max cm^-1 (liquid film): 3300,
 3076, 2980, 2937, 1740, 1657, 1544, 1466, 1446, 1
373, 1242, 1045, 794, 604 Example 47 (d)(2R) -2-amino-2-methyl-4- [2- (3-
Phenylpropyloxy) thiophen-5-yl] buta
N-1-ol tartrate Sodium in 3-phenyl-1-propanol (1 ml)
(0.06 g, 2.6 mmol) was added, and the temperature was gradually raised.
Then, the mixture was stirred at 80 ° C to 90 ° C for 3 hours. Let it cool down
Acetic acid (2R) -acetylamino obtained in Example 47 (c)
-2-methyl-4- (5-bromothiophen-2-i
Ru) butyl (0.177 g, 0.51 mmol), iodine
Potassium iodide (0.8 mg, 0.005 mmol) and
Copper (II) oxide (21.0 mg, 0.26 mmol) was added.
Then, the mixture was stirred at 90 ° C. for 19 hours. After cooling, the reaction solution was silica
Gel column chromatography (elution solvent: dichlorometh
Tan: methanol: triethylamine, 10: 1: 0
100: 10: 1, V / V / V) and basic silica gel
Column chromatography (elution solvent: dichlorometa)
(Methanol, 100: 1, V / V).
(2R) -2-amino-2-methyl-4- [2- (3-f
Enylpropyloxy) thiophen-5-yl] butane
-1-ol (9.1 mg, yield 6%) was obtained. Obtained
(2R) -2-amino-2-methyl-4- [2- (3-
Phenylpropyloxy) thiophen-5-yl] buta
1-ol (15.2 mg, 0.048 mmol)
Was dissolved in methanol (1 ml) and tartaric acid (4.5 m
g, 0.049 mmol) at room temperature for 1 hour 30 minutes
While stirring. Concentrate under reduced pressure, add ethyl acetate to this
The precipitated crystals are collected by filtration, washed with ethyl acetate and dried.
The title compound (18.5 mg, 95%) was obtained. Nuclear magnetic resonance spectrum (400MHz, CD_ThreeOD) δ ppm: 1.30 (3
H, s), 1.86-2.07 (4H, m), 2.68-2.79 (4H, m), 3.51 (1
H, d, J = 11.6Hz), 3.59 (1H, d, J = 11.6Hz), 3.97 (2H,
t, J = 6.5Hz), 6.00 (1H, d, J = 3.7Hz), 6.44 (1H, d, J =
3.7Hz), 7.14-7.28 (5H, m) Mass spectrum (ESI) m / z: 342 (M + Na)⁺, 320 (M + H)⁺.

Example 48 (2R) -Amino -2-methyl-4- {5- [3- (3
-Acetylphenoxy) propynyl] thiophen-2-
Ildibutan -1-ol oxalate (Exemplified Compound No. 1-2287) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 1.31 (3H,
s), 1.88-2.10 (2H, m), 2.60 (3H, s), 2.82-2.95 (2
H, m), 3.51 (1H, d, J = 11.6 Hz), 3.60 (1H, d, J = 11.6
Hz), 5.02 (2H, s), 6.78 (1H, d, J = 3.6 Hz), 7.06
(1H, d, J = 3.6 Hz), 7.26 (1H, m), 7.44 (1H, m), 7.6
1-7.67 (2H, m) infrared absorption spectrum ν _max cm ^-1 (KBr): 3346, 3213, 29
29, 2224, 1679, 1595, 1582, 1277, 1205, 721 Example 49 (2R) -amino-2-methyl-4- [5- (5-fe
Nilpent-1-ynyl) thiophen-2-yl] buta
Example 49 (a) Acetic acid (2R) -acetylamino-2-methyl-4 -oxalate (Exemplary Compound No. 1-824)
[5- (5-phenylpent-1-ynyl) thiophene
-2-yl] butyl 1.60 g (4.59 mmol) of (2R) -acetylamino-2-methyl-4- (5-bromothiophen-2-yl) butyl acetate synthesized in Example 47 (c) was added to 16 ml of dimethylformamide. And dissolved in 5-phenylpent-1-yne 1.99
g (13.8 mmol), triethylamine 6.40 ml (45.9
Mmol), 175 mg (0.92 mmol) of copper (I) iodide
And 322 mg (0.46 mmol) of dichlorobis (triphenylphosphine) palladium at 80 ° C. under a nitrogen atmosphere.
For 2 hours. The reaction solution was poured into water, extracted with ethyl acetate, and the ethyl acetate layer was dried over anhydrous magnesium sulfate.
The solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (elution solvent; hexane: ethyl acetate = 2: 1 to 1).
2: 3) to give 1.41 g (75%) of the title compound. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ): δ 1.36 (3H,
s), 1.85-2.05 (3H, m), 1.94 (3H, s), 2.10 (3H,
s), 2.25-2.35 (1H, m), 2.43 (2H, t, J = 7.0 Hz), 3.70
-3.80 (4H, m), 4.17 (1H, d, J = 11.2 Hz), 4.31 (1H,
d, J = 11.2 Hz), 5.38 (1H, brs), 6.64 (1H, d, J = 3.6
Hz), 6.94 (1H, d, J = 3.6 Hz), 7.15-7.42 (5H, m) Infrared absorption spectrum ν _max cm ^-1 (CHCl ₃ ): 3443, 2946,
2862, 1737, 1681, 1511, 1374, 1251, 1042 Example 49 (b) (2R) -amino-2-methyl-4- [5- (5-fe
Nilpent-1-ynyl) thiophen-2-yl] buta
1-ol oxalate (2R) -acetylamino-2-methyl-4- [5- (5-phenylpent-1) acetic acid obtained in Example 49 (a)
-Inyl) thiophen-2-yl] butyl 1.40 g (3.40 g
Mmol) in tetrahydrofuran: methanol: water =
Dissolved in 14 ml of a 1: 1: 1 solution, added 1.43 g (34.0 mmol) of lithium hydroxide monohydrate, and stirred at 50 ° C. for 4 hours. The reaction solution was poured into water, extracted with methylene chloride, the methylene chloride layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: methylene chloride: methanol: aqueous ammonia = 20: 1: 0 to 10: 1: 0.1) to give (2
R) -Amino-2-methyl-4- [5- (5-phenylpent-1-ynyl) thiophen-2-yl] butane-
1.11 g (100%) of 1-ol were obtained. Obtained (2R)
-Amino-2-methyl-4- [5- (5-phenylpent-1-ynyl) thiophen-2-yl] butane-1-
360 mg (1.10 mmol) of all was dissolved in methanol, 99 mg (1.10 mmol) of oxalic acid was added, and the precipitated crystals were recrystallized from methanol to obtain 394 mg (86%) of the title compound as white crystals. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 1.31 (3H,
s), 1.82-2.10 (4H, m), 2.40 (2H, t, J = 7.0 Hz), 2.
75 (2H, t, J = 7.5 Hz), 2.80-2.95 (2H, m), 3.52 (1H,
d, J = 11.5 Hz), 3.61 (1H, d, J = 11.5 Hz), 6.73 (1H,
d, J = 3.6 Hz), 6.94 (1H, d, J = 3.6 Hz), 7.13-7.30
(5H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3383, 3106, 3
026, 2980, 2942, 2622,2514, 1721, 1609, 1539, 119
8, 699 Mass spectrum (FAB) m / z: 328 (M + H) + (Free form) Elemental _{analysis; (C 20 H 25 NOS ·} C 2 H 2 O 4 · 0.2H% as ₂ O) Calculated : C, 62.75; H, 6.55 ; N, 3.32; S, 7.61 Found: C, 62.50; H, 6.29 ; N, 3.39; S, 7.70 [α] D 25 -0.9 (c 1.00, methanol) example 50 (2R) -amino-2-methyl-4- [5- (5-fe
Nylpentanoyl) thiophen-2-yl] butane-1
-All oxalate (Exemplified Compound No. 1-1344) (2R) -amino-2-methyl-4 obtained in Example 49
387 mg (1.18 mmol) of-[5- (5-phenylpent-1-ynyl) thiophen-2-yl] butan-1-ol is dissolved in 4 ml of methanol, and 4 ml of 6N sulfuric acid is dissolved.
Was added and heated under reflux for 4 hours. After cooling the reaction solution to 0 ° C, 1
Alkaline with normal sodium hydroxide solution (pH 14)
And extracted with methylene chloride. After the methylene chloride layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography (Chromatorex NH (1
00-200 mesh)) (elution solvent; methylene chloride: methanol = 1: 0 to 50: 1) to give (2R) -amino-2-methyl-4- [5- (5-phenylpentanoyl) Thiophen-2-yl] butan-1-ol 336 mg
(82%). This is dissolved in methanol and oxalic acid 88
mg (0.97 mmol), and the resulting crystals were recrystallized from methanol to give the title compound as white crystals.
2 mg (78%) were obtained. Nuclear magnetic resonance spectrum _{(400MHz, DMSO-d 6)} : δ 1.19 (3
H, s), 1.55-1.67 (4H, m), 1.80-1.98 (2H, m), 2.60
(2H, t, J = 6.7 Hz), 2.83-2.96 (4H, m), 3.40 (1H, d,
J = 11.3 Hz), 3.47 (1H, d, J = 11.3 Hz), 7.00 (1H, d,
J = 3.7 Hz), 7.13-7.22 (3H, m), 7.23-7.31 (2H, m),
7.80 (1H, d, J = 3.7 Hz) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3126, 2942, 26
57, 1915, 1718, 1649, 1609, 1547, 1445, 1205, 700 Mass spectrum (FAB) m / z: 346 (M + H) ⁺ (free form) Elemental analysis; (C ₂₀ H ₂₇ NO ₂ S C ₂ H ₂ O ₄ .0.5H ₂ O%) Calculated: C, 59.44; H, 6.80; N, 3.15; S, 7.21 Found: C, 59.62; H, 6.53; N, 3.31; S, 7.43 Example 51 (2R) -amino-2-methyl-4- [5- (5-fe
Nilpentyl) thiophen-2-yl] butan-1-o
Oxalate (Exemplified Compound No. 1-152) Acetic acid (2R) -acetylamino-2-methyl-4- [5- (5-phenylpent-1) obtained in Example 49 (a)
-Inyl) thiophen-2-yl] butyl 337 mg (0.82
Was dissolved in 17 ml of methanol, 170 mg of 10% palladium-carbon was added, and the mixture was stirred under a hydrogen atmosphere for 16 hours. After filtering off the catalyst with Celite, the filtrate was distilled off under reduced pressure.
Acetic acid (2R) -acetylamino-2-methyl-4-
[5- (5-phenylpentyl) thiophen-2-yl]
318 mg (93%) of butyl were obtained. Acetic acid obtained (2
R) -acetylamino-2-methyl-4- [5- (5-
Phenylpentyl) thiophen-2-yl] butyl 298m
g (0.72 mmol) was dissolved in 6 ml of a solution of 1: 1: 1 tetrahydrofuran: methanol: water, and 301 mg (7.17 mmol) of lithium hydroxide monohydrate was added thereto.
For 6 hours. The reaction solution was poured into water, extracted with methylene chloride, the methylene chloride layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. 243 mg of the residue was dissolved in methanol, 65 mg (0.72 mmol) of oxalic acid was added, and the precipitated crystals were collected by filtration to give the title compound as white crystals.
mg (83%). Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 1.31 (3H,
s), 1.32-1.42 (2H, m), 1.58-1.70 (4H, m), 1.88-2.
08 (2H, m), 2.59 (2H, t, J = 7.6 Hz), 2.74 (2H, t, J
= 7.4 Hz), 2.75-2.91 (2H, m), 3.52 (1H, d, J = 11.6 H
z), 3.61 (1H, d, J = 11.6 Hz), 6.56 (1H, d, J = 3.3 H
z), 6.63 (1H, d, J = 3.3 Hz), 7.09-7.17 (3H, m), 7.1
9-7.27 (2H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3458, 3134, 29
29, 2855, 2595, 1724, 1642, 1543, 1219, 710 cm ^-1 Example 52 (2R) -amino-2-methyl-4- [5- [3- (4-chlorophenoxy)
Cis) propynyl] thiophen-2-yl] butan-1-ol
Oxalate (Exemplified Compound No. 1-2273) Example 52 (a) Acetic acid (2R) -acetylamino-2-methyl-4- [5- (3-h
( Droxypropynyl) thiophen-2-yl] butyl (2R) -acetylaminoacetic acid synthesized in Example 47 (c)
2-methyl-4- (5-bromothiophen-2-yl) butyl 1.38
g (3.95 mmol) was dissolved in 20 ml of dimethylformamide, and 0.69 ml (11.9 mmol) of propargyl alcohol, 5.60 ml (40.1 mmol) of triethylamine,
76 mg (0.40 mmol) of copper (I) iodide and 276 mg of dichlorobis (triphenylphosphine) palladium (0.39
Mmol) and the mixture was stirred at 80 ° C for 1 hour under a nitrogen atmosphere. The reaction solution was poured into water, extracted with ethyl acetate, and the ethyl acetate layer was washed with saturated saline. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (elution solvent; hexane: ethyl acetate = 3: 1 to 1: 3) to give the title compound as white crystals (685 mg, 54%). Nuclear magnetic resonance spectrum (500MHz, CDCl ₃ ): δ 1.35 (3H,
s), 1.91 (1H, brs), 1.94 (3H, s), 1.97-2.05 (1H,
m), 2.10 (3H, s), 2.27-2.35 (1H, m), 2.75-2.82 (2
H, m), 4.16 (1H, d, J = 11.2 Hz), 4.31 (1H, d, J = 11.
2 Hz), 4.49 (2H, s), 5.43 (1H, brs), 6.66 (1H, d, J
= 3.6 Hz), 7.02 (1H, d, J = 3.6 Hz) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3295, 3077, 2
981, 2217, 1740, 1644, 1556, 1373, 1251, 1028 Example 52 (b) (2R) -amino-2-methyl-4- [5- [3- (4-chlorophenoxy)
Cis) propynyl] thiophen-2-yl] butan-1-ol
Oxalate (2R) -acetylaminoacetic acid synthesized in Example 52 (a)
2-methyl-4- [5- (3-hydroxypropynyl) thiophene
285 mg (0.88 mmol) of 2--2-yl] butyl and 136 mg (1.06 mmol) of 4-chlorophenol were dissolved in 5 ml of anhydrous tetrahydrofuran, and under ice-cooling, 230 mg (1.32 mmol) of azodicarboxylic acid diethyl ester and 346 mg of triphenylphosphine ( 1.32 mmol)
The mixture was stirred at room temperature for 4 hours. Water was poured into the reaction mixture, which was extracted with ethyl acetate. After the ethyl acetate layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel chromatography (elution solvent: hexane: ethyl acetate =
2: 1 to 1: 3) to give (2R) -acetylamino-2-methyl-4- [5- [3- (4-chlorophenoxy) propynyl] thiophen-2-yl] butyl acetate. 195 as a yellow oil
mg (51%). This was dissolved in 6 ml of a 1: 1: 1 solution of tetrahydrofuran: methanol: water, and 370 mg (8.82 mmol) of lithium hydroxide monohydrate was added.
Stirred at C for 6 hours. The reaction solution was poured into water, extracted with methylene chloride, the methylene chloride layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. 175 mg (0.50 mmol) of the residue was dissolved in 5 ml of ethyl acetate, and 45 mg of oxalic acid (0.
50 mmol), and the precipitated crystals were collected by filtration to give 198 mg (86%) of the title compound as white crystals. Nuclear magnetic resonance spectrum (400MHz, DMSO-d ₆ ): δ 1.18 (3
H, s), 1.7-2.0 (2H, m), 2.84 (2H, t, J = 8.7Hz), 3.4
3 (2H, m), 5.07 (2H, s), 6.83 (1H, d, J = 3.6Hz), 7.
05 (2H, d, J = 9.0Hz), 7.19 (1H, d, J = 3.6Hz), 7.37
(2H, d, J = 9.0Hz) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3416, 1719, 15
97, 1490, 1375, 1241,1201,1092, 1006,830 Mass spectrum (FAB) m / z: 350 (M + H) ⁺ (Free form) Elemental analysis; (C ₂₀ H ₂₇ NO ₂ S · C ₂ % As H ₂ O ₄ ) Calculated: C, 54.61; H, 5.04; N, 3.18; S, 7.29; Cl, 8.06 Found: C, 54.61; H, 5.04; N, 3.01; S, 7.16; Cl, 7.77 Example 53 (2R) -amino-2-methyl-4- [5- (1-hydrido)
Roxy-5-phenylpentyl) thiophen-2-i
Ru] butan-1-ol oxalate (Exemplified Compound No. 1-1686) (2R) -amino- obtained in Example 50
2-methyl-4- [5- (5-phenylpentanoyl)
Thiophen-2-yl] butan-1-ol 130 mg (0.
38 mmol) was dissolved in 3 ml of methanol, and 17 mg (0.45 mmol) of sodium borohydride was added under ice-cooling.
Stirred at room temperature for 1 hour. Under ice-cooling, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in methanol, oxalic acid (34 mg, 0.38 mmol) was added, and the solvent was distilled off under reduced pressure. Thereto, 3 ml of ethanol was added, and the precipitate was collected by filtration to obtain 95 mg (58%) of the title compound as white crystals. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 1.25-1.50
(2H, m), 1.30 (3H, s), 1.58-1.68 (2H, m), 1.70-2.
08 (4H, m), 2.52-2.64 (2H, m), 2.80-2.94 (2H, m),
3.53 (1H, d, J = 11.7 Hz), 3.59 (1H, d, J = 11.7 Hz),
4.74 (1H, t, J = 6.8 Hz), 6.69 (1H, d, J = 3.6 Hz), 6.
74 (1H, d, J = 3.6 Hz), 7.08-7.27 (5H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3357, 2933, 28
57, 1579, 1496, 1454, 1310, 1070, 699 Example 54 (2R) -amino-2-methyl-4- [5- (4- fe
Nilbut-1-ynyl) thiophen-2-yl] butane
-1-ol oxalate (Exemplified Compound No. 1-756) As in Example 49, acetic acid (2R) -acetylamino-
2-methyl-4- (5-bromothiophen-2-yl)
The title compound was obtained using butyl and 4-phenylbut-1-yne. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 1.31 (3
H, s), 1.88-2.09 (2H, m), 2.68 (2H, t, J = 7.3 Hz),
2.78-2.93 (4H, m), 3.52 (1H, d, J = 11.6 Hz), 3.61
(1H, d, J = 11.6 Hz), 6.72 (1H, d, J = 3.6Hz), 6.88 (1
H, d, J = 3.6Hz), 7.16-7.31 (5H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3204, 3110, 30
26, 2981, 2929, 2887, 1719, 1608, 1541, 1202, 699 Example 55 (2R) -amino-2-methyl-4- [5- (4-fe
Nilbutanoyl) thiophen-2-yl] butane-1-
All oxalate (Exemplified compound 1-1330) As in Example 50, (2R) -amino-2-methyl-4- [5- (4-phenylbut-1-) obtained in Example 54.
The title compound was obtained using (inyl) thiophen-2-yl] butan-1-ol. Nuclear magnetic resonance spectrum _{(400MHz, DMSO-d 6)} : δ 1.19 (3
H, s), 1.82-1.98 (4H, m), 2.62 (2H, t, J = 7.7 Hz),
2.85-2.97 (4H, m), 3.39 (1H, d, J = 11.7 Hz), 3.45 (1
H, d, J = 11.7 Hz), 7.00 (1H, d, J = 3.8Hz), 7.15-7.33
(5H, m), 7.76 (1H, d, J = 3.8Hz) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3410, 3210, 29
41, 2653, 2576, 1665, 1641, 1530, 1452, 1325 Example 56 (2R) -amino-2-methyl-4- [5- (4- cyclyl )
Rohexylbut-1-ynyl) thiophen-2-yl]
Butan -1-ol (Exemplified Compound No. 1-743) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 0.87-0.99
(2H, m), 1.08 (3H, s), 1.11-1.50 (6H, m), 1.62-1.
81 (7H, m), 2.41 (2H, t, J = 7.2 Hz), 2.74-2.88 (2H,
m), 3.34 (1H, d, J = 11.0 Hz), 3.37 (1H, d, J = 11.0
Hz), 6.66 (1H, d, J = 3.6 Hz), 6.87 (1H, d, J = 3.6 H
z) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3334, 3269, 3
153, 2922, 2851, 1618, 1449, 1060, 804 Example 57 (2R) -amino-2-methyl-4- [5- (4- cyclyl )
Rohexylbutyl) thiophen-2-yl] butane-1
- ol (Compound No. 1-71) obtained in Example 56 (2R) - amino-2-methyl-4
The title compound was obtained in the same manner as in Example 11 using-[5- (4-cyclohexylbut-1-ynyl) thiophen-2-yl] butan-1-ol. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 0.80-0.95
(2H, m), 1.08 (3H, s), 1.10-1.40 (8H, m), 1.54-1.
81 (9H, m), 2.68-2.87 (4H, m), 3.34 (1H, d, J = 10.9
Hz), 3.37 (1H, d, J = 10.9 Hz), 6.53 (1H, d, J = 3.2 H
z), 6.58 (1H, d, J = 3.2 Hz) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3333, 3269, 3
170, 2923, 2850, 1619,1461, 1447, 1059, 801 Example 58 (2R) -amino-2-methyl-4- [5- (4- cycl
Rohexylbutanoyl) thiophen-2-yl] butane
-1-ol (Exemplified Compound No. 1-1329) (2R) -amino-2-methyl-4 obtained in Example 56
The title compound was obtained in the same manner as in Example 17 using-[5- (4-cyclohexylbut-1-ynyl) thiophen-2-yl] butan-1-ol. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 0.83-0.97
(2H, m), 1.09 (3H, s), 1.10-1.33 (6H, m), 1.61-1.
86 (9H, m), 2.82-3.00 (4H, m), 3.35 (1H, d, J = 10.9
Hz), 3.39 (1H, d, J = 10.9 Hz), 6.94 (1H, d, J = 3.7 H
z), 7.69 (1H, d, J = 3.7 Hz) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3333, 3268, 3
142, 2921, 2849, 1648, 1457, 1208, 1057, 923, 816 EXAMPLE 59 2-Amino-2-methyl-4- [5- (3-cyclohexyl)
Silmethoxypropynyl) thiophen-2-yl] buta
1-ol maleate (Exemplified Compound No. 1-118)
5) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 0.92-1.04
(2H, m), 1.13-1.37 (3H, m), 1.31 (3H, s), 1.53-1.
82 (6H, m), 1.89-2.11 (2H, m), 2.82-2.96 (2H, m),
3.35 (2H, d, J = 6.4 Hz), 3.51 (1H, d, J = 11.5 Hz),
3.61 (1H, d, J = 11.5 Hz), 4.87 (2H, s), 6.25 (2H,
s), 6.78 (1H, d, J = 3.6 Hz), 7.05 (1H, d, J = 3.6 Hz) Infrared absorption spectrum ν _max cm ^-1 (KBr): 2924, 2852, 2
Example 218, 1577, 1496, 1386, 1356, 1195, 1089, 866 Example 60 (2R) -amino-2-methyl-4- [5- (4- cyclic )
Rohexyloxybutyl) thiophen-2-yl] buta
N-1-ol maleate (Exemplary Compound No. 1-40
0) (2R) -amino-2-methyl-4 obtained in Example 31
The title compound was obtained in the same manner as in Example 11 using-[5- (4-cyclohexyloxybut-1-yl) thiophen-2-yl] butan-1-ol. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 1.15-1.35
(5H, m), 1.31 (3H, s), 1.50-1.80 (7H, m), 1.85-2.
08 (4H, m), 2.73-2.92 (4H, m), 3.20-3.30 (1H, m),
3.45-3.55 (3H, m), 3.60 (1H, d, J = 11.6 Hz), 6.25
(2H, s), 6.59 (1H, d, J = 3.3 Hz), 6.64 (1H, d, J = 3.
3 Hz) Infrared absorption spectrum ν _max cm ^-1 (KBr): 2931, 2856, 1
577, 1490, 1471, 1459, 1388, 1357, 1108, 1081, 868 Example 61 (2R) -amino-2-methyl-4- {5- [4- (4
-Fluorophenoxy) butyl] thiophen-2-i
Rubutan -1-ol (Exemplified Compound No. 1-463) (2R) -amino-2-methyl-4- [5 obtained in Example 45
The title compound was obtained in the same manner as in Example 11 using-[4- (4-fluorophenoxy) but-1-ynyl] thiophen-2-yl] butan-1-ol. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 1.08 (3H,
s), 1.70-1.85 (6H, m), 2.73-2.88 (4H, m), 3.34 (1
H, d, J = 10.9 Hz), 3.38 (1H, d, J = 10.9 Hz), 3.94 (2
H, t, J = 5.9 Hz), 6.58 (1H, d, J = 3.7 Hz), 6.60 (1H,
d, J = 3.7 Hz), 6.83-6.90 (2H, m), 6.93-7.00 (2H,
m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3333, 3268, 3
162, 2940, 2865, 1509,1474, 1244, 1220, 1060, 830,
763 Example 62 (2R) -amino-2-methyl-4- {5- [4- (4
-Methoxyphenoxy) butyl] thiophen-2-i
Rubutan -1-ol (Exemplified Compound No. 1-479) (4R) -Methyl-4- [2- obtained in the same manner as in Example 1h
[4- (4-Methoxyphenoxy) but-1-ynyl]] ethyloxazolidine was prepared according to Example 26 to obtain the title compound. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 1.08 (3H,
s), 1.68-1.84 (6H, m), 2.73-2.87 (4H, m), 3.34 (1
H, d, J = 10.8 Hz), 3.38 (1H, d, J = 10.8 Hz), 3.72 (3
H, s), 3.91 (2H, t, J = 6.0 Hz), 6.58 (1H, d, J = 3.1
Hz), 6.60 (1H, d, J = 3.1 Hz), 6.81 (4H, s) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3335, 3273, 3
Example 183, 2945, 2868, 1514, 1473, 1233, 1045, 825, 735 Example 63 (2R) -amino-2-methyl-4- [5- (4-ben
(Diloxybut-1-ynyl) thiophen-2-yl] but
Tan-1-ol oxalate (Exemplary Compound No. 1-126
6) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 1.31 (3H,
s), 1.89-2.10 (2H, m), 2.70 (2H, t, J = 6.8 Hz), 2.
80-2.94 (2H, m), 3.52 (1H, d, J = 11.6 Hz), 3.61 (1
H, d, J = 11.6 Hz), 3.64 (2H, t, J = 6.8 Hz), 4.57 (2
H, s), 6.74 (1H, d, J = 3.6Hz), 6.94 (1H, d, J = 3.6H
z), 7.23-7.39 (5H, m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 3358, 3028, 29
26, 2544, 1719, 1702,1605, 1496, 1468, 1454, 1402,
1279, 1204, 1105, 806, 739, 720, 699, 500 Mass spectrum (FAB) m / z: 344 (M + H) ⁺ (Free form) Example 64 (2R) -amino-2-methyl-4- [5- (4-ben
(Diloxybutyl) thiophen-2-yl] butane-1
-All maleate (Exemplified Compound No. 1-594) (2R) -amino-2-methyl- obtained in Example 64
The title compound was obtained in the same manner as in Example 11 using 4- [5- (4-benzyloxybut-1-ynyl) thiophen-2-yl] butan-1-ol. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 1.31 (3H,
s), 1.59-1.76 (4H, m), 1.88-2.08 (2H, m), 2.76 (2
H, t, J = 7.2 Hz), 2.79-2.91 (2H, m), 3.49 (2H, t, J
= 6.4 Hz), 3.51 (1H, d, J = 11.6 Hz), 3.60 (1H, d, J =
11.6 Hz), 4.48 (2H, s), 6.25 (2H, s), 6.58 (1H, d,
J = 3.6Hz), 6.64 (1H, d, J = 3.6 Hz), 7.23-7.38 (5H,
m) Infrared absorption spectrum ν _max cm ^-1 (KBr): 2935, 2862, 15
79, 1496, 1386, 1363,1195, 1104, 1077, 1012, 875,
866, 804, 737, 698, 569 Mass spectrum (FAB) m / z: 348 (M + H) ⁺ (free form) Example 65 (2R) -amino-2-methyl-4- {5- [3- (4
-Methylcyclohexyloxy) propynyl] thiophene
2- (2-yl) butan-1-ol maleate (Exemplified Compound No. 1-1050) The title compound was obtained in the same manner as in Example 1. Nuclear magnetic resonance spectrum (400MHz, CD ₃ OD): δ 0.89, 0.9
0 (Total 3H, d, J = 6.4 Hz), 1.31 (3H, s), 0.92-1.56, 1.7
0-2.12 (Total 11H, m), 2.81-2.96 (2H, m), 3.40-3.49,
3.73-3.79 (Total 1H, m), 3.52 (1H, d, J = 11.2 Hz), 3.61
(1H, d, J = 11.2Hz), 4.36, 4.39 (total 2H, s), 6.25 (2
H, s), 6.78 (1H, d, J = 3.6 Hz), 7.04 (1H, d, J = 3.6
Hz) Infrared absorption spectrum ν _max cm ^-1 (KBr): 2927, 2864, 22
19, 1579, 1508, 1386,1366, 1193, 1093, 1077, 876,
865, 807, 717, 568 Mass spectrum (FAB) m / z: 336 (M + H) ⁺ (free form) Example 66 (4R) -methyl-4- [2- (thiophen-2-yl) ethyl] Oxa
Zorijin 2-one (Compound No. 4-4) Example 66 (a) (2R)-t-butoxycarbonylamino -3-n-Hekisanoiruo
Xy-2- methyl-1-propanol 2-t-butoxycarbonylamino-2-methyl-1,3-propanediol 20.0 g (97.4 mmol) in diisopropyl ether 2
Suspended in 00 ml, n-hexanoic acid vinyl ester 16.3 ml
(0.10 mol) and lipase [Immobilized lipase from Ps
eudomonas sp. (TOYOBO; 0.67 U / mg)] and stirred vigorously at room temperature for 2 hours. After filtering the reaction solution, the filtrate was distilled off under reduced pressure. The obtained residue is subjected to silica gel column chromatography (elution solvent: hexane: ethyl acetate = 10:
1-2: 1) to give 25.0 g (85%) of the title compound
Was obtained as a colorless oil.

The obtained (2R) -t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanol was analyzed using an analytical optically active HPLC column (ChiralCel OF (Daicel), (0.46 cm × 25 cm), elution solvent: n-hexane: 2-
The optical purity was determined by propanol = 70: 30, flow rate; 0.5 ml / min).

The eluted first (8.2 minutes) was the 2S form and the later eluted (10.5 minutes) was the 2R form, and it was confirmed that the optical purity in this reaction was 85% ee. [α] ^D ₂₅ -8.5 (c 1.86, CHCl ₃ ) Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 4.86
(s, 1H), 4.25 (d, 1H, J = 11.2 Hz), 4.19 (d, 1H, J
= 11.2 Hz), 3.86 (brs, 1H), 3.70-3.55 (m, 2H), 2.3
6 (t, 2H, J = 7.4 Hz), 1.68-1.58 (m, 2H), 1.44 (s,
9H), 1.40-1.30 (m, 4H), 1.25 (s, 3H), 0.90 (t, 3H,
J = 7.0 Hz) Infrared absorption spectrum νmax cm ^-1 (Liquid Film): 3415,
3380, 2961, 2935, 2874, 1721, 1505, 1458, 1392, 1
368, 1293, 1248, 1168, 1076 Mass spectrum (FAB) m / z: 304 ((M + H) ⁺ ) Example 66 (b) (2R) -t-butoxycarbonylamino-3-n-hexanoylo
Xy-2-methyl-1-propanal 30.7 g of (2R) -t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanol obtained in Example 66 (a) (0.10 mol ) In 600 ml of methylene chloride,
4Å220 g of molecular sieve and 43.6 g (0.20 mol) of pyridinium chlorochromate were added under ice-cooling, followed by stirring at room temperature for 2 hours. The reaction solution was diluted with ether and filtered. The filtrate was evaporated under reduced pressure, and the residue was subjected to silica gel column chromatography (elution solvent: n-hexane: ethyl acetate =
10: 1-5: 1) to give 28.8 g of the title compound
(95%) as a colorless oil. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 9.45
(s, 1H), 5.26 (brs, 1H), 4.44 (d, 1H, J = 11.2 H
z), 4.32 (d, 1H, J = 11.2 Hz), 2.32 (t, 2H, J = 7.6
Hz), 1.70-1.55 (m, 2H), 1.45 (s, 9H), 1.38 (s, 3
H), 1.40-1.25 (m, 4H), 0.90 (t, 3H, J = 7.0 Hz) Infrared absorption spectrum νmax cm ^-1 (Liquid Film): 3367,
2961, 2935, 2874, 1742, 1707, 1509, 1458, 1392, 1
369, 1290, 1274, 1254, 1166, 1100, 1078 Mass spectrum (FAB) m / z: 302 ((M + H) ⁺ ) Example 66 (c) (2R) -t-butoxycarbonylamino-1-n -Hexanoylo
Xy-2-methyl-4- (thiophen-2-yl) -3-butene bromide 2-thienylmethyltriphenylphosphonium salt 67.
1 g (0.15 mol) is suspended in 750 ml of tetrahydrofuran,
17.2 g (0.15 mol) of potassium t-butoxide was added thereto,
The mixture was stirred at room temperature under a nitrogen atmosphere for 20 minutes. 23.0 g (76.4) of (2R) -t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanal obtained in Example 66 (b) dissolved in 250 ml of tetrahydrofuran was added to the reaction solution. mmo
l) was added dropwise under ice cooling, and after the completion of the dropwise addition, the mixture was stirred for 30 minutes under ice cooling. Thereafter, water was added to the reaction solution, and extracted with ethyl acetate.
The ethyl acetate layer was washed with saturated saline. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure.
The residue was purified by silica gel column chromatography (eluent: n-hexane: ethyl acetate = 20: 1) to give the title compound (27.8 g, 96%) as a colorless oil. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.32-
7.26, 7.16-7.14 (m, 1H in total), 7.04-7.01, 7.01-6.93
(m, 2H in total), 6.63 (d, 0.5 H, J = 16.0 Hz), 6.60 (d,
0.5 H, J = 13.6 Hz), 6.10 (d, 0.5 H, J = 16.0 Hz),
5.58 (d, 0.5 H, J = 13.6 Hz), 4.94, 4.93 (brs, total 1
H), 4.40-4.10 (m, 2H), 2.34 (t, 2H, J = 7.4 Hz), 1.
70-1.55 (m, 2H), 1.57, 1.50, 1.44 (s, 9H in total), 1.40-
1.25 (m, 7H), 0.88 (t, 3H, J = 7.0 Hz) Infrared absorption spectrum νmax cm ^-1 (Liquid Film): 3370,
2961, 2933, 1725, 1495, 1456, 1391, 1367, 1247, 1
167, 1109, 1100, 1072, 697 Mass spectrum (FAB) m / z: 381 (M ⁺ ) Example 66 (d) (4R) -methyl-4- [2- (thiophen-2-yl) ethenyl] oxo
Sazolidine-2-one (2R) -t-butoxycarbonylamino-1-n-hexanoyloxy-2-methyl-4- (thiophene) obtained in Example 66 (c)
40.5 g (0.11 mol) of 2--2-yl) -3-butene was dissolved in 150 ml of tetrahydrofuran and 150 ml of methanol, and 530 ml of a 1N aqueous solution of sodium hydroxide was added thereto under ice-cooling. Stirred at room temperature for 1 hour. After the reaction solution was concentrated under reduced pressure, water was added, and the mixture was extracted with methylene chloride. The methylene chloride layer was washed with saturated saline. After drying the methylene chloride layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain crude product 35.0.
g was obtained. This crude product was dissolved in 300 ml of tetrahydrofuran, 17.8 g (0.16 mol) of potassium t-butoxide was added under ice cooling, and the mixture was stirred under ice cooling for 10 minutes and at room temperature for 40 minutes. Water was added to the reaction solution, extracted with ethyl acetate, and the ethyl acetate layer was washed with saturated saline. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent; hexane: ethyl acetate = 3: 1 to 1: 1) to give the title compound 1
8.0 g (81%) were obtained as a white solid. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.34
(d, 0.5H, J = 5.1Hz), 7.19 (d, 0.5H, J = 5.0Hz), 7.0
7-6.91 (m, 2H), 6.74 (d, 0.5H, J = 16.0Hz), 6.59 (d,
0.5H, J = 12.5), 6.17 (brs, 1H), 6.06 (d, 0.5H, J = 1
6.0Hz), 5.65 (d, 0.5H, J = 12.5Hz), 4.41 (d, 0.5H, J
= 8.6Hz), 4.31-4.16 (m, 1.5H), 1.60 (s, 1.5H), 1.55
(s, 1.5H) Infrared absorption spectrum νmax cm ^-1 (KBr): 3275, 3110, 2
974, 1752, 1391, 1376, 1281, 1169, 1039, 960, 704 Mass spectrum (FAB) m / z: 209 (M ⁺ ) Example 66 (e) (4R) -methyl-4- [2- (thiophene) -2-yl) ethyl] oxa
Zolidin-2 -one 18.0 g of (4R) -methyl-4- [2- (thiophen-2-yl) ethenyl] oxazolidin-2-one obtained in Example 66 (d) (8
6.0 mmol) was dissolved in 150 ml of methanol, 4.5 g of 10% palladium-carbon was added, and the mixture was stirred at room temperature for 10 hours under a hydrogen atmosphere. The palladium-carbon in the reaction solution was filtered using a Kiriyama funnel thinly covered with silica gel, and the filtrate was distilled off under reduced pressure. The obtained solid was washed with diethyl ether and dried to give the title compound (16.5 g, 91%) as a white solid.

(4R) -Methyl-4- [2- (thiophene-2)
-Yl) ethyl] oxazolidin-2-one was analyzed using an optically active analytical HPLC column (ChiralCel OD-H (Daicel), (0.46 cm x
25cm), elution solvent: n-hexane: 2-propanol = 6
Optical purity was determined at 0:40, flow rate: 0.5 ml / min).

The eluted first (16.8 minutes) was the 2S form and the later eluted (17.6 minutes) was the 2R form, and it was confirmed that the optical purity in this reaction was 85% ee. [α] ^D ₂₅ +5.1 (c 2.4, CHCl ₃ ) Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 7.15
(d, 1H, J = 5.2 Hz), 6.93 (dd, 1H, J = 5.2, 3.6 H
z), 6.81 (d, 1H, J = 3.6 Hz), 5.39 (brs, 1H), 4.19
(d, 1H, J = 8.4 Hz), 4.08 (d, 1H, J = 8.4 Hz), 3.0
0-2.84 (m, 2H), 2.08-1.92 (m, 2H), 1.42 (s, 3H) Infrared absorption spectrum νmax cm ^-1 (KBr): 3283, 1770, 1
399, 1244, 1043, 941,846, 775, 706, 691 Mass spectrum (EI) m / z: 211 (M ⁺ ) (4R) -methyl-4- [2- (thiophen-2
-Yl) ethyl] oxazolidine-2-one in 11 g of ethyl acetate
After adding 25 ml and 5.0 ml of n-hexane and dissolving by heating,
It was left at room temperature for 2 hours. The precipitated white crystals were collected by filtration and dried to obtain 4.0 g of the title compound having an optical purity of 99% ee. [α] ^D ₂₅ +7.8 (c 2.0, CHCl ₃ ) Example 67 (4R) -Methyl -4- [2- (thiophen-2-yl) ethyl] oxa
Zorijin 2-one (Compound No. 4-4) Example 67 (a) (2R)-t-butoxycarbonylamino -1-n-Hekisanoiruo
Xy-2-methyl-4- (thiophen-2-yl) butane (2R) -t-butoxycarbonylamino-1-n-hexanoyloxy-2-methyl-4- obtained in Example 66 (c) (Thiophene
2-7.6) -2-butene (27.6 g, 72.4 mmol) in ethanol 450
The mixture was dissolved in ml, 10% palladium-carbon (14.0 g) was added, and the mixture was stirred at room temperature for 4 days under a hydrogen atmosphere. After filtering the palladium-carbon in the reaction solution through celite, the filtrate was distilled off under reduced pressure. The residue is subjected to silica gel column chromatography (elution solvent;
Hexane: ethyl acetate = 20: 1 to 10: 1) gave 22.1 g (80%) of the title compound as a colorless oil. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.02
(d, 1H, J = 5.2 Hz), 6.91 (dd, 1H, J = 5.2, 3.6 H
z), 6.80 (d, 1H, J = 3.6 Hz), 4.53 (brs, 1H), 4.26-
4.12 (m, 2H), 2.85 (t, 2H, J = 8.4 Hz), 2.34 (t, 2
H, J = 7.6 Hz), 2.26-2.16 (m, 1H), 2.01-1.90 (m, 1
H), 1.68-1.56 (m, 2H), 1.44 (s, 9H), 1.31 (s, 3H),
1.40-1.26 (m, 4H), 0.89 (t, 3H, J = 7.6Hz) Infrared absorption spectrum νmax cm ^-1 (Liquid Film): 3371,
2961, 2933, 2872, 2864, 1721, 1502, 1466, 1455, 1
392, 1367, 1246, 1168, 1074, 694, mass spectrum (FAB) m / z: 384 ((M + H) ⁺ ) Example 67 (b) (2R) -t-butoxycarbonylamino-2-methyl- 4- (Thioff
(En-2-yl) -1-butanol (2R) -t-butoxycarbonylamino-1-n-hexanoyloxy-2-methyl-4- (thiophene obtained in Example 67 (a)
22.0 g (57.4 mmol) of 2--2-yl) butane was dissolved in a mixture of 140 ml of tetrahydrofuran and 280 ml of methanol, and 280 ml of a 1N aqueous sodium hydroxide solution was added thereto under ice-cooling.
The mixture was stirred for 30 minutes under ice cooling and for 1 hour at room temperature. After the reaction solution was concentrated under reduced pressure, water was added, and the mixture was extracted with methylene chloride. The methylene chloride layer was washed with saturated saline. After the methylene chloride layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain 15.5 g (95%) of the title compound as a white solid. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ) δppm: 7.11
(d, 1H, J = 5.2 Hz), 6.92 (dd, 1H, J = 5.2, 3.6 H
z), 6.81 (d, 1H, J = 3.6 Hz), 4.64 (brs, 1H), 4.08
(brs, 1H), 3.74-3.60 (m, 2H), 2.98-2.76 (m, 2H),
2.20-2.10 (m, 1H), 2.03-1.90 (m, 1H), 1.44 (s, 9
H), 1.22 (s, 3H) Infrared absorption spectrum νmax cm ^-1 (KBr): 3279, 3250, 3
067, 2973, 2929, 2908,2857, 1679, 1552, 1367, 129
1, 1245, 1167, 1076, 1064, 1009, 861, 851, 701 Mass spectrum (FAB) m / z: 286 ((M + H) ⁺ ) Example 67 (c) (4R) -methyl-4- [ 2- (thiophen-2-yl) ethyl] oxa
Zolidin-2-one (2R) -t-butoxycarbonylamino-2-methyl-4- (thiophen-2-yl) -1-butanol 1 obtained in Example 67 (b)
5.4 g (53.9 mmol) in N, N-dimethylformamide 200 ml
, And 9.07 g (80.8 mmol) of potassium t-butoxide was added under ice cooling, and the mixture was stirred under ice cooling for 10 minutes and at room temperature for 40 minutes. Water was added to the reaction solution, extracted with ethyl acetate, and the ethyl acetate layer was washed with saturated saline. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: hexane: ethyl acetate = 3: 1 to 1: 1) to obtain 11.5 g (100%) of the title compound as a white solid. Various device data were consistent with those obtained in Example 1.

Example 68 (4R)-[2- (Benzo [b] thiophen-6-yl) ethyl] -4-methyl
Luoxazolidin-2-one (Exemplary Compound No .: 4-17) Example 68 (a) (2R) -t-butoxycarbonylamino-1-n-hexanoylo
Xy-2-methyl-4- (benzo [b] thiophen-6-yl) -3-bu
Synthesized in ten Example 66 (b) (2R) -t- butoxycarbonylamino -3-n-hexanoyloxy-2-methyl-1-propanal 28.2 g (93.6 mmol) and 6-bromo-triphenyl phosphonium 45.8 g (93.6 mmol) of ammonium benzo [b] thiophene was suspended in 700 ml of tetrahydrofuran, and 11.6 g (0.10 mol) of potassium t-butoxide was added thereto, followed by stirring at room temperature for 30 minutes. Thereafter, water was added to the reaction solution, extracted with ethyl acetate, and the ethyl acetate layer was washed with saturated saline. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: hexane: ethyl acetate = 10: 1) to give the title compound (28.0 g, 69%) as a colorless oil. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 7.82
(d, 1H, J = 9.7 Hz), 7.75 (d, 1H, J = 8.2 Hz), 7.4
4-7.39 (m, 1H), 7.32-7.26 (m, 2H), 6.74, 5.73 (d,
1H, J = 12.6Hz), 6.61, 6.34 (d, 1H, J = 16.2H
z), 4.87, 4.69 (br s, 1H in total), 4.34-4.16, (m, 2H),
2.37-2.32 (m, 2H), 1.67-1.15 (m, 20H), 0.91-0.84
(m, 3H). Infrared absorption spectrum νmax cm ^-1 (Liquid Film): 3440,
3373, 2961, 2932, 2872, 1724, 1597, 1498, 1457, 1
390, 1367, 1247, 1167, 1099, 1073. Mass spectrum (FAB) m / z: 431 (M ⁺ ) Example 68 (b) (2R) -t-butoxycarbonylamino-1-n-hexanoylo
Xy-2-methyl-4- (benzo [b] thiophen-6-yl) butane (2R) -t-butoxycarbonylamino-1-n-hexanoyloxy-2- obtained in Example 68 (a) Methyl-4- (benzo [b]
28.0 g (64.9 mmol) of thiophen-6-yl) -3-butene were dissolved in 700 ml of methanol, and 10% palladium-carbon was 14.0 g.
Was added and stirred at room temperature for 6 days under a hydrogen atmosphere. After filtering the palladium-carbon in the reaction solution through celite, the filtrate was distilled off under reduced pressure. Silica gel column chromatography of the residue
(Eluent solvent: hexane: ethyl acetate = 15: 1 to 10:
Purification according to 1) gave 24.30 g (87%) of the title compound as a colorless oil. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 7.73
(d, 1H, J = 8.2 Hz), 7.69 (s, 1H), 7.36 (d, 1H, J
= 5.2 Hz), 7.28 (d, 1H, J = 5.6 Hz), 7.19 (d, 1H,
J = 8.1 Hz), 4.56 (br s, 1H), 4.28 (d, 1H, J = 11.
0 Hz), 4.14 (d, 1H, J = 11.0 Hz), 2.73 (t, 2H, J =
8.7 Hz), 2.34 (t, 2H, J = 7.5 Hz), 1.68-1.61 (m,
2H), 1.45 (s, 9H), 1.41-1.38 (m, 8H), 0.89 (t, 3H,
J = 6.7Hz). Infrared absorption spectrum νmax cm ^-1 (Liquid Film): 3371,
2960, 2933, 2870, 1720, 1604, 1501, 1466, 1392, 1
367, 1248, 1167, 1074. Mass spectrum (FAB) m / z: 456 ((M + Na) ⁺ ) Example 68 (c) (4R)-[2- (benzo [b] thiophen-6-yl) Ethyl] -4-methyl
Luoxazolidin-2-one (2R) -t-butoxycarbonylamino-1-n-hexanoyloxy-2-methyl-4- (benzo [b] obtained in Example 68 (b)
Thiophen-6-yl) butane (24.3 g, 56.0 mmol) was dissolved in tetrahydrofuran (220 ml) and methanol (110 ml). Stirred at room temperature for 2 hours.
After the reaction solution was concentrated under reduced pressure, water was added, and the mixture was extracted with methylene chloride. The methylene chloride layer was washed with saturated saline. After the methylene chloride layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain 18.8 g (100%) of a crude product. The obtained crude product was dissolved in 380 ml of dimethylformamide, and 9.43 g (84.1 mmol) of potassium t-butoxide was added under ice cooling.
And stirred at room temperature for 1 hour. Water was added to the reaction solution, extracted with ethyl acetate, and the ethyl acetate layer was washed with saturated saline.
After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (elution solvent: hexane: ethyl acetate = 3: 2-2:
Purification according to 1) gave 13.8 g (94%) of the title compound as a white solid.

The obtained (4R)-[2- (benzo [b] thiophene-6
-Yl) ethyl] -4-methyloxazolidine-2-one is an optically active HPLC column for analysis (ChiralCel AD (Daicel),
(0.46 cm × 25 cm), elution solvent; n-hexane: 2-propanol = 70: 30, flow rate: 0.5 ml / min), and the optical purity was determined.

The eluted first (15.9 minutes) was the 4S form and the later eluted (17.6 minutes) was the 4R form, and it was confirmed that the optical purity in this reaction was 80% ee. [α] ^D ₂₄ +2.3 (c 0.6, CHCl ₃ ) Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 7.73
(d, 1H, J = 8.2 Hz), 7.68 (s, 1H), 7.38 (d, 1H, J
= 5.7 Hz), 7.29 (d, 1H, J = 13.0 Hz), 7.18 (d, 1H,
J = 13.6 Hz), 5.91 (br s, 1H), 4.21 (d, 1H, J = 8.
7 Hz), 4.09 (d, 1H, J = 8.7 Hz), 2.84-2.76 (m, 2H),
1.97 (t, J = 8.5 Hz, 3H). Infrared absorption spectrum νmax cm ^-1 (KBr): 3292, 2970, 2
930, 1749, 1722, 1601,1479, 1461, 1397, 1277, 104
5. Mass spectrum (EI) m / z: 261 (M ⁺ ) Example 69 (2R) -t-butoxycarbonylamino-3-n-f
Xanoyloxy-2-methyl-1-propanol 2-t-butoxycarbonylamino-2-methyl-1,
200 mg (0.97 mmol) of 3-propanediol
Was dissolved in 2 ml of diisopropyl ether, and 0.16 ml (1.02 mmol) of n-hexanoic acid vinyl ester and lipase [Immobilized lipase from Pseudomo
nas sp. (TOYOBO; 0.67 U / mg)] 20 m
g was added and stirred at room temperature for 4 hours.

After the insoluble matter of the reaction mixture was removed by filtration, the residue was concentrated under reduced pressure, and the residue was subjected to flash silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 1).
0: 1 to 7: 3) to give 258 mg (87%) of the title compound as a colorless oil.

The obtained (2R) -t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-
1-propanol was analyzed using an analytical optically active HPLC column (ChiralCel OF, Daicel, 0.46 cm (x25c
m, elution solvent: hexane: 2-propanol = 70: 3
0; flow rate: 0.5 ml / min).

The first elution (8.2 minutes) was 2S
The body and the substance eluted later (10.5 minutes) were the 2R form. It was confirmed that the optical purity in this reaction was 89% ee.

The absolute configuration is described in the literature (Tetrahedron Asymme) which can be easily synthesized from this compound.
try 10 (1999) 4653-4661) Specific rotation of a known compound, (2R) -t-butoxycarbonylamino-2-methyl-3-buten-1-ol, produced in Reference Example 1 (a) Was determined by comparison. Nuclear magnetic resonance spectrum (400MHz, CD ₃ CL ₃ ) δ ppm: 4.89 (1H, br.s),
4.24 (1H, d, J = 11.2Hz), 4.19 (1H, d, J = 11.2Hz), 3.66-3.5
4 (2H, m), 2.36 (2H, t, J = 7.4Hz), 1.69-1.57 (2H, m), 1.44
(9H, s), 1.39-1.22 (4H, m), 1.25 (3H, s), 0.90 (3H, t, J =
6.6 Hz) Infrared absorption spectrum ν _max cm ^-1 (CHCL ₃ ): 3411
3380,2961,2934,1722,1504,1459,1392,1368,1292,1248,
1168,1077,1015 Optical rotation [α] ²⁴ _D : -1.1 ° (c = 0.81, methanol) Example 70 (2R) -t-butoxycarbonylamino-3-n-f
Xanoyloxy-2-ethyl-1-propanol 2-t-butoxycarbonylamino-2-ethyl-1,
200 mg (0.91 mmol) of 3-propanediol
In the same manner as in Example 69, 252 mg (87%) of the title compound was obtained as a colorless oil.

The obtained (2R) -t-butoxycarbonylamino-3-n-hexanoyloxy-2-ethyl-
1-propanol was analyzed using an analytical optically active HPLC column (ChiralCel OF, Daicel, 0.46 cm (x25c
m, elution solvent: hexane: 2-propanol = 70: 3
0; flow rate: 0.5 ml / min).

The eluted first (8.5 minutes) was 2S
The body and the substance eluted later (10.7 minutes) were the 2R form. It was confirmed that the optical purity in this reaction was 95% ee.

The absolute configuration can be easily synthesized from this compound (Helvetica Chimica).
Acta 69 (1986) 1365-1377) A known compound, (+)-(R) -α-ethyl-, prepared in Reference Example 5 (f).
The specific rotation of α-vinylglycine was determined by comparison. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 4.78 (1H, b
rs), 4.28 (1H, d, J = 11.1Hz), 4.13 (1H, d, J = 11.1Hz), 3.
72-3.57 (2H, m), 2.35 (2H, t, J = 7.6Hz), 1.83-1.54 (4H, m
m), 1.44 (9H, s), 1.38-1.24 (4H, m), 0.95-0.86 (6H, m) Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3371,2966,293
5,1722,1503,1460,1368,1249,1168,1086,1028,866,781 Optical rotation [α] ²⁴ _D : -2.4 ° (c = 0.72, methanol) Using the compound synthesized in Example 69 or Example 70 Known useful compound, (-)-(R) -α-methyl-
α-vinylglycine (Reference Example 1), (+)-(S) -α
-Methyl-α-ethynylglycine (Reference Example 2) and (+)-(R) -α-ethyl-α-vinylglycine (Reference Example 3).

Reference Example 1 (-)-(R) -α-methyl-α-vinylglycine Reference Example 1 (a) (2R) -t-butoxycarbonylamino-2-methyl
-3-buten-1-ol (2R) -t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-prepared as in Example 69
To a solution of 1.5 g (4.9 mmol) of 1-propanol in methylene chloride (18 ml) was added molecular sieves 4A.
(10.5 g) and stirred at room temperature for 10 minutes, then 2.1 g (9.8 mmol) of pyridinium chlorochromate was added and stirred for 1 hour.

After diethyl ether was added to the reaction solution, insolubles were removed by filtration using a silica gel short column (eluent: diethyl ether). The organic solvent was distilled off under reduced pressure, and 1.5 g of the obtained residue was used in the next reaction.

To a suspension of 4.5 g (12.5 mmol) of methyltriphenylphosphonium bromide (10 ml) in tetrahydrofuran was added 1.3 g (11.5 mmol) of potassium t-butoxide at 0 ° C., followed by stirring for 1 hour. .

To this reaction solution, a tetrahydrofuran solution (10 ml) of the residue obtained in the previous reaction was added dropwise.

This reaction solution was stirred at 0 ° C. for 30 minutes, distilled water was added, and the mixture was extracted with ethyl acetate. This is distilled water,
The extract was washed with saturated saline in this order, and dried over magnesium sulfate. After the solvent was distilled off, insolubles were removed with a silica gel short column (eluent; hexane: ethyl acetate = 10: 1).

After concentrating the solvent, 1.2 g of the obtained residue was converted into a methanol solution (20 ml), to which was added a 1N aqueous sodium hydroxide solution (20 ml), and the mixture was stirred at room temperature for 30 minutes. After diethyl ether was added to the reaction solution, the reaction solution was washed with distilled water and saturated saline in this order, and dried over magnesium sulfate.

After the solvent was distilled off, the residue was purified by preparative thin-layer chromatography (eluent; hexane: ethyl acetate = 1: 1) to obtain 180 mg (0.894 mmol, yield 18%) of the title compound. . Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 5.89 (1H, d
dd, J = 11.0,6.6,1.5Hz), 5.21 (1H, d, J = 1.5Hz), 5.17 (1H,
d, J = 6.6Hz), 4.84 (1H, br.s), 3.76 (1H, br.s), 3.62 (2H,
m), 1.44 (9H, s), 1.32 (3H, s) Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3418,3348,297
9,1692,1499,1455,1393,1368,1283,1253,1170,1074,918 Optical rotation [α] ²⁴ _D : + 10.4 ° (c = 0.51, methanol) Reference Example 1 (b) (2R) -t -Butoxycarbonylamino-2-methyl
(2R) -t-butoxycarbonylamino-2-methyl-3-buten-1-ol 18 obtained in -3-butenal Reference Example 1 (a)
0 mg (0.894 mmol) in methylene chloride 5.0 m
, and under ice-cooling, molecular sieves 4A 2.0
g, 386 mg of pyridinium chlorochromate (1.79
Mmol) and stirred at room temperature for 1 hour. Ether was added to the reaction solution, the insoluble matter of the reaction mixture was filtered off, and the residue was concentrated under reduced pressure.

The residue was purified by flash silica gel column chromatography (elution solvent: n-hexane: ethyl acetate =
Purification was performed at 10: 1) to give 160 mg (90%) of the title compound as a colorless oil. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 9.26 (1H, s), 5.83 (1H, dd, J = 17.5, 10.6 Hz), 5.35 (1H, d, J
= 10.6Hz), 5.32 (1H, d, J = 17.5Hz), 5.22 (1H, br.s), 1.48
(3H, s), 1.45 (9H, s) Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3350,2980,173
7,1707,1505,1455,1369,1279,1256,1168,1069,925,867 Reference Example 1 (c) (2R) -t-butoxycarbonylamino-2-methyl
160 mg of (2R) -t-butoxycarbonylamino-2-methyl-3-butenal obtained in -3-butenoic acid reference example 1 (b)
(0.803 mmol) in 8.0 m of t-butanol
l, dissolved in 2.0 ml of water, 0.38 ml (3.61 mmol) of 2-methyl-2-butene, 96 mg (0.803 mmol) of sodium dihydrogen phosphate dihydrate, 254 mg of sodium chlorite ( (2.81 mmol) and stirred at room temperature for 1 hour.

[0476] Ethyl acetate was added to the reaction solution, and the ethyl acetate layer was washed with saturated saline. After the ethyl acetate layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure.

The residue was subjected to flash silica gel column chromatography (elution solvent: n-hexane: ethyl acetate =
20: 1 to 1: 1) to give 130 mg (75%) of the title compound as a colorless oil. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 5.07 (1H, b
rs), 5.68 (1H, br.s), 5.12 (1H, d, J = 17.4Hz), 5.05 (1H, br
d, J = 10.6Hz), 1.48 (3H, s), 1.40 (9H, s) Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3394,2980,169
1,1602,1483,1455,1368,1253,1172,1066,756 Reference Example 1 (d) (-)-(R) -α-methyl-α- vinylglycine hydrochloride
120 mg of (2R) -t-butoxycarbonylamino-2-methyl-3-butenoic acid obtained in Salt Reference Example 1 (c)
(0.557 mmol) was dissolved in 1.5 ml of ethanol, 1.5 ml of 4N hydrochloric acid in dioxane was added, and the mixture was stirred at room temperature for 18 hours.

The reaction solution was concentrated under reduced pressure, washed with ether,
Drying afforded 72 mg (85%) as a white solid. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 6.07 (1H, d
d, J = 17.6,11.0Hz), 5.48 (1H, d, J = 11.1Hz), 5.47 (1H, d, J
= 17.6Hz), 1.66 (3H, s) Infrared absorption spectrum ν _max (KBr) cm ^-1 : 3349,3029,1751,
1524,1200,954 Optical rotation [α] ²⁵ _D : -18.7 ° (c = 0.70, H ₂ O) Reference Example 1 (e) (−)-(R) -α-methyl-α-vinylglycine Reference Example 1 (-)-(R) -α-methyl- obtained in (d)
60 mg (0.40 milligrams) of α-vinylglycine hydrochloride was dissolved in 1.5 ml of ethanol, 1.5 ml of propylene oxide was added, and the mixture was heated under reflux for 2 hours. The white solid in the reaction solution was filtered to obtain 32 mg (70%) of the title compound as a white solid. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 6.17 (1H, d
d, J = 17.2,10.6Hz), 5.56 (1H, d, J = 10.6Hz), 5.54 (1H, d, J
= 17.2Hz), 1.43 (3H, s) Infrared absorption spectrum ν _max (KBr) cm ^-1 : 3600-2500,1605,
1535,1455,1415,1385,1360,1280,1235,1150,1000,940 Optical rotation [α] ²⁵ _D : -27.6 ° (c = 0.62, H ₂ O) Reference example 2 (+)-(S)- α-Methyl-α-ethynylglycine Reference Example 2 (a) 3-t-butoxycarbonyl-2,2-dimethyl- (4
R) -n-Hexanoyloxymethyl-4-methyloxy
Sazolidine (2R) -t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl- obtained in Example 69.
1-Propanol (10.1 g, 33.3 mmol) was dissolved in methylene chloride (152 ml), and acetone dimethyl acetal (16.4 ml, 133 mmol) and p-toluenesulfonic acid (172 mg, 1.00 mmol) were added. Stirred.

The reaction solution was concentrated, and the residue was purified by flash silica gel column chromatography (eluent: n-hexane: ethyl acetate = 10: 1) to give the title compound as a colorless oil (5.72 g, 50%). )Obtained. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 4.29 (1H,
s), 4.18 (1H, s), 3.99 (1H, m), 3.64 (1H, m), 2.28-2.34
(2H, m), 1.26-1.25 (24H, m), 0.89 (3H, t) Optical rotation [α] ²⁵ _D : + 17.2 ° (c = 1.50, CHCl ₃ ) Reference example 2 (b) 3-t- Butoxycarbonyl-2,2-dimethyl- (4
S) -Hydroxymethyl-4-methyloxazolidine 3-t-butoxycarbonyl- obtained in Reference Example 2 (a)
13.7 g of 2,2-dimethyl- (4R) -n-hexanoyloxymethyl-4-methyloxazolidine (39.
9 mmol) in 200 ml of methylene chloride and -7
At 8 ° C., diisobutylaluminum hydride (1.0 M
Hexane solution (99 ml, 99.7 mmol) was added dropwise.

After stirring at -78 ° C for 30 minutes, the temperature was returned to room temperature.
10m% sodium-potassium tartrate aqueous solution 200m
and stirred vigorously for 30 minutes.

The reaction solution was extracted with diethyl ether, the ether layer was dried over anhydrous sodium sulfate, the residue was concentrated under reduced pressure, and the residue was flash silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 5: 2).
And purified the title compound as white crystals in 10.5.
g (100%). Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 4.49 (1H, b
rs), 3.55-3.71 (4H, m), 1.56 (3H, s), 1.49 (12H, s), 1.4
2 (3H, s) Optical rotation [α] ²⁵ _D : −1.67 ° (c = 1.45, CHCl ₃ ). Reference Example 2 (c) 3-t-butoxycarbonyl-2,2-dimethyl- (4
R) -Formyl-4-methyloxazolidine 3-t-butoxycarbonyl- obtained in Reference Example 2 (b)
2,2-dimethyl- (4S) -hydroxymethyl-4-
9.79 g (39.9 mmol) of methyl oxazolidine
Was dissolved in 150 ml of methylene chloride, 13.0 g (59.8 mmol) of pyridinium chlorochromate and 65.0 g of molecular sieves 4A were added under ice cooling, and the mixture was stirred at room temperature for 1 hour.

After diethyl ether was added to the reaction solution, the reaction solution was filtered using a silica gel column, and the filtrate was concentrated under reduced pressure. Flash silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 8:
Purification was performed in 1) to give the title compound as white crystals.
07 g (88%) were obtained. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 9.40-9.48
(1H, s), 3.91 (1H, d, J = 9.2Hz), 3.67 (1H, d, J = 9.2Hz), 1.
14-1.66 (18H, m) Optical rotation [α] ²⁵ _D + 20.6 ° (c = 1.25, CHCl ₃ ) Reference Example 2 (d) 3-t-butoxycarbonyl-2,2-dimethyl- (4
S)-(2,2-Dibromo) ethenyl-4-methyloxy
Sazorijin dissolved triphenylphosphine 17.3g of (65.8 mmol) in methylene chloride 25 ml, under ice-cooling, methylene chloride, carbon tetrabromide 10.9 g (32.9 mmol) 1
A solution dissolved in 5 ml was added dropwise, and the mixture was stirred under ice cooling for 5 minutes. 4.00 g (16.4 mm) of 3-t-butoxycarbonyl-2,2-dimethyl- (4S) -formyl-4-methyloxazolidine obtained in Reference Example 2 (c) was added to the reaction solution.
ol) in 40 ml of methylene chloride was added, and the mixture was stirred at room temperature for 14 hours. After the insoluble matter of the reaction mixture was removed by filtration, the residue was concentrated under reduced pressure, and 4.70 g of the unpurified title compound was obtained as a colorless oil. (71.2%).

Reference Example 2 (e) 3-tert-butoxycarbonyl-2,2-dimethyl- (4
S) -Ethynyl-4-methyloxazolidine 3-t-butoxycarbonyl- obtained in Reference Example 2 (d)
4.70 g of 2,2-dimethyl- (4S)-(2,2-dibromo) ethenyl-4-methyloxazolidine (11.
8 mmol) was dissolved in 94 ml of tetrahydrofuran, and stirred at -78 ° C with n-butyllithium (1.6).
N hexane solution) was added dropwise, and the mixture was stirred at -78 ° C for 3.5 hours.

The reaction solution was added with a saturated aqueous solution of ammonium chloride 10
0 ml was added and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, the residue was concentrated under reduced pressure, and the residue was purified by flash silica gel column chromatography (eluent: n-hexane: ethyl acetate = 15: 1) to give the title compound as white crystals 2.21 g (7
8%). Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 4.13 (1H,
d, J = 8.4Hz), 3.84 (1H, d, J = 8.4Hz), 2.32 (1H, s), 1.49-
1.69 (18H, m) Optical rotation [α] ²⁵ _D : + 65.6 ° (c = 1.10, CHCl ₃ ) Reference Example 2 (f) (2S) -amino-2-methyl-3-butyn-1-o
Obtained in Le Reference Example 2 (e), 3-t- butoxycarbonyl -
To 350 mg (1.46 mmol) of 2,2-dimethyl- (4S) -ethynyl-4-methyloxazolidine was added hydrochloric acid 1
0 ml was added and the mixture was stirred at room temperature for 2 hours.
mg.

Reference Example 2 (g) (2S) -tert-butoxycarbonylamino-2-methyl
3 obtained in butyn-1-ol in Reference Example 2 (f), (2S) - amino-2-methyl-3-butyn-1-ol 127 mg (1.28 ml)
Was dissolved in 1 ml of water and 5 ml of tetrahydrofuran, and 380 mg of di-t-butyl carbonate (1.74)
Mmol) and 385 mg of anhydrous sodium carbonate (3.6
3 mmol) and stirred at room temperature for 14 hours.

The reaction solution was saturated aqueous ammonium chloride solution (6 m).
The mixture was extracted with ethyl acetate, the ethyl acetate layer was dried over anhydrous sodium sulfate, and the residue was concentrated under reduced pressure.

The residue was subjected to flash silica gel column chromatography (elution solvent: n-hexane: ethyl acetate =
Purification was performed in 1: 1) to give 154 mg (53%) of the title compound as white crystals. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 5.00 (1H, b
rs), 3.78 (1H, dd, J = 6.0and 11.2Hz), 3.67 (1H, dd, J = 7.
9 and 11.2Hz), 3.20 (1H, br.s), 2.40 (1H, s), 1.55 (3H,
s), 1.46 (9H, s) Optical rotation [α] ²⁵ _D : + 1.89 ° (c = 0.70, CHCl ₃ ) Reference Example 2 (h) (2S) -t-butoxycarbonylamino-2-methyl
(2S) -tert-butoxycarbonylamino-2-methyl-3-butyn-1-ol obtained in Reference Example 2 (g) -3-butyric acid .
20 g (6.02 mmol) was dissolved in 30 ml of acetone, and 3.48 ml (9.03 of Jones reagent) was dissolved under ice-cooling.
Mmol), and the mixture was stirred under ice cooling for 2 hours. Further, 3.48 ml (9.03 mmol) of Jones reagent was added, and the mixture was stirred at room temperature for 14 hours.

[0488] To the reaction solution, 5 ml of 2-propanol and 30 ml of water were added, and the mixture was extracted with ethyl acetate. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the residue was concentrated under reduced pressure to obtain 1.38 g of an unpurified title compound as a yellow oily substance.

Reference Example 2 (i) (+)-(S) -α-methyl-α-ethynylglycine salt
Obtained in salt Reference Example 2 (h), (2S) -t- butoxycarbonylamino-2-methyl-3-butyn acid 1.38g
(6.02 mmol) was dissolved in 20 ml of tetrahydrofuran, 10 ml of hydrochloric acid was added, and the mixture was stirred at room temperature for 5 hours. The reaction solution was concentrated under reduced pressure, and water (20 ml) and ethyl acetate (1) were added.
0 ml was added, and the water tank was concentrated under reduced pressure to obtain 0.24 g (27%) of the crude title compound as yellow crystals.

Reference Example 2 (j) (+)-(S) -α-methyl-α-ethynylglycine (+)-(S) -α-methyl- obtained in Reference Example 2 (i).
9 ml of ethanol and 3 ml of propylene oxide were added to 0.24 g (6.02 mmol) of α-ethynylglycine hydrochloride, and the mixture was heated under reflux for 2 hours. The reaction was filtered and the solid was washed with ether to give 108 mg (60%) of the title compound as white crystals. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 3.06 (1H,
s), 1.77 (3H, s) Optical rotation [α] ²⁵ _D : + 41.7 ° (c = 0.96, H ₂ O) Reference Example 3 (+)-(R) -α-ethyl-α-vinylglycine Reference Example 3 (a) (2S) -t-butoxycarbonylamino-2-ethyl
-3-n-Hexanoyloxy-1-propanal (2R) -tert-butoxycarbonylamino-3-n-hexanoyloxy-2-ethyl- obtained in Example 70.
3 g (9.45 mmol) of 1-propanol was dissolved in 60 ml of methylene chloride, and the mixture was dissolved in molecular sieves 4 under ice-cooling.
A20 g, pyridinium chlorochromate 4.07 g (1
8.9 mmol) and stirred at room temperature for 1 hour. Ether was added to the reaction solution, the insoluble matter of the reaction mixture was filtered off, and the residue was concentrated under reduced pressure.

The residue was purified by flash silica gel column chromatography (elution solvent: n-hexane: ethyl acetate =
Purification was performed at 10: 1) to give 2.79 g (94%) of the title compound as a colorless oil. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 9.34 (1H,
s), 5.29 (1H, br.s), 4.60 (1H, d, J = 11.5Hz), 4.40 (1H, br.s)
d, J = 11.5Hz), 2.28 (2H, t, J = 7.5Hz), 2.05-2.20 (1H, m),
1.70-1.80 (1H, m), 1.55-1.65 (2H, m), 1.45 (9H, s), 1.25
-1.40 (4H, m), 0.90 (3H, t, J = 7.0Hz), 0.81 (3H, t, J = 7.5H
z) Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3418,2979,293
4,2873,1737,1710,1496,1369,1251,1160 Mass spectrum (FAB) m / z: 316 ((M + H) ⁺ ) Reference example 3 (b) (2R) -t-butoxycarbonylamino-2 -Ethyl
7.90 g of -3-buten-1-ol-n-hexanoic acid ester methyltriphenylphosphonium bromide
(22.0 mmol) was suspended in 25 ml of tetrahydrofuran, and 2.28 g of potassium t-butoxide was added under ice-cooling.
(20.3 mmol), and the mixture was stirred under a nitrogen atmosphere for 1 hour.

Thereafter, (2S) obtained in Reference Example 3 (a) was obtained.
-T-butoxycarbonylamino-2-ethyl-3-n
-Hexanoyloxy-1-propanal 2.79 g
(8.85 mmol) was dissolved in 25 ml of tetrahydrofuran, added dropwise to the reaction solution under ice cooling, and stirred for 15 minutes.

[0493] Water was added to the reaction solution, and the mixture was extracted with ethyl acetate.
After washing the ethyl acetate layer with saturated saline, the ethyl acetate layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.

The residue was purified by flash silica gel column chromatography (elution solvent: n-hexane: ethyl acetate =
Purification was carried out at 40: 1 to 20: 1) to give 1.30 g (47%) of the title compound as a colorless oil. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 5.78 (1H, d
d, J = 17.6,11.0Hz), 5.22 (1H, d, J = 11.0Hz), 5.12 (1H, d, J
= 17.6Hz), 4.62 (1H, br.s), 4.29 (2H, s), 2.31 (2H, t, J =
7.5Hz), 1.83-1.95 (1H, m), 1.55-1.75 (3H, m), 1.44 (9H,
s), 1.25-1.35 (4H, m), 0.83-0.93 (6H, m) Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3448,2972,293
4,2873,1721,1494,1368,1249,1163 Mass spectrum (FAB) m / z: 314 ((M + H) ⁺ ) Reference example 3 (c) (2R) -t-butoxycarbonylamino-2-ethyl
-3-buten-1-ol (2R) -tert-butoxycarbonylamino-2-ethyl-3-buten-1-ol-n obtained in Reference Example 3 (b)
1.30 g (4.15 mmol) of hexanoic acid ester was dissolved in 20 ml of methanol, 40 ml of 1N sodium hydroxide was added under ice cooling, and the mixture was stirred at room temperature for 2 hours.

Water was added to the reaction solution, and the mixture was extracted with diethyl ether. The ether layer was washed with saturated saline, and the ether layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.

The residue was subjected to flash silica gel column chromatography (elution solvent: n-hexane: ethyl acetate =
9: 1 to 4: 1) to give 0.85 g (95%) of the title compound as a white solid. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 5.77 (1H, d
d, J = 17.0,10.7Hz), 5.25 (1H, d, J = 10.7Hz), 5.16 (1H, d, J
= 17.0Hz), 4.77 (1H, br.s), 4.10 (1H, br.s), 3.65-3.75
(2H, m), 1.58-1.83 (2H, m), 1.45 (9H, s), 0.87 (3H, t, J =
7.5Hz) Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3348,3275,298
7,2969,2935,1685,1541,1277,1170,1053 Mass spectrum (FAB) m / z: 216 ((M + H) ⁺ ) Optical rotation [α] ²⁴ _D : + 2.8 ° (c = 1.03, methanol Reference Example 3 (d) (2R) -t-butoxycarbonylamino-2-ethyl
3-butenal Reference Example was obtained in 3 (c), (2R) -t- butoxycarbonylamino-2-ethyl-3-buten-1-ol 0.
Using 79 g (3.67 mmol) of 0.63 g (80%) of the title compound as a white solid in the same manner as in Reference Example 3 (a).
%). Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 9.24 (1H,
s), 5.83 (1H, dd, J = 17.5,10.7Hz), 5.39 (1H, d, J = 10.7Hz),
5.31 (1H, d, J = 17.5Hz), 5.29 (1H, br.s), 1.85-2.15 (2H,
m), 1.57 (9H, s), 0.85 (3H, t, J = 7.5Hz) Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3443,3416,298
0,1712,1489,1369,1249,1162 Mass spectrum (FAB) m / z: 2
14 ((M + H) ⁺ ) Optical rotation [α] ²⁵ _D : + 69 ° (c = 1.00, methanol) Reference Example 3 (e) (2R) -t-butoxycarbonylamino-2-ethyl
0.60 g of (2R) -t-butoxycarbonylamino-2-ethyl-3-butenal obtained in -3-butenoic acid reference example 3 (d)
(2.81 mmol) in 8 ml of t-butanol and water 2
Dissolve in 2-ml 2-methyl-2-butene 1.34ml
(12.7 mmol), 0.44 g (2.81 mmol) of sodium dihydrogen phosphate dihydrate, and 0.89 g (9.85 mmol) of sodium chlorite were added, and the mixture was stirred at room temperature for 1 hour.

[0497] Ethyl acetate was added to the reaction solution, and the ethyl acetate layer was washed with saturated saline. After the ethyl acetate layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure.

The residue was purified by flash silica gel column chromatography (eluent: n-hexane: ethyl acetate = 20: 1 to 1: 1) to obtain 0.42 g (65%) of the title compound as a white solid. Was. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δppm: 6.05 (1H, d
d, J = 17.3,10.7Hz), 5.25-5.35 (3H, m), 1.95-2.20 (2H,
m), 1.44 (9H, s), 0.90 (3H, t, J = 7.4Hz) Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3430,2981,171
3,1493,1369,1252,1166 Mass spectrum (FAB) m / z: 230 ((M
+ H) ⁺ ) Optical rotation [α] ²⁵ _D : + 19.4 ° (c = 1.00, methanol) Reference Example 3 (f) (+)-(R) -α-ethyl-α-vinylglycine Reference Example 3 (e) 379 mg of (2R) -t-butoxycarbonylamino-2-ethyl-3-butenoic acid obtained in
(1.65 mmol) in 2 ml of ethanol,
2 ml of 4N dioxane hydrochloride solution was added, and the mixture was stirred at room temperature for 18 hours.

The reaction solution was concentrated under reduced pressure, washed with ether,
Dried. Dissolve the obtained white solid in ethanol 6ml
And add 2 ml of propylene oxide and heat for 2 hours.
Flow and label the white solid in the reaction solution by filtration.
83 mg of the compound was obtained as a white solid. The filtrate is concentrated under reduced pressure
After that, the residue is dissolved in water, and Bondelut HF
(C ₁₈) And concentrated under reduced pressure to give the title compound 6
1 mg was obtained (144 mg in total, 75% yield). Nuclear magnetic resonance spectrum (400 MHz, CDCl_Three) δppm: 6.08 (1H, d
d, J = 17.7,11.1Hz), 5.41 (1H, d, J = 11.1Hz), 5.34 (1H, d, J
= 17.7Hz), 1.82-2.12 (2H, m), 0.95 (3H, t, J = 7.6Hz) Infrared absorption spectrum ν_max(KBr) cm^-1: 3200-2400,1623,
1605,1511,1369 Mass spectrum (FAB) m / z: 130 ((M + H)⁺) Optical rotation [α]^{twenty five} _D： + 20.6 ° (c = 1.00, H_TwoO) Reference example 45- (4-fluorophenyl) pent-1-yne 2.11 g (48.4 mmol) of sodium hydride in anhydrous tetra
Suspend in 60 ml of hydrofuran, and add
10.84 g of phosphonoacetic acid ethyl ester (48.4 mmol
) Was added dropwise and stirred for 10 minutes. Then 4-fluorobe
5.00 g (40.3 mmol) of aldehyde
A solution dissolved in 60 ml of drofuran was added dropwise at the same temperature.
After the reaction solution was stirred for 3 hours, it was poured into 150 ml of ice water and acetic acid was added.
Extracted with ethyl. Dry the organic layer over magnesium sulfate
Then, the solvent is distilled off under reduced pressure, and the residue is flash silica gel
Ram chromatography (elution solvent: hexane: acetic acid
Purification was carried out using chill = 10: 1 to 3: 1).
6.69 g (86%) of ethyl cinnamate as a colorless oil
%)Obtained.

6.52 g (33.6 mmol) of this ester was dissolved in 100 ml of ethyl acetate and 5% rhodium / alumina 1.
30 g was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 8 hours.
The reaction mixture was filtered through celite, the filtrate was concentrated under reduced pressure, and the residue was dissolved in 30 ml of anhydrous tetrahydrofuran. The solution was cooled on ice with 1.26 g of lithium aluminum hydride (33.2 g).
Mmol) was added dropwise to a suspension in 60 ml of anhydrous tetrahydrofuran. After stirring the reaction mixture at the same temperature for 30 minutes, a saturated aqueous solution of sodium sulfate was added, and the mixture was further added at room temperature for 10 minutes.
Stirred for minutes. The mixture was filtered through celite, and the filtrate was extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by flash silica gel column chromatography (elution solvent: hexane: ethyl acetate = 5: 1 to 1: 1) to give 4-fluorophenylpropan-1-ol as a colorless oil. 4.86 g (95%).

The obtained 4-fluorophenylpropane-
4.83 g (31.3 mmol) of 1-ol in methylene chloride 50 m
of ethyl triethylamine under ice-cooling.
7.0 mmol) and 2.91 ml of methanesulfonyl chloride
(37.6 mmol), and the mixture was stirred under a nitrogen atmosphere for 30 minutes. The reaction mixture was diluted with 50 ml of methylene chloride, washed sequentially with ice-cooled 10% hydrochloric acid and saturated saline, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was treated with acetone 10
Dissolved in 0 ml. Then 9.39 g of sodium iodide (62.
6 mmol), and the mixture was stirred at 50 ° C. for 2 hours under a nitrogen atmosphere. After diluting the reaction mixture with 250 ml of ethyl acetate, 10%
After washing with sodium thiosulfate aqueous solution and saturated saline solution in order,
Dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by flash silica gel column chromatography (eluent: hexane: ethyl acetate = 5: 1 to 2: 1) to give 4-fluorophenyl-1-iodopropane as a pale yellow oil. As a result, 7.12 g (86%) was obtained.

To 20 ml of hexamethylphosphoramide was added 50 ml of sodium acetylide (18% xylene suspension), and the mixture was cooled under ice-cooling.
A solution of 7.00 g (26.5 mmol) of iodopropane dissolved in 20 ml of anhydrous dimethylformamide was added. The reaction mixture was stirred at room temperature for 2 hours. Ice water was carefully poured under ice cooling, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by flash silica gel column chromatography (elution solvent: hexane).
2.67 g (62%) of the title compound were obtained as a colorless oil. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ): δ 1.82 (2H,
m), 1.99 (1H, t, J = 2.6 Hz), 2.19 (2H, m), 2.71 (2
H, t, J = 7.5 Hz), 6.97 (2H, m), 7.14 (2H, m) Mass spectrum (EI) m / z: 162 (M ⁺ ) Reference Example 5 5- (4-methoxyphenyl) pent- 3- (4-methoxyphenyl) -1 as in Reference Example 4
Using iodopropane and sodium acetylide,
The title compound was obtained. Nuclear magnetic resonance spectrum (500MHz, CDCl ₃ ): δ 1.78-1.88
(2H, m), 1.98 (1H, t, J = 2.6 Hz), 2.15-2.22 (2H,
m), 2.67 (2H, t, J = 7.5 Hz), 3.79 (3H, s), 6.83 (2
H, d, J = 8.6 Hz), 7.11 (2H, d, J = 8.6 Hz) Mass spectrum (EI) m / z: 174 (M ⁺ ) Reference Example 6 Reference Example 4 for 5-phenylpent-1-yne Similarly, the title compound was obtained using 3-phenyl-1-iodopropane and sodium acetylide. Nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ): δ 1.81-1.89
(2H, m), 1.99 (1H, t, J = 2.8 Hz), 2.21 (2H, dt, J =
2.8, 7.6 Hz), 2.74 (2H, t, J = 7.6 Hz), 7.16-7.23 (3
H, m), 7.26-7.32 (2H, m) mass spectrum (EI) m / z: 144 (M ⁺ ) Reference Example 7 5-Cyclohexylpent-1- yne As in Reference Example 4, 3-cyclohexyl-1 -The title compound was obtained using iodopropane and sodium acetylide. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ): δ 0.75-1.38
(13H, m), 1.48-1.59 (2H, m), 1.94 (1H, t, J = 2.8 H
z), 2.16 (2H, dt, J = 2.8, 7.2 Hz) Mass spectrum (EI) m / z: 150 (M ⁺ ) Reference Example 8 4- (4-fluorophenyloxy) but-1-yne- 4-fluoro Phenol 5.00 g (44.6 mmol), 3-
3.38 ml (44.6 mmol) of butyn-1-ol and 17.5 g (66.9 mmol) of triphenylphosphine were dissolved in 100 ml of tetrahydrofuran, and 11.7 g (66.9 mmol) of diethyl azodicarboxylate was added under ice-cooling, followed by 18 hours at room temperature. Stirred. After the solvent was concentrated under reduced pressure, 200 ml of hexane and 20 ml of ethyl acetate were added, the deposited precipitate was removed by filtration, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by flash silica gel column chromatography (elution solvent: hexane: ethyl acetate = 1: 0) to obtain the title compound. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ): δ 2.05 (1H,
t, J = 2.7 Hz), 2.63-2.70 (2H, m), 4.07 (2H, t, J =
7.0 Hz), 6.82-6.90 (2H, m), 6.94-7.02 (2H, m) Mass spectrum (EI) m / z: 164 (M ⁺ ) Reference Example 9 3- (4-methylphenyloxy) -1- The title compound was obtained using 4-methylphenol and propargyl alcohol in the same manner as in Reference Example 8 for propyne . Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ): δ 2.29 (3H,
s), 2.50 (1H, t, J = 2.4 Hz), 4.67 (2H, d, J = 2.4 H
z), 6.88 (2H, d, J = 8.4 Hz), 7.10 (2H, d, J = 8.4 Hz) Mass spectrum (EI) m / z: 146 (M ⁺ ) Reference example 10 3-[(4-methylthio) ) Phenyloxy] -1-propyl
Like the emissions in Reference Example 8, using 4- (methylthio) phenol and propargyl alcohol, to give the title compound. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ): δ 2.45 (3
H, s), 2.52 (1H, t, J = 2.4 Hz), 4.68 (2H, d, J = 2.4
Hz), 6.93 (2H, d, J = 8.9 Hz), 7.27 (2H, d, J = 8.9 H
z) Mass spectrum (EI) m / z: 178 (M ⁺ ) Reference Example 11 3- (3-methoxyphenyloxy) -1-propyne As in Reference Example 8, using 3-methoxyphenol and propargyl alcohol, The title compound was obtained. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ): δ 2.52 (1
H, t, J = 2.4 Hz), 3.79 (3H, s), 4.67 (2H, d, J = 2.4
Hz), 6.53-6.60 (3H, m), 7.16-7.23 (1H, m) Mass spectrum (EI) m / z: 162 (M ⁺ ) Reference Example 12 3- (3,4-dimethylphenyloxy) -1 −propi
In the same manner as in Reference Example 8, the title compound was obtained using 3,4-dimethylphenol and propargyl alcohol. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ): δ 2.20 (3H,
s), 2.24 (3H, s), 2.49 (1H, t, J = 2.4 Hz), 4.65 (2
H, d, J = 2.4 Hz), 6.72 (1H, dd, J = 2.4, 8.0 Hz), 6.7
8 (1H, d, J = 2.4 Hz), 7.04 (1H, d, J = 8.0 Hz) Mass spectrum (EI) m / z: 160 (M ⁺ ) Reference Example 13 4- (4-methylphenyloxy) bute -1-In the same manner as in Reference Example 8, the title compound was obtained using 4-methylphenol and 3-butyn-1-ol. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ): δ 2.03 (1
H, t, J = 2.8 Hz), 2.28 (3H, s), 2.66 (2H, dt, J = 2.
8, 7.2 Hz), 4.07 (2H, t, J = 7.2 Hz), 6.81 (2H, d, J =
8.8 Hz), 7.08 (2H, d, J = 8.8 Hz) Mass spectrum (EI) m / z: to 160 (M ⁺⁾ Reference Example 14 4-cyclohexyloxy-but-1-in anhydrous methylene chloride 950 ml, cyclohexanone 32ml
(0.31 mol) 33.5 ml of 1,3-propanediol (0.
46 mol), 51.5 ml (0.31 mol) of triethyl orthoformate, and 1.44 g (6.18 mmol) of zirconium chloride were stirred for 1 hour at room temperature under a nitrogen atmosphere. Ice cold 1
1.5 L of a normal aqueous sodium hydroxide solution was added, and the mixture was extracted with methylene chloride, and the methylene chloride layer was washed with water. After the methylene chloride layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue is purified by distillation under reduced pressure, and cyclohexanone
26.8 g (55%) of trimethyl ketal were obtained.

To 24.9 g (0.11 mol) of zirconium chloride suspended in 500 ml of tetrahydrofuran, 20.5 g (0.54 mmol) of sodium borohydride was slowly added under a nitrogen atmosphere, followed by stirring at room temperature for 20 minutes. There, 16.9 g of cyclohexanone trimethyl ketal obtained earlier
(0.11 mol) in tetrahydrofuran (170 ml) was added dropwise under a nitrogen atmosphere under ice-cooling. After completion of the addition, the mixture was stirred at room temperature for 24 hours. Under ice-cooling, 600 ml of 2N hydrochloric acid exemplified in ice was added to terminate the reaction, and tetrahydrofuran was distilled off under reduced pressure. The remaining aqueous phase was extracted with ethyl acetate, and the ethyl acetate layer was washed with saturated saline. After the ethyl acetate layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (elution solvent; hexane: ethyl acetate = 10: 1 to 5: 2), and 13.4 g (78%) of 3-cyclohexyloxypropan-1-ol was purified.
I got

[0504] 11.5 g (72.9 mmol) of the obtained 3-cyclohexyloxypropan-1-ol was mixed with methylene chloride.
Dissolve in 240ml and cool on ice with molecular sieve 4A5
8 g and 23.8 g (0.11 mol) of pyridinium chlorochromate were added, and the mixture was stirred for 1 hour and 40 minutes under a nitrogen atmosphere. Diethyl ether was added to the reaction solution, which was filtered through celite. After washing Celite with diethyl ether, the filtrates were combined, and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (elution solvent: hexane: ethyl acetate = 20: 1 to 10:
The crude purification was performed according to 1) to obtain 8.60 g of crude 3-cyclohexyloxypropionaldehyde.

In 120 ml of methylene chloride containing 36.5 g (0.11 mol) of carbon tetrabromide, 57.7 g of triphenylphosphine was added.
(0.22 mol) of methylene chloride (120 ml) was added dropwise under a nitrogen atmosphere under ice-cooling. After completion of the addition, the mixture was further stirred for 5 minutes.
90 ml of methylene chloride containing 8.60 g of the obtained crude 3-cyclohexyloxypropionaldehyde was added dropwise thereto under ice cooling under a nitrogen atmosphere, and the mixture was stirred for 25 minutes after completion of the addition. The reaction solution was diluted with methylene chloride, and the reaction solution was washed with a saturated aqueous solution of sodium hydrogen carbonate and a saturated saline solution. After the methylene chloride layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. Silica gel chromatography of the residue (elution solvent; hexane: ethyl acetate = 100: 1 to 33: 1)
To give 12.6 g (55%, two steps) of 4-cyclohexyloxy-1,1-dibromobut-1-ene.

The obtained 4-cyclohexyloxy-1,
In a nitrogen atmosphere, 130 ml of tetrahydrofuran containing 12.6 g (40.4 mmol) of 1-dibromobut-1-ene was added under a nitrogen atmosphere.
At 78 ° C., 54 ml (81.0 mmol) of a 1.5 N n-butyllithium hexane solution was added dropwise. After the completion of the dropwise addition, the mixture was stirred for 1 hour, and then the temperature was slowly raised to room temperature. After stirring at room temperature for 50 minutes, water was added under ice cooling to terminate the reaction. Extract with diethyl ether,
The diethyl ether layer was washed with saturated saline. After the diethyl ether layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (elution solvent; hexane: ethyl acetate = 100: 1 to 50:
Purification according to 1) gave 4.35 g (71%) of the title compound. Nuclear magnetic resonance spectrum (400MHz, CDCl ₃ ): δ 1.13-1.3
6 (5H, m), 1.48-1.58 (1H, m), 1.67-1.81 (2H, m),
1.85-1.95 (2H, m), 1.97 (1H, t, J = 2.8 Hz), 2.45 (2
H, dt, J = 2.8, 7.2 Hz), 3.23-3.32 (1H, m), 3.59 (2
(H, t, J = 7.2 Hz) Mass spectrum (EI) m / z: 153 (M + H) ⁺ Test example 1 Inhibition against rat HvGR (Host versus Graft Reaction)
Measurement of anti -activity (1) Two strains of rats [Lewis (male, 6 weeks old, Charles River Japan) and WKAH / Hkm (male, 7 weeks old) Japan SLC, Inc.] were used. Five rats (host) were used per group. (2) Induction of HvGR Spleen cells were isolated from spleens of WKAH / Hkm rats or Lewis rats, and RPMI1640 medium (LIFE TECHNOLOGIES, Rockvill)
e MD USA) at 1 × 10 ⁸ cells / ml. Subcutaneously under both hind limb foot pads of Lewis rats, WKAH / Hkm rats or Le
Wis rat spleen cell suspension 100 μl (1 spleen cell count
x10 ⁷⁾ were injected with. (3) Administration of Compound The compound was suspended in 0.5% tragacanth solution. The suspended compound was administered to the compound administration group (Lewis rats to which the spleen cells of WKAH / Hkm rat were injected and the specimen was administered) at a rate of 5 ml / kg once a day for 4 consecutive days from the day of spleen cell injection. Rats were orally administered. The same group (Lewis rat group injected with Lewis rat spleen cells) and control group (Lewis rat injected with WKAH / Hkm rat spleen cells and not administered with the sample) received 0.5% tragacanth solution instead of the sample. Oral administration. (4) Method for measuring inhibitory activity against HvGR Average popli of syngeneic group from popliteal lymph node weight of each individual
Subtract the teal lymph node weight ("popliteal lymph node weight by HvGR") and calculate the inhibition rate from the "popliteal lymph node weight by HvGR" of each compound in the group to which the compound was administered compared to the average "popliteal lymph node weight by HvGR" in the control group did.
The inhibitory activity of the compound was represented by an ID50 value (mg / kg) calculated from the dose of the compound and the inhibition rate using the least squares method.

As a result of this test, the compound of the present invention showed excellent inhibitory activity.

[0508]

[Table 5] Compound HvGR ID50 value (mg / kg) Example 1 0.0843 Example 11 0.0844 Example 40 0.0683 Example 43 0.0730 Example 46 0.0454. . . . . . . . . . . . . . Comparative Compound 1 0.354 In the above table, Comparative Compound 1 is described in WO94 / 0894.
Compound No. 3 in Example 29.

Test Example 2 Measurement of inhibitory activity against adjuvant arthritis Preparation of adjuvant 2 m dead bacteria of Mycobacterium butyricum in liquid paraffin
It was suspended at a ratio of g / ml and sonicated to prepare. 2. Preparation of Test Compound The test compound was suspended or dissolved in a 0.5% tragacanth solution. 3. Induction of adjuvant arthritis 0.05 ml of the adjuvant prepared in
injection) into the right hind footpad. Normally, the number of animals per group was 5. In addition, one group to which no adjuvant was injected (normal group) was provided. 4. 1. Administration of compound The compound prepared in 1) was orally administered once a day from the day of adjuvant injection for 21 days at a ratio of 5 ml per 1 kg of the body weight of the rat. In addition, 0.5% tragacanth solution was administered to one group to which adjuvant was administered (control group) and a group to which no adjuvant was injected. 5. One day after the final administration, the volume of the right hind limb was measured with a footpad measuring device, and the average value of the normal group was subtracted from the value of each individual, and the value was defined as the swelling volume. The inhibition rate was calculated from the swelling volume of each individual to which the compound was administered relative to the average swelling volume of the control group. ID50 from compound dose and respective (average group) inhibition rate
Values were calculated.

As a result of the test, the compound of the present invention showed excellent inhibitory activity.

[0511]

[Table 6] Compound ID50 value (mg / kg) Example 1 0.0897 Example 34 0.0470. . . . . . . . . . . . . . Comparative compound 1 0.166 In the above table, Comparative Compound 1 is described in WO94 / 0894.
Compound No. 3 in Example 29.

[0512]

The amino alcohol derivative having the general formula (I) of the present invention, a pharmaceutically acceptable salt thereof, an ester or other derivative thereof has a low toxicity and an excellent immunosuppressive action, and has an autoimmune disease. Or, it is useful as a prophylactic or therapeutic agent for other immune-related diseases.

The novel optically active amino alcohol compounds (La) and (Lb) of the present invention are useful as intermediates for producing pharmaceuticals.

As an intermediate for synthesizing the optically active amino alcohol compounds (La) and (Lb), an optically active 2-substituted-2-amino-1,3-propanediol is used.
Monoester derivative (XLIVa) or (XLIVb)
Is preferable, and such an optically active 2-substituted-2-amino-
1,3-propanediol monoester derivative (XL
IVa) and (XLIVb) are obtained by using a 2-substituted-2-amino-1,3-propanediol derivative (XLII) as a raw material and using a vinyl carboxylate derivative (XLIII) in the presence of a lipase. By selective acylation of only one of the hydroxyl groups, the compound can be easily and simply produced in a high yield.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (Reference) A61P 7/04 A61P 7/04 7/06 7/06 9/00 9/00 9/10 9/10 9 / 12 9/12 11/00 11/00 11/06 11/06 13/12 13/12 17/00 17/00 17/02 17/02 17/06 17/06 19/02 19/02 21/00 21/00 21/04 21/04 25/00 25/00 25/14 25/14 27/02 27/02 29/00 101 29/00 101 31/00 31/00 31/12 31/12 35/00 35/00 37/06 37/06 C07D 413/06 C07D 413/06 C12P 41/00 C12P 41 / 00H // C07M 7:00 C07M 7:00 (72) Inventor Futa Nara 1 Hiromachi, Shinagawa-ku, Tokyo No. 2-58 Sankyo Co., Ltd. (72) Inventor Ryuichi Shimozato 1-2-58 Hiromachi, Shinagawa-ku, Tokyo F-term (reference) 4B064 AE01 BH01 CA21 CB24 CD27 DA01 4C023 CA04 4C063 AA01 BB03 CC92 CC94 DD52 EE05 4C086 AA02 AA03 AA04 BB02 GA 16 NA14 ZA02 ZA22 ZA33 ZA36 ZA42 ZA45 ZA53 ZA55 ZA59 ZA66 ZA68 ZA75 ZA81 ZA89 ZA94 ZA96 ZB08 ZB15 ZB26 ZB33 ZB35 ZC35

Claims (64)

[Claims] 1. A compound of the general formula (I) [Wherein, R ¹ and R ² are the same or different and each represent a hydrogen atom or an amino-protecting group, R ³ represents a hydrogen atom or a hydroxy-protecting group, and R ⁴ represents a lower alkyl group. And n represents an integer of 1 to 6, X represents an ethylene group, a vinylene group, an ethynylene group, a formula -D
A group having —CH ₂ — (wherein D represents a carbonyl group, a group having the formula —CH (OH) —, an oxygen atom, a sulfur atom or a nitrogen atom), an aryl group or a substituent group a. Represents an aryl group substituted with 1 to 3 substituents, and Y represents 1 to 3 substituted with a single bond, a C ₁ -C ₁₀ alkylene group, or a group selected from substituent groups a and b. C ₁ -C
_{A 10-} alkylene group, a C ₁ -C ₁₀ alkylene group having an oxygen atom or a sulfur atom in a carbon chain or at a chain end, or a carbon chain substituted with 1 to 3 groups selected from substituent groups a and b. Or a C ₁ -C ₁₀ alkylene group having an oxygen atom or a sulfur atom at a chain end, wherein R ⁵ is selected from a hydrogen atom, a cycloalkyl group, an aryl group, a heterocyclic group, and substituent groups a and b. 1 to 3
A monosubstituted cycloalkyl group, an aryl group substituted by 1 to 3 groups selected from substituent groups a and b, or 1 to 3 substituted groups selected from substituent groups a and b R ⁶ and R ⁷ are the same or different and represent a hydrogen atom or a group selected from substituent group a. Provided that when R ⁵ is a hydrogen atom, Y represents a group other than C ₁ -C ₁₀ alkylene group a single bond and linear. ], A pharmacologically acceptable salt thereof, an ester thereof, or another derivative thereof. <Substituent group a> halogen atom, lower alkyl group, halogeno lower alkyl group, lower alkoxy group, lower alkylthio group, carboxyl group, lower alkoxycarbonyl group,
Hydroxy group, lower aliphatic acyl group, amino group, mono-
Lower alkylamino group, di-lower alkylamino group, lower aliphatic acylamino group, cyano group and nitro group <Substituent group b> selected from cycloalkyl group, aryl group, heterocyclic group and substituent group a A cycloalkyl group substituted by 1 to 3 groups, 1 group selected from substituent group a
An aryl group substituted with 1 to 3 substituents, and a heterocyclic group substituted with 1 to 3 substituent (s) selected from Substituent Group a. 2. The method according to claim 1, wherein the compound of formula (Ia) Or a pharmacologically acceptable salt thereof, an ester or other derivative thereof. 3. The method of claim 1, wherein the compound of formula (Ib) Or a pharmacologically acceptable salt thereof, an ester or other derivative thereof. 4. One of the first to third aspects
In the above item, R ¹ and R ² are the same or different and each are a hydrogen atom, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group or an aralkyloxycarbonyl group substituted by 1 to 3 groups selected from a substituent group a. A compound or a pharmacologically acceptable salt thereof. 5. One of the first to third aspects
In the above item, the compound or a pharmaceutically acceptable salt thereof, wherein R ¹ and R ² are a hydrogen atom. 6. One of the first to fifth aspects.
Wherein R ³ is a hydrogen atom, a lower alkyl group, a lower aliphatic acyl group, an aromatic acyl group or an aromatic acyl group substituted by 1 to 3 groups selected from a substituent group a, or Its pharmacologically acceptable salts. 7. One of the first to fifth aspects selected from the above.
In the above item, the compound wherein R ³ is a hydrogen atom, or a pharmacologically acceptable salt thereof. 8. One of the first to seventh aspects selected from the above.
In the above item, the compound or a pharmaceutically acceptable salt thereof, wherein R ⁴ is a C ₁ -C ₄ alkyl group. 9. Any one selected from claims 1 to 7
In the above item, the compound or a pharmaceutically acceptable salt thereof, wherein R ⁴ is a C ₁ -C ₂ alkyl group. 10. The compound according to any one of claims 1 to 7, wherein R ⁴ is a methyl group, or a pharmaceutically acceptable salt thereof. 11. The compound according to any one of claims 1 to 10, wherein n is 2 or 3, or a pharmacologically acceptable salt thereof. 12. The compound according to claim 1, wherein n is 2, or a pharmacologically acceptable salt thereof. 13. An alkenyl group according to claim 1, wherein X is 1 to 3 substituted with an ethylene group, an ethynylene group, an aryl group or a group selected from substituent group a. −
Or a pharmacologically acceptable salt thereof. 14. The compound according to any one of claims 1 to 12, wherein X is an ethylene group, or a pharmacologically acceptable salt thereof. 15. The compound according to any one of claims 1 to 12, wherein X is an ethynylene group, or a pharmacologically acceptable salt thereof. 16. The compound according to any one of claims 1 to 12, wherein X is a group having the formula —D—CH ₂ — or a pharmaceutically acceptable salt thereof. 17. The method according to claim 1, wherein X is a group having the formula —D—CH ₂ —, wherein D is a carbonyl group or a formula —CH (OH) —. Represents a group having
Or a pharmacologically acceptable salt thereof. 18. The method according to claim 1, wherein 1 to 3 Y are substituted with a C ₁ -C ₁₀ alkylene group or a group selected from substituent groups a and b. C ₁ -C ₁₀ compound or pharmacologically acceptable salt thereof is an alkylene group. 19. The method according to any one of claims 1 to 17, wherein 1 to 3 Y are substituted with a C ₁ -C ₆ alkylene group or a group selected from substituent groups a and b. A compound which is a C ₁ -C ₆ alkylene group or a pharmacologically acceptable salt thereof. 20. The method according to claim 1, wherein Y is an ethylene group, a trimethylene group, a tetramethylene group, or a group selected from the group of substituents a and b.
An individually substituted ethylene, trimethylene or tetramethylene group or a pharmaceutically acceptable salt thereof. 21. The compound according to any one of claims 1 to 17, wherein Y is an ethylene group, a trimethylene group or a tetramethylene group, or a pharmaceutically acceptable salt thereof. 22. The compound according to any one of claims 1 to 17, wherein Y is an ethylene group or a trimethylene group, or a pharmaceutically acceptable salt thereof. 23. The method according to any one of claims 1 to 17, wherein Y is a C ₁ -C ₁₀ alkylene group having an oxygen atom or a sulfur atom in a carbon chain or at a chain end, or a substituent group a And a group having 1 to 3 carbon atoms having an oxygen atom or a sulfur atom in the carbon chain or at the chain end substituted with 1 to 3 groups selected from
₁ -C ₁₀ compound or pharmacologically acceptable salt thereof is an alkylene group. 24. The compound according to any one of claims 1 to 17, wherein Y is a C ₁ -C ₁₀ alkylene group having an oxygen atom or a sulfur atom in a carbon chain or at a chain end, or a pharmacological compound thereof. Above acceptable salts. 25. The method according to any one of claims 1 to 17, wherein Y is C ₁ -C having an oxygen atom in a carbon chain or at a chain end.
A compound which is a C ₁₀ alkylene group or a pharmacologically acceptable salt thereof. 26. The method according to claim 1, wherein Y is C ₁ -C having an oxygen atom in a carbon chain or at a chain end.
A compound which is a C ₆ alkylene group or a pharmacologically acceptable salt thereof. 27. The method according to any one of claims 1 to 17, wherein Y is —O—CH ₂ —, —O— (CH ₂ ) ₂ —, —O—
_{(CH 2) 3 -, -} CH 2 -O -, - (CH 2) 2 -O- or - (CH ₂₎ group, compound or pharmacologically acceptable salt thereof having ₃ -O-. 28. The compound according to any one of claims 1 to 17, wherein Y is a group having —CH ₂ —O— or a pharmaceutically acceptable salt thereof. 29. The compound according to any one of claims 1 to 17, wherein Y is a group having —O— (CH ₂ ) ₂ — or — (CH ₂ ) ₂ —O— or a compound thereof. Pharmacologically acceptable salt. 30. The compound according to any one of claims 1 to 29, wherein R ⁵ is a hydrogen atom, or a pharmaceutically acceptable salt thereof. 31. The method according to any one of claims 1 to 29, wherein 1 to 3 R ⁵ are substituted with a group selected from a cycloalkyl group, a heterocyclic group, a substituent group a and b. Or a pharmacologically acceptable salt thereof, which is a heterocyclic group substituted by 1 to 3 cycloalkyl groups or groups selected from substituent groups a and b. 32. The cycloalkyl group according to any one of claims 1 to 29, wherein R ⁵ is substituted with 1 to 3 cycloalkyl groups or groups selected from substituent groups a and b. Or a pharmacologically acceptable salt thereof. 33. The compound according to any one of claims 1 to 29, wherein R ⁵ is a cycloalkyl group, or a pharmaceutically acceptable salt thereof. 34. The compound according to any one of claims 1 to 29, wherein R ⁵ is a cyclohexyl group, or a pharmaceutically acceptable salt thereof. 35. The aryl group according to any one of claims 1 to 29, wherein R ⁵ is substituted with one to three R ⁵ by an aryl group or a group selected from substituent groups a and b. Or a pharmacologically acceptable salt thereof. 36. The method according to any one of claims 1 to 29, wherein R ⁵ is an aryl group or an aryl group having 1 to 3 substituents, wherein the substituent is a halogen atom, An alkyl group, a halogeno lower alkyl group, a lower alkoxy group, a lower alkylthio group and a lower aliphatic acyl group) or a pharmaceutically acceptable salt thereof. 37. The method according to any one of claims 1 to 29, wherein R ⁵ is an aryl group or an aryl group having 1 to 3 substituents, wherein the substituent is a halogen atom, Or a pharmacologically acceptable salt thereof, which is a group selected from the group consisting of an alkyl group, a halogeno lower alkyl group, a lower alkoxy group and a lower aliphatic acyl group. 38. The method according to any one of claims 1 to 29, wherein R ⁵ is a phenyl group or a phenyl group having 1 to 3 substituents, wherein the substituent is a halogen atom, a lower alkyl group, a halogeno Or a pharmacologically acceptable salt thereof, which is a group selected from the group consisting of a lower alkyl group, a lower alkoxy group and a lower aliphatic acyl group. 39. The method according to any one of claims 1 to 29, wherein R ⁵ is a phenyl group or a phenyl group having 1 to 3 substituents (the substituent is a fluorine atom, a chlorine atom, a methyl, Or a pharmaceutically acceptable salt thereof, which is a group selected from the group consisting of trifluoromethyl, methoxy and acetyl groups. 40. The method according to any one of claims 1 to 29, wherein R ⁵ is phenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 3-methylphenyl, 4-methylphenyl,
3,4-dimethylphenyl, 3,5-dimethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,4-ditrifluoromethylphenyl, 3,5-ditrifluoromethylphenyl, 3-methoxyphenyl , 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,
A compound having a 4,5-trimethoxyphenyl, 3-acetylphenyl or 4-acetylphenyl group or a pharmacologically acceptable salt thereof. 41. The method according to any one of claims 1 to 40, wherein R ⁶ and R ⁷ are the same or different and each is a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group. Or a compound having a lower alkylthio group or a pharmacologically acceptable salt thereof. 42. The compound according to any one of claims 1 to 40, wherein R ⁶ and R ⁷ are a hydrogen atom, or a pharmaceutically acceptable salt thereof. 43. The compound according to claim 1, wherein the compound is selected from the following, a pharmacologically acceptable salt thereof, an ester thereof and other derivatives. 2-amino-2-methyl-4- [5- (6-cyclohexylhexyl)
Thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexylpentyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl -4- [5- (4-cyclohexylbutyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (6-cyclohexylhexyl)
-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexylpent-1-ynyl) thiophen-2-yl] butan-1- All, 2-amino-2-
Methyl-4- [5- (4-cyclohexylbut-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4-
[5- (6-cyclohexylhexanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexylpentanoyl) thiophen-2-yl] butane- 1-
All, 2-amino-2-methyl-4- [5- (4-cyclohexylbutanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4- [5- (6- Cyclohexylhexyl) thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4-
[5- (5-cyclohexylpentyl) thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4- [5- (4-cyclohexylbutyl) thiophen-2-yl] butane-1- Oar, 2-
Amino-2-ethyl-4- [5- (6-cyclohexylhex-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2
-Ethyl-4- [5- (5-cyclohexylpent-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4
-[5- (4-cyclohexylbut-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4- [5- (6-cyclohexylhexanoyl) thiophen-2- Il] butane-1-
All, 2-amino-2-ethyl-4- [5- (5-cyclohexylpentanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4- [5- (4- Cyclohexylbutanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl
-4- [5- (6-phenylhexyl) thiophen-2-yl] butane
-1-ol, 2-amino-2-methyl-4- [5- (5-phenylpentyl) thiophen-2-yl] butan-1-ol, 2-amino-2
-Methyl-4- [5- (4-phenylbutyl) thiophen-2-yl]
Butan-1-ol, 2-amino-2-methyl-4- [5- (6-phenylhex-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-phenylpent-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2
-Methyl-4- [5- (4-phenylbut-1-ynyl) thiophene-2
-Yl] butan-1-ol, 2-amino-2-methyl-4- [5- (6-
Phenylhexanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-phenylpentanoyl) thiophen-2-yl] butan-1-ol, 2- Amino-2-
Methyl-4- [5- (4-phenylbutanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexyloxypent-1-ynyl) Thiophene-2-yl]
Butan-1-ol, 2-amino-2-methyl-4- [5- (4-cyclohexyloxybut-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl- 4- [5- (3-cyclohexyloxypropynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexyloxypentyl) thiophen-2-yl] Butan-1-ol, 2-amino-2-methyl-4- [5- (4-cyclohexyloxybutyl)
Thiophene-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (3-cyclohexyloxypropyl) thiophene
-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5
-Cyclohexyloxypentanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-cyclohexyloxybutanoyl) thiophen-2-yl] butan-1-ol , 2-Amino-2-methyl-4- [5- (3-cyclohexyloxypropanoyl) thiophen-2-yl] butane-1-
All, 2-amino-2-methyl-4- [5- (5-phenoxypent
-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-phenoxybut-1-ynyl) thiophen-2-yl] butane-1- All, 2-amino-2-methyl-4
-[5- (3-phenoxypropynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-phenoxypentyl) thiophen-2-yl] butane-1 -All, 2-amino-2-methyl-4- [5- (4-phenoxybutyl) thiophen-2-
Yl] butan-1-ol, 2-amino-2-methyl-4- [5- (3-phenoxypropyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [ 5- (5-phenoxypentanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-
Methyl-4- [5- (4-phenoxybutanoyl) thiophen-2-
Yl] butan-1-ol, 2-amino-2-methyl-4- [5- (3-phenoxypropanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-benzyloxyphenyl) thiophen-2-yl] butan-1-ol, 2-amino-2
-Methyl-4- [5- (4-cyclohexylmethoxyphenyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl
-4- [5- (4-cyclohexylethoxyphenyl) thiophene
-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4
-Cyclohexylmethoxypropynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-cyclohexylmethoxypropyl) thiophen-2-yl] butan-1-ol, and 2-Amino-2-methyl-4- [5- (4-cyclohexylmethoxypropanoyl) thiophen-2-yl] butan-1-ol. 44. The compound according to claim 1, wherein the compound is selected from the following, a pharmacologically acceptable salt thereof, an ester thereof, and other derivatives. 2-amino-2-methyl-4- [5- (4-cyclohexylbutyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl
-4- [5- (5-cyclohexylpentyl) thiophen-2-yl]
Butan-1-ol, 2-amino-2-methyl-4- [5- (5-phenylpentyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-cyclohexyloxybutyl)
Thiophene-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [4- (4-fluorophenoxy) butyl] thiophene
-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [4
-(4-methoxyphenoxy) butyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4-benzyloxybutyl) thiophen-2-yl] butane-1 -All, 2-
Amino-2-methyl-4- [5- (4-cyclohexylbut-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-
Methyl-4- [5- (4-phenylbut-1-ynyl) thiophen-2-
Yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-cyclohexylpent-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl -4- [5- (5-phenylpent-1-ynyl) thiophen-2-yl] butan-1-ol, 2
-Amino-2-methyl-4- [5- [5- (4-fluorophenyl) pent-1-ynyl] thiophen-2-yl] butan-1-ol, 2-
Amino-2-methyl-4- [5- [5- (4-methoxyphenyl) pent]
-1-ynyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [3- (4-methylcyclohexyloxy) propynyl] thiophen-2-yl] butane- 1-all, 2
-Amino-2-methyl-4- [5- [3- (4-methylphenoxy) propynyl] thiophen-2-yl] butan-1-ol, 2-amino
-2-methyl-4- [5- [3- (4-ethylphenoxy) propynyl]
Thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [3- (4-methylthiophenoxy) propynyl] thiophen-2-yl] butan-1-ol, 2- Amino-2-methyl-4
-[5- (4-cyclohexyloxybut-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5-
[4- (4-fluorophenoxy) but-1-ynyl] thiophene-
2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [4-
(4-methylphenoxy) but-1-ynyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (3-cyclohexylmethoxypropynyl) thiophen-2-yl] Butan-1-ol, 2-amino-2-methyl-4- [5- (4-phenylmethoxybut-1-ynyl) thiophen-2-yl] butan-1-
All, 2-amino-2-methyl-4- [5- (4-cyclohexylbutanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (4- (Phenylbutanoyl) thiophene-
2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-
Cyclohexylpentanoyl) thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- (5-phenylpentanoyl) thiophen-2-yl] butan-1-ol, 2- Amino-2-methyl-4- [5- [5- (4-fluorophenyl) pentanoyl] thiophen-2-yl] butan-1-ol, 2-amino-2
-Ethyl-4- [5- (5-cyclohexylpentyl) thiophene-
2-yl] butan-1-ol, 2-amino-2-ethyl-4- [5- (5-
Cyclohexylpent-1-ynyl) thiophen-2-yl] butan-1-ol, 2-amino-2-ethyl-4- [5- (5-cyclohexylpentanoyl) thiophen-2-yl] butan-1-ol , 2-amino-2-methyl-4- [5- [3- (4-chlorophenoxy)
Propynyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4- [5- [3- (3-methylphenoxy) propynyl] thiophen-2-yl] butan-1-ol, 2-amino-2
-Methyl-4- [5- [3- (3,4-dimethylphenoxy) propynyl] thiophen-2-yl] butan-1-ol, 2-amino-2-
Methyl-4- [5- [3- (3-methoxyphenoxy) propynyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl
-4- [5- [3- (3,4-dimethoxyphenoxy) propynyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4
-[5- [3- (3,5-dimethoxyphenoxy) propynyl] thiophen-2-yl] butan-1-ol, 2-amino-2-methyl-4-
[5- [3- (3-acetylphenoxy) propynyl] thiophene-
2-yl] butan-1-ol and 2-amino-2-methyl-4- [5
-[3- (4-acetylphenoxy) propynyl] thiophen-2-
Il] butan-1-ol. 45. A compound of the formula (La) or (Lb)[Where R¹And R^TwoIs the same or different and is a hydrogen atom or amino
A protecting group for the group;^3aRepresents a protecting group for a hydrogen atom or a hydroxy group,
Or R¹Is a hydrogen atom, and R^TwoAnd R^3aBut together
Represents a group of the formula (-(C = O)-),^4aIs C₁-C₂₀Alkyl group, intervening heteroatom
C_Two-C₂₀Alkyl group, aryl group or aromatic hetero
C substituted with a ring group₁-C₂₀Alkyl group, C_Two-C ₂₀Al
C with a quinyl group or heteroatom_Three-C₂₀Alkynyl
Substituted with an aryl group, an aryl group or an aromatic heterocyclic group
_Two-C₂₀Alkynyl group, C_Two-C₂₀Alkenyl group, hetero
C atom intervening_Three-C₂₀Alkenyl group, aryl group
Or C substituted with an aromatic heterocyclic group_Two-C₂₀Alkene
Substituted with an aryl group, an aryl group or an aromatic heterocyclic group
C with heteroatom_Two-C₂₀An alkyl group or
A cycloalkyl group; m represents an integer of 0 to 4; Ar represents an aryl group, an aromatic heterocyclic group,
Aryl group substituted with 1 to 5 groups by a selected group, substitution
Aromatic substituted with 1 to 5 groups selected from group a
Shows a heterocyclic group. However, when Ar is an aryl group,
R¹Represents no hydrogen atom and R^TwoAnd / or R^3aIs hydrogen field
Do not show children. ] The compound represented by these. <Substituent group a> Halogen atom, lower alkyl group, halogen
Lower alkyl group, lower alkoxy group, lower alkyl group
O group, carboxyl group, lower alkoxycarbonyl group,
Hydroxy group, lower aliphatic acyl group, amino group, mono-
Lower alkylamino group, di-lower alkylamino group, lower
Lower aliphatic acylamino, cyano and nitro groups 46. The compound according to claim 45, having the general formula (La). 47. The method according to claim 45, wherein R ¹ is
A compound that is a hydrogen atom. 48. The compound according to any one of claims 45 to 47, wherein R ² and R ^3a together are a group of the formula (— (C ＝ O) —). 49. The compound according to any one of claims 45 to 47, wherein R ^3a is a hydrogen atom. 50. The method according to claim 45, wherein R ^4a is a C ₁ -C ₁₀ alkyl group, a C ₂ -C ₁₀ alkyl group having a heteroatom, an aryl group or an aromatic group. A C ₁ -C ₁₀ alkyl group substituted with a heterocyclic group, a C ₂ -C ₁₀ alkynyl group, a C ₃ -C ₁₀ alkynyl group intervening with a hetero atom,
C ₂ -C ₁₀ substituted with an aryl group or an aromatic heterocyclic group
Alkynyl group, C ₂ -C ₁₀ alkenyl group, C ₃ -C ₁₀ alkenyl group which heteroatom is interposed, C ₂ -C ₁₀ alkenyl group substituted with an aryl group or an aromatic heterocyclic group, an aryl group or an aromatic heterocyclic Compounds which are a C ₂ -C ₁₀ alkyl group or a C ₅ -C ₁₀ cycloalkyl group interposed by a heteroatom substituted with a ring group. 51. The method according to claim 45, wherein R ^4a is a C ₁ -C ₁₀ alkyl group, a C ₂ -C ₁₀ alkyl group having a hetero atom, an aryl group, or an aromatic group. heterocycle C ₁ -C ₁₀ alkyl group substituted with a group, C ₂ -C ₁₀ alkynyl group, C ₂ -C ₁₀ alkenyl group, or a compound which is a C ₅ -C ₁₀ cycloalkyl group. 52. The compound according to any one of the items 45 to 49, wherein R ^4a is a C ₁ -C ₁₀ alkyl group. 53. The compound according to any one of claims 45 to 49, wherein R ^4a is a C ₁ -C ₆ alkyl group. 54. The compound according to any one of the items 45 to 49, wherein R ^4a is a methyl or ethyl group. 55. The method according to claim 45, wherein Ar is substituted by 1 to 4 phenyl, furyl, thienyl, benzothienyl groups or a group selected from the substituent group a. Compounds which are phenyl, furyl, thienyl or benzothienyl groups. 56. The compound according to any one of claims 45 to 54, wherein Ar is a thienyl group or a thienyl group substituted by 1 to 4 groups selected from the above-mentioned substituent group a. 57. The method according to any one of claims 45 to 54, wherein Ar is a benzothienyl group or a benzothienyl group substituted by 1 to 4 groups selected from the above-mentioned substituent group a. Compound. (58) The compound according to any one of (45) to (54), wherein m is 0. 59. The method according to any one of claims 45 to 58, wherein the substituent group a is a halogen atom, a hydroxyl group, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, a carboxy group, a lower aliphatic group. Compounds which are an acyl group, a lower aliphatic acylamino group, an amino group, a cyano group and a nitro group. 60. A compound of the formula (XLII)[Wherein, R¹And R^TwoAre the same or different and each represents a hydrogen atom or
Represents a protecting group for an amino group;^4aIs C₁-C₂₀Alkyl group, intervening heteroatom
C_Two-C₂₀Alkyl group, aryl group or aromatic hetero
C substituted with a ring group₁-C₂₀Alkyl group, C_Two-C ₂₀Al
C with a quinyl group or heteroatom_Three-C₂₀Alkynyl
Substituted with an aryl group, an aryl group or an aromatic heterocyclic group
_Two-C₂₀Alkynyl group, C_Two-C₂₀Alkenyl group, hetero
C atom intervening_Three-C₂₀Alkenyl group, aryl group
Or C substituted with an aromatic heterocyclic group_Two-C₂₀Alkene
Substituted with an aryl group, an aryl group or an aromatic heterocyclic group
C with heteroatom_Two-C₂₀An alkyl group or
Represents a cycloalkyl group. 2-substituted-2-a represented by the formula:
One hydro of the mino-1,3-propanediol derivative
Only the xy group is converted to a compound of formula (XLIII) R in the presence of lipase.¹¹COOCH = CH_Two (XLIII) A carboxylic acid vinyl ester derivative having the formula:¹¹
Is R^4aAnd the same groups as in the definition of )
Wherein the compound has the general formula (X)
2-substituted-represented by LIVa) or (XLIVb)
2-amino-1,3-propanediol monoester
Derivative embedded image[Wherein, R¹, R^Two, R^4aAnd R¹¹Indicates the same as above
You. ] Manufacturing method. 61. The production method according to claim 60, wherein ^one of R ¹ and R ² is a hydrogen atom and the other is a protecting group for an amino group. 62. The compound according to claim 60 or 61, wherein R ^4a is substituted by a C ₁ -C ₁₀ alkyl group, a C ₂ -C ₁₀ alkyl group having a heteroatom, an aryl group or an aromatic heterocyclic group. ₁ -C ₁₀ alkyl group, C ₂ -C ₁₀ alkynyl group, C ₃ -C ₁₀ alkynyl group heteroatoms are interposed,
C ₂ -C ₁₀ substituted with an aryl group or an aromatic heterocyclic group
Alkynyl group, C ₂ -C ₁₀ alkenyl group, C ₃ -C ₁₀ alkenyl group which heteroatom is interposed, C ₂ -C ₁₀ alkenyl group substituted with an aryl group or an aromatic heterocyclic group, an aryl group or an aromatic heterocyclic C ₂ -C ₁₀ alkyl group hetero atom substituted with a cyclic group is interposed, or method is C ₅ -C ₁₀ cycloalkyl group. 63. The compound according to claim 60 or 61, wherein R ^4a is substituted by a C ₁ -C ₁₀ alkyl group, a C ₂ -C ₁₀ alkyl group having a heteroatom, an aryl group or an aromatic heterocyclic group. ₁ -C ₁₀ alkyl group, C ₂ -C ₁₀ alkynyl group, C ₂ -C ₁₀ alkenyl group, or a method is C ₅ -C ₁₀ cycloalkyl group. In 64. any one selected from claims 60 to 62, R ¹¹ is, C ₁ -C ₂₀ alkyl group, or, C ₁ -C ₂₀ substituted with an aryl or heteroaryl group A production method which is an alkyl group.