JP2001089452A - Pyrimidine derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a compound having CD40 function-inhibiting action. SOLUTION: This pyrimidine derivative is a compound having the general formula (I) R1, R3 and R4 are each H, OH, a halogen, an alkyl, an alkoxy, an alkylthio, a halogenated alkyl, an aryl which may be substituted, an heteroaryl which may be substituted, an aralkyl which may be substituted or N(Ra)Rb [Ra and Rb are each H, OH, an alkyl, a cycloalkyl, an aryl which may be substituted, a heteroaryl which may be substituted, an aralkyl which may be substituted or the like]; R2 is NO2, CN, COOH or an alkoxycarbonyl (R1 and R2 together may form a cyclic group); X and Y are each N or CH) or its pharmacologically permissible salt.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a pyrimidine derivative having a CD40 function inhibitory action and its use.

[0002]

It is known that allergic diseases are mainly caused by binding of allergen-reactive immunoglobulin E to mast cells and the like to produce chemical messengers such as histamine and leukotrin. I have. From these points, drugs that inhibit the action of these chemical mediators have been developed and used, but the clinical efficacy rate is still low at present.

[0003] In rheumatism and other autoimmune diseases, anti-inflammatory drugs such as steroids are used for inflammatory reactions caused by abnormal immune reactions, but these are control therapies and fundamental treatments. It is not a law.

[0004] CD40 is a molecule expressed on B lymphocytes, and a signal from T lymphocytes is transmitted to B lymphocytes via CD40 ligand to have an action of differentiating B lymphocytes (Immun. Today 13, 431 ( 1992)). It is also known that the function of this CD40-CD40 ligand molecule is involved in autoimmune diseases such as rheumatism, encephalomyelitis, and multiple sclerosis (Proceedings of Natio).
nal Academy of Science 93, 2499 1996, Science 261,
1328 1993), and these molecules have been shown to cause pathogenesis in arteriosclerosis and contact dermatitis (Nature 393, 478 1998, European Journal of Immunology).
logy 27, 3143 1997).

[0005] Therefore, a substance that inhibits the function of CD40 may be a fundamental therapeutic agent for these diseases, but a low-molecular compound having such an action is not known.

[0006]

DISCLOSURE OF THE INVENTION The present inventors have proposed CD4
As a result of many years of intensive studies on the synthesis of low molecular weight compounds having a 0-function inhibitory action, they have found that pyrimidine derivatives have an excellent CD40-function inhibitory action,
The present invention has been completed.

Another object of the present invention is to provide a medicine containing a compound having a CD40 function inhibitory activity (particularly, an immunosuppressant or an allergic agent, rheumatism, an autoimmune disease or arteriosclerosis). Medicine).

[0008]

The present invention provides (1) a CD40 function inhibitor comprising a compound having the following general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient:

[0009]

Embedded image[Wherein, R¹, R^ThreeAnd R^FourAre the same or different,
A hydrogen atom, a hydroxyl group, a halogen atom,
1 to 15 alkyl groups, 1 to 15 carbon alcohols
Xyl group, alkylthio group having 1 to 15 carbon atoms, carbon number
1 to 15 halogenated alkyl groups, aryl groups,
Substituted with one to three groups selected from the
Selected from a reel group, a heteroaryl group, and a substituent group α.
A heteroaryl group substituted with one to three groups,
Alkyl group, 1 to 3 groups selected from substituent group α
A substituted aralkyl group, or a compound of the formula -N (R^a) R^bRepresented by
Group (wherein R^aAnd R^bAre the same or different,
A hydrogen atom, an alkyl of 1 to 15 carbon atoms, respectively
Group, cycloalkyl group having 3 to 8 carbon atoms, aryl
And 1 to 3 groups selected from the substituent group α.
Selected from aryl groups, heteroaryl groups and substituent group α
Heteroaryl substituted with one to three groups selected
1 to 1 selected from a group, an aralkyl group or a substituent group α
Represents an aralkyl group substituted with three groups, or
R^aAnd R^bTogether with the nitrogen atom to which they are attached
To form a cyclic amino group. ) And R^TwoIs
Nitro group, nitrile group, carboxy group or C2-C2
Represents 6 alkoxycarbonyl groups, or R¹
And R^TwoTogether with the carbon atom to which they are attached
1 to 3 selected from an aryl ring and a substituent group α
An aryl ring, a heteroaryl ring,
Is substituted with 1 to 3 groups selected from the substituent group α.
X and Y are the same or different
Is different and each represents a nitrogen atom or CH. ]
About. [Substituent group α] halogen atom, lower alkyl group, halogen
Lower alkyl group, lower alkoxy group, lower halogenated
Lower alkoxy group, lower alkylthio group, lower halogenated group
Alkylthio group, lower alkylsulfinyl group, lower
Rukylsulfonyl group, group -NR ^cR^d(Where R^cAnd R^d
Are the same or different and are a hydrogen atom, a lower alkyl group
Or an aralkyl group. ), Hydroxyl, nitro, shear
No group.

In the above, preferred CD40 function inhibitors include (2) R ¹ , R ³ and R ^{4 which} are the same or different and each are a hydroxyl group, an alkyl group having 1 to 15 carbon atoms, From 15 to 15 alkoxy groups, alkylthio groups having 1 to 15 carbon atoms, aryl groups, aryl groups substituted with 1 to 3 groups selected from substituent groups α, heteroaryl groups, and substituent groups α A heteroaryl group substituted with 1 to 3 groups selected, an aralkyl group, an aralkyl group substituted with 1 to 3 groups selected from substituent group α, or a formula -N (R ^a ) R a group represented by ^b (wherein, R ^a and R ^b are the same or different and are each a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, and an aryl group; Is selected from the substituent group α 1 selected from an aryl group, a heteroaryl group, and a substituent group α substituted with 1 to 3 groups
A heteroaryl group, an aralkyl group, or an aralkyl group substituted with 1 to 3 groups selected from a substituent group α, or R ^a and R
^b together with the nitrogen atom to which they are attached form a cyclic amino group. A) a CD40 function inhibitor,
(3) R ¹ is substituted with 1 to 3 groups selected from a hydroxyl group, an alkyl group having 1 to 15 carbon atoms, an alkylthio group having 1 to 15 carbon atoms, an aryl group, and a substituent group α. Aryl group, heteroaryl group, heteroaryl group substituted with 1 to 3 groups selected from substituent group α, aralkyl group, 1 to 3 selected from substituent group α
Aralkyl group substituted with three groups, or a formula -N (R ^a )
A group represented by R ^b (where R ^a and R ^b are the same or different and are each a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, aryl Group, an aryl group substituted with one to three groups selected from a substituent group α, a heteroaryl group, a substituent group α
A heteroaryl group, an aralkyl group, or a group selected from a substituent group α substituted with 1 to 3 groups selected from
Represents an aralkyl group substituted with from 3 to 3 groups, or R ^a and R ^b together with the nitrogen atom to which they are attached form a cyclic amino group. And (4) R ¹ is selected from an aryl group, an aryl group substituted with 1 to 3 groups selected from a substituent group α, a heteroaryl group, and a substituent group α. A heteroaryl group substituted with 1 to 3 groups,
(R ^a ) a group represented by R ^b (wherein R ^a and R ^b are the same or different and each represent a hydrogen atom, a carbon number of 1 to 1
5 alkyl groups, cycloalkyl groups having 3 to 8 carbon atoms, aryl groups, aryl groups substituted with 1 to 3 groups selected from substituent group α, heteroaryl groups, and substituent group α Represents a heteroaryl group, an aralkyl group, or an aralkyl group substituted with 1 to 3 groups selected from the substituent group α, or R ^a and R ^b together with the nitrogen atom to which they are attached form a cyclic amino group. ) Is a CD
40 function inhibitor, (5) R ¹ is represented by an aryl group, an aryl group substituted by 1 to 3 groups selected from substituent group α, or a formula —N (R ^a ) R ^b. Groups (wherein R ^a
Represents a hydrogen atom, R ^b represents an alkyl group having 1 to 15 carbon atoms, an aryl group, or an aryl group substituted with 1 to 3 groups selected from a substituent group α, or , R ^a and R ^b together with the nitrogen atom to which they are attached form a cyclic amino group. And (6) R ³ is a hydroxyl group, an alkoxy group having 1 to 15 carbon atoms, or a group represented by the formula —N (R ^a ) R ^b (wherein R ^a and R ^b is the same or different and each represents a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an aryl group, and 1 to 3 carbon atoms selected from a substituent group α. Selected from an aryl group, a heteroaryl group, and a substituent group α substituted with a group
A heteroaryl group, an aralkyl group, or an aralkyl group substituted with 1 to 3 groups selected from a substituent group α, or R ^a and R
^b together with the nitrogen atom to which they are attached form a cyclic amino group. A) a CD40 function inhibitor,
(7) R ³ is a hydroxyl group, an alkoxy group having 1 to 7 carbon atoms, or a group represented by the formula —N (R ^a ) R ^b (wherein R ^a
Represents a hydrogen atom, R ^b represents an alkyl group having 1 to 15 carbon atoms, or R ^a and R ^b together with the nitrogen atom to which they are attached form a cyclic amino group I do. A) a CD40 function inhibitor (8) wherein R ³ is a group represented by the formula —N (R ^a ) R ^b (where R ^a and R ^b are the same as the nitrogen atom to which they are bonded) To form a cyclic amino group), (9) R ³
Is a morpholino or thiomorpholino CD40 function inhibitor, (10) R ⁴ is substituted by 1 to 3 groups selected from an alkyl group having 1 to 15 carbon atoms, an aryl group, and a substituent group α. Aryl group, heteroaryl group,
A CD40 function that is a heteroaryl group or an aralkyl group substituted with one to three groups selected from the substituent group α, or an aralkyl group substituted with one to three groups selected from the substituent group α. Inhibitor, (11) R ⁴ is an aryl group, an aryl group substituted with 1 to 3 groups selected from substituent group α, a heteroaryl group, or 1 to 3 selected from substituent group α A CD40 function inhibitor which is a heteroaryl group substituted with 3 groups, (12) a CD40 function inhibitor wherein R ² is a nitrile group, a carboxy group or an alkoxycarbonyl group having 2 to 6 carbon atoms, (13)
(14) a CD40 function inhibitor wherein R ² is a nitrile group or an alkoxycarbonyl group having 2 to 6 carbon atoms;
R ² is a nitrile group or an ethoxycarbonyl group;
D40 function inhibitor, (15) ^one to three groups selected from an aryl ring, a heteroaryl ring, and a substituent group α together with R ¹ and R ² together with the carbon atom to which they are attached. A CD40 function inhibitor showing an aryl ring substituted with, or a heteroaryl ring substituted with 1 to 3 groups selected from the substituent group α, (16) R ¹ and R ² A CD40 function inhibitor showing an aryl ring or an aryl ring substituted with 1 to 3 groups selected from the substituent group α together with the carbon atom which is present, and (17) at least one of X and Y CD18 function inhibitors in which one is a nitrogen atom, and (18) CD40 function inhibitors in which both X and Y are nitrogen atoms.

Among the above, particularly preferred CD40 function inhibitors are (19) CD40 containing, as an active ingredient, a compound selected from the following or a pharmacologically acceptable salt thereof.
It is a function inhibitor: 4-morpholin-4-yl-2,6-diphenyl-pyrimidine-5-
Carboxylic acid ethyl ester, 4-Phenylamino-2-pyridin-3-yl-6-thiomorpholin-4-yl-pyrimidin-5-carboxylic acid ethyl ester, 2-Morpholin-4-yl-4,6- Diphenyl-nicotinonitrile.

Further, the present invention relates to the compound itself as an active ingredient of the above CD40 function inhibitor, that is, (20) a compound having the following general formula (I) or a pharmaceutically acceptable salt thereof:

[0013]

Embedded image[Wherein, R¹Is hydrogen atom, halogen atom, carbon number 3
Up to 15 alkyl groups, alkyl with 2 to 15 carbon atoms
1 to 1 selected from a thio group, an aryl group, and a substituent group α
Aryl group substituted with three groups (provided that a halogen atom
Excludes groups substituted only by ), Heteroaryl group, position
Substituted with one to three groups selected from the substituted group α.
Selected from a teloaryl group, an aralkyl group, and a substituent group α.
An aralkyl group substituted with 1 to 3 groups,
−N (R^a) R^bA group represented by the formula:^aAnd R^bIs the same
One or different, respectively, hydrogen atom, carbon number 1
Up to 15 alkyl groups, cycloalkyl having 3 to 8 carbon atoms
1 to 1 selected from a kill group, an aryl group, and a substituent group α
Aryl group substituted with three groups (provided that a halogen atom
Excludes groups substituted only by ), Heteroaryl group, position
Substituted with one to three groups selected from the substituted group α.
Select from teloaryl group, aralkyl group or substituent group α
Represents an aralkyl group substituted with 1 to 3 groups
Or R^aAnd R^bIs the nitrogen to which they are attached
Together with the atom, it forms a cyclic amino group. Where R^aPassing
And R^bDo not simultaneously represent a hydrogen atom. ) And R^TwoIs
Nitro group, nitrile group, carboxy group or C2-C2
Represents 6 alkoxycarbonyl groups, or R¹
And R^TwoTogether with the carbon atom to which they are attached,
Selected from aryl ring, heteroaryl ring and substituent group α
Aryl ring substituted with 1 to 3 groups, or substituted
Hetero substituted with one to three groups selected from the group α.
Forming a loaryl ring;^ThreeIs a halogen atom, carbon number
3 to 15 alkoxy groups, 2 to 10 carbon atoms
Select from alkylthio group, heteroaryl group and substituent group α
A heteroaryl group substituted with 1 to 3 groups represented by
Aralkyl group, 1 to 3 groups selected from substituent group α
An aralkyl group substituted with a group of the formula -N (R^a) R^bso
A group represented by the formula (wherein R^aAnd R^bIs equivalent to the above
You. ) And R^FourIs an alkyl having 1 to 15 carbons
Group, an alkylthio group having 2 to 15 carbon atoms, 1 carbon atom
Up to 15 halogenated alkyl, aryl, and substituent groups
Aryl substituted with 1 to 3 groups selected from the group α
(Excluding groups substituted only with halogen),
Heteroaryl group, 1 to 3 selected from substituent group α
Heteroaryl group, aralkyl group,
Substituted with 1 to 3 groups selected from substituent group α.
Aralkyl groups (excluding groups substituted only with halogen)
Good. ) Or -N (R^a) R^bA group represented by the formula:
^aAnd R^bIs as defined above. ), X and Y
Represents a nitrogen atom, respectively. Where R¹, R^TwoAnd R
^ThreeOne or two groups are aryl, heteroaryl,
Containing aryl, aryl-containing groups, or heteroaryl
R represents a group¹And R^FourIs phenyl and R^TwoBut
If it is a trill, R^ThreeIs methylamino, morpholino,
Cyclopropylamino, cyclobutylamino or chlorine source
Without showing offspring, R^ThreeIs a chlorine atom, and R^FourIs phenyl
If R¹Represents a chlorine atom, methylamino, ethylamido
, Phenylamino, p-methylphenylamino or p-meth
Does not show tylthiophenyl;¹Is β-naphthyl
R^TwoIs a nitrile, and R^FourIs phenyl,
R¹Is cyclopropylamino, cyclobutylamino
Not shown, R¹, R^TwoAnd R^ThreeTwo of the groups are cyclic
The remaining groups are phenyl or p-methoxy.
Does not show cyphenyl, R^ThreeIs a chlorine atom, and R^FourBut
If it is luthio, R¹Represents thienyl or furyl
R¹And R^FourAre simultaneously p-methylphenyl or pyrazine
If nil, R^ThreeRepresents a chlorine atom or morpholino
And R¹Is phenyl and R^TwoIs ethoxycarbo
Nil and R^ThreeIs methylamino, and R^FourIs phenyl
Are excluded. ]. [Substituent group α] halogen atom, lower alkyl group, halogen
Lower alkyl group, lower alkoxy group, lower halogenated
Lower alkoxy group, lower alkylthio group, lower halogenated group
Alkylthio group, lower alkylsulfinyl group, lower
Rukylsulfonyl group, group -NR ^cR^d(Where R^cAnd R^d
Are the same or different and are a hydrogen atom, a lower alkyl group
Or an aralkyl group. ), Hydroxyl, nitro, shear
No group.

In the above, preferred compounds include
(21) R ¹ is an alkyl group having 3 to 15 carbon atoms,
An alkylthio group having 2 to 15 carbon atoms, an aryl group, an aryl group substituted with 1 to 3 groups selected from the substituent group α (however, excluding a group substituted only with a halogen atom), and hetero. Aryl group, heteroaryl group substituted with 1 to 3 groups selected from substituent group α, aralkyl group, aralkyl group substituted with 1 to 3 groups selected from substituent group α, or A group represented by the formula —N (R ^a ) R ^b (wherein R ^a and R ^b are the same or different and are each a hydrogen atom, an alkyl group having 1 to 15 carbon atoms,
A cycloalkyl group having 3 to 8 carbon atoms, an aryl group, an aryl group substituted with 1 to 3 groups selected from the substituent group α (however, excluding a group substituted only with a halogen atom); A heteroaryl group, a heteroaryl group substituted with 1 to 3 groups selected from substituent group α, an aralkyl group or an aralkyl group substituted with 1 to 3 groups selected from substituent group α. Show or R ^a and R ^b
Together with the nitrogen atom to which they are attached form a cyclic amino group. However, ^Ra and ^Rb do not simultaneously represent a hydrogen atom. (22) wherein R ¹ is an aryl group, an aryl group substituted with 1 to 3 groups selected from a substituent group α, a heteroaryl group, or a group selected from a substituent group α. A heteroaryl group substituted with three groups, or a group represented by the formula -N (R ^a ) R ^b (where R ^a and R ^b are the same or different and each represent a hydrogen atom, a carbon number 1 to 15 alkyl groups, 3 to 8 carbon atoms
Substituted with 1 to 3 groups selected from cycloalkyl group, aryl group, and 1 to 3 substituent groups α, substituted with 1 to 3 groups selected from substituent group α A substituted or unsubstituted heteroaryl group, an aralkyl group, or an aralkyl group substituted by 1 to 3 groups selected from the substituent group α, or R ^a and R ^b represent a nitrogen atom to which they are bonded. Together with form a cyclic amino group. (23) R ¹ is an aryl group,
During substituted with 1 to 3 groups selected from Substituent group α aryl group, or the formula -N (R ^a) group represented by R ^b (wherein, R ^a represents a hydrogen atom, R ^b represents 1 to 15 carbon atoms
Represents an alkyl group, an aryl group, or an aryl group substituted with 1 to 3 groups selected from the substituent group α, or R ^a and R ^b represent a nitrogen atom to which they are bonded. Together with form a cyclic amino group. (24) a compound wherein R ² is a nitrile group, a carboxy group or an alkoxycarbonyl group having 2 to 6 carbon atoms, and (25) a compound wherein R ² is a nitrile group or a C ² to 6 carbon atom.
(26) compounds which are two alkoxycarbonyl groups
A compound in which R ² is a nitrile group or an ethoxycarbonyl group, (27) a compound in which R ³ is an alkoxy group having 3 to 15 carbon atoms, an alkylthio group having 2 to 15 carbon atoms, a heteroaryl group, or a substituent group α A heteroaryl group substituted with 1 to 3 groups selected, an aralkyl group, an aralkyl group substituted with 1 to 3 groups selected from substituent group α, or a formula -N (R ^a ) R a group represented by ^b (wherein, R
^a and R ^b are as defined above. ) Is a compound
(28) R ³ is an alkoxy group having 3 to 15 carbon atoms or a group represented by the formula —N (R ^a ) R ^b (where R ^a and R ^b are as defined above. ), (2)
9) R ³ is a group represented by the formula —N (R ^a ) R ^b (wherein,
R ^a and R ^b together with the nitrogen atom to which they are attached form a cyclic amino group. ), (3)
0) a compound in which R ³ is morpholino or thiomorpholino; (31) R ⁴ is selected from an alkyl group having 1 to 15 carbon atoms, an alkylthio group having 2 to 15 carbon atoms, an aryl group, and a substituent group α. Aryl group substituted with 1 to 3 groups (excluding a group substituted only with halogen), heteroaryl group, and 1 to 3 groups selected from a substituent group α. A heteroaryl group, an aralkyl group, an aralkyl group substituted with one to three groups selected from the substituent group α (however, excluding a group substituted only with halogen), or a compound of the formula -N (R ^a A) a compound represented by R ^b (wherein, R ^a and R ^b have the same meanings as described above); and (32) R ⁴ is an alkyl group having 1 to 15 carbon atoms or an aryl group. , An group substituted with one to three groups selected from the substituent group α. Lumpur group, a heteroaryl group,
A compound which is a heteroaryl group substituted with 1 to 3 groups selected from the substituent group α, an aralkyl group, or an aralkyl group substituted with 1 to 3 groups selected from the substituent group α. And (33) R ⁴ is an aryl group, an aryl group substituted with one to three groups selected from a substituent group α, a heteroaryl group, or one to three R 3 selected from a substituent group α. And a pharmacologically acceptable salt thereof.

In the above, particularly preferred compounds include (34) compounds selected from the following, or pharmaceutically acceptable salts thereof: 4-morpholin-4-yl-2,6- Diphenyl-pyrimidine-5-
Carboxylic acid ethyl ester, • 4-phenylamino-2-pyridin-3-yl-6-thiomorpholin-4-yl-pyrimidin-5-carboxylic acid ethyl ester.

In the above general formula (I), R ¹ , R ³ , R
“Halogen atom” in the definition of ⁴ and [Substituent group α]
Represents a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

The “alkyl group having 1 to 15 carbon atoms” in the definition of R ¹ , R ³ , R ⁴ , R ^a and R ^b is methyl,
Ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, 4-methylpentyl,
-Methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, , 3-dimethylbutyl, 2-ethylbutyl, heptyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1-propylbutyl, 4,4-dimethylpentyl, octyl , 1-methylheptyl, 2-methylheptyl, 3-methylheptyl,
4-methylheptyl, 5-methylheptyl, 6-methylheptyl, 1-propylpentyl, 2-ethylhexyl, 5,5-dimethylhexyl, nonyl, 3-methyloctyl, 4-methyloctyl, 5-methyloctyl, 6
-Methyloctyl, 1-propylhexyl, 2-ethylheptyl, 6,6-dimethylheptyl, decyl, 1-methylnonyl, 3-methylnonyl, 8-methylnonyl,
-Ethyloctyl, 3,7-dimethyloctyl, 7,7
-Represents a linear or branched alkyl group having 1 to 15 carbon atoms, such as dimethyloctyl, undecyl, 4,8-dimethylnonyl, dodecyl, tridecyl, tetradecyl, pentadecyl, 3,7,11-trimethyldodecyl. .

When R ¹ or R ³ represents an alkyl group, it is preferably a straight-chain or branched-chain alkyl group having 3 to 15 carbon atoms, more preferably a straight-chain or branched alkyl group having 3 to 10 carbon atoms. A chain or branched chain alkyl group, even more preferably
It is a linear or branched alkyl group having 3 to 7 carbon atoms.

When R ⁴ , R ^a or R ^b is an alkyl group, it is preferably a linear or branched alkyl group having 1 to 10 carbon atoms, more preferably 1 to 7 carbon atoms. And more preferably a straight-chain or branched-chain alkyl group having 1 to 4 carbon atoms.

In the definition of R ¹ , R ³ and R ⁴ , the “alkoxy group having 1 to 15 carbon atoms” refers to a group in which an oxygen atom is bonded to the “alkyl group having 1 to 15 carbon atoms”, It is preferably an alkoxy group having 1 to 10 carbon atoms, more preferably methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, pentyloxy, 2-pentyloxy, -Pentyloxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-
Dimethylpropoxy, 2,2-dimethylpropoxy, hexyloxy, 2-hexyloxy, 3-hexyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 4-methylpentyloxy, 1,1-dimethylbutoxy, 1, 2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1,1,2-
And represents a linear or branched alkoxy group having 1 to 7 carbon atoms such as trimethylpropoxy, 1,2,2-trimethylpropoxy and heptyloxy.

When R ³ represents an alkoxy group, it is preferably an alkoxy group having 3 to 15 carbon atoms, more preferably an alkoxy group having 3 to 10 carbon atoms, even more preferably It is an alkoxy group having 3 to 7 carbon atoms.

In the definition of R ¹ , R ³ and R ⁴ , “an alkylthio group having 1 to 15 carbon atoms” refers to the aforementioned “alkylthio group having 1 to 15 carbon atoms”.
And a group in which a sulfur atom is bonded to `` 15 alkyl groups '', preferably an alkylthio group having 1 to 10 carbon atoms, more preferably ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, s-butylthio, t-butylthio, pentylthio, 2-pentylthio, 3-pentylthio, 2-methylbutylthio, 3-
Methylbutylthio, 1,1-dimethylpropylthio,
1,2-dimethylpropylthio, 2,2-dimethylpropylthio, hexylthio, 2-hexylthio, 3-hexylthio, 2-methylpentylthio, 3-methylpentylthio, 4-methylpentylthio, 1,1-dimethylbutyl Thio, 1,2-dimethylbutylthio, 1,3-dimethylbutylthio, 2,2-dimethylbutylthio, 2,3
-Dimethylbutylthio, 3,3-dimethylbutylthio,
1 carbon atom such as 1,1,2-trimethylpropylthio, 1,2,2-trimethylpropylthio, heptylthio
Represents from 7 to 7 straight or branched chain alkylthio groups,
Even more preferably, it represents a linear or branched alkylthio group having 2 to 7 carbon atoms. “Halogenated alkyl group having 1 to 15 carbon atoms” in the definition of R ¹ , R ³ and R ⁴
Is a group in which the “alkyl group having 1 to 15 carbon atoms” is substituted with the “halogen atom”, preferably a halogenated alkyl group having 1 to 7 carbon atoms, more preferably Is trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, dibromomethyl, fluoromethyl, chloromethyl, bromomethyl, 2,2,2
1 to 1 carbon atoms such as trichloroethyl, 2,2,2-trifluoroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2,2-dibromoethyl, 3-fluoropropyl, 4-fluorobutyl There are four halogenated alkyl groups.

In the definition of R ¹ , R ³ , R ⁴ , R ^a and R ^b , “aryl group” and “aryl group substituted by 1 to 3 groups selected from substituent group α” An aryl group is a group having 6 to 10 carbon atoms such as phenyl and naphthyl.
Represents a monovalent group of aromatic hydrocarbons, more preferably,
Phenyl.

The "aryl group" may be condensed with a cycloalkyl group having 3 to 10 carbon atoms, and examples of such a group include 5-indanyl.

In the definition of R ¹ , R ³ , R ⁴ , R ^a and R ^b , “heteroaryl group” and “heteroaryl group substituted by 1 to 3 groups selected from substituent group α” "
Represents a monovalent group of a 5- to 7-membered aromatic heterocyclic ring containing 1 to 3 sulfur atoms, oxygen atoms and / or nitrogen atoms, for example, furanyl, thienyl, pyrrolyl, azepinyl, pyrazolyl , Imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl,
Examples include rings such as 1,2,3-oxadiazolyl, triazolyl, thiadiazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, and pyrazinyl.
Preferably, 2-imidazolyl, 4-imidazolyl, 1-
Pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-isoxazolyl, 4-isoxazolyl, 5
-Isoxazolyl, 2-pyrrolyl, 3-pyrrolyl, 2
-Furyl, 3-furyl, 2-thienyl, 3-thienyl,
5 to 5 containing one or two sulfur, oxygen or / and nitrogen atoms, such as 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl A monovalent group of a 6-membered aromatic heterocycle, more preferably 2-furyl, 2-thienyl,
It is a monovalent group of a 5- or 6-membered aromatic heterocycle containing one or two sulfur atoms, oxygen atoms and / or nitrogen atoms, such as pyrrolyl, 2-pyridyl, 3-pyridyl and 4-pyridyl.

The above “heteroaryl group” may be condensed with another cyclic group, and examples of such a ring include 2-benzofuryl, 3-benzofuryl, 4-benzofuryl, 5-benzofuryl and Benzofuryl, 6-benzofuryl, 1-
Isobenzofuryl, 4-isobenzofuryl, 5-isobenzofuryl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl, 1-isoindolyl, 2-isoindolyl, 4
-Isoindolyl, 5-isoindolyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 5-inolyl, 6-
Quinolyl, 7-quinolyl, 8-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-
Isoquinolyl can be mentioned.

In the definition of R ¹ , R ³ , R ⁴ , R ^a , R ^b , R ^c and R ^d , the substituent is substituted with “aralkyl group” and 1 to 3 groups selected from substituent group α. The aralkyl group of the “aralkyl group” represents a group in which the “aryl group” is bonded to the “alkyl group having 1 to 15 carbon atoms”. Examples of such a group include benzyl and indenylmethyl. Phenanthrenylmethyl, anthracenylmethyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, 9-anthrylmethyl, piperonyl,
1-phenethyl, 2-phenethyl, 1-naphthylethyl, 2-naphthylethyl, 1-phenylpropyl, 2-
Phenylpropyl, 3-phenylpropyl, 1-naphthylpropyl, 2-naphthylpropyl, 3-naphthylpropyl, 1-phenylbutyl, 2-phenylbutyl, 3-
Phenylbutyl, 4-phenylbutyl, 1-naphthylbutyl, 2-naphthylbutyl, 3-naphthylbutyl, 4-
Naphthylbutyl, 1-phenylpentyl, 2-phenylpentyl, 3-phenylpentyl, 4-phenylpentyl, 5-phenylpentyl, 1-naphthylpentyl, 2
-Naphthylpentyl, 3-naphthylpentyl, 4-naphthylpentyl, 5-naphthylpentyl, 1-phenylhexyl, 2-phenylhexyl, 3-phenylhexyl, 4-phenylhexyl, 5-phenylhexyl, 6
-Phenylhexyl, 1-naphthylhexyl, 2-naphthylhexyl, 3-naphthylhexyl, 4-naphthylhexyl, 5-naphthylhexyl, and 6-naphthylhexyl. Preferably, the "aryl group"
Is a group bonded to an alkyl group having 1 to 4 carbon atoms,
More preferably, it is benzyl, 2-phenethyl or 3-phenylpropyl, particularly preferably benzyl.

The term "cycloalkyl group having 3 to 8 carbon atoms" in the definition of ^Ra and ^Rb refers to a 3- to 8-membered saturated group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl and cyclooctyl. It represents a cyclic hydrocarbon group, preferably a 5- to 8-membered saturated cyclic hydrocarbon group, and more preferably cyclopentyl or cyclohexyl.

The “cyclic amino group” formed by R ^a and R ^b together with the nitrogen atom to which they are bonded contains at least one nitrogen atom, and further includes a nitrogen atom, an oxygen atom And / or a monovalent group of a 3- to 8-membered saturated heterocyclic ring or a partially saturated heterocyclic ring which may contain one or two sulfur atoms. Preferably, it is a monovalent group of a 4- to 8-membered saturated heterocyclic ring or a partially saturated heterocyclic ring which contains at least one nitrogen atom and may further contain one nitrogen atom, oxygen atom or sulfur atom. There are such groups as, for example, aziridinyl, azetidinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, 1,3-oxazolidinyl,
1,3-thiazolidinyl, piperidyl, piperazyl, morpholinyl, thiomorpholinyl, 1,3-perhydrooxazinyl, 1,3-perhydrothiazinyl, 1,3-
Perhydrodiazinyl, perhydroazepinyl, 1,3
-Perhydrodiazepinyl, 1,3-perhydrooxazepinyl, 1,3-perhydrothiazepinyl, 1,4-
Perhydrodiazepinyl, 1,4-perhydrooxazepinyl, 1,4-perhydrothiazepinyl, perhydroazosinyl, 1,3-perhydrodiazosynyl, 1,3
-Perhydrooxazosinyl, 1,3-perhydrothiazosinyl, 1,4-perhydrodiazosinyl, 1,4-
Examples thereof include perhydrooxazosinyl and 1,4-perhydrothiazosinyl, and more preferably contain at least one nitrogen atom and further contain one nitrogen, oxygen or sulfur atom. And is a monovalent group of a 5- to 7-membered saturated heterocyclic ring or a partially saturated heterocyclic ring, which is particularly preferably morpholinyl or thiomorpholinyl.

The above "cyclic amino group" includes 2 or 3
And a group containing such a nitrogen atom protected by an amino-protecting group. Examples of such a group include N-butoxycarbonylpiperazyl. And the like.

Examples of the “alkoxycarbonyl group having 2 to 6 carbon atoms” in the definition of R ² include, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, 2-butoxycarbonyl, t-butoxy Examples thereof include carbonyl, pentyloxycarbonyl, 2-pentyloxycarbonyl, 3-pentyloxycarbonyl, 2-methylbutyloxycarbonyl, and 3-methylbutyloxycarbonyl. Preferably, it is methoxycarbonyl or ethoxycarbonyl.

R ¹ and R ² together with the carbon atom to which they are attached form an “aryl ring”;
The aryl ring of the “aryl ring substituted with 1 to 3 groups selected from the substituent group α” refers to an aromatic hydrocarbon ring having 6 to 14 carbon atoms such as benzene, naphthalene, and anthracene. In particular, benzene is preferred.

R ¹ and R ² form together with the carbon atom to which they are attached a “heteroaryl ring” and “substituted with one to three groups selected from the substituent group α. A heteroaryl ring of the "modified heteroaryl ring" is one to three nitrogen atoms such as imidazole, pyrazole, isothiazole, isoxazole, pyrrole, furan, thiophene, pyridine, pyrazine, pyrimidine,
It represents a 5- to 7-membered aromatic heterocycle containing an oxygen atom and / or a sulfur atom. Preferably, it is a 5- or 6-membered aromatic heterocycle containing one or two nitrogen, oxygen and / or sulfur atoms, more preferably furan, thiophene, pyrrole or pyridine.

The above heteroaryl ring may be condensed with another cyclic group. Examples of such a ring include benzofuran, isobenzofuran, indole, quinoline and isoquinoline. it can.

The term "lower alkyl group" in the definition of R ^c , R ^d and the substituent α indicates a straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms. Methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl,
2-pentyl, 3-pentyl, 2-methylbutyl, 3-
Methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 2-hexyl, 3-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1, 1
-Dimethylbutyl, 1,2-dimethylbutyl, 1,3-
Dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1,1,2-
Trimethylpropyl and 1,2,2-trimethylpropyl can be mentioned. Preferably, it is an alkyl group having 1 to 4 carbon atoms, and more preferably, a methyl group, an ethyl group or a propyl group.

The term "halogenated lower alkyl group" in the definition of the substituent α means a group in which the above "lower alkyl group" is substituted by the above "halogen atom", and is preferably trifluoromethyl, trichloromethyl, Difluoromethyl,
Dichloromethyl, dibromomethyl, fluoromethyl, chloromethyl, bromomethyl, 2,2,2-trichloroethyl, 2,2,2-trifluoroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2,2
-Represents a straight-chain or branched-chain halogenated alkyl group having 1 to 6 carbon atoms such as dibromoethyl, 3-fluoropropyl and 4-fluorobutyl. More preferably, trifluoromethyl, trichloromethyl, difluoromethyl,
A halogenated alkyl group having 1 to 4 carbon atoms such as fluoromethyl, chloromethyl, bromomethyl, 2-fluoroethyl, 3-fluoropropyl and 4-fluorobutyl, particularly preferably trifluoromethyl, trichloromethyl , Difluoromethyl or fluoromethyl.

The term "lower alkoxy group" in the definition of the substituent group α means a group in which an oxygen atom is bonded to the above "lower alkyl group", preferably methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy. , S-
Butoxy, t-butoxy, pentyloxy, 2-pentyloxy, 3-pentyloxy, 2-methylbutoxy,
3-methylbutoxy, 1,1-dimethylpropoxy,
1,2-dimethylpropoxy, 2,2-dimethylpropoxy, hexyloxy, 2-hexyloxy, 3-hexyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 4-methylpentyloxy, 1,1-dimethyl Butoxy, 1,2-dimethylbutoxy, 1,3-
Dimethylbutoxy, 2,2-dimethylbutoxy, 2,3
-Dimethylbutoxy, 3,3-dimethylbutoxy, 1,
And represents a linear or branched alkoxy group having 1 to 6 carbon atoms such as 1,2-trimethylpropoxy and 1,2,2-trimethylpropoxy. More preferably, it is an alkoxy group having 1 to 4 carbon atoms, particularly preferably methoxy or ethoxy.

The term "halogenated lower alkoxy group" in the definition of the substituent group α refers to a group in which an oxygen atom is bonded to the above-mentioned "halogenated lower alkyl group", and is preferably fluoromethoxy, difluoromethoxy, or trifluoromethoxy. Methoxy, 2-fluoroethoxy, 3-fluoropropoxy,
A straight-chain or branched-chain halogenated alkoxy group having 1 to 6 carbon atoms such as 4-fluorobutoxy, 2-chloroethoxy and 2-bromoethoxy; More preferably,
It is a halogenated alkoxy group having 1 to 4 carbon atoms, more preferably difluoromethoxy or trifluoromethoxy, particularly preferably difluoromethoxy.

The "lower alkylthio group" in the definition of the substituent group α is a group in which a sulfur atom is bonded to the above "lower alkyl group", and is preferably methylthio, ethylthio,
Propylthio, isopropylthio, butylthio, isobutylthio, s-butylthio, t-butylthio, pentylthio, 2-pentylthio, 3-pentylthio, 2-methylbutylthio, 3-methylbutylthio, 1,1-dimethylpropylthio, 2-dimethylpropylthio, 2,
2-dimethylpropylthio, hexylthio, 2-hexylthio, 3-hexylthio, 2-methylpentylthio,
3-methylpentylthio, 4-methylpentylthio,
1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3-dimethylbutylthio, 2,2-dimethylbutylthio, 2,3-dimethylbutylthio, 3,3-dimethylbutylthio, 1, And represents a linear or branched alkylthio group having 1 to 6 carbon atoms such as 1,2-trimethylpropylthio and 1,2,2-trimethylpropylthio. More preferably, it is an alkylthio group having 1 to 4 carbon atoms, and particularly preferably, a methylthio group.

The term "halogenated lower alkylthio group" in the definition of the substituent group α refers to a group in which a sulfur atom is bonded to the above-mentioned "halogenated lower alkyl group", and is preferably fluoromethylthio, difluoromethylthio, trifluoromethyl or the like. C 1-6 such as methylthio, 2-fluoroethylthio, 3-fluoropropylthio, 4-fluorobutylthio, 2-chloroethylthio, 2-bromoethylthio
Represents a straight or branched halogenated alkylthio group. More preferably, it is a halogenated alkylthio group having 1 to 4 carbon atoms, more preferably difluoromethylthio or trifluoromethylthio, particularly preferably difluoromethylthio.

The term "lower alkylsulfinyl group" in the definition of the substituent group α means a group in which a sulfinyl is bonded to the above "lower alkyl group", preferably methylsulfinyl, ethylsulfinyl, propylsulfinyl,
Isopropylsulfinyl, butylsulfinyl, isobutylsulfinyl, s-butylsulfinyl, t-butylsulfinyl, pentylsulfinyl, 2-pentylsulfinyl, 3-pentylsulfinyl, 2-methylbutylsulfinyl, 3-methylbutylsulfinyl, 1,1-dimethylpropyl Sulfinyl, 1,2-
Dimethylpropylsulfinyl, 2,2-dimethylpropylsulfinyl, hexylsulfinyl, 2-hexylsulfinyl, 3-hexylsulfinyl, 2-methylpentylsulfinyl, 3-methylpentylsulfinyl, 4-methylpentylsulfinyl, 1,1-dimethylbutylsulfinyl 1,2-dimethylbutylsulfinyl, 1,3-dimethylbutylsulfinyl, 2,
2-dimethylbutylsulfinyl, 2,3-dimethylbutylsulfinyl, 3,3-dimethylbutylsulfinyl, 1,1,2-trimethylpropylsulfinyl,
And represents a linear or branched alkylsulfinyl group having 1 to 6 carbon atoms such as 1,2,2-trimethylpropylsulfinyl. More preferred is an alkylsulfinyl group having 1 to 4 carbon atoms, and particularly preferred is a methylsulfinyl group.

The term "lower alkylsulfonyl group" in the definition of the substituent group α means a group in which a sulfonyl is bonded to the above "lower alkyl group", preferably methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, Butylsulfonyl, isobutylsulfonyl, s-butylsulfonyl, t-butylsulfonyl,
Pentylsulfonyl, 2-pentylsulfonyl, 3-pentylsulfonyl, 2-methylbutylsulfonyl, 3-
Methylbutylsulfonyl, 1,1-dimethylpropylsulfonyl, 1,2-dimethylpropylsulfonyl, 2,
2-dimethylpropylsulfonyl, hexylsulfonyl, 2-hexylsulfonyl, 3-hexylsulfonyl, 2-methylpentylsulfonyl, 3-methylpentylsulfonyl, 4-methylpentylsulfonyl, 1,1
-Dimethylbutylsulfonyl, 1,2-dimethylbutylsulfonyl, 1,3-dimethylbutylsulfonyl, 2,
2-dimethylbutylsulfonyl, 2,3-dimethylbutylsulfonyl, 3,3-dimethylbutylsulfonyl,
1,1,2-trimethylpropylsulfonyl, 1,2,2
And represents a linear or branched alkylsulfonyl group having 1 to 6 carbon atoms such as 2-trimethylpropylsulfonyl. More preferred is an alkylsulfonyl group having 1 to 4 carbon atoms, and particularly preferred is a methylsulfonyl group.

"Pharmacologically acceptable salt" means that when the compound of the general formula (I) has, for example, a carboxy group and / or a phenolic hydroxyl group, it can be converted into a salt by a conventional method. Salts, such salts preferably include sodium salts, potassium salts, lithium salts, metal salts such as calcium salts, ammonium salts, and base addition salts such as organic amine compound salts such as monomethylamine and triethylamine. Can be mentioned.

The compound of the present invention having the general formula (I) or a pharmacologically acceptable salt thereof may be left in the air or recrystallized to absorb water and form adsorbed water. , Hydrates, and such hydrates are also included in the present invention.

The compound having the general formula (I) of the present invention is
An asymmetric carbon atom is present in the molecule and may have various isomers. In the compounds of the present invention, these isomers and mixtures of these isomers are all represented by a single formula, that is, the general formula (I). Accordingly, the present invention includes all these isomers and mixtures of these isomers.

Specific examples of the compound having the general formula (I) of the present invention include the compounds shown in Tables 1 to 4 below.

[0047]

Embedded image Table 1 −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− Compound No.R ¹ R ^Two R ^Three R ^Four −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− 1 Ph CN OH 2-Thi 2 Ph CN OH 3-Thi 3 Ph CN OH 2- Fur 4 Ph CN OH 3-Fur 5 Ph CN OH 2-Pyrr 6 Ph CN OH 3-Pyrr 7 Ph CN OH 3-Pyza 8 Ph CN OH 4-Pyza 9 Ph CN OH 5-Pyza 10 Ph CN OH 2-Imid 11 Ph CN OH 4-Imid 12 Ph CN OH 5-Imid 13 Ph CN OH 2-Oxa 14 Ph CN OH 4-Oxa 15 Ph CN OH 5-Oxa 16 Ph CN OH 2-Thiz 17 Ph CN OH 4-Thiz 18 Ph CN OH 5-Thiz 19 Ph CN OH Ph 20 Ph CN OH 2-Pyr 21 Ph CN OH 3-Pyr 22 Ph CN OH 4-Pyr 23 Ph CN OH 3-Pyzn 24 Ph CN OH 4-Pyzn 25 Ph CN OH 5-Pyzn 26 Ph CN OH 6-Pyzn 27 Ph CN OH 2-Pym 28 Ph CN OH 4-Pym 29 Ph CN OH 5-Pym 30 Ph CN OH 6-Pym 31 Ph CN OH 2-Pyz 32 Ph CN OH 3 -Pyz 33 Ph CN OH 2-BeFur 34 Ph CN OH 3-BeFur 35 Ph CN OH 4-BeFur 36 Ph CN OH 5-BeFur 37 Ph CN OH 6-BeFur 38 Ph CN OH 7-BeFur 39 Ph CN OH 1- Np 40 Ph CN OH 2-Np 41 Ph CN OH 1-Pyrd 42 Ph CN OH 1-Pip 43 Ph CN OH 4-Mor 44 Ph CN OH 4-Thm 45 Ph CN OH 4-Piz 46 Ph CN OH N- ( t-Bu) -Piz 47 Ph CN OH MeS 48 Ph CN OH EtS 49 Ph CN OH PrS 50 Ph CN OH i-PrS 51 Ph CN OH n-BuS 52 Ph CN OH i-BuS 53 Ph CN OH s-BuS 54 Ph CN OH t-BuS 55 Ph CN OH PnS 56 Ph CN OH n-HxS 57 Ph CN OH HepS 58 Ph CN OH n-OcS 59 Ph CN OH NnS 60 Ph CN OH DcS 61 Ph CN OH UdcS 62 Ph CN OH BzS 63 Ph CN OH Bz 64 Ph CN OH Ph- (CH _Two ) _Two 65 Ph CN OH Ph- (CH _Two ) _Three 66 Ph CN OH Ph- (CH _Two ) _Three 67 Ph CN OH 1-Np-CH _Two 68 Ph CN OH 2-Np-CH _Two 69 Ph CN OH 1-Np- (CH _Two ) _Two 70 Ph CN OH 2-Np- (CH _Two ) _Two 71 Ph CN OH cPr 72 Ph CN OH cBu 73 Ph CN OH cPn 74 Ph CN OH cHx 75 Ph CN OH cHep 76 Ph CN OH cOc 77 Ph CN OH Me 78 Ph CN OH Et 79 Ph CN OH Pr 80 Ph CN OH i -Pr 81 Ph CN OH n-Bu 82 Ph CN OH i-Bu 83 Ph CN OH s-Bu 84 Ph CN OH t-Bu 85 Ph CN OH Pn 86 Ph CN OH n-Hx 87 Ph CN OH Hep 88 Ph CN OH n-Oc 89 Ph CN OH Nn 90 Ph CN OH Dc 91 Ph CN OH Udc 92 Ph CN OH Ddc 93 Ph CN OH OH 94 Ph CN OH H 95 Ph CN MeO 2-Thi 96 Ph CN MeO 3-Thi 97 Ph CN MeO 2-Fur 98 Ph CN MeO 3-Fur 99 Ph CN MeO 2-Pyrr 100 Ph CN MeO 3-Pyrr 101 Ph CN MeO 3-Pyza 102 Ph CN MeO 4-Pyza 103 Ph CN MeO 5-Pyza 104 Ph CN MeO 2-Imid 105 Ph CN MeO 4-Imid 106 Ph CN MeO 5-Imid 107 Ph CN MeO 2-Oxa 108 Ph CN MeO 4-Oxa 109 Ph CN MeO 5-Oxa 110 Ph CN MeO 2-Thiz 111 Ph CN MeO 4-Thiz 112 Ph CN MeO 5-Thiz 113 Ph CN MeO Ph 114 Ph CN MeO 2-Pyr 115 Ph CN MeO 3-Pyr 116 Ph CN MeO 4-Pyr 117 Ph CN MeO 3-Pyzn 118 Ph CN MeO 4-Pyzn 119 Ph CN MeO 5-Pyzn 120 Ph CN MeO 6-Pyzn 121 Ph CN MeO 2-Pym 122 Ph CN MeO 4-Pym 123 Ph CN MeO 5-Pym 124 Ph CN MeO 6-Pym 125 Ph CN MeO 2-Pyz 126 Ph CN MeO 3-Pyz 127 Ph CN MeO 2-BeFur 128 Ph CN MeO 3-BeFur 129 Ph CN MeO 4-BeFur 130 Ph CN MeO 5-BeFur 131 Ph CN MeO 6-BeFur 132 Ph CN MeO 7-BeFur 133 Ph CN MeO 1-Np 134 Ph CN MeO 2-Np 135 Ph CN MeO 1-Pyrd 136 Ph CN MeO 1-Pip 137 Ph CN MeO 4-Mor 138 Ph CN MeO 4-Thm 139 Ph CN MeO 4 -Piz 140 Ph CN MeO N- (t-Bu) -Piz 141 Ph CN MeO MeS 142 Ph CN MeO EtS 143 Ph CN MeO PrS 144 Ph CN MeO i-PrS 145 Ph CN MeO n-BuS 146 Ph CN MeO i- BuS 147 Ph CN MeO s-BuS 148 Ph CN MeO t-BuS 149 Ph CN MeO PnS 150 Ph CN MeO n-HxS 151 Ph CN MeO HepS 152 Ph CN MeO n-OcS 153 Ph CN MeO NnS 154 Ph CN MeO DcS 155 Ph CN MeO UdcS 156 Ph CN MeO DdcS 157 Ph CN MeO Bz 158 Ph CN MeO Ph- (CH _Two ) _Two 159 Ph CN MeO Ph- (CH _Two ) _Three 160 Ph CN MeO Ph- (CH _Two ) _Four 161 Ph CN MeO 1-Np-CH _Two 162 Ph CN MeO 2-Np-CH _Two 163 Ph CN MeO 1-Np- (CH _Two ) _Two 164 Ph CN MeO 2-Np- (CH _Two ) _Two 165 Ph CN MeO cPr 166 Ph CN MeO cBu 167 Ph CN MeO cPn 168 Ph CN MeO cHx 169 Ph CN MeO cHep 170 Ph CN MeO cOc 171 Ph CN MeO Me 172 Ph CN MeO Et 173 Ph CN MeO Pr 174 Ph CN MeO i -Pr 175 Ph CN MeO n-Bu 176 Ph CN MeO i-Bu 177 Ph CN MeO s-Bu 178 Ph CN MeO t-Bu 179 Ph CN MeO Pn 180 Ph CN MeO n-Hx 181 Ph CN MeO Hep 182 Ph CN MeO n-Oc 183 Ph CN MeO Nn 184 Ph CN MeO Dc 185 Ph CN MeO Udc 186 Ph CN MeO Ddc 187 Ph CN MeO OH 188 Ph CN MeO H 189 Ph CN EtO 2-Thi 190 Ph CN EtO 3-Thi 191 Ph CN EtO 2-Fur 192 Ph CN EtO 3-Fur 193 Ph CN EtO 2-Pyrr 194 Ph CN EtO 3-Pyrr 195 Ph CN EtO 3-Pyza 196 Ph CN EtO 4-Pyza 197 Ph CN EtO 5-Pyza 198 Ph CN EtO 2-Imid 199 Ph CN EtO 4-Imid 200 Ph CN EtO 5-Imid 201 Ph CN EtO 2-Oxa 202 Ph CN EtO 4-Oxa 203 Ph CN EtO 5-Oxa 204 Ph CN EtO 2-Thiz 205 Ph CN EtO 4-Thiz 206 Ph CN EtO 5-Thiz 207 Ph CN EtO Ph 208 Ph CN EtO 2-Pyr 209 Ph CN EtO 3-Pyr 210 Ph CN EtO 4-Pyr 211 Ph CN EtO 3-Pyzn 212 Ph CN EtO 4-Pyzn 213 Ph CN EtO 5-Pyzn 214 Ph CN EtO 6-Pyzn 215 Ph CN EtO 2-Pym 216 Ph CN EtO 4-P ym 217 Ph CN EtO 5-Pym 218 Ph CN EtO 6-Pym 219 Ph CN EtO 2-Pyz 220 Ph CN EtO 3-Pyz 221 Ph CN EtO 2-BeFur 222 Ph CN EtO 3-BeFur 223 Ph CN EtO 4-BeFur 224 Ph CN EtO 5-BeFur 225 Ph CN EtO 6-BeFur 226 Ph CN EtO 7-BeFur 227 Ph CN EtO 1-Np 228 Ph CN EtO 2-Np 229 Ph CN EtO 1-Pyrd 230 Ph CN EtO 1-Pip 231 Ph CN EtO 4-Mor 232 Ph CN EtO 4-Thm 233 Ph CN EtO 4-Piz 234 Ph CN EtO t-Bupip 235 Ph CN EtO MeS 236 Ph CN EtO EtS 237 Ph CN EtO PrS 238 Ph CN EtO i-PrS 239 Ph CN EtO n-BuS 240 Ph CN EtO i-BuS 241 Ph CN EtO s-BuS 242 Ph CN EtO t-BuS 243 Ph CN EtO PnS 244 Ph CN EtO n-HxS 245 Ph CN EtO HepS 246 Ph CN EtO n- OcS 247 Ph CN EtO NnS 248 Ph CN EtO DcS 249 Ph CN EtO UdcS 250 Ph CN EtO DdcS 251 Ph CN EtO Bz 252 Ph CN EtO Ph- (CH _Two ) _Two 253 Ph CN EtO Ph- (CH _Two ) _Three 254 Ph CN EtO Ph- (CH _Two ) _Three 255 Ph CN EtO 1-Np-CH _Two 256 Ph CN EtO 2-Np-CH _Two 257 Ph CN EtO 1-Np- (CH _Two ) _Two 258 Ph CN EtO 2-Np- (CH _Two ) _Two 259 Ph CN EtO cPr 260 Ph CN EtO cBu 261 Ph CN EtO cPn 262 Ph CN EtO cHx 263 Ph CN EtO cHep 264 Ph CN EtO cOc 265 Ph CN EtO Me 266 Ph CN EtO Et 267 Ph CN EtO Pr 268 Ph CN EtO i -Pr 269 Ph CN EtO n-Bu 270 Ph CN EtO i-Bu 271 Ph CN EtO s-Bu 272 Ph CN EtO t-Bu 273 Ph CN EtO Pn 274 Ph CN EtO n-Hx 275 Ph CN EtO Hep 276 Ph CN EtO n-Oc 277 Ph CN EtO Nn 278 Ph CN EtO Dc 279 Ph CN EtO Udc 280 Ph CN EtO Ddc 281 Ph CN EtO OH 282 Ph CN EtO H 283 Ph CN PnO 2-Thi 284 Ph CN PnO 3-Thi 285 Ph CN PnO 2-Fur 286 Ph CN PnO 3-Fur 287 Ph CN PnO 2-Pyrr 288 Ph CN PnO 3-Pyrr 289 Ph CN PnO 3-Pyza 290 Ph CN PnO 4-Pyza 291 Ph CN PnO 5-Pyza 292 Ph CN PnO 2-Imid 293 Ph CN PnO 4-Imid 294 Ph CN PnO 5-Imid 295 Ph CN PnO 2-Oxa 296 Ph CN PnO 4-Oxa 297 Ph CN PnO 5-Oxa 298 Ph CN PnO 2-Thiz 299 Ph CN PnO 4-Thiz 300 Ph CN PnO 5-Thiz 301 Ph CN PnO Ph 302 Ph CN PnO 2-Pyr 303 Ph CN PnO 3-Pyr 304 Ph CN PnO 4-Pyr 305 Ph CN PnO 3-Pyzn 306 Ph CN PnO 4-Pyzn 307 Ph CN PnO 5-Pyzn 308 Ph CN PnO 6-Pyzn 309 Ph CN PnO 2-Pym 310 Ph CN PnO 4-P ym 311 Ph CN PnO 5-Pym 312 Ph CN PnO 6-Pym 313 Ph CN PnO 2-Pyz 314 Ph CN PnO 3-Pyz 315 Ph CN PnO 2-BeFur 316 Ph CN PnO 3-BeFur 317 Ph CN PnO 4-BeFur 318 Ph CN PnO 5-BeFur 319 Ph CN PnO 6-BeFur 320 Ph CN PnO 7-BeFur 321 Ph CN HepO Ph 322 Ph CN HepO 2-Pyr 323 Ph CN HepO 3-Pyr 324 Ph CN HepO 4-Pyr 325 Ph CN HepO 3-Pyzn 326 Ph CN HepO 4-Pyzn 327 Ph CN HepO 5-Pyzn 328 Ph CN HepO 6-Pyzn 329 Ph CN HepO 2-Pym 330 Ph CN HepO 4-Pym 331 Ph CN HepO 5-Pym 332 Ph CN HepO 6-Pym 333 Ph CN HepO 2-Pyz 334 Ph CN HepO 3-Pyz 335 Ph CN 4-Mor 2-Thi 336 Ph CN 4-Mor 3-Thi 337 Ph CN 4-Mor 2-Fur 338 Ph CN 4-Mor 3-Fur 339 Ph CN 4-Mor 2-Pyrr 340 Ph CN 4-Mor 3-Pyrr 341 Ph CN 4-Mor 3-Pyza 342 Ph CN 4-Mor 4-Pyza 343 Ph CN 4-Mor 5-Pyza 344 Ph CN 4-Mor 2-Imid 345 Ph CN 4-Mor 4-Imid 346 Ph CN 4-Mor 5-Imid 347 Ph CN 4-Mor 2-Oxa 348 Ph CN 4-Mor 4-Oxa 349 Ph CN 4-Mor 5 -Oxa 350 Ph CN 4-Mor 2-Thiz 351 Ph CN 4-Mor 4-Thiz 352 Ph CN 4-Mor 5-Thiz 353 Ph CN 4-Mor Ph 354 Ph CN 4-Mor 2-Pyr 355 Ph CN 4- Mor 3-Pyr 356 Ph CN 4-Mor 4-Py r 357 Ph CN 4-Mor 3-Pyzn 358 Ph CN 4-Mor 4-Pyzn 359 Ph CN 4-Mor 5-Pyzn 360 Ph CN 4-Mor 6-Pyzn 361 Ph CN 4-Mor 2-Pym 362 Ph CN 4 -Mor 4-Pym 363 Ph CN 4-Mor 5-Pym 364 Ph CN 4-Mor 6-Pym 365 Ph CN 4-Mor 2-Pyz 366 Ph CN 4-Mor 3-Pyz 367 Ph CN 4-Mor 2-BeFur 368 Ph CN 4-Mor 3-BeFur 369 Ph CN 4-Mor 4-BeFur 370 Ph CN 4-Mor 5-BeFur 371 Ph CN 4-Mor 6-BeFur 372 Ph CN 4-Mor 7-BeFur 373 Ph CN 4- Mor 1-Np 374 Ph CN 4-Mor 2-Np 375 Ph CN 4-Mor 1-Pyrd 376 Ph CN 4-Mor 1-Pip 377 Ph CN 4-Mor 4-Mor 378 Ph CN 4-Mor 4-Thm 379 Ph CN 4-Mor 4-Piz 380 Ph CN 4-Mor N- (t-Bu) -Piz 381 Ph CN 4-Mor MeS 382 Ph CN 4-Mor EtS 383 Ph CN 4-Mor PrS 384 Ph CN 4-Mor i-PrS 385 Ph CN 4-Morn-BuS 386 Ph CN 4-Mor i-BuS 387 Ph CN 4-Mor s-BuS 388 Ph CN 4-Mort-BuS 389 Ph CN 4-Mor PnS 390 Ph CN 4 -Mor n-HxS 391 Ph CN 4-Mor HepS 392 Ph CN 4-Mor n-OcS 393 Ph CN 4-Mor NnS 394 Ph CN 4-Mor DcS 395 Ph CN 4-Mor UdcS 396 Ph CN 4-Mor DdcS 397 Ph CN 4-Mor Bz 398 Ph CN 4-Mor Ph- (CH _Two ) _Two 399 Ph CN 4-Mor Ph- (CH _Two ) _Three 400 Ph CN 4-Mor Ph- (CH _Two ) _Three 401 Ph CN 4-Mor 1-Np-CH _Two 402 Ph CN 4-Mor 2-Np-CH _Two 403 Ph CN 4-Mor 1-Np- (CH _Two ) _Two 404 Ph CN 4-Mor 2-Np- (CH _Two ) _Two 405 Ph CN 4-Mor cPr 406 Ph CN 4-Mor cBu 407 Ph CN 4-Mor cPn 408 Ph CN 4-Mor cHx 409 Ph CN 4-Mor cHep 410 Ph CN 4-Mor cOc 411 Ph CN 4-Mor Me 412 Ph CN 4-Mor Et 413 Ph CN 4-Mor Pr 414 Ph CN 4-Mor i-Pr 415 Ph CN 4-Mor n-Bu 416 Ph CN 4-Mor i-Bu 417 Ph CN 4-Mor s-Bu 418 Ph CN 4-Mor t-Bu 419 Ph CN 4-Mor Pn 420 Ph CN 4-Mor n-Hx 421 Ph CN 4-Mor Hep 422 Ph CN 4-Mor n-Oc 423 Ph CN 4-Mor Nn 424 Ph CN 4-Mor Dc 425 Ph CN 4-Mor Udc 426 Ph CN 4-Mor Ddc 427 Ph CN 4-Mor OH 428 Ph CN 4-Mor H 429 Ph CN 4-Thm 2-Thi 430 Ph CN 4-Thm 3-Thi 431 Ph CN 4-Thm 2-Fur 432 Ph CN 4-Thm 3-Fur 433 Ph CN 4-Thm 2-Pyrr 434 Ph CN 4-Thm 3-Pyrr 435 Ph CN 4-Thm 3-Pyza 436 Ph CN 4- Thm 4-Pyza 437 Ph CN 4-Thm 5-Pyza 438 Ph CN 4-Thm 2-Imid 439 Ph CN 4-Thm 4-Imid 440 Ph CN 4-Thm 5-Imid 441 Ph CN 4-Thm 2-Oxa 442 Ph CN 4-Thm 4-Oxa 443 Ph CN 4-Thm 5-Oxa 444 Ph CN 4-Thm 2-Thiz 445 Ph CN 4-Thm 4-Thiz 446 Ph CN 4-Thm 5-Thiz 447 Ph CN 4-Thm Ph 448 Ph CN 4-Thm 2-Pyr 449 Ph CN 4-Thm 3-Pyr 450 Ph CN 4-Thm 4-Pyr 451 Ph CN 4-Thm 3-Pyzn 452 Ph CN 4-Thm 4-Pyzn 453 Ph CN 4-Thm 5-Pyzn 454 Ph CN 4-Thm 6-Pyzn 455 Ph CN 4-Thm 2-Pym 456 Ph CN 4-Thm 4-Pym 457 Ph CN 4-Thm 5 -Pym 458 Ph CN 4-Thm 6-Pym 459 Ph CN 4-Thm 2-Pyz 460 Ph CN 4-Thm 3-Pyz 461 Ph CN 4-Thm 2-BeFur 462 Ph CN 4-Thm 3-BeFur 463 Ph CN 4-Thm 4-BeFur 464 Ph CN 4-Thm 5-BeFur 465 Ph CN 4-Thm 6-BeFur 466 Ph CN 4-Thm 7-BeFur 467 Ph CN 4-Thm 1-Np 468 Ph CN 4-Thm 2- Np 469 Ph CN 4-Thm 1-Pyrd 470 Ph CN 4-Thm 1-Pip 471 Ph CN 4-Thm 4-Mor 472 Ph CN 4-Thm 4-Thm 473 Ph CN 4-Thm 4-Piz 474 Ph CN 4 -Thm N- (t-Bu) -Piz 475 Ph CN 4-Thm MeS 476 Ph CN 4-Thm EtS 477 Ph CN 4-Thm PrS 478 Ph CN 4-Thm i-PrS 479 Ph CN 4-Thm n-BuS 480 Ph CN 4-Thm i-BuS 481 Ph CN 4-Thm s-BuS 482 Ph CN 4-Thm t-BuS 483 Ph CN 4-Thm PnS 484 Ph CN 4-Thm n-HxS 485 Ph CN 4-Thm HepS 486 Ph CN 4-Thm n-OcS 487 Ph CN 4-Thm NnS 488 Ph CN 4-Thm DcS 489 Ph CN 4-Thm UdcS 490 Ph CN 4-Thm DdcS 491 Ph CN 4-Thm Bz 492 Ph CN 4-Thm Ph- (CH _Two ) _Two 493 Ph CN 4-Thm Ph- (CH _Two ) _Three 494 Ph CN 4-Thm Ph- (CH _Two ) _Three 495 Ph CN 4-Thm 1-Np-CH _Two 496 Ph CN 4-Thm 2-Np-CH _Two 497 Ph CN 4-Thm 1-Np- (CH _Two ) _Two 498 Ph CN 4-Thm 2-Np- (CH _Two ) _Two 499 Ph CN 4-Thm cPr 500 Ph CN 4-Thm cBu 501 Ph CN 4-Thm cPn 502 Ph CN 4-Thm cHx 503 Ph CN 4-Thm cHep 504 Ph CN 4-Thm cOc 505 Ph CN 4-Thm Me 506 Ph CN 4-Thm Et 507 Ph CN 4-Thm Pr 508 Ph CN 4-Thm i-Pr 509 Ph CN 4-Thm n-Bu 510 Ph CN 4-Thm i-Bu 511 Ph CN 4-Thm s-Bu 512 Ph CN 4-Thm t-Bu 513 Ph CN 4-Thm Pn 514 Ph CN 4-Thm n-Hx 515 Ph CN 4-Thm Hep 516 Ph CN 4-Thm n-Oc 517 Ph CN 4-Thm Nn 518 Ph CN 4-Thm Dc 519 Ph CN 4-Thm Udc 520 Ph CN 4-Thm Ddc 521 Ph CN 4-Thm OH 522 Ph CN 4-Thm H 523 Ph CN 1-Pip 2-Thi 524 Ph CN 1-Pip 3-Thi 525 Ph CN 1-Pip 2-Fur 526 Ph CN 1-Pip 3-Fur 527 Ph CN 1-Pip 2-Pyrr 528 Ph CN 1-Pip 3-Pyrr 529 Ph CN 1-Pip 3-Pyza 530 Ph CN 1- Pip 4-Pyza 531 Ph CN 1-Pip 5-Pyza 532 Ph CN 1-Pip 2-Imid 533 Ph CN 1-Pip 4-Imid 534 Ph CN 1-Pip 5-Imid 535 Ph CN 1-Pip 2-Oxa 536 Ph CN 1-Pip 4-Oxa 537 Ph CN 1-Pip 5-Oxa 538 Ph CN 1-Pip 2-Thiz 539 Ph CN 1-Pip 4-Thiz 540 Ph CN 1-Pip 5-Thiz 541 Ph CN 1-Pip Ph 542 Ph CN 1-Pip 2-Pyr 543 Ph CN 1-Pip 3-Pyr 544 Ph CN 1-Pip 4-Pyr 545 Ph CN 1-Pip 3-Pyzn 546 Ph CN 1-Pip 4-Pyzn 547 Ph CN 1-Pip 5-Pyzn 548 Ph CN 1-Pip 6-Pyzn 549 Ph CN 1-Pip 2-Pym 550 Ph CN 1-Pip 4-Pym 551 Ph CN 1-Pip 5 -Pym 552 Ph CN 1-Pip 6-Pym 553 Ph CN 1-Pip 2-Pyz 554 Ph CN 1-Pip 3-Pyz 555 Ph CN 1-Pip 2-BeFur 556 Ph CN 1-Pip 3-BeFur 557 Ph CN 1-Pip 4-BeFur 558 Ph CN 1-Pip 5-BeFur 559 Ph CN 1-Pip 6-BeFur 560 Ph CN 1-Pip 7-BeFur 561 Ph CN 1-Pip 1-Np 562 Ph CN 1-Pip 2- Np 563 Ph CN 1-Pip 1-Pyrd 564 Ph CN 1-Pip 1-Pip 565 Ph CN 1-Pip 4-Mor 566 Ph CN 1-Pip 4-Thm 567 Ph CN 1-Pip 4-Piz 568 Ph CN 1 -Pip N- (t-Bu) -Piz 569 Ph CN 1-Pip MeS 570 Ph CN 1-Pip EtS 571 Ph CN 1-Pip PrS 572 Ph CN 1-Pip i-PrS 573 Ph CN 1-Pip n-BuS 574 Ph CN 1-Pip i-BuS 575 Ph CN 1-Pip s-BuS 576 Ph CN 1-Pip t-BuS 577 Ph CN 1-Pip PnS 578 Ph CN 1-Pip n-HxS 579 Ph CN 1-Pip HepS 580 Ph CN 1-Pip n-OcS 581 Ph CN 1-Pip NnS 582 Ph CN 1-Pip DcS 583 Ph CN 1-Pip UdcS 584 Ph CN 1-Pip DdcS 585 Ph CN 1-Pip Bz 586 Ph CN 1-Pip Ph- (CH _Two ) _Two 587 Ph CN 1-Pip Ph- (CH _Two ) _Three 588 Ph CN 1-Pip Ph- (CH _Two ) _Three 589 Ph CN 1-Pip 1-Np-CH _Two 590 Ph CN 1-Pip 2-Np-CH _Two 591 Ph CN 1-Pip 1-Np- (CH _Two ) _Two 592 Ph CN 1-Pip 2-Np- (CH _Two ) _Two 593 Ph CN 1-Pip cPr 594 Ph CN 1-Pip cBu 595 Ph CN 1-Pip cPn 596 Ph CN 1-Pip cHx 597 Ph CN 1-Pip cHep 598 Ph CN 1-Pip cOc 599 Ph CN 1-Pip Me 600 Ph CN 1-Pip Et 601 Ph CN 1-Pip Pr 602 Ph CN 1-Pip i-Pr 603 Ph CN 1-Pip n-Bu 604 Ph CN 1-Pip i-Bu 605 Ph CN 1-Pip s-Bu 606 Ph CN 1-Pip t-Bu 607 Ph CN 1-Pip Pn 608 Ph CN 1-Pip n-Hx 609 Ph CN 1-Pip Hep 610 Ph CN 1-Pip n-Oc 611 Ph CN 1-Pip Nn 612 Ph CN 1-Pip Dc 613 Ph CN 1-Pip Udc 614 Ph CN 1-Pip Ddc 615 Ph CN 1-Pip OH 616 Ph CN 1-Pip H 617 Ph CN 4-Piz 2-Thi 618 Ph CN 4-Piz 3-Thi 619 Ph CN 4-Piz 2-Fur 620 Ph CN 4-Piz 3-Fur 621 Ph CN 4-Piz 2-Pyrr 622 Ph CN 4-Piz 3-Pyrr 623 Ph CN 4-Piz 3-Pyza 624 Ph CN 4- Piz 4-Pyza 625 Ph CN 4-Piz 5-Pyza 626 Ph CN 4-Piz 2-Imid 627 Ph CN 4-Piz 4-Imid 628 Ph CN 4-Piz 5-Imid 629 Ph CN 4-Piz 2-Oxa 630 Ph CN 4-Piz 4-Oxa 631 Ph CN 4-Piz 5-Oxa 632 Ph CN 4-Piz 2-Thiz 633 Ph CN 4-Piz 4-Thiz 634 Ph CN 4-Piz 5-Thiz 635 Ph CN 4-Piz Ph 636 Ph CN 4-Piz 2-Pyr 637 Ph CN 4-Piz 3-Pyr 638 Ph CN 4-Piz 4-Pyr 639 Ph CN 4-Piz 3-Pyzn 640 Ph CN 4-Piz 4-Pyzn 641 Ph CN 4-Piz 5-Pyzn 642 Ph CN 4-Piz 6-Pyzn 643 Ph CN 4-Piz 2-Pym 644 Ph CN 4-Piz 4-Pym 645 Ph CN 4-Piz 5 -Pym 646 Ph CN 4-Piz 6-Pym 647 Ph CN 4-Piz 2-Pyz 648 Ph CN 4-Piz 3-Pyz 649 Ph CN 4-Piz 2-BeFur 650 Ph CN 4-Piz 3-BeFur 651 Ph CN 4-Piz 4-BeFur 652 Ph CN 4-Piz 5-BeFur 653 Ph CN 4-Piz 6-BeFur 654 Ph CN 4-Piz 7-BeFur 655 Ph CN 4-Piz 1-Np 656 Ph CN 4-Piz 2- Np 657 Ph CN 4-Piz 1-Pyrd 658 Ph CN 4-Piz 1-Pip 659 Ph CN 4-Piz 4-Mor 660 Ph CN 4-Piz 4-Thm 661 Ph CN 4-Piz 4-Piz 662 Ph CN 4 -Piz N- (t-Bu) -Piz 663 Ph CN 4-Piz MeS 664 Ph CN 4-Piz EtS 665 Ph CN 4-Piz PrS 666 Ph CN 4-Piz i-PrS 667 Ph CN 4-Piz n-BuS 668 Ph CN 4-Piz i-BuS 669 Ph CN 4-Piz s-BuS 670 Ph CN 4-Piz t-BuS 671 Ph CN 4-Piz PnS 672 Ph CN 4-Piz n-HxS 673 Ph CN 4-Piz HepS 674 Ph CN 4-Piz n-OcS 675 Ph CN 4-Piz NnS 676 Ph CN 4-Piz DcS 677 Ph CN 4-Piz UdcS 678 Ph CN 4-Piz DdcS 679 Ph CN 4-Piz Bz 680 Ph CN 4-Piz Ph- (CH _Two ) _Two 681 Ph CN 4-Piz Ph- (CH _Two ) _Three 682 Ph CN 4-Piz Ph- (CH _Two ) _Three 683 Ph CN 4-Piz 1-Np-CH _Two 684 Ph CN 4-Piz 2-Np-CH _Two 685 Ph CN 4-Piz 1-Np- (CH _Two ) _Two 686 Ph CN 4-Piz 2-Np- (CH _Two ) _Two 687 Ph CN 4-Piz cPr 688 Ph CN 4-Piz cBu 689 Ph CN 4-Piz cPn 690 Ph CN 4-Piz cHx 691 Ph CN 4-Piz cHep 692 Ph CN 4-Piz cOc 693 Ph CN 4-Piz Me 694 Ph CN 4-Piz Et 695 Ph CN 4-Piz Pr 696 Ph CN 4-Piz i-Pr 697 Ph CN 4-Piz n-Bu 698 Ph CN 4-Piz i-Bu 699 Ph CN 4-Piz s-Bu 700 Ph CN 4-Piz t-Bu 701 Ph CN 4-Piz Pn 702 Ph CN 4-Piz n-Hx 703 Ph CN 4-Piz Hep 704 Ph CN 4-Piz n-Oc 705 Ph CN 4-Piz Nn 706 Ph CN 4-Piz Dc 707 Ph CN 4-Piz Udc 708 Ph CN 4-Piz Ddc 709 Ph CN 4-Piz OH 710 Ph CN 4-Piz H 711 Ph CN (Et) _Two N Ph 712 Ph CN (Et) _Two N 2-Pyr 713 Ph CN (Et) _Two N 3-Pyr 714 Ph CN (Et) _Two N 4-Pyr 715 Ph CN (Et) _Two N 3-Pyzn 716 Ph CN (Et) _Two N 4-Pyzn 717 Ph CN (Et) _Two N 5-Pyzn 718 Ph CN (Et) _Two N 6-Pyzn 719 Ph CN (Et) _Two N 2-Pym 720 Ph CN (Et) _Two N 4-Pym 721 Ph CN (Et) _Two N 5-Pym 722 Ph CN (Et) _Two N 6-Pym 723 Ph CN (Et) _Two N 2-Pyz 724 Ph CN (Et) _Two N 3-Pyz 725 Ph CN cHx-NH Ph 726 Ph CN cHx-NH 2-Pyr 727 Ph CN cHx-NH 3-Pyr 728 Ph CN cHx-NH 4-Pyr 729 Ph CN cHx-NH 3-Pyzn 730 Ph CN cHx-NH 4-Pyzn 731 Ph CN cHx-NH 5-Pyzn 732 Ph CN cHx-NH 6-Pyzn 733 Ph CN cHx-NH 2-Pym 734 Ph CN cHx-NH 4-Pym 735 Ph CN cHx-NH 5- Pym 736 Ph CN cHx-NH 6-Pym 737 Ph CN cHx-NH 2-Pyz 738 Ph CN cHx-NH 3-Pyz 739 Ph CN Ph-NH Ph 740 Ph CN Ph-NH 2-Pyr 741 Ph CN Ph-NH 3-Pyr 742 Ph CN Ph-NH 4-Pyr 743 Ph CN Ph-NH 3-Pyzn 744 Ph CN Ph-NH 4-Pyzn 745 Ph CN Ph-NH 5-Pyzn 746 Ph CN Ph-NH 6-Pyzn 747 Ph CN Ph-NH 2-Pym 748 Ph CN Ph-NH 4-Pym 749 Ph CN Ph-NH 5-Pym 750 Ph CN Ph-NH 6-Pym 751 Ph CN Ph-NH 2-Pyz 752 Ph CN Ph-NH 3 -Pyz 753 Ph CN 3-Cl-Ph-NH Ph 754 Ph CN 3-Cl-Ph-NH 2-Pyr 755 Ph CN 3-Cl-Ph-NH 3-Pyr 756 Ph CN 3-Cl-Ph-NH 4 -Pyr 757 Ph CN 3-Cl-Ph-NH 3-Pyzn 758 Ph CN 3-Cl-Ph-NH 4-Pyzn 759 Ph CN 3-Cl-Ph-NH 5-Pyzn 760 Ph CN 3-Cl-Ph- NH 6-Pyzn 761 Ph CN 3-Cl-Ph-NH 2-Pym 762 Ph CN 3-Cl-Ph-NH 4-Pym 763 Ph CN 3-Cl-Ph-NH 5-Pym 764 Ph CN 3-Cl- Ph-NH 6-Pym 765 Ph CN 3-Cl-Ph-NH 2-Pyz 766 Ph C N 3-Cl-Ph-NH 3-Pyz 767 Ph CN 2-Me-Ph-NH Ph 768 Ph CN 2-Me-Ph-NH 2-Pyr 769 Ph CN 2-Me-Ph-NH 3-Pyr 770 Ph CN 2-Me-Ph-NH 4-Pyr 771 Ph CN 2-Me-Ph-NH 3-Pyzn 772 Ph CN 2-Me-Ph-NH 4-Pyzn 773 Ph CN 2-Me-Ph-NH 5-Pyzn 774 Ph CN 2-Me-Ph-NH 6-Pyzn 775 Ph CN 2-Me-Ph-NH 2-Pym 776 Ph CN 2-Me-Ph-NH 4-Pym 777 Ph CN 2-Me-Ph-NH 5 -Pym 778 Ph CN 2-Me-Ph-NH 6-Pym 779 Ph CN 2-Me-Ph-NH 2-Pyz 780 Ph CN 2-Me-Ph-NH 3-Pyz 781 Ph CN 3-Me-Ph- NH Ph 782 Ph CN 3-Me-Ph-NH 2-Pyr 783 Ph CN 3-Me-Ph-NH 3-Pyr 784 Ph CN 3-Me-Ph-NH 4-Pyr 785 Ph CN 3-Me-Ph- NH 3-Pyzn 786 Ph CN 3-Me-Ph-NH 4-Pyzn 787 Ph CN 3-Me-Ph-NH 5-Pyzn 788 Ph CN 3-Me-Ph-NH 6-Pyzn 789 Ph CN 3-Me- Ph-NH 2-Pym 790 Ph CN 3-Me-Ph-NH 4-Pym 791 Ph CN 3-Me-Ph-NH 5-Pym 792 Ph CN 3-Me-Ph-NH 6-Pym 793 Ph CN 3- Me-Ph-NH 2-Pyz 794 Ph CN 3-Me-Ph-NH 3-Pyz 795 Ph CN 4-Me-Ph-NH Ph 796 Ph CN 4-Me-Ph-NH 2-Pyr 797 Ph CN 4- Me-Ph-NH 3-Pyr 798 Ph CN 4-Me-Ph-NH 4-Pyr 799 Ph CN 4-Me-Ph-NH 3-Pyzn 800 Ph CN 4-Me-Ph-NH 4-Pyzn 801 Ph CN 4-Me-Ph-NH 5-Pyzn 802 Ph CN 4-Me-Ph-NH 6-Pyzn 803 Ph CN 4-Me-Ph-NH 2-Pym 804 Ph CN 4-Me-Ph-NH 4-Pym 805 Ph CN 4-Me-Ph-NH 5-Pym 806 Ph CN 4-Me-Ph-NH 6-Pym 807 Ph CN 4-Me-Ph-NH 2-Pyz 808 Ph CN 4-Me-Ph-NH 3-Pyz 809 Ph CN n-Hx-NH Ph 810 Ph CN n-Hx-NH 2-Pyr 811 Ph CN n -Hx-NH 3-Pyr 812 Ph CN n-Hx-NH 4-Pyr 813 Ph CN n-Hx-NH 3-Pyzn 814 Ph CN n-Hx-NH 4-Pyzn 815 Ph CN n-Hx-NH 5- Pyzn 816 Ph CN n-Hx-NH 6-Pyzn 817 Ph CN n-Hx-NH 2-Pym 818 Ph CN n-Hx-NH 4-Pym 819 Ph CN n-Hx-NH 5-Pym 820 Ph CN n- Hx-NH 6-Pym 821 Ph CN n-Hx-NH 2-Pyz 822 Ph CN n-Hx-NH 3-Pyz 823 Ph CN EtO- (CH _Two ) _Two -NH Ph 824 Ph CN EtO- (CH _Two ) _Two -NH 2-Pyr 825 Ph CN EtO- (CH _Two ) _Two -NH 3-Pyr 826 Ph CN EtO- (CH _Two ) _Two -NH 4-Pyr 827 Ph CN EtO- (CH _Two ) _Two -NH 3-Pyzn 828 Ph CN EtO- (CH _Two ) _Two -NH 4-Pyzn 829 Ph CN EtO- (CH _Two ) _Two -NH 5-Pyzn 830 Ph CN EtO- (CH _Two ) _Two -NH 6-Pyzn 831 Ph CN EtO- (CH _Two ) _Two -NH 2-Pym 832 Ph CN EtO- (CH _Two ) _Two -NH 4-Pym 833 Ph CN EtO- (CH _Two ) _Two -NH 5-Pym 834 Ph CN EtO- (CH _Two ) _Two -NH 6-Pym 835 Ph CN EtO- (CH _Two ) _Two -NH 2-Pyz 836 Ph CN EtO- (CH _Two ) _Two -NH 3-Pyz 837 Ph CN 3-Pyr Ph 838 Ph CN 3-Pyr 2-Pyr 839 Ph CN 3-Pyr 3-Pyr 840 Ph CN 3-Pyr 4-Pyr 841 Ph CN 3-Pyr 3-Pyzn 842 Ph CN 3-Pyr 4-Pyzn 843 Ph CN 3-Pyr 5-Pyzn 844 Ph CN 3-Pyr 6-Pyzn 845 Ph CN 3-Pyr 2-Pym 846 Ph CN 3-Pyr 4-Pym 847 Ph CN 3-Pyr 5 -Pym 848 Ph CN 3-Pyr 6-Pym 849 Ph CN 3-Pyr 2-Pyz 850 Ph CN 3-Pyr 3-Pyz 851 Ph CN 4-Pyr Ph 852 Ph CN 4-Pyr 2-Pyr 853 Ph CN 4- Pyr 3-Pyr 854 Ph CN 4-Pyr 4-Pyr 855 Ph CN 4-Pyr 3-Pyzn 856 Ph CN 4-Pyr 4-Pyzn 857 Ph CN 4-Pyr 5-Pyzn 858 Ph CN 4-Pyr 6-Pyzn 859 Ph CN 4-Pyr 2-Pym 860 Ph CN 4-Pyr 4-Pym 861 Ph CN 4-Pyr 5-Pym 862 Ph CN 4-Pyr 6-Pym 863 Ph CN 4-Pyr 2-Pyz 864 Ph CN 4-Pyr 3-Pyz 865 Ph CN 2-Thi Ph 866 Ph CN 2-Thi 2-Pyr 867 Ph CN 2-Thi 3-Pyr 868 Ph CN 2-Thi 4-Pyr 869 Ph CN 2-Thi 3-Pyzn 870 Ph CN 2 -Thi 4-Pyzn 871 Ph CN 2-Thi 5-Pyzn 872 Ph CN 2-Thi 6-Pyzn 873 Ph CN 2-Thi 2-Pym 874 Ph CN 2-Thi 4-Pym 875 Ph CN 2-Thi 5-Pym 876 Ph CN 2-Thi 6-Pym 877 Ph CN 2-Thi 2-Pyz 878 Ph CN 2-Thi 3-Pyz 879 Ph COOEt OH 2-Thi 880 Ph COOEt OH 3-Thi 881 Ph COOEt OH 2-F ur 882 Ph COOEt OH 3-Fur 883 Ph COOEt OH 2-Pyrr 884 Ph COOEt OH 3-Pyrr 885 Ph COOEt OH 3-Pyza 886 Ph COOEt OH 4-Pyza 887 Ph COOEt OH 5-Pyza 888 Ph COOEt OH 2-Imid 889 Ph COOEt OH 4-Imid 890 Ph COOEt OH 5-Imid 891 Ph COOEt OH 2-Oxa 892 Ph COOEt OH 4-Oxa 893 Ph COOEt OH 5-Oxa 894 Ph COOEt OH 2-Thiz 895 Ph COOEt OH 4-Thiz 896 Ph COOEt OH 5-Thiz 897 Ph COOEt OH Ph 898 Ph COOEt OH 2-Pyr 899 Ph COOEt OH 3-Pyr 900 Ph COOEt OH 4-Pyr 901 Ph COOEt OH 3-Pyzn 902 Ph COOEt OH 4-Pyzn 903 Ph COOEt OH 5-Pyzn 904 Ph COOEt OH 6-Pyzn 905 Ph COOEt OH 2-Pym 906 Ph COOEt OH 4-Pym 907 Ph COOEt OH 5-Pym 908 Ph COOEt OH 6-Pym 909 Ph COOEt OH 2-Pyz 910 Ph COOEt OH 3 -Pyz 911 Ph COOEt OH 2-BeFur 912 Ph COOEt OH 3-BeFur 913 Ph COOEt OH 4-BeFur 914 Ph COOEt OH 5-BeFur 915 Ph COOEt OH 6-BeFur 916 Ph COOEt OH 7-BeFur 917 Ph COOEt OH 1- Np 918 Ph COOEt OH 2-Np 919 Ph COOEt OH 1-Pyrd 920 Ph COOEt OH 1-Pip 921 Ph COOEt OH 4-Mor 922 Ph COOEt OH 4-Thm 923 Ph COOEt OH 4-Piz 924 Ph COOEt OH N- ( t-Bu) -Piz 925 Ph COOEt OH MeS 9 26 Ph COOEt OH EtS 927 Ph COOEt OH PrS 928 Ph COOEt OH i-PrS 929 Ph COOEt OH n-BuS 930 Ph COOEt OH i-BuS 931 Ph COOEt OH s-BuS 932 Ph COOEt OH t-BuS 933 Ph COOEt OH PnS 934 Ph COOEt OH n-HxS 935 Ph COOEt OH HepS 936 Ph COOEt OH n-OcS 937 Ph COOEt OH NnS 938 Ph COOEt OH DcS 939 Ph COOEt OH UdcS 940 Ph COOEt OH DdcS 941 Ph COOEt OH Bz 942 Ph COOEt (CH _Two ) _Two 943 Ph COOEt OH Ph- (CH _Two ) _Three 944 Ph COOEt OH Ph- (CH _Two ) _Three 945 Ph COOEt OH 1-Np-CH _Two 946 Ph COOEt OH 2-Np-CH _Two 947 Ph COOEt OH 1-Np- (CH _Two ) _Two 948 Ph COOEt OH 2-Np- (CH _Two ) _Two 949 Ph COOEt OH cPr 950 Ph COOEt OH cBu 951 Ph COOEt OH cPn 952 Ph COOEt OH cHx 953 Ph COOEt OH cHep 954 Ph COOEt OH Ad 955 Ph COOEt OH Me 956 Ph COOEt OH Et 957 Ph COOEt OH Pr 958 Ph COOEt -Pr 959 Ph COOEt OH n-Bu 960 Ph COOEt OH i-Bu 961 Ph COOEt OH s-Bu 962 Ph COOEt OH t-Bu 963 Ph COOEt OH Pn 964 Ph COOEt OH n-Hx 965 Ph COOEt OH Hep 966 Ph COOEt OH n-Oc 967 Ph COOEt OH Nn 968 Ph COOEt OH Dc 969 Ph COOEt OH Udc 970 Ph COOEt OH Ddc 971 Ph COOEt OH OH 972 Ph COOEt OH H 973 Ph COOEt MeO 2-Thi 974 Ph COOEt MeO 3-Thi 975 Ph COOEt MeO 2-Fur 976 Ph COOEt MeO 3-Fur 977 Ph COOEt MeO 2-Pyrr 978 Ph COOEt MeO 3-Pyrr 979 Ph COOEt MeO 3-Pyza 980 Ph COOEt MeO 4-Pyza 981 Ph COOEt MeO 5-Pyza 982 Ph COOEt MeO 2-Imid 983 Ph COOEt MeO 4-Imid 984 Ph COOEt MeO 5-Imid 985 Ph COOEt MeO 2-Oxa 986 Ph COOEt MeO 4-Oxa 987 Ph COOEt MeO 5-Oxa 988 Ph COOEt MeO 2-Thiz 989 Ph COOEt MeO 4-Thiz 990 Ph COOEt MeO 5-Thiz 991 Ph COOEt MeO Ph 992 Ph COOEt MeO 2-Pyr 993 Ph COOEt MeO 3-Pyr 994 Ph COOEt MeO 4-Pyr 995 Ph C OOEt MeO 3-Pyzn 996 Ph COOEt MeO 4-Pyzn 997 Ph COOEt MeO 5-Pyzn 998 Ph COOEt MeO 6-Pyzn 999 Ph COOEt MeO 2-Pym 1000 Ph COOEt MeO 4-Pym 1001 Ph COOEt MeO 5-Pym 1002 Ph COOEt MeO 6-Pym 1003 Ph COOEt MeO 2-Pyz 1004 Ph COOEt MeO 3-Pyz 1005 Ph COOEt MeO 2-BeFur 1006 Ph COOEt MeO 3-BeFur 1007 Ph COOEt MeO 4-BeFur 1008 Ph COOEt MeO 5-BeFur 1009 Ph COOEt MeO 6-BeFur 1010 Ph COOEt MeO 7-BeFur 1011 Ph COOEt MeO 1-Np 1012 Ph COOEt MeO 2-Np 1013 Ph COOEt MeO 1-Pyrd 1014 Ph COOEt MeO 1-Pip 1015 Ph COOEt MeO 4-Mor 1016 Ph COOEt MeO 4 -Thm 1017 Ph COOEt MeO 4-Piz 1018 Ph COOEt MeO N- (t-Bu) -Piz 1019 Ph COOEt MeO MeS 1020 Ph COOEt MeO EtS 1021 Ph COOEt MeO PrS 1022 Ph COOEt MeO i-PrS 1023 Ph COOEt MeO n- BuS 1024 Ph COOEt MeO i-BuS 1025 Ph COOEt MeO s-BuS 1026 Ph COOEt MeO t-BuS 1027 Ph COOEt MeO PnS 1028 Ph COOEt MeO n-HxS 1029 Ph COOEt MeO HepS 1030 Ph COOEt MeO n-OcS 1031 Ph COOEt MeO NnS 1032 Ph COOEt MeO DcS 1033 Ph COOEt MeO UdcS 1034 Ph COOEt MeO DdcS 1035 Ph COOEt MeO Bz 1036 Ph COOEt MeO Ph- (CH _Two ) _Two 1037 Ph COOEt MeO Ph- (CH _Two ) _Three 1038 Ph COOEt MeO Ph- (CH _Two ) _Three 1039 Ph COOEt MeO 1-Np-CH _Two 1040 Ph COOEt MeO 2-Np-CH _Two 1041 Ph COOEt MeO 1-Np- (CH _Two ) _Two 1042 Ph COOEt MeO 2-Np- (CH _Two ) _Two 1043 Ph COOEt MeO cPr 1044 Ph COOEt MeO cBu 1045 Ph COOEt MeO cPn 1046 Ph COOEt MeO cHx 1047 Ph COOEt MeO cHep 1048 Ph COOEt MeO cOc 1049 Ph COOEt MeO Me 1050 Ph COOEt MeO Et 1051 Ph COOEt MeO Pr 1052 Ph COOE -Pr 1053 Ph COOEt MeO n-Bu 1054 Ph COOEt MeO i-Bu 1055 Ph COOEt MeO s-Bu 1056 Ph COOEt MeO t-Bu 1057 Ph COOEt MeO Pn 1058 Ph COOEt MeO n-Hx 1059 Ph COOEt MeO Hep 1060 Ph COOEt MeO n-Oc 1061 Ph COOEt MeO Nn 1062 Ph COOEt MeO Dc 1063 Ph COOEt MeO Udc 1064 Ph COOEt MeO Ddc 1065 Ph COOEt MeO OH 1066 Ph COOEt MeO H 1067 Ph COOEt EtO 2-Thi 1068 Ph COOEt EtO 3-Thi 1069 Ph COOEt EtO 2-Fur 1070 Ph COOEt EtO 3-Fur 1071 Ph COOEt EtO 2-Pyrr 1072 Ph COOEt EtO 3-Pyrr 1073 Ph COOEt EtO 3-Pyza 1074 Ph COOEt EtO 4-Pyza 1075 Ph COOEt EtO 5-Pyza 1076 Ph COOEt EtO 2-Imid 1077 Ph COOEt EtO 4-Imid 1078 Ph COOEt EtO 5-Imid 1079 Ph COOEt EtO 2-Oxa 1080 Ph COOEt EtO 4-Oxa 1081 Ph COOEt EtO 5-Oxa 1082 Ph COOEt EtO 2-Thiz 1083 Ph COOEt EtO 4-Thiz 1084 Ph COOEt EtO 5-Thiz 1085 Ph COOEt EtO Ph 1086 Ph C OOEt EtO 2-Pyr 1087 Ph COOEt EtO 3-Pyr 1088 Ph COOEt EtO 4-Pyr 1089 Ph COOEt EtO 3-Pyzn 1090 Ph COOEt EtO 4-Pyzn 1091 Ph COOEt EtO 5-Pyzn 1092 Ph COOEt EtO 6-Pyzn 1093 Ph COOEt EtO 2-Pym 1094 Ph COOEt EtO 4-Pym 1095 Ph COOEt EtO 5-Pym 1096 Ph COOEt EtO 6-Pym 1097 Ph COOEt EtO 2-Pyz 1098 Ph COOEt EtO 3-Pyz 1099 Ph COOEt EtO 2-BeFur 1100 Ph COOEt EtO 3-BeFur 1101 Ph COOEt EtO 4-BeFur 1102 Ph COOEt EtO 5-BeFur 1103 Ph COOEt EtO 6-BeFur 1104 Ph COOEt EtO 7-BeFur 1105 Ph COOEt EtO 1-Np 1106 Ph COOEt EtO 2-Np 1107 Ph COOEt EtO 1 -Pyrd 1108 Ph COOEt EtO 1-Pip 1109 Ph COOEt EtO 4-Mor 1110 Ph COOEt EtO 4-Thm 1111 Ph COOEt EtO 4-Piz 1112 Ph COOEt EtO N- (t-Bu) -Piz 1113 Ph COOEt EtO MeS 1114 Ph COOEt EtO EtS 1115 Ph COOEt EtO PrS 1116 Ph COOEt EtO i-PrS 1117 Ph COOEt EtO n-BuS 1118 Ph COOEt EtO i-BuS 1119 Ph COOEt EtO s-BuS 1120 Ph COOEt EtO t-BuS 1121 Ph COOEt EtO PnS 1122 Ph COOEt EtO n-HxS 1123 Ph COOEt EtO HepS 1124 Ph COOEt EtO n-OcS 1125 Ph COOEt EtO NnS 1126 Ph COOEt EtO DcS 1127 Ph COOEt Et O UdcS 1128 Ph COOEt EtO DdcS 1129 Ph COOEt EtO Bz 1130 Ph COOEt EtO Ph- (CH _Two ) _Two 1131 Ph COOEt EtO Ph- (CH _Two ) _Three 1132 Ph COOEt EtO Ph- (CH _Two ) _Three 1133 Ph COOEt EtO 1-Np-CH _Two 1134 Ph COOEt EtO 2-Np-CH _Two 1135 Ph COOEt EtO 1-Np- (CH _Two ) _Two 1136 Ph COOEt EtO 2-Np- (CH _Two ) _Two 1137 Ph COOEt EtO cPr 1138 Ph COOEt EtO cBu 1139 Ph COOEt EtO cPn 1140 Ph COOEt EtO cHx 1141 Ph COOEt EtO cHep 1142 Ph COOEt EtO cOc 1143 Ph COOEt EtO Me 1144 Ph COOEt EtO Et 1145 Ph COOEt EtO Et 1140 Ph COOE -Pr 1147 Ph COOEt EtO n-Bu 1148 Ph COOEt EtO i-Bu 1149 Ph COOEt EtO s-Bu 1150 Ph COOEt EtO t-Bu 1151 Ph COOEt EtO Pn 1152 Ph COOEt EtO n-Hx 1153 Ph COOEt EtO Hep 1154 Ph COOEt EtO n-Oc 1155 Ph COOEt EtO Nn 1156 Ph COOEt EtO Dc 1157 Ph COOEt EtO Udc 1158 Ph COOEt EtO Ddc 1159 Ph COOEt EtO OH 1160 Ph COOEt EtO H 1161 Ph COOEt MeS 2-Thi 1162 Ph COOEt MeS 3-Thi 1163 Ph COOEt MeS 2-Fur 1164 Ph COOEt MeS 3-Fur 1165 Ph COOEt MeS 2-Pyrr 1166 Ph COOEt MeS 3-Pyrr 1167 Ph COOEt MeS 3-Pyza 1168 Ph COOEt MeS 4-Pyza 1169 Ph COOEt MeS 5-Pyza 1170 Ph COOEt MeS 2-Imid 1171 Ph COOEt MeS 4-Imid 1172 Ph COOEt MeS 5-Imid 1173 Ph COOEt MeS 2-Oxa 1174 Ph COOEt MeS 4-Oxa 1175 Ph COOEt MeS 5-Oxa 1176 Ph COOEt MeS 2-Thiz 1177 Ph COOEt MeS 4-Thiz 1178 Ph COOEt MeS 5-Thiz 1179 Ph COOEt MeS Ph 1180 Ph C OOEt MeS 2-Pyr 1181 Ph COOEt MeS 3-Pyr 1182 Ph COOEt MeS 4-Pyr 1183 Ph COOEt MeS 3-Pyzn 1184 Ph COOEt MeS 4-Pyzn 1185 Ph COOEt MeS 5-Pyzn 1186 Ph COOEt MeS 6-Pyzn 1187 Ph COOEt MeS 2-Pym 1188 Ph COOEt MeS 4-Pym 1189 Ph COOEt MeS 5-Pym 1190 Ph COOEt MeS 6-Pym 1191 Ph COOEt MeS 2-Pyz 1192 Ph COOEt MeS 3-Pyz 1193 Ph COOEt MeS 2-BeFur 1194 Ph COOEt MeS 3-BeFur 1195 Ph COOEt MeS 4-BeFur 1196 Ph COOEt MeS 5-BeFur 1197 Ph COOEt MeS 6-BeFur 1198 Ph COOEt MeS 7-BeFur 1199 Ph COOEt HepO Ph 1200 Ph COOEt HepO 2-Pyr 1201 Ph COOEt HepO 3-Pyr 1202 Ph COOEt HepO 4-Pyr 1203 Ph COOEt HepO 3-Pyzn 1204 Ph COOEt HepO 4-Pyzn 1205 Ph COOEt HepO 5-Pyzn 1206 Ph COOEt HepO 6-Pyzn 1207 Ph COOEt HepO 2-Pym 1208 Ph COOEt HepO 4-Pym 1209 Ph COOEt HepO 5-Pym 1210 Ph COOEt HepO 6-Pym 1211 Ph COOEt HepO 2-Pyz 1212 Ph COOEt HepO 3-Pyz 1213 Ph COOEt 4-Mor 2-Thi 1214 Ph COOEt 4-Mor 3-Thi 1215 Ph COOEt 4- Mor 2-Fur 1216 Ph COOEt 4-Mor 3-Fur 1217 Ph COOEt 4-Mor 2-Pyrr 1218 Ph COOEt 4-Mor 3-Pyrr 1219 Ph COOEt 4-Mor 3-Pyza 1 220 Ph COOEt 4-Mor 4-Pyza 1221 Ph COOEt 4-Mor 5-Pyza 1222 Ph COOEt 4-Mor 2-Imid 1223 Ph COOEt 4-Mor 4-Imid 1224 Ph COOEt 4-Mor 5-Imid 1225 Ph COOEt 4- Mor 2-Oxa 1226 Ph COOEt 4-Mor 4-Oxa 1227 Ph COOEt 4-Mor 5-Oxa 1228 Ph COOEt 4-Mor 2-Thiz 1229 Ph COOEt 4-Mor 4-Thiz 1230 Ph COOEt 4-Mor 5-Thiz 1231 Ph COOEt 4-Mor Ph 1232 Ph COOEt 4-Mor 2-Pyr 1233 Ph COOEt 4-Mor 3-Pyr 1234 Ph COOEt 4-Mor 4-Pyr 1235 Ph COOEt 4-Mor 3-Pyzn 1236 Ph COOEt 4-Mor 4- Pyzn 1237 Ph COOEt 4-Mor 5-Pyzn 1238 Ph COOEt 4-Mor 6-Pyzn 1239 Ph COOEt 4-Mor 2-Pym 1240 Ph COOEt 4-Mor 4-Pym 1241 Ph COOEt 4-Mor 5-Pym 1242 Ph COOEt 4 -Mor 6-Pym 1243 Ph COOEt 4-Mor 2-Pyz 1244 Ph COOEt 4-Mor 3-Pyz 1245 Ph COOEt 4-Mor 2-BeFur 1246 Ph COOEt 4-Mor 3-BeFur 1247 Ph COOEt 4-Mor 4-BeFur 1248 Ph COOEt 4-Mor 5-BeFur 1249 Ph COOEt 4-Mor 6-BeFur 1250 Ph COOEt 4-Mor 7-BeFur 1251 Ph COOEt 4-Mor 1-Np 1252 Ph COOEt 4-Mor 2-Np 1253 Ph COOEt 4- Mor 1-Pyrd 1254 Ph COOEt 4-Mor 1-Pip 1255 Ph COOEt 4-Mor 4-Mor 1256 Ph COOEt 4-Mor 4-Thm 1257 Ph COOEt 4-Mor 4-Piz 1258 Ph COOEt 4-Mor N- (t-Bu) -Piz 1259 Ph COOEt 4-Mor MeS 1260 Ph COOEt 4-Mor EtS 1261 Ph COOEt 4-Mor PrS 1262 Ph COOEt 4-Mor i-PrS 1263 Ph COOEt 4-Mor n-BuS 1264 Ph COOEt 4-Mor i-BuS 1265 Ph COOEt 4-Mor s-BuS 1266 Ph COOEt 4-Mor t-BuS 1267 Ph COOEt 4-Mor PnS 1268 Ph COOEt 4-Mor n-HxS 1269 Ph COOEt 4-Mor HepS 1270 Ph COOEt 4-Mor n-OcS 1271 Ph COOEt 4-Mor NnS 1272 Ph COOEt 4-Mor DcS 1273 Ph COOEt 4-Mor UdcS 1274 Ph COOEt 4-Mor DdcS 1275 Ph COOEt 4-Mor Bz 1276 Ph COOEt 4-Mor Ph- (CH _Two ) _Two 1277 Ph COOEt 4-Mor Ph- (CH _Two ) _Three 1278 Ph COOEt 4-Mor Ph- (CH _Two ) _Three 1279 Ph COOEt 4-Mor 1-Np-CH _Two 1280 Ph COOEt 4-Mor 2-Np-CH _Two 1281 Ph COOEt 4-Mor 1-Np- (CH _Two ) _Two 1282 Ph COOEt 4-Mor 2-Np- (CH _Two ) _Two 1283 Ph COOEt 4-Mor cPr 1284 Ph COOEt 4-Mor cBu 1285 Ph COOEt 4-Mor cPn 1286 Ph COOEt 4-Mor cHx 1287 Ph COOEt 4-Mor cHep 1288 Ph COOEt 4-Mor cOc 1289 Ph COOEt 4-Mor Me 1290 Ph COOEt 4-Mor Et 1291 Ph COOEt 4-Mor Pr 1292 Ph COOEt 4-Mor i-Pr 1293 Ph COOEt 4-Mor n-Bu 1294 Ph COOEt 4-Mor i-Bu 1295 Ph COOEt 4-Mor s-Bu 1296 Ph COOEt 4-Mor t-Bu 1297 Ph COOEt 4-Mor Pn 1298 Ph COOEt 4-Mor n-Hx 1299 Ph COOEt 4-Mor Hep 1300 Ph COOEt 4-Mor n-Oc 1301 Ph COOEt 4-Mor CF _Three 1302 Ph COOEt 4-Mor Dc 1303 Ph COOEt 4-Mor Udc 1304 Ph COOEt 4-Mor Ddc 1305 Ph COOEt 4-Mor OH 1306 Ph COOEt 4-Mor H 1307 Ph COOEt 4-Thm 2-Thi 1308 Ph COOEt 4-Thm 3-Thi 1309 Ph COOEt 4-Thm 2-Fur 1310 Ph COOEt 4-Thm 3-Fur 1311 Ph COOEt 4-Thm 2-Pyrr 1312 Ph COOEt 4-Thm 3-Pyrr 1313 Ph COOEt 4-Thm 3-Pyza 1314 Ph COOEt 4-Thm 4-Pyza 1315 Ph COOEt 4-Thm 5-Pyza 1316 Ph COOEt 4-Thm 2-Imid 1317 Ph COOEt 4-Thm 4-Imid 1318 Ph COOEt 4-Thm 5-Imid 1319 Ph COOEt 4-Thm 2 -Oxa 1320 Ph COOEt 4-Thm 4-Oxa 1321 Ph COOEt 4-Thm 5-Oxa 1322 Ph COOEt 4-Thm 2-Thiz 1323 Ph COOEt 4-Thm 4-Thiz 1324 Ph COOEt 4-Thm 5-Thiz 1325 Ph COOEt 4-Thm Ph 1326 Ph COOEt 4-Thm 2-Pyr 1327 Ph COOEt 4-Thm 3-Pyr 1328 Ph COOEt 4-Thm 4-Pyr 1329 Ph COOEt 4-Thm 3-Pyzn 1330 Ph COOEt 4-Thm 4-Pyzn 1331 Ph COOEt 4-Thm 5-Pyzn 1332 Ph COOEt 4-Thm 6-Pyzn 1333 Ph COOEt 4-Thm 2-Pym 1334 Ph COOEt 4-Thm 4-Pym 1335 Ph COOEt 4-Thm 5-Pym 1336 Ph COOEt 4-Thm 6-Pym 1337 Ph COOEt 4-Thm 2-Pyz 1338 Ph COOEt 4-Thm 3-Pyz 1339 Ph COOEt 4-Thm 2-BeFur 1340 Ph COOE t 4-Thm 3-BeFur 1341 Ph COOEt 4-Thm 4-BeFur 1342 Ph COOEt 4-Thm 5-BeFur 1343 Ph COOEt 4-Thm 6-BeFur 1344 Ph COOEt 4-Thm 7-BeFur 1345 Ph COOEt 4-Thm 1 -Np 1346 Ph COOEt 4-Thm 2-Np 1347 Ph COOEt 4-Thm 1-Pyrd 1348 Ph COOEt 4-Thm 1-Pip 1349 Ph COOEt 4-Thm 4-Mor 1350 Ph COOEt 4-Thm 4-Thm 1351 Ph COOEt 4-Thm 4-Piz 1352 Ph COOEt 4-Thm N- (t-Bu) -Piz 1353 Ph COOEt 4-Thm MeS 1354 Ph COOEt 4-Thm EtS 1355 Ph COOEt 4-Thm PrS 1356 Ph COOEt 4-Thm i- PrS 1357 Ph COOEt 4-Thm n-BuS 1358 Ph COOEt 4-Thm i-BuS 1359 Ph COOEt 4-Thm s-BuS 1360 Ph COOEt 4-Thm t-BuS 1361 Ph COOEt 4-Thm PnS 1362 Ph COOEt 4-Thm n-HxS 1363 Ph COOEt 4-Thm HepS 1364 Ph COOEt 4-Thm n-OcS 1365 Ph COOEt 4-Thm NnS 1366 Ph COOEt 4-Thm DcS 1367 Ph COOEt 4-Thm UdcS 1368 Ph COOEt 4-Thm DdcS 1369 Ph COOEt 4-Thm Bz 1370 Ph COOEt 4-Thm Ph- (CH _Two ) _Two 1371 Ph COOEt 4-Thm Ph- (CH _Two ) _Three 1372 Ph COOEt 4-Thm Ph- (CH _Two ) _Three 1373 Ph COOEt 4-Thm 1-Np-CH _Two 1374 Ph COOEt 4-Thm 2-Np-CH _Two 1375 Ph COOEt 4-Thm 1-Np- (CH _Two ) _Two 1376 Ph COOEt 4-Thm 2-Np- (CH _Two ) _Two 1377 Ph COOEt 4-Thm cPr 1378 Ph COOEt 4-Thm cBu 1379 Ph COOEt 4-Thm cPn 1380 Ph COOEt 4-Thm cHx 1381 Ph COOEt 4-Thm cHep 1382 Ph COOEt 4-Thm cOc 1383 Ph COOEt 4-Thm Me 1384 Ph COOEt 4-Thm Et 1385 Ph COOEt 4-Thm Pr 1386 Ph COOEt 4-Thm i-Pr 1387 Ph COOEt 4-Thm n-Bu 1388 Ph COOEt 4-Thm i-Bu 1389 Ph COOEt 4-Thm s-Bu 1390 Ph COOEt 4-Thm t-Bu 1391 Ph COOEt 4-Thm Pn 1392 Ph COOEt 4-Thm n-Hx 1393 Ph COOEt 4-Thm Hep 1394 Ph COOEt 4-Thm n-Oc 1395 Ph COOEt 4-Thm Nn 1396 Ph COOEt 4-Thm Dc 1397 Ph COOEt 4-Thm Udc 1398 Ph COOEt 4-Thm Ddc 1399 Ph COOEt 4-Thm OH 1400 Ph COOEt 4-Thm H 1401 Ph COOEt 1-Pip 2-Thi 1402 Ph COOEt 1-Pip 3-Thi 1403 Ph COOEt 1-Pip 2-Fur 1404 Ph COOEt 1-Pip 3-Fur 1405 Ph COOEt 1-Pip 2-Pyrr 1406 Ph COOEt 1-Pip 3-Pyrr 1407 Ph COOEt 1-Pip 3-Pyza 1408 Ph COOEt 1- Pip 4-Pyza 1409 Ph COOEt 1-Pip 5-Pyza 1410 Ph COOEt 1-Pip 2-Imid 1411 Ph COOEt 1-Pip 4-Imid 1412 Ph COOEt 1-Pip 5-Imid 1413 Ph COOEt 1-Pip 2-Oxa 1414 Ph COOEt 1-Pip 4-Oxa 1415 Ph COOEt 1-Pip 5-Oxa 1416 Ph COOEt 1-Pip 2-Thiz 1417 Ph COOEt 1-Pip 4-Thiz 1418 Ph COOEt 1-Pip 5-Thiz 1419 Ph COOEt 1-Pip Ph 1420 Ph COOEt 1-Pip 2-Pyr 1421 Ph COOEt 1-Pip 3-Pyr 1422 Ph COOEt 1-Pip 4 -Pyr 1423 Ph COOEt 1-Pip 3-Pyzn 1424 Ph COOEt 1-Pip 4-Pyzn 1425 Ph COOEt 1-Pip 5-Pyzn 1426 Ph COOEt 1-Pip 6-Pyzn 1427 Ph COOEt 1-Pip 2-Pym 1428 Ph COOEt 1-Pip 4-Pym 1429 Ph COOEt 1-Pip 5-Pym 1430 Ph COOEt 1-Pip 6-Pym 1431 Ph COOEt 1-Pip 2-Pyz 1432 Ph COOEt 1-Pip 3-Pyz 1433 Ph COOEt 1-Pip 2- BeFur 1434 Ph COOEt 1-Pip 3-BeFur 1435 Ph COOEt 1-Pip 4-BeFur 1436 Ph COOEt 1-Pip 5-BeFur 1437 Ph COOEt 1-Pip 6-BeFur 1438 Ph COOEt 1-Pip 7-BeFur 1439 Ph COOEt 1 -Pip 1-Np 1440 Ph COOEt 1-Pip 2-Np 1441 Ph COOEt 1-Pip 1-Pyrd 1442 Ph COOEt 1-Pip 1-Pip 1443 Ph COOEt 1-Pip 4-Mor 1444 Ph COOEt 1-Pip 4-Thm 1445 Ph COOEt 1-Pip 4-Piz 1446 Ph COOEt 1-Pip N- (t-Bu) -Piz 1447 Ph COOEt 1-Pip MeS 1448 Ph COOEt 1-Pip EtS 1449 Ph COOEt 1-Pip PrS 1450 Ph COOEt 1- Pip i-PrS 1451 Ph COOEt 1-Pip n-BuS 1452 Ph COOEt 1-Pip i-BuS 1453 Ph COOEt 1-Pip s-BuS 1454 Ph COOEt 1-Pip tB uS 1455 Ph COOEt 1-Pip PnS 1456 Ph COOEt 1-Pip n-HxS 1457 Ph COOEt 1-Pip HepS 1458 Ph COOEt 1-Pip n-OcS 1459 Ph COOEt 1-Pip NnS 1460 Ph COOEt 1-Pip DcS 1461 Ph COOEt 1-Pip UdcS 1462 Ph COOEt 1-Pip DdcS 1463 Ph COOEt 1-Pip Bz 1464 Ph COOEt 1-Pip Ph- (CH _Two ) _Two 1465 Ph COOEt 1-Pip Ph- (CH _Two ) _Three 1466 Ph COOEt 1-Pip Ph- (CH _Two ) _Three 1467 Ph COOEt 1-Pip 1-Np-CH _Two 1468 Ph COOEt 1-Pip 2-Np-CH _Two 1469 Ph COOEt 1-Pip 1-Np- (CH _Two ) _Two 1470 Ph COOEt 1-Pip 2-Np- (CH _Two ) _Two 1471 Ph COOEt 1-Pip cPr 1472 Ph COOEt 1-Pip cBu 1473 Ph COOEt 1-Pip cPn 1474 Ph COOEt 1-Pip cHx 1475 Ph COOEt 1-Pip cHep 1476 Ph COOEt 1-Pip cOc 1477 Ph COOEt 1-Pip Me 1478 Ph COOEt 1-Pip Et 1479 Ph COOEt 1-Pip Pr 1480 Ph COOEt 1-Pip i-Pr 1481 Ph COOEt 1-Pip n-Bu 1482 Ph COOEt 1-Pip i-Bu 1483 Ph COOEt 1-Pip s-Bu 1484 Ph COOEt 1-Pip t-Bu 1485 Ph COOEt 1-Pip Pn 1486 Ph COOEt 1-Pip n-Hx 1487 Ph COOEt 1-Pip Hep 1488 Ph COOEt 1-Pip n-Oc 1489 Ph COOEt 1-Pip Nn 1490 Ph COOEt 1-Pip Dc 1491 Ph COOEt 1-Pip Udc 1492 Ph COOEt 1-Pip Ddc 1493 Ph COOEt 1-Pip OH 1494 Ph COOEt 1-Pip H 1495 Ph COOEt 4-Piz 2-Thi 1496 Ph COOEt 4-Piz 3-Thi 1497 Ph COOEt 4-Piz 2-Fur 1498 Ph COOEt 4-Piz 3-Fur 1499 Ph COOEt 4-Piz 2-Pyrr 1500 Ph COOEt 4-Piz 3-Pyrr 1501 Ph COOEt 4-Piz 3-Pyza 1502 Ph COOEt 4- Piz 4-Pyza 1503 Ph COOEt 4-Piz 5-Pyza 1504 Ph COOEt 4-Piz 2-Imid 1505 Ph COOEt 4-Piz 4-Imid 1506 Ph COOEt 4-Piz 5-Imid 1507 Ph COOEt 4-Piz 2-Oxa 1508 Ph COOEt 4-Piz 4-Oxa 1509 Ph COOEt 4-Piz 5-Oxa 1510 Ph COOEt 4-Piz 2-Thiz 1511 Ph COOEt 4-Piz 4-Thiz 1512 Ph COOEt 4-Piz 5-Thiz 1513 Ph COOEt 4-Piz Ph 1514 Ph COOEt 4-Piz 2-Pyr 1515 Ph COOEt 4-Piz 3-Pyr 1516 Ph COOEt 4-Piz 4 -Pyr 1517 Ph COOEt 4-Piz 3-Pyzn 1518 Ph COOEt 4-Piz 4-Pyzn 1519 Ph COOEt 4-Piz 5-Pyzn 1520 Ph COOEt 4-Piz 6-Pyzn 1521 Ph COOEt 4-Piz 2-Pym 1522 Ph COOEt 4-Piz 4-Pym 1523 Ph COOEt 4-Piz 5-Pym 1524 Ph COOEt 4-Piz 6-Pym 1525 Ph COOEt 4-Piz 2-Pyz 1526 Ph COOEt 4-Piz 3-Pyz 1527 Ph COOEt 4-Piz 2- BeFur 1528 Ph COOEt 4-Piz 3-BeFur 1529 Ph COOEt 4-Piz 4-BeFur 1530 Ph COOEt 4-Piz 5-BeFur 1531 Ph COOEt 4-Piz 6-BeFur 1532 Ph COOEt 4-Piz 7-BeFur 1533 Ph COOEt 4 -Piz 1-Np 1534 Ph COOEt 4-Piz 2-Np 1535 Ph COOEt 4-Piz 1-Pyrd 1536 Ph COOEt 4-Piz 1-Pip 1537 Ph COOEt 4-Piz 4-Mor 1538 Ph COOEt 4-Piz 4-Thm 1539 Ph COOEt 4-Piz 4-Piz 1540 Ph COOEt 4-Piz N- (t-Bu) -Piz 1541 Ph COOEt 4-Piz MeS 1542 Ph COOEt 4-Piz EtS 1543 Ph COOEt 4-Piz PrS 1544 Ph COOEt 4- Piz i-PrS 1545 Ph COOEt 4-Piz n-BuS 1546 Ph COOEt 4-Piz i-BuS 1547 Ph COOEt 4-Piz s-BuS 1548 Ph COOEt 4-Piz tB uS 1549 Ph COOEt 4-Piz PnS 1550 Ph COOEt 4-Piz n-HxS 1551 Ph COOEt 4-Piz HepS 1552 Ph COOEt 4-Piz n-OcS 1553 Ph COOEt 4-Piz NnS 1554 Ph COOEt 4-Piz DcS 1555 Ph COOEt 4-Piz UdcS 1556 Ph COOEt 4-Piz DdcS 1557 Ph COOEt 4-Piz Bz 1558 Ph COOEt 4-Piz Ph- (CH _Two ) _Two 1559 Ph COOEt 4-Piz Ph- (CH _Two ) _Three 1560 Ph COOEt 4-Piz Ph- (CH _Two ) _Three 1561 Ph COOEt 4-Piz 1-Np-CH _Two 1562 Ph COOEt 4-Piz 2-Np-CH _Two 1563 Ph COOEt 4-Piz 1-Np- (CH _Two ) _Two 1564 Ph COOEt 4-Piz 2-Np- (CH _Two ) _Two 1565 Ph COOEt 4-Piz cPr 1566 Ph COOEt 4-Piz cBu 1567 Ph COOEt 4-Piz cPn 1568 Ph COOEt 4-Piz cHx 1569 Ph COOEt 4-Piz cHep 1570 Ph COOEt 4-Piz cOc 1571 Ph COOEt 4-Piz Me 1572 Ph COOEt 4-Piz Et 1573 Ph COOEt 4-Piz Pr 1574 Ph COOEt 4-Piz i-Pr 1575 Ph COOEt 4-Piz n-Bu 1576 Ph COOEt 4-Piz i-Bu 1577 Ph COOEt 4-Piz s-Bu 1578 Ph COOEt 4-Piz t-Bu 1579 Ph COOEt 4-Piz Pn 1580 Ph COOEt 4-Piz n-Hx 1581 Ph COOEt 4-Piz Hep 1582 Ph COOEt 4-Piz n-Oc 1583 Ph COOEt 4-Piz Nn 1584 Ph COOEt 4-Piz Dc 1585 Ph COOEt 4-Piz Udc 1586 Ph COOEt 4-Piz Ddc 1587 Ph COOEt 4-Piz OH 1588 Ph COOEt 4-Piz H 1589 Ph COOEt (Et) _Two N Ph 1590 Ph COOEt (Et) _Two N 2-Pyr 1591 Ph COOEt (Et) _Two N 3-Pyr 1592 Ph COOEt (Et) _Two N 4-Pyr 1593 Ph COOEt (Et) _Two N 3-Pyzn 1594 Ph COOEt (Et) _Two N 4-Pyzn 1595 Ph COOEt (Et) _Two N 5-Pyzn 1596 Ph COOEt (Et) _Two N 6-Pyzn 1597 Ph COOEt (Et) _Two N 2-Pym 1598 Ph COOEt (Et) _Two N 4-Pym 1599 Ph COOEt (Et) _Two N 5-Pym 1600 Ph COOEt (Et) _Two N 6-Pym 1601 Ph COOEt (Et) _Two N 2-Pyz 1602 Ph COOEt (Et) _Two N 3-Pyz 1603 Ph COOEt cHx-NH Ph 1604 Ph COOEt cHx-NH 2-Pyr 1605 Ph COOEt cHx-NH 3-Pyr 1606 Ph COOEt cHx-NH 4-Pyr 1607 Ph COOEt cHx-NH 3-Pyzn 1608 Ph COOEt cHx-NH 4-Pyzn 1609 Ph COOEt cHx-NH 5-Pyzn 1610 Ph COOEt cHx-NH 6-Pyzn 1611 Ph COOEt cHx-NH 2-Pym 1612 Ph COOEt cHx-NH 4-Pym 1613 Ph COOEt cHx-NH 5- Pym 1614 Ph COOEt cHx-NH 6-Pym 1615 Ph COOEt cHx-NH 2-Pyz 1616 Ph COOEt cHx-NH 3-Pyz 1617 Ph COOEt Ph-NH Ph 1618 Ph COOEt Ph-NH 2-Pyr 1619 Ph COOEt Ph-NH 3-Pyr 1620 Ph COOEt Ph-NH 4-Pyr 1621 Ph COOEt Ph-NH 3-Pyzn 1622 Ph COOEt Ph-NH 4-Pyzn 1623 Ph COOEt Ph-NH 5-Pyzn 1624 Ph COOEt Ph-NH 6-Pyzn 1625 Ph COOEt Ph-NH 2-Pym 1626 Ph COOEt Ph-NH 4-Pym 1627 Ph COOEt Ph-NH 5-Pym 1628 Ph COOEt Ph-NH 6-Pym 1629 Ph COOEt Ph-NH 2-Pyz 1630 Ph COOEt Ph-NH 3 -Pyz 1631 Ph COOEt 3-Cl-Ph-NH Ph 1632 Ph COOEt 3-Cl-Ph-NH 2-Pyr 1633 Ph COOEt 3-Cl-Ph-NH 3-Pyr 1634 Ph COOEt 3-Cl-Ph-NH 4 -Pyr 1635 Ph COOEt 3-Cl-Ph-NH 3-Pyzn 1636 Ph COOEt 3-Cl-Ph-NH 4-Pyzn 1637 Ph COOEt 3-Cl-Ph-NH 5-Pyzn 1638 Ph COOEt 3-Cl-Ph- NH 6-Pyzn 1639 Ph COOEt 3-Cl-Ph-NH 2-Pym 1640 Ph COOEt 3-Cl-Ph-NH 4-Pym 1641 Ph COOEt 3-Cl-Ph-NH 5-Pym 1642 Ph COOEt 3-Cl-Ph-NH 6 -Pym 1643 Ph COOEt 3-Cl-Ph-NH 2-Pyz 1644 Ph COOEt 3-Cl-Ph-NH 3-Pyz 1645 Ph COOEt 2-Me-Ph-NH Ph 1646 Ph COOEt 2-Me-Ph-NH 2 -Pyr 1647 Ph COOEt 2-Me-Ph-NH 3-Pyr 1648 Ph COOEt 2-Me-Ph-NH 4-Pyr 1649 Ph COOEt 2-Me-Ph-NH 3-Pyzn 1650 Ph COOEt 2-Me-Ph- NH 4-Pyzn 1651 Ph COOEt 2-Me-Ph-NH 5-Pyzn 1652 Ph COOEt 2-Me-Ph-NH 6-Pyzn 1653 Ph COOEt 2-Me-Ph-NH 2-Pym 1654 Ph COOEt 2-Me- Ph-NH 4-Pym 1655 Ph COOEt 2-Me-Ph-NH 5-Pym 1656 Ph COOEt 2-Me-Ph-NH 6-Pym 1657 Ph COOEt 2-Me-Ph-NH 2-Pyz 1658 Ph COOEt 2- Me-Ph-NH 3-Pyz 1659 Ph COOEt 3-Me-Ph-NH Ph 1660 Ph COOEt 3-Me-Ph-NH 2-Pyr 1661 Ph COOEt 3-Me-Ph-NH 3-Pyr 1662 Ph COOEt 3- Me-Ph-NH 4-Pyr 1663 Ph COOEt 3-Me-Ph-NH 3-Pyzn 1664 Ph COOEt 3-Me-Ph-NH 4-Pyzn 1665 Ph COOEt 3-Me-Ph-NH 5-Pyzn 1666 Ph COOEt 3-Me-Ph-NH 6-Pyzn 1667 Ph COOEt 3-Me-Ph-NH 2-Pym 1668 Ph COOEt 3-Me-Ph-NH 4-Pym 1669 Ph COOEt 3-Me-Ph-NH 5-Pym 1670 Ph COOEt 3-Me-Ph-NH 6-Pym 1671 Ph COOEt 3-Me-Ph-NH 2-Pyz 1672 Ph COOEt 3-Me-Ph-NH 3-Pyz 1673 Ph COOEt 4-Me-Ph-NH Ph 1674 Ph COOEt 4-Me-Ph-NH 2-Pyr 1675 Ph COOEt 4-Me-Ph-NH 3-Pyr 1676 Ph COOEt 4-Me-Ph-NH 4-Pyr 1677 Ph COOEt 4-Me-Ph-NH 3-Pyzn 1678 Ph COOEt 4-Me-Ph-NH 4- Pyzn 1679 Ph COOEt 4-Me-Ph-NH 5-Pyzn 1680 Ph COOEt 4-Me-Ph-NH 6-Pyzn 1681 Ph COOEt 4-Me-Ph-NH 2-Pym 1682 Ph COOEt 4-Me-Ph-NH 4-Pym 1683 Ph COOEt 4-Me-Ph-NH 5-Pym 1684 Ph COOEt 4-Me-Ph-NH 6-Pym 1685 Ph COOEt 4-Me-Ph-NH 2-Pyz 1686 Ph COOEt 4-Me-Ph -NH 3-Pyz 1687 Ph COOEt n-Hx-NH Ph 1688 Ph COOEt n-Hx-NH 2-Pyr 1689 Ph COOEt n-Hx-NH 3-Pyr 1690 Ph COOEt n-Hx-NH 4-Pyr 1691 Ph COOEt n-Hx-NH 3-Pyzn 1692 Ph COOEt n-Hx-NH 4-Pyzn 1693 Ph COOEt n-Hx-NH 5-Pyzn 1694 Ph COOEt n-Hx-NH 6-Pyzn 1695 Ph COOEt n-Hx-NH 2 -Pym 1696 Ph COOEt n-Hx-NH 4-Pym 1697 Ph COOEt n-Hx-NH 5-Pym 1698 Ph COOEt n-Hx-NH 6-Pym 1699 Ph COOEt n-Hx-NH 2-Pyz 1700 Ph COOEt n -Hx-NH 3-Pyz 1701 Ph COOEt EtO- (CH _Two ) _Two -NH Ph 1702 Ph COOEt EtO- (CH _Two ) _Two -NH 2-Pyr 1703 Ph COOEt EtO- (CH _Two ) _Two -NH 3-Pyr 1704 Ph COOEt EtO- (CH _Two ) _Two -NH 4-Pyr 1705 Ph COOEt EtO- (CH _Two ) _Two -NH 3-Pyzn 1706 Ph COOEt EtO- (CH _Two ) _Two -NH 4-Pyzn 1707 Ph COOEt EtO- (CH _Two ) _Two -NH 5-Pyzn 1708 Ph COOEt EtO- (CH _Two ) _Two -NH 6-Pyzn 1709 Ph COOEt EtO- (CH _Two ) _Two -NH 2-Pym 1710 Ph COOEt EtO- (CH _Two ) _Two -NH 4-Pym 1711 Ph COOEt EtO- (CH _Two ) _Two -NH 5-Pym 1712 Ph COOEt EtO- (CH _Two ) _Two -NH 6-Pym 1713 Ph COOEt EtO- (CH _Two ) _Two -NH 2-Pyz 1714 Ph COOEt EtO- (CH _Two ) _Two -NH 3-Pyz 1715 Ph COOEt 3-Pyr Ph 1716 Ph COOEt 3-Pyr 2-Pyr 1717 Ph COOEt 3-Pyr 3-Pyr 1718 Ph COOEt 3-Pyr 4-Pyr 1719 Ph COOEt 3-Pyr 3-Pyzn 1720 Ph COOEt 3-Pyr 4-Pyzn 1721 Ph COOEt 3-Pyr 5-Pyzn 1722 Ph COOEt 3-Pyr 6-Pyzn 1723 Ph COOEt 3-Pyr 2-Pym 1724 Ph COOEt 3-Pyr 4-Pym 1725 Ph COOEt 3-Pyr 5 -Pym 1726 Ph COOEt 3-Pyr 6-Pym 1727 Ph COOEt 3-Pyr 2-Pyz 1728 Ph COOEt 3-Pyr 3-Pyz 1729 Ph COOEt 4-Pyr Ph 1730 Ph COOEt 4-Pyr 2-Pyr 1731 Ph COOEt 4- Pyr 3-Pyr 1732 Ph COOEt 4-Pyr 4-Pyr 1733 Ph COOEt 4-Pyr 3-Pyzn 1734 Ph COOEt 4-Pyr 4-Pyzn 1735 Ph COOEt 4-Pyr 5-Pyzn 1736 Ph COOEt 4-Pyr 6-Pyzn 1737 Ph COOEt 4-Pyr 2-Pym 1738 Ph COOEt 4-Pyr 4-Pym 1739 Ph COOEt 4-Pyr 5-Pym 1740 Ph COOEt 4-Pyr 6-Pym 1741 Ph COOEt 4-Pyr 2-Pyz 1742 Ph COOEt 4-Pyr 3-Pyz 1743 Ph COOEt 2-Thi Ph 1744 Ph COOEt 2-Thi 2-Pyr 1745 Ph COOEt 2-Thi 3-Pyr 1746 Ph COOEt 2-Thi 4-Pyr 1747 Ph COOEt 2-Thi 3-Pyzn 1748 Ph COOEt 2 -Thi 4-Pyzn 1749 Ph COOEt 2-Thi 5-Pyzn 1750 Ph COOEt 2-Thi 6-Pyzn 1751 Ph COOEt 2-Thi 2-Pym 1752 Ph COOEt 2-Thi 4-Pym 1753 Ph COOEt 2-Thi 5-Pym 1754 Ph COOEt 2-Thi 6-Pym 1755 Ph COOEt 2-Thi 2-Pyz 1756 Ph COOEt 2-Thi 3-Pyz 1757 Ph COOH 4-Mor Ph 1758 Ph COOH 4-Mor 2 -Pyr 1759 Ph COOH 4-Mor 3-Pyr 1760 Ph COOH 4-Mor 4-Pyr 1761 Ph COOH 4-Mor 3-Pyzn 1762 Ph COOH 4-Mor 4-Pyzn 1763 Ph COOH 4-Mor 5-Pyzn 1764 Ph COOH 4-Mor 6-Pyzn 1765 Ph COOH 4-Mor 2-Pym 1766 Ph COOH 4-Mor 4-Pym 1767 Ph COOH 4-Mor 5-Pym 1768 Ph COOH 4-Mor 6-Pym 1769 Ph COOH 4-Mor 2- Pyz 1770 Ph COOH 4-Mor 3-Pyz 1771 Ph COOH 4-Piz Ph 1772 Ph COOH 4-Piz 2-Pyr 1773 Ph COOH 4-Piz 3-Pyr 1774 Ph COOH 4-Piz 4-Pyr 1775 Ph COOH cHx-NH Ph 1776 Ph COOH cHx-NH 2-Pyr 1777 Ph COOH cHx-NH 3-Pyr 1778 Ph COOH cHx-NH 4-Pyr 1779 Ph COOH Ph-NH Ph 1780 Ph COOH Ph-NH 2-Pyr 1781 Ph COOH Ph-NH 3-Pyr 1782 Ph COOH Ph-NH 4-Pyr 1783 Ph COOH Et _Two N Ph 1784 Ph COOH Et _Two N 3-Pyr 1785 Ph NO _Two 4-Mor Ph 1786 Ph NO _Two 4-Mor 2-Pyr 1787 Ph NO _Two 4-Mor 3-Pyr 1788 Ph NO _Two 4-Mor 4-Pyr 1789 Ph NO _Two 4-Mor 3-Pyzn 1790 Ph NO _Two 4-Mor 4-Pyzn 1791 Ph NO _Two 4-Mor 5-Pyzn 1792 Ph NO _Two 4-Mor 6-Pyzn 1793 Ph NO _Two 4-Mor 2-Pym 1794 Ph NO _Two 4-Mor 4-Pym 1795 Ph NO _Two 4-Mor 5-Pym 1796 Ph NO _Two 4-Mor 6-Pym 1797 Ph NO _Two 4-Mor 2-Pyz 1798 Ph NO _Two 4-Mor 3-Pyz 1799 Ph-NH CN OH 2-Thi 1800 Ph-NH CN OH 3-Thi 1801 Ph-NH CN OH 2-Fur 1802 Ph-NH CN OH 3-Fur 1803 Ph-NH CN OH 2- Pyrr 1804 Ph-NH CN OH 3-Pyrr 1805 Ph-NH CN OH 3-Pyza 1806 Ph-NH CN OH 4-Pyza 1807 Ph-NH CN OH 5-Pyza 1808 Ph-NH CN OH 2-Imid 1809 Ph-NH CN OH 4-Imid 1810 Ph-NH CN OH 5-Imid 1811 Ph-NH CN OH 2-Oxa 1812 Ph-NH CN OH 4-Oxa 1813 Ph-NH CN OH 5-Oxa 1814 Ph-NH CN OH 2-Thiz 1815 Ph-NH CN OH 4-Thiz 1816 Ph-NH CN OH 5-Thiz 1817 Ph-NH CN OH Ph 1818 Ph-NH CN OH 2-Pyr 1819 Ph-NH CN OH 3-Pyr 1820 Ph-NH CN OH 4 -Pyr 1821 Ph-NH CN OH 3-Pyzn 1822 Ph-NH CN OH 4-Pyzn 1823 Ph-NH CN OH 5-Pyzn 1824 Ph-NH CN OH 6-Pyzn 1825 Ph-NH CN OH 2-Pym 1826 Ph- NH CN OH 4-Pym 1827 Ph-NH CN OH 5-Pym 1828 Ph-NH CN OH 6-Pym 1829 Ph-NH CN OH 2-Pyz 1830 Ph-NH CN OH 3-Pyz 1831 Ph-NH CN OH 2- BeFur 1832 Ph-NH CN OH 3-BeFur 1833 Ph-NH CN OH 4-BeFur 1834 Ph-NH CN OH 5-BeFur 1835 Ph-NH CN OH 6-BeFur 1836 Ph-NH CN OH 7-BeFur 1837 Ph-NH CN OH 1-Np 1838 Ph-NH CN OH 2-Np 1839 Ph-NH CN OH 1-Pyrd 1840 Ph-NH CN OH 1-Pip 1841 Ph-NH CN OH 4-Mor 1842 Ph-NH CN OH 4-Thm 1843 Ph-NH CN OH 4-Piz 1844 Ph-NH CN OH N- (t-Bu) -Piz 1845 Ph-NH CN OH MeS 1846 Ph-NH CN OH EtS 1847 Ph-NH CN OH PrS 1848 Ph-NH CN OH i-PrS 1849 Ph-NH CN OH n-BuS 1850 Ph-NH CN OH i-BuS 1851 Ph-NH CN OH s-BuS 1852 Ph-NH CN OH t-BuS 1853 Ph-NH CN OH PnS 1854 Ph-NH CN OH n-HxS 1855 Ph-NH CN OH HepS 1856 Ph-NH CN OH n-OcS 1857 Ph-NH CN OH NnS 1858 Ph- NH CN OH DcS 1859 Ph-NH CN OH UdcS 1860 Ph-NH CN OH DdcS 1861 Ph-NH CN OH Bz 1862 Ph-NH CN OH Ph- (CH _Two ) _Two 1863 Ph-NH CN OH Ph- (CH _Two ) _Three 1864 Ph-NH CN OH Ph- (CH _Two ) _Three 1865 Ph-NH CN OH 1-Np-CH _Two 1866 Ph-NH CN OH 2-Np-CH _Two 1867 Ph-NH CN OH 1-Np- (CH _Two ) _Two 1868 Ph-NH CN OH 2-Np- (CH _Two ) _Two 1869 Ph-NH CN OH cPr 1870 Ph-NH CN OH cBu 1871 Ph-NH CN OH cPn 1872 Ph-NH CN OH cHx 1873 Ph-NH CN OH cHep 1874 Ph-NH CN OH cOc 1875 Ph-NH CN OH Me 1876 Ph-NH CN OH Et 1877 Ph-NH CN OH Pr 1878 Ph-NH CN OH i-Pr 1879 Ph-NH CN OH n-Bu 1880 Ph-NH CN OH i-Bu 1881 Ph-NH CN OH s-Bu 1882 Ph-NH CN OH t-Bu 1883 Ph-NH CN OH Pn 1884 Ph-NH CN OH n-Hx 1885 Ph-NH CN OH Hep 1886 Ph-NH CN OH n-Oc 1887 Ph-NH CN OH Nn 1888 Ph- NH CN OH Dc 1889 Ph-NH CN OH Udc 1890 Ph-NH CN OH Ddc 1891 Ph-NH CN OH OH 1892 Ph-NH CN OH H 1893 Ph-NH CN MeO 2-Thi 1894 Ph-NH CN MeO 3-Thi 1895 Ph-NH CN MeO 2-Fur 1896 Ph-NH CN MeO 3-Fur 1897 Ph-NH CN MeO 2-Pyrr 1898 Ph-NH CN MeO 3-Pyrr 1899 Ph-NH CN MeO 3-Pyza 1900 Ph-NH CN MeO 4-Pyza 1901 Ph-NH CN MeO 5-Pyza 1902 Ph-NH CN MeO 2-Imid 1903 Ph-NH CN MeO 4-Imid 1904 Ph-NH CN MeO 5-Imid 1905 Ph-NH CN MeO 2-Oxa 1906 Ph-NH CN MeO 4-Oxa 1907 Ph-NH CN MeO 5-Oxa 1908 Ph-NH CN MeO 2-Thiz 1909 Ph-NH CN MeO 4-Thiz 1910 Ph-NH CN MeO 5-Thiz 1911 Ph-NH CN MeO Ph 1912 Ph-NH CN MeO 2-Pyr 1913 Ph-N H CN MeO 3-Pyr 1914 Ph-NH CN MeO 4-Pyr 1915 Ph-NH CN MeO 3-Pyzn 1916 Ph-NH CN MeO 4-Pyzn 1917 Ph-NH CN MeO 5-Pyzn 1918 Ph-NH CN MeO 6- Pyzn 1919 Ph-NH CN MeO 2-Pym 1920 Ph-NH CN MeO 4-Pym 1921 Ph-NH CN MeO 5-Pym 1922 Ph-NH CN MeO 6-Pym 1923 Ph-NH CN MeO 2-Pyz 1924 Ph-NH CN MeO 3-Pyz 1925 Ph-NH CN MeO 2-BeFur 1926 Ph-NH CN MeO 3-BeFur 1927 Ph-NH CN MeO 4-BeFur 1928 Ph-NH CN MeO 5-BeFur 1929 Ph-NH CN MeO 6-BeFur 1930 Ph-NH CN MeO 7-BeFur 1931 Ph-NH CN MeO 1-Np 1932 Ph-NH CN MeO 2-Np 1933 Ph-NH CN MeO 1-Pyrd 1934 Ph-NH CN MeO 1-Pip 1935 Ph-NH CN MeO 4-Mor 1936 Ph-NH CN MeO 4-Thm 1937 Ph-NH CN MeO 4-Piz 1938 Ph-NH CN MeO N- (t-Bu) -Piz 1939 Ph-NH CN MeO MeS 1940 Ph-NH CN MeO EtS 1941 Ph-NH CN MeO PrS 1942 Ph-NH CN MeO i-PrS 1943 Ph-NH CN MeO n-BuS 1944 Ph-NH CN MeO i-BuS 1945 Ph-NH CN MeO s-BuS 1946 Ph-NH CN MeO t-BuS 1947 Ph-NH CN MeO PnS 1948 Ph-NH CN MeO n-HxS 1949 Ph-NH CN MeO HepS 1950 Ph-NH CN MeO n-OcS 1951 Ph-NH CN MeO NnS 1952 Ph-NH CN MeO DcS 1953 Ph-NH CN MeO UdcS 1954 Ph-NH CN MeO DdcS 1955 Ph-NH CN MeO Bz 1956 Ph-NH CN MeO Ph- (CH _Two ) _Two 1957 Ph-NH CN MeO Ph- (CH _Two ) _Three 1958 Ph-NH CN MeO Ph- (CH _Two ) _Three 1959 Ph-NH CN MeO 1-Np-CH _Two 1960 Ph-NH CN MeO 2-Np-CH _Two 1961 Ph-NH CN MeO 1-Np- (CH _Two ) _Two 1962 Ph-NH CN MeO 2-Np- (CH _Two ) _Two 1963 Ph-NH CN MeO cPr 1964 Ph-NH CN MeO cBu 1965 Ph-NH CN MeO cPn 1966 Ph-NH CN MeO cHx 1967 Ph-NH CN MeO cHep 1968 Ph-NH CN MeO cOc 1969 Ph-NH CN MeO Me 1970 Ph-NH CN MeO Et 1971 Ph-NH CN MeO Pr 1972 Ph-NH CN MeO i-Pr 1973 Ph-NH CN MeO n-Bu 1974 Ph-NH CN MeO i-Bu 1975 Ph-NH CN MeO s-Bu 1976 Ph-NH CN MeO t-Bu 1977 Ph-NH CN MeO Pn 1978 Ph-NH CN MeO n-Hx 1979 Ph-NH CN MeO Hep 1980 Ph-NH CN MeO n-Oc 1981 Ph-NH CN MeO Nn 1982 Ph- NH CN MeO Dc 1983 Ph-NH CN MeO Udc 1984 Ph-NH CN MeO Ddc 1985 Ph-NH CN MeO OH 1986 Ph-NH CN MeO H 1987 Ph-NH CN EtO 2-Thi 1988 Ph-NH CN EtO 3-Thi 1989 Ph-NH CN EtO 2-Fur 1990 Ph-NH CN EtO 3-Fur 1991 Ph-NH CN EtO 2-Pyrr 1992 Ph-NH CN EtO 3-Pyrr 1993 Ph-NH CN EtO 3-Pyza 1994 Ph-NH CN EtO 4-Pyza 1995 Ph-NH CN EtO 5-Pyza 1996 Ph-NH CN EtO 2-Imid 1997 Ph-NH CN EtO 4-Imid 1998 Ph-NH CN EtO 5-Imid 1999 Ph-NH CN EtO 2-Oxa 2000 Ph-NH CN EtO 4-Oxa 2001 Ph-NH CN EtO 5-Oxa 2002 Ph-NH CN EtO 2-Thiz 2003 Ph-NH CN EtO 4-Thiz 2004 Ph-NH CN EtO 5-Thiz 2005 Ph-NH CN EtO Ph 2006 Ph-N H CN EtO 2-Pyr 2007 Ph-NH CN EtO 3-Pyr 2008 Ph-NH CN EtO 4-Pyr 2009 Ph-NH CN EtO 3-Pyzn 2010 Ph-NH CN EtO 4-Pyzn 2011 Ph-NH CN EtO 5- Pyzn 2012 Ph-NH CN EtO 6-Pyzn 2013 Ph-NH CN EtO 2-Pym 2014 Ph-NH CN EtO 4-Pym 2015 Ph-NH CN EtO 5-Pym 2016 Ph-NH CN EtO 6-Pym 2017 Ph-NH CN EtO 2-Pyz 2018 Ph-NH CN EtO 3-Pyz 2019 Ph-NH CN EtO 2-BeFur 2020 Ph-NH CN EtO 3-BeFur 2021 Ph-NH CN EtO 4-BeFur 2022 Ph-NH CN EtO 5-BeFur 2023 Ph-NH CN EtO 6-BeFur 2024 Ph-NH CN EtO 7-BeFur 2025 Ph-NH CN EtO 1-Np 2026 Ph-NH CN EtO 2-Np 2027 Ph-NH CN EtO 1-Pyrd 2028 Ph-NH CN EtO 1-Pip 2029 Ph-NH CN EtO 4-Mor 2030 Ph-NH CN EtO 4-Thm 2031 Ph-NH CN EtO 4-Piz 2032 Ph-NH CN EtO N- (t-Bu) -Piz 2033 Ph-NH CN EtO MeS 2034 Ph-NH CN EtO EtS 2035 Ph-NH CN EtO PrS 2036 Ph-NH CN EtO i-PrS 2037 Ph-NH CN EtO n-BuS 2038 Ph-NH CN EtO i-BuS 2039 Ph-NH CN EtO s-BuS 2040 Ph-NH CN EtO t-BuS 2041 Ph-NH CN EtO PnS 2042 Ph-NH CN EtO n-HxS 2043 Ph-NH CN EtO HepS 2044 Ph-NH CN EtO n-OcS 2045 Ph-NH CN EtO NnS 2046 Ph-NH CN EtO DcS 2047 Ph-NH CN Et O UdcS 2048 Ph-NH CN EtO DdcS 2049 Ph-NH CN EtO Bz 2050 Ph-NH CN EtO Ph- (CH _Two ) _Two 2051 Ph-NH CN EtO Ph- (CH _Two ) _Three 2052 Ph-NH CN EtO Ph- (CH _Two ) _Three 2053 Ph-NH CN EtO 1-Np-CH _Two 2054 Ph-NH CN EtO 2-Np-CH _Two 2055 Ph-NH CN EtO 1-Np- (CH _Two ) _Two 2056 Ph-NH CN EtO 2-Np- (CH _Two ) _Two 2057 Ph-NH CN EtO cPr 2058 Ph-NH CN EtO cBu 2059 Ph-NH CN EtO cPn 2060 Ph-NH CN EtO cHx 2061 Ph-NH CN EtO cHep 2062 Ph-NH CN EtO cOc 2063 Ph-NH CN EtO Me 2064 Ph-NH CN EtO Et 2065 Ph-NH CN EtO Pr 2066 Ph-NH CN EtO i-Pr 2067 Ph-NH CN EtO n-Bu 2068 Ph-NH CN EtO i-Bu 2069 Ph-NH CN EtO s-Bu 2070 Ph-NH CN EtO t-Bu 2071 Ph-NH CN EtO Pn 2072 Ph-NH CN EtO n-Hx 2073 Ph-NH CN EtO Hep 2074 Ph-NH CN EtO n-Oc 2075 Ph-NH CN EtO Nn 2076 Ph- NH CN EtO Dc 2077 Ph-NH CN EtO Udc 2078 Ph-NH CN EtO Ddc 2079 Ph-NH CN EtO OH 2080 Ph-NH CN EtO H 2081 Ph-NH CN PnO 2-Thi 2082 Ph-NH CN PnO 3-Thi 2083 Ph-NH CN PnO 2-Fur 2084 Ph-NH CN PnO 3-Fur 2085 Ph-NH CN PnO 2-Pyrr 2086 Ph-NH CN PnO 3-Pyrr 2087 Ph-NH CN PnO 3-Pyza 2088 Ph-NH CN PnO 4-Pyza 2089 Ph-NH CN PnO 5-Pyza 2090 Ph-NH CN PnO 2-Imid 2091 Ph-NH CN PnO 4-Imid 2092 Ph-NH CN PnO 5-Imid 2093 Ph-NH CN PnO 2-Oxa 2094 Ph-NH CN PnO 4-Oxa 2095 Ph-NH CN PnO 5-Oxa 2096 Ph-NH CN PnO 2-Thiz 2097 Ph-NH CN PnO 4-Thiz 2098 Ph-NH CN PnO 5-Thiz 2099 Ph-NH CN PnO Ph 2100 Ph-N H CN PnO 2-Pyr 2101 Ph-NH CN PnO 3-Pyr 2102 Ph-NH CN PnO 4-Pyr 2103 Ph-NH CN PnO 3-Pyzn 2104 Ph-NH CN PnO 4-Pyzn 2105 Ph-NH CN PnO 5- Pyzn 2106 Ph-NH CN PnO 6-Pyzn 2107 Ph-NH CN PnO 2-Pym 2108 Ph-NH CN PnO 4-Pym 2109 Ph-NH CN PnO 5-Pym 2110 Ph-NH CN PnO 6-Pym 2111 Ph-NH CN PnO 2-Pyz 2112 Ph-NH CN PnO 3-Pyz 2113 Ph-NH CN PnO 2-BeFur 2114 Ph-NH CN PnO 3-BeFur 2115 Ph-NH CN PnO 4-BeFur 2116 Ph-NH CN PnO 5-BeFur 2117 Ph-NH CN PnO 6-BeFur 2118 Ph-NH CN PnO 7-BeFur 2119 Ph-NH CN HepO Ph 2120 Ph-NH CN HepO 2-Pyr 2121 Ph-NH CN HepO 3-Pyr 2122 Ph-NH CN HepO 4 -Pyr 2123 Ph-NH CN HepO 3-Pyzn 2124 Ph-NH CN HepO 4-Pyzn 2125 Ph-NH CN HepO 5-Pyzn 2126 Ph-NH CN HepO 6-Pyzn 2127 Ph-NH CN HepO 2-Pym 2128 Ph- NH CN HepO 4-Pym 2129 Ph-NH CN HepO 5-Pym 2130 Ph-NH CN HepO 6-Pym 2131 Ph-NH CN HepO 2-Pyz 2132 Ph-NH CN HepO 3-Pyz 2133 Ph-NH CN 4-Mor 2-Thi 2134 Ph-NH CN 4-Mor 3-Thi 2135 Ph-NH CN 4-Mor 2-Fur 2136 Ph-NH CN 4-Mor 3-Fur 2137 Ph-NH CN 4-Mor 2-Pyrr 2138 Ph- NH CN 4-Mor 3-Pyrr 2139 Ph-NH CN 4-Mor 3-Pyza 2 140 Ph-NH CN 4-Mor 4-Pyza 2141 Ph-NH CN 4-Mor 5-Pyza 2142 Ph-NH CN 4-Mor 2-Imid 2143 Ph-NH CN 4-Mor 4-Imid 2144 Ph-NH CN 4 -Mor 5-Imid 2145 Ph-NH CN 4-Mor 2-Oxa 2146 Ph-NH CN 4-Mor 4-Oxa 2147 Ph-NH CN 4-Mor 5-Oxa 2148 Ph-NH CN 4-Mor 2-Thiz 2149 Ph-NH CN 4-Mor 4-Thiz 2150 Ph-NH CN 4-Mor 5-Thiz 2151 Ph-NH CN 4-Mor Ph 2152 Ph-NH CN 4-Mor 2-Pyr 2153 Ph-NH CN 4-Mor 3 -Pyr 2154 Ph-NH CN 4-Mor 4-Pyr 2155 Ph-NH CN 4-Mor 3-Pyzn 2156 Ph-NH CN 4-Mor 4-Pyzn 2157 Ph-NH CN 4-Mor 5-Pyzn 2158 Ph-NH CN 4-Mor 6-Pyzn 2159 Ph-NH CN 4-Mor 2-Pym 2160 Ph-NH CN 4-Mor 4-Pym 2161 Ph-NH CN 4-Mor 5-Pym 2162 Ph-NH CN 4-Mor 6- Pym 2163 Ph-NH CN 4-Mor 2-Pyz 2164 Ph-NH CN 4-Mor 3-Pyz 2165 Ph-NH CN 4-Mor 2-BeFur 2166 Ph-NH CN 4-Mor 3-BeFur 2167 Ph-NH CN 4-Mor 4-BeFur 2168 Ph-NH CN 4-Mor 5-BeFur 2169 Ph-NH CN 4-Mor 6-BeFur 2170 Ph-NH CN 4-Mor 7-BeFur 2171 Ph-NH CN 4-Mor 1-Np 2172 Ph-NH CN 4-Mor 2-Np 2173 Ph-NH CN 4-Mor 1-Pyrd 2174 Ph-NH CN 4-Mor 1-Pip 2175 Ph-NH CN 4-Mor 4-Mor 2176 Ph-NH CN 4 -Mor 4-Thm 2177 Ph-NH CN 4-Mor 4-Piz 2178 Ph-NH CN 4-Mor N- (t-Bu) -Piz 2179 Ph-NH CN 4-Mor MeS 2180 Ph-NH CN 4-Mor EtS 2181 Ph-NH CN 4-Mor PrS 2182 Ph- NH CN 4-Mor i-PrS 2183 Ph-NH CN 4-Mor n-BuS 2184 Ph-NH CN 4-Mor i-BuS 2185 Ph-NH CN 4-Mor s-BuS 2186 Ph-NH CN 4-Mort -BuS 2187 Ph-NH CN 4-Mor PnS 2188 Ph-NH CN 4-Mor n-HxS 2189 Ph-NH CN 4-Mor HepS 2190 Ph-NH CN 4-Mor n-OcS 2191 Ph-NH CN 4-Mor NnS 2192 Ph-NH CN 4-Mor DcS 2193 Ph-NH CN 4-Mor UdcS 2194 Ph-NH CN 4-Mor DdcS 2195 Ph-NH CN 4-Mor Bz 2196 Ph-NH CN 4-Mor Ph- (CH _Two ) _Two 2197 Ph-NH CN 4-Mor Ph- (CH _Two ) _Three 2198 Ph-NH CN 4-Mor Ph- (CH _Two ) _Three 2199 Ph-NH CN 4-Mor 1-Np-CH _Two 2200 Ph-NH CN 4-Mor 2-Np-CH _Two 2201 Ph-NH CN 4-Mor 1-Np- (CH _Two ) _Two 2202 Ph-NH CN 4-Mor 2-Np- (CH _Two ) _Two 2203 Ph-NH CN 4-Mor cPr 2204 Ph-NH CN 4-Mor cBu 2205 Ph-NH CN 4-Mor cPn 2206 Ph-NH CN 4-Mor cHx 2207 Ph-NH CN 4-Mor cHep 2208 Ph-NH CN 4-Mor cOc 2209 Ph-NH CN 4-Mor Me 2210 Ph-NH CN 4-Mor Et 2211 Ph-NH CN 4-Mor Pr 2212 Ph-NH CN 4-Mor i-Pr 2213 Ph-NH CN 4-Mor n-Bu 2214 Ph-NH CN 4-Mor i-Bu 2215 Ph-NH CN 4-Mor s-Bu 2216 Ph-NH CN 4-Mor t-Bu 2217 Ph-NH CN 4-Mor Pn 2218 Ph-NH CN 4-Mor n-Hx 2219 Ph-NH CN 4-Mor Hep 2220 Ph-NH CN 4-Mor n-Oc 2221 Ph-NH CN 4-Mor Nn 2222 Ph-NH CN 4-Mor Dc 2223 Ph-NH CN 4 -Mor Udc 2224 Ph-NH CN 4-Mor Ddc 2225 Ph-NH CN 4-Mor OH 2226 Ph-NH CN 4-Mor H 2227 Ph-NH CN 4-Thm 2-Thi 2228 Ph-NH CN 4-Thm 3 -Thi 2229 Ph-NH CN 4-Thm 2-Fur 2230 Ph-NH CN 4-Thm 3-Fur 2231 Ph-NH CN 4-Thm 2-Pyrr 2232 Ph-NH CN 4-Thm 3-Pyrr 2233 Ph-NH CN 4-Thm 3-Pyza 2234 Ph-NH CN 4-Thm 4-Pyza 2235 Ph-NH CN 4-Thm 5-Pyza 2236 Ph-NH CN 4-Thm 2-Imid 2237 Ph-NH CN 4-Thm 4- Imid 2238 Ph-NH CN 4-Thm 5-Imid 2239 Ph-NH CN 4-Thm 2-Oxa 2240 Ph-NH CN 4-Thm 4-Oxa 2241 Ph-NH CN 4-Thm 5-Oxa 2242 Ph-NH CN 4-Thm 2-Thiz 2243 Ph-NH CN 4-Thm 4-Thiz 2244 Ph-NH CN 4-Thm 5-Thiz 2245 Ph-NH CN 4-Thm Ph 2246 Ph-NH CN 4-Thm 2-Pyr 2247 Ph-NH CN 4-Thm 3-Pyr 2248 Ph-NH CN 4-Thm 4-Pyr 2249 Ph-NH CN 4-Thm 3-Pyzn 2250 Ph-NH CN 4-Thm 4-Pyzn 2251 Ph-NH CN 4-Thm 5-Pyzn 2252 Ph- NH CN 4-Thm 6-Pyzn 2253 Ph-NH CN 4-Thm 2-Pym 2254 Ph-NH CN 4-Thm 4-Pym 2255 Ph-NH CN 4-Thm 5-Pym 2256 Ph-NH CN 4-Thm 6 -Pym 2257 Ph-NH CN 4-Thm 2-Pyz 2258 Ph-NH CN 4-Thm 3-Pyz 2259 Ph-NH CN 4-Thm 2-BeFur 2260 Ph-NH CN 4-Thm 3-BeFur 2261 Ph-NH CN 4-Thm 4-BeFur 2262 Ph-NH CN 4-Thm 5-BeFur 2263 Ph-NH CN 4-Thm 6-BeFur 2264 Ph-NH CN 4-Thm 7-BeFur 2265 Ph-NH CN 4-Thm 1- Np 2266 Ph-NH CN 4-Thm 2-Np 2267 Ph-NH CN 4-Thm 1-Pyrd 2268 Ph-NH CN 4-Thm 1-Pip 2269 Ph-NH CN 4-Thm 4-Mor 2270 Ph-NH CN 4-Thm 4-Thm 2271 Ph-NH CN 4-Thm 4-Piz 2272 Ph-NH CN 4-Thm N- (t-Bu) -Piz 2273 Ph-NH CN 4-Thm MeS 2274 Ph-NH CN 4- Thm EtS 2275 Ph-NH CN 4-Thm PrS 2276 Ph-NH CN 4-Thm i-PrS 2277 Ph-NH CN 4-Thm n-BuS 2278 Ph-NH CN 4-Thm i-BuS 2279 Ph-NH CN 4 -Thm s-BuS 2280 Ph-NH CN 4-Thm tB uS 2281 Ph-NH CN 4-Thm PnS 2282 Ph-NH CN 4-Thm n-HxS 2283 Ph-NH CN 4-Thm HepS 2284 Ph-NH CN 4-Thm n-OcS 2285 Ph-NH CN 4-Thm NnS 2286 Ph-NH CN 4-Thm DcS 2287 Ph-NH CN 4-Thm UdcS 2288 Ph-NH CN 4-Thm DdcS 2289 Ph-NH CN 4-Thm Bz 2290 Ph-NH CN 4-Thm Ph- (CH _Two ) _Two 2291 Ph-NH CN 4-Thm Ph- (CH _Two ) _Three 2292 Ph-NH CN 4-Thm Ph- (CH _Two ) _Three 2293 Ph-NH CN 4-Thm 1-Np-CH _Two 2294 Ph-NH CN 4-Thm 2-Np-CH _Two 2295 Ph-NH CN 4-Thm 1-Np- (CH _Two ) _Two 2296 Ph-NH CN 4-Thm 2-Np- (CH _Two ) _Two 2297 Ph-NH CN 4-Thm cPr 2298 Ph-NH CN 4-Thm cBu 2299 Ph-NH CN 4-Thm cPn 2300 Ph-NH CN 4-Thm cHx 2301 Ph-NH CN 4-Thm cHep 2302 Ph-NH CN 4-Thm cOc 2303 Ph-NH CN 4-Thm Me 2304 Ph-NH CN 4-Thm Et 2305 Ph-NH CN 4-Thm Pr 2306 Ph-NH CN 4-Thm i-Pr 2307 Ph-NH CN 4-Thm n-Bu 2308 Ph-NH CN 4-Thm i-Bu 2309 Ph-NH CN 4-Thms s-Bu 2310 Ph-NH CN 4-Thm t-Bu 2311 Ph-NH CN 4-Thm Pn 2312 Ph-NH CN 4-Thm n-Hx 2313 Ph-NH CN 4-Thm Hep 2314 Ph-NH CN 4-Thm n-Oc 2315 Ph-NH CN 4-Thm Nn 2316 Ph-NH CN 4-Thm Dc 2317 Ph-NH CN 4 -Thm Udc 2318 Ph-NH CN 4-Thm Ddc 2319 Ph-NH CN 4-Thm OH 2320 Ph-NH CN 4-Thm H 2321 Ph-NH CN 1-Pip 2-Thi 2322 Ph-NH CN 1-Pip 3 -Thi 2323 Ph-NH CN 1-Pip 2-Fur 2324 Ph-NH CN 1-Pip 3-Fur 2325 Ph-NH CN 1-Pip 2-Pyrr 2326 Ph-NH CN 1-Pip 3-Pyrr 2327 Ph-NH CN 1-Pip 3-Pyza 2328 Ph-NH CN 1-Pip 4-Pyza 2329 Ph-NH CN 1-Pip 5-Pyza 2330 Ph-NH CN 1-Pip 2-Imid 2331 Ph-NH CN 1-Pip 4- Imid 2332 Ph-NH CN 1-Pip 5-Imid 2333 Ph-NH CN 1-Pip 2-Oxa 2334 Ph-NH CN 1-Pip 4-Oxa 2335 Ph-NH CN 1-Pip 5-Oxa 2336 Ph-NH CN 1-Pip 2-Thiz 2337 Ph-NH CN 1-Pip 4-Thiz 2338 Ph-NH CN 1-Pip 5-Thiz 2339 Ph-NH CN 1-Pip Ph 2340 Ph-NH CN 1-Pip 2-Pyr 2341 Ph-NH CN 1-Pip 3-Pyr 2342 Ph-NH CN 1-Pip 4-Pyr 2343 Ph-NH CN 1-Pip 3-Pyzn 2344 Ph-NH CN 1-Pip 4-Pyzn 2345 Ph-NH CN 1-Pip 5-Pyzn 2346 Ph- NH CN 1-Pip 6-Pyzn 2347 Ph-NH CN 1-Pip 2-Pym 2348 Ph-NH CN 1-Pip 4-Pym 2349 Ph-NH CN 1-Pip 5-Pym 2350 Ph-NH CN 1-Pip 6 -Pym 2351 Ph-NH CN 1-Pip 2-Pyz 2352 Ph-NH CN 1-Pip 3-Pyz 2353 Ph-NH CN 1-Pip 2-BeFur 2354 Ph-NH CN 1-Pip 3-BeFur 2355 Ph-NH CN 1-Pip 4-BeFur 2356 Ph-NH CN 1-Pip 5-BeFur 2357 Ph-NH CN 1-Pip 6-BeFur 2358 Ph-NH CN 1-Pip 7-BeFur 2359 Ph-NH CN 1-Pip 1- Np 2360 Ph-NH CN 1-Pip 2-Np 2361 Ph-NH CN 1-Pip 1-Pyrd 2362 Ph-NH CN 1-Pip 1-Pip 2363 Ph-NH CN 1-Pip 4-Mor 2364 Ph-NH CN 1-Pip 4-Thm 2365 Ph-NH CN 1-Pip 4-Piz 2366 Ph-NH CN 1-Pip N- (t-Bu) -Piz 2367 Ph-NH CN 1-Pip MeS 2368 Ph-NH CN 1- Pip EtS 2369 Ph-NH CN 1-Pip PrS 2370 Ph-NH CN 1-Pip i-PrS 2371 Ph-NH CN 1-Pip n-BuS 2372 Ph-NH CN 1-Pip i-BuS 2373 Ph-NH CN 1 -Pip s-BuS 2374 Ph-NH CN 1-Pip tB uS 2375 Ph-NH CN 1-Pip PnS 2376 Ph-NH CN 1-Pip n-HxS 2377 Ph-NH CN 1-Pip HepS 2378 Ph-NH CN 1-Pip n-OcS 2379 Ph-NH CN 1-Pip NnS 2380 Ph-NH CN 1-Pip DcS 2381 Ph-NH CN 1-Pip UdcS 2382 Ph-NH CN 1-Pip DdcS 2383 Ph-NH CN 1-Pip Bz 2384 Ph-NH CN 1-Pip Ph- (CH _Two ) _Two 2385 Ph-NH CN 1-Pip Ph- (CH _Two ) _Three 2386 Ph-NH CN 1-Pip Ph- (CH _Two ) _Three 2387 Ph-NH CN 1-Pip 1-Np-CH _Two 2388 Ph-NH CN 1-Pip 2-Np-CH _Two 2389 Ph-NH CN 1-Pip 1-Np- (CH _Two ) _Two 2390 Ph-NH CN 1-Pip 2-Np- (CH _Two ) _Two 2391 Ph-NH CN 1-Pip cPr 2392 Ph-NH CN 1-Pip cBu 2393 Ph-NH CN 1-Pip cPn 2394 Ph-NH CN 1-Pip cHx 2395 Ph-NH CN 1-Pip cHep 2396 Ph-NH CN 1-Pip cOc 2397 Ph-NH CN 1-Pip Me 2398 Ph-NH CN 1-Pip Et 2399 Ph-NH CN 1-Pip Pr 2400 Ph-NH CN 1-Pip i-Pr 2401 Ph-NH CN 1-Pip n-Bu 2402 Ph-NH CN 1-Pip i-Bu 2403 Ph-NH CN 1-Pip s-Bu 2404 Ph-NH CN 1-Pip t-Bu 2405 Ph-NH CN 1-Pip Pn 2406 Ph-NH CN 1-Pip n-Hx 2407 Ph-NH CN 1-Pip Hep 2408 Ph-NH CN 1-Pip n-Oc 2409 Ph-NH CN 1-Pip Nn 2410 Ph-NH CN 1-Pip Dc 2411 Ph-NH CN 1 -Pip Udc 2412 Ph-NH CN 1-Pip Ddc 2413 Ph-NH CN 1-Pip OH 2414 Ph-NH CN 1-Pip H 2415 Ph-NH CN 4-Piz 2-Thi 2416 Ph-NH CN 4-Piz 3 -Thi 2417 Ph-NH CN 4-Piz 2-Fur 2418 Ph-NH CN 4-Piz 3-Fur 2419 Ph-NH CN 4-Piz 2-Pyrr 2420 Ph-NH CN 4-Piz 3-Pyrr 2421 Ph-NH CN 4-Piz 3-Pyza 2422 Ph-NH CN 4-Piz 4-Pyza 2423 Ph-NH CN 4-Piz 5-Pyza 2424 Ph-NH CN 4-Piz 2-Imid 2425 Ph-NH CN 4-Piz 4- Imid 2426 Ph-NH CN 4-Piz 5-Imid 2427 Ph-NH CN 4-Piz 2-Oxa 2428 Ph-NH CN 4-Piz 4-Oxa 2429 Ph-NH CN 4-Piz 5-Oxa 2430 Ph-NH CN 4-Piz 2-Thiz 2431 Ph-NH CN 4-Piz 4-Thiz 2432 Ph-NH CN 4-Piz 5-Thiz 2433 Ph-NH CN 4-Piz Ph 2434 Ph-NH CN 4-Piz 2-Pyr 2435 Ph-NH CN 4-Piz 3-Pyr 2436 Ph-NH CN 4-Piz 4-Pyr 2437 Ph-NH CN 4-Piz 3-Pyzn 2438 Ph-NH CN 4-Piz 4-Pyzn 2439 Ph-NH CN 4-Piz 5-Pyzn 2440 Ph- NH CN 4-Piz 6-Pyzn 2441 Ph-NH CN 4-Piz 2-Pym 2442 Ph-NH CN 4-Piz 4-Pym 2443 Ph-NH CN 4-Piz 5-Pym 2444 Ph-NH CN 4-Piz 6 -Pym 2445 Ph-NH CN 4-Piz 2-Pyz 2446 Ph-NH CN 4-Piz 3-Pyz 2447 Ph-NH CN 4-Piz 2-BeFur 2448 Ph-NH CN 4-Piz 3-BeFur 2449 Ph-NH CN 4-Piz 4-BeFur 2450 Ph-NH CN 4-Piz 5-BeFur 2451 Ph-NH CN 4-Piz 6-BeFur 2452 Ph-NH CN 4-Piz 7-BeFur 2453 Ph-NH CN 4-Piz 1- Np 2454 Ph-NH CN 4-Piz 2-Np 2455 Ph-NH CN 4-Piz 1-Pyrd 2456 Ph-NH CN 4-Piz 1-Pip 2457 Ph-NH CN 4-Piz 4-Mor 2458 Ph-NH CN 4-Piz 4-Thm 2459 Ph-NH CN 4-Piz 4-Piz 2460 Ph-NH CN 4-Piz N- (t-Bu) -Piz 2461 Ph-NH CN 4-Piz MeS 2462 Ph-NH CN 4- Piz EtS 2463 Ph-NH CN 4-Piz PrS 2464 Ph-NH CN 4-Piz i-PrS 2465 Ph-NH CN 4-Piz n-BuS 2466 Ph-NH CN 4-Piz i-BuS 2467 Ph-NH CN 4 -Piz s-BuS 2468 Ph-NH CN 4-Piz tB uS 2469 Ph-NH CN 4-Piz PnS 2470 Ph-NH CN 4-Piz n-HxS 2471 Ph-NH CN 4-Piz HepS 2472 Ph-NH CN 4-Piz n-OcS 2473 Ph-NH CN 4-Piz NnS 2474 Ph-NH CN 4-Piz DcS 2475 Ph-NH CN 4-Piz UdcS 2476 Ph-NH CN 4-Piz DdcS 2477 Ph-NH CN 4-Piz Bz 2478 Ph-NH CN 4-Piz Ph- (CH _Two ) _Two 2479 Ph-NH CN 4-Piz Ph- (CH _Two ) _Three 2480 Ph-NH CN 4-Piz Ph- (CH _Two ) _Three 2481 Ph-NH CN 4-Piz 1-Np-CH _Two 2482 Ph-NH CN 4-Piz 2-Np-CH _Two 2483 Ph-NH CN 4-Piz 1-Np- (CH _Two ) _Two 2484 Ph-NH CN 4-Piz 2-Np- (CH _Two ) _Two 2485 Ph-NH CN 4-Piz cPr 2486 Ph-NH CN 4-Piz cBu 2487 Ph-NH CN 4-Piz cPn 2488 Ph-NH CN 4-Piz cHx 2489 Ph-NH CN 4-Piz cHep 2490 Ph-NH CN 4-Piz cOc 2491 Ph-NH CN 4-Piz Me 2492 Ph-NH CN 4-Piz Et 2493 Ph-NH CN 4-Piz Pr 2494 Ph-NH CN 4-Piz i-Pr 2495 Ph-NH CN 4-Piz n-Bu 2496 Ph-NH CN 4-Piz i-Bu 2497 Ph-NH CN 4-Piz s-Bu 2498 Ph-NH CN 4-Piz t-Bu 2499 Ph-NH CN 4-Piz Pn 2500 Ph-NH CN 4-Piz n-Hx 2501 Ph-NH CN 4-Piz Hep 2502 Ph-NH CN 4-Piz n-Oc 2503 Ph-NH CN 4-Piz Nn 2504 Ph-NH CN 4-Piz Dc 2505 Ph-NH CN 4 -Piz Udc 2506 Ph-NH CN 4-Piz Ddc 2507 Ph-NH CN 4-Piz OH 2508 Ph-NH CN 4-Piz H 2509 Ph-NH CN (Et) _Two N Ph 2510 Ph-NH CN (Et) _Two N 2-Pyr 2511 Ph-NH CN (Et) _Two N 3-Pyr 2512 Ph-NH CN (Et) _Two N 4-Pyr 2513 Ph-NH CN (Et) _Two N 3-Pyzn 2514 Ph-NH CN (Et) _Two N 4-Pyzn 2515 Ph-NH CN (Et) _Two N 5-Pyzn 2516 Ph-NH CN (Et) _Two N 6-Pyzn 2517 Ph-NH CN (Et) _Two N 2-Pym 2518 Ph-NH CN (Et) _Two N 4-Pym 2519 Ph-NH CN (Et) _Two N 5-Pym 2520 Ph-NH CN (Et) _Two N 6-Pym 2521 Ph-NH CN (Et) _Two N 2-Pyz 2522 Ph-NH CN (Et) _Two N 3-Pyz 2523 Ph-NH CN cHx-NH Ph 2524 Ph-NH CN cHx-NH 2-Pyr 2525 Ph-NH CN cHx-NH 3-Pyr 2526 Ph-NH CN cHx-NH 4-Pyr 2527 Ph-NH CN cHx-NH 3-Pyzn 2528 Ph-NH CN cHx-NH 4-Pyzn 2529 Ph-NH CN cHx-NH 5-Pyzn 2530 Ph-NH CN cHx-NH 6-Pyzn 2531 Ph-NH CN cHx-NH 2- Pym 2532 Ph-NH CN cHx-NH 4-Pym 2533 Ph-NH CN cHx-NH 5-Pym 2534 Ph-NH CN cHx-NH 6-Pym 2535 Ph-NH CN cHx-NH 2-Pyz 2536 Ph-NH CN cHx-NH 3-Pyz 2537 Ph-NH CN Ph-NH Ph 2538 Ph-NH CN Ph-NH 2-Pyr 2539 Ph-NH CN Ph-NH 3-Pyr 2540 Ph-NH CN Ph-NH 4-Pyr 2541 Ph -NH CN Ph-NH 3-Pyzn 2542 Ph-NH CN Ph-NH 4-Pyzn 2543 Ph-NH CN Ph-NH 5-Pyzn 2544 Ph-NH CN Ph-NH 6-Pyzn 2545 Ph-NH CN Ph-NH 2-Pym 2546 Ph-NH CN Ph-NH 4-Pym 2547 Ph-NH CN Ph-NH 5-Pym 2548 Ph-NH CN Ph-NH 6-Pym 2549 Ph-NH CN Ph-NH 2-Pyz 2550 Ph- NH CN Ph-NH 3-Pyz 2551 Ph-NH CN 3-Cl-Ph-NH Ph 2552 Ph-NH CN 3-Cl-Ph-NH 2-Pyr 2553 Ph-NH CN 3-Cl-Ph-NH 3- Pyr 2554 Ph-NH CN 3-Cl-Ph-NH 4-Pyr 2555 Ph-NH CN 3-Cl-Ph-NH 3-Pyzn 2556 Ph-NH CN 3-Cl-Ph-NH 4-Pyzn 2557 Ph-NH CN 3-Cl-Ph-NH 5-Pyzn 2558 Ph-NH CN 3-Cl-Ph-NH 6-Pyzn 2559 Ph-NH CN 3-Cl-Ph-NH 2-Pym 2560 Ph-NH CN 3-Cl-Ph-NH 4-Pym 2561 Ph-NH CN 3-Cl-Ph-NH 5-Pym 2562 Ph-NH CN 3-Cl-Ph-NH 6-Pym 2563 Ph-NH CN 3-Cl-Ph-NH 2-Pyz 2564 Ph-NH CN 3-Cl-Ph-NH 3-Pyz 2565 Ph-NH CN 2-Me-Ph -NH Ph 2566 Ph-NH CN 2-Me-Ph-NH 2-Pyr 2567 Ph-NH CN 2-Me-Ph-NH 3-Pyr 2568 Ph-NH CN 2-Me-Ph-NH 4-Pyr 2569 Ph -NH CN 2-Me-Ph-NH 3-Pyzn 2570 Ph-NH CN 2-Me-Ph-NH 4-Pyzn 2571 Ph-NH CN 2-Me-Ph-NH 5-Pyzn 2572 Ph-NH CN 2- Me-Ph-NH 6-Pyzn 2573 Ph-NH CN 2-Me-Ph-NH 2-Pym 2574 Ph-NH CN 2-Me-Ph-NH 4-Pym 2575 Ph-NH CN 2-Me-Ph-NH 5-Pym 2576 Ph-NH CN 2-Me-Ph-NH 6-Pym 2577 Ph-NH CN 2-Me-Ph-NH 2-Pyz 2578 Ph-NH CN 2-Me-Ph-NH 3-Pyz 2579 Ph -NH CN 3-Me-Ph-NH Ph 2580 Ph-NH CN 3-Me-Ph-NH 2-Pyr 2581 Ph-NH CN 3-Me-Ph-NH 3-Pyr 2582 Ph-NH CN 3-Me- Ph-NH 4-Pyr 2583 Ph-NH CN 3-Me-Ph-NH 3-Pyzn 2584 Ph-NH CN 3-Me-Ph-NH 4-Pyzn 2585 Ph-NH CN 3-Me-Ph-NH 5- Pyzn 2586 Ph-NH CN 3-Me-Ph-NH 6-Pyzn 2587 Ph-NH CN 3-Me-Ph-NH 2-Pym 2588 Ph-NH CN 3-Me-Ph-NH 4-Pym 2589 Ph-NH CN 3-Me-Ph-NH 5-Pym 2590 Ph-NH CN 3-Me-Ph-NH 6-Pym 2591 Ph-NH CN 3-Me-Ph-NH 2-Pyz 2592 Ph-NH CN 3-Me-Ph-NH 3-Pyz 2593 Ph-NH CN 4-Me-Ph-NH Ph 2594 Ph-NH CN 4-Me -Ph-NH 2-Pyr 2595 Ph-NH CN 4-Me-Ph-NH 3-Pyr 2596 Ph-NH CN 4-Me-Ph-NH 4-Pyr 2597 Ph-NH CN 4-Me-Ph-NH 3 -Pyzn 2598 Ph-NH CN 4-Me-Ph-NH 4-Pyzn 2599 Ph-NH CN 4-Me-Ph-NH 5-Pyzn 2600 Ph-NH CN 4-Me-Ph-NH 6-Pyzn 2601 Ph- NH CN 4-Me-Ph-NH 2-Pym 2602 Ph-NH CN 4-Me-Ph-NH 4-Pym 2603 Ph-NH CN 4-Me-Ph-NH 5-Pym 2604 Ph-NH CN 4-Me -Ph-NH 6-Pym 2605 Ph-NH CN 4-Me-Ph-NH 2-Pyz 2606 Ph-NH CN 4-Me-Ph-NH 3-Pyz 2607 Ph-NH CN n-Hx-NH Ph 2608 Ph -NH CN n-Hx-NH 2-Pyr 2609 Ph-NH CN n-Hx-NH 3-Pyr 2610 Ph-NH CN n-Hx-NH 4-Pyr 2611 Ph-NH CN n-Hx-NH 3-Pyzn 2612 Ph-NH CN n-Hx-NH 4-Pyzn 2613 Ph-NH CN n-Hx-NH 5-Pyzn 2614 Ph-NH CN n-Hx-NH 6-Pyzn 2615 Ph-NH CN n-Hx-NH 2 -Pym 2616 Ph-NH CN n-Hx-NH 4-Pym 2617 Ph-NH CN n-Hx-NH 5-Pym 2618 Ph-NH CN n-Hx-NH 6-Pym 2619 Ph-NH CN n-Hx- NH 2-Pyz 2620 Ph-NH CN n-Hx-NH 3-Pyz 2621 Ph-NH CN EtO- (CH _Two ) _Two -NH Ph 2622 Ph-NH CN EtO- (CH _Two ) _Two -NH 2-Pyr 2623 Ph-NH CN EtO- (CH _Two ) _Two -NH 3-Pyr 2624 Ph-NH CN EtO- (CH _Two ) _Two -NH 4-Pyr 2625 Ph-NH CN EtO- (CH _Two ) _Two -NH 3-Pyzn 2626 Ph-NH CN EtO- (CH _Two ) _Two -NH 4-Pyzn 2627 Ph-NH CN EtO- (CH _Two ) _Two -NH 5-Pyzn 2628 Ph-NH CN EtO- (CH _Two ) _Two -NH 6-Pyzn 2629 Ph-NH CN EtO- (CH _Two ) _Two -NH 2-Pym 2630 Ph-NH CN EtO- (CH _Two ) _Two -NH 4-Pym 2631 Ph-NH CN EtO- (CH _Two ) _Two -NH 5-Pym 2632 Ph-NH CN EtO- (CH _Two ) _Two -NH 6-Pym 2633 Ph-NH CN EtO- (CH _Two ) _Two -NH 2-Pyz 2634 Ph-NH CN EtO- (CH _Two ) _Two -NH 3-Pyz 2635 Ph-NH CN 3-Pyr Ph 2636 Ph-NH CN 3-Pyr 2-Pyr 2637 Ph-NH CN 3-Pyr 3-Pyr 2638 Ph-NH CN 3-Pyr 4-Pyr 2639 Ph- NH CN 3-Pyr 3-Pyzn 2640 Ph-NH CN 3-Pyr 4-Pyzn 2641 Ph-NH CN 3-Pyr 5-Pyzn 2642 Ph-NH CN 3-Pyr 6-Pyzn 2643 Ph-NH CN 3-Pyr 2 -Pym 2644 Ph-NH CN 3-Pyr 4-Pym 2645 Ph-NH CN 3-Pyr 5-Pym 2646 Ph-NH CN 3-Pyr 6-Pym 2647 Ph-NH CN 3-Pyr 2-Pyz 2648 Ph-NH CN 3-Pyr 3-Pyz 2649 Ph-NH CN 4-Pyr Ph 2650 Ph-NH CN 4-Pyr 2-Pyr 2651 Ph-NH CN 4-Pyr 3-Pyr 2652 Ph-NH CN 4-Pyr 4-Pyr 2653 Ph-NH CN 4-Pyr 3-Pyzn 2654 Ph-NH CN 4-Pyr 4-Pyzn 2655 Ph-NH CN 4-Pyr 5-Pyzn 2656 Ph-NH CN 4-Pyr 6-Pyzn 2657 Ph-NH CN 4- Pyr 2-Pym 2658 Ph-NH CN 4-Pyr 4-Pym 2659 Ph-NH CN 4-Pyr 5-Pym 2660 Ph-NH CN 4-Pyr 6-Pym 2661 Ph-NH CN 4-Pyr 2-Pyz 2662 Ph -NH CN 4-Pyr 3-Pyz 2663 Ph-NH CN 2-Thi Ph 2664 Ph-NH CN 2-Thi 2-Pyr 2665 Ph-NH CN 2-Thi 3-Pyr 2666 Ph-NH CN 2-Thi 4- Pyr 2667 Ph-NH CN 2-Thi 3-Pyzn 2668 Ph-NH CN 2-Thi 4-Pyzn 2669 Ph-NH CN 2-Thi 5-Pyzn 2670 Ph-NH CN 2-Thi 6-Pyzn 2671 Ph-NH CN 2-Thi 2-Pym 2672 Ph-NH CN 2-Thi 4-Pym 2673 Ph-NH CN 2-Thi 5-Pym 2674 Ph-NH CN 2-Thi 6-Pym 2675 Ph-NH CN 2-Thi 2-Pyz 2676 Ph-NH CN 2-Thi 3-Pyz 2677 Ph-NH COOEt OH 2-Thi 2678 Ph-NH COOEt OH 3-Thi 2679 Ph-NH COOEt OH 2-Fur 2680 Ph-NH COOEt OH 3-Fur 2681 Ph-NH COOEt OH 2-Pyrr 2682 Ph-NH COOEt OH 3-Pyrr 2683 Ph -NH COOEt OH 3-Pyza 2684 Ph-NH COOEt OH 4-Pyza 2685 Ph-NH COOEt OH 5-Pyza 2686 Ph-NH COOEt OH 2-Imid 2687 Ph-NH COOEt OH 4-Imid 2688 Ph-NH COOEt OH 5 -Imid 2689 Ph-NH COOEt OH 2-Oxa 2690 Ph-NH COOEt OH 4-Oxa 2691 Ph-NH COOEt OH 5-Oxa 2692 Ph-NH COOEt OH 2-Thiz 2693 Ph-NH COOEt OH 4-Thiz 2694 Ph- NH COOEt OH 5-Thiz 2695 Ph-NH COOEt OH Ph 2696 Ph-NH COOEt OH 2-Pyr 2697 Ph-NH COOEt OH 3-Pyr 2698 Ph-NH COOEt OH 4-Pyr 2699 Ph-NH COOEt OH 3-Pyzn 2700 Ph-NH COOEt OH 4-Pyzn 2701 Ph-NH COOEt OH 5-Pyzn 2702 Ph-NH COOEt OH 6-Pyzn 2703 Ph-NH COOEt OH 2-Pym 2704 Ph-NH COOEt OH 4-Pym 2705 Ph-NH COOEt OH 5-Pym 2706 Ph-NH COOEt OH 6-Pym 2707 Ph-NH COOEt OH 2-Pyz 2708 Ph-NH COOEt OH 3-Pyz 2709 Ph-NH COOEt OH 2-BeFur 2710 Ph-NH COOEt OH 3-B eFur 2711 Ph-NH COOEt OH 4-BeFur 2712 Ph-NH COOEt OH 5-BeFur 2713 Ph-NH COOEt OH 6-BeFur 2714 Ph-NH COOEt OH 7-BeFur 2715 Ph-NH COOEt OH 1-Np 2716 Ph-NH COOEt OH 2-Np 2717 Ph-NH COOEt OH 1-Pyrd 2718 Ph-NH COOEt OH 1-Pip 2719 Ph-NH COOEt OH 4-Mor 2720 Ph-NH COOEt OH 4-Thm 2721 Ph-NH COOEt OH 4-Piz 2722 Ph-NH COOEt OH N- (t-Bu) -Piz 2723 Ph-NH COOEt OH MeS 2724 Ph-NH COOEt OH EtS 2725 Ph-NH COOEt OH PrS 2726 Ph-NH COOEt OH i-PrS 2727 Ph-NH COOEt OH n-BuS 2728 Ph-NH COOEt OH i-BuS 2729 Ph-NH COOEt OH s-BuS 2730 Ph-NH COOEt OH t-BuS 2731 Ph-NH COOEt OH PnS 2732 Ph-NH COOEt OH n-HxS 2733 Ph- NH COOEt OH HepS 2734 Ph-NH COOEt OH n-OcS 2735 Ph-NH COOEt OH NnS 2736 Ph-NH COOEt OH DcS 2737 Ph-NH COOEt OH UdcS 2738 Ph-NH COOEt OH DdcS 2739 Ph-NH COOEt OH Bz 2740 Ph -NH COOEt OH Ph- (CH _Two ) _Two 2741 Ph-NH COOEt OH Ph- (CH _Two ) _Three 2742 Ph-NH COOEt OH Ph- (CH _Two ) _Three 2743 Ph-NH COOEt OH 1-Np-CH _Two 2744 Ph-NH COOEt OH 2-Np-CH _Two 2745 Ph-NH COOEt OH 1-Np- (CH _Two ) _Two 2746 Ph-NH COOEt OH 2-Np- (CH _Two ) _Two 2747 Ph-NH COOEt OH cPr 2748 Ph-NH COOEt OH cBu 2749 Ph-NH COOEt OH cPn 2750 Ph-NH COOEt OH cHx 2751 Ph-NH COOEt OH cHep 2752 Ph-NH COOEt OH cOc 2753 Ph-NH COOEt OH Me 2754 Ph-NH COOEt OH Et 2755 Ph-NH COOEt OH Pr 2756 Ph-NH COOEt OH i-Pr 2757 Ph-NH COOEt OH n-Bu 2758 Ph-NH COOEt OH i-Bu 2759 Ph-NH COOEt OH s-Bu 2760 Ph-NH COOEt OH t-Bu 2761 Ph-NH COOEt OH Pn 2762 Ph-NH COOEt OH n-Hx 2763 Ph-NH COOEt OH Hep 2764 Ph-NH COOEt OH n-Oc 2765 Ph-NH COOEt OH Nn 2766 Ph- NH COOEt OH Dc 2767 Ph-NH COOEt OH Udc 2768 Ph-NH COOEt OH Ddc 2769 Ph-NH COOEt OH OH 2770 Ph-NH COOEt OH H 2771 Ph-NH COOEt MeO 2-Thi 2772 Ph-NH COOEt MeO 3-Thi 2773 Ph-NH COOEt MeO 2-Fur 2774 Ph-NH COOEt MeO 3-Fur 2775 Ph-NH COOEt MeO 2-Pyrr 2776 Ph-NH COOEt MeO 3-Pyrr 2777 Ph-NH COOEt MeO 3-Pyza 2778 Ph-NH COOEt MeO 4-Pyza 2779 Ph-NH COOEt MeO 5-Pyza 2780 Ph-NH COOEt MeO 2-Imid 2781 Ph-NH COOEt MeO 4-Imid 2782 Ph-NH COOEt MeO 5-Imid 2783 Ph-NH COOEt MeO 2-Oxa 2784 Ph-NH COOEt MeO 4-Oxa 2785 Ph-NH COOEt MeO 5-Oxa 2786 Ph-NH C OOEt MeO 2-Thiz 2787 Ph-NH COOEt MeO 4-Thiz 2788 Ph-NH COOEt MeO 5-Thiz 2789 Ph-NH COOEt MeO Ph 2790 Ph-NH COOEt MeO 2-Pyr 2791 Ph-NH COOEt MeO 3-Pyr 2792 Ph -NH COOEt MeO 4-Pyr 2793 Ph-NH COOEt MeO 3-Pyzn 2794 Ph-NH COOEt MeO 4-Pyzn 2795 Ph-NH COOEt MeO 5-Pyzn 2796 Ph-NH COOEt MeO 6-Pyzn 2797 Ph-NH COOEt MeO 2 -Pym 2798 Ph-NH COOEt MeO 4-Pym 2799 Ph-NH COOEt MeO 5-Pym 2800 Ph-NH COOEt MeO 6-Pym 2801 Ph-NH COOEt MeO 2-Pyz 2802 Ph-NH COOEt MeO 3-Pyz 2803 Ph- NH COOEt MeO 2-BeFur 2804 Ph-NH COOEt MeO 3-BeFur 2805 Ph-NH COOEt MeO 4-BeFur 2806 Ph-NH COOEt MeO 5-BeFur 2807 Ph-NH COOEt MeO 6-BeFur 2808 Ph-NH COOEt MeO 7- BeFur 2809 Ph-NH COOEt MeO 1-Np 2810 Ph-NH COOEt MeO 2-Np 2811 Ph-NH COOEt MeO 1-Pyrd 2812 Ph-NH COOEt MeO 1-Pip 2813 Ph-NH COOEt MeO 4-Mor 2814 Ph-NH COOEt MeO 4-Thm 2815 Ph-NH COOEt MeO 4-Piz 2816 Ph-NH COOEt MeO N- (t-Bu) -Piz 2817 Ph-NH COOEt MeO MeS 2818 Ph-NH COOEt MeO EtS 2819 Ph-NH COOEt MeO PrS 2820 Ph-NH COOEt MeO i-PrS 2821 Ph-NH COOEt MeO n-BuS 2822 Ph-NH COOEt MeO iB uS 2823 Ph-NH COOEt MeO s-BuS 2824 Ph-NH COOEt MeO t-BuS 2825 Ph-NH COOEt MeO PnS 2826 Ph-NH COOEt MeO n-HxS 2827 Ph-NH COOEt MeO HepS 2828 Ph-NH COOEt MeO n- OcS 2829 Ph-NH COOEt MeO NnS 2830 Ph-NH COOEt MeO DcS 2831 Ph-NH COOEt MeO UdcS 2832 Ph-NH COOEt MeO DdcS 2833 Ph-NH COOEt MeO Bz 2834 Ph-NH COOEt MeO Ph- (CH _Two ) _Two 2835 Ph-NH COOEt MeO Ph- (CH _Two ) _Three 2836 Ph-NH COOEt MeO Ph- (CH _Two ) _Three 2837 Ph-NH COOEt MeO 1-Np-CH _Two 2838 Ph-NH COOEt MeO 2-Np-CH _Two 2839 Ph-NH COOEt MeO 1-Np- (CH _Two ) _Two 2840 Ph-NH COOEt MeO 2-Np- (CH _Two ) _Two 2841 Ph-NH COOEt MeO cPr 2842 Ph-NH COOEt MeO cBu 2843 Ph-NH COOEt MeO cPn 2844 Ph-NH COOEt MeO cHx 2845 Ph-NH COOEt MeO cHep 2846 Ph-NH COOEt MeO cOc 2847 Ph-NH COOEt MeO Me 2848 Ph-NH COOEt MeO Et 2849 Ph-NH COOEt MeO Pr 2850 Ph-NH COOEt MeO i-Pr 2851 Ph-NH COOEt MeO n-Bu 2852 Ph-NH COOEt MeO i-Bu 2853 Ph-NH COOEt MeO s-Bu 2854 Ph-NH COOEt MeO t-Bu 2855 Ph-NH COOEt MeO Pn 2856 Ph-NH COOEt MeO n-Hx 2857 Ph-NH COOEt MeO Hep 2858 Ph-NH COOEt MeO n-Oc 2859 Ph-NH COOEt MeO Nn 2860 Ph- NH COOEt MeO Dc 2861 Ph-NH COOEt MeO Udc 2862 Ph-NH COOEt MeO Ddc 2863 Ph-NH COOEt MeO OH 2864 Ph-NH COOEt MeO H 2865 Ph-NH COOEt EtO 2-Thi 2866 Ph-NH COOEt EtO 3-Thi 2867 Ph-NH COOEt EtO 2-Fur 2868 Ph-NH COOEt EtO 3-Fur 2869 Ph-NH COOEt EtO 2-Pyrr 2870 Ph-NH COOEt EtO 3-Pyrr 2871 Ph-NH COOEt EtO 3-Pyza 2872 Ph-NH COOEt EtO 4-Pyza 2873 Ph-NH COOEt EtO 5-Pyza 2874 Ph-NH COOEt EtO 2-Imid 2875 Ph-NH COOEt EtO 4-Imid 2876 Ph-NH COOEt EtO 5-Imid 2877 Ph-NH COOEt EtO 2-Oxa 2878 Ph-NH COOEt EtO 4-Oxa 2879 Ph-NH COOE t EtO 5-Oxa 2880 Ph-NH COOEt EtO 2-Thiz 2881 Ph-NH COOEt EtO 4-Thiz 2882 Ph-NH COOEt EtO 5-Thiz 2883 Ph-NH COOEt EtO Ph 2884 Ph-NH COOEt EtO 2-Pyr 2885 Ph -NH COOEt EtO 3-Pyr 2886 Ph-NH COOEt EtO 4-Pyr 2887 Ph-NH COOEt EtO 3-Pyzn 2888 Ph-NH COOEt EtO 4-Pyzn 2889 Ph-NH COOEt EtO 5-Pyzn 2890 Ph-NH COOEt EtO 6 -Pyzn 2891 Ph-NH COOEt EtO 2-Pym 2892 Ph-NH COOEt EtO 4-Pym 2893 Ph-NH COOEt EtO 5-Pym 2894 Ph-NH COOEt EtO 6-Pym 2895 Ph-NH COOEt EtO 2-Pyz 2896 Ph- NH COOEt EtO 3-Pyz 2897 Ph-NH COOEt EtO 2-BeFur 2898 Ph-NH COOEt EtO 3-BeFur 2899 Ph-NH COOEt EtO 4-BeFur 2900 Ph-NH COOEt EtO 5-BeFur 2901 Ph-NH COOEt EtO 6- BeFur 2902 Ph-NH COOEt EtO 7-BeFur 2903 Ph-NH COOEt EtO 1-Np 2904 Ph-NH COOEt EtO 2-Np 2905 Ph-NH COOEt EtO 1-Pyrd 2906 Ph-NH COOEt EtO 1-Pip 2907 Ph-NH COOEt EtO 4-Mor 2908 Ph-NH COOEt EtO 4-Thm 2909 Ph-NH COOEt EtO 4-Piz 2910 Ph-NH COOEt EtO N- (t-Bu) -Piz 2911 Ph-NH COOEt EtO MeS 2912 Ph-NH COOEt EtO EtS 2913 Ph-NH COOEt EtO PrS 2914 Ph-NH COOEt EtO i-PrS 2915 Ph-NH COOEt EtO n-BuS 2916 Ph-NH COOEt EtO i-BuS 2917 Ph-NH COOEt EtO s-BuS 2918 Ph-NH COOEt EtO t-BuS 2919 Ph-NH COOEt EtO PnS 2920 Ph-NH COOEt EtO n-HxS 2921 Ph-NH COOEt EtO HepS 2922 Ph-NH COOEt EtO n-OcS 2923 Ph-NH COOEt EtO NnS 2924 Ph-NH COOEt EtO DcS 2925 Ph-NH COOEt EtO UdcS 2926 Ph-NH COOEt EtO DdcS 2927 Ph-NH COOEt EtO Bz 2928 Ph-NH COOEt EtO Ph- (CH _Two ) _Two 2929 Ph-NH COOEt EtO Ph- (CH _Two ) _Three 2930 Ph-NH COOEt EtO Ph- (CH _Two ) _Three 2931 Ph-NH COOEt EtO 1-Np-CH _Two 2932 Ph-NH COOEt EtO 2-Np-CH _Two 2933 Ph-NH COOEt EtO 1-Np- (CH _Two ) _Two 2934 Ph-NH COOEt EtO 2-Np- (CH _Two ) _Two 2935 Ph-NH COOEt EtO cPr 2936 Ph-NH COOEt EtO cBu 2937 Ph-NH COOEt EtO cPn 2938 Ph-NH COOEt EtO cHx 2939 Ph-NH COOEt EtO cHep 2940 Ph-NH COOEt EtO cOc 2941 Ph-NH COOEt EtO Me 2942 Ph-NH COOEt EtO Et 2943 Ph-NH COOEt EtO Pr 2944 Ph-NH COOEt EtO i-Pr 2945 Ph-NH COOEt EtO n-Bu 2946 Ph-NH COOEt EtO i-Bu 2947 Ph-NH COOEt EtO s-Bu 2948 Ph-NH COOEt EtO t-Bu 2949 Ph-NH COOEt EtO Pn 2950 Ph-NH COOEt EtO n-Hx 2951 Ph-NH COOEt EtO Hep 2952 Ph-NH COOEt EtO n-Oc 2953 Ph-NH COOEt EtO Nn 2954 Ph- NH COOEt EtO Dc 2955 Ph-NH COOEt EtO Udc 2956 Ph-NH COOEt EtO Ddc 2957 Ph-NH COOEt EtO OH 2958 Ph-NH COOEt EtO H 2959 Ph-NH COOEt PnO 2-Thi 2960 Ph-NH COOEt PnO 3-Thi 2961 Ph-NH COOEt PnO 2-Fur 2962 Ph-NH COOEt PnO 3-Fur 2963 Ph-NH COOEt PnO 2-Pyrr 2964 Ph-NH COOEt PnO 3-Pyrr 2965 Ph-NH COOEt PnO 3-Pyza 2966 Ph-NH COOEt PnO 4-Pyza 2967 Ph-NH COOEt PnO 5-Pyza 2968 Ph-NH COOEt PnO 2-Imid 2969 Ph-NH COOEt PnO 4-Imid 2970 Ph-NH COOEt PnO 5-Imid 2971 Ph-NH COOEt PnO 2-Oxa 2972 Ph-NH COOEt PnO 4-Oxa 2973 Ph-NH COOE t PnO 5-Oxa 2974 Ph-NH COOEt PnO 2-Thiz 2975 Ph-NH COOEt PnO 4-Thiz 2976 Ph-NH COOEt PnO 5-Thiz 2977 Ph-NH COOEt PnO Ph 2978 Ph-NH COOEt PnO 2-Pyr 2979 Ph -NH COOEt PnO 3-Pyr 2980 Ph-NH COOEt PnO 4-Pyr 2981 Ph-NH COOEt PnO 3-Pyzn 2982 Ph-NH COOEt PnO 4-Pyzn 2983 Ph-NH COOEt PnO 5-Pyzn 2984 Ph-NH COOEt PnO 6 -Pyzn 2985 Ph-NH COOEt PnO 2-Pym 2986 Ph-NH COOEt PnO 4-Pym 2987 Ph-NH COOEt PnO 5-Pym 2988 Ph-NH COOEt PnO 6-Pym 2989 Ph-NH COOEt PnO 2-Pyz 2990 Ph- NH COOEt PnO 3-Pyz 2991 Ph-NH COOEt PnO 2-BeFur 2992 Ph-NH COOEt PnO 3-BeFur 2993 Ph-NH COOEt PnO 4-BeFur 2994 Ph-NH COOEt PnO 5-BeFur 2995 Ph-NH COOEt PnO 6- BeFur 2996 Ph-NH COOEt PnO 7-BeFur 2997 Ph-NH COOEt HepO Ph 2998 Ph-NH COOEt HepO 2-Pyr 2999 Ph-NH COOEt HepO 3-Pyr 3000 Ph-NH COOEt HepO 4-Pyr 3001 Ph-NH COOEt HepO 3-Pyzn 3002 Ph-NH COOEt HepO 4-Pyzn 3003 Ph-NH COOEt HepO 5-Pyzn 3004 Ph-NH COOEt HepO 6-Pyzn 3005 Ph-NH COOEt HepO 2-Pym 3006 Ph-NH COOEt HepO 4-Pym 3007 Ph -NH COOEt HepO 5-Pym 3008 Ph-NH COOEt HepO 6-Pym 3009 Ph-NH COO Et HepO 2-Pyz 3010 Ph-NH COOEt HepO 3-Pyz 3011 Ph-NH COOEt 4-Mor 2-Thi 3012 Ph-NH COOEt 4-Mor 3-Thi 3013 Ph-NH COOEt 4-Mor 2-Fur 3014 Ph- NH COOEt 4-Mor 3-Fur 3015 Ph-NH COOEt 4-Mor 2-Pyrr 3016 Ph-NH COOEt 4-Mor 3-Pyrr 3017 Ph-NH COOEt 4-Mor 3-Pyza 3018 Ph-NH COOEt 4-Mor 4 -Pyza 3019 Ph-NH COOEt 4-Mor 5-Pyza 3020 Ph-NH COOEt 4-Mor 2-Imid 3021 Ph-NH COOEt 4-Mor 4-Imid 3022 Ph-NH COOEt 4-Mor 5-Imid 3023 Ph-NH COOEt 4-Mor 2-Oxa 3024 Ph-NH COOEt 4-Mor 4-Oxa 3025 Ph-NH COOEt 4-Mor 5-Oxa 3026 Ph-NH COOEt 4-Mor 2-Thiz 3027 Ph-NH COOEt 4-Mor 4- Thiz 3028 Ph-NH COOEt 4-Mor 5-Thiz 3029 Ph-NH COOEt 4-Mor Ph 3030 Ph-NH COOEt 4-Mor 2-Pyr 3031 Ph-NH COOEt 4-Mor 3-Pyr 3032 Ph-NH COOEt 4- Mor 4-Pyr 3033 Ph-NH COOEt 4-Mor 3-Pyzn 3034 Ph-NH COOEt 4-Mor 4-Pyzn 3035 Ph-NH COOEt 4-Mor 5-Pyzn 3036 Ph-NH COOEt 4-Mor 6-Pyzn 3037 Ph -NH COOEt 4-Mor 2-Pym 3038 Ph-NH COOEt 4-Mor 4-Pym 3039 Ph-NH COOEt 4-Mor 5-Pym 3040 Ph-NH COOEt 4-Mor 6-Pym 3041 Ph-NH COOEt 4-Mor 2-Pyz 3042 Ph-NH COOEt 4-Mor 3-Pyz 3043 Ph-NH COOEt 4 -Mor 2-BeFur 3044 Ph-NH COOEt 4-Mor 3-BeFur 3045 Ph-NH COOEt 4-Mor 4-BeFur 3046 Ph-NH COOEt 4-Mor 5-BeFur 3047 Ph-NH COOEt 4-Mor 6-BeFur 3048 Ph-NH COOEt 4-Mor 7-BeFur 3049 Ph-NH COOEt 4-Mor 1-Np 3050 Ph-NH COOEt 4-Mor 2-Np 3051 Ph-NH COOEt 4-Mor 1-Pyrd 3052 Ph-NH COOEt 4- Mor 1-Pip 3053 Ph-NH COOEt 4-Mor 4-Mor 3054 Ph-NH COOEt 4-Mor 4-Thm 3055 Ph-NH COOEt 4-Mor 4-Piz 3056 Ph-NH COOEt 4-Mor N- (t- Bu) -Piz 3057 Ph-NH COOEt 4-Mor MeS 3058 Ph-NH COOEt 4-Mor EtS 3059 Ph-NH COOEt 4-Mor PrS 3060 Ph-NH COOEt 4-Mor i-PrS 3061 Ph-NH COOEt 4-Mor n-BuS 3062 Ph-NH COOEt 4-Mor i-BuS 3063 Ph-NH COOEt 4-Mor s-BuS 3064 Ph-NH COOEt 4-Mor t-BuS 3065 Ph-NH COOEt 4-Mor PnS 3066 Ph-NH COOEt 4-Mor n-HxS 3067 Ph-NH COOEt 4-Mor HepS 3068 Ph-NH COOEt 4-Mor n-OcS 3069 Ph-NH COOEt 4-Mor NnS 3070 Ph-NH COOEt 4-Mor DcS 3071 Ph-NH COOEt 4 -Mor UdcS 3072 Ph-NH COOEt 4-Mor DdcS 3073 Ph-NH COOEt 4-Mor Bz 3074 Ph-NH COOEt 4-Mor Ph- (CH _Two ) _Two 3075 Ph-NH COOEt 4-Mor Ph- (CH _Two ) _Three 3076 Ph-NH COOEt 4-Mor Ph- (CH _Two ) _Three 3077 Ph-NH COOEt 4-Mor 1-Np-CH _Two 3078 Ph-NH COOEt 4-Mor 2-Np-CH _Two 3079 Ph-NH COOEt 4-Mor 1-Np- (CH _Two ) _Two 3080 Ph-NH COOEt 4-Mor 2-Np- (CH _Two ) _Two 3081 Ph-NH COOEt 4-Mor cPr 3082 Ph-NH COOEt 4-Mor cBu 3083 Ph-NH COOEt 4-Mor cPn 3084 Ph-NH COOEt 4-Mor cHx 3085 Ph-NH COOEt 4-Mor cHep 3086 Ph-NH COOEt 4-Mor cOc 3087 Ph-NH COOEt 4-Mor Me 3088 Ph-NH COOEt 4-Mor Et 3089 Ph-NH COOEt 4-Mor Pr 3090 Ph-NH COOEt 4-Mor i-Pr 3091 Ph-NH COOEt 4-Mor n-Bu 3092 Ph-NH COOEt 4-Mor i-Bu 3093 Ph-NH COOEt 4-Mor s-Bu 3094 Ph-NH COOEt 4-Mor t-Bu 3095 Ph-NH COOEt 4-Mor Pn 3096 Ph-NH COOEt 4-Mor n-Hx 3097 Ph-NH COOEt 4-Mor Hep 3098 Ph-NH COOEt 4-Mor n-Oc 3099 Ph-NH COOEt 4-Mor Nn 3100 Ph-NH COOEt 4-Mor Dc 3101 Ph-NH COOEt 4 -Mor Udc 3102 Ph-NH COOEt 4-Mor Ddc 3103 Ph-NH COOEt 4-Mor OH 3104 Ph-NH COOEt 4-Mor H 3105 Ph-NH COOEt 4-Thm 2-Thi 3106 Ph-NH COOEt 4-Thm 3 -Thi 3107 Ph-NH COOEt 4-Thm 2-Fur 3108 Ph-NH COOEt 4-Thm 3-Fur 3109 Ph-NH COOEt 4-Thm 2-Pyrr 3110 Ph-NH COOEt 4-Thm 3-Pyrr 3111 Ph-NH COOEt 4-Thm 3-Pyza 3112 Ph-NH COOEt 4-Thm 4-Pyza 3113 Ph-NH COOEt 4-Thm 5-Pyza 3114 Ph-NH COOEt 4-Thm 2-Imid 3115 Ph-NH COOEt 4-Thm 4- Imid 3116 Ph-NH COOEt 4-Thm 5-Im id 3117 Ph-NH COOEt 4-Thm 2-Oxa 3118 Ph-NH COOEt 4-Thm 4-Oxa 3119 Ph-NH COOEt 4-Thm 5-Oxa 3120 Ph-NH COOEt 4-Thm 2-Thiz 3121 Ph-NH COOEt 4-Thm 4-Thiz 3122 Ph-NH COOEt 4-Thm 5-Thiz 3123 Ph-NH COOEt 4-Thm Ph 3124 Ph-NH COOEt 4-Thm 2-Pyr 3125 Ph-NH COOEt 4-Thm 3-Pyr 3126 Ph -NH COOEt 4-Thm 4-Pyr 3127 Ph-NH COOEt 4-Thm 3-Pyzn 3128 Ph-NH COOEt 4-Thm 4-Pyzn 3129 Ph-NH COOEt 4-Thm 5-Pyzn 3130 Ph-NH COOEt 4-Thm 6-Pyzn 3131 Ph-NH COOEt 4-Thm 2-Pym 3132 Ph-NH COOEt 4-Thm 4-Pym 3133 Ph-NH COOEt 4-Thm 5-Pym 3134 Ph-NH COOEt 4-Thm 6-Pym 3135 Ph- NH COOEt 4-Thm 2-Pyz 3136 Ph-NH COOEt 4-Thm 3-Pyz 3137 Ph-NH COOEt 4-Thm 2-BeFur 3138 Ph-NH COOEt 4-Thm 3-BeFur 3139 Ph-NH COOEt 4-Thm 4 -BeFur 3140 Ph-NH COOEt 4-Thm 5-BeFur 3141 Ph-NH COOEt 4-Thm 6-BeFur 3142 Ph-NH COOEt 4-Thm 7-BeFur 3143 Ph-NH COOEt 4-Thm 1-Np 3144 Ph-NH COOEt 4-Thm 2-Np 3145 Ph-NH COOEt 4-Thm 1-Pyrd 3146 Ph-NH COOEt 4-Thm 1-Pip 3147 Ph-NH COOEt 4-Thm 4-Mor 3148 Ph-NH COOEt 4-Thm 4- Thm 3149 Ph-NH COOEt 4-Thm 4-Piz 3150 Ph-NH COOEt 4-Thm N- (t-Bu) -Piz 3151 Ph-NH COOEt 4-Thm MeS 3152 Ph-NH COOEt 4-Thm EtS 3153 Ph-NH COOEt 4-Thm PrS 3154 Ph-NH COOEt 4-Thm i-PrS 3155 Ph-NH COOEt 4-Thm n-BuS 3156 Ph-NH COOEt 4-Thm i-BuS 3157 Ph-NH COOEt 4-Thms s-BuS 3158 Ph-NH COOEt 4-Thm t-BuS 3159 Ph-NH COOEt 4-Thm PnS 3160 Ph -NH COOEt 4-Thm n-HxS 3161 Ph-NH COOEt 4-Thm HepS 3162 Ph-NH COOEt 4-Thm n-OcS 3163 Ph-NH COOEt 4-Thm NnS 3164 Ph-NH COOEt 4-Thm DcS 3165 Ph- NH COOEt 4-Thm UdcS 3166 Ph-NH COOEt 4-Thm DdcS 3167 Ph-NH COOEt 4-Thm Bz 3168 Ph-NH COOEt 4-Thm Ph- (CH _Two ) _Two 3169 Ph-NH COOEt 4-Thm Ph- (CH _Two ) _Three 3170 Ph-NH COOEt 4-Thm Ph- (CH _Two ) _Three 3171 Ph-NH COOEt 4-Thm 1-Np-CH _Two 3172 Ph-NH COOEt 4-Thm 2-Np-CH _Two 3173 Ph-NH COOEt 4-Thm 1-Np- (CH _Two ) _Two 3174 Ph-NH COOEt 4-Thm 2-Np- (CH _Two ) _Two 3175 Ph-NH COOEt 4-Thm cPr 3176 Ph-NH COOEt 4-Thm cBu 3177 Ph-NH COOEt 4-Thm cPn 3178 Ph-NH COOEt 4-Thm cHx 3179 Ph-NH COOEt 4-Thm cHep 3180 Ph-NH COOEt 4-Thm cOc 3181 Ph-NH COOEt 4-Thm Me 3182 Ph-NH COOEt 4-Thm Et 3183 Ph-NH COOEt 4-Thm Pr 3184 Ph-NH COOEt 4-Thm i-Pr 3185 Ph-NH COOEt 4-Thm n-Bu 3186 Ph-NH COOEt 4-Thm i-Bu 3187 Ph-NH COOEt 4-Thms s-Bu 3188 Ph-NH COOEt 4-Thm t-Bu 3189 Ph-NH COOEt 4-Thm Pn 3190 Ph-NH COOEt 4-Thm n-Hx 3191 Ph-NH COOEt 4-Thm Hep 3192 Ph-NH COOEt 4-Thm n-Oc 3193 Ph-NH COOEt 4-Thm Nn 3194 Ph-NH COOEt 4-Thm Dc 3195 Ph-NH COOEt 4 -Thm Udc 3196 Ph-NH COOEt 4-Thm Ddc 3197 Ph-NH COOEt 4-Thm OH 3198 Ph-NH COOEt 4-Thm H 3199 Ph-NH COOEt 1-Pip 2-Thi 3200 Ph-NH COOEt 1-Pip 3 -Thi 3201 Ph-NH COOEt 1-Pip 2-Fur 3202 Ph-NH COOEt 1-Pip 3-Fur 3203 Ph-NH COOEt 1-Pip 2-Pyrr 3204 Ph-NH COOEt 1-Pip 3-Pyrr 3205 Ph-NH COOEt 1-Pip 3-Pyza 3206 Ph-NH COOEt 1-Pip 4-Pyza 3207 Ph-NH COOEt 1-Pip 5-Pyza 3208 Ph-NH COOEt 1-Pip 2-Imid 3209 Ph-NH COOEt 1-Pip 4- Imid 3210 Ph-NH COOEt 1-Pip 5-Im id 3211 Ph-NH COOEt 1-Pip 2-Oxa 3212 Ph-NH COOEt 1-Pip 4-Oxa 3213 Ph-NH COOEt 1-Pip 5-Oxa 3214 Ph-NH COOEt 1-Pip 2-Thiz 3215 Ph-NH COOEt 1-Pip 4-Thiz 3216 Ph-NH COOEt 1-Pip 5-Thiz 3217 Ph-NH COOEt 1-Pip Ph 3218 Ph-NH COOEt 1-Pip 2-Pyr 3219 Ph-NH COOEt 1-Pip 3-Pyr 3220 Ph -NH COOEt 1-Pip 4-Pyr 3221 Ph-NH COOEt 1-Pip 3-Pyzn 3222 Ph-NH COOEt 1-Pip 4-Pyzn 3223 Ph-NH COOEt 1-Pip 5-Pyzn 3224 Ph-NH COOEt 1-Pip 6-Pyzn 3225 Ph-NH COOEt 1-Pip 2-Pym 3226 Ph-NH COOEt 1-Pip 4-Pym 3227 Ph-NH COOEt 1-Pip 5-Pym 3228 Ph-NH COOEt 1-Pip 6-Pym 3229 Ph- NH COOEt 1-Pip 2-Pyz 3230 Ph-NH COOEt 1-Pip 3-Pyz 3231 Ph-NH COOEt 1-Pip 2-BeFur 3232 Ph-NH COOEt 1-Pip 3-BeFur 3233 Ph-NH COOEt 1-Pip 4 -BeFur 3234 Ph-NH COOEt 1-Pip 5-BeFur 3235 Ph-NH COOEt 1-Pip 6-BeFur 3236 Ph-NH COOEt 1-Pip 7-BeFur 3237 Ph-NH COOEt 1-Pip 1-Np 3238 Ph-NH COOEt 1-Pip 2-Np 3239 Ph-NH COOEt 1-Pip 1-Pyrd 3240 Ph-NH COOEt 1-Pip 1-Pip 3241 Ph-NH COOEt 1-Pip 4-Mor 3242 Ph-NH COOEt 1-Pip 4- Thm 3243 Ph-NH COOEt 1-Pip 4-Piz 3244 Ph-NH COOEt 1-Pip N- (t-Bu) -Piz 3245 Ph-NH COOEt 1-Pip MeS 3246 Ph-NH COOEt 1-Pip EtS 3247 Ph-NH COOEt 1-Pip PrS 3248 Ph-NH COOEt 1-Pip i-PrS 3249 Ph-NH COOEt 1-Pip n-BuS 3250 Ph-NH COOEt 1-Pip i-BuS 3251 Ph-NH COOEt 1-Pip s-BuS 3252 Ph-NH COOEt 1-Pip t-BuS 3253 Ph-NH COOEt 1-Pip PnS 3254 Ph -NH COOEt 1-Pip n-HxS 3255 Ph-NH COOEt 1-Pip HepS 3256 Ph-NH COOEt 1-Pip n-OcS 3257 Ph-NH COOEt 1-Pip NnS 3258 Ph-NH COOEt 1-Pip DcS 3259 Ph- NH COOEt 1-Pip UdcS 3260 Ph-NH COOEt 1-Pip DdcS 3261 Ph-NH COOEt 1-Pip Bz 3262 Ph-NH COOEt 1-Pip Ph- (CH _Two ) _Two 3263 Ph-NH COOEt 1-Pip Ph- (CH _Two ) _Three 3264 Ph-NH COOEt 1-Pip Ph- (CH _Two ) _Three 3265 Ph-NH COOEt 1-Pip 1-Np-CH _Two 3266 Ph-NH COOEt 1-Pip 2-Np-CH _Two 3267 Ph-NH COOEt 1-Pip 1-Np- (CH _Two ) _Two 3268 Ph-NH COOEt 1-Pip 2-Np- (CH _Two ) _Two 3269 Ph-NH COOEt 1-Pip cPr 3270 Ph-NH COOEt 1-Pip cBu 3271 Ph-NH COOEt 1-Pip cPn 3272 Ph-NH COOEt 1-Pip cHx 3273 Ph-NH COOEt 1-Pip cHep 3274 Ph-NH COOEt 1-Pip cOc 3275 Ph-NH COOEt 1-Pip Me 3276 Ph-NH COOEt 1-Pip Et 3277 Ph-NH COOEt 1-Pip Pr 3278 Ph-NH COOEt 1-Pip i-Pr 3279 Ph-NH COOEt 1-Pip n-Bu 3280 Ph-NH COOEt 1-Pip i-Bu 3281 Ph-NH COOEt 1-Pip s-Bu 3282 Ph-NH COOEt 1-Pip t-Bu 3283 Ph-NH COOEt 1-Pip Pn 3284 Ph-NH COOEt 1-Pip n-Hx 3285 Ph-NH COOEt 1-Pip Hep 3286 Ph-NH COOEt 1-Pip n-Oc 3287 Ph-NH COOEt 1-Pip Nn 3288 Ph-NH COOEt 1-Pip Dc 3289 Ph-NH COOEt 1 -Pip Udc 3290 Ph-NH COOEt 1-Pip Ddc 3291 Ph-NH COOEt 1-Pip OH 3292 Ph-NH COOEt 1-Pip H 3293 Ph-NH COOEt 4-Piz 2-Thi 3294 Ph-NH COOEt 4-Piz 3 -Thi 3295 Ph-NH COOEt 4-Piz 2-Fur 3296 Ph-NH COOEt 4-Piz 3-Fur 3297 Ph-NH COOEt 4-Piz 2-Pyrr 3298 Ph-NH COOEt 4-Piz 3-Pyrr 3299 Ph-NH COOEt 4-Piz 3-Pyza 3300 Ph-NH COOEt 4-Piz 4-Pyza 3301 Ph-NH COOEt 4-Piz 5-Pyza 3302 Ph-NH COOEt 4-Piz 2-Imid 3303 Ph-NH COOEt 4-Piz 4- Imid 3304 Ph-NH COOEt 4-Piz 5-Im id 3305 Ph-NH COOEt 4-Piz 2-Oxa 3306 Ph-NH COOEt 4-Piz 4-Oxa 3307 Ph-NH COOEt 4-Piz 5-Oxa 3308 Ph-NH COOEt 4-Piz 2-Thiz 3309 Ph-NH COOEt 4-Piz 4-Thiz 3310 Ph-NH COOEt 4-Piz 5-Thiz 3311 Ph-NH COOEt 4-Piz Ph 3312 Ph-NH COOEt 4-Piz 2-Pyr 3313 Ph-NH COOEt 4-Piz 3-Pyr 3314 Ph -NH COOEt 4-Piz 4-Pyr 3315 Ph-NH COOEt 4-Piz 3-Pyzn 3316 Ph-NH COOEt 4-Piz 4-Pyzn 3317 Ph-NH COOEt 4-Piz 5-Pyzn 3318 Ph-NH COOEt 4-Piz 6-Pyzn 3319 Ph-NH COOEt 4-Piz 2-Pym 3320 Ph-NH COOEt 4-Piz 4-Pym 3321 Ph-NH COOEt 4-Piz 5-Pym 3322 Ph-NH COOEt 4-Piz 6-Pym 3323 Ph- NH COOEt 4-Piz 2-Pyz 3324 Ph-NH COOEt 4-Piz 3-Pyz 3325 Ph-NH COOEt 4-Piz 2-BeFur 3326 Ph-NH COOEt 4-Piz 3-BeFur 3327 Ph-NH COOEt 4-Piz 4 -BeFur 3328 Ph-NH COOEt 4-Piz 5-BeFur 3329 Ph-NH COOEt 4-Piz 6-BeFur 3330 Ph-NH COOEt 4-Piz 7-BeFur 3331 Ph-NH COOEt 4-Piz 1-Np 3332 Ph-NH COOEt 4-Piz 2-Np 3333 Ph-NH COOEt 4-Piz 1-Pyrd 3334 Ph-NH COOEt 4-Piz 1-Pip 3335 Ph-NH COOEt 4-Piz 4-Mor 3336 Ph-NH COOEt 4-Piz 4- Thm 3337 Ph-NH COOEt 4-Piz 4-Piz 3338 Ph-NH COOEt 4-Piz N- (t-Bu) -Piz 3339 Ph-NH COOEt 4-Piz MeS 3340 Ph-NH COOEt 4-Piz EtS 3341 Ph-NH COOEt 4-Piz PrS 3342 Ph-NH COOEt 4-Piz i-PrS 3343 Ph-NH COOEt 4-Piz n-BuS 3344 Ph-NH COOEt 4-Piz i-BuS 3345 Ph-NH COOEt 4-Piz s-BuS 3346 Ph-NH COOEt 4-Piz t-BuS 3347 Ph-NH COOEt 4-Piz PnS 3348 Ph -NH COOEt 4-Piz n-HxS 3349 Ph-NH COOEt 4-Piz HepS 3350 Ph-NH COOEt 4-Piz n-OcS 3351 Ph-NH COOEt 4-Piz NnS 3352 Ph-NH COOEt 4-Piz DcS 3353 Ph- NH COOEt 4-Piz UdcS 3354 Ph-NH COOEt 4-Piz DdcS 3355 Ph-NH COOEt 4-Piz Bz 3356 Ph-NH COOEt 4-Piz Ph- (CH _Two ) _Two 3357 Ph-NH COOEt 4-Piz Ph- (CH _Two ) _Three 3358 Ph-NH COOEt 4-Piz Ph- (CH _Two ) _Three 3359 Ph-NH COOEt 4-Piz 1-Np-CH _Two 3360 Ph-NH COOEt 4-Piz 2-Np-CH _Two 3361 Ph-NH COOEt 4-Piz 1-Np- (CH _Two ) _Two 3362 Ph-NH COOEt 4-Piz 2-Np- (CH _Two ) _Two 3363 Ph-NH COOEt 4-Piz cPr 3364 Ph-NH COOEt 4-Piz cBu 3365 Ph-NH COOEt 4-Piz cPn 3366 Ph-NH COOEt 4-Piz cHx 3367 Ph-NH COOEt 4-Piz cHep 3368 Ph-NH COOEt 4-Piz cOc 3369 Ph-NH COOEt 4-Piz Me 3370 Ph-NH COOEt 4-Piz Et 3371 Ph-NH COOEt 4-Piz Pr 3372 Ph-NH COOEt 4-Piz i-Pr 3373 Ph-NH COOEt 4-Piz n-Bu 3374 Ph-NH COOEt 4-Piz i-Bu 3375 Ph-NH COOEt 4-Piz s-Bu 3376 Ph-NH COOEt 4-Piz t-Bu 3377 Ph-NH COOEt 4-Piz Pn 3378 Ph-NH COOEt 4-Piz n-Hx 3379 Ph-NH COOEt 4-Piz Hep 3380 Ph-NH COOEt 4-Piz n-Oc 3381 Ph-NH COOEt 4-Piz Nn 3382 Ph-NH COOEt 4-Piz Dc 3383 Ph-NH COOEt 4 -Piz Udc 3384 Ph-NH COOEt 4-Piz Ddc 3385 Ph-NH COOEt 4-Piz OH 3386 Ph-NH COOEt 4-Piz H 3387 Ph-NH COOEt (Et) _Two N Ph 3388 Ph-NH COOEt (Et) _Two N 2-Pyr 3389 Ph-NH COOEt (Et) _Two N 3-Pyr 3390 Ph-NH COOEt (Et) _Two N 4-Pyr 3391 Ph-NH COOEt (Et) _Two N 3-Pyzn 3392 Ph-NH COOEt (Et) _Two N 4-Pyzn 3393 Ph-NH COOEt (Et) _Two N 5-Pyzn 3394 Ph-NH COOEt (Et) _Two N 6-Pyzn 3395 Ph-NH COOEt (Et) _Two N 2-Pym 3396 Ph-NH COOEt (Et) _Two N 4-Pym 3397 Ph-NH COOEt (Et) _Two N 5-Pym 3398 Ph-NH COOEt (Et) _Two N 6-Pym 3399 Ph-NH COOEt (Et) _Two N 2-Pyz 3400 Ph-NH COOEt (Et) _Two N 3-Pyz 3401 Ph-NH COOEt cHx-NH Ph 3402 Ph-NH COOEt cHx-NH 2-Pyr 3403 Ph-NH COOEt cHx-NH 3-Pyr 3404 Ph-NH COOEt cHx-NH 4-Pyr 3405 Ph-NH COOEt cHx-NH 3-Pyzn 3406 Ph-NH COOEt cHx-NH 4-Pyzn 3407 Ph-NH COOEt cHx-NH 5-Pyzn 3408 Ph-NH COOEt cHx-NH 6-Pyzn 3409 Ph-NH COOEt cHx-NH 2- Pym 3410 Ph-NH COOEt cHx-NH 4-Pym 3411 Ph-NH COOEt cHx-NH 5-Pym 3412 Ph-NH COOEt cHx-NH 6-Pym 3413 Ph-NH COOEt cHx-NH 2-Pyz 3414 Ph-NH COOEt cHx-NH 3-Pyz 3415 Ph-NH COOEt Ph-NH Ph 3416 Ph-NH COOEt Ph-NH 2-Pyr 3417 Ph-NH COOEt Ph-NH 3-Pyr 3418 Ph-NH COOEt Ph-NH 4-Pyr 3419 Ph -NH COOEt Ph-NH 3-Pyzn 3420 Ph-NH COOEt Ph-NH 4-Pyzn 3421 Ph-NH COOEt Ph-NH 5-Pyzn 3422 Ph-NH COOEt Ph-NH 6-Pyzn 3423 Ph-NH COOEt Ph-NH 2-Pym 3424 Ph-NH COOEt Ph-NH 4-Pym 3425 Ph-NH COOEt Ph-NH 5-Pym 3426 Ph-NH COOEt Ph-NH 6-Pym 3427 Ph-NH COOEt Ph-NH 2-Pyz 3428 Ph- NH COOEt Ph-NH 3-Pyz 3429 Ph-NH COOEt 3-Cl-Ph-NH Ph 3430 Ph-NH COOEt 3-Cl-Ph-NH 2-Pyr 3431 Ph-NH COOEt 3-Cl-Ph-NH 3- Pyr 3432 Ph-NH COOEt 3-Cl-Ph-NH 4-Pyr 3433 Ph-NH COOEt 3-Cl-Ph-NH 3-P yzn 3434 Ph-NH COOEt 3-Cl-Ph-NH 4-Pyzn 3435 Ph-NH COOEt 3-Cl-Ph-NH 5-Pyzn 3436 Ph-NH COOEt 3-Cl-Ph-NH 6-Pyzn 3437 Ph-NH COOEt 3-Cl-Ph-NH 2-Pym 3438 Ph-NH COOEt 3-Cl-Ph-NH 4-Pym 3439 Ph-NH COOEt 3-Cl-Ph-NH 5-Pym 3440 Ph-NH COOEt 3-Cl- Ph-NH 6-Pym 3441 Ph-NH COOEt 3-Cl-Ph-NH 2-Pyz 3442 Ph-NH COOEt 3-Cl-Ph-NH 3-Pyz 3443 Ph-NH COOEt 2-Me-Ph-NH Ph 3444 Ph-NH COOEt 2-Me-Ph-NH 2-Pyr 3445 Ph-NH COOEt 2-Me-Ph-NH 3-Pyr 3446 Ph-NH COOEt 2-Me-Ph-NH 4-Pyr 3447 Ph-NH COOEt 2 -Me-Ph-NH 3-Pyzn 3448 Ph-NH COOEt 2-Me-Ph-NH 4-Pyzn 3449 Ph-NH COOEt 2-Me-Ph-NH 5-Pyzn 3450 Ph-NH COOEt 2-Me-Ph- NH 6-Pyzn 3451 Ph-NH COOEt 2-Me-Ph-NH 2-Pym 3452 Ph-NH COOEt 2-Me-Ph-NH 4-Pym 3453 Ph-NH COOEt 2-Me-Ph-NH 5-Pym 3454 Ph-NH COOEt 2-Me-Ph-NH 6-Pym 3455 Ph-NH COOEt 2-Me-Ph-NH 2-Pyz 3456 Ph-NH COOEt 2-Me-Ph-NH 3-Pyz 3457 Ph-NH COOEt 3 -Me-Ph-NH Ph 3458 Ph-NH COOEt 3-Me-Ph-NH 2-Pyr 3459 Ph-NH COOEt 3-Me-Ph-NH 3-Pyr 3460 Ph-NH COOEt 3-Me-Ph-NH 4 -Pyr 3461 Ph-NH COOEt 3-Me-Ph-NH 3-Pyzn 3462 Ph-NH COOEt 3-Me-Ph-NH 4-Pyzn 3463 Ph -NH COOEt 3-Me-Ph-NH 5-Pyzn 3464 Ph-NH COOEt 3-Me-Ph-NH 6-Pyzn 3465 Ph-NH COOEt 3-Me-Ph-NH 2-Pym 3466 Ph-NH COOEt 3- Me-Ph-NH 4-Pym 3467 Ph-NH COOEt 3-Me-Ph-NH 5-Pym 3468 Ph-NH COOEt 3-Me-Ph-NH 6-Pym 3469 Ph-NH COOEt 3-Me-Ph-NH 2-Pyz 3470 Ph-NH COOEt 3-Me-Ph-NH 3-Pyz 3471 Ph-NH COOEt 4-Me-Ph-NH Ph 3472 Ph-NH COOEt 4-Me-Ph-NH 2-Pyr 3473 Ph-NH COOEt 4-Me-Ph-NH 3-Pyr 3474 Ph-NH COOEt 4-Me-Ph-NH 4-Pyr 3475 Ph-NH COOEt 4-Me-Ph-NH 3-Pyzn 3476 Ph-NH COOEt 4-Me- Ph-NH 4-Pyzn 3477 Ph-NH COOEt 4-Me-Ph-NH 5-Pyzn 3478 Ph-NH COOEt 4-Me-Ph-NH 6-Pyzn 3479 Ph-NH COOEt 4-Me-Ph-NH 2- Pym 3480 Ph-NH COOEt 4-Me-Ph-NH 4-Pym 3481 Ph-NH COOEt 4-Me-Ph-NH 5-Pym 3482 Ph-NH COOEt 4-Me-Ph-NH 6-Pym 3483 Ph-NH COOEt 4-Me-Ph-NH 2-Pyz 3484 Ph-NH COOEt 4-Me-Ph-NH 3-Pyz 3485 Ph-NH COOEt n-Hx-NH Ph 3486 Ph-NH COOEt n-Hx-NH 2-Pyr 3487 Ph-NH COOEt n-Hx-NH 3-Pyr 3488 Ph-NH COOEt n-Hx-NH 4-Pyr 3489 Ph-NH COOEt n-Hx-NH 3-Pyzn 3490 Ph-NH COOEt n-Hx-NH 4 -Pyzn 3491 Ph-NH COOEt n-Hx-NH 5-Pyzn 3492 Ph-NH COOEt n-Hx-NH 6-Pyzn 3493 Ph -NH COOEt n-Hx-NH 2-Pym 3494 Ph-NH COOEt n-Hx-NH 4-Pym 3495 Ph-NH COOEt n-Hx-NH 5-Pym 3496 Ph-NH COOEt n-Hx-NH 6-Pym 3497 Ph-NH COOEt n-Hx-NH 2-Pyz 3498 Ph-NH COOEt n-Hx-NH 3-Pyz 3499 Ph-NH COOEt EtO- (CH _Two ) _Two -NH Ph 3500 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 2-Pyr 3501 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 3-Pyr 3502 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 4-Pyr 3503 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 3-Pyzn 3504 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 4-Pyzn 3505 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 5-Pyzn 3506 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 6-Pyzn 3507 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 2-Pym 3508 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 4-Pym 3509 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 5-Pym 3510 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 6-Pym 3511 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 2-Pyz 3512 Ph-NH COOEt EtO- (CH _Two ) _Two -NH 3-Pyz 3513 Ph-NH COOEt 3-Pyr Ph 3514 Ph-NH COOEt 3-Pyr 2-Pyr 3515 Ph-NH COOEt 3-Pyr 3-Pyr 3516 Ph-NH COOEt 3-Pyr 4-Pyr 3517 Ph- NH COOEt 3-Pyr 3-Pyzn 3518 Ph-NH COOEt 3-Pyr 4-Pyzn 3519 Ph-NH COOEt 3-Pyr 5-Pyzn 3520 Ph-NH COOEt 3-Pyr 6-Pyzn 3521 Ph-NH COOEt 3-Pyr 2 -Pym 3522 Ph-NH COOEt 3-Pyr 4-Pym 3523 Ph-NH COOEt 3-Pyr 5-Pym 3524 Ph-NH COOEt 3-Pyr 6-Pym 3525 Ph-NH COOEt 3-Pyr 2-Pyz 3526 Ph-NH COOEt 3-Pyr 3-Pyz 3527 Ph-NH COOEt 4-Pyr Ph 3528 Ph-NH COOEt 4-Pyr 2-Pyr 3529 Ph-NH COOEt 4-Pyr 3-Pyr 3530 Ph-NH COOEt 4-Pyr 4-Pyr 3531 Ph-NH COOEt 4-Pyr 3-Pyzn 3532 Ph-NH COOEt 4-Pyr 4-Pyzn 3533 Ph-NH COOEt 4-Pyr 5-Pyzn 3534 Ph-NH COOEt 4-Pyr 6-Pyzn 3535 Ph-NH COOEt 4- Pyr 2-Pym 3536 Ph-NH COOEt 4-Pyr 4-Pym 3537 Ph-NH COOEt 4-Pyr 5-Pym 3538 Ph-NH COOEt 4-Pyr 6-Pym 3539 Ph-NH COOEt 4-Pyr 2-Pyz 3540 Ph -NH COOEt 4-Pyr 3-Pyz 3541 Ph-NH COOEt 2-Thi Ph 3542 Ph-NH COOEt 2-Thi 2-Pyr 3543 Ph-NH COOEt 2-Thi 3-Pyr 3544 Ph-NH COOEt 2-Thi 4- Pyr 3545 Ph-NH COOEt 2-Thi 3-Pyzn 3546 Ph-NH COOEt 2-Thi 4-Pyzn 354 7 Ph-NH COOEt 2-Thi 5-Pyzn 3548 Ph-NH COOEt 2-Thi 6-Pyzn 3549 Ph-NH COOEt 2-Thi 2-Pym 3550 Ph-NH COOEt 2-Thi 4-Pym 3551 Ph-NH COOEt 2 -Thi 5-Pym 3552 Ph-NH COOEt 2-Thi 6-Pym 3553 Ph-NH COOEt 2-Thi 2-Pyz 3554 Ph-NH COOEt 2-Thi 3-Pyz 3555 Ph-NH COOH 4-Mor Ph 3556 Ph- NH COOH 4-Mor 2-Pyr 3557 Ph-NH COOH 4-Mor 3-Pyr 3558 Ph-NH COOH 4-Mor 4-Pyr 3559 Ph-NH COOH 4-Mor 3-Pyzn 3560 Ph-NH COOH 4-Mor 4 -Pyzn 3561 Ph-NH COOH 4-Mor 5-Pyzn 3562 Ph-NH COOH 4-Mor 6-Pyzn 3563 Ph-NH COOH 4-Mor 2-Pym 3564 Ph-NH COOH 4-Mor 4-Pym 3565 Ph-NH COOH 4-Mor 5-Pym 3566 Ph-NH COOH 4-Mor 6-Pym 3567 Ph-NH COOH 4-Mor 2-Pyz 3568 Ph-NH COOH 4-Mor 3-Pyz 3569 Ph-NH COOH 4-Piz Ph 3570 Ph-NH COOH 4-Piz 2-Pyr 3571 Ph-NH COOH 4-Piz 3-Pyr 3572 Ph-NH COOH 4-Piz 4-Pyr 3573 Ph-NH COOH 4-Piz 3-Pyzn 3574 Ph-NH COOH 4- Piz 4-Pyzn 3575 Ph-NH COOH 4-Piz 5-Pyzn 3576 Ph-NH COOH 4-Piz 6-Pyzn 3577 Ph-NH COOH 4-Piz 2-Pym 3578 Ph-NH COOH 4-Piz 4-Pym 3579 Ph -NH COOH 4-Piz 5-Pym 3580 Ph-NH COOH 4-Piz 6-Pym 3581 Ph-NH COOH 4-Piz 2-Pyz 3582 Ph-NH COOH 4-Piz 3-Pyz 3583 Ph-NH NO _Two 4-Mor Ph 3584 Ph-NH NO _Two 4-Mor 2-Pyr 3585 Ph-NH NO _Two 4-Mor 3-Pyr 3586 Ph-NH NO _Two 4-Mor 4-Pyr 3587 Ph-NH NO _Two 4-Mor 3-Pyzn 3588 Ph-NH NO _Two 4-Mor 4-Pyzn 3589 Ph-NH NO _Two 4-Mor 5-Pyzn 3590 Ph-NH NO _Two 4-Mor 6-Pyzn 3591 Ph-NH NO _Two 4-Mor 2-Pym 3592 Ph-NH NO _Two 4-Mor 4-Pym 3593 Ph-NH NO _Two 4-Mor 5-Pym 3594 Ph-NH NO _Two 4-Mor 6-Pym 3595 Ph-NH NO _Two 4-Mor 2-Pyz 3596 Ph-NH NO _Two 4-Mor 3-Pyz 3597 Bz CN 4-Mor Ph 3598 Bz CN 4-Mor 2-Pyr 3599 Bz CN 4-Mor 3-Pyr 3600 Bz CN 4-Mor 4-Pyr 3601 Bz CN 4-Mor 3-Pyzn 3602 Bz CN 4-Mor 4-Pyzn 3603 Bz CN 4-Mor 5-Pyzn 3604 Bz CN 4-Mor 6-Pyzn 3605 Bz CN 4-Mor 2-Pym 3606 Bz CN 4-Mor 4-Pym 3607 Bz CN 4-Mor 5-Pym 3608 Bz CN 4-Mor 6-Pym 3609 Bz CN 4-Mor 2-Pyz 3610 Bz CN 4-Mor 3-Pyz 3611 Bz CN 4-Thm Ph 3612 Bz CN 4-Thm 2-Pyr 3613 Bz CN 4 -Thm 3-Pyr 3614 Bz CN 4-Thm 4-Pyr 3615 Bz CN 4-Thm 3-Pyzn 3616 Bz CN 4-Thm 4-Pyzn 3617 Bz CN 4-Thm 5-Pyzn 3618 Bz CN 4-Thm 6-Pyzn 3619 Bz CN 4-Thm 2-Pym 3620 Bz CN 4-Thm 4-Pym 3621 Bz CN 4-Thm 5-Pym 3622 Bz CN 4-Thm 6-Pym 3623 Bz CN 4-Thm 2-Pyz 3624 Bz CN 4- Thm 3-Pyz 3625 Bz COOH 4-Mor Ph 3626 Bz COOH 4-Mor 2-Pyr 3627 Bz COOH 4-Mor 3-Pyr 3628 Bz COOH 4-Mor 4-Pyr 3629 Bz COOH 4-Mor 3-Pyzn 3630 Bz COOH 4-Mor 4-Pyzn 3631 Bz COOH 4-Mor 5-Pyzn 3632 Bz COOH 4-Mor 6-Pyzn 3633 Bz COOH 4-Mor 2-Pym 3634 Bz COOH 4-Mor 4-Pym 3635 Bz COOH 4-Mor 5- Pym 3636 Bz COOH 4-Mor 6-Pym 3637 Bz COOH 4-Mor 2-Pyz 3638 Bz COOH 4-M or 3-Pyz 3639 Bz COOH 4-Thm Ph 3640 Bz COOH 4-Thm 2-Pyr 3641 Bz COOH 4-Thm 3-Pyr 3642 Bz COOH 4-Thm 4-Pyr 3643 Bz COOH 4-Thm 3-Pyzn 3644 Bz COOH 4-Thm 4-Pyzn 3645 Bz COOH 4-Thm 5-Pyzn 3646 Bz COOH 4-Thm 6-Pyzn 3647 Bz COOH 4-Thm 2-Pym 3648 Bz COOH 4-Thm 4-Pym 3649 Bz COOH 4-Thm 5- Pym 3650 Bz COOH 4-Thm 6-Pym 3651 Bz COOH 4-Thm 2-Pyz 3652 Bz COOH 4-Thm 3-Pyz 3653 Bz-NH CN 4-Mor Ph 3654 Bz-NH CN 4-Mor 2-Pyr 3655 Bz -NH CN 4-Mor 3-Pyr 3656 Bz-NH CN 4-Mor 4-Pyr 3657 Bz-NH CN 4-Mor 3-Pyzn 3658 Bz-NH CN 4-Mor 4-Pyzn 3659 Bz-NH CN 4-Mor 5-Pyzn 3660 Bz-NH CN 4-Mor 6-Pyzn 3661 Bz-NH CN 4-Mor 2-Pym 3662 Bz-NH CN 4-Mor 4-Pym 3663 Bz-NH CN 4-Mor 5-Pym 3664 Bz- NH CN 4-Mor 6-Pym 3665 Bz-NH CN 4-Mor 2-Pyz 3666 Bz-NH CN 4-Mor 3-Pyz 3667 Bz-NH CN 4-Thm Ph 3668 Bz-NH CN 4-Thm 2-Pyr 3669 Bz-NH CN 4-Thm 3-Pyr 3670 Bz-NH CN 4-Thm 4-Pyr 3671 Bz-NH CN 4-Thm 3-Pyzn 3672 Bz-NH CN 4-Thm 4-Pyzn 3673 Bz-NH CN 4 -Thm 5-Pyzn 3674 Bz-NH CN 4-Thm 6-Pyzn 3675 Bz-NH CN 4-Thm 2-Pym 3676 Bz-NH CN 4-Thm 4-Pym 3677 Bz-NH CN 4-Thm 5-Pym 3678 Bz-NH CN 4-Thm 6-Pym 3679 Bz-NH CN 4-Thm 2-Pyz 3680 Bz-NH CN 4-Thm 3-Pyz 3681 Bz-NH COOEt 4-Mor Ph 3682 Bz -NH COOEt 4-Mor 2-Pyr 3683 Bz-NH COOEt 4-Mor 3-Pyr 3684 Bz-NH COOEt 4-Mor 4-Pyr 3685 Bz-NH COOEt 4-Mor 3-Pyzn 3686 Bz-NH COOEt 4-Mor 4-Pyzn 3687 Bz-NH COOEt 4-Mor 5-Pyzn 3688 Bz-NH COOEt 4-Mor 6-Pyzn 3689 Bz-NH COOEt 4-Mor 2-Pym 3690 Bz-NH COOEt 4-Mor 4-Pym 3691 Bz- NH COOEt 4-Mor 5-Pym 3692 Bz-NH COOEt 4-Mor 6-Pym 3693 Bz-NH COOEt 4-Mor 2-Pyz 3694 Bz-NH COOEt 4-Mor 3-Pyz 3695 Bz-NH COOEt 4-Thm Ph 3696 Bz-NH COOEt 4-Thm 2-Pyr 3697 Bz-NH COOEt 4-Thm 3-Pyr 3698 Bz-NH COOEt 4-Thm 4-Pyr 3699 Bz-NH COOEt 4-Thm 3-Pyzn 3700 Bz-NH COOEt 4 -Thm 4-Pyzn 3701 Bz-NH COOEt 4-Thm 5-Pyzn 3702 Bz-NH COOEt 4-Thm 6-Pyzn 3703 Bz-NH COOEt 4-Thm 2-Pym 3704 Bz-NH COOEt 4-Thm 4-Pym 3705 Bz-NH COOEt 4-Thm 5-Pym 3706 Bz-NH COOEt 4-Thm 6-Pym 3707 Bz-NH COOEt 4-Thm 2-Pyz 3708 Bz-NH COOEt 4-Thm 3-Pyz 3709 MeS CN 4-Mor Ph 3710 MeS CN 4-Mor 2-Pyr 3711 MeS CN 4-Mor 3-Pyr 3712 MeS CN 4-Mor 4-Pyr 371 3 MeS CN 4-Mor 3-Pyzn 3714 MeS CN 4-Mor 4-Pyzn 3715 MeS CN 4-Mor 5-Pyzn 3716 MeS CN 4-Mor Me 3717 MeS CN 4-Pip Ph 3718 MeS CN 4-Pip 2-Pyr 3719 MeS CN 4-Pip 3-Pyr 3720 MeS CN 4-Pip 4-Pyr 3721 MeS CN 4-Pip 2-Pyz 3722 MeS CN 4-Pip 3-Pyz 3723 MeS CN 4-Piz Ph 3724 MeS CN 4-Piz 2 -Pyr 3725 MeS CN 4-Piz 3-Pyr 3726 MeS CN 4-Piz 4-Pyr 3727 MeS CN 4-Piz Me 3728 MeS CN 4-Piz Et 3729 MeS CN 4-Piz Bn 3730 MeS CN 4-Boc-1- Piz Ph 3731 MeS CN 4-Boc-1-Piz Me 3732 MeS CN (Et) _Two N Ph 3733 MeS CN (Et) _Two N 2-Pyr 3734 MeS CN (Et) _Two N 3-Pyr 3735 MeS CN (Et) _Two N 4-Pyr 3736 MeS CN (Et) _Two N Me 3737 MeS COOEt 4-Mor Ph 3738 MeS COOEt 4-Mor 2-Pyr 3739 MeS COOEt 4-Mor 3-Pyr 3740 MeS COOEt 4-Mor 4-Pyr 3741 MeS COOEt 4-Mor 3-Pyzn 3742 MeS COOEt 4- Mor 4-Pyzn 3743 MeS COOEt 4-Mor 5-Pyzn 3744 MeS COOEt 4-Mor 6-Pyzn 3745 MeS COOEt 4-Mor 2-Pym 3746 MeS COOEt 4-Mor 4-Pym 3747 MeS COOEt 4-Mor 5-Pym 3748 MeS COOEt 4-Mor 6-Pym 3749 MeS COOEt 4-Mor 2-Pyz 3750 MeS COOEt 4-Mor 3-Pyz 3751 MeS COOEt 4-Thm Ph 3752 MeS COOEt 4-Thm 2-Pyr 3753 MeS COOEt 4-Thm 3- Pyr 3754 MeS COOEt 4-Thm 4-Pyr 3755 MeS COOEt 4-Thm 3-Pyzn 3756 MeS COOEt 4-Thm 4-Pyzn 3757 MeS COOEt 4-Thm 5-Pyzn 3758 MeS COOEt 4-Thm 6-Pyzn 3759 MeS COOEt 4 -Thm 2-Pym 3760 MeS COOEt 4-Thm 4-Pym 3761 MeS COOEt 4-Thm 5-Pym 3762 MeS COOEt 4-Thm 6-Pym 3763 MeS COOEt 4-Thm 2-Pyz 3764 MeS COOEt 4-Thm 3-Pyz 3765 Me CN 4-Mor Ph 3766 Me CN 4-Mor 2-Pyr 3767 Me CN 4-Mor 3-Pyr 3768 Me CN 4-Mor 4-Pyr 3769 Me CN 4-Mor 3-Pyzn 3770 Me CN 4-Mor 4 -Pyzn 3771 Me CN 4-Mor 5-Pyzn 3772 Me CN 4-Mor 6-Pyzn 3773 Me CN 4-Mor 2-Pym 3774 Me CN 4-Mor 4-Pym 3775 M e CN 4-Mor 5-Pym 3776 Me CN 4-Mor 6-Pym 3777 Me CN 4-Mor 2-Pyz 3778 Me CN 4-Mor 3-Pyz 3779 Me CN 4-Thm Ph 3780 Me CN 4-Thm 2- Pyr 3781 Me CN 4-Thm 3-Pyr 3782 Me CN 4-Thm 4-Pyr 3783 Me CN 4-Thm 3-Pyzn 3784 Me CN 4-Thm 4-Pyzn 3785 Me CN 4-Thm 5-Pyzn 3786 Me CN 4 -Thm 6-Pyzn 3787 Me CN 4-Thm 2-Pym 3788 Me CN 4-Thm 4-Pym 3789 Me CN 4-Thm 5-Pym 3790 Me CN 4-Thm 6-Pym 3791 Me CN 4-Thm 2-Pyz 3792 Me CN 4-Thm 3-Pyz 3793 Me COOH 4-Mor Ph 3794 Me COOH 4-Mor 2-Pyr 3795 Me COOH 4-Mor 3-Pyr 3796 Me COOH 4-Mor 4-Pyr 3797 Me COOH 4-Mor 3 -Pyzn 3798 Me COOH 4-Mor 4-Pyzn 3799 Me COOH 4-Mor 5-Pyzn 3800 Me COOH 4-Mor 6-Pyzn 3801 Me COOH 4-Mor 2-Pym 3802 Me COOH 4-Mor 4-Pym 3803 Me COOH 4-Mor 5-Pym 3804 Me COOH 4-Mor 6-Pym 3805 Me COOH 4-Mor 2-Pyz 3806 Me COOH 4-Mor 3-Pyz 3807 Me COOEt 4-Mor Ph 3808 Me COOEt 4-Mor 2-Pyr 3809 Me COOEt 4-Mor 3-Pyr 3810 Me COOEt 4-Mor 4-Pyr 3811 Me COOEt 4-Mor 3-Pyzn 3812 Me COOEt 4-Mor 4-Pyzn 3813 Me COOEt 4-Mor 5-Pyzn 3814 Me COOEt 4-Mor 6-Pyzn 3815 Me COOH 4-Thm 2-Pym 3816 M e COOH 4-Thm 4-Pym 3817 Me COOH 4-Thm 5-Pym 3818 Me COOH 4-Thm 6-Pym 3819 Me COOH 4-Thm 2-Pyz 3820 Me COOH 4-Thm 3-Pyz 3821 H CN 4-Mor Ph 3822 H CN 4-Mor 2-Pyr 3823 H CN 4-Mor 3-Pyr 3824 H CN 4-Mor 4-Pyr 3825 H CN 4-Mor 3-Pyzn 3826 H CN 4-Mor 4-Pyzn 3827 H CN 4 -Mor 5-Pyzn 3828 H CN 4-Mor 6-Pyzn 3829 H CN 4-Mor 2-Pym 3830 H CN 4-Mor 4-Pym 3831 H CN 4-Mor 5-Pym 3832 H CN 4-Mor 6-Pym 3833 H CN 4-Mor 2-Pyz 3834 H CN 4-Mor 3-Pyz 3835 H CN 4-Thm Ph 3836 H CN 4-Thm 2-Pyr 3837 H CN 4-Thm 3-Pyr 3838 H CN 4-Thm 4 -Pyr 3839 H CN 4-Thm 3-Pyzn 3840 H CN 4-Thm 4-Pyzn 3841 H CN 4-Thm 5-Pyzn 3842 H CN 4-Thm 6-Pyzn 3843 H CN 4-Thm 2-Pym 3844 H CN 4-Thm 4-Pym 3845 H CN 4-Thm 5-Pym 3846 H CN 4-Thm 6-Pym 3847 H CN 4-Thm 2-Pyz 3848 H CN 4-Thm 3-Pyz 3849 H COOEt 4-Mor Ph 3850 H COOEt 4-Mor 2-Pyr 3851 H COOEt 4-Mor 3-Pyr 3852 H COOEt 4-Mor 4-Pyr 3853 H COOEt 4-Mor 3-Pyzn 3854 H COOEt 4-Mor 4-Pyzn 3855 H COOEt 4-Mor 5-Pyzn 3856 H COOEt 4-Mor 6-Pyzn 3857 H COOEt 4-Mor 2-Pym 3858 H COOEt 4-Mor 4-Pym 3859 H COOEt 4-Mor 5-Pym 3860 H COOEt 4-Mor 6-Pym 3861 H COOEt 4-Mor MeS 3862 H COOEt 4-Mor Et 3863 H COOEt 4-Thm Ph 3864 H COOEt 4-Thm 2-Pyr 3865 H COOEt 4- Thm 3-Pyr 3866 H COOEt 4-Thm 4-Pyr 3867 H COOEt 4-Thm 3-Pyzn 3868 H COOEt 4-Thm 4-Pyzn 3869 H COOEt 4-Thm 5-Pyzn 3870 H COOEt 4-Thm 6-Pyzn 3871 H COOEt 4-Thm 2-Pym 3872 H COOEt 4-Thm 4-Pym 3873 H COOEt 4-Thm 5-Pym 3874 H COOEt 4-Thm 6-Pym 3875 H COOEt 4-Thm 2-Pyz 3876 H COOEt 4-Thm 3-Pyz 3877 4-Mor CN 4-Mor Ph 3878 4-Mor CN 4-Mor 2-Pyr 3879 4-Mor CN 4-Mor 3-Pyr 3880 4-Mor CN 4-Mor 4-Pyr 3881 4-Mor CN 4-Mor 3-Pyzn 3882 4-Mor CN 4-Mor 4-Pyzn 3883 4-Mor CN 4-Mor 5-Pyzn 3884 4-Mor CN 4-Mor 6-Pyzn 3885 4-Mor CN 4-Mor 2-Pym 3886 4-Mor CN 4-Mor 4-Pym 3887 4-Mor CN 4-Mor 5-Pym 3888 4-Mor CN 4-Mor 6-Pym 3889 4-Mor CN 4-Mor 2-Pyz 3890 4-Mor CN 4 -Mor 3-Pyz 3891 4-Mor CN 4-Thm Ph 3892 4-Mor CN 4-Thm 2-Pyr 3893 4-Mor CN 4-Thm 3-Pyr 3894 4-Mor CN 4-Thm 4-Pyr 3895 4- Mor CN 4-Thm 3-Pyzn 3896 4-Mor CN 4-Thm 4-Pyzn 3897 4-Mor CN 4-Thm 5-Pyzn 3898 4-Mor CN 4-Thm 6-Pyzn 3899 4-Mor CN 4-Thm 2-Pym 3900 4-Mor CN 4-Thm 4-Pym 3901 4-Mor CN 4-Thm 5-Pym 3902 4-Mor CN 4-Thm 6-Pym 3903 4- Mor CN 4-Thm 2-Pyz 3904 4-Mor CN 4-Thm 3-Pyz 3905 4-Mor COOEt 4-Mor Ph 3906 4-Mor COOEt 4-Mor 2-Pyr 3907 4-Mor COOEt 4-Mor 3-Pyr 3908 4-Mor COOEt 4-Mor 4-Pyr 3909 4-Mor COOEt 4-Mor 3-Pyzn 3910 4-Mor COOEt 4-Mor 4-Pyzn 3911 4-Mor COOEt 4-Mor 5-Pyzn 3912 4-Mor COOEt 4 -Mor 6-Pyzn 3913 4-Mor COOEt 4-Mor 2-Pym 3914 4-Mor COOEt 4-Mor 4-Pym 3915 4-Mor COOEt 4-Mor 5-Pym 3916 4-Mor COOEt 4-Mor 6-Pym 3917 4-Mor COOEt 4-Mor 2-Pyz 3918 4-Mor COOEt 4-Mor 3-Pyz 3919 4-Mor NO _Two 4-Mor Ph 3920 4-Mor NO _Two 4-Mor 2-Pyr 3921 4-Mor NO _Two 4-Mor 3-Pyr 3922 4-Mor NO _Two 4-Mor 4-Pyr 3923 4-Mor NO _Two 4-Mor 3-Pyzn 3924 4-Mor NO _Two 4-Mor 4-Pyzn 3925 4-Mor NO _Two 4-Mor 5-Pyzn 3926 4-Mor NO _Two 4-Mor 6-Pyzn 3927 4-Mor NO _Two 4-Mor H 3928 4-Mor NO _Two 4-Mor Me 3929 4-Mor NO _Two 4-Mor Et 3930 4-Mor NO _Two 4-Mor Pr 3931 4-Mor NO _Two 4-Mor Bz 3932 4-Mor NO _Two 4-Mor n-Hx 3933 Cl CN 4-Mor Ph 3934 Cl CN 4-Mor 2-Pyr 3935 Cl CN 4-Mor 3-Pyr 3936 Cl CN 4-Mor 4-Pyr 3937 Cl CN 4-Mor 3-Pyzn 3938 Cl CN 4-Mor 4-Pyzn 3939 Cl CN 4-Mor 5-Pyzn 3940 Cl CN 4-Mor 6-Pyzn 3941 Cl CN 4-Mor 2-Pym 3942 Cl CN 4-Mor 4-Pym 3943 Cl CN 4-Mor 5-Pym 3944 Cl CN 4-Mor 6-Pym 3945 Cl CN 4-Mor 2-Pyz 3946 Cl CN 4-Mor 3-Pyz 3947 Cl CN 4-Thm Ph 3948 Cl CN 4-Thm 2-Pyr 3949 Cl CN 4 -Thm 3-Pyr 3950 Cl CN 4-Thm 4-Pyr 3951 Cl CN 4-Thm 3-Pyzn 3952 Cl CN 4-Thm 4-Pyzn 3953 Cl CN 4-Thm 5-Pyzn 3954 Cl CN 4-Thm 6-Pyzn 3955 Cl CN 4-Thm 2-Pym 3956 Cl CN 4-Thm 4-Pym 3957 Cl CN 4-Thm 5-Pym 3958 Cl CN 4-Thm 6-Pym 3959 Cl CN 4-Thm 2-Pyz 3960 Cl CN 4- Thm 3-Pyz 3961 Cl COOEt 4-Mor Ph 3962 Cl COOEt 4-Mor 2-Pyr 3963 Cl COOEt 4-Mor 3-Pyr 3964 Cl COOEt 4-Mor 4-Pyr 3965 Cl COOEt 4-Mor 3-Pyzn 3966 Cl COOEt 4-Mor 4-Pyzn 3967 Cl COOEt 4-Mor 5-Pyzn 3968 Cl COOEt 4-Mor 6-Pyzn 3969 Cl COOEt 4-Mor 2-Pym 3970 Cl COOEt 4-Mor 4-Pym 3971 Cl COOEt 4-Mor 5- Pym 3972 Cl COOEt 4-Mor 6-Pym 3973 Cl COOEt 4-Mor 2-Pyz 3974 Cl COOEt 4-Mor 3-Pyz 3975 Cl COOEt 4-Thm Ph 3976 Cl COOEt 4-Thm 2-Pyr 3977 Cl COOEt 4-Thm 3-Pyr 3978 Cl COOEt 4-Thm 4-Pyr 3979 Cl COOEt 4-Thm 3- Pyzn 3980 Cl COOEt 4-Thm 4-Pyzn 3981 Cl COOEt 4-Thm 5-Pyzn 3982 Cl COOEt 4-Thm 6-Pyzn 3983 Cl COOEt 4-Thm 2-Pym 3984 Cl COOEt 4-Thm 4-Pym 3985 Cl COOEt 4 -Thm 5-Pym 3986 Cl COOEt 4-Thm 6-Pym 3987 Cl COOEt 4-Thm 2-Pyz 3988 Cl COOEt 4-Thm 3-Pyz 3989 OH CN 4-Mor Ph 3990 OH CN 4-Mor 2-Pyr 3991 OH CN 4-Mor 3-Pyr 3992 OH CN 4-Mor 4-Pyr 3993 OH CN 4-Mor 3-Pyzn 3994 OH CN 4-Mor 4-Pyzn 3995 OH CN 4-Mor 5-Pyzn 3996 OH CN 4-Mor 6 -Pyzn 3997 OH CN 4-Mor 2-Pym 3998 OH CN 4-Mor 4-Pym 3999 OH CN 4-Mor 5-Pym 4000 OH CN 4-Mor 6-Pym 4001 OH CN 4-Mor 2-Pyz 4002 OH CN 4-Mor 3-Pyz 4003 OH CN 4-Thm Ph 4004 OH CN 4-Thm 2-Pyr 4005 OH CN 4-Thm 3-Pyr 4006 OH CN 4-Thm 4-Pyr 4007 OH CN 4-Thm 3-Pyzn 4008 OH CN 4-Thm 4-Pyzn 4009 OH CN 4-Thm 5-Pyzn 4010 OH CN 4-Thm 6-Pyzn 4011 OH CN 4-Thm 2-Pym 4012 OH CN 4-Thm 4-Pym 4013 OH CN 4-Thm 5-Pym 4014 OH CN 4-Thm 6-Pym 4015 OH CN 4- Thm 2-Pyz 4016 OH CN 4-Thm 3-Pyz 4017 OH COOEt 4-Mor Ph 4018 OH COOEt 4-Mor 2-Pyr 4019 OH COOEt 4-Mor 3-Pyr 4020 OH COOEt 4-Mor 4-Pyr 4021 OH COOEt 4-Mor 3-Pyzn 4022 OH COOEt 4-Mor 4-Pyzn 4023 OH COOEt 4-Mor 5-Pyzn 4024 OH COOEt 4-Mor 6-Pyzn 4025 OH COOEt 4-Mor 2-Pym 4026 OH COOEt 4-Mor 4- Pym 4027 OH COOEt 4-Mor 5-Pym 4028 OH COOEt 4-Mor 6-Pym 4029 OH COOEt 4-Mor 2-Pyz 4030 OH COOEt 4-Mor 3-Pyz 4031 OH COOEt 4-Thm Ph 4032 OH COOEt 4-Thm 2-Pyr 4033 OH COOEt 4-Thm 3-Pyr 4034 OH COOEt 4-Thm 4-Pyr 4035 OH COOEt 4-Thm 3-Pyzn 4036 OH COOEt 4-Thm 4-Pyzn 4037 OH COOEt 4-Thm 5-Pyzn 4038 OH COOEt 4-Thm 6-Pyzn 4039 OH COOEt 4-Thm 2-Pym 4040 OH COOEt 4-Thm 4-Pym 4041 OH COOEt 4-Thm 5-Pym 4042 OH COOEt 4-Thm 6-Pym 4043 OH COOEt 4-Thm 2 -Pyz 4044 OH COOEt 4-Thm 3-Pyz 4045 n-Bu CN 4-Mor Ph 4046 n-Bu CN 4-Mor 2-Pyr 4047 n-Bu CN 4-Mor 3-Pyr 4048 n-Bu CN 4-Mor 4-Pyr 4049 n-Bu CN 4-Mor 3-Pyzn 4050 n-Bu CN 4-Mor 4-Pyzn 4051 n-Bu CN 4-Mor 5-Pyzn 4052 n-Bu CN 4-Mor 6-Pyzn 4053 n- Bu CN 4-Mor 2-Pym 4054 n-Bu C N 4-Mor 4-Pym 4055 n-Bu CN 4-Mor 5-Pym 4056 n-Bu CN 4-Mor 6-Pym 4057 n-Bu CN 4-Mor 2-Pyz 4058 n-Bu CN 4-Mor 3- Pyz 4059 n-Bu CN 4-Thm Ph 4060 n-Bu CN 4-Thm 2-Pyr 4061 n-Bu CN 4-Thm 3-Pyr 4062 n-Bu CN 4-Thm 4-Pyr 4063 n-Bu CN 4- Thm 3-Pyzn 4064 n-Bu CN 4-Thm 4-Pyzn 4065 n-Bu CN 4-Thm 5-Pyzn 4066 n-Bu CN 4-Thm 6-Pyzn 4067 n-Bu CN 4-Thm 2-Pym 4068 n -Bu CN 4-Thm 4-Pym 4069 n-Bu CN 4-Thm 5-Pym 4070 n-Bu CN 4-Thm 6-Pym 4071 n-Bu CN 4-Thm 2-Pyz 4072 n-Bu CN 4-Thm 3-Pyz 4073 n-Bu COOEt 4-Mor Ph 4074 n-Bu COOEt 4-Mor 2-Pyr 4075 n-Bu COOEt 4-Mor 3-Pyr 4076 n-Bu COOEt 4-Mor 4-Pyr 4077 n-Bu COOEt 4-Mor 3-Pyzn 4078 n-Bu COOEt 4-Mor 4-Pyzn 4079 n-Bu COOEt 4-Mor 5-Pyzn 4080 n-Bu COOEt 4-Mor 6-Pyzn 4081 n-Bu COOEt 4-Mor 2-Pym 4082 n-Bu COOEt 4-Mor 4-Pym 4083 n-Bu COOEt 4-Mor 5-Pym 4084 n-Bu COOEt 4-Mor 6-Pym 4085 n-Bu COOEt 4-Mor 2-Pyz 4086 n-Bu COOEt 4 -Mor 3-Pyz 4087 n-Bu COOEt 4-Thm Ph 4088 n-Bu COOEt 4-Thm 2-Pyr 4089 n-Bu COOEt 4-Thm 3-Pyr 4090 n-Bu COOEt 4-Thm 4-Pyr 4091 n- Bu COOEt 4-Thm 3-Pyzn 4092 n-Bu COOEt 4-Thm 4-Pyzn 4093 n-Bu COOEt 4-Thm 5-Pyzn 4094 n-Bu COOEt 4-Thm 6-Pyzn 4095 n-Bu COOEt 4-Thm 2-Pym 4096 n-Bu COOEt 4- Thm 4-Pym 4097 n-Bu COOEt 4-Thm 5-Pym 4098 n-Bu COOEt 4-Thm 6-Pym 4099 n-Bu COOEt 4-Thm 2-Pyz 4100 n-Bu COOEt 4-Thm 3-Pyz 4101 n -Oc CN 4-Mor Ph 4102 n-Oc CN 4-Mor 2-Pyr 4103 n-Oc CN 4-Mor 3-Pyr 4104 n-Oc CN 4-Mor 4-Pyr 4105 n-Oc CN 4-Mor 3- Pyzn 4106 n-Oc CN 4-Mor 4-Pyzn 4107 n-Oc CN 4-Mor 5-Pyzn 4108 n-Oc CN 4-Mor 6-Pyzn 4109 n-Oc CN 4-Mor 2-Pym 4110 n-Oc CN 4-Mor 4-Pym 4111 n-Oc CN 4-Mor 5-Pym 4112 n-Oc CN 4-Mor 6-Pym 4113 n-Oc CN 4-Mor 2-Pyz 4114 n-Oc CN 4-Mor 3-Pyz 4115 n-Oc CN 4-Thm Ph 4116 n-Oc CN 4-Thm 2-Pyr 4117 n-Oc CN 4-Thm 3-Pyr 4118 n-Oc CN 4-Thm 4-Pyr 4119 n-Oc CN 4-Thm 3-Pyzn 4120 n-Oc CN 4-Thm 4-Pyzn 4121 n-Oc CN 4-Thm 5-Pyzn 4122 n-Oc CN 4-Thm 6-Pyzn 4123 n-Oc CN 4-Thm 2-Pym 4124 n- Oc CN 4-Thm 4-Pym 4125 n-Oc CN 4-Thm 5-Pym 4126 n-Oc CN 4-Thm 6-Pym 4127 n-Oc CN 4-Thm 2-Pyz 4128 n-Oc CN 4-Thm 3 -Pyz 4129 n-Oc COOEt 4-Mor Ph 4130 n-Oc COOEt 4-Mor 2-Pyr 4131 n-Oc COOEt 4-Mor 3-Pyr 4132 n-Oc COOEt 4-Mor 4-Pyr 4133 n-Oc COOEt 4-Mor 3-Pyzn 4134 n-Oc COOEt 4-Mor 4-Pyzn 4135 n- Oc COOEt 4-Mor 5-Pyzn 4136 n-Oc COOEt 4-Mor 6-Pyzn 4137 n-Oc COOEt 4-Mor 2-Pym 4138 n-Oc COOEt 4-Mor 4-Pym 4139 n-Oc COOEt 4-Mor 5 -Pym 4140 n-Oc COOEt 4-Mor 6-Pym 4141 n-Oc COOEt 4-Mor 2-Pyz 4142 n-Oc COOEt 4-Mor 3-Pyz 4143 n-Oc COOEt 4-Thm Ph 4144 n-Oc COOEt 4 -Thm 2-Pyr 4145 n-Oc COOEt 4-Thm 3-Pyr 4146 n-Oc COOEt 4-Thm 4-Pyr 4147 n-Oc COOEt 4-Thm 3-Pyzn 4148 n-Oc COOEt 4-Thm 4-Pyzn 4149 n-Oc COOEt 4-Thm 5-Pyzn 4150 n-Oc COOEt 4-Thm 6-Pyzn 4151 n-Oc COOEt 4-Thm 2-Pym 4152 n-Oc COOEt 4-Thm 4-Pym 4153 n-Oc COOEt 4- Thm 5-Pym 4154 n-Oc COOEt 4-Thm 6-Pym 4155 n-Oc COOEt 4-Thm 2-Pyz 4156 n-Oc COOEt 4-Thm 3-Pyz 4157 n-Hx CN 4-Mor Ph 4158 n-Hx CN 4-Mor 2-Pyr 4159 n-Hx CN 4-Mor 3-Pyr 4160 n-Hx CN 4-Mor 4-Pyr 4161 n-Hx CN 4-Mor 3-Pyzn 4162 n-Hx CN 4-Mor 4- Pyzn 4163 n-Hx CN 4-Mor 5-Pyzn 4164 n-Hx CN 4-Mor 6-Pyzn 4165 n-Hx CN 4-Mor 2-Pym 4166 n-Hx CN 4-Mor 4-Pym 4167 n-Hx CN 4-Mor 5-Pym 4168 n-Hx CN 4-Mor 6-Pym 4169 n-Hx CN 4-Mor 2-Pyz 4170 n-Hx CN 4-Mor 3-Pyz 4171 n-Hx CN 4-Thm Ph 4172 n-Hx CN 4-Thm 2-Pyr 4173 n-Hx CN 4-Thm 3-Pyr 4174 n-Hx CN 4-Thm 4-Pyr 4175 n-Hx CN 4-Thm 3-Pyzn 4176 n-Hx CN 4- Thm 4-Pyzn 4177 n-Hx CN 4-Thm 5-Pyzn 4178 n-Hx CN 4-Thm 6-Pyzn 4179 n-Hx CN 4-Thm 2-Pym 4180 n-Hx CN 4-Thm 4-Pym 4181 n -Hx CN 4-Thm 5-Pym 4182 n-Hx CN 4-Thm 6-Pym 4183 n-Hx CN 4-Thm 2-Pyz 4184 n-Hx CN 4-Thm 3-Pyz 4185 n-Hx COOEt 4-Mor Ph 4186 n-Hx COOEt 4-Mor 2-Pyr 4187 n-Hx COOEt 4-Mor 3-Pyr 4188 n-Hx COOEt 4-Mor 4-Pyr 4189 n-Hx COOEt 4-Mor 3-Pyzn 4190 n-Hx COOEt 4-Mor 4-Pyzn 4191 n-Hx COOEt 4-Mor 5-Pyzn 4192 n-Hx COOEt 4-Mor 6-Pyzn 4193 n-Hx COOEt 4-Mor 2-Pym 4194 n-Hx COOEt 4-Mor 4-Pym 4195 n-Hx COOEt 4-Mor 5-Pym 4196 n-Hx COOEt 4-Mor 6-Pym 4197 n-Hx COOEt 4-Mor 2-Pyz 4198 n-Hx COOEt 4-Mor 3-Pyz 4199 n-Hx COOEt 4 -Thm Ph 4200 n-Hx COOEt 4-Thm 2-Pyr 4201 n-Hx COOEt 4-Thm 3-Pyr 4202 n-Hx COOEt 4-Thm 4-Pyr 4203 n-Hx COOEt 4-Thm 3-Pyzn 4204 n- Hx COOEt 4-Thm 4-Pyzn 4205 n-Hx COOEt 4-Thm 5-Pyzn 4206 n-Hx COOEt 4-Thm 6-Pyzn 4207 n-Hx COOEt 4-Thm 2-Pym 4208 n-Hx COOEt 4-Thm 4-Pym 4209 n-Hx COOEt 4 -Thm 5-Pym 4210 n-Hx COOEt 4-Thm 6-Pym 4211 n-Hx COOEt 4-Thm 2-Pyz 4212 n-Hx COOEt 4-Thm 3-Pyz 4213 Me H 4-Mor 4-Mor −−− --------------------------------------------------------

[0048]

Embedded image Table 2 −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− Compound No.R ¹ R ² R ³ R ⁴ −−−−−−− −−−−−−−−−−−−−−−−−−−−−−−−− 4214 Ph CN OH 2-Pyr 4215 Ph COOEt OH 3-Pyr 4216 Ph COOEt OH 4-Pyr 4217 Ph COOEt OH Ph 4218 Ph COOH OH Ph 4219 Ph COOEt 4-Mor 2-Pyr 4220 Ph COOEt 4-Mor 3-Pyr 4221 Ph COOEt 4-Mor 4-Pyr 4222 3-Pyr COOEt OH Ph 4223 3-Pyr COOEt OH 2-Pyr 4224 3- Pyr COOEt OH 3-Pyr 4225 3-Pyr COOEt OH 4-Pyr 4226 3-Pyr COOH OH Ph 4227 3-Pyr COOH OH 2-Pyr 4228 3-Pyr COOH OH 3-Pyr 4229 3-Pyr COOH OH 4-Pyr 4230 3-Pyr CN OH Ph 4231 3-Pyr CN OH 2-Pyr 4232 3-Pyr CN OH 3-Pyr 4233 3-Pyr CN OH 4-Pyr −−−−−−−−−−−−−−−−−− −−−−−−−−−−−−−−−

[0049]

Embedded image Table 3 ------------------------------ compound number ^{R 1 R 2 R 3 R 4} ------- −−−−−−−−−−−−−−−−−−−−−−−− 4234 Ph COOEt OH Ph 4235 Ph COOEt OH 2-Pyr 4236 Ph COOEt OH 3-Pyr 4237 Ph COOEt OH 4-Pyr 4238 Ph COOH OH Ph 4239 Ph COOH OH 2-Pyr 4240 Ph COOH OH 3-Pyr 4241 Ph COOH OH 4-Pyr 4242 Ph CN OH Ph 4243 Ph CN OH 2-Pyr 4244 Ph CN OH 3-Pyr 4245 Ph CN OH 4- Pyr 4246 3-Pyr COOEt OH Ph 4247 3-Pyr COOEt OH 2-Pyr 4248 3-Pyr COOEt OH 3-Pyr 4249 3-Pyr COOEt OH 4-Pyr 4250 3-Pyr COOH OH Ph 4251 3-Pyr COOH OH 2- Pyr 4252 3-Pyr COOH OH 3-Pyr 4253 3-Pyr COOH OH 4-Pyr 4254 3-Pyr CN OH Ph 4255 3-Pyr CN OH 2-Pyr 4256 3-Pyr CN OH 3-Pyr 4257 3-Pyr CN OH 4-Pyr 4258 Ph COOEt 4-Mor Ph 4259 Ph COOEt 4-Mor 2-Pyr 4260 Ph COOEt 4-Mor 3-Pyr 4261 Ph COOEt 4-Mor 4-Pyr 4262 Ph COOH 4-Mor Ph 4263 Ph COOH 4-Mor 2-Pyr 4264 Ph COOH 4-Mor 3-Pyr 4265 Ph COOH 4-Mor 4-Pyr 4266 Ph CN 4-Mor Ph 4267 Ph CN 4-Mor 2-Py r 4268 Ph CN 4-Mor 3-Pyr 4269 Ph CN 4-Mor 4-Pyr 4270 Ph COOEt 4-Piz Ph 4271 Ph COOEt 4-Piz 2-Pyr 4272 Ph COOEt 4-Piz 3-Pyr 4273 Ph COOEt 4-Piz 4-Pyr 4274 Ph COOH 4-Piz Ph 4275 Ph COOH 4-Piz 2-Pyr 4276 Ph COOH 4-Piz 3-Pyr 4277 Ph COOH 4-Piz 4-Pyr 4278 Ph CN 4-Piz Ph 4279 Ph CN 4-Piz 2-Pyr 4280 Ph CN 4-Piz 3-Pyr 4281 Ph CN 4-Piz 4-Pyr 4282 OH COOEt Ph Ph 4283 OH COOEt Ph 2-Pyr 4284 OH COOEt Ph 3-Pyr 4285 OH COOEt Ph 4-Pyr 4286 OH COOH Ph Ph 4287 OH COOH Ph 2-Pyr 4288 OH COOH Ph 3-Pyr 4289 OH COOH Ph 4-Pyr 4290 OH CN Ph Ph 4291 OH CN Ph 2-Pyr 4292 OH CN Ph 3-Pyr 4293 OH CN Ph 4-Pyr 4294 OH COOEt 3-Pyr Ph 4295 OH COOEt 3-Pyr 2-Pyr 4296 OH COOEt 3-Pyr 3-Pyr 4297 OH COOEt 3-Pyr 4-Pyr 4298 OH COOH 3-Pyr Ph 4299 OH COOH 3-Pyr 2-Pyr 4300 OH COOH 3-Pyr 3-Pyr 4301 OH COOH 3-Pyr 4-Pyr 4302 OH CN 3-Pyr Ph 4303 OH CN 3-Pyr 2-Pyr 4304 OH CN 3-Pyr 3-Pyr 4305 OH CN 3-Pyr 4- Pyr 4306 4-Mor COOEt Ph Ph 4307 4-Mor COOEt Ph 2-Pyr 4308 4-Mor COOEt Ph 3-Pyr 4309 4-Mor COOEt Ph 4-Pyr 4310 4-Mor COOH Ph Ph 4311 4-Mor COOH Ph 2-Pyr 4312 4-Mor COOH Ph 3-Pyr 4313 4-Mor COOH Ph 4-Pyr 4314 4-Mor CN Ph Ph 4315 4-Mor CN Ph 2-Pyr 4316 4-Mor CN Ph 3- Pyr 4317 4-Mor CN Ph 4-Pyr 4318 4-Piz COOEt Ph Ph 4319 4-Piz COOEt Ph 2-Pyr 4320 4-Piz COOEt Ph 3-Pyr 4321 4-Piz COOEt Ph 4-Pyr 4322 4-Piz COOH Ph Ph 4323 4-Piz COOH Ph 2-Pyr 4324 4-Piz COOH Ph 3-Pyr 4325 4-Piz COOH Ph 4-Pyr 4326 4-Piz CN Ph Ph 4327 4-Piz CN Ph 2-Pyr 4328 4-Piz CN Ph 3-Pyr 4329 4-Piz CN Ph 4-Pyr 4330 2-Thi CN OH 3-Pyr −−−−−−−−−−−−−−−−−−−−−−−−−−−−− −

[0050]

Embedded image Table 4 −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− Compound No.R ³ R ⁴ −−−−−−−−−−−− −−−−−−−−−−−−−−−−−−−− 4331 4-Mor Ph 4332 4-Mor 2-Pyr 4333 4-Mor 3-Pyr 4334 4-Mor 4-Pyr 4335 1-Pip Ph 4336 1-Pip 2-Pyr 4337 1-Pip 3-Pyr 4338 1-Pip 4-Pyr 4339 4-Thm Ph 4340 4-Thm 2-Pyr 4341 4-Thm 3-Pyr 4342 4-Thm 4-Pyr 4343 1- Piz Ph 4344 1-Piz 2-Pyr 4345 1-Piz 3-Pyr 4346 1-Piz 4-Pyr 4347 (Et) ₂ N Ph 4348 (Et) ₂ N 2-Pyr 4349 (Et) ₂ N 3-Pyr 4350 ( Et) ₂ N 4-Pyr 4351 cHx-NH Ph 4352 cHx-NH 2-Pyr 4353 cHx-NH 3-Pyr 4354 cHx-NH 4-Pyr 4355 Ph-NH Ph 4356 Ph-NH 2-Pyr 4357 Ph-NH 3 -Pyr 4358 Ph-NH 4-Pyr 4359 4-Boc-1-Piz Ph 4360 4-Boc-1-Piz 2-Pyr 4361 4-Boc-1-Piz 3-Pyr 4362 4-Boc-1-Piz 4- Pyr 4363 OH Ph 4364 OH 2-Pyr 4365 OH 3-Pyr 4366 OH 4-Pyr 4367 MeO Ph 4368 MeO 2-Pyr 4369 MeO 3-Pyr 4370 MeO 4-Pyr 4371 EtO Ph 4372 EtO 2-Pyr 4373 EtO 3-Pyr 4374 EtO 4-Pyr −−−−−−−−−−−−−−−−−−−− In the above table, `` Ph '' indicates phenyl, `` Thi '' indicates thienyl, `` Fur '' indicates furyl, `` Pyrr '' indicates pyrrolyl, `` Pyza '' Represents pyrazolyl, “Imid” represents imidazolyl, “Oxa” represents oxazolyl, “T
"hiz" indicates thiazolyl, "Pyr" indicates pyridyl,
`` Pyzn '' indicates pyridazinyl, `` Pym '' indicates pyrimidyl, `` Pyz '' indicates pyrazyl, `` BeFur '' indicates benzofuryl, `` Np '' indicates naphthyl, `` Pyrd '' indicates pyrrolidinyl, `` Pip "" Indicates piperidinyl and "M
`` or '' indicates morpholinyl, `` Thm '' indicates thiomorpholinyl, `` Piz '' indicates piperazinyl, `` Me '' indicates methyl, `` Et '' indicates ethyl, `` Pr '' indicates propyl, and `` i- “Pr” indicates isopropyl, and “n-Bu” indicates n
-Butyl, "i-Bu" indicates isobutyl, "sB
"u" indicates s-butyl, "t-Bu" indicates t-butyl, "Pn" indicates pentyl, "n-Hx" indicates n-hexyl, "Hep" indicates heptyl, `` n-Oc '' indicates n-octyl, `` Nn '' indicates nonyl, `` Dc '' indicates decyl, `` Udc '' indicates undecyl, `` Ddc '' indicates dodecyl, `` Bz '' indicates benzyl , “CPr” denotes cyclopropyl, “cBu” denotes cyclobutyl, “cPr”
“n” indicates cyclopentyl, “cHx” indicates cyclohexyl, “cHep” indicates cycloheptyl, and “cOc” indicates cyclooctyl.

In the above table, preferred compounds include
Exemplary Compound No. 47, 355, 1181, 1231, 1
603, 1557, 1759, 3031, 3032, 3
125, 3311, 3312, 3313, 3314, 3
625, 3626, 3627, 3628, 3709, 3
717, 3723, 3727, 3731, 3732, 3
795, 3796, 3927, 3989, 4073, 4
214, 4222, 4243, 4266, 4331, 4
335, and more preferable compounds are exemplified compound Nos. 1181, 1231, and 160.
3, 1757, 1759, 3031, 3125, 331
1,3717, 3732, 4073, and 4266.

Particularly preferred compounds include: 4-morpholin-4-yl-2,6-diphenyl-pyrimidine-5-
Carboxylic acid ethyl ester (Exemplary Compound No. 123
1) 4-ethylamino-2-pyridin-3-yl-6-thiomorpholin-4-yl-pyrimidin-5-carboxylic acid ethyl ester (Exemplary Compound No. 3125), 2-morpholin-4-yl-
4,6-diphenyl-nicotinonitrile (Exemplary Compound No. 4
266), and most preferably, compounds of Exemplified Compound Nos. 1231, 3125.

[0053]

BEST MODE FOR CARRYING OUT THE INVENTION The compounds of the present invention include, for example,
Can be produced by the method described in (1). [Method A] In the method A, X and Y in the general formula (I) are
Each is a nitrogen atom; ^TwoIs a carboxy group or
A compound which is an alkoxycarbonyl group having 2 to 6 carbon atoms
It is a method of manufacturing a product.

[0054]

Embedded image [Wherein, R ¹ , R ³ and R ⁴ have the same meanings as above, and R ⁵ represents an alkyl group having 1 to 6 carbon atoms (preferably methyl or ethyl, particularly preferably ethyl). , M represents a hydrogen atom or an alkali metal such as lithium, sodium, potassium, cesium, and Z and Z ′ are the same or different and are each a halogen atom (preferably a chlorine atom or a bromine atom. , Particularly preferably a chlorine atom). In step 1, a condensation reaction of the acyl halide compound (1) with the dialkyl malonate (2) is performed in a solvent in the presence of a base, and then diazomethane is added to produce methyl vinyl ether (3). This is the step of performing

The base is not particularly limited as long as it is used as a base in a usual reaction.
Alkali metal carbonates such as sodium carbonate, potassium carbonate and lithium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate, potassium hydrogen carbonate and lithium hydrogen carbonate; such as lithium hydride, sodium hydride and potassium hydride Alkali metal hydrides; inorganic bases such as alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, barium hydroxide and lithium hydroxide;
Alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide and lithium methoxide; alkali metal salts of organic acids such as sodium acetate and sodium propionate; mercaptans such as sodium methyl mercaptan and sodium ethyl mercaptan Alkali metals; 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] Undec-7-ene (DB
Organic bases such as U) or organic metal bases such as butyllithium and lithium diisopropylamide, and preferably organic bases such as sodium hydride, sodium methoxide, sodium acetate, triethylamine and diisopropylethylamine. Is a base.

In order to carry out the reaction effectively, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride,
Crown ethers such as dibenzo-18-crown-6 can also be added.

The solvent used in the first-stage condensation reaction is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. Examples thereof include hexane, heptane, ligroin and petroleum ether. Aliphatic hydrocarbons; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethyl formate, ethyl acetate; Esters such as propyl acetate, butyl acetate and diethyl carbonate; diethyl ether, diisopropyl ether
Ethers such as ter, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; nitro compounds such as nitroethane and nitrobenzene; acetonitrile, isobutyi Nitriles such as lonitrile; amides such as formamide, dimethylformamide, dimethylacetamide, and hexamethylphosphorotriamide; aromatic heterocycles such as dimethylsulfoxide and sulfolane such as sulfolane; and pyridine. , Preferably ethers and pyridine.

The reaction temperature is from -100 ° C to 100 ° C, preferably from -78 ° C to 40 ° C.

The reaction time varies depending on conditions such as the compound and the reaction temperature, but is usually 30 minutes to 50 hours, preferably 1 hour to 18 hours.

The solvent used in the subsequent reaction is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent.
Aliphatic hydrocarbons such as ligroin and petroleum ether;
Aromatic hydrocarbons such as benzene, toluene, xylene; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, halogenated hydrocarbons such as dichlorobenzene; ethyl formate, ethyl acetate;
Esters such as propyl acetate, butyl acetate, diethyl carbonate; diethyl ether, diisopropyl ether,
Tetrahydrofuran, dioxane, dimethoxyethane,
Ethers such as diethylene glycol dimethyl ether; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; nitro compounds such as nitroethane and nitrobenzene; nitriles such as acetonitrile and isobutyronitrile; formamide And amides such as dimethylformamide, dimethylacetamide, and hexamethylphosphorotriamide; and sulfoxides such as dimethylsulfoxide and sulfolane. Preferred are ethyl acetate, ether, and a mixed solvent thereof.

The reaction temperature is from -50 ° C to 100 ° C,
Preferably it is in the range from 0 ° C to 50 ° C. The reaction time varies depending on the conditions such as the compound and the reaction temperature, but is usually 3 hours to 50 hours, preferably 5 hours to 18 hours. Step 2 comprises reacting the compound (3) with an amidine hydrochloride in the presence of a base to obtain a pyrimidine derivative (4)
This is the step of manufacturing.

The base is not particularly limited as long as it is used as a base in a usual reaction.
Alkali metal carbonates such as sodium carbonate, potassium carbonate and lithium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate, potassium hydrogen carbonate and lithium hydrogen carbonate; such as lithium hydride, sodium hydride and potassium hydride Alkali metal hydrides; lithium,
Alkali metals such as sodium and potassium; inorganic bases such as alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, barium hydroxide and lithium hydroxide; sodium methoxide, sodium ethoxide and potassium t Alkali metal alkoxides such as butoxide and lithium methoxide; alkali metal salts of organic acids such as sodium acetate and sodium propionate; mercaptan alkali metals such as sodium methyl mercaptan and ethyl mercaptan; triethylamine, tributylamine, diisopropyl Ethylamine, 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] undec-7-ene (D
Organic bases such as BU) or organometallic bases such as butyllithium, lithium diisopropylamide, and lithium hexamethyldisilazane; and preferably, sodium hydride, sodium methoxide, lithium hexamethyldiethyl. Silazane, sodium.

In order to carry out the reaction effectively, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride,
Crown ethers such as dibenzo-18-crown-6 can also be added.

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. For example, hexane, heptane, ligroin,
Aliphatic hydrocarbons such as petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; methanol Alcohols such as ethanol, tertiary butanol, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone;
Ketones such as cyclohexanone; nitro compounds such as nitroethane and nitrobenzene; nitriles such as acetonitrile and isobutyronitrile; formamide, dimethylformamide, dimethylacetamide;
Examples include amides such as hexamethyl phosphorotriamide; sulfoxides such as dimethyl sulfoxide and sulfolane; and aromatic heterocycles such as pyridine, and preferred are alcohols.

The reaction temperature is from 0 ° C. to 100 ° C., preferably from 10 ° C. to the reflux temperature of the solvent.

The reaction time varies depending on conditions such as the compound and the reaction temperature, but is usually about 30 minutes to 50 hours.
Preferably, it is 1 hour to 18 hours.

In the compound (4), the compound wherein M is a hydrogen atom has the following tautomerism.

[0068]

Embedded image Step 3 is a step of reacting compound (4) with a halogenating agent in the presence or absence of an additive, in the presence or absence of a solvent, to produce a halogenated compound (5). .

The halogenating agent to be used is not particularly limited as long as it is usually used in halogenation.
For example, phosphorus halides such as phosphorus oxychloride, phosphorus pentachloride, phosphorus tribromide and phosphorus oxybromide; thionyl chloride and oxalyl chloride can be mentioned. This is Rin.

The additive to be used is not particularly limited as long as it is an additive used in ordinary halogenation. Examples thereof include organic bases such as pyridine and triethylamine; salts such as lithium phosphate; Organic acids such as acids; methanesulfonyl chloride;

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent.
Aliphatic hydrocarbons such as petroleum ether; Aromatic hydrocarbons such as benzene, chlorobenzene, toluene and xylene; Halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene Alcohols such as methanol, ethanol, tertiary butanol;
Ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone, cyclohexanone;
Nitro compounds such as nitroethane and nitrobenzene; nitriles such as acetonitrile and isobutyronitrile; amides such as formamide, dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide; sulfoxides such as dimethyl sulfoxide and sulfolane And pyridine and the like, and preferred are toluene, chlorobenzene and dimethylformamide.

The reaction temperature is between 0 ° C. and 250 ° C., preferably between 10 ° C. and 200 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
It is about from minutes to 50 hours, preferably from 1 hour to 24 hours. Step 4 is a step of substituting the halogen atom (Z ′) of the compound (5) with the substituent R ³ to obtain the compound (I) of the present invention.
This is the step of manufacturing a).

The reagent used for introducing the substituent R ³ is not particularly limited as long as it is generally used for a substitution reaction with a halide.
Examples thereof include sulfides, alcohols or alkali metal salts thereof, and organic alkali metal reagents.

The reaction is usually carried out in a solvent, and the solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Aliphatic hydrocarbons such as benzene, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene. Ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether;
, Ethanol, n-propanol, isopropanol,
n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin,
Alcohols such as octanol, cyclohexanol and methyl cellosolve; nitro compounds such as nitroethane and nitrobenzene; nitriles such as acetonitrile and isobutyronitrile; formamide, dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide And sulfoxides such as dimethyl sulfoxide and sulfolane.

The reaction temperature is from 0 ° C. to 250 ° C., preferably from 10 ° C. to 150 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
It is from about minutes to 50 hours, preferably from 30 minutes to 24 hours. Step 5 is a step of hydrolyzing the ester moiety of compound (Ia) in the presence of a base or acid to produce compound (Ib) of the present invention.

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

In order to carry out the reaction effectively, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride,
Crown ethers such as dibenzo-18-crown-6 can also be added.

The acid to be used is not particularly limited as long as it is used as an acid catalyst in a usual reaction. Preferably, the acid is hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid or phosphoric acid. Inorganic acids or Bronsted acids such as acetic acid, formic acid, oxalic acid, methanesulfonic acid, paratoluenesulfonic acid, organic acids such as trifluoroacetic acid and trifluoromethanesulfonic acid can be mentioned, and inorganic acids are preferred.

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferably, the solvent is an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; diethyl ether, diisopropyl ether; Ethers such as tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol , Isoamyl alcohol, diethylene glycol, Alcohols such as serine, octanol, cyclohexanol, and methyl cellosolve; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; Amides; sulfoxides such as dimethyl sulfoxide and sulfolane; water, or a mixed solvent thereof.

The reaction temperature is between 0 ° C. and 250 ° C., preferably between 10 ° C. and 150 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
It is from about minutes to 50 hours, preferably from 30 minutes to 24 hours.

In this case, a salt of compound (Ib) may be formed by this step. In such a case, after the reaction is completed, the obtained salt is added to water, and an acid such as hydrochloric acid is further added. The compound (Ib) can be obtained by adding acid and adding a water-immiscible solvent such as ethyl acetate, followed by extraction. [Method B] Method B is a separate method for producing the halogenated compound (5).

[0082]

Embedded image (In the formula, R ¹ , R ³ , R ⁴ and R ⁵ have the same meanings as described above.) In Step 6, the 2-cyanoacetic acid ester (6) and carbon disulfide are reacted with sodium hydride in ethanol. This is a step of producing 2-dimethylthiomethylidene-2-cyanoacetic acid ester (7) after condensation in the presence and then methylation with dimethyl sulfate, which is described in the literature (R. Gompper and W. Topf).
1, Chem. Ber., 95 , 2871 (1962)). Step 7 comprises 2-dimethylthiomethylidene-
This is a step of reacting 2-cyanoacetic acid ester (7) with various nucleophiles to introduce a group R ¹ and obtain a 1,4-adduct (8).

As the nucleophile to be used, ordinary 1,1
There is no particular limitation as long as it is used in the four-addition reaction, and examples thereof include organic amines such as aniline, benzylamine and morpholine; phenyllithium, phenyl Grignard reagent, benzyl lithium, butyl lithium, octyl lithium, butyl Grignard reagent Organic metal reagents; alkyl mercaptans such as ethyl mercaptan; and the like, preferably organic amines and organic metal reagents. In some cases, these may be used as catalysts,
A catalyst that promotes 1,4 addition such as copper salts such as cuprous chloride and cuprous bromide can be used.

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Preferably, the solvent is an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethyl formate, ethyl acetate, propyl acetate; Esters such as butyl acetate, diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol , Isopropanol, n-butanol, i Sobutanol, t-butanol, isoamyl alcohol, diethylene glycol,
Alcohols such as glycerin, octanol, cyclohexanol and methyl cellosolve; acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone,
Ketones such as cyclohexanone; nitro compounds such as nitroethane and nitrobenzene; nitriles such as acetonitrile and isobutyronitrile; formamide, dimethylformamide, dimethylacetamide;
Amides such as hexamethyl phosphorotriamide; sulfoxides such as dimethyl sulfoxide and sulfolane.

The reaction temperature ranges from -100 ° C to 200 ° C, preferably from -78 ° C to 100 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature, but is usually about 10 minutes to 50 hours, preferably 30 minutes.
Minutes to 24 hours. Step 8 is a step of producing an amidine adduct (9) by reacting the 1,4-adduct (8) with various amidines in the presence or absence of a base catalyst.

The base to be used is not particularly limited as long as it is used as a base in a usual reaction. 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 Inorganic bases such as alkali metal hydroxides such as barium and lithium hydroxide; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide and lithium methoxide; triethylamine, tributylamine, diisopropyl Ethylamine, N-methylmol Phosphorus, 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] undec-7-ene (D
Organic bases such as BU) or organometallic bases such as butyllithium and lithium diisopropylamide.

In order to carry out the reaction effectively, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride,
Crown ethers such as dibenzo-18-crown-6 can also be added.

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 aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; diethyl ether, diisopropyl ether; Ethers such as tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol , Isoamyl alcohol, diethylene glycol, Alcohols such as serine, octanol, cyclohexanol and methyl cellosolve; nitro compounds such as nitroethane and nitrobenzene; nitriles such as acetonitrile and isobutyronitrile; formamide, dimethylformamide, dimethylacetamide, hexamethylphospho Amides such as rotriamide; and sulfoxides such as dimethyl sulfoxide and sulfolane.

The reaction temperature is from 0 ° C. to 200 ° C., preferably from 10 ° C. to 150 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
It is about from minutes to 50 hours, preferably from 1 hour to 24 hours. Step 9 is a step in which the amidine adduct (9) is closed in the presence of an acid catalyst to produce a halogenated compound (5).

The acid to be used is not particularly limited as long as it is used as an acid catalyst in a usual reaction. Inorganic acid or Bronsted acid such as acetic acid, formic acid, oxalic acid, methanesulfonic acid, organic acid such as paratoluenesulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid or zinc chloride, tin tetrachloride, boron trichloride, boron trifluorofluoride Examples thereof include Lewis acids such as lido and boron tribromide, and are preferably inorganic acids.

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 an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; diethyl ether, diisopropyl ether; Ethers such as tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol , Isoamyl alcohol, diethylene glycol, glycerin Octanol, cyclohexanol, alcohol such as methyl cellosolve - Le acids; nitroethane, nitro compounds such as nitrobenzene;
Nitriles such as acetonitrile and isobutyronitrile; amides such as formamide, dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide; and sulfoxides such as dimethyl sulfoxide and sulfolane.

The reaction temperature is from 0 ° C. to 200 ° C.
Range from 10 ° C to 100 ° C. Reaction time
Varies depending on conditions such as compound and reaction temperature.
Between about 60 hours, preferably 8 hours to 32:00
Between. [Method C] In the method C, X and Y in the general formula (I) are
Each is a nitrogen atom; ^TwoIs a nitrile group
This is a method for producing a compound.

[0093]

Embedded image (Wherein, R ¹ , R ³ , R ⁴ , R ⁵ and Z ′ have the same meanings as described above.) In step 10, the amidine adduct (9) is closed to produce a hydroxypyrimidine derivative (10). It is a process.

The reaction is usually carried out in the presence of a solvent. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Aliphatic hydrocarbons such as benzene, heptane, ligroin, petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated compounds such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene. Hydrocarbons;
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,
Alcohols such as glycerin, octanol, cyclohexanol and methyl cellosolve; nitro compounds such as nitroethane and nitrobenzene; nitriles such as acetonitrile and isobutyronitrile; formamide, dimethylformamide, dimethylacetamide;
Amides such as hexamethyl phosphorotriamide; sulfoxides such as dimethyl sulfoxide and sulfolane.

The reaction temperature is between 20 ° C. and 250 ° C., preferably between 50 ° C. and 200 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
0 minutes to 50 hours, preferably 1 hour to 24 hours
Time. Step 11 is a step for producing a halopyrimidine derivative (11) by reacting a hydroxypyrimidine derivative (10) with a halogenating agent in the presence or absence of a solvent to convert a hydroxyl group into a halogen. .

The halogenating agent to be used is not particularly limited as long as it is used in a usual halogenation reaction. Preferably, thionyl halides such as thionyl chloride, thionyl bromide and thionyl iodide are used. Sulfuryl chloride, sulfuryl bromide, sulfuryl halides such as sulfuryl iodide, phosphorus trichloride, phosphorus tribromide, phosphorus trihalides such as phosphorus triiodide,
Phosphorus pentahalides such as phosphorus pentachloride, phosphorus pentabromide and phosphorus pentaiodide or phosphorus oxyhalides such as phosphorus oxychloride, phosphorus oxybromide and phosphorus oxyiodide are preferred. Are phosphorus oxyhalides.

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethyl formate, ethyl acetate, propyl acetate; Esters such as butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; nitro compounds such as nitroethane and nitrobenzene; acetonitrile, Nitriles such as Chironitoriru; formamide, dimethyl formamide, dimethyl acetamide, can be mentioned amides such as hexamethylphosphoric triamide.

The reaction temperature is from -50 ° C to 250 ° C,
It is preferably in the range of 0 ° C to 200 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
0 minutes to 50 hours, preferably 1 hour to 24 hours
Time. Step 12 is a process for preparing a halopyrimidine derivative (1
In this step, the compound (Ic) of the present invention is produced by converting the halogen atom (Z ′) in 1) into a substituent R ³ . This step can be performed according to step 4. [Method D] Method D is a separate method for producing the halogenated compound (5).

[0099]

Embedded image Step 13 comprises reacting 2-dimethylthiomethylidenemalonic diester (12) with various nucleophiles to form a group R
^This is a step of introducing ¹ , and obtaining a 1,4-adduct (13). This step can be performed according to step 7.

Step 14 is a step of producing an amidine adduct (15) by reacting the 1,4-adduct (13) with various amidines in the presence or absence of a base catalyst. This step can be performed according to step 8.

Step 15 is a step in which the amidine adduct (15) is closed in the presence of an acid catalyst to produce a halogenated compound (5). This step can be performed according to step 9. In the compound (I) of the present invention, a compound wherein X and Y are nitrogen atoms, that is, a pyrimidine derivative is represented by [E
[Method F] and [Method F]. [Method E]

[0102]

Embedded image (In the above formula, R ¹ , R ³ and R ⁵ have the same meanings as described above.) Step 16 uses methylthiourea (16), aldehyde compound (17) and 2-cyanoacetate (6). A step of obtaining a pyrimidine derivative at once in the presence of a base.

The base to be used is not particularly limited as long as it is used as a base in a usual reaction, but is preferably an alkyl metal of a carboxylic acid such as lithium acetate, sodium acetate and potassium acetate. Salts; alkali metal carbonates such as sodium carbonate, potassium carbonate and lithium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate, potassium hydrogen carbonate and lithium hydrogen carbonate; sodium hydroxide, potassium hydroxide, barium hydroxide; Inorganic bases such as alkali metal hydroxides such as lithium hydroxide; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide and lithium methoxide; sodium methyl mercaptan, ethyl mercaptan sodium Such as mercaptan Cali metals; 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) and organic bases such as 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU).

In order to carry out the reaction effectively, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride,
Crown ethers such as dibenzo-18-crown-6 can also be added.

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 a solvent such as tributylamine, diisopropylethylamine or N-methylmorpholine. Organic amines; aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether; benzene, toluene,
Aromatic hydrocarbons such as xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene; such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate, and diethyl carbonate Esters such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; methano-
, Ethanol, n-propanol, isopropanol
, N-butanol, isobutanol, t-butanol
Alcohols such as toluene, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; nitro compounds such as nitroethane and nitrobenzene; acetonitrile;
Nitriles such as isobutyronitrile; amides such as formamide, dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide; and sulfoxides such as dimethylsulfoxide and sulfolane.

The reaction temperature is between 0 ° C. and 250 ° C., preferably between 50 ° C. and 200 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature, but is usually about 1 hour to 50 hours, preferably 3 hours to 24 hours. [Method F]

[0107]

Embedded image (In the above formula, R ¹ , R ² and R ⁵ have the same meaning as described above, and R ⁶ represents an alkyl group having 1 to 15 carbon atoms.

[0108] The alkyl group of 1 to 15 carbon atoms in the definition of R ^6, described for R ¹ 'carbon atoms 1 to 1
And the same group as "5 alkyl groups". It is preferably an alkyl group having 1 to 10 carbon atoms, more preferably a linear or branched alkyl group having 1 to 7 carbon atoms, and still more preferably 2 to 7 carbon atoms. Linear or branched alkyl groups. In step 17, a perhydro-1,3-diazin-6-one derivative (20) is produced from the aldehyde compound (17), thiourea (18) and carboxylic acid ester compound (19) in the presence of a base. It is a process.

The base to be used is not particularly limited as long as it is used as a base in a usual reaction, but is preferably an alkyl metal of a carboxylic acid such as lithium acetate, sodium acetate and potassium acetate. Salts; alkali metal carbonates such as sodium carbonate, potassium carbonate and lithium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate, potassium hydrogen carbonate and lithium hydrogen carbonate; sodium hydroxide, potassium hydroxide, barium hydroxide; Inorganic bases such as alkali metal hydroxides such as lithium hydroxide; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide, lithium methoxide; sodium methyl mercaptan, ethyl mercaptan sodium; Mercaptanah like Cali metals; 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) and organic bases such as 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU).

In order to carry out the reaction effectively, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride,
Crown ethers such as dibenzo-18-crown-6 can also be added.

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. Organic amines; aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether; benzene, toluene,
Aromatic hydrocarbons such as xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene; such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate, and diethyl carbonate Esters such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; methano-
, Ethanol, n-propanol, isopropanol
, N-butanol, isobutanol, t-butanol
Alcohols such as toluene, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; nitro compounds such as nitroethane and nitrobenzene; acetonitrile;
Nitriles such as isobutyronitrile; amides such as formamide, dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide; and sulfoxides such as dimethylsulfoxide and sulfolane.

The reaction temperature is from 0 ° C. to 250 ° C., preferably from 50 ° C. to 200 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature, but is usually about 1 hour to 50 hours, preferably 3 hours to 24 hours. Step 18 comprises alkylating the thiocarbonyl group of the perhydrodiazin-6-one derivative (20) in the presence of a base to obtain an alkylthiopyrimidine derivative (1e)
This is the step of manufacturing.

The base to be used is not particularly limited, as long as it is used as a base in a usual reaction. 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 Inorganic bases such as alkali metal hydroxides such as barium and lithium hydroxide; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide and lithium methoxide; triethylamine, tributylamine, diisopropyl Ethylamine, N-methylmol Phosphorus, 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] undec-7-ene (D
Examples thereof include organic bases such as BU) and organic metal bases such as butyllithium and lithium diisopropylamide, and preferred are alkali metal carbonates such as sodium carbonate and potassium carbonate.

In order to carry out the reaction effectively, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride,
Crown ethers such as dibenzo-18-crown-6 can also be added. General formula (I) of the present invention
Wherein one of X and Y is a nitrogen atom and the other is C
The compound H can be produced, for example, by the following Method G or H. [Method G]

[0115]

Embedded image [In the above formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ have the same meanings as described above, and Z is a halogen atom (preferably a chlorine atom or a bromine atom, particularly preferably Chlorine atom). Step 19 is a step of condensing the aldehyde compound (17) and the methyl ketone compound (21) in the presence of a base to produce an enone compound (22).

The base to be used is not particularly limited as long as it is used as a base in a usual reaction. Preferably, lithium hydride, sodium hydride,
Alkali metal hydrides such as potassium hydride; inorganic bases such as alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, barium hydroxide and lithium hydroxide; sodium methoxide, sodium ethoxide;
Alkali metal alkoxides such as potassium t-butoxide and lithium methoxide; 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), organic bases such as 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) or organic metal bases such as butyllithium and lithium diisopropylamide. Preferred are alkali metal hydroxides such as sodium hydroxide.

In order to carry out the reaction effectively, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride,
Crown ethers such as dibenzo-18-crown-6 can also be added.

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethyl formate, ethyl acetate, propyl acetate; Esters such as butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; methanol, ethanol, n-propanol , Isopropanol, n-butano- , Isobutanol - Le, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; formamide, dimethylformamide, dimethylacetamide;
Examples thereof include amides such as hexamethyl phosphorotriamide; sulfoxides such as dimethyl sulfoxide and sulfolane; and mixed solvents of these solvents and water.

The reaction temperature is from -10 ° C to 200 ° C,
Preferably, it is in the range of 0 ° C to 100 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature, but is usually about 1 hour to 50 hours, preferably 2 hours to 1 hour.
5 hours. Step 20 is a step in which an acetic acid derivative (19) and an ammonium salt are allowed to act on the enone compound (22) to obtain a pyridine derivative (If).

Examples of the ammonium salt used include ammonium salts of organic acids such as ammonium formate and ammonium acetate; and ammonium salts of inorganic acids such as ammonium chloride and ammonium sulfate. is there.

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. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethyl formate, ethyl acetate, propyl acetate; Esters such as butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; methanol, ethanol, n-propanol , Isopropanol, n-butano- , Isobutanol - Le, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; nitro compounds such as nitroethane and nitrobenzene; nitriles such as acetonitrile and isobutyronitrile; Examples include amides such as formamide, dimethylformamide, dimethylacetamide, and hexamethylphosphorotriamide; and sulfoxides such as dimethyl sulfoxide and sulfolane, and are preferably alcohols.

The reaction temperature ranges from 0 ° C. to 250 ° C., preferably from 50 ° C. to 150 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
About 50 to 50 hours, preferably 5 to 20 hours.
Time. Step 21 is a step of producing a halogenated compound (23) by reacting a halogenating agent on the compound (If) to replace the hydroxyl group with a halogen atom.

Examples of the halogenating agent to be used include phosphorus oxychloride, phosphorus pentachloride, and mixtures thereof, phosphorus chlorides such as benzoyl chloride-5 phosphorus chloride; triphenylphosphine-phosgene; and triphenphosphine-bromine. And preferably phosphorus oxychloride.

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 a chlorinating agent itself or hexane, heptane, ligroin, petroleum ether. Aliphatic hydrocarbons such as benzene, toluene, xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene; ethyl formate; Esters such as ethyl acetate, propyl acetate, butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; nitro such as nitroethane and nitrobenzene Compounds; Nitriles such as tonitrile and isobutyronitrile; mixed solvents of amides such as formamide, dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide with a chlorinating agent; more preferably chlorination It is a mixed solvent of an agent and an amide.

The reaction temperature ranges from 30 ° C. to 250 ° C., preferably from 80 ° C. to 180 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature, but is usually about 1 hour to 50 hours, preferably 3 hours to 1 hour.
5 hours. Step 22 is a step of reacting the halogenated compound (23) obtained in step 21 with various nucleophilic reagents to produce a compound (Ig).

The nucleophilic reagent to be used is not particularly limited as long as it is one used in a usual nucleophilic reaction. Preferably, alkylamines such as methylamine, dimethylamine, ethylamine and diethylamine; aniline , 4
Aromatic amines such as chloroaniline; aralkylamines such as benzylamine and phenethylamine; cyclic amines such as pyrrolidine, piperidine, morpholine and thiomorpholine; alkylthiols such as methanethiol and ethanethiol; Aromatic thiols; alcohols such as methanol and ethanol; and organic metals such as methyl Grignard can be mentioned, and preferred are cyclic amines.

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 an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethyl formate, ethyl acetate, propyl acetate; Esters such as butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; methanol, ethanol, n-propanol , Isopropanol, n-butanol , Isobutanol - Le, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; and nitroethane and nitrobenzene Nitro compounds; nitriles such as acetonitrile and isobutyronitrile;
Examples include amides such as formamide, dimethylformamide, dimethylacetamide, and hexamethylphosphorotriamide; sulfoxides such as dimethylsulfoxide and sulfolane; or nucleophilic reagents themselves and mixed solvents with the above solvents.

The reaction temperature is from 0 ° C. to 250 ° C., preferably from 30 ° C. to 150 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
It is about from minutes to 50 hours, preferably from 5 minutes to 10 hours. [Method H]

[0129]

Embedded image (In the above formula, R ¹ , R ³ , R ⁴ and R ⁵ have the same meanings as described above.) In step 23, Michael addition of the cyanoacetate (6) to the enone compound (22) in the presence of a base. This is the step of producing compound (24).

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 Inorganic bases such as alkali metal hydroxides such as barium and lithium hydroxide; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide and lithium methoxide; triethylamine, tributylamine, diisopropyl Ethylamine, N-methylmol Phosphorus, 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] undec-7-ene (D
Examples thereof include organic bases such as BU) and organic metal bases such as butyllithium and lithium diisopropylamide, and are preferably alkali metal alkoxides.

In order to carry out the reaction effectively, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride,
Crown ethers such as dibenzo-18-crown-6 can also be added.

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 an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; diethyl ether, diisopropyl ether; Ethers such as tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol , Isoamyl alcohol, diethylene glycol, Alcohols such as serine, octanol, cyclohexanol and methyl cellosolve; nitro compounds such as nitroethane and nitrobenzene; nitriles such as acetonitrile and isobutyronitrile; formamide, dimethylformamide, dimethylacetamide, hexamethylphospho Amides such as rotriamide; and sulfoxides such as dimethyl sulfoxide and sulfolane.

The reaction temperature is from 0 ° C. to 250 ° C., preferably from 30 ° C. to 150 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
0 minutes to 50 hours, preferably 30 minutes to 10 hours
Time. Step 24 is a step of producing a brominated compound (25) by reacting compound (24) with bromine to close the ring.

The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. Preferably, the solvent is an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethyl formate, ethyl acetate, propyl acetate; Esters such as butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; methanol, ethanol, n-propanol , Isopropanol, n-butanol , Isobutanol - Le, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; and nitroethane and nitrobenzene Nitro compounds; nitriles such as acetonitrile and isobutyronitrile;
Organic acids such as formic acid and acetic acid; amides such as formamide, dimethylformamide, dimethylacetamide, and hexamethylphosphorotriamide; and sulfoxides such as dimethyl sulfoxide and sulfolane, and acetic acid is preferred.

The reaction temperature is from 0 ° C. to 250 ° C., preferably from 30 ° C. to 150 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
About 50 hours, preferably about 2 hours to 10 hours.
Time. Step 25 is a step of producing a compound (Ih) by substituting a bromine atom of the brominated compound (25) with various nucleophiles, and can be performed in the same manner as in step 22.
Step 26 is a step of hydrolyzing an ester bond of compound (Ih) to give carboxylic acid derivative (Ii), and can be performed in the same manner as in step 5. In the general formula (I) of the present invention, the compound wherein X and Y are CH at the same time can be produced, for example, according to the following method I. [Method I]

[0136]

Embedded image (In the above formula, R ¹ , R ⁴ , R ⁵ and Z have the same meanings as described above.) In step 27, the acetoacetic ester (26) is converted to a halogen (Z
₂ ) to react to form 4-haloacetoacetate (2)
This is the step of manufacturing 7).

Examples of the halogen used include chlorine, bromine and iodine.

The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. Preferably, the solvent is an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene, xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene; ethyl formate, ethyl acetate, propyl acetate; Esters such as butyl acetate, diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol , Isopropanol, n-butano- , Isobutanol - Le, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; formamide, dimethylformamide, dimethylacetamide;
Amides such as hexamethyl phosphorotriamide can be mentioned, and preferred are halogenated hydrocarbons.

The reaction temperature is from -50 ° C to 150 ° C,
Preferably, it is in the range of -20C to 50C. The reaction time varies depending on the conditions such as the compound and the reaction temperature, but is usually about 1 hour to 50 hours, preferably 5 hours to 20 hours. Step 28 is a step of producing pyridinium salt (28) by reacting pyridine with 4-haloacetoacetic ester (27).

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. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethyl formate, ethyl acetate, propyl acetate; Esters such as butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; methanol, ethanol, n-propanol , Isopropanol, n-butanol , Isobutanol - Le, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; and nitroethane and nitrobenzene Nitro compounds; nitriles such as acetonitrile and isobutyronitrile;
Examples include amides such as formamide, dimethylformamide, dimethylacetamide, and hexamethylphosphorotriamide; and sulfoxides such as dimethyl sulfoxide and sulfolane, and preferably esters.

The reaction temperature is between 0 ° C. and 200 ° C., preferably between 10 ° C. and 100 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
About 50 hours, preferably about 2 hours to 10 hours.
Time. Step 29 is a step of producing a benzoate (Ij) by closing the ring by reacting the pyridinium salt (28) with the compound (22) in the presence of a base.

The base to be used is not particularly limited as long as it is used as a base in a usual reaction. 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 Inorganic bases such as alkali metal hydroxides such as barium and lithium hydroxide; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide and lithium methoxide; sodium formate, sodium acetate; Alkali metal salts of organic carboxylic acids such as potassium acetate Triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N-dimethylamino) pyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3 .0] Nona-5
-Ene, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo [5.4.
0] Organic bases such as undec-7-ene (DBU) or organic metal bases such as butyllithium and lithium diisopropylamide.

In order to carry out the reaction effectively, quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride,
Crown ethers such as dibenzo-18-crown-6 can also be added.

The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. Preferably, the solvent is an aliphatic hydrocarbon such as hexane, heptane, ligroin or petroleum ether. Hydrogens; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethyl formate, ethyl acetate, propyl acetate; Esters such as butyl acetate and diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether; methanol, ethanol, n-propanol , Isopropanol, n-butano- , Isobutanol - Le, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; formamide, dimethylformamide, dimethylacetamide;
Amides such as hexamethyl phosphorotriamide; sulfoxides such as dimethyl sulfoxide and sulfolane can be mentioned, and preferred are alcohols.

The reaction temperature is from 0 ° C. to 250 ° C., preferably from 30 ° C. to 150 ° C. The reaction time varies depending on conditions such as the compound and the reaction temperature.
About 50 hours, preferably about 2 hours to 10 hours.
Time. Step 30 is a step of hydrolyzing the benzoic acid ester (Ij) to produce a benzoic acid derivative (Ik), and can be performed in the same manner as in step 5. After completion of each of the above reactions, the target compound is collected from the reaction mixture according to a conventional method.

For example, the reaction mixture is appropriately neutralized, and if there is any insoluble matter, it is removed by filtration. Then, an immiscible organic solvent such as water and ethyl acetate is added. An organic layer containing the compound is separated, dried over anhydrous magnesium sulfate or the like, and then obtained by distilling off the solvent.

If necessary, the obtained target compound can be obtained by a conventional method.
For example, recrystallization, reprecipitation, or a method commonly used for separation and purification of organic compounds, for example, adsorption column chromatography using a carrier such as silica gel, alumina, and magnesium-silica gel type florisil; Sephadex LH-20 (manufactured by Pharmacia), Amberlite XAD-11 (manufactured by Rohm and Haas),
A method using a synthetic adsorbent such as distribution column chromatography using a carrier such as Diaion HP-20 (manufactured by Mitsubishi Chemical Corporation), a method using ion exchange chromatography,
Alternatively, separation and purification can be performed by appropriately combining a normal phase / reverse phase column chromatography method with silica gel or alkylated silica gel (preferably high performance liquid chromatography) and eluting with a suitable eluent. . The compound of the present invention having the general formula (I) exhibits excellent CD40 function inhibitory activity and is therefore effective as a medicine. Such drugs include, for example, immunosuppressants,
Alternatively, a drug for preventing or treating allergy, rheumatism, autoimmune disease or arteriosclerosis can be mentioned.

The administration form of the compound of the present invention having the general formula (I), a pharmaceutically acceptable salt or derivative thereof includes:
For example, oral administration such as tablets, capsules, granules, powders or syrups, or parenteral administration such as injections or suppositories can be mentioned. These preparations are manufactured by a known method using additives such as excipients, lubricants, binders, disintegrants, stabilizers, flavoring agents, and diluents.

Here, as the excipient, for example, sugar derivatives such as lactose, sucrose, glucose, mannitol, sorbite; corn starch, potato starch, α-
Starch derivatives such as starch, dextrin, carboxymethyl starch; cellulose derivatives such as crystalline cellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium, internally cross-linked sodium carboxymethylcellulose; gum arabic; dextran; Organic excipients such as pullulan; and silicate derivatives such as light silicic anhydride, synthetic aluminum silicate, magnesium metasilicate aluminate; phosphates such as calcium phosphate; carbonates such as calcium carbonate; And inorganic excipients such as sulfates.

Examples of the lubricant include metal stearates such as stearic acid, calcium stearate and magnesium stearate; talc; colloidal silica; waxes such as veegum and gay wax; boric acid: adipic acid; Sodium sulfate, DL-leucine; fatty acid sodium salt; lauryl sulfate such as sodium lauryl sulfate, magnesium lauryl sulfate; silicic acids such as silicic anhydride, silicic acid hydrate; And the above-mentioned starch derivatives.

Examples of the binder include polyvinylpyrrolidone, macrogol, and the same compounds as the above-mentioned excipients.

Examples of the disintegrant include the same compounds as the above-mentioned excipients and chemically modified starch and cellulose such as croscarmellose sodium, sodium carboxymethyl starch and crosslinked polyvinylpyrrolidone.

As the stabilizer, for example, methyl paraben,
Paraoxybenzoic acid esters such as propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol; thimerosal; dehydroacetic acid; and sorbic acid. be able to.

Examples of the flavoring agent include, for example, commonly used sweeteners, acidulants, flavors and the like.

The amount of the compound having the general formula (I) of the present invention, or a pharmaceutically acceptable salt or derivative thereof, varies depending on the condition, age, administration method and the like. 0.1m as a minimum per day
g (preferably 0.5 mg), with an upper limit of 2000 m
g (preferably 500 mg) is desirably administered once or several times depending on the condition. In the case of intravenous administration, the lower limit is 0.1 per day for adults.
01 mg (preferably 0.05 mg), with an upper limit of 2 mg
It is desirable to administer 00 mg (preferably 50 mg) once or in several divided doses according to the symptoms.

Hereinafter, the present invention will be described in more detail with reference to Examples, Preparation Examples and Test Examples, but the present invention is not limited thereto.

[0157]

【Example】

[0158]

Example 1 4-morpholin-4-yl-2,6-diphenyl-
Pyrimidine-5-carboxylic acid ethyl ester (Exemplary Compound No. 1231) (1) 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester A solution of diethyl malonate (2.0 g, 12.48 mmole) in tetrahydrofuran (100 ml) at 0 ° C. Then, sodium hydride (515 mg) was added thereto, followed by stirring for 10 minutes. Furthermore, benzoyl chloride (1.48 ml)
Was added dropwise, and the mixture was stirred at room temperature for 3 hours, and extracted with 1N sodium hydroxide solution. The aqueous layer was acidified by adding concentrated hydrochloric acid and extracted with ether. After the organic layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 2.1 g of a residue. This was dissolved in 50 ml of ethyl acetate, and N-methyl-N-
An ether solution of diazomethane prepared from nitrosoureas (5.5 g) was added, and the mixture was stirred at room temperature for 10 hours. The residue obtained by evaporating the solvent from the reaction solution under reduced pressure was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1), and 1.23 g of 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester Was obtained (34% yield). (2) 4-morpholin-4-yl-2,6-diphenyl-pyrimidine-5-carboxylic acid ethyl ester 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (505 mg, 1.8 mmole) in ethanol (50 ml) ) Was dissolved with benzamidine hydrochloride (360 mg, 2.3 mmole), cooled to 0 ° C., and sodium hydride (250 mg) was added. After the addition was completed, the temperature was raised and the mixture was refluxed under heating for 5 hours. After evaporation of the solvent, the residue was neutralized by adding 1N hydrochloric acid, and extracted with ethyl acetate.
The organic layer was washed with saturated saline, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. Phosphorus oxychloride (6 ml) was added to the obtained residue, and the mixture was stirred at 110 ° C for 30 minutes. After completion of the reaction, phosphorus oxychloride was distilled off under reduced pressure, and morpholine was added to the residue.
(6 ml) was added, and the mixture was heated again to 110 ° C. and stirred for 30 minutes.
After evaporating the solvent to dryness under reduced pressure, the residue was extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over magnesium sulfate. The solvent was distilled off, and the residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1) to obtain 364.5 mg of 4-morpholin-4-yl-2,6-diphenyl-pyrimidine-5-carboxylic acid. The acid ethyl ester was obtained (yield 52%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.00 (t, 3H, J = 7.1 Hz), 3.70 (m, 4H), 3.82 (m, 4H), 4.
05 (q, 2H, J = 7.1Hz), 7.45 (m, 6H), 7.55 (m, 2H), 8.45
(m, 2H).

[0159]

Embodiment 24-morpholin-4-yl-6-phenyl-2-pi
Lysine-3-yl-pyrimidine-5-carboxylic acid potassium salt
(Exemplary Compound No. 1759, potassium salt) (1) 4-morpholin-4-yl-6-phenyl-2-pyridine-
3-yl-pyrimidine-5-carboxylic acid ethyl ester nicotinamidine hydrochloride (638 mg) and 2- (methoxy-fe
Nyl-methylene) -malonic acid diethyl ester (647 mg)
In the same manner as in Example 1- (1), (2) and (3),
560 mg of 4-morpholin-4-yl-6-phenyl-2-
Pyridin-3-yl-pyrimidine-5-carboxylic acid ethyles
Ter was obtained (62% yield). (2) 4-morpholin-4-yl-6-phenyl-2-pyridine-
3-yl-pyrimidin-5-carboxylic acid potassium salt 4-morpholin-4-yl-6-phenyl-2-pyridin-3-yl-
Pyrimidine-5-carboxylic acid ethyl ester (91 mg)
Dissolved in 10 ml of ethanol, and added potassium hydroxide (333 mg).
The mixture was stirred for 24 hours while heating under reflux. After distilling off the solvent, CHP-20 (1%
Acetone aqueous solution) and 72 mg of 4-morpholine
-4-yl-6-phenyl-2-pyridin-3-yl-pyrimidin-5-
A potassium carboxylate was obtained (77% yield).¹ H-nuclear magnetic resonance spectrum (400MHz, DMSO-d₆) δ ppm: 3.70 (m, 4H), 3.90 (m, 4H), 7.37 (m, 3H), 7.44 (m, 1
H), 7.96 (m, 2H), 8.60 (m, 2H), 9.42 (d, 1H, J = 0.9H
z).

[0160]

Embodiment 34-morpholin-4-yl-6-phenyl-2-pi
Lysine-2-yl-pyrimidine-5-carboxylic acid potassium salt
(Exemplary Compound No. 1958, potassium salt) Pyridine-2-carboxyamidine hydrochloride (210 mg) and 2-
(Methoxy-phenyl-methylene) -malonic acid diethyles
Same as Example 2- (1) and (2) using tel (244 mg)
The reaction was carried out as described above, and 33 mg of 4-morpholin-4-yl-6-fe
Nil-2-pyridin-2-yl-pyrimidine-5-carboxylic acid
Lithium salt was obtained (yield 9.3%).¹ H-nuclear magnetic resonance spectrum (400 MHz, CD_ThreeOD) δ ppm: 3.
70 (m, 4H), 3.85 (m, 4H), 7.22 (m, 3H), 7.39 (m, 1H),
7.75 (m, 2H), 7.86 (m, 1H), 8.34 (m, 1H), 8.56 (m, 1
H).

[0161]

Embodiment 44-morpholin-4-yl-6-phenyl-2-pi
Lysine-4-yl-pyrimidine-5-carboxylic acid potassium salt
(Exemplary Compound No. 1760 potassium salt) Isonicotinamidine hydrochloride (207 mg) and 2- (methoxy-
Phenyl-methylene) -malonic acid diethyl ester (248m
Using g), the reaction was carried out in the same manner as in Example 2- (1) and (2).
Perform 118 mg of 4-morpholin-4-yl-6-phenyl-2-pi
Lysine-4-yl-pyrimidine-5-carboxylic acid potassium salt
Was obtained (20% yield).¹ H-nuclear magnetic resonance spectrum (400MHz, DMSO-d₆) δ ppm:
3.70 (m, 4H), 3.90 (m, 4H), 7.40 (m, 3H), 7.95 (m, 2
H), 8.20 (d, 2H, J = 7.8 Hz), 8.85 (d, 2H, J = 7.8 Hz).

[0162]

Example 5 4-morpholin-4-yl-2,6-diphenyl-
Pyrimidine-5-carboxylic acid (Exemplary Compound No. 1775) 4-morpholin-4-yl-2,6-diphenyl- obtained in Example 1
Pyrimidine-5-carboxylic acid ethyl ester (71.4 mg) was dissolved in ethanol (10 ml), potassium hydroxide (478 mg) was added, and the mixture was stirred with heating under reflux for 24 hours. After evaporation of the solvent, 1
The mixture was acidified by adding normal hydrochloric acid, and concentrated under reduced pressure to dryness. Separated and purified with CHP-20 (2% acetone aqueous solution), 45mg
4-morpholin-4-yl-2,6-diphenyl-pyrimidine-5-
A carboxylic acid was obtained. (68% yield) ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
8.35 (m, 2H), 7.96 (m, 2H), 7.46 (m, 3H), 7.35 (m, 3
H), 3.88 (m, 4H), 3.70 (m, 4H).

[0163]

Embodiment 64-benzyl-6-morpholin-4-yl-2-pi
Lysine-2-yl-pyrimidine-5-carboxylic acid potassium salt
(Exemplary Compound No. 3626, potassium salt) (1) 2- (1-methoxy-2-phenyl-ethylidene) -malo
Diethyl ester of diethyl malonate (2.1 g, 13.1 mmole)
Lithium hexamethyldisila at -78 ° C in a run solution (100 ml)
Zan in tetrahydrofuran solution (1.0 M solution, 15 ml) was added dropwise.
And stirred for 10 minutes. Drop of phenylacetyl chloride (2.2 g)
The mixture was stirred at -78 ° C for 1 hour. 1N sodium hydroxide
The aqueous layer was acidified by adding concentrated hydrochloric acid to the aqueous layer.
Then, the mixture was extracted with ether. Organic layer with magnesium sulfate
After drying, the solvent was distilled off under reduced pressure to obtain 1.5 g of a residue. this
Was dissolved in 50 ml of ethyl acetate, and N-methyl-N-nitros
Diazomethane ether solution prepared from rare (2.4 g)
In addition, the mixture was stirred at room temperature for 10 hours. Solvent is distilled from the reaction solution under reduced pressure
The residue obtained is silica gel column chromatography.
(Hexane: ethyl acetate = 5: 1).
2- (1-methoxy-2-phenyl-ethylidene) -malonic acid
The tyl ester was obtained (yield 32%). (2) 4-benzyl-6-morpholin-4-yl-2-pyridine-
2-yl-pyrimidine-5-carboxylic acid ethyl ester pyridine-2-carboxyamidine hydrochloride (177 mg)
Dissolved in 10 ml of ethanol, and
Razan in tetrahydrofuran (1.0 M solution, 1.1 ml) was added dropwise.
After lowering, the mixture was stirred for 10 minutes. In addition, 2- (1-methoxy-2-
Phenyl-ethylidene) -malonic acid diethyl ester (293
mg) in ethanol (5 ml) and stirred under reflux for 2 hours.
Stirred. After completion of the reaction, the solvent was distilled off under reduced pressure to dryness. Profit
5 ml of phosphorus oxychloride was added to the residue obtained, and
While stirring. The solvent was distilled off under reduced pressure to dryness. Got
The residue was extracted with ethyl acetate, silica gel column chromatography
Separation and purification by chromatography (hexane: ethyl acetate = 4: 1).
25.7 mg of 4-benzyl-6-morpholin-4-yl-2-pyri
Gin-2-yl-pyrimidine-5-carboxylic acid ethyl ester
Was obtained (yield 6.5%). (3) 4-benzyl-6-morpholin-4-yl-2-pyridine-
2-yl-pyrimidine-5-carboxylic acid potassium salt 4-benzyl-6-morpholin-4-yl-2-pyridin-2-yl-
Pyrimidine-5-carboxylic acid ethyl ester (25.7 mg) was added.
Dissolve in 10 ml of ethanol, add potassium hydroxide (300 mg)
Then, the mixture was stirred under heating and reflux for 10 hours. Evaporate the solvent under reduced pressure
To dryness. Separated and purified by CHP-20 (10% acetone aqueous solution), 1
5 mg of 4-benzyl-6-morpholin-4-yl-2-pyridin-2-
Yl-pyrimidine-5-carboxylic acid potassium salt was obtained (yield
60%).¹ H-nuclear magnetic resonance spectrum (400 MHz, CD_ThreeOD) δ ppm: 3.
70 (m, 4H), 3.75 (m, 4H), 4.10 (s, 2H), 7.10 (t, 1H, J
= 7.8Hz), 7.18 (t, 1H, J = 7.8Hz), 7.39 (m, 3H), 7.86 (m,
 1H), 8.34 (m, 1H), 8.56 (m, 1H).

[0164]

Embodiment 74-benzyl-6-morpholin-4-yl-2-pi
Lysine-3-yl-pyrimidine-5-carboxylic acid potassium salt
(Exemplary Compound No. 3627. Potassium Salt) (1) 4-benzyl-6-morpholin-4-yl-2-pyridine-
Dissolve 3-yl-pyrimidine-5-carboxylic acid ethyl ester nicotinamidine hydrochloride (126 mg) in 10 ml of ethanol
At room temperature
After dropwise addition of a hydrofuran solution (1.0 M solution, 0.9 ml), 10
Stirred for minutes. To this, 2- (1-methoxy-2-phenyl-e
(Tylidene) -malonic acid diethyl ester (208mg)
Then, the reaction mixture was added with stirring and refluxed for 2 hours. reaction
After completion, the solvent was distilled off under reduced pressure to dryness. To the obtained residue
5 ml of phosphorus oxychloride was added, and the mixture was stirred at 100 ° C. for 2 hours.
The solvent was distilled off under reduced pressure to dryness. Acetic acid from the obtained residue
Extract with chilled silica gel column chromatography
(Hexane: ethyl acetate = 4: 1).
Benzyl-6-morpholin-4-yl-2-pyridin-3-yl-pi
Limidine-5-carboxylic acid ethyl ester was obtained (yield 26
%). (2) 4-benzyl-6-morpholin-4-yl-2-pyridine-
3-yl-pyrimidin-5-carboxylic acid potassium salt 4-benzyl-6-morpholin-4-yl-2-pyridin-3-yl-
Pyrimidine-5-carboxylic acid ethyl ester (76 mg)
Dissolved in 10 ml of ethanol, and added potassium hydroxide (281 mg).
Then, the mixture was stirred under heating and reflux for 10 hours. Evaporate the solvent under reduced pressure
To dryness. Separation and purification with CHP-20 (8% acetone aqueous solution), 21
mg of 4-benzyl-6-morpholin-4-yl-2-pyridin-3-i
This yielded potassium pyr-pyrimidine-5-carboxylate (yield 30
%).¹ H-nuclear magnetic resonance spectrum (400 MHz, CD_ThreeOD) δ ppm: 3.
75 (m, 2H), 3.85 (m, 2H), 4.20 (s, 2H), 7.20 (m, 3H),
7.50 (m, 3H), 8,50 (m, 2H), 8.70 (m, 1H), 9,38 (s, 1
H).

[0165]

Embodiment 84-benzyl-6-morpholin-4-yl-2-pi
Lysine-4-yl-pyrimidine-5-carboxylic acid potassium salt
(Exemplified Compound No. 3628 potassium salt) Isonicotinamidine hydrochloride (137 mg) and 2- (1-methoxy)
(Cy-2-phenyl-ethylidene) -malonic acid diethyl ester
The reaction was carried out in the same manner as in Example 7- (1) using toluene (228 mg).
121 mg of 4-benzyl-6-morpholin-4-yl-2-pyridi
4-ethyl-pyrimidine-5-carboxylic acid ethyl ester
Was obtained (38% yield).

This was treated in the same manner as in Example 7- (2) to give 81 mg of 4-benzyl-6-morpholin-4-yl-2-pyridin-4-yl-pyrimidine-5-carboxylic acid potassium salt Got
(66% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 3.
75 (m, 2H), 3.85 (m, 2H), 4.20 (s, 2H), 7.15 (t, 1H, J
= 8.2Hz), 7.25 (t, 2H, J = 8.2Hz), 7.45 (t, 2H, J = 8.2H
z), 8.25 (d, 2H, J = 7.6Hz), 8.60 (d, 2H, J = 7.6Hz).

[0167]

Example 9 4-benzyl-6-morpholin-4-yl-2-fu
Phenyl-pyrimidine-5-carboxylic acid potassium salt (exemplified compound No. 3625, potassium salt) benzamidine hydrochloride (125 mg) and 2- (1-methoxy-2-phenyl-ethylidene) -malonic acid diethyl ester (202 m
g) was used to carry out a reaction in the same manner as in Example 7- (1).
g of 4-benzyl-6-morpholin-4-yl-2-phenyl-pyrimidine-5-carboxylic acid ethyl ester was obtained (yield 35
%).

This was treated in the same manner as in Example 7- (2) to obtain 45 mg of potassium 4-benzyl-6-morpholin-4-yl-2-phenyl-pyrimidine-5-carboxylic acid potassium salt ( Yield 46
%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 3.
70 (m, 4H), 3.75 (m, 4H), 4.10 (s, 2H), 7.10 (t, 1H, J
= 7.8Hz), 7.19 (t, 2H, J = 7.8Hz), 7.35 (m, 3H), 7.39 (d,
2H, J = 7.8Hz), 8.19 (m, 2H).

[0169]

Embodiment 104-methyl-6-morpholin-4-yl-2-pi
Lysine-2-yl-pyrimidine-5-carboxylic acid potassium salt
(Exemplary Compound No. 3794, potassium salt) (1) 2- (1-Methoxy-ethylidene) -malonic acid diethyl
(Method 1) Diethyl malonate (2.1 g, 13.1 mmole)
To a drofuran solution (100 ml) at -78 ° C
Ludisilazane in tetrahydrofuran solution (1.0 M solution, 15 m
l) was added dropwise and stirred for 10 minutes. Drop of acetyl chloride (1 ml)
The mixture was stirred at -78 ° C for 1 hour. To this, add 1N hydrochloric acid dropwise.
After stopping the reaction by lowering, the mixture was diluted and extracted with ethyl acetate. Organic layer
Was washed with saturated saline and dried over anhydrous magnesium sulfate.
The solvent was distilled off under reduced pressure. The obtained residue is washed with 50 ml of ethyl acetate.
Dissolve in N-methyl-N-nitrosourea (2.4 g)
Add the prepared diazomethane ether solution and add
While stirring. The residue obtained by evaporating the solvent from the reaction solution under reduced pressure
To silica gel column chromatography (hexane: vinegar)
(Ethyl acetate = 2: 1).
(Tylidene) -malonic acid diethyl ester was obtained (yield 37
%).

(Method 2) Sodium hydride (643 mg) was dissolved in 100 ml of tetrahydrofuran, and diethyl malonate was added at 0 ° C.
(2.4 ml) was added dropwise. After stirring at 0 ° C for 15 minutes, the mixture was cooled to -78 ° C, acetyl chloride was added dropwise, and the mixture was further stirred at -78 ° C for 2 hours. To this, a 1N aqueous hydrochloric acid solution was added dropwise to stop the reaction. After diluting and extracting with ether, the organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 100 ml of ethyl acetate, and an ether solution of diazomethane prepared from N-nitrosomethylurea (7.4 g) was added thereto, followed by stirring at room temperature for 10 hours.
The solvent was distilled off under reduced pressure, and the residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give 2- (1-methoxy-ethylidene) -malonic acid diethyl ester (2.29
g) was obtained.

Pyridine-2-carboxyamidine hydrochloride (3
51 mg) was dissolved in 10 ml of ethanol, and a solution of lithium hexamethyldisilazane in tetrahydrofuran (2.2 ml of a 1.0 M solution) was added dropwise at room temperature. After stirring for 10 minutes, an ethanol solution (5 ml) of 2- (1-methoxy-ethylidene) -malonic acid diethyl ester (417 mg) was added, and the mixture was stirred with heating under reflux for 2 hours. After completion of the reaction, the solvent was distilled off under reduced pressure to dryness. 5 ml of phosphorus oxychloride was added to the obtained residue, and the mixture was stirred at 100 ° C for 2 hours.
The solvent was distilled off under reduced pressure to dryness. The residue obtained was extracted with ethyl acetate and subjected to silica gel column chromatography.
(Hexane: ethyl acetate = 4: 1).
Methyl-6-morpholin-4-yl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid ethyl ester (12%) was obtained. (2) 4-methyl-6-morpholin-4-yl-2-pyridin-2-
Ethyl-pyrimidine-5-carboxylic acid potassium salt 4-methyl-6-morpholin-4-yl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid ethyl ester (80 mg) was dissolved in ethanol (10 ml) and hydroxylated. Add potassium (300mg),
The mixture was stirred for 10 hours under reflux. The solvent was distilled off under reduced pressure to dryness. Separated and purified with CHP-20 (10% acetone aqueous solution), 63mg
4-Methyl-6-morpholin-4-yl-2-pyridin-2-yl-
Pyrimidine-5-carboxylic acid potassium salt was obtained (yield 76
%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 2.
53 (s, 3H), 3.78 (m, 4H), 3.88 (m, 4H), 7.45 (dd, 1H,
J = 7.8, 1.2Hz), 7.95 (dt, 1H, J = 7.8, 1.2Hz), 8.35 (d,
1H, J = 7.8Hz), 8.65 (dd, 1H, J = 7.8, 1.2Hz).

[0172]

Embodiment 114-methyl-6-morpholin-4-yl-2-pi
Lysine-3-yl-pyrimidine-5-carboxylic acid potassium salt
(Exemplary Compound No. 3795. Potassium Salt) (1) 4-Methyl-6-morpholin-4-yl-2-pyridin-3-i
Dissolve pyrimidine-5-carboxylic acid ethyl ester nicotinamidine hydrochloride (162 mg) in 10 ml of ethanol.
At room temperature
Hydrofuran solution (1.0 M solution, 1.1 ml) was added dropwise. 10 minutes
After stirring for 2 hours, 2- (1-methoxy-ethylidene) -malonic acid die
A solution of tyl ester (196 mg) in ethanol (10 ml) was added and 2
The mixture was stirred with heating under reflux for an hour. After completion of the reaction, the solvent is distilled off under reduced pressure.
Left to dryness. 5 ml of phosphorus oxychloride was added to the obtained residue.
Then, the mixture was stirred at 100 ° C. for 2 hours.

The solvent was distilled off under reduced pressure to dryness. The residue obtained was extracted with ethyl acetate, separated and purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1), and 56 mg of 4-methyl-6-morpholin-4-yl-2-pyridine-
3-yl-pyrimidine-5-carboxylic acid ethyl ester was obtained (18% yield). (2) 4-methyl-6-morpholin-4-yl-2-pyridine-3-
Ill-pyrimidine-5-carboxylic acid potassium salt 4-methyl-6-morpholin-4-yl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid ethyl ester (56 mg) was dissolved in ethanol 10 ml, and Add potassium (280mg),
The mixture was stirred for 10 hours under reflux. The solvent was distilled off under reduced pressure to dryness. Separated and purified with CHP-20 (distilled water), 32 mg of 4-methyl-6
-Morpholin-4-yl-2-pyridin-3-yl-pyrimidin-5-
A potassium carboxylate was obtained (56% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 2.
40 (s, 3H), 3.65 (m, 4H), 3.78 (m, 4H), 7.40 (t, 1H, J
= 7.8Hz), 8.45 (d, 1H, J = 7.8), 8.50 (dd, 1H, J = 7.8, 1.
1 Hz), 9.38 (d, 1H, J = 1.1 Hz).

[0174]

Embodiment 124-methyl-6-morpholin-4-yl-2-pi
Lysine-4-yl-pyrimidine-5-carboxylic acid potassium salt
(Exemplary Compound No. 3796 potassium salt) Isonicotinamidine hydrochloride (390 mg) and 2- (1-methoxy)
(Diethylidene) -malonic acid diethyl ester (452mg)
The reaction was carried out in the same manner as in Example 11- (1), and 110 mg
4-Methyl-6-morpholin-4-yl-2-pyridin-4-yl-
Pyrimidine-5-carboxylic acid ethyl ester was obtained (yield 1
Five%).

This was treated with ethanol-potassium hydroxide in the same manner as in Example 1- (2) to give 94 mg of 4-methyl-6-
Morpholin-4-yl-2-pyridin-4-yl-pyrimidin-5-
A potassium carboxylate was obtained (83% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 2.
50 (s, 3H), 3.75 (m, 4H), 3.85 (m, 4H), 8.26 (d, 2H, J
= 7.5Hz), 8.62 (d, 2H, J = 7.5Hz).

[0176]

Example 13 4-Methyl-6-morpholin-4-yl-2-fu
Enyl-pyrimidine-5-carboxylic acid potassium salt (exemplified compound No. 3793, potassium salt) Example 11- using benzamidine hydrochloride (440 mg) and 2- (1-methoxy-ethylidene) -malonic acid diethyl ester (560 mg) The reaction was carried out in the same manner as in (1) to obtain 360 mg of ethyl 4-methyl-6-morpholin-4-yl-2-phenyl-pyrimidine-5-carboxylate (yield 42%).

24 mg of this was treated with ethanol-potassium hydroxide in the same manner as in Example 1- (2), and 19 mg of 4-
Methyl-6-morpholin-4-yl-2-phenyl-pyrimidine-5
-Potassium carboxylate was obtained (78% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 2.
40 (s, 3H), 3.66 (m, 4H), 3.78 (m, 4H), 7.35 (m, 3H),
8.18 (m, 2H).

[0178]

Example 14 4-cyclohexylamino-6-phenyl-
2-pyridin-3-yl-pyrimidine-5-carboxylic acid ethyl ester
Stell (Exemplified Compound No. 1603) 2- (Methoxy-phenyl-methylene) -malonic acid diethyl ester (2.2 g) and nicotinamidine hydrochloride (1.3 g) were dissolved in 200 ml of ethanol, and metal sodium (532 mg) was added at 0 ° C.
And stirred. After the metallic sodium was completely dissolved, the temperature was raised and the mixture was refluxed for 24 hours. The solvent was distilled off, 1N hydrochloric acid was added dropwise, and the deposited precipitate was collected by filtration, sufficiently washed with hexane and ether, and dried, and 910 mg of 6-oxo-4-phenyl-2-pyridine-3-y. Yl-1,6-dihydro-pyrimidine-5
-Carboxylic acid ethyl ester was obtained (36% yield).

6-oxo-4-phenyl-2-pyridin-3-yl-
1,6-Dihydro-pyrimidine-5-carboxylic acid ethyl ester (138 mg) was dissolved in phosphorus oxychloride (4 ml),
Stirred for hours. The solvent was distilled off under reduced pressure, and the obtained residue was extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off.
The residue was dissolved in cyclohexylamine (4ml) and at 110 ° C for 1.
Stir for 5 hours. The solvent was distilled off under reduced pressure, and the obtained residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1) to obtain 113 mg of 4-cyclohexylamino-6-phenyl-2-pyridin-3-yl -Pyrimidine-5-carboxylic acid ethyl ester was obtained (yield 65%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
20-1.70 (m, 6H), 1.82 (m, 2H), 2.15 (m, 2H), 3.98 (q,
2H, J = 6.8Hz), 4.30 (m, 1H), 7.42 (m, 3H), 7.58 (m, 2
H), 7.65 (br.s, 1H), 8.70 (m, 2H), 9.70 (d, 1H, J = 1.1H
z).

[0180]

Example 15 2-methyl-4-morpholin-4-yl-6-fu
Ethyl-pyrimidine-5-carboxylic acid ethyl ester (Exemplary Compound No. 1289) Acetamidine hydrochloride (309 mg) and 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (860 mg) were dissolved in 50 ml of ethanol and hydrogenated. Sodium (400 mg) was added, and the mixture was heated under reflux for 10 hours. The solvent was distilled off and the residue was dried, phosphorus oxychloride (4 ml) was added to the residue, and the mixture was stirred at 110 ° C for 2 hours. The solvent was distilled off under reduced pressure, morpholine (4 ml) was added to the residue, and the mixture was stirred at 110 ° C for 2 hours. The solvent was distilled off under reduced pressure, and the residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1) to give 348 mg of 2-methyl-4-morpholin-4-yl-6-phenyl-pyrimidine-5-carboxylic acid. The acid ethyl ester was obtained (yield 35%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 0.
85 (t, 3H, J = 6.8Hz), 2.51 (s, 3H), 3.55 (m, 4H), 3.72
(m, 4H), 3.91 (q, 2H, J = 6.8Hz), 7,34 (m, 5H).

[0181]

Example 16 4-Methyl-6-morpholin-4-yl-2-fu
Enyl-pyrimidine-5-carboxylic acid ethyl ester (exemplified compound No. 3807) Example 11- (1) using benzamidine hydrochloride (440 mg) and 2- (1-methoxy-ethylidene) -malonic acid diethyl ester (560 mg) The reaction was carried out in the same manner as described above to obtain 360 mg of ethyl 4-methyl-6-morpholin-4-yl-2-phenyl-pyrimidine-5-carboxylate (yield 42%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
36 (t, 3H, J = 6.8Hz), 3.60 (m, 4H), 3.70 (m, 4H), 4.28
(q, 2H, J = 6.8Hz), 7.38 (m, 3H), 8.30 (m, 2H).

[0182]

Embodiment 172-benzyl-4-morpholin-4-yl-6-
Phenyl-pyrimidine-5-carboxylic acid ethyl ester
(Exemplary Compound No. 1275) (1) Dissolve 2-phenyl-acetamidine hydrochloride phenylacetonitrile (9.8 g) in 200 ml of ethanol
And saturated with hydrogen chloride gas at 0 ° C, and stirred at -20 ° C for 48 hours.
Stirring. A large amount of ether was added to dilute the reaction solution,
The crystals were collected by filtration and dried sufficiently. Dissolve this in an appropriate amount of water
Then, the mixture was neutralized with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate.
The organic layer was washed with saturated saline and then dried over anhydrous magnesium sulfate.
It was dried and the solvent was distilled off under reduced pressure. This is ethanol 10
Dissolve in 0 ml, add ammonium chloride (2.05 g) and heat to reflux
Stirred for 5 hours. The solvent was distilled off under reduced pressure to dryness. Remaining
The residue is crystallized and washed thoroughly with ethyl acetate to give 5.92 g of 2
-Phenyl-acetamidine hydrochloride was obtained (90% yield). (2) 2-benzyl-4-morpholin-4-yl-6-phenyl-
Pyrimidine-5-carboxylic acid ethyl ester 2-phenyl-acetamidine hydrochloride (371 mg) and 2- (meth
(Xy-phenyl-methylene) -malonic acid diethyl ester
(594 mg) in 50 ml of ethanol
(216 mg) was added at 0 ° C., and the mixture was stirred. Sodium hydride is complete
After complete dissolution, the mixture was heated and stirred under heating and reflux for 10 hours.
The solvent was distilled off under reduced pressure to dryness. Phosphorus oxychloride (4
ml) and stirred at 110 ° C. for 2 hours. Bring the reaction to room temperature
After cooling under reduced pressure, phosphorus oxychloride was distilled off under reduced pressure.
Morpholine (5 ml) was added to the residue and stirred at 110 ° C for 4 hours.
Stirred. The solvent was distilled off under reduced pressure to dryness. Acetic acid from the residue
Extracted with chill. After washing the organic layer with saturated saline,
Dry with magnesium silicate and use silica gel column chromatography
Raffy (hexane: ethyl acetate = 4: 1).
66 mg of 2-benzyl-4-morpholin-4-yl-6-phenyl-pi
Limidine-5-carboxylic acid ethyl ester was obtained (yield 43
%).¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl_Three) δ ppm: 0.
95 (t, 3H, J = 6.8Hz), 3.64 (m, 4H), 3,74 (m, 4H), 3.98
(q, 2H, J = 6.8Hz), 4.16 (s, 2H), 7.26 (m, 3H), 7.24
(m, 7H).

[0183]

Example 18 2-butyl-4-morpholin-4-yl-6-fu
Ethyl-pyrimidine-5-carboxylic acid ethyl ester (Exemplary Compound No. 1293) (1) Butylamidine hydrochloride Capronitrile (7.4 g) was added to ethanol (6 ml), and hydrogen chloride gas was saturated. This was stirred at −20 ° C. for 48 hours.
The solvent was distilled off under reduced pressure to dryness. Hexane was added thereto, and the mixture was vigorously stirred, and the precipitated crystals were collected by filtration and dried sufficiently. This was dissolved in an appropriate amount of ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, and the organic layer was dried over anhydrous magnesium sulfate. The obtained residue was dissolved in 100 ml of ethanol, to which 1.38 g of ammonium chloride was added, and the mixture was stirred with heating under reflux for 4 hours. After completion of the reaction, the solvent was distilled off under reduced pressure to dryness. The obtained residue was sufficiently washed with hexane and ether, and then dried to obtain 2.5 g of butylamidine hydrochloride
(Yield 20%). (2) 2-butyl-4-morpholin-4-yl-6-phenyl-pyrimidine-5-carboxylic acid ethyl ester butylamidine hydrochloride (279 mg) and 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester ( (512 mg) was dissolved in 50 ml of ethanol, and sodium hydride (222 mg) was added thereto, followed by stirring. After the sodium hydride was completely dissolved, the mixture was heated and stirred for 10 hours while heating under reflux. The solvent was distilled off under reduced pressure to dryness. The residue was sufficiently washed with hexane, acidified with 1N hydrochloric acid, and then concentrated to dryness under reduced pressure. The residue was dissolved in chloroform, washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. To this was added phosphorus oxychloride, and the mixture was stirred at 110 ° C for 1.5 hours. The reaction solution was added dropwise to ice water, stirred sufficiently, and extracted with ethyl acetate.
The organic layer was washed with a 1N sodium hydroxide solution and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Morpholine (4 ml) was added to the obtained residue, and the mixture was heated to 110 ° C.
For 2 hours. Dilute the reaction solution with ethyl acetate and water,
After sufficiently washing with saturated saline, drying over anhydrous magnesium sulfate, separation and purification by silica gel column chromatography (hexane: ethyl acetate = 4: 1), 293 mg of 2-butyl-4-morpholin-4-yl-6 -Phenyl-pyrimidine-5-carboxylic acid ethyl ester was obtained (yield 43%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 0.
96 (t, 6H, J = 6.8Hz), 1.40 (m, 2H), 1.79 (quint, 2H, J
= 6.8Hz), 2.80 (q, 2H, J = 6.8Hz), 3.64 (m, 4H), 3.76 (m,
4H), 4.01 (q, 2H, J = 6.8Hz), 7.23 (m, 3H), 7.26 (m, 2
H).

[0184]

Embodiment 194-morpholin-4-yl-6-octyl-2-
Phenyl-pyrimidine-5-carboxylic acid ethyl ester
(Exemplary Compound No. 4129) (1) 2-Nonanoyl-malonic acid diethyl ester Diethyl malonate (2.49 g) is added to 100 ml of tetrahydrofuran.
Dissolve and add sodium hydride at 0 ° C under nitrogen atmosphere
(622 mg) was added and the mixture was stirred at 0 ° C for 1 hour. Cool the reaction to -78 ° C
Nonanoyl chloride (2.7 g) was added dropwise. 2 at -78 ° C
After stirring for an hour, ether was added for dilution extraction. Organic layer
After washing with saturated ammonium chloride solution and saturated saline,
The extract was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure.
Ricagel column chromatography (hexane: acetic acid
Chill = 8: 1) and purified by 3g of 2-nonanoyl-malone
The acid diethyl ester was obtained (65% yield). (2) 2- (1-methoxy-nonylidene) -malonic acid diethyl
2-nonanoyl-malonic acid diethyl ester obtained in (1)
(3 g) was dissolved in ethyl acetate (100 ml) and N-methyl-N-nitro
Diazomethane ether solution prepared from sourea (5g)
Was added dropwise and the mixture was stirred at room temperature for 10 hours. Evaporate the solvent under reduced pressure
The residue was subjected to silica gel column chromatography (hexane:
Separation and purification with ethyl acetate = 5: 1), 2.6 g of 2- (1-methoxy)
-Nonylidene) -malonic acid diethyl ester was obtained (yield 8
6%). (3) 4-morpholin-4-yl-6-octyl-2-phenyl-
Pyrimidine-5-carboxylic acid ethyl ester benzamidine hydrochloride (271 mg), 2- (1-methoxy-nonylyl)
(Den) -malonic acid diethyl ester (532mg) in ethanol
It was dissolved in 50 ml, and 171 mg of sodium hydride was added at 0 ° C.
After the sodium hydride is completely dissolved, raise the temperature and return
The mixture was stirred for 10 hours under flowing water. The solvent was distilled off under reduced pressure, and the residue was treated with acetic acid
The mixture was diluted with ethyl and washed with 1N hydrochloric acid. Saturate organic layer
After washing with brine, dry over anhydrous magnesium sulfate and depressurizing
The solvent was distilled off under. Add 6 ml of phosphorus oxychloride to this and add 1
The mixture was stirred at 10 ° C for 2 hours. Add the reaction solution to ice water and stir well
After that, the mixture was extracted with ethyl acetate. Organic layer with saturated saline
After washing, the extract is dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure.
Removed and concentrated. Add 6 ml of morpholine to this and add
Stirred for hours. Dilute the reaction with ethyl acetate and saturate with water
After washing with brine, dry over anhydrous magnesium sulfate and depressurizing
The solvent was distilled off under. The obtained residue is applied to a silica gel column.
Separation by chromatography (hexane: ethyl acetate = 2: 1)
Purified to give 325 mg of 4-morpholin-4-yl-6-octyl-2-
Phenyl-pyrimidine-5-carboxylic acid ethyl ester (45
%).¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl_Three) δ ppm: 0.
92 (t, 3H, J = 6.8Hz), 1.2-1.5 (br.m, 13H), 1.8 (br.s,
2H), 2.9 (br.s, 2H), 3.70 (m, 4H), 3.81 (m, 4H), 4.40
(q, 2H, J = 6.8Hz), 7.50 (br.s, 2H), 8.45 (br.s, 2H).

[0185]

Example 20 4-morpholin-4-yl-6-phenyl-2-
Ethyl trifluoromethyl-pyrimidine-5-carboxylate
Ester (Exemplified Compound No. 1301) 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (558 mg) and trifluoroacetamidine (256 mg)
Was dissolved in 50 ml of ethanol, and sodium hydride (23
0 mg) was added. After the sodium hydride is completely dissolved,
The temperature was raised, and the mixture was stirred for 10 hours under heating and reflux. The solvent was concentrated under reduced pressure to dryness. 6 ml of phosphorus oxychloride was added to the obtained residue, and the mixture was stirred at 110 ° C for 2 hours. After the reaction solution was poured into ice water and sufficiently stirred, it was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. 4 ml of morpholine was added thereto, and the mixture was stirred at 110 ° C. for 4 hours. The reaction solution was diluted with ethyl acetate, washed sufficiently with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Separation and purification by silica gel column chromatography (hexane: ethyl acetate = 4: 1), 163 mg
To give 4-morpholin-4-yl-6-phenyl-2-trifluoromethyl-pyrimidine-5-carboxylic acid ethyl ester (22%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 0.
95 (t, 3H, J = 6.4Hz), 3.70 (m, 4H), 3.80 (m, 4H), 4.06
(q, 2H, J = 6.4), 7.43 (m, 3H), 7.52 (m, 2H).

[0186]

Example 21 4-butyl-6-morpholin-4-yl-2-f
Enyl-pyrimidine-5-carboxylic acid ethyl ester (Exemplary Compound No. 4073) (1) 2- (1-methoxy-pentylidene) -malonic acid diethyl ester Diethyl malonate (2.5 g) was dissolved in 100 ml of tetrahydrofuran, and sodium hydride was added. (700 mg) was added and the mixture was stirred at room temperature for 10 minutes. After cooling to -78 ° C, valeryl chloride (1.9 ml) was added dropwise. After stirring at -78 ° C for 1.5 hours, a saturated aqueous ammonium chloride solution was added dropwise to stop the reaction, and the reaction solution was diluted with ether and extracted. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 100 ml of ethyl acetate, and N-methyl-N-
An ether solution of diazomethane prepared from nitrosoureas (6 g) was added, and the mixture was stirred at room temperature for 10 hours. The residue obtained by evaporating the solvent under reduced pressure was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 8: 1) to give 2.6 g of 2
-(1-Methoxy-pentylidene) -malonic acid diethyl ester was obtained (yield 43%). (2) 4-Butyl-6-morpholin-4-yl-2-phenyl-pyrimidine-5-carboxylic acid ethyl ester Benzamidine hydrochloride (233 mg) was dissolved in 40 ml of ethanol, and sodium hydride was added at 0 ° C. After the addition was completed, the temperature was raised to room temperature, and the mixture was stirred for 10 minutes. To this solution 2- (1-methoxy-pentylidene) -malonic acid diethyl ester (370mg)
Was added dropwise at room temperature. After the completion of the dropwise addition, the temperature was raised, and the mixture was stirred for 2 hours under reflux. The solvent was distilled off under reduced pressure and concentrated. Ethyl acetate was added to the residue for dilution, and the organic layer was washed with 1N hydrochloric acid and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. To this was added 6 ml of phosphorus oxychloride, and the mixture was stirred at 110 ° C. for 1.5 hours. The reaction solution was diluted with ethyl acetate, poured into ice water and stirred sufficiently. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.

4 ml of morpholine was added to the obtained residue,
For 2 hours. The solvent was distilled off under reduced pressure, and the residue was diluted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Silica gel column chromatography (hexane: ethyl acetate = 5: 1)
176 mg of 4-butyl-6-morpholin-4-yl-
2-Phenyl-pyrimidine-5-carboxylic acid ethyl ester was obtained (33% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 0.
95 (t, 3H, J = 6.6Hz), 1.40 (m, 5H), 1.78 (m, 2H), 2.79
(t, 2H, J = 6.7Hz), 3.65 (m, 4H), 3.80 (m, 4H), 4.39 (q,
2H, J = 6.6Hz), 7.55 (m, 3H), 8.40 (m, 2H).

[0188]

Example 22 5-Cyano-6- (methylthio) -4-morpholine
No-2-phenylpyrimidine (Exemplified Compound No. 3709) 0.8 ml of morpholine is added to 4-chloro-5-cyano-6- (methylthio) -2-phenylpyrimidine (100 mg, 0.37 mmol), and the mixture is heated to 80 ° C.
After stirring for 1 hour, the mixture was poured into ice water and the precipitate was collected by filtration. The precipitate was dissolved in chloroform, dried over magnesium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography (dichloromethane) to give 100 mg of the title compound.
Was obtained (yield 84%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2202, 1532, 1
384, 986. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 2.
73 (s, 3H,), 3.79-3.89 (m, 4H), 4.05-4.12 (m, 4H), 7.4
0-7.60 (m, 3H), 8.35-8.45 (m, 2H). Mass spectrum (m / z): 312 (M ⁺ ).

[0189]

Example 23 4-Morpholino-2-phenylquinazoline (exemplary compound number) Using 4-chloro-2-phenylquinazoline (100 mg, 0.40 mmol), the reaction was carried out in the same manner as in the latter part of Example 21- (2). ,
86 mg of the title compound was obtained (yield 73%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 1566, 1538, 1
503, 1354, 1113, 770, 711. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 3.
86 (t, 4H, J = 4.6Hz), 3.96 (t, 4H, J = 4.6Hz), 7.41
-8.59 (m, 9H). Mass spectrum (m / z): 292 (M ⁺⁺ 1).

[0190]

Example 24 5-Cyano-2-methyl-6- (methylthio) -4
-Morpholino-pyrimidine (Exemplary Compound No. 3716) In the same manner as in the latter part of Example 21- (2) using 4-chloro-5-cyano-2-methyl-6- (methylthio) -pyrimidine (100 mg, 0.50 mmol). The reaction was carried out to obtain 82 mg of the title compound (yield 65.
6%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2201, 1537, 1
521, 1117cm ^{-1 1} H- nuclear magnetic resonance spectrum _{(400MHz, CDCl 3) δ ppm} : 2.
48 (s, 3H), 2.58 (s, 3H,), 3.77 (t, 4H, J = 4.8Hz), 3.
96 (t, 4H, J = 4.8 Hz). Mass spectrum (m / z): 250 (M ⁺ ).

[0191]

Example 25 2- (methylthio) -4-morpholino-5-pyri
Ethyl spermidine carboxylic acid [using (Compound No. 3861) of ethyl 4-chloro-2-methylthio-5-pyrimidine carboxylate (100 mg, 0.42 mmol) Example 21 (2)
The reaction was carried out in the same manner as in the latter step to obtain 100 mg of the title compound.
(Yield 84%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 1704, 1563, 1
536, 1157. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
36 (t, 3H, J = 7.3Hz), 2.51 (s, 3H), 3.62 (t, 4H, J =
4.8Hz), 3.78 (t, 4H, J = 4.8Hz), 4.32 (q, 2H, J = 7.
3Hz), 8.59 (s, 1H). Mass spectrum (m / z): 283 (M ⁺ ).

[0192]

Example 26 6-Methyl-2,4-dimorpholino-pyrimidi
Down (Compound No. 4213) 2,4-dichloro-6-methylpyrimidine (100 mg, 0.61 mmol) subjected to the same reaction as the subsequent Example 21- (2) using a silica gel column chromatography (chloroform: acetic acid Purification with ethyl (3: 1) yielded 30 mg of the title compound (19% yield). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2853, 1577, 1
555, 1240, 1119. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 2.
24 (s, 3H), 3.59 (m, 4H), 3.74-3.77 (m, 12H), 5.76 (s,
1H). Mass spectrum (m / z): 264 (M ⁺ ).

[0193]

Example 27 2,4-Dimethoxy-6-morpholinopyrim
Gin 6-chloro-2,4-dimethoxypyrimidine (100 mg, 0.57 mmol)
The reaction was carried out in the same manner as in the latter part of Example 21- (2) using the above to obtain 60 mg (47%) of the title compound 6. Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 1605, 1371, 1
228, 792. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 3.
55 (t, 4H, J = 5.0Hz), 3.76 (t, 4H, J = 5.0Hz), 3.91
(s, 3H), 3.92 (s, 3H), 5.49 (s, 1H). Mass spectrum (m / z): 225 (M ⁺ ).

[0194]

Example 28 4,6-Dimorpholino-5-nitropyrimidi
Down performs the same reaction as the subsequent implementation using (Compound No. 3927) 4,6-dichloro-5-nitropyrimidine (100 mg, 0.5 mmol) Example 21 (2), to give 135mg of the title compound (yield Rate 92%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 1558, 1292, 1
234, 1114. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 3.
74 (t, 4H, J = 4.7Hz), 3.83 (t, 4H, J = 4.7Hz), 7.94
(s, 1H). Mass spectrum (m / z): 295 (M ⁺ ).

[0195]

Example 29 5-cyano-6- (methylthio) -2-phenyl
-4-piperidinyl pyrimidine (Exemplary Compound No. 371)
7) 0.8 ml of piperidine is added to 4-chloro-5-cyano-6- (methylthio) -2-phenylpyrimidine (100 mg, 0.37 mmol), and the mixture is heated to 80 ° C.
After stirring for 1 hour, the mixture was poured into ice water and the precipitate was collected by filtration. The precipitate was dissolved in chloroform, dried over magnesium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography (chloroform: hexane = 1: 1-5: 1) to obtain 110 mg of the title compound (yield). 96%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2942, 2196, 1
537. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
74 (br.s, 6H), 2.71 (s, 3H,), 4.00 (m, 4H), 7.46-7.51
(m, 3H), 8.41-8.43 (m, 2H). Mass spectrum (m / z): 310 (M ⁺ ).

[0196]

Example 30 2-Phenyl-4-piperidylquinazoline (Exemplary Compound No. 4335) Using 4-chloro-2-phenylquinazoline (100 mg, 0.40 mmol), a reaction was carried out in the same manner as in Example 29, and silica gel column chromatography was performed. Chromatography (hexane: ethyl acetate = 1: 1-5:
Purification in 1) gave 90 mg of the title compound (78% yield). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2940, 1534, 1
504, 1357, 762, 707. ¹ H-nuclear magnetic resonance spectrum (400
MHz, CDCl ₃ ) δ ppm: 1.78-1.87 (m, 3H), 3.79-3.82 (m,
2H), 7.26-8.57 (m, 9H). Mass spectrum (m / z): 289 (M ⁺ ).

[0197]

Example 31 4- (5-cyano-6-methylthio-2-phenyi)
L-pyrimidinyl) piperazinecarboxylate t-butyl ester
Le (Compound No. 3730) 4-chloro-5-cyano-6- (methylthio) -2-phenyl-pyrimidine (100 mg, 0.37 mmol) in dimethylformamide (1.5 ml)
Dissolved in t-butyl 1-piperazinecarboxylate (84
mg, 0.45 mmol), stirred at 50 ° C. for 1 hour, and poured into ice water. After extraction with ethyl acetate, washing with water and saturated saline,
It was dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 7: 1) to obtain 130 mg of the title compound (yield: 83).
%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3424, 2203, 1
698, 1536, 1522, 1421. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
49 (s, 9H), 2.73 (s, 3H,), 3.59-3.62 (m, 4H), 4.02-4.
05 (m, 4H), 7.46-7.55 (m, 3H), 8.40-8.43 (m, 2H). Mass spectrum (m / z): 412 (M ⁺⁺ 1).

[0198]

Example 32 5-Cyano-6- (methylthio) -2-phenyl
-4-piperazinylpyrimidine hydrochloride (Exemplary Compound No. 3
723.hydrochloride) Dissolve 4- (5-cyano-6-methylthio-2-phenylpyrimidinyl) piperazinecarboxylic acid t-butyl ester (mg) in dichloromethane (1.0 ml), cool with ice water, and add 4N hydrochloric acid.
Ethyl acetate (0.2 ml) was added. After 30 minutes, the temperature was returned to room temperature, and the mixture was further reacted for 1 hour, concentrated and dried, and the residue was washed with chloroform and ethyl acetate to obtain 80 mg of the title compound (yield 8).
Four%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3436, 2924, 2
208, 1525, 1449, 980. ¹ H-nuclear magnetic resonance spectrum (DMSO) δ ppm: 2.73 (s, 3
H), 3.27-3.29 (m, 4H), 4.19-4.21 (m, 4H), 7.53-7.61
(m, 3H), 8.41-8.44 (m, 2H), 9.45 (br.s, 1H). Mass spectrum (m / z): 311 (M ⁺ ).

[0199]

Example 33 4- (5-cyano-2-methyl-6-methylthio-
Pyrimidin-4-yl) -piperazine-1-carboxylic acid t-buty
Ester (Exemplified Compound No. 3731) A reaction was carried out in the same manner as in Example 31 using 4-chloro-5-cyano-2-methyl-6-(-methylthio) -pyrimidine (100 mg, 0.40 mmol), and 166 mg of the title compound was obtained. (95% yield). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2203, 1698, 1
534, 1517, 1398, 995. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
48 (s, 9H), 2.48 (s, 3H,), 2.58 (s, 3H,) 3.53-3.54 (m,
4H), 3.91-3.94 (m, 4H). Mass spectrum (m / z): 349 (M ⁺ ).

[0200]

Example 34 2-Methyl-4-methylthio-6-piperazine
1-yl-pyrimidin-5-carbonitrile hydrochloride (Exemplary Compound No. 3727, hydrochloride) 4- (5-cyano-2-methyl-6-methylthio-pyrimidin-4-yl) -piperazine-1-carboxylic acid t-butyl ester (150m
g, 0.42 mmol) to carry out a reaction in the same manner as in Example 32 to obtain 86 mg of the title compound (yield: 80%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3382, 2923, 2
217, 1567, 1450, 1296. Mass spectrum (m / z): 249 (M ⁺ ).

[0201]

Example 35 4- (2-phenyl-quinazolin-4-yl)-
Piperazine-1-carboxylic acid t-butyl ester (Exemplary Compound No. 4359) The reaction was carried out in the same manner as in Example 31 using 4-chloro-2-phenylquinazoline (100 mg, 0.40 mmol) to give the title compound as 15
0 mg was obtained (93% yield). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2976, 1612, 1
502, 1248, 707. Mass spectrum (m / z): 390 (M ⁺ ).

[0202]

Example 36 2-Phenyl-4-piperazinoquinazoline
Hydrochloride (Exemplified Compound No. 4343, hydrochloride) In the same manner as in Example 32, using 4- (2-phenyl-quinazolin-4-yl) -piperazine-1-carboxylic acid t-butyl ester (150 mg, 0.42 mmol). Perform the reaction to obtain 50 mg of the title compound
(56% yield). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3378, 2789, 1
619, 1565, 706. ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO) δ ppm: 3.3
8 (br.s, 4H), 4.36 (br.s, 4H), 7.63-8.55 (m, 9H), 9.8
0 (br.s, 1H). Mass spectrum (m / z): 290 (M ⁺ ).

[0203]

Example 37 4-Diethylamino-6- (methylthio) -2-
Phenyl-pyrimidine-5-carbonitrile (Exemplary Compound No. 3732) 4-Chloro-5-cyano-6- (methylthio) -2-phenylpyrimidine (100 mg, 0.37 mmol) was converted to dimethylformamide (1.5 ml).
And added 0.11 ml of diethylamine, stirred for 1 hour, and poured into ice water. The mixture was extracted with ethyl acetate, washed with water and saturated saline, dried over magnesium sulfate, and evaporated to dryness under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 7: 1) to give the title compound (107m).
g was obtained (100% yield). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2200, 1544, 1
391, 1033. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
35 (t, 6H, J = 7.0Hz), 3.83 (q, 4H, J = 7.0Hz), 7.44
-7.51 (m, 3H), 8.41-8.43 (m, 2H). Mass spectrum (m / z): 298 (M ⁺ ).

[0204]

Example 38 4-Cyclohexylamino-6-phenyl-
Potassium 2-pyridin-3-yl-pyrimidine-5-carboxylate
Salt (exemplary compound No. 1777, potassium salt) (1) 6-oxo-4-phenyl-2-pyridin-3-yl-1,6-
Dihydro-pyrimidine-5-carboxylic acid ethyl ester 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (2.2 g) and nicotinamidine hydrochloride (1.3 g) were dissolved in 200 ml of ethanol, and metallic sodium (532 mg) was added. 0 ℃
And stirred. After the metallic sodium was completely dissolved, the temperature was raised and the mixture was refluxed for 24 hours. The solvent was distilled off, 1N hydrochloric acid was added dropwise, and the deposited precipitate was collected by filtration, sufficiently washed with hexane and ether, and dried, and 910 mg of 6-oxo-4-phenyl-2-pyridin-3-yl -1,6-dihydro-pyrimidine-5-
The carboxylic acid ethyl ester was obtained (36% yield). (2) 4-cyclohexylamino-6-phenyl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid ethyl ester 6-oxo-4-phenyl-2-pyridin-3-yl-1,6-dihydro
-Pyrimidine-5-carboxylic acid ethyl ester (138 mg) was dissolved in phosphorus oxychloride (4 ml) and stirred at 110 ° C for 2 hours. The solvent was distilled off under reduced pressure, and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was dissolved in cyclohexylamine (4 ml) and stirred at 110 ° C for 1.5 hours. The solvent was distilled off under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (hexane: ethyl acetate = 4:
Separated and purified in 1), 113 mg of 4-cyclohexylamino-6-
Phenyl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid ethyl ester was obtained (65% yield). (3) 4-cyclohexylamino-6-phenyl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid potassium salt 4-cyclohexylamino-6-phenyl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid Acid ethyl ester (100 mg, 0.
(25 mmol) was dissolved in ethanol (1 ml).
After adding 10% ethanol solution (0.5 ml) and refluxing for 3 hours,
The mixture was concentrated under reduced pressure and then separated and purified with CHP20 to obtain 75 mg of potassium 4-cyclohexylamino-6-phenyl-2-pyridin-3-yl-pyrimidine-5-carboxylate (yield 73%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3375, 2930, 1
588, 1356, 704. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 1.
24-2.17 (m, 10H), 4.88 (br.s, 1H), 7.10 (d, 1H, J =
7.3Hz), 7.38-7.84 (m, 5H), 8.59 (m, 1H), 8.77 (m, 1H),
9.50 (d, J = 1.1 Hz). Mass spectrum (m / z): 413 (M ⁺⁺ 1).

[0205]

Example 39 4-phenyl-6-phenylamino-2-pyri
Gin-3-yl-pyrimidin-5-carboxylic acid potassium salt (exemplified compound No. 1781, potassium salt) (1) 6-oxo-4-phenyl-2-pyridin-3-yl-1,6-
Dihydro-pyrimidine-5-carboxylic acid ethyl ester 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (2.2 g) and nicotinamidine hydrochloride (1.3 g) were dissolved in 200 ml of ethanol, and metallic sodium (532 mg) was added. 0 ℃
And stirred. After the metallic sodium was completely dissolved, the temperature was raised and the mixture was refluxed for 24 hours. The solvent was distilled off, 1N hydrochloric acid was added dropwise, and the deposited precipitate was collected by filtration, sufficiently washed with hexane and ether, and dried, and 910 mg of 6-oxo-4-phenyl-2-pyridine-3-y. Yl-1,6-dihydro-pyrimidine-5
-Carboxylic acid ethyl ester was obtained (36% yield). (2) 4-phenyl-6-phenylamino-2-pyridine-3-
Il-pyrimidine-5-carboxylic acid ethyl ester 6-oxo-4-phenyl-2-pyridin-3-yl-1,6-dihydro
-Pyrimidine-5-carboxylic acid ethyl ester (123 mg) was dissolved in phosphorus oxychloride (4 ml) and stirred at 110 ° C for 2 hours. The solvent was distilled off under reduced pressure, and the obtained residue was extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was dissolved in aniline (4 ml) and stirred at 110 ° C for 1.5 hours. The solvent was distilled off under reduced pressure, and the obtained residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 6: 1), and 100 mg of 4-phenyl-6-phenylamino-2-pyridine-
3-yl-pyrimidine-5-carboxylic acid ethyl ester was obtained (66% yield). (3) 4-phenyl-6-phenylamino-2-pyridine-3-
Ill-pyrimidine-5-carboxylic acid potassium salt 4-phenyl-6-phenylamino-2-pyridin-3-yl-pyrimidine-5-carboxylic acid ethyl ester (97 mg, 0.24 mmol) was dissolved in ethanol (1 ml), A 10% ethanol solution of potassium hydroxide (0.5 ml) was added, and the mixture was refluxed for 6 hours. -Pyrimidine-5-carboxylic acid potassium salt was obtained (yield 97%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3333, 1588, 1
444, 1356, 702. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 7.
10 (m, 1H), 7.37-7.59 (m, 6H), 7.79-7.90 (m, 4H), 8.61
-8.63 (m, 1H), 8.80-8.83 (m, 1H), 9.55-9.56 (m, 1H). Mass spectrum (m / z): 407 (M ⁺⁺ 1).

[0206]

Example 40 4-Phenyl-6-piperazin-1-yl-2-
Pyridin-3-yl-pyrimidin-5-carboxylic acid potassium salt (Exemplary Compound No. 1773, potassium salt) According to the method of Example 39- (1), 6-oxo-4-phenyl-2-pyridin-3-yl- After obtaining 1,6-dihydro-pyrimidine-5-carboxylic acid ethyl ester (166 mg), it was dissolved in phosphorus oxychloride (4 ml) and stirred at 110 ° C. for 2 hours. The solvent was distilled off under reduced pressure, and the obtained residue was extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and evaporated. The residue was dissolved in dimethylformamide (4.0 ml), t-butyl 1-piperazinecarboxylate (156 mg, 0.84 mmol) was added, and the mixture was stirred at 50 ° C. for 1 hour and poured into ice water. The mixture was extracted with ethyl acetate, washed with water and saturated saline, dried over magnesium sulfate, and dried under reduced pressure.
The residue was subjected to silica gel column chromatography (hexane
/ Ethyl acetate = 1/1) and then 212 mg of ethyl 4- (4-t-butoxycarbonyl-piperazin-1-yl) -6-phenyl-2-pyridin-3-yl-pyrimidine-5-carboxylate (Yield
89%).

This compound (212 mg) was added to dichloromethane (1.0 m
l) and cooled with ice water, then 4N hydrochloric acid-dioxane (0.2m
l) was added. After 30 minutes, return to room temperature, react for another 1 hour, concentrate to dryness, wash the residue with ether, dissolve in ethanol (1 ml), and add a 10% ethanol solution of potassium hydroxide.
(0.5 ml) and refluxed for 3 hours, concentrated under reduced pressure, separated and purified by CHP20, and 130 mg of 4-phenyl-6-piperazin-1-yl-
2-Pyridin-3-yl-pyrimidine-5-carboxylic acid potassium salt was obtained (76% yield). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3376, 1584, 1
536, 1360, 977, 703. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 2.
96-3.00 (m, 4H), 4.83-4.93 (m, 4H), 7.39-7.43 (m, 3
H), 7.50-7.54 (m, 1H), 7.79-7.83 (m, 2H), 8.58 (dd, 1H,
J = 4.7, 1.8Hz), 8.73 (dt, 1H, J = 8.0, 2.0Hz), 9.4
5 (m, 1H). Mass spectrum (m / z): 362 (M ⁺⁺ 1).

[0208]

Example 41 4-Diethylamino-6-phenyl-2-pyri
Gin-3-yl-pyrimidine-5-carboxylic acid potassium salt (exemplified compound No. 1784, potassium salt) (1) 6-oxo-4-phenyl-2-pyridin-3-yl-1,6-
Dihydro-pyrimidine-5-carboxylic acid ethyl ester 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (2.2 g) and nicotinamidine hydrochloride (1.3 g) were dissolved in 200 ml of ethanol, and metallic sodium (532 mg) was added. 0 ℃
And stirred. After the metallic sodium was completely dissolved, the temperature was raised and the mixture was refluxed for 24 hours. The solvent was distilled off, 1N hydrochloric acid was added dropwise, and the deposited precipitate was collected by filtration, sufficiently washed with hexane and ether, and dried, and 910 mg of 6-oxo-4-phenyl-2-pyridin-3-yl -1,6-dihydro-pyrimidine-5-
The carboxylic acid ethyl ester was obtained (36% yield). (2) 4-diethylamino-6-phenyl-2-pyridine-3-
Il-pyrimidine-5-carboxylic acid ethyl ester 6-oxo-4-phenyl-2-pyridin-3-yl-1,6-dihydro
-Pyrimidine-5-carboxylic acid ethyl ester (110 mg) was dissolved in phosphorus oxychloride (4 ml) and stirred at 110 ° C for 2 hours. The solvent was distilled off under reduced pressure, and the obtained residue was extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was dissolved in diethylamine (4 ml) and stirred at 110 ° C for 1.5 hours.
The solvent was distilled off under reduced pressure, and the obtained residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1) to give 62 mg of 4-diethylamino-6-phenyl-2-pyridin-3-yl-. Pyrimidine-5-carboxylic acid ethyl ester was obtained (yield 48%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3389, 1582, 1
540, 1362, 1166, 704. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 1.
30-1.34 (m, 6H), 3.78-3.84 (m, 4H), 7.37-7.79 (m, 6
H), 8.56-8.72 (m, 2H), 9.43-9.45 (m, 1H). Mass spectrum (m / z): 387 (M ⁺ +1) (3) 4-Diethylamino-6-phenyl-2-pyridine-3-
As in Example 39- (3), using yl-pyrimidine-5-carboxylic acid potassium salt 4-diethylamino-6-phenyl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid ethyl ester (97 mg). The reaction was carried out to give the title compound 96
mg (97% yield).

[0209]

Example 42 4-ethoxy-6-phenyl-2-pyridine-3
-Yl-pyrimidin-5-carboxylic acid potassium salt 4-chloro-6-phenyl-2-pyridin-3-yl-pyrimidine-5
-Ethyl carboxylate (150 mg, 0.45 mmol) was added with 28% sodium methoxide, and the mixture was stirred at room temperature for 30 minutes. And concentrated under reduced pressure. The obtained residue was dissolved in ethanol (1 ml), a 10% potassium hydroxide in ethanol solution (0.5 ml) was added, and the mixture was heated under reflux for 6 hours, dried and purified with CHP20 to obtain 83 mg of 4-ethoxy-6-. Phenyl-2-
Pyridin-3-yl-pyrimidine-5-carboxylic acid potassium salt was obtained (yield 53%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3404, 1583, 1
538, 1366, 1339, 1025, 701. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 1.
48 (t, 3H, J = 7.05), 4.65 (q, 2H, J = 7.05Hz), 7.44
-7.48 (m, 3H), 7.55-7.59 (m, 1H), 8.10-8.13 (m, 2H),
8.62-8.64 (m, 1H), 8.84-8.87 (m, 1H), 9.57 (d, 1H, J =
2.05Hz). Mass spectrum (m / z): 360 (M ⁺⁺ 1).

[0210]

Example 43 4-Cyclohexyloxy-6-phenyl-
Potassium 2-pyridin-3-yl-pyrimidine-5-carboxylate
Salt 4-chloro-6-phenyl-2-pyridin-3-yl-pyrimidine-5
-Carboxylic acid ethyl ester (50 mg, 0.15 mmol) was added with cyclohexanol (1 ml) and potassium hydroxide (30 mg),
After stirring at 0 ° C for 4 hours, water and diethyl ether were added,
After washing several times with diethyl ether, the organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified on CHP20,
49 mg of the title compound was obtained (81% yield). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3402, 2936, 1
590,1550, 1361, 984. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 1.
38-2.17 (m, 10H), 5.40 (m, 1H), 7.43-7.59 (m, 4H), 8.
10-8.13 (m, 2H), 8.61-8.64 (m, 1H), 8.80-8.84 (m, 1H),
9.54 (m, 1H). Mass spectrum (m / z): 414 (M ⁺⁺ 1).

[0211]

Example 44 4-heptyloxy-6-phenyl-2-pyri
Zin-3-yl-pyrimidin-5-carboxylic acid potassium salt 4-chloro-6-phenyl-2-pyridin-3-yl-pyrimidin-5
-Carboxylic acid ethyl ester (50 mg, 0.15 mmol), the reaction was carried out in the same manner as in Example 43 using 1-heptanol (1 ml) and potassium hydroxide (30 mg) to obtain 32 mg of the title compound (51% yield). . Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3404, 2928, 1
581,1552,1365,702. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 0.
88-1.89 (m, 13H), 4.59 (t, 2H, J = 6.6Hz), 7.44-7.59
(m, 4H), 8.10-8.13 (m, 2H), 8.61-8.64 (m, 1H), 8.83-
8.85 (m, 1H), 9.56 (m, 1H). Mass spectrum (m / z): 430 (M ⁺⁺ 1).

[0212]

Example 45 4-Pentyloxy-6-phenyl-2-pyri
Zin-3-yl-pyrimidin-5-carboxylic acid potassium salt 4-chloro-6-phenyl-2-pyridin-3-yl-pyrimidin-5
-Carboxylic acid ethyl ester (50 mg, 0.15 mmol), 1-pentanol (1 ml) and potassium hydroxide (30 mg) were reacted in the same manner as in Example 43 to obtain 50 mg of the title compound (85% yield). ). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3404, 2957, 1
588,1552,1365,702. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 0.
95 (t, 3H, J = 7.1Hz), 1.40-1.92 (m, 6H), 4.88 (m, 2
H), 7.44-7.59 (m, 4H), 8.10-8.13 (m, 2H), 8.61-8.64
(m, 1H), 8.83-8.85 (m, 1H), 9.56 (m, 1H). Mass spectrum (m / z): 402 (M ⁺⁺ 1).

[0213]

Example 46 4-Methylthio-6-phenyl-2-pyridine
3-yl-pyrimidine-5-carboxylic acid potassium salt (exemplified compound number 1181) 4-chloro-6-phenyl-2-pyridin-3-yl-pyrimidine-5
-Carboxylic acid ethyl ester (150 mg, 0.44 mmol) was dissolved in methanol (3 ml), thiourea (110 mg, 1.44 mmol) was added, and the mixture was refluxed overnight. After concentration under reduced pressure, 1.5 ml of a 2N aqueous sodium hydroxide solution was added, and the mixture was further refluxed overnight. The precipitated solid was collected by filtration and purified by silica gel column chromatography (hexane: ethyl acetate = 1: 2). 27 mg of the title compound were obtained (18% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 2.
71 (s, 3H), 7.44-7.61 (m, 4H), 8.04-8.07 (m, 2H), 8.6
1-8.65 (m, 1H), 8.86-8.92 (m, 1H), 9.62 (m, 1H). Mass spectrum (m / z): 362 (M ⁺⁺ 1).

[0214]

Example 47 4-hydroxy-6-phenyl-2-pyridine
-3-yl-pyrimidine-5-carboxylic acid disodium salt (1) 6-oxo-4-phenyl-2-pyridin-3-yl-1,6-
Dihydro-pyrimidine-5-carboxylic acid ethyl ester 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (2.2 g) and nicotinamidine hydrochloride (1.3 g) were dissolved in 200 ml of ethanol, and metallic sodium (532 mg) was added. 0 ℃
And stirred. After the metallic sodium was completely dissolved, the temperature was raised and the mixture was refluxed for 24 hours. The solvent was distilled off, 1N hydrochloric acid was added dropwise, and the deposited precipitate was collected by filtration, sufficiently washed with hexane and ether, and dried, and 910 mg of 6-oxo-4-phenyl-2-pyridine-3-y. Yl-1,6-dihydro-pyrimidine-5
-Carboxylic acid ethyl ester was obtained (36% yield). (2) 4-hydroxy-6-phenyl-2-pyridin-3-yl-
Pyrimidine-5-carboxylic acid disodium salt 6-oxo-4-phenyl-2-pyridin-3-yl-1,6-dihydro
-Pyrimidine-5-carboxylic acid ethyl ester (100 mg, 0.31
(mmol) to a 10% solution of sodium hydroxide (0.8 ml),
The mixture was stirred at ℃ for 1.5 hours. After the completion of the reaction, the reaction solution was concentrated under reduced pressure until the volume became about 1/3, washed several times with diethyl ether, and made acidic by adding concentrated hydrochloric acid to the aqueous layer. The precipitated solid was washed with water, recrystallized from methanol, and treated with a 1N aqueous sodium hydroxide solution to obtain 24 mg of the title compound (yield: 26%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3261, 1567, 1
504, 1360, 1182. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 7.
47-7.56 (m, 3H), 7.81-7.88 (m, 2H), 8.11-8.16 (m, 1
H), 8.96 (dd, 1H, J = 1.30, 5.60Hz), 9.33 (br.d, 1H,
J = 8.62), 9.63 (br.s, 1H). Mass spectrum (m / z): 338 (M ⁺⁺ 1).

[0215]

Example 48 2-adamantan-1-yl-4-hydroxy
-6-Phenyl-pyrimidine-5-carboxylic acid ethyl ester (Exemplary Compound No. 954) 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (200 mg, 0.72 mmol) and 1-adamantanecarbamidine hydrochloride (160 mg, 0.72 mmol) in 10 ml of ethanol,
Sodium hydride (72 mg) was added, and the mixture was heated under reflux for 24 hours. The solvent was distilled off, washed lightly with hexane, cooled to 0 ° C., added with 1N hydrochloric acid, and stirred. The deposited precipitate was collected by filtration, sufficiently washed with hexane and ether, and dried to obtain 60 mg of the title compound (yield: 22%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 1.
09 (t, 3H, J = 7.14Hz), 1.83-1.84 (m, 6H), 2.09-2.11
(m, 9H), 4.15 (q, 2H, J = 7.14Hz), 7.41-7.49 (m, 3H),
7.61-7.67 (m, 2H), 7.43-7.52 (m, 3H), 7.76 (br.d, 2H,
J = 7.76 Hz). Mass spectrum (m / z): 378 (M ⁺ ).

[0216]

Example 49 2-adamantan-1-yl-4-hydroxy
-6-Phenyl-pyrimidine-5-carboxylic acid disodium salt 2-adamantan-1-yl-4-hydroxy-6-phenyl-pyrimidine-5-carboxylic acid ethyl ester (60 mg, 0.16 mmol) and sodium hydroxide 3 % Solution (2.0 ml) was added, refluxed for 5 hours, returned to room temperature, and concentrated hydrochloric acid was added until the solution became acidic. The precipitated solid was washed with water, recrystallized from methanol, and treated with a 1N aqueous sodium hydroxide solution to obtain 25 mg of the title compound (yield: 40%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3393, 2904, 1
645,1561, 1503, 1004. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 1.
86-1.87 (m, 6H), 2.11-2.14 (m, 9H), 7.43-7.52 (m, 3
H), 7.76 (br.d, 2H, J = 6.57 Hz) Mass spectrum (m / z): 395 (M ⁺ +1).

[0219]

Example 50 4-hydroxy-6-phenyl-2-pyridine
-4-yl-pyrimidine-5-carboxylic acid ethyl ester (exemplified compound number 900) 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (200 m, 0.72 mmol) and isonicotinamidine hydrochloride (114 mg, 0.72 mmol) ) Was dissolved in 10 ml of ethanol, and sodium hydride (72 mg) was added at 0 ° C and the mixture was stirred. After completion of the addition, the mixture was heated and refluxed for 24 hours. The solvent was distilled off, washed lightly with hexane, cooled to 0 ° C., added with 1N hydrochloric acid, and stirred. The deposited precipitate was collected by filtration, sufficiently washed with hexane and ether, and dried to obtain 81 mg of the title compound (yield: 35%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 1.
12 (t, 3H, J = 7.15Hz), 4.21 (q, 2H, J = 7.15Hz), 7.
46-7.54 (m, 3H), 7.73-7.76 (m, 2H), 8.17-8.19 (m, 2H),
8.74-8.76 (m, 2H). Mass spectrum (m / z): 321 (M ⁺ ).

[0218]

Example 51 4-hydroxy-2- (4-methyl-benzyl)
-6-Phenyl-pyrimidine-5-carboxylic acid disodium salt 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (200 m, 0.72 mmol) and 2- (4-methylphenyl) acetamidine hydrochloride (114 mg, (0.72 mmol) was dissolved in 10 ml of ethanol, sodium hydride (72 mg) was added thereto, the mixture was stirred, heated, and refluxed for 24 hours. The solvent was distilled off, washed lightly with hexane, cooled to 0 ° C., added with 1N hydrochloric acid, and stirred. The deposited precipitate was collected by filtration, sufficiently washed with hexane and ether, and dried to obtain 57 mg of the title compound (yield: 25%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3403, 1560, 1
505, 1039. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 2.
31 (s, 3H), 3.96 (s, 2H), 7.14-7.16 (m, 2H), 7.24-7.2
6 (m, 2H), 7.43-7.47 (m, 3H), 7.64-7.66 (m, 2H). Mass spectrum (m / z): 365 (M ⁺⁺ 1).

[0219]

Example 52 4-hydroxy-6-phenyl-2-pyridine
Hydroxylation of disodium salt of 2-yl-pyrimidine-5-carboxylic acid 4-hydroxy-2- (4-methyl-benzyl) -6-phenyl-pyrimidine-5-carboxylic acid (57 mg, 0.18 mmol) A 3% solution of sodium (2.0 ml) was added, and after refluxing for 4 hours, the temperature was returned to room temperature, and concentrated hydrochloric acid was added until the solution became acidic. The precipitated solid was washed with water, recrystallized from methanol, and treated with a 1N aqueous sodium hydroxide solution to obtain 32 mg of the title compound (yield: 56%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3402, 1557, 1
505, 1361. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 7.
47-7.65 (m, 4H), 7.83-7.86 (m, 2H), 8.01-8.06 (m, 1
H), 8.53-8.55 (m, 1H), 8.78-8.79 (m, 1H). Mass spectrum (m / z): 338 (M ⁺⁺ 1).

[0220]

Example 53 4-hydroxy-2-methyl-6-phenyl-
Pyrimidine-5-carboxylic acid disodium salt (1) 4-hydroxy-2-methyl-6-phenyl-pyrimidine-5-carboxylic acid ethyl ester 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (250m, 0.90 mmol) and acetamidine hydrochloride (85 m
g, 0.90 mmol) was dissolved in ethanol (10 ml), sodium hydride (80 mg) was added, the mixture was stirred, heated, and refluxed for 24 hours. The solvent was distilled off, washed lightly with hexane, cooled to 0 ° C., added with 1N hydrochloric acid, and stirred. The precipitated precipitate was collected by filtration, washed sufficiently with hexane and ether, and dried to obtain 95 mg of ethyl 4-hydroxy-2-methyl-6-phenyl-pyrimidine-5-carboxylate (yield: 41%). . (2) 4-hydroxy-2-methyl-6-phenyl-pyrimidine-5-carboxylic acid disodium salt 4-hydroxy-2-methyl-6-phenyl-pyrimidine-5-carboxylic acid ethyl ester (95 mg, 0.37 mmol) To the mixture was added a 3% solution of sodium hydroxide (2.0 ml), and the mixture was refluxed for 2 hours. After returning to room temperature, concentrated hydrochloric acid was added until the mixture became acidic. The precipitated solid was washed with water, recrystallized from methanol, and treated with a 1N aqueous sodium hydroxide solution to give the title compound as a solid.
mg (yield 38%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3349, 1566, 1
512, 1418. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 2.
47 (s, 3H), 7.44-7.46 (m, 3H), 7.62-7.64 (m, 2H). Mass spectrum (m / z): 275 (M ⁺⁺ 1).

[0221]

Example 54 2-butyl-4-hydroxy-6-phenyl-
Pyrimidine-5-carboxylic acid disodium salt (1) 2-butyl-4-hydroxy-6-phenyl-pyrimidine-5-carboxylic acid ethyl ester 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (250 m, 0.90 mmol) and caproamidine hydrochloride (123 m
g, 0.90 mmol) was dissolved in 10 ml of ethanol, sodium hydride (80 mg) was added, and the mixture was stirred, heated and refluxed for 24 hours. The solvent was distilled off, washed lightly with hexane, cooled to 0 ° C., added with 1N hydrochloric acid, and stirred. The deposited precipitate was collected by filtration, washed sufficiently with hexane and ether, and dried to give 154 m
g of 2-butyl-4-hydroxy-6-phenyl-pyrimidine-5-
The carboxylic acid ethyl ester was obtained (51% yield). (2) 2-butyl-4-hydroxy-6-phenyl-pyrimidine-5-carboxylic acid disodium salt 2-butyl-4-hydroxy-6-phenyl-pyrimidine-5-carboxylic acid ethyl ester (154 mg, 0.51 mmol) A 5% solution of sodium hydroxide (2.0 ml) was added to the mixture, and the mixture was refluxed for 3.5 hours. After returning to room temperature, concentrated hydrochloric acid was added until the mixture became acidic. The precipitated solid was washed with water, recrystallized from methanol, and treated with a 1N aqueous sodium hydroxide solution to obtain 55 mg of the title compound (yield: 34%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3369, 2956, 1
638, 1561, 697. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 0.
98 (t, 3H, J = 7.32), 1.44 (dd, 2H, J = 7.32Hz), 1.74
1.81 (m, 2H), 2.69 (t, 2H, J = 7.69Hz), 7.42-7.47 (m,
3H), 7.65 to 7.68 (m, 2H). Mass spectrum (m / z): 317 (M ⁺⁺ 1).

[0222]

Example 55 4-hydroxy-2-naphthalen-2-yl-6
-Phenyl-pyrimidine-5-carboxylic acid disodium salt (1) 4-hydroxy-2-naphthalen-2-yl-6-phenyl-pyrimidine-5-carboxylic acid ethyl ester 2- (methoxy-phenyl-methylene) -malone Dissolve acid diethyl ester (250m, 0.90mmol) and naphthalene-2-carboxyamidine hydrochloride (186mg, 0.90mmol) in 10ml of ethanol, add sodium hydride (80mg), stir and raise the temperature.
The mixture was refluxed for 24 hours. The solvent was distilled off, washed lightly with hexane, cooled to 0 ° C., added with 1N hydrochloric acid, and stirred. The deposited precipitate was collected by filtration, washed sufficiently with hexane and ether,
Dry to give 62 mg of 4-hydroxy-2-naphthalen-2-yl-6
-Phenyl-pyrimidine-5-carboxylic acid ethyl ester was obtained (yield 19%). (2) 4-hydroxy-2-naphthalen-2-yl-6-phenyl-pyrimidine-5-carboxylic acid disodium salt 4-hydroxy-2-naphthalen-2-yl-6-phenyl-pyrimidine-5-carboxylic acid A 5% solution of sodium hydroxide (2.0 ml) was added to the ethyl ester (62 mg, 0.17 mmol), and the mixture was refluxed for 3.5 hours. After returning to room temperature, concentrated hydrochloric acid was added until the solution became acidic.
After washing the precipitated solid with water and recrystallizing from methanol,
By treating with 1N aqueous sodium hydroxide,
37 mg of the title compound was obtained (58% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 7.
45-8.74 (m, 12H). Mass spectrum (m / z): 342 (M ⁺ -2Na).

[0223]

Example 56 2-benzyl-4-hydroxy-6-phenyl
-Pyrimidine-5-carboxylic acid disodium salt (1) 2-benzyl-4-hydroxy-6-phenyl-pyrimidine-5-carboxylic acid ethyl ester 2- (methoxy-phenyl-methylene) -malonic acid diethyl ester (250m, 0.90 mmol) and 2-phenyl-acetamidine hydrochloride (153 mg, 0.90 mmol) were dissolved in 10 ml of ethanol, sodium hydride (89 mg) was added, the mixture was stirred, heated to reflux for 24 hours. After distilling off the solvent and washing gently with hexane,
The mixture was cooled to ° C, 1N hydrochloric acid was added, and the mixture was stirred. The deposited precipitate was collected by filtration, washed sufficiently with hexane and ether, and dried to obtain 115 mg of ethyl 2-benzyl-4-hydroxy-6-phenyl-pyrimidine-5-carboxylate (yield 38).
%). (2) 2-benzyl-4-hydroxy-6-phenyl-pyrimidine-5-carboxylic acid disodium salt 2-benzyl-4-hydroxy-6-phenyl-pyrimidine-5-carboxylic acid ethyl ester (115 mg, 0.34 mmol) To the mixture was added a 5% solution of sodium hydroxide (2.0 ml). After refluxing for 3 hours, the mixture was returned to room temperature, and concentrated hydrochloric acid was added until the mixture became acidic. The precipitated solid was washed with water, recrystallized from methanol, and treated with a 1N aqueous sodium hydroxide solution to obtain 68 mg of the title compound (57% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 7.
45-8.74 (m, 12H). Mass spectrum (m / z): 342 (M ⁺ -2Na).

[0224]

Example 57 4-butyl-6-hydroxy-2-pyridine-3
-Yl-pyrimidine-5-carboxylic acid disodium salt (1) 4-butyl-6-hydroxy-2-pyridin-3-yl-pyrimidine-5-carboxylic acid ethyl ester 2- (butyl-methoxy-methylene) -malone Acid diethyl ester (100m, 0.39mmol) and nicotinamidine hydrochloride (61m
g, 0.39 mmol) was dissolved in 5 ml of ethanol, sodium hydride (39 mg) was added, the mixture was stirred, heated to reflux for 4 hours.
The solvent was distilled off, washed lightly with hexane, cooled to 0 ° C,
Normal hydrochloric acid was added and stirred. The precipitated oil was extracted with ethyl acetate, and the organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (ethyl acetate: methanol = 10: 1), and 40 mg of 4-butyl-6-hydroxy-2-pyridin-3-yl- was obtained.
Pyrimidine-5-carboxylic acid ethyl ester was obtained (yield 3
Four%). (2) 4-butyl-6-hydroxy-2-pyridin-3-yl-pyrimidine-5-carboxylic acid disodium salt 4-butyl-6-hydroxy-2-pyridin-3-yl-pyrimidine
A 5% solution of sodium hydroxide (2.0 ml) was added to -5-carboxylic acid ethyl ester (40 mg, 0.13 mmol), and the mixture was refluxed for 3 hours, returned to room temperature, and concentrated hydrochloric acid was added until the solution became acidic. The precipitated solid was washed with water, recrystallized from methanol, and treated with a 1N aqueous sodium hydroxide solution to give 36 mg of the title compound.
Obtained (100% yield). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3307, 2955, 1
567, 1490, 1363, 821, 704. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 0.
99 (t, 3H, J = 7.32Hz), 1.43-1.53 (m, 2H), 1.71-1.79
(m, 2H), 3.20 (t, 2H, J = 7.69Hz), 7.63-7.67 (m, 1H),
8.53-8.56 (m, 1H), 9.27 (s, 1H). Mass spectrum (m / z): 318 (M ⁺⁺ 1).

[0225]

Example 58 4-Hydroxy-6-naphthalen-1-yl-2
-Pyridin-3-yl-pyrimidine-5-carboxylic acid dinatri
Ium salt (1) 4-hydroxy-6-naphthalen-1-yl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid ethyl ester 2- (methoxy-naphthalen-1-yl-methylene) -malonic acid
Dissolve diethyl ester (200m, 0.58mmol) and nicotinamidine hydrochloride (96mg, 0.61mmol) in ethanol 10ml,
Sodium hydride (61 mg) was added and the mixture was stirred, heated to reflux for 72 hours. After distilling off the solvent and washing lightly with hexane,
The mixture was cooled to 0 ° C, 1N hydrochloric acid was added, and the mixture was stirred. The deposited precipitate was collected by filtration, washed sufficiently with hexane and ether, and dried, and 59 mg of 4-hydroxy-6-naphthalen-1-yl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid ethyl ester Was obtained (38% yield). (2) 4-hydroxy-6-naphthalen-1-yl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid disodium salt 4-hydroxy-6-naphthalen-1-yl-2-pyridin-3- Il
-Pyrimidine-5-carboxylic acid ethyl ester (59mg, 0.16m
mol), a 5% solution of sodium hydroxide (2.0 ml) was added, and the mixture was refluxed for 2 hours, returned to room temperature, and concentrated hydrochloric acid was added until the mixture became acidic.
The precipitated solid was washed with water, recrystallized from methanol, and treated with a 1 N aqueous sodium hydroxide solution to give 20 mg of the title compound (33% yield). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3320, 1566, 1
491, 1373. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 7.
45-7.62 (m, 5H), 7.81 (d, 1H, J = 8.42Hz), 7.92-7.99
(m, 2H), 8.57 (d, 1H, J = 8.06Hz), 8.73 (d, 1H, J =
4.76Hz), 9.28 (s, 1H). Mass spectrum (m / z): 388 (M ⁺⁺ 1).

[0226]

Example 59 4-morpholin-4-yl-2-phenyl-6-
Phenylamino-pyrimidine-5-carboxylic acid ethyles
Ter (Exemplified Compound No. 3029) (1) 2-cyano-3-methylthio-3-phenylamino-acrylic acid ethyl ester 2-cyano-3,3-bismethylthio
-Acrylic acid ethyl ester (2.46 g, 11.32 mmol) and aniline (1.2 ml, 12.45 mmol) in ethanol (50 ml) in 80
Heated at C for 4 hours. After concentration under reduced pressure, purification was performed by silica gel column chromatography (hexane: ethyl acetate = 3: 1), and 2-cyano-3-methylthio-3-phenylamino was purified.
-2.9 g of ethyl acrylate was obtained (98% yield). (2) 3- (benzimidoyl-amino) -2-cyano-3-phenylamino-acrylic acid ethyl ester 2-cyano-3-methylthio-3-phenylamino-acrylic acid
Ethyl ester (1.85 g, 7.07 mmol) and benzamidine (9
(35 mg, 7.78 mmol) was refluxed in ethanol for 3 hours. After concentration under reduced pressure, purification was carried out by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to obtain 750 mg of ethyl 3- (benzimidyl-amino) -2-cyano-3-phenylamino-acrylate (yield). Rate 32%). (3) 4-chloro-2-phenyl-6-phenylamino-pyrimidine-5-carboxylic acid ethyl ester 3- (benzimidyl-amino) -2-cyano-3-phenylamino-acrylic acid ethyl ester (0.41 g, 1.13 4 mmol)
A normal hydrochloric acid solution in 1,4-dioxane (75 ml) was added, and the mixture was stirred at room temperature for 3 days. After concentration under reduced pressure, purification by column chromatography (hexane: ethyl acetate = 5: 1) was performed to obtain 316 mg of ethyl 4-chloro-2-phenyl-6-phenylamino-pyrimidine-5-carboxylate (yield). 79%). (4) 4-morpholin-4-yl-2-phenyl-6-phenylamino-pyrimidine-5-carboxylic acid ethyl ester 4-chloro-2-phenyl-6-phenylamino-pyrimidine-5-
Morpholine (0.6 ml) is added to carboxylic acid ethyl ester (46 mg, 0.143 mmol), and the mixture is heated and stirred at 80 ° C. for 30 minutes. After cooling, silica gel column chromatography (hexane:
Purification by ethyl acetate = 5: 1) was performed, and the target compound was
mg (99% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 39
(t, 3H, J = 7.Hz ) , 3.71-3.72 (m, 4H), 3.77-3.79 (m,
4H), 4.35 (q, 2H, J = 7.1 Hz), 7.09-8.39 (m, 10H), 1
0.0 (s, 1H). Mass spectrum (m / z): 404 (M ⁺ ).

[0227]

Example 60 4-morpholin-4-yl-6-phenylamido
No-2-pyridin-2-yl-pyrimidine-5-carboxylic acid
Glycol ester (Compound No. 3030) using pyridine-2-carboxamidine hydrochloride in place of benzamidine, Example 59-(1), (2),
The reaction was carried out in the same manner as in (3) and (4), and the title compound was
9 mg was obtained. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
39 (t, 3H, J = 7.1 Hz), 3.76-3.79 (m, 8H), 4.36 (q, 2
H, J = 7.1 Hz), 7.08-8.80 (m, 9H), 8.98 (s, 1H). Mass spectrum (m / z): 405 (M ⁺ ).

[0228]

Example 61 4-morpholin-4-yl-6-phenylamido
No-2-pyridin-3-yl-pyrimidine-5-carboxylic acid
Luster (Exemplified Compound No. 3031) The reaction was carried out in the same manner as in Examples 59- (1), (2), (3) and (4) using nicotinamidine hydrochloride instead of benzamidine to obtain 118 mg of the title compound. Was. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
40 (t, 3H, J = 7.1 Hz), 3.70-3.72 (m, 4H), 3.77-3.79
(m, 4H), 4.36 (q, 2H, J = 7.1 Hz), 7.10-9.57 (m, 9H),
10.0 (s, 1H). Mass spectrum (m / z): 405 (M ⁺ ).

[0229]

Example 62 4-morpholin-4-yl-6-phenylamido
No-2-pyridin-4-yl-pyrimidine-5-carboxylic acid
Ester (Exemplified Compound No. 3032) The reaction was carried out in the same manner as in Examples 38- (1) and (2), using isonicotine amidine hydrochloride instead of nicotine amidine hydrochloride, and using morpholine instead of cyclohexylamine. 54 mg of the title compound were obtained. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
41 (t, 3H, J = 7.1 Hz), 3.71-3.74 (m, 4H), 3.78-3.80
(m, 4H), 4.38 (q, 2H, J = 7.1 Hz), 7.12-8.73 (m, 9H),
9.98 (s, 1H). Mass spectrum (m / z): 405 (M ⁺ ).

[0230]

Example 63 4-Phenylamino-2-pyridin-3-yl
-6-thiomorpholin-4-yl-pyrimidine-5-carboxylic acid
Ethyl ester (Exemplified Compound No. 3125) The reaction was carried out in the same manner as in Examples 38- (1) and (2) using thiomorpholine instead of cyclohexylamine,
68 mg of the title compound was obtained (96% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
40 (t, 3H, J = 7.1 Hz), 2.72-2.75 (m, 4H), 3.93-3.95
(m, 4H), 4.37 (q, 2H, J = 7.1 Hz), 7.10-9.60 (m, 9H),
10.0 (s, 1H). Mass spectrum (m / z): 421 (M ⁺ ).

[0231]

Example 64 2-Phenyl-4-phenylamino-6-thio
Morpholin-4-yl-pyrimidine-5-carboxylate ethyl ester
Stell (Exemplified Compound No. 3123) The reaction was carried out in the same manner as in Examples 38- (1) and (2) using benzamidine hydrochloride instead of nicotinamidine hydrochloride and thiomorpholine instead of cyclohexylamine, and 94 mg of the compound were obtained. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
38 (t, 3H, J = 7.1 Hz), 2.74 (m, 4H), 3.93-3.94 (m, 4
H), 4.34 (q, 2H, J = 7.1 Hz), 7.09-8.39 (m, 10H), 10.
0 (s, 1H). Mass spectrum (m / z): 420 (M ⁺ ).

[0232]

Example 65 2-Phenyl-4-phenylamino-6-pipe
Razin-1-yl-pyrimidine-5-carboxylic acid ethyl ester
Le monohydrochloride (Compound No. 3311 monohydrochloride) (1) 4- (4- t- butoxycarbonyl-1-yl) -2-phenyl-6-phenylamino - pyrimidine-5-carboxylic acid ethyl ester 4-chloro-2-phenyl-6-phenylamino-pyrimidine-5-
Ethyl carboxylate (58 mg, 0.16 mmol) was dissolved in ethanol (2 ml), N- (t-butoxycarbonyl) piperazine (47 mg, 0.25 mmol) was added, and the mixture was heated with stirring at 80 ° C. for 4 hours. After concentration under reduced pressure, purification was performed by silica gel column chromatography (hexane: ethyl acetate = 5: 1), and 4- (4
-t-butoxycarbonylpiperazin-1-yl) -2-phenyl
83 mg of ethyl 6-phenylamino-pyrimidine-5-carboxylic acid was obtained (99% yield). (2) 2-phenyl-4-phenylamino-6-piperazine-1
-Yl-pyrimidine-5-carboxylic acid ethyl ester monohydrochloride 4- (4-t-butoxycarbonylpiperazin-1-yl) -2-phenyl-6-phenylamino-pyrimidine-5-carboxylic acid ethyl ester (83 mg, 0.17 mmol) was added 4N hydrochloric acid-1,4-dioxane solution (25 ml), and the mixture was stirred for 1 day. After concentration under reduced pressure, the residue was washed with ether to give the title compound (59 mg, yield 90%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
1.33 (t, 3H, J = 7.1 Hz), 3.17 (m, 4H), 3.87 (m, 4H),
4.34 (q, 2H, J = 7.1 Hz), 7.09-8.31 (m, 10H), 9.76 (b
rs, 2H), 9.97 (s, 1H). Mass spectrum (m / z): 403 (M ⁺ ).

[0233]

Example 66 4-Phenylamino-6-piperazine-1-i
Ru-2-pyridin-2-yl-pyrimidine-5-carboxylic acid
Luster monohydrochloride (Exemplary Compound No. 3312 / monohydrochloride) 4-Chloro-2-phenyl-6-phenylamino-pyrimidine-5-
Similar to Examples 65- (1) and (2), except that ethyl 4-chloro-6-phenylamino-2-pyridin-2-yl-pyrimidine-5-carboxylate was used in place of ethyl carboxylate. The reaction was performed to obtain 177 mg of the title compound. ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
1.36 (t, 3H, J = 7.1 Hz), 3.18 (m, 4H), 3.99-4.01 (m,
4H), 4.38 (q, 2H, J = 7.1 Hz), 7.14-9.97 (m, 11H). Mass spectrum (m / z): 404 (M ⁺ ).

[0234]

Example 67 4-Phenylamino-6-piperazine-1-i
Ethyl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid
Luster monohydrochloride (Exemplary compound No. 3313 / monohydrochloride) 4-chloro-2-phenyl-6-phenylamino-pyrimidine-5-
Similar to Examples 65- (1) and (2), except that 4-chloro-6-phenylamino-2-pyridin-3-yl-pyrimidine-5-carboxylic acid ethyl ester was used instead of carboxylic acid ethyl ester. The reaction was performed to obtain 12 mg of the title compound. ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
1.34 (t ,, 3H, J = 7.1 Hz), 3.16 (m, 4H), 3.91 (m, 4
H), 4.35 (q, 2H, J = 7.1 Hz), 7.12-9.47 (m, 9H), 9.88
(br.s, 2H), 9.93 (s, 1H). Mass spectrum (m / z): 404 (M ⁺ ).

[0235]

Example 68 4-Phenylamino-6-piperazine-1-i
Ethyl-2-pyridin-4-yl-pyrimidine-5-carboxylic acid
Luster monohydrochloride (Exemplary Compound No. 3314 / monohydrochloride) 4-chloro-2-phenyl-6-phenylamino-pyrimidine-5-
Similar to Examples 65- (1) and (2) except that 4-chloro-6-phenylamino-2-pyridin-4-yl-pyrimidine-5-carboxylic acid ethyl ester was used instead of carboxylic acid ethyl ester. The reaction was performed to obtain 123 mg of the title compound. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 1.
36 (t, 3H, J = 7.1 Hz), 3.20 (m, 4H), 3.89-3.92 (m, 4
H), 4.38 (q, 2H, J = 7.1 Hz), 7.16-9.94 (m, 11H). Mass spectrum (m / z): 404 (M ⁺ ).

[0236]

Example 69 2-Phenyl-4-phenylamino-6-pipe
Radin-1-yl-pyrimidine-5-carboxylic acid sodium salt 4- (4-t-butoxycarbonyl-piperazin-1-yl) -2-phenyl-6-phenylamino-pyrimidine-5-carboxylic acid ethyl ester (85 mg , 0.17 mmol), 4N hydrochloric acid-1,4-dioxane solution (10 ml) was added, and the mixture was stirred for 1 day. After concentration under reduced pressure,
Dissolve in ethanol-tetrahydrafuran (2: 1) solution (3 ml), add 1N aqueous sodium hydroxide solution (2 ml),
The mixture was heated and refluxed at 100 degrees for 3 hours. After allowing to cool, the mixture was concentrated and recrystallized from 1N sodium hydroxide to obtain 26 mg of the title compound (yield: 39%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
2.74-2.75 (m, 4H), 3.52-3.53 (m, 4H), 6.89-8.34 (m, 1
0H), 11.71 (s, 1H). Mass spectrum (m / z): 387 (M ⁺ ).

[0237]

Example 70 4-Hydroxy-2-isopropylthio-6-
Phenyl-pyrimidine-5-carbonitrile (Exemplary Compound No. 50) 4-oxo-6-phenyl-2-thiooxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile (100 mg, 0.44 mmol) in ethanol (5 ml) solution, isobutyl bromide (41 μl, 0.44 mm
ol) and potassium carbonate (61 μg, 0.44 mmol), and the mixture was heated under reflux for 3 hours. After cooling, the mixture was filtered, the filtrate was concentrated, and recrystallized from ethanol to obtain 77 mg of a target compound (yield: 60%).
%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
1.40 (s, 3H), 1.42 (s, 3H), 4.01-4.07 (m, 1H), 7.45-
7.95 (m, 5H). Mass spectrum (m / z): 293 (M ⁺ ).

[0238]

Example 71 2-benzylthio-4-hydroxy-6-fe
Nyl-pyrimidine-5-carbonitrile (Exemplary Compound No. 6
2) The reaction was carried out in the same manner as in Example 70 using benzyl bromide instead of isobutyl bromide to obtain 77 mg of the title compound. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 4.
64 (s, 2H), 7.13-7.89 (m, 10H). Mass spectrum (m / z): 319 (M ⁺ ).

[0239]

Example 72 4-Chloro-2-phenyl-6-phenylamido
No-pyrimidine-5-carboxylic acid sodium salt 4-chloro-2-phenyl-6-phenylamino-pyrimidine-5-
To a solution of carboxylic acid ethyl ester (500 mg, 1.54 mmol) in 1,4-dioxane (15 ml) was added 1N sodium hydroxide (8 m
l) was added and the mixture was heated to reflux at 100 ° C. for 6 hours. After cooling, the mixture is acidified with concentrated hydrochloric acid, water is added, and the precipitated crystals are filtered.
Recrystallization from a 1N aqueous solution of sodium hydroxide gave 433 mg of the title compound (80% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
7.05-8.32 (m, 10H), 12.43 (s, 1H). Mass spectrum (m / z): 348 (M + H) ⁺ .

[0240]

Example 73 4-benzylamino-6-chloro-2-pheni
4- pyrimidine-5-carboxylic acid sodium salt 4- (4-t-butoxycarbonyl-piperazin-1-yl) -2-phenyl-6-phenylamino-pyrimidine-5-carboxylic acid 4-benzyl instead of ethyl ester Amino-6-chloro-2-
Using phenyl-pyrimidine-5-carboxylic acid ethyl ester, the reaction was carried out in the same manner as in Example 69, to give the title compound
99 mg were obtained. ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
4.73 (d, 2H, J = 5.8 Hz), 7.22-9.70 (m, 11H). Mass spectrum (m / z): 362 (M + H) ⁺ .

[0241]

Example 74 4-Hydroxy-2-phenyl-6-phenyl
Amino-pyrimidine-5-carbonitrile (Exemplary Compound No. 2695) 2-cyano-3-methylthio-3-phenylamino-acrylic acid
Ethyl ester (1.85 g, 7.07 mmol) and benzamidine (9
(35 mg, 7.78 mmol) was refluxed in ethanol for 3 hours. After concentration under reduced pressure, purification was performed by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to obtain the title compound (10% yield). ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
7.17-8.04 (m, 10H), 9.87 (s, 1H). Mass spectrum (m / z): 288 (M ⁺ ).

[0242]

Embodiment 754-hydroxy-2-phenyl-6-phenyl
Amino-pyrimidine-5-carbonitrile sodium salt
(Exemplary Compound No. 2695 / sodium salt) 4-hydroxy-2-phenyl-6-phenylamino-pyrimidi
-5-carbonitrile (100 mg, 0.35 mmol)
Recrystallization from sodium chloride solution
60 mg of the compound was obtained (56% yield).¹ H-nuclear magnetic resonance spectrum (400MHz, DMSO-d₆) δ ppm:
6.94-8.21 (m, 11H).

[0243]

Working Example 76 4-Hydroxy-6-morpholin-4-yl-2
-Phenyl-pyrimidine-5-carbonitrile sodium salt (Exemplary compound No. 3989, sodium salt) Same as Example 75 using 4-hydroxy-6-morpholin-4-yl-2-phenyl-pyrimidine-5-carbonitrile To give 60 mg of the title compound. ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
3.68-3.69 (m, 8H), 7.38 (m, 3H), 8.24 (m, 2H).

[0244]

Example 77 2-morpholin-4-yl-4,6-diphenyl
- nicotinonitrile (Compound No. 4266) (1) 2- (3-oxo-1,3-diphenyl-propyl) - - malononitrile 1,3-diphenyl - propenone (208 mg, 1.00 mmol) and malononitrile (0.056 ml, 1.00 was dissolved in 5 ml of methanol, 2 ml of a 28% solution of sodium methoxide in methanol was added, and the mixture was stirred for 1 hour and concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with water and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. After purification by silica gel column chromatography (hexane / ethyl acetate = 10/1), 2- (3-
(Oxo-1,3-diphenyl-propyl) -malononitrile to 21
3 mg was obtained (78% yield). (2) 2-Bromo-4,6-diphenyl-nicotinonitrile 2- (3-oxo-1,3-diphenyl-propyl) -malononitrile (213 mg, 0.78 mmol) was dissolved in 1 ml of acetic acid, and bromine (35 mg) was dissolved. Acetic acid solution (0.5 ml) was added dropwise, and the mixture was stirred at 70 ° C. for 1 hour. The reaction solution was poured into water, and the precipitate was collected by filtration to obtain 53 mg of 2-bromo-4,6-diphenyl-nicotinonitrile (yield 87%). (3) 2-morpholin-4-yl-4,6-diphenyl-nicotinonitrile 2-bromo-4,6-diphenyl-nicotinonitrile (53 mg, 0.0
Morpholine (1 ml) was added to 9 mmol), and the mixture was stirred at 80 ° C. for 10 minutes, poured into water, and the precipitated oil was extracted with ethyl acetate, washed with water and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10/1) to obtain 26 mg of the title compound (yield: 85%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
3.79-3.94 (m, 8H), 7.35 (s, 1H), 7.47-7.62 (m, 8H,),
8.06-8.08 (m, 2H). Mass spectrum (m / z): 341 (M ⁺ ).

[0245]

Example 78 6-Hydroxy-4-phenyl- [2,3 ′]-bi
Pyridinyl-5-carbonitrile (Exemplary Compound No. 424
4) 3-phenyl-1-pyridin-3-yl-propenone (200 mg, 0.9
6 mmol) in ethanol (10 ml), ethyl cyanoacetate (0.1 ml, 0.98 mmol), ammonium acetate (148 mg,
1.92 mmol), and the mixture was heated under reflux for 24 hours. After cooling to room temperature, the precipitate was collected by filtration and recrystallized from ethyl acetate to obtain 62 mg of the title compound (yield 23%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
7.42-9.20 (m, 10H). Mass spectrum (m / z): 273 (M ⁺ ).

[0246]

Example 79 2′-Hydroxy-6′-phenyl- [3,4 ′] bi
Pyridinyl-5'-carbonitrile (Exemplary Compound No. 425
4) 1-phenyl-3-pyridin-3-yl-propenone (200 mg, 0.9
The reaction was carried out in the same manner as in Example 78 using 6 mmol) to obtain 11 mg of the title compound (yield: 4%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2956, 2220, 1
652,768. ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
6.98 (br.s, 1H), 7.52-7.64 (m, 5H), 7.92 (m, 2H), 8.18
(dt, 1H, J = 1.80, 8.13Hz), 8.76 (dd, 1H, J = 1.43, 5.0
8Hz), 8.93 (d, 1H, J = 2.45Hz) Mass spectrum (m / z): 273 (M ⁺ )

[0247]

Example 80 6-Hydroxy-4-phenyl- [2,2 ′] bipi
Lysinyl-5-carbonitrile (Exemplary Compound No. 424
3) 3-phenyl-1-pyridin-2-yl-propenone (200 mg, 0.
The reaction was carried out in the same manner as in Example 78 by using 96 mmol) to obtain 10 mg of the title compound (yield 4%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2935, 2221, 7
63. ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
7.31 (br.s, 1H), 7.58-7.61 (m, 5H), 7.74-7.76 (m, 2
H), 8.02-8.06 (m, 1H), 8.33 (d, 1H, J = 8.01Hz), 8.77
(d, 1H, J = 4.65Hz) Mass spectrum (m / z): 273 (M ⁺ )

[0248]

Example 81 6-Hydroxy-4-phenyl- [2,4 ′] bipi
Lysinyl-5-carbonitrile (Exemplary Compound No. 424
5) 3-phenyl-1-pyridin-4-yl-propenone (200 mg, 0.9
The reaction was carried out in the same manner as in Example 78 using 6 mmol) to obtain 23 mg of the title compound (yield: 8%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 3034, 2853, 2
205, 1538. ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
6.83 (br.s, 1H), 7.48-7.54 (m, 3H), 7.63 (d, 1H, J = 1.
41Hz), 7.65 (d, 1H, J = 2.05Hz), 7.93 (dd, 2H, J = 1.44,
4.49Hz), 8.65 (dd, 2H, J = 1.41, 4.50Hz). Mass spectrum (m / z): 273 (M ⁺ )

[0249]

Example 82 2-Hydroxy-4,6-diphenyl-nicotine
Nonitrile (Exemplified Compound No. 4242) The reaction was carried out in the same manner as in Example 78 using 1,3-diphenyl-propenone (200 mg, 0.96 mmol) to obtain 26 mg of the title compound.
(10% yield). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2915, 2219, 1
645, 700. ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
6.82 (br.s, 1H), 7.32-7.45 (m, 1H), 7.51-7.59 (m, 5
H), 7.73-7.76 (m, 2H,), 7.90 (d, 2H, J = 6.79 Hz). Mass spectrum (m / z): 272 (M ⁺ )

[0250]

Working Example 83 6-Hydroxy-4-thiophen-2-yl-
[2,3] Bipyridinyl-5-carbonitrile (Exemplary Compound No. 4330) 1-pyridin-3-yl-3-thiophen-2-yl-propenone
(200 mg, 0.93 mmol) was dissolved in ethanol (10 ml), ethyl cyanoacetate (0.1 ml, 0.98 mmol) and ammonium acetate (148 mg, 1.84 mmol) were added, and the mixture was heated under reflux for 24 hours.
After cooling to room temperature, the precipitate was collected by filtration and recrystallized from ethyl acetate to obtain 11 mg of the title compound (yield: 4%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
7.01-9.08 (m, 8H). Mass spectrum (m / z): 279 (M ⁺ ).

[0251]

Working Example 84 2-Morpholin-4-yl-4,6-diphenyl
-Nicotinic acid (Exemplary Compound No. 4262) (1) Ethyl 2-cyano-5-oxo-3,5-diphenyl-pentanoate 1,3-diphenyl-propenone (208 mg, 1.00 mmol) and ethyl cyanoacetate (0.13 ml, 1.2 mmol) in methanol 2 ml
Dissolved in 28% methanol solution of sodium methoxide 2
Drops were added, and the mixture was stirred at 50 ° C. for 1 hour and concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with water and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. After purification by silica gel column chromatography (hexane / ethyl acetate = 5/1), 2-cyano-5-oxo-3,5-diphenyl-pentanoic acid
271 mg of ethyl ester was obtained (88% yield). (2) 2-bromo-4,6-diphenyl-nicotinic acid methyl ester 2-cyano-5-oxo-3,5-diphenyl-pentanoic acid ethyl ester (176 mg, 0.57 mmol) was dissolved in 2 ml of acetic acid, and bromine was dissolved.
An acetic acid solution (1 ml) of (100 mg) was added dropwise, and the mixture was stirred at 100 ° C. for 0.5 hour and concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, water, and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. After purification by silica gel column chromatography (hexane / ethyl acetate = 5/1), 2-bromo-
40 mg of 4,6-diphenyl-nicotinic acid methyl ester was obtained.
(19% yield). (3) 2-morpholin-4-yl-4,6-diphenyl-nicotinic acid methyl ester 2-bromo-4,6-diphenyl-nicotinic acid methyl ester
(40 mg, 0.08 mmol) and 0.7 ml of morpholine,
Stirred for hours. The reaction solution was poured into water, and the precipitated oil was extracted with ethyl acetate, washed with water and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10/1) to obtain 25 mg of 2-morpholin-4-yl-4,6-diphenyl-nicotinic acid methyl ester (yield: 84).
%). (4) 2-morpholin-4-yl-4,6-diphenyl-nicotinic acid 2-morpholin-4-yl-4,6-diphenyl-nicotinic acid methyl ester (10 mg, 0.03 mmol) and 10% of potassium hydroxide An ethanol solution (0.5 ml) was added, and the mixture was heated under reflux for 3 hours, concentrated under reduced pressure, and 1N hydrochloric acid was added. The precipitated oil was extracted with ethyl acetate, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 7 mg of the title compound (yield 73%). Infrared absorption spectrum (KBr) νmax (cm ^-1 ): 2854, 1723, 1
543, 1263, 1116, 697. ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d ₆ ) δ ppm:
3.46-3.49 (m, 4H), 3.58 (s, 3H), 3.83-3.85 (m, 4H),
7.30 (s, 1H), 7.35-7.48 (m, 8H), 8.05 (dd, J = 1.47, 8.05
Hz). Mass spectrum (m / z): 360 (M ⁺ )

[0252]

Working Example 85 6-morpholin-4-yl-4-phenyl- [2,
3 ′] Bipyridinyl-5-carboxylic acid (Exemplary Compound No. 426
4) (1) 2-cyano-5-oxo-3-phenyl-5-pyridine-3-
Yl-pentanoic acid ethyl ester 3-phenyl-1-pyridin-3-yl-propenone (209 mg, 1.0
0 mmol) and ethyl cyanoacetate (0.13 ml, 1.2 mmol)
Was dissolved in 5 ml of methanol, and 28% of sodium methoxide was dissolved.
Two drops of a methanol solution were added, and the mixture was stirred at 50 ° C. for 1 hour and concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with water and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. After purification by silica gel column chromatography (hexane / ethyl acetate = 1/1 to 10/1), 160 mg of ethyl 2-cyano-5-oxo-3-phenyl-5-pyridin-3-yl-pentanoate was obtained. (52% yield). (2) 6-bromo-4-phenyl- [2,3 '] bipyridinyl-5-
Carboxylic acid methyl ester 2-cyano-5-oxo-3-phenyl-5-pyridin-3-yl-pentanoic acid ethyl ester (154 mg, 0.50 mmol) in 2 ml of acetic acid
And bromine (150 mg) in acetic acid (1 ml) was added dropwise at 100 ° C.
, And concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, water, and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. After purification by silica gel column chromatography (hexane / ethyl acetate = 2/1), 22 mg of 6-bromo-4-phenyl- [2,3 '] bipyridinyl-5-carboxylic acid methyl ester was obtained (yield 31%). ). (3) Methyl 6-morpholin-4-yl-4-phenyl- [2,3 '] bipyridinyl-5-carboxylate Methyl 6-bromo-4-phenyl- [2,3'] bipyridinyl-5-carboxylate 0.7 ml of morpholine in ester (22 mg, 0.05 mmol)
Was added and stirred at 80 ° C. for 1 hour. Pour the reaction solution into water,
The precipitated oil was extracted with ethyl acetate, washed with water and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2/1), and then purified with 6-morpholine-4-
25 mg of yl-4-phenyl- [2,3 ′] bipyridinyl-5-carboxylic acid methyl ester was obtained (60% yield). (4) 6-morpholin-4-yl-4-phenyl- [2,3 '] bipyridinyl-5-carboxylic acid 6-morpholin-4-yl-4-phenyl- [2,3'] bipyridinyl-
To a 5-carboxylic acid methyl ester (20 mg, 0.03 mmol) was added a 10% ethanol solution of potassium hydroxide (0.5 ml), and the mixture was refluxed for 24 hours, concentrated under reduced pressure, and 1N hydrochloric acid was added. The precipitate was collected to obtain 5 mg of the title compound (yield: 26%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CD ₃ OD) δ ppm: 3.
52-3.55 (m, 4H), 3.82-3.85 (m, 4H), 7.44-7.49 (m, 4
H), 7.66 (s, 1H), 8.07-8.08 (m, 1H), 8.83-8.84 (m, 1
H), 9.19-9.21 (m, 1H), 9.52 (br.s, 1H). Mass spectrum (m / z): 361 (M ⁺ )

[0253]

Working Example 86 5-Hydroxy-3-pyridin-3-yl-bi
Phenyl-4-carboxylic acid ethyl ester (Exemplary Compound No. 4222) and 3-hydroxy-5-pyridin-3-yl-bi
Phenyl-2-carboxylic acid ethyl ester (Exemplary Compound No. 4215) 1-phenyl-3-pyridin-3-yl-propenone (50 mg, 0.24
mmol) in ethanol (5.0 ml).
(58 mg, 0.71 mmol) and 1- (3-ethoxycarbonyl-2-oxopropyl) pyridinium bromide (103 mg, 0.36 mmol) were added, and the mixture was heated under reflux for 3 hours. After concentration under reduced pressure, the mixture was extracted with chloroform, washed with water and saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by preparative TLC (chloroform / ethyl acetate = 20/1),
5-hydroxy-3-pyridin-3-yl-biphenyl-4-carboxylic acid ethyl ester (Rf value: 0.4, 22 mg, 29%), and 3-
Hydroxy-5-pyridin-3-yl-biphenyl-2-carboxylic acid ethyl ester (Rf value: 0.3, 35 mg, 46%) was obtained. 5-Hydroxy-3-pyridin-3-yl-biphenyl-4-carboxylic acid ethyl ester ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 0.
82 (t, 3H, J = 6.98Hz), 4.05 (q, 2H, J = 6.98Hz), 7.01 (d,
1H, J = 2.20Hz), 7.30-7.35 (m, 2H), 7.40-7.48 (m, 3
H), 7.60-7.64 (m, 3H), 8.55-8.61 (m, 2H), 11.26 (s, 1
H).

Mass spectrum (m / z): 319 (M ⁺ ). 3-Hydroxy-5-pyridin-3-yl-biphenyl-2-carboxylic acid ethyl ester ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 0.
81 (t, 3H, J = 7.32Hz), 4.02 (q, 2H, J = 7.32), 7.26-7.3
6 (m, 6H), 7.49 (d, 1H, J = 1.47Hz), 7.62 (d, 1H, J = 2.20
Hz), 7.77-7.79 (m, 2H), 10.94 (s, 1H).

Mass spectrum (m / z): 319 (M ⁺ )

[0256]

Working Example 87 5-Hydroxy-3-pyridin-3-yl-bi
Phenyl-4-carboxylic acid (Exemplified Compound No. 4226) 5-hydroxy-3-pyridin-3-yl-biphenyl-4-carboxylic acid ethyl ester obtained in Example 86 (58 mg, 0.18 mmol)
To l), a 10% ethanol solution of potassium hydroxide (0.5 ml) was added, and the mixture was heated under reflux for 24 hours, concentrated under reduced pressure, and 1N hydrochloric acid was added. The precipitate was collected to obtain 31 mg of the title compound (yield: 59%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl ₃ ) δ ppm: 7.
20 (s, 1H), 7.28-7.46 (m, 6H), 7.63-8.01 (m, 4H), 11.
20 (s, 1H). Mass spectrum (m / z): 361 (M ⁺ )

[0257]

Working Example 88 5′-Hydroxy- [1,1 ′; 3 ′, 1 ″] ter
Phenyl-4 'carboxylic acid (Exemplary Compound No. 4218) (1) 5'-hydroxy- [1,1'; 3 ', 1 "] terphenyl-4'
-Carboxylic acid ethyl ester 1,3-diphenyl-propenone (24 mg, 0.12 mmol) was dissolved in ethanol (2.0 ml), and sodium acetate (28 mg, 0.34 mmo
l) and 1- (3-ethoxycarbonyl-2-oxopropyl) pyridinium bromide (50 mg, 0.17 mmol) were added, and the mixture was heated under reflux for 5 hours. The mixture was acidified with 1N hydrochloric acid, extracted with ethyl acetate, dried over magnesium sulfate, and concentrated under reduced pressure.
The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10/1), and then ethyl 5′-hydroxy- [1,1 ′; 3 ′, 1 ″] terphenyl-4′-carboxylate was used. 20 mg of the ester was obtained (54% yield). (2) 5′-hydroxy- [1,1 ′; 3 ′, 1 ″] terphenyl-
4 'carboxylic acid 5'-hydroxy- [1,1'; 3 ', 1'']terphenyl-4'-carboxylic acid ethyl ester (20 mg, 0.06 mmol) in 10% ethanol solution of potassium hydroxide (0.5 ml ), Heated under reflux for 24 hours, concentrated under reduced pressure, and 1N hydrochloric acid was added. The precipitate was collected to give the title compound (17 mg, yield 93%). ¹ H-nuclear magnetic resonance spectrum (400 MHz, DMSO) δ ppm: 7.2
6 (s, 1H), 7.28-7.46 (m, 6H), 7.63-7.77 (m, 3H), 8.63
(d, 1H, J = 2.93Hz), 10.95 (s, 1H). Mass spectrum (m / z): 290 (M ⁺ ).

[0258]

[Formulation Examples] The preparations of the present invention containing the compound having the above general formula (I) or a pharmaceutically acceptable salt, ester or other derivative thereof as an active ingredient can be produced, for example, by the following method.

[0259]

Formulation Example 1 Powder 5 g of the compound of Example 1, 895 g of lactose, and 100 g of corn starch are mixed with a blender.
A powder is obtained.

[0260]

Formulation Example 2 Granules 5 g of the compound of Example 63, 865 g of lactose and 100 g of low-substituted hydroxypropylcellulose are mixed, and then a 10% aqueous solution of hydroxypropylcellulose 3
Add 00 g and knead. This is granulated using an extrusion granulator and dried to obtain a granule.

[0261]

Formulation Example 3 Capsule 5 g of the compound of Example 77, 115 g of lactose, 58 g of corn starch and 2 g of magnesium stearate are mixed using a V-type mixer, and then filled into a No. 3 capsule by 180 mg to obtain a capsule. .

[0262]

Formulation Example 4 Tablets 5 g of the compound of Example 1, 90 g of lactose, 34 g of corn starch, 20 g of crystalline cellulose and 1 g of magnesium stearate are mixed in a blender, and the mixture is compressed with a tablet machine to give tablets.

[0263]

[Test example]

[0264]

[Test Example 1] CD40 function inhibition test Ramos cells [American Type Culture Collection
(ATCC) CRL-1596, Rockville, MD]
RPM containing 10% fetal calf serum (Cansera International)
20,000 cells / I medium (Life Technologies)
The cell concentration was adjusted to 0.2 ml, and 0.2 ml was dispensed into a 96-well flat bottom plate (manufactured by Corning). To this, an anti-CD40 antibody (manufactured by SEROTEC; final dilution ratio 1: 200)
0) and the test compound were added, and 37 ° C. in 5% CO ₂
After culturing for 72 hours, the presence or absence of cell aggregation was observed under a microscope.

The compounds of the present invention inhibited cell agglutination by anti-CD40 antibody.

[0266]

Test Example 2 Immunoglobulin E Production Inhibition Test First, human peripheral blood lymphocytes were prepared as follows.

20 ml of the provided healthy human peripheral blood was
1 ml in 0 ml plastic tube (manufactured by Corning)
It was overlaid on 5 ml of Ficoll-Paque solution (Pharmacia), and the human peripheral blood mononuclear cell fraction was separated as an intermediate layer by density gradient centrifugation.

The obtained human peripheral blood lymphocytes were cultured in RPMI medium (manufactured by Life Technologies) containing 10% fetal bovine serum (manufactured by Cansera International) at 100,000 cells / 0.
The cell concentration was adjusted to 2 ml, and 0.2 ml was dispensed into a 96-well flat bottom plate (manufactured by Corning). In addition, anti-C
D40 antibody (manufactured by SEROTEC; final dilution 1: 200)
0), human interleukin 4 (manufactured by Genzyme; final concentration 2000 U / ml) and a test compound were added, and 5% CO ₂ was added.
After culturing for 2 weeks at 37 ° C in medium, Eldia IgE ELISA
Immunoglobulin E in the culture supernatant was quantified by KIT (manufactured by Kokusai Reagent Co., Ltd.).

The compounds of the present invention suppressed the production of immunoglobulin E.

[0270]

[Test Example 3] Human lymphocyte mixed culture reaction inhibition test First, from 20 ml of peripheral blood provided by two healthy persons,
Human peripheral blood lymphocytes were separated by the method described in "Test Example 2".

Only one human peripheral blood lymphocyte had 600
The cells were irradiated with 0 rad X-rays to obtain dysproliferative stimulated cells. On the other hand, cells that were not irradiated with X-rays were defined as proliferating responder cells. Stimulator cells and responder cells were replaced with 10% fetal bovine serum (Cansera
RPMI medium (Life Technologi) containing International Technology
es) (100,000 cells / 0.1 ml), and 0.1 ml was dispensed into a 96-well round bottom plate (Corning) to mix. The test compound was added thereto, and the cells were cultured in 5% CO ₂ at 37 ° C. for 96 hours. Then, 5 μCi of [ ³ H] thymidine (manufactured by Amersham) was further added, and the cells were cultured for 18 hours. After completion of the culture, the radioactivity of [ ³ H] thymidine incorporated into the cells was measured using a beta plate (WALLAC) and used as an index for the human lymphocyte mixed culture reaction.

Inhibition rate of human lymphocyte mixed culture reaction −−−−−−−−−−−−−−−−−−−−−−− Concentration of test compound Test compound 5 μM 25 μM −−− −−−−−−−−−−−−−−−−−−−−−−−−−−− The compound of Example 63 90% 100% The compound of Example 77 96% 100% −−−−−− −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−- In judging from the above-mentioned table, the compound of this invention inhibited human lymphocyte mixed culture reaction.

[0273]

[Test Example 4] Interleukin-12 (IL-12) production inhibition test Human monocyte cell THP-1 [American Type Culture Co
llection (ATCC) TIB-202, Rockville, MD]
With 10% fetal bovine serum (Cansera International)
In RPMI medium (Life Technologies) containing
2,000 cells / 0.2 ml
Each was dispensed into a 96-well round bottom plate (manufactured by Corning Incorporated). To this, human interferon gamma (Genzyme; final concentration 2000 U / ml) and dimethyl sulfoxide (Wako Pure Chemicals; final concentration 1.2%) were added, and 3% in 5% CO ₂ was added.
The cells were cultured at 7 ° C. for 48 hours. Furthermore, an anti-CD40 antibody (SE
ROTEC; final dilution 1: 200) and a test compound were added, and the mixture was cultured at 37 ° C. for 18 hours in 5% CO ₂ , followed by IL-12 ELISA KIT (Genzyme) in the culture supernatant. IL-12 was quantified.

Inhibition rate of IL-12 production: concentration of test compound 25 μM of test compound 25 μM −−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− −−−−−−−−−−−−−−−−−−−−−−−−− The compound of Example 1 88% The compound of Example 63 86% The compound of Example 77 86% −−−−− As can be seen from the above table, the compound of the present invention has an IL
-12 production was inhibited.

[0275]

The compound of the present invention has an excellent CD40 function inhibitory effect, has good oral absorbability and low toxicity, and is useful as a medicament.
It is useful as an immunosuppressant or a medicament for preventing or treating allergy, rheumatism, autoimmune disease or arteriosclerosis.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 31/5377 A61K 31/5377 31/541 31/541 A61P 9/10 A61P 9/10 29/00 101 29 / 00 101 37/02 37/02 37/06 37/06 37/08 37/08 C07C 62/06 C07C 62/06 69/88 69/88 C07D 213/80 C07D 213/80 239/42 239/42 Z 401/04 401/04 // A61K 31/44 A61K 31/44 31/444 31/444 (72) Inventor Katsumi Fujimoto 1-258 Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Invention Person Akio Shiraishi 1-58 Hiromachi, Shinagawa-ku, Tokyo, Japan Sankyo Co., Ltd. (72) Inventor Shinichi Kurata 1-2-58 Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Inventor Hiroaki Maeda 2-58, Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Inventor Tatsuta 1-58 Hiromachi, Shinagawa-ku, Tokyo F-term (reference) 4C055 AA01 BA03 BA05 BA08 BA52 BB02 BB10 CA02 CA57 CA59 CB01 CB02 DA05 DA08 4C063 AA01 BB01 CC29 DD10 EE01 4C086 AA01 AA02 BC21 BC17 BC46 BC50 BC73 GA07 GA12 MA01 ZA45 ZB07 ZB08 ZB13 ZB15 4C206 AA01 AA02 AA03 DA19 DB18 DB43 ZA45 ZB07 ZB08 ZB13 ZB15 4H006 AA01 AB22 BJ50 BN30 BS30 BT32

Claims (34)

[Claims] (1) a compound having the following general formula (I) or
Containing a pharmacologically acceptable salt of as an active ingredient
0 function inhibitor:[Where R¹, R^ThreeAnd R^FourAre the same or different
Hydrogen atom, hydroxyl group, halogen atom, carbon number 1 to 1
5 alkyl groups, alkoxy having 1 to 15 carbon atoms
Group, alkylthio group having 1 to 15 carbon atoms, 1 carbon atom
Up to 15 halogenated alkyl, aryl, and substituent groups
Aryl substituted with 1 to 3 groups selected from the group α
1 selected from the group consisting of
A heteroaryl group substituted with 3 to 3 groups, aralkyl
Group, substituted with 1 to 3 groups selected from substituent group α
An aralkyl group or a compound of the formula —N (R^a) R^bRepresented by
Group (wherein R^aAnd R^bAre the same or different
A hydrogen atom, an alkyl group having 1 to 15 carbon atoms,
A cycloalkyl group having 3 to 8 primes, an aryl group, substitution
Ali substituted with 1 to 3 groups selected from group α
Or a heteroaryl group or a substituent group α.
Heteroaryl group substituted with 1 to 3 groups, aral
1 to 3 groups selected from a kill group or a substituent group α
Represents a substituted aralkyl group, or R^aAnd R^b
Together with the nitrogen atom to which they are attached
To form an amino group. ), R^TwoIs a nitro, nitrile, carboxy or carbon
Represents 2 to 6 alkoxycarbonyl groups, or
Is R¹And R^TwoTogether with the carbon atom to which they are attached
And 1 to 1 selected from an aryl ring and a substituent group α
An aryl ring substituted with three groups, a heteroaryl ring,
Or 1 to 3 groups selected from substituent group α.
X and Y are the same or different and are each a nitrogen atom
Child or CH. [Substituent group α] halogen atom, lower alkyl group, halogen
Lower alkyl group, lower alkoxy group, lower halogenated
Lower alkoxy group, lower alkylthio group, lower halogenated group
Alkylthio group, lower alkylsulfinyl group, lower
Rukylsulfonyl group, group -NR ^cR^d(Where R^cAnd R^d
Are the same or different and are a hydrogen atom, a lower alkyl group
Or an aralkyl group. ), Hydroxyl, nitro, shear
No group. 2. The method of claim 1, wherein R ¹ , R ³ and R
⁴ is the same or different, respectively, a hydroxyl group, an alkyl group having 1 to 15 carbon atoms, an alkoxy group having 1 to 15 carbon atoms, an alkylthio group having 1 to 15 carbon atoms, an aryl group, and a substituent group α Aryl group, heteroaryl group, substituent group α substituted with one to three selected groups
A heteroaryl group substituted with 1 to 3 groups selected from the group consisting of an aralkyl group, an aralkyl group substituted with 1 to 3 groups selected from the substituent group α, or a compound represented by the formula -N (R
^a ) a group represented by R ^b (where R ^a and R ^b are the same or different and are each a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms) ,
An aryl group, an aryl group substituted with 1 to 3 groups selected from a substituent group α, a heteroaryl group, a heteroaryl group substituted with 1 to 3 groups selected from a substituent group α, An aralkyl group or an aralkyl group substituted with 1 to 3 groups selected from the substituent group α, or R ^a and R ^b are, together with the nitrogen atom to which they are attached, Form a group. A) a CD40 function inhibitor; 3. The method according to claim 1, wherein
¹ is a hydroxyl group, an alkyl group having 1 to 15 carbon atoms, an alkylthio group having 1 to 15 carbon atoms, an aryl group, an aryl group substituted with 1 to 3 groups selected from a substituent group α, 1 selected from an aryl group and a substituent group α
A heteroaryl group substituted with 1 to 3 groups, an aralkyl group, an aralkyl group substituted with 1 to 3 groups selected from a substituent group α, or a formula —N (R ^a ) R ^b. Wherein R ^a and R ^b are the same or different and are each a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an aryl group, aryl group, heteroaryl group substituted with 1 to 3 groups selected from α, heteroaryl group, aralkyl group or substituent group substituted with 1 to 3 groups selected from substituent group α an aralkyl group substituted with 1 to 3 groups selected from α, or R ^a and R ^b
Together with the nitrogen atom to which they are attached form a cyclic amino group. A) a CD40 function inhibitor; 4. The method according to claim 1, wherein
¹ is an aryl group, 1 to 3 selected from a substituent group α
Represented by the formula —N (R ^a ) R ^b , an aryl group substituted with 3 groups, a heteroaryl group, a heteroaryl group substituted with 1 to 3 groups selected from the substituent group α. Groups (wherein R ^a and R ^b are the same or different and are each a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an aryl group, a substituent group α An aryl group, a heteroaryl group, or a group selected from a substituent group α, which is substituted with 1 to 3 groups selected from
A heteroaryl group, an aralkyl group, or an aralkyl group substituted with 1 to 3 groups selected from a substituent group α, or R ^a and R
^b together with the nitrogen atom to which they are attached form a cyclic amino group. A) a CD40 function inhibitor; 5. The method according to claim 1, wherein
¹ is an aryl group, 1 to 3 selected from a substituent group α
Or an aryl group substituted with a group of the formula —N (R ^a ) R ^b
Wherein R ^a represents a hydrogen atom, and R ^b represents
Represents an alkyl group having 1 to 15 carbon atoms, an aryl group, or an aryl group substituted with 1 to 3 groups selected from the substituent group α, or R ^a and R ^b are Together with the nitrogen atom, a cyclic amino group is formed. A) a CD40 function inhibitor; 6. A method selected from claims 1 to 4.
In one of the terms, R ^ThreeHas a hydroxyl group and 1 to 1 carbon atoms
5 alkoxy groups or a formula -N (R^a) R^bRepresented by
Group (wherein R^aAnd R^bAre the same or different
A hydrogen atom, an alkyl group having 1 to 15 carbon atoms,
A cycloalkyl group having 3 to 8 primes, an aryl group, substitution
Ali substituted with 1 to 3 groups selected from group α
Or a heteroaryl group or a substituent group α.
Heteroaryl group substituted with 1 to 3 groups, aral
1 to 3 groups selected from a kill group or a substituent group α
Represents a substituted aralkyl group, or R^aAnd R^b
Together with the nitrogen atom to which they are attached
To form a group. A) a CD40 function inhibitor; 7. A method selected from claims 1 to 4.
In one of the terms, R ^ThreeHas a hydroxyl group and 1 to 7 carbon atoms
Alkoxy groups or a group of formula -N (R^a) R^bGroup represented by
(Where R^aRepresents a hydrogen atom, and R^bIs from 1 carbon atom
Represents 15 alkyl groups, or R^aAnd R^bIs
Together with the nitrogen atom to which they are attached, a cyclic amino group
To form A) a CD40 function inhibitor; 8. A method selected from claims 1 to 4.
In one of the terms, R ^ThreeIs the formula -N (R^a) R^bRepresented by
Group (wherein R^aAnd R^bAre the
Together with the elemental atom, it forms a cyclic amino group. ) Is C
D40 function inhibitor. 9. A method selected from claims 1 to 4.
In one of the terms, R ^ThreeIs morpholino or thiomol
A CD40 function inhibitor that is holino. 10. The method according to claim 1, wherein R ⁴ is selected from an alkyl group having 1 to 15 carbon atoms, an aryl group, and a substituent group α.
Aryl group, heteroaryl group substituted with 1 to 3 groups, heteroaryl group substituted with 1 to 3 groups selected from a substituent group α, aralkyl group, or substituent group α
A CD40 function inhibitor, which is an aralkyl group substituted with one to three groups selected from the group consisting of: 11. The method according to claim 1, wherein R ⁴ is an aryl group, an aryl group substituted with 1 to 3 groups selected from a substituent group α, C is a heteroaryl group or a heteroaryl group substituted with 1 to 3 groups selected from substituent group α.
D40 function inhibitors. 12. The CD40 function inhibitor according to any one of claims 1 to 11, wherein R ² is a nitrile group, a carboxy group, or an alkoxycarbonyl group having 2 to 6 carbon atoms. 13. The CD40 according to any one of claims 1 to 11, wherein R ² is a nitrile group or an alkoxycarbonyl group having 2 to 6 carbon atoms.
Function inhibitors. 14. The CD40 function inhibitor according to any one of claims 1 to 11, wherein R ² is a nitrile group or an ethoxycarbonyl group. 15. The method according to claim 1, wherein R ¹ and R ² together with the carbon atom to which they are attached are selected from an aryl ring, a heteroaryl ring and a substituent group α. And a heteroaryl ring substituted with 1 to 3 groups selected from the substituent group α. 16. The method according to claim 1, wherein R ¹ and R ² together with the carbon atom to which they are attached are an aryl ring or one to three groups selected from the substituent group α. A CD40 function inhibitor exhibiting a substituted aryl ring. 17. The CD40 function inhibitor according to any one of claims 1 to 16, wherein at least one of X and Y is a nitrogen atom. 18. The CD40 function inhibitor according to any one of claims 1 to 16, wherein X and Y are both nitrogen atoms. 19. The CD40 function inhibitor according to claim 1, comprising a compound selected from the following or a pharmacologically acceptable salt thereof as an active ingredient: • 4-morpholin-4-yl-2,6-diphenyl -Pyrimidine-5-
Carboxylic acid ethyl ester, 4-Phenylamino-2-pyridin-3-yl-6-thiomorpholin-4-yl-pyrimidin-5-carboxylic acid ethyl ester, 2-Morpholin-4-yl-4,6- Diphenyl-nicotinonitrile. 20. A compound having the following general formula (I), or
Its pharmacologically acceptable salt:[Where R¹Represents a hydrogen atom, a halogen atom, and 3 to 15 carbon atoms
An alkyl group, an alkylthio group having 2 to 15 carbon atoms,
Aryl group, 1 to 3 groups selected from substituent group α
Aryl group substituted with only a halogen atom
Excludes substituted groups. ), Heteroaryl group, substituent group α
Heteroaryl substituted with 1 to 3 groups selected from
A group selected from the group consisting of
An aralkyl group substituted with up to three groups, or a formula -N (R
^a) R^bA group represented by the formula:^aAnd R^bAre the same young
Are different, each being a hydrogen atom, 1 to 15 carbon atoms
An alkyl group, a cycloalkyl group having 3 to 8 carbon atoms,
Aryl group, 1 to 3 groups selected from substituent group α
Aryl group substituted with only a halogen atom
Excludes substituted groups. ), Heteroaryl group, substituent group α
Heteroaryl substituted with 1 to 3 groups selected from
A group selected from the group consisting of a hydroxyl group, an aralkyl group and a substituent group α
Represents an aralkyl group substituted with 3 to 3 groups, or
Is R^aAnd R^bIs the same as the nitrogen atom to which they are attached.
In the meantime, a cyclic amino group is formed. Where R^aAnd R^bIs the same
Sometimes does not show a hydrogen atom. ), R^TwoIs a nitro, nitrile, carboxy or carbon
Represents 2 to 6 alkoxycarbonyl groups, or
Is R¹And R^TwoTogether with the carbon atom to which they are attached
Selected from an aryl ring, a heteroaryl ring, and a substituent group α.
An aryl ring substituted with one to three groups selected, or
Substituted with 1 to 3 groups selected from substituent group α.
Forming a heteroaryl ring, R^ThreeIs a halogen atom, an alkoxy having 3 to 15 carbon atoms
Group, an alkylthio group having 2 to 10 carbon atoms,
Reel group, 1 to 3 groups selected from substituent group α
Substituted heteroaryl group, aralkyl group, substituent group
aralkyl substituted with one to three groups selected from α
Or a group of the formula —N (R^a) R^bA group represented by the formula:^a
And R^bIs as defined above. ), R^FourIs an alkyl group having 1 to 15 carbon atoms, 2 carbon atoms
Up to 15 alkylthio groups, halo having 1 to 15 carbon atoms
Genated alkyl group, aryl group, selected from substituent group α
Aryl group substituted with 1 to 3 groups (provided that
Excludes groups substituted only with logene. ), Heteroaryl
And 1 to 3 groups selected from the substituent group α.
Heteroaryl group, aralkyl group, substituent group α
An aralkyl group substituted with one to three selected groups
(However, a group substituted only with halogen.), Or
The formula -N (R^a) R^bA group represented by the formula:^aAnd R^bIs
The meaning is as defined above. X and Y each represent a nitrogen atom. Where R¹, R^TwoAnd R^ThreeOne or two of the groups
, Heteroaryl, aryl-containing groups, or
A group containing a loaryl,¹And R^FourIs phenyl and R^TwoWhere is a nitrile
If R^ThreeIs methylamino, morpholino, cyclopropyl
Does not represent an amino, cyclobutylamino or chlorine atom;^ThreeIs a chlorine atom, and R^FourR is phenyl¹
Is a chlorine atom, methylamino, ethylamino, phenyl
Amino, p-methylphenylamino or p-methylthiophene
Does not show nil, R¹Is β-naphthyl, and R^TwoIs a nitrile, and R^Four
R is phenyl¹Is cyclopropylamino
No, does not show cyclobutylamino, R¹, R^TwoAnd R^ThreeTwo of the groups are cyclic amino groups
Phenyl or p-methoxyphenyl
Do not indicate^ThreeIs a chlorine atom, and R^FourIs ethylthio
In some cases, R¹Does not represent thienyl or furyl;¹And R^FourAre simultaneously p-methylphenyl or pyrazinyl
If R^ThreeDoes not represent a chlorine atom or morpholino;¹Is phenyl and R^TwoIs ethoxycarbonyl
And R^ThreeIs methylamino, and R^FourIs phenyl
Excluding compounds. [Substituent group α] halogen atom, lower alkyl group, halogen
Lower alkyl group, lower alkoxy group, lower halogenated
Lower alkoxy group, lower alkylthio group, lower halogenated group
Alkylthio group, lower alkylsulfinyl group, lower
Rukylsulfonyl group, group -NR ^cR^d(Where R^cAnd R^d
Are the same or different and are a hydrogen atom, a lower alkyl group
Or an aralkyl group. ), Hydroxyl, nitro, shear
No group. 21. The method according to claim 20, wherein R ¹ is selected from an alkyl group having 3 to 15 carbon atoms, an alkylthio group having 2 to 15 carbon atoms, an aryl group, and a substituent group α.
An aryl group substituted with 1 to 3 groups (excluding a group substituted only with a halogen atom), a heteroaryl group, and a heteroaryl substituted with 1 to 3 groups selected from a substituent group α. Aryl group, aralkyl group, aralkyl group substituted with 1 to 3 groups selected from substituent group α,
Or a group represented by the formula —N (R ^a ) R ^b (wherein R ^a and R ^b
Are the same or different and are each a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an aryl group, and 1 to 3 groups selected from a substituent group α. , An aryl group substituted with only a halogen atom, a heteroaryl group, a heteroaryl group substituted with 1 to 3 groups selected from a substituent group α, and an aralkyl group Or an aralkyl group substituted with 1 to 3 groups selected from the substituent group α, or R ^a and R ^b together with a nitrogen atom to which they are attached, a cyclic amino group Form. However,
^Ra and ^Rb do not simultaneously represent a hydrogen atom. Or a pharmacologically acceptable salt thereof. 22. The method according to claim 20, wherein R ¹ is selected from an aryl group, an aryl group substituted with one to three groups selected from a substituent group α, a heteroaryl group, and a substituent group α. A heteroaryl group substituted with 1 to 3 groups, or a group represented by the formula -N (R ^a ) R ^b (where R ^a and R ^b are the same or different and are each a hydrogen atom, Alkyl group having 1 to 15 carbon atoms, 3 to 8 carbon atoms
Substituted with 1 to 3 groups selected from cycloalkyl group, aryl group, and 1 to 3 substituent groups α, substituted with 1 to 3 groups selected from substituent group α A substituted or unsubstituted heteroaryl group, an aralkyl group, or an aralkyl group substituted by 1 to 3 groups selected from the substituent group α, or R ^a and R ^b represent a nitrogen atom to which they are bonded. Together with form a cyclic amino group. Or a pharmacologically acceptable salt thereof. 23. The method according to claim 20, wherein R ¹ is an aryl group, an aryl group substituted with 1 to 3 groups selected from a substituent group α, or a formula —N (R ^a ) R ^b . Wherein R ^a represents a hydrogen atom, and R ^b is substituted with an alkyl group having 1 to 15 carbon atoms, an aryl group, or 1 to 3 groups selected from a substituent group α. Wherein R ^a and R ^b together with the nitrogen atom to which they are attached form a cyclic amino group), or a pharmaceutically acceptable salt thereof. 24. The compound according to any one of claims 20 to 23, wherein R ² is a nitrile group, a carboxy group or an alkoxycarbonyl group having 2 to 6 carbon atoms, or a pharmacologically active compound thereof. Acceptable salt. 25. The compound according to any one of claims 20 to 23, wherein R ² is a nitrile group or an alkoxycarbonyl group having 2 to 6 carbon atoms, or a pharmacologically acceptable compound thereof. salt. 26. The compound according to any one of claims 20 to 23, wherein R ² is a nitrile group or an ethoxycarbonyl group, or a pharmaceutically acceptable salt thereof. 27. A method selected from claims 20 to 26.
In any one of^ThreeHas 3 to 15 carbon atoms
Alkoxy groups, alkylthio having 2 to 15 carbon atoms
Group, heteroaryl group, a substituent selected from substituent group α
Heteroaryl group substituted with up to 3 groups, aralkyl
And 1 to 3 groups selected from the substituent group α.
Or an aralkyl group of the formula —N (R^a) R^bGroup represented by
(Where R ^aAnd R^bIs as defined above. )
A compound or a pharmacologically acceptable salt thereof. 28. The method according to any one of claims 20 to 26, wherein R ³ has 3 to 15 carbon atoms.
Or a compound represented by the formula —N (R ^a ) R ^b (where R ^a and R ^b are as defined above), or a pharmacologically acceptable one thereof. salt. 29. The method according to any one of claims 20 to 26, wherein R ³ is a group represented by the formula —N (R ^a ) R ^b.
Wherein R ^a and R ^b together with the nitrogen atom to which they are attached form a cyclic amino group, or a pharmaceutically acceptable salt thereof. 30. The compound according to any one of claims 20 to 26, wherein R ³ is morpholino or thiomorpholino, or a pharmaceutically acceptable salt thereof. 31. The method according to any one of claims 20 to 30, wherein R ⁴ is a group having 1 to 15 carbon atoms.
Alkyl groups, alkylthio groups having 2 to 15 carbon atoms, aryl groups, aryl groups substituted with 1 to 3 groups selected from substituent group α (excluding groups substituted only with halogen) .), Heteroaryl group, substituent group α
A heteroaryl group substituted with 1 to 3 groups selected from the group consisting of: an aralkyl group, and an aralkyl group substituted by 1 to 3 groups selected from the substituent group α (however, Or a group of the formula —N (R ^a ) R ^b
(Wherein ^Ra and ^Rb have the same meanings as described above), or a pharmaceutically acceptable salt thereof. 32. The method according to any one of claims 20 to 30, wherein R ⁴ is a group having 1 to 15 carbon atoms.
Alkyl groups, aryl groups, aryl groups substituted with 1 to 3 groups selected from substituent group α, heteroaryl groups, substituted with 1 to 3 groups selected from substituent group α Or a pharmaceutically acceptable salt thereof, which is a heteroaryl group, an aralkyl group, or an aralkyl group substituted with 1 to 3 groups selected from the substituent group α. 33. The method according to any one of claims 20 to 30, wherein R ⁴ is an aryl group, an aryl group substituted with 1 to 3 groups selected from a substituent group α, A compound which is a heteroaryl group or a heteroaryl group substituted with 1 to 3 groups selected from the substituent group α, or a pharmacologically acceptable salt thereof. 34. The compound according to claim 20, wherein the compound is selected from the following, or a pharmacologically acceptable salt thereof: 4-morpholin-4-yl-2,6-diphenyl-pyrimidine-5-
Carboxylic acid ethyl ester, • 4-phenylamino-2-pyridin-3-yl-6-thiomorpholin-4-yl-pyrimidin-5-carboxylic acid ethyl ester.