MX2007014936A - Cyclic amine derivative having substituted alkyl group. - Google Patents

Abstract

Disclosed is a compound represented by the general formula (I) below, a pharmacologically acceptable salt thereof, or a prodrug thereof. [Chemical formula 1] (I) (In the formula, R¹ represents a hydrogen atom, an optionally substituted C₁-C₆ alkyl group, an optionally substituted C₃-C₆ cycloalkyl group or the like; R² represents a hydrogen atom, a halogen atom, a carboxy group, a C₂-C₇ alkoxycarbonyl group, a carbamoyl group, a cyano group, a C₁-C₆ alkyl group, a halogeno C₁-C₆ alkyl group, a C₁-C₆ alkyl group substituted with a heteroaryl group or the like; R³ represents a substituted C₁-C₆ alkyl group, a heterocyclyl group, or a mono- to penta-substituted heterocyclyl group; X¹, X², X³, X⁴ and X⁵ independently represent a hydrogen atom, a halogen atom, an amino group, a carboxy group, a carbamoyl group, a cyano group, a nitro group, a C₁-C₆ alkyl group or the like; and n represents an integer of 0-2.).

Description

AMYCLIC AMINE DERIVATIVE WITH ALQUI GROUP REPLACED Technical field The present invention relates to compounds that show activity in the inhibition of platelet aggregation, pharmacologically acceptable salts thereof, and prodrugs thereof. BACKGROUND OF THE INVENTION Recently, the number of patients with cardiovascular diseases associated with the aging of the population and with changes in eating habits and lifestyle has increased markedly. Since thrombotic diseases such as cerebral infarction, myocardial infarction and peripheral circulatory disorders not only have high morbidity but also produce a poor prognosis and limitation of activities of daily living, the patient with these disorders has an undue burden of personal disability And social. It is well known that the direct causes of these diseases are angiostenoses caused by thrombi induced by the activation of platelets (adhesion to damaged areas of blood vessels, release of physiologically active substances, formation of clots and the like) and ischemia associated with angiostenosis. Thus, antifrombóficos agents that inhibit the activation of platelets play important roles in the prevention of the appearance and recurrence of these diseases, as well as in their treatment.

Additionally, it is considered that these agents become more and more important in the future as the number of patients with thrombotic diseases increases. Various biological substances related to platelet aggregation, such as adenosine 5'-diphosphate (ADP), thromboxane A2 (TXA2), collagen, serotonin (5-hydroxytryptamine, 5-HT) and the like, are known. Moreover, the P2Y receptors? and the P2Y receptors? 2 are known as ADP receptors. Some existing antithrombotic agents act by antagonizing these receptors. Examples of these antithrombotic agents are ticlopidine and clopidogrel, which have thienopyridine structures. In addition, the compounds described in patent documents 1 and 2 are known as compounds with non-thienopyridine structures and with antagonistic action against ADP receptors. However, there are certain problems in which these compounds are chemically unstable or weakly active. Patent Document 1: WO98 / 0881 1 Patent Document 2: W099 / 43648 DESCRIPTION OF THE INVENTION Problems that the invention will solve The inventors of the present, in order to create novel antithrombotic agents, have diligently explored stable compounds having non-thienopyridine structures and having activity in the inhibition of platelet aggregation, and found that the compounds having the general formula (I) of the present invention, pharmacologically acceptable salts thereof and prodrugs thereof have desirable characteristics , and in this way realized the present invention. The present invention provides compounds having the general formula (I), salts thereof or prodrugs thereof pharmacologically acceptable; pharmaceutical compositions containing compounds having the general formula (I), pharmacologically acceptable salts thereof or prodrugs thereof, as active ingredients (particularly pharmaceutical compositions for prophylactic or therapeutic agents for diseases related to thrombus or embolus formation); use of the compound having the general formula (I), pharmacologically acceptable salts thereof or prodrugs thereof to make pharmaceutical compositions (particularly pharmaceutical compositions for prophylactic or therapeutic agents for diseases related to thrombus or embolus formation); use of the compounds having the general formula (I), salts thereof or prodrugs thereof pharmacologically acceptable for prophylactic or therapeutic agents for diseases related to thrombus or embolus formation; and prophylactic or therapeutic methods for diseases (particularly diseases related to thrombus formation or emboli) by administering pharmacologically effective doses of the compounds having the general formula (I), salts thereof or prodrugs thereof pharmacologically acceptable to warm-blooded animals (especially humans). Means for solving problems The present invention relates to the compound having the general formula (I) shown below, [wherein R1 represents a hydrogen atom, an alkyl group of 1 to 6 carbon atoms which may be substituted (said substituent group represents a halogen atom or an alkoxy group of 1 to 6 carbon atoms), a cycloalkyl group of 3 to 6 carbon atoms which may be substituted (said substituent group represents a halogen atom or an alkoxy group of 1 to 6 carbon atoms), an alkoxy group of 1 to 6 carbon atoms which may be substituted (said substituent group represents a halogen atom or an alkoxy group of 1 to 6 carbon atoms), or an aryl group of 6 to 10 carbon atoms which may be substituted (said substituent group represents a halogen atom, an alkyl group of 1 to 6 carbon atoms, an alkoxy group of 1 to 6 carbon atoms, a cyano group or a nitro group); R 2 represents a hydrogen atom, a halogen atom, a carboxy group, an alkoxycarbonyl group of 2 to 7 carbon atoms, a carbamoyl group, a cyano group, an alkyl group of 1 to 6 carbon atoms, a halogenated alkyl group from 1 to 6 carbon atoms, an alkyl group of 1 to 6 carbon atoms substituted by a heteroaryl group, an alkoxy group of 1 to 6 carbon atoms, a halogenated alkoxy group of 1 to 6 carbon atoms, a hydroxy group alkyl of 1 to 6 carbon atoms, an alkoxyalkyl group of 2 to 1 2 carbon atoms, a formyl group, an alkanoyl group of 2 to 7 carbon atoms, a cycloalkylcarbonyl group of 4 to 7 carbon atoms, an alkylcarbamoyl group from 2 to 7 carbon atoms, a di (C 1-6) alkyl group, carbamoyl, a group of the formula R -CO-CR 5 R 6 - (CH 2) m-. { wherein R 4 represents a hydroxyl group, an amino group, an alkyl group of 1 to 6 carbon atoms, an alkylamino group of 1 to 6 carbon atoms, a di (alkyi) group of 1 to 6 carbon atoms) amino, a hydroxyamino group, an alkoxyamino group of 1 to 6 carbon atoms or an alkoxy group of 1 to 6 carbon atoms; R5 and R6 are the same or different and each represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms; and m represents an integer from 0 to 5.}. , a group of the formula R7-CO- (CH2), - N (R8) -. { wherein R7 represents a hydroxyl group, an amino group, an alkyl group of 1 to 6 carbon atoms, an alkylamino group of 1 to 6 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) amino group, an hydroxyamino group, an alkoxyamino group of 1 to 6 carbon atoms or an alkoxy group of 1 to 6 carbon atoms; R8 represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms; and I represents an integer from 0 to 5.}. or a sulfamoyl alkyl group of 1 to 6 carbon atoms; R3 represents a substituted alkyl group of 1 to 6 carbon atoms. { said substituent group represents an aryl group of 6 to 10 carbon atoms or an aryl group of 6 to 10 carbon atoms substituted with from 1 to 5 substituents selected from < Substituent group a >; a heterocyclyl group or a heterocyclyl group substituted with from 1 to 5 substituents selected from < Substituent group a > (said heterocyclyl groups may be substituted with from 1 to 4 oxo groups); a heteroaryl group or a heteroaryl group substituted with from 1 to 5 substituents selected from < Substituent group a >; or a substituent selected from < Substituent group ß > } , or a heterocyclyl group or a heterocyclyl group substituted with from 1 to 5 substituents selected from < Substituent group a > (said heterocyclyl groups may be substituted with from 1 to 4 oxo groups); X1, X2, X3, X4 and X5 each independently represent a hydrogen atom, a halogen atom, an amino group, a carboxy group, a carbamoyl group, a cyano group, a nitro group, an alkyl group of 1 to 6 carbon atoms, a halogenated alkyl group of 1 to 6 carbon atoms, an alkoyl group of 1 to 6 carbon atoms or a halogenated alkoxy group of 1 to 6 carbon atoms; n represents an integer from 0 to 2, the < Substituent group a > is defined by a halogen atom, an amino group, a carboxy group, an alkoxycarbonyl group of 2 to 7 carbon atoms, a carbamoyl group, a cyano group, a hydroxyl group, a nitro group, an alkyl group of 1 to 6 carbon atoms, a halogenated alkyl group of 1 to 6 carbon atoms, an alkyl group of 1 to 6 carbon atoms substituted with heteroaryl group (s), an alkoxy group of 1 to 6 carbon atoms, a halogenated alkoxy group of 1 to 6 carbon atoms, a hydroxy alkyl group of 1 to 6 carbon atoms, an alkoxyalkyl group of 2 to 1 2 carbon atoms, a formyl group, an alkanoyl group of 2 to 7 carbon atoms, a cycloalkylcarbonyl group of 4 to 7 carbon atoms, an alkylamino group of 1 to 6 carbon atoms, a di (alkyi) group of 1 to 6 carbon atoms) amino, an alkylcarbamoyl group of 2 to 7 carbon atoms, a di (alkyl) group from 1 to 6 carbon atoms) carbamoyl, a group of the formula R 4 -CO-CR 5 R 6 - (CH 2) m-. { wherein R 4 represents a hydroxyl group, an amino group, an alkyl group of 1 to 6 carbon atoms, an alkylamino group of 1 to 6 carbon atoms, a di (alkyi) group of 1 to 6 carbon atoms) amino, a hydroxyamino group, an alkoamino group of 1 to 6 carbon atoms or an alkoxy group of 1 to 6 carbon atoms; R5 and R6 are the same or different and each represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms; and m represents an integer from 0 to 5.}. and a sulfamoyl alkyl group of 1 to 6 carbon atoms; and The < Substituent group ß > is defined by a halogen atom, an amino group, a carboxy group, an alkoxycarbonyl group of 2 to 7 carbon atoms, a carbamoyl group, a cyano group, a hydroxyl group, a nitro group, an alco? i group of 1 to 6 carbon atoms, a halogenated alkoxy group of 1 to 6 carbon atoms, a formyl group, an alkanoyl group of 2 to 7 carbon atoms, a cycloalkylcarbonyl group of 4 to 7 carbon atoms, an alkylamino group of 1 to 6 carbon atoms, a di (C 1-6 alkyl) amino group, an alkylcarbamoyl group of 2 to 7 carbon atoms, a di (C 1-6) alkyl group, carbamoyl, a hydroxyaminocarbonyl group, a (C 1 -C 6 -alkoxy) aminocarbonyl group, a group of the formula R 9 -CO- (CH 2) kN (R 10) -. { wherein R 9 represents a hydroxyl group, an amino group, an alkyl group of 1 to 6 carbon atoms, an alkylamino group of 1 to 6 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) amino group, an hydroxyamino group, an alkoxyamino group of 1 to 6 carbon atoms or an alkoxy group of 1 to 6 carbon atoms; R 1 0 represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms; and k represents an integer from 0 to 5.}. and a sulfamoyl alkyl group of 1 to 6 carbon atoms], salts thereof or prodrugs thereof pharmacologically acceptable. A compound having the general formula (I) shown above, a pharmacologically acceptable salt thereof or a prodrug thereof, preferably is (1) a compound wherein R represents an alkyl group of 1 to 6 carbon atoms, halogenated alkyl group of 1 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, a halogenated cycloalkyl group of 3 to 6 carbon atoms or an alkoxy group of 1 to 6 carbon atoms, salts thereof or prodrugs of it pharmacologically acceptable; (2) a compound wherein R 1 represents a cycloalkyl group of 3 to 6 carbon atoms, a halogenated cycloalkyl group of 3 to 6 carbon atoms or an alkoxy group of 1 to 6 carbon atoms, salts thereof or prodrugs thereof pharmacologically acceptable; (3) a compound wherein R1 represents a cycloalkyl group of 3 to 6 carbon atoms or an alkoxy group of 1 to 6 carbon atoms, salts thereof or prodrugs thereof pharmacologically acceptable; (4) a compound wherein R 1 represents a cyclopropyl group or a methoxy group, salts thereof or prodrugs thereof pharmacologically acceptable; (5) a compound wherein R 1 represents a cyclopropyl group, salts thereof or prodrugs thereof pharmacologically acceptable; (6) a compound wherein R 2 represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms, salts thereof or prodrugs thereof pharmacologically acceptable; (7) a compound wherein R 2 represents a hydrogen atom or a methyl group, salts thereof or prodrugs thereof pharmacologically acceptable; (8) a compound wherein R 2 represents a hydrogen atom, salts thereof or prodrugs thereof pharmacologically acceptable; (9) a compound wherein R3 represents a substituted alkyl group of 1 to 6 carbon atoms. { said substituent group represents a heterocyclyl group or a heterocyclyl group substituted with 1 or 2 substituents selected from < Substituent group a > (said heterocyclyl groups may be substituted by 1 or 2 oxo groups), a heteroaryl group or a heteroaryl group substituted with 1 or 2 substituents selected from < Substituent group a > or a substituent selected from < Substituent group ß > } , or a heterocyclyl group or a heterocyclyl group substituted with 1 or 2 substituents selected from < Substituent group > (said heterocyclyl groups may be substituted by 1 or 2 oxo groups), salts thereof or pharmacologically acceptable prodrugs thereof; (10) a compound wherein R3 represents a substituted alkyl group of 1 to 6 carbon atoms. { said substituent group represents a 4- to 7-membered heterocyclyl group containing at least one nitrogen atom which may be substituted with 1 or 2 substituents selected from < Substituent group a1 > (said heterocyclyl group may be substituted by an oxo group), a heteroaryl group containing at least one nitrogen atom which may be substituted with 1 or 2 substituents selected from < Substituent group a1 > , a carboxy group, an alkoxycarbonyl group of 2 to 7 carbon atoms, a cyano group, a hydroxyl group, an alkoxy group of 1 to 6 carbon atoms or a group of the formula R9-CO- (CH2) kN (R1 0) - (wherein R9 represents a hydroxyl group or an alkoxy group of 1 to 6 carbon atoms, R10 represents an alkyl group of 1 to 6 carbon atoms, and k represents an integer from 1 to 5)} , or a 4- to 7-membered heterocyclyl group containing at least one nitrogen atom which may be substituted with a substituent selected from < Substituent group a1 > (said heterocyclyl group may be substituted by an oxo group), and The < Substituent group a1 > is a group consisting of a carboxy group, an alkoxycarbonyl group of 2 to 7 carbon atoms and a group of the formula R 4 -CO-CR 5 R 6 - (CH 2) m- (wherein R 4 represents a hydroxyl group, an amino group, an alkylamino group of 1 to 6 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) amino group, a hydroxyamino group, an alkoxyamino group of 1 to 6 carbon atoms or an alkoxy group of 1 to 6 carbon atoms carbon; R5 and R6 each represent a hydrogen atom; and m represents an integer from 0 to 5), pharmacologically acceptable salts thereof or prodrugs thereof; (11) a compound wherein R 3 represents a substituted alkyl group of 1 to 3 carbon atoms. { said substituent group represents a pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, pyrazolyl, triazolyl or tetrazolyl group which may be substituted with 1 or 2 substituents selected from < Substituent group a2 >; (said pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl or piperazinyl group can be substituted by an oxo group), a carboxy group, an alkoxycarbonyl group of 2 to 4 carbon atoms, a hydroxyl group or a group of the formula R9-CO- ( CH2) kN (R1 0) - (wherein R9 represents a hydroxyl group or an alkoxy group of 1 to 3 carbon atoms, R10 represents an alkyl group of 1 to 3 carbon atoms and k represents an integer from 1 to 3)} , or a pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl or piperazinyl group which may be substituted with a substituent selected from < Substituent group a2 > (said pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl or piperazinyl group may be substituted by an oxo group), and The < Substituent group a2 > is a group consisting of a carboxy group, an alkoxycarbonyl group of 2 to 4 carbon atoms and a group of the formula R 4 -CO-CR 5 R 6 - (CH 2) m- (wherein R 4 represents a hydroxyl group or an alkoxy group of 1 to 3 carbon atoms, R5 and R6 each represent a hydrogen atom, and m represents an integer from 0 to 2), pharmacologically acceptable salts thereof, or prodrugs thereof; (12) a compound wherein R 3 represents a substituted methyl or ethyl group. { said substituent group represents a pyrrolidinyl, piperidinyl, piperazinyl or pyrazolyl group which may be substituted with 1 or 2 substituents selected from < Substituent group a3 > (said pyrrolidinyl, piperidinyl or piperazinyl group may be substituted by an oxo group), a carboxy group or a group of the formula R9-CO- (CH2) kN (R1 0) - (wherein R9 represents a hydroxyl group, a group methoxy or an ethoxy group, R 1 0 represents a methyl group, an ethyl group or an isopropyl group, and k represents an integer from 1 to 3), and < Substituent group a3 > is a group consisting of a carboxy group, a methoxycarbonyl group, an ethoxycarbonyl group, a carboxymethyl group, a methoxycarbonylmethyl group, an ethoxycarbonylmethyl group, a 2- (carboxy) ethyl group, a 2- (methoxycarbonyl) ethyl group and a group 2- (ethoxycarbonyl) ethyl, salts thereof or prodrugs thereof pharmacologically acceptable; (1 3) a compound wherein X1, X2, X3, X4 and X5 independently represent a hydrogen atom or a halogen atom, salts thereof or prodrugs thereof pharmacologically acceptable; (14) a compound wherein X1 and X2 independently represent a hydrogen atom or a halogen atom; and X3, X4 and X5 represent a hydrogen atom, salts thereof or prodrugs thereof pharmacologically acceptable; (1 5) a compound wherein X 1 represents a halogen atom; and X2, X3, X4 and X5 represent a hydrogen atom, salts thereof or prodrugs thereof pharmacologically acceptable; (1 6) a compound wherein X 1 represents a fluorine atom; and X2, X3, X4 and X5 represent a hydrogen atom, salts thereof or prodrugs thereof pharmacologically acceptable; (17) a compound wherein n represents 0 or 1, salts thereof or prodrugs thereof pharmacologically acceptable; and (18) a compound wherein n represents 1, pharmacologically acceptable salts thereof or prodrugs thereof. Additionally, in each group of (1) - (5), (6) - (8), (9) - (12), (13) - (16) and (17) - (18) described above, is shown a more preferable compound as the number increases [the same concept applies to each group of (19) - (22) described later]. A compound obtained by selecting R1 from each group of (1) - (5); R2 of each group of (6) - (8); R3 of each group of (9) - (12); X1, X2, X3, X4 and X5 of each group of (13) - (16); and n of each group of (17) - (18), respectively, followed by the arbitrary combination of these selected groups, is also preferable, and may be, for example, the following: (19) a compound wherein R represents a group cycloalkyl of 3 to 6 carbon atoms or an alkoxy group of 1 to 6 carbon atoms; R2 represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms; R3 represents a substituted alkyl group of 1 to 6 carbon atoms. { said substituent group represents a heterocyclyl group or a heterocyclyl group substituted with 1 or 2 substituents selected from < Substituent group a > (said heterocyclyl groups may be substituted by 1 or 2 oxo groups), a heteroaryl group or a heteroaryl group substituted with 1 or 2 substituents selected from < Substituent group a > , or a substituent selected from < Substituent group ß > } , or a heterocyclyl group or a heterocyclyl group substituted with 1 or 2 substituents selected from < Substituent group a > (said heterocyclyl groups may be substituted by 1 or 2 oxo groups); X1 and X2 independently represent a hydrogen atom or a halogen atom; X3, X4, and X5 represent a hydrogen atom; and n is 0 or 1, a pharmacologically acceptable salt thereof, or a prodrug thereof; (20) a compound wherein R 1 represents a cyclopropyl group or a methoxy group; R2 represents a hydrogen atom or a methyl group; R3 represents a substituted alkyl group of 1 to 6 carbon atoms. { said substituent group represents a 4- to 7-membered heterocyclyl group containing at least one nitrogen atom which may be substituted with 1 or 2 substituents selected from < Substituent group a1 > (said heterocyclyl group may be substituted by an oxo group), a heteroaryl group containing at least one nitrogen atom which may be substituted with 1 or 2 substituents selected from < Substituent group a1 > , a carboxy group, an alkoxycarbonyl group of 2 to 7 carbon atoms, a cyano group, a hydroxyl group, an alkoxy group of 1 to 6 carbon atoms or a group of the formula R9-CO- (CH2) kN (R10 ) - (wherein R9 represents a hydroxyl group or an alkoxy group of 1 to 6 carbon atoms, R1 represents an alkyl group of 1 to 6 carbon atoms, and k represents an integer from 1 to 5)} , or a 4- to 7-membered heterocyclyl group containing at least one nitrogen atom which may be substituted with a substituent selected from < Substituent group a1 > (said heterocyclyl group may be substituted by an oxo group), and The < Substituent group a1 > is a group consisting of a carboxy group, an alkoxycarbonyl group of 2 to 7 carbon atoms, and a group of the formula R 4 -CO-CR 5 R 6 - (CH 2) m- (wherein R 4 represents a hydroxyl group, an amino group , an alkylamino group of 1 to 6 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) amino group, a hydroxyamino group, an alkoxyamino group of 1 to 6 carbon atoms or an alkoxy group of 1 to 6 atoms of carbon, R5 and R6 each represent a hydrogen atom, and m represents an integer from 0 to 5); X1 represents a halogen atom; X2, X3, X4 and X5 represent a hydrogen atom; and n represents 1, pharmacologically acceptable salts thereof or prodrugs thereof; (21) a compound wherein R 1 represents a cyclopropyl group; R2 represents a hydrogen atom; R3 represents a substituted alkyl group of 1 to 3 carbon atoms. { said substituent group represents a pyidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, pyrazolyl, triazolyl or tetrazolyl group which may be substituted with 1 or 2 substituents selected from < Substituent group 2 > (said pyidinyl, piperidinyl, morpholinyl, thiomorpholinyl or piperazinyl group can be substituted by an oxo group), a carboxy group, an alkoxycarbonyl group of 2 to 4 carbon atoms, a hydroxyl group or a group of the formula R9-CO- ( CH2) kN (R10) - (wherein R9 represents a hydroxyl group or an alkoxy group of 1 to 3 carbon atoms, R10 represents an alkyl group of 1 to 3 carbon atoms and k represents an integer from 1 to 3)} , or a pyidinyl, piperidinyl, morpholinyl, thiomorpholinyl or piperazinyl group which may be substituted with a substituent selected from <Substituent group a2 > (said pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, or piperazinyl group may be substituted by an oxo group), and The < Substituent group a2 > is a group consisting of a carboxy group, an alkoxycarbonyl group of 2 to 4 carbon atoms, and a group of the formula R 4 -CO-CR 5 R 6 - (CH 2) m- (wherein R 4 represents a hydroxyl group or an alkoxy group from 1 to 3 carbon atoms, R5 and R6 each represent a hydrogen atom, and m represents an integer from 0 to 2); X1 represents a fluorine atom; X2, X3, X4 and X5 represent a hydrogen atom; and n represents 1, pharmacologically acceptable salts thereof or prodrugs thereof, and (22) a compound wherein R 1 represents a cyclopropyl group; R2 represents a hydrogen atom; R3 represents a substituted methyl or ethyl group. { said substituent group represents a pyrrolidinyl, piperidinyl, piperazinyl or pyrazolyl group which may be substituted with 1 or 2 substituents selected from < Substituent group a3 > (said pyrrolidinyl, piperidinyl or piperazinyl group may be substituted by an oxo group), a carboxy group or a group of the formula R9-CO- (CH2) kN (R1 0) - (wherein R9 represents a hydroxyl group, a group methoxy or an ethoxy group, R 10 represents a methyl group, an ethyl group or an isopropyl group, and k represents an integer from 1 to 3), and < Substituent group a3 > It is a group consisting of a carboxy group, a methoxycarbonyl group, an ethoxycarbonyl group, a carboxymethyl group, a methoxycarbonylmethyl group, an ethoxycarbonylmethyl group, a 2- (carboxy) ethyl group, 2- (methoxycarbonyl) ethyl and a group 2- (ethoxycarbonyl) ethyl; X1 represents a fluorine atom; X2, X3, X4 and X5 represent a hydrogen atom; and n represents 1, pharmacologically acceptable salts thereof or prodrugs thereof. In addition, another aspect of the present invention relates to a medicament containing the compound, pharmaceutically acceptable salts or prodrugs thereof described in (1) - (22) above (preferably an antithrombotic agent); use of the compound, salts thereof or prodrugs thereof pharmacologically acceptable to manufacture pharmaceutical compositions; use of the compound, salts thereof or prodrugs thereof pharmacologically acceptable for prophylactic or therapeutic agents for diseases related to formation of thrombi or emboli; and prophylactic or therapeutic methods for diseases (particularly diseases related to thrombus or embolus formation) by administration of pharmacologically effective dose of the compound, salts thereof or pharmacologically acceptable prodrugs thereof to warm-blooded animals (especially humans). The "alkyl group of 1 to 6 carbon atoms" in the general formula (I) shown above can be, for example, a straight or branched chain alkyl group having from 1 to 6 carbon atoms such as a group methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, isopentyl, 2-methylbutyl, neopentyl, 1 -etilpropilo, hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1 - methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1, 1 -dimetilbutilo, 1, 2-dimethylbutyl, 1, 3-dimetiibutilo, 2,3-dimethylbutyl or 2-ethylbutyl, and is preferably a chain alkyl group straight or branched having from 1 to 4 carbon atoms, more preferably a straight or branched chain alkyl group having from 1 to 3 carbon atoms, more preferably a methyl or ethyl group, and most preferably a methyl group. The "halogen atom" in the general formula (I) shown above can be, for example, a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and preferably it is a fluorine atom or a chlorine atom, and more preferably a fluorine atom. The "C 1 -C 6 alkoxy group" in the general formula (I) shown above indicates a group wherein said "C 1 -C 6 alkyl group" is attached to an oxygen atom, and can be, for example, an alkoxy group of straight or branched chain alkyl having from 1 to 6 carbon atoms such as butoxy t-methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy, n-pentyloxy, isopentyloxy, 2-metilbutox¡, neopentyloxy, n-hexyloxy, 4-methylpentyloxy, 3-methylpentyl? i, 2-methylpentyloxy, 3,3-dimetilbuto? i, 2,2-dimetilbuto? i, 1, 1 dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy or 2,3-dimethylbutoxy, and preferably is a straight or branched chain alkoxy group having from 1 to 4 carbon atoms, more preferably an alkoxy group of straight or branched chain that has from 1 to 3 carbon atoms, and much more preferably a group meto? i or eto? i. The "cycloalkyl group of 3 to 6 carbon atoms" in the general formula (I) shown above can be, for example, a saturated cyclic hydrocarbon group of 3 to 6 members such as a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group ilo, and preferably it is a cyclopropyl group. The "aryl group of 6 to 10 carbon atoms" in the general formula (I) shown above can be, for example, an aromatic hydrocarbon group having from 6 to 10 carbon atoms such as a phenyl group or naphthyl, and preferably it is a phenyl group. The "alkoxycarbonyl group of 2 to 7 carbon atoms" in the general formula (I) shown above can be, for example, a straight or branched chain alkoxycarbonyl group having from 2 to 7 carbon atoms such as a group methoxycarbonyl, ethocarbonyl, n-propocarbonyl, isopropocarbonyl, n-butocarbonyl, isobutocarbonyl, s-butocarbonyl, t-butocarbonyl, n-pentylcarbonyl, isopentylcarbonyl, 2- methylbutyl? -carbonyl, neopentyl? -carbonyl, n-he? yl? -carbonyl, 4-methylpentyl? -carbonyl, 3-methylpentyl? -carbonyl, 2-methylpentyloxycarbonyl, 3,3-dimethylbutoxycarbonyl, 2,2-dimethylbutocarbonyl, 1.1- dimethylbutoxycarbonyl, 1,2-dimethylbutoxycarbonyl, 1,3-dimethylbutoxycarbonyl or 2,3-dimethylbutocarbonyl, and preferably is a straight or branched alkoxycarbonyl group having from 2 to 5 carbon atoms, more preferably a straight or branched chain alkoxycarbonyl group having from 2 to 4 carbon atoms carbon, and most preferably a methoxycarbonyl or ethocarbonyl group. The "halogenated alkyl group of 1 to 6 carbon atoms" in the general formula (I) shown above indicates a group wherein said "alkyl group of 1 to 6 carbon atoms" is substituted with halogen atom (s). , and may be, for example, a trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, dibromomethyl, fluoromethyl, 2,2, 2-trifluoroethyl, 2,2,2-trichloroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2-iodoethyl, 3-chloropropyl, 4-fluorobutyl, 6-iodohexyl or 2,2-dibromoethyl, and preferably is a trifluoromethyl group. The "heteroaryl group" in the general formula (I) shown above can be, for example, a 5 to 7 membered aromatic heterocyclic group containing from 1 to 4 sulfur atom (s), oxygen atom (s). and / or nitrogen atom (s) such as a furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl group, or an aromatic heterocyclic group fused with other cyclic groups such as an isoindolyl, indolyl, isoquinolyl and quinolyl group, and preferably is a 5- to 7-membered aromatic heterocyclic group containing at least one nitrogen atom, and more preferably a pyrazolyl, triazolyl group or tetrazolyl. The "halogenated alkoxy group of 1 to 6 carbon atoms" in the general formula (I) shown above indicates a group wherein said "alkoxy group of 1 to 6 carbon atoms" is substituted with halogen atom (s). , and may be, for example, a trifluoromethoxy, trichloromethane, difluoromethate, dichloromethoxy, dibromomethoxy, fluoromethoxy, 2,2,2-trichloroethoxy, 2,2,2-trifluoroethoxy, 2-bromoethoxy group, 2-chloroethoxy, 2-fluoroetho-io 2, 2-dibromoetho-i, and preferably is a 2-bromoetho-i, 2-chloroethoxy or 2-fluoroetho-i group. The "hydroxy alkyl group of 1 to 6 carbon atoms" in the general formula (I) shown above indicates a group wherein said "alkyl group of 1 to 6 carbon atoms" is substituted with hydroxyl group (s), and may be, for example, a hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxy-2-methylethyl, 2-hydroxy-2-methylethyl, 1-hydroxypropyl, 2-hydroxy group. ? ipropyl, 3-hydro? ipropyl, 1 -hydro? -butyl, 2-hydro? -butyl, 3-hydro? -butyl, 4-hydro? -butyl, 5-hydro? -pentyl or 6-hydro? Iheyl, and preferably is a hydro-imethyl group, 2- hydrophilic or 3-hydro? ipropyl. The "alkoxyalkyl group of 2 to 12 carbon atoms" in the general formula (I) shown above indicates a group wherein said "alkoxy group of 1 to 6 carbon atoms" is attached to said "alkyl group of 1 to 6 carbon atoms ", and can be, for example, a methoxymethyl, etho? Imethyl, n-propo? Imethyl, isopropo? Imethyl, n-buto? Imethyl, isobuto? Imethyl, s-buto? Imethyl, t -butoxymethyl, n-pentyloxymethyl, isopentyl-imethyl, 2-methylbuto-imethyl, neopentyl-imethyl, n-heyl-1-ethyl, 4-methylpentyl-imethyl, 3-methylpentyl-imethyl, 2-methylpentyl-imethyl, 3.3 dimethylbute: imethyl, 2,2-dimethylbuto-imethyl, 1,1-dimethylbutoxymethyl, 1,2-dimethylbuto-imethyl, 1,3-dimethylbuto-imethyl, 2,3-dimethylbuto-imethyl, 2-methoxyethyl, -ethoxyethyl, 2- (n-propoxy) ethyl, 2- (isopropoxy) ethyl, 2- (n-butoxy) ethyl, 2- (isobuto? i) ethyl, 2- (s-butoxy) ethyl, 2- (t -butoxy) ethyl, 2- (n-pentyloxy) ethyl, 2- (isopentyloxy) ethyl, 2- (2-methylbuto? i) ethyl, 2- (neopentyloxy) ethyl, 2- (n-hexyl? i) ethyl, 2- (4-methyl) pentyloxy) ethyl, 2- (3-methylpentyloxy) ethyl, 2- (2-methylpentyl? i) ethyl, 2- (3,3-dimethylbutoxy) ethyl, 2,2-dimethylbutoxyethyl, 1,1-dimethylbutyrate, 1 , 2-dimethylbuto-ethyl, 1,3-dimethylbuto-ethyl or 2,3-dimethylbuto-ethyl, and preferably is a straight or branched-chain alkoxyalkyl group having from 2 to 4 carbon atoms, and more preferably a Metho? imethyl or metoethyl group. The "alkanoyl group of 2 to 7 carbon atoms" in the general formula (I) shown above can be, for example, a straight or branched chain alkanoyl group having from 2 to 7 carbon atoms such as a group acetyl, propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl, valeryl, isovaleryl, heteroaryl or heptanoyl, and preferably is a straight or branched chain alkanoyl group having from 2 to 5 carbon atoms, more preferably a chain alkanoyl group straight or branched having from 2 to 4 carbon atoms, and even more preferably an acetyl group. The "cycloalkylcarbonyl group of 4 to 7 carbon atoms" in the general formula (I) shown above indicates a group wherein said "cycloalkyl group of 3 to 6 carbon atoms" is attached to a carbonyl group, and may be , for example, a cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl or cyclohexylcarbonyl group, and preferably is a cyclopropylcarbonyl group. The "alkylcarbamoyl group of 2 to 7 carbon atoms" in the general formula (I) shown above indicates a group wherein an "alkyl group of 1 to 6 carbon atoms" is attached to a carbamoyl group, and can be , for example, a methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, isobutylcarbamoyl, s-butylcarbamoyl, t-butylcarbamoyl, pentylcarbamoyl, isopentylcarbamoyl, 2-methyl I butylcarbamoyl, neopen ti I carbamoyl, 1-ethyl propylcarbamoyl, heterocarbamoyl group , 4-methylpentylcarbamoyl, 3-methylpentylcarbamoyl, 2-methylpentylcarbamoyl, 1-methylpentylcarbamoyl, 3,3-dimethylbutylcarbamoyl, 2,2-dimethylbutylcarbamoyl, 1,1-dimethylbutylcarbamoyl, 1,2-dimethylbutylcarbamoyl, 1,3-dimethylbutylcarbamoyl, 2,3 -dimethylbutylcarbamoyl or 2-ethylbutylcarbamoyl, and preferably is an alkylcarbamoyl group having from 2 to 5 carbon atoms, and more preferably a methylcarbamoyl or ethylcarbamoyl group. The "carbamoyl di (C1-C6 alkyl) group" in the general formula (I) shown above indicates a group in which a carbamoyl group is disubstituted with two "alkyl groups of 1 to 6 carbon atoms" , and may be, for example, a dimethylcarbamoyl, methylethylcarbamoyl, diethylcarbamoyl, di-n-propylcarbamoyl, diisopropylcarbamoyl, N- (n-propyl) -N-ethylcarbamoyl, di-n-butylcarbamoyl, diisobutylcarbamoyl group, Di-s-butylcarbamoyl, t-butylcarbamoyl-di, di-n-pentylcarbamoyl, diisopentílcarbamoilo, di-2-methy I butylcarbamoyl, dineopentilcarbamoilo, di-1 -etilpropilcarbamoilo, di-n-hexylcarbamoyl, di-4-metilpentilcarbamoilo, di -3-metilpentilcarbamoilo, di-2-metilpentilcarbamoilo, di-1 -metilpentilcarbamoilo, di-3,3-dimetilbutilcarbamoílo, di-2,2- dimetilbutilcarbamoilo, di-1, 1 -dimetilbutilcarbamoilo, di-1, 2-dimetilbutilcarbamoilo, di -1,3-dimethylbutylcarbamoyl, di-2,3-dimethylbutylcarbamoyl or di-2-ethylbutylcarbamoyl, and preferably is a dimethylcarbamoyl, methylethylcarbamoyl or diethylcarbamoyl group. The "C 1 -C 6 alkylamino group" in the general formula (I) shown above indicates a group in which an "alkyl group of 1 to 6 carbon atoms" is attached to an amino group, and can be , for example, a straight or branched chain alkylamino group having from 1 to 6 carbon atoms such as a methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, s-butylamino, t-butylamino, pentylamino, isopentylamino group, -metilbutilamino, neopentylamino, 1 -etilpropilamino, I? ylamino, 4-methylpentylamino, 3-methylpentylamino, 2-methylpentylamino, 1 -metilpentilamino, 3,3-dimethylbutylamino, 2,2-dimethylbutylamino, 1, 1 -dimetilbutilamino, 1, 2 -dimethylbutylamino, 1,3-dimethylbutylamino, 2,3-dimethylbutylamino or 2-ethylbutylamino, and preferably is a straight or branched chain alkylamino group having from 1 to 4 carbon atoms, more preferably a straight or branched chain alkylamino group that has from 1 up 3 carbon atoms, and even more preferably a methylamino group. The "di (C 1-6 alkyl) amino" group in the general formula (I) shown above indicates a group in which one amino group is substituted with two "C 1-6 alkyl groups" , and may be, for example, a dimethylamino, methylethylamino, diethylamino, di-n-propylamino, diisopropylamino, N- (n-propyl) -N-ethylamino, di-n-butylamino, diisobutylamino, di-s-butylamino, di-t-butylamino, di-n-pentylamino, diisopentylamino, di-2-methylbutylamino, dineopentilamino, di-1 -etilpropilamino, di-n-I? ylamino, di-4-methylpentylamino, di-3-methylpentylamino, di- 2-methylpentylamino, di-1-methylpentylamino, di-3,3-dimethylbutylamino, di-2,2-dimethylbutylamino, di-1,1-dimethylbutylamino, di-1,2-dimethylbutylamino, di-1,3-dimethylbutylamino, di-2,3-dimethylbutylamino or di-2-ethylbutylamino, and preferably is a dimethylamino, methylethylamino or diethylamino group. The "alkoxy group of 1 to 6 carbon atoms" in the general formula (I) shown above indicates a group in which the oxygen atom of a hydroxyamino group is substituted with said "alkyl group". 1 to 6 carbon atoms ", and may be, for example, a metho-iamino, etho-amino, n-propoxyamino, isopropoamino, n-buto-amino, isobuto-diamino, s-buto-amino , t-buto? iamino, n-pentyl? iamino, isopentyl? iamino, 2-metilbuto? iamino, neopentyl? iamino, n-I? yl? iamino, 4-methylpentyl? iamino, 3-methylpentyl? iamino, 2-methylpentyl ιmino, 3,3-dimethylbuto diamine, 2,2-dimethylbuto diamine, 1,1-dimethylbuto diamine, 1,2-dimethylbuto diamine, 1,3-dimethylbuto diamine or 2,3-dimethylbuto diamino , and preferably is a straight or branched chain alkoxyamide group having from 1 to 4 carbon atoms, more preferably a straight or branched chain alkoxyamide group having from 1 to 3 carbon atoms, and still more preferably a meto? iamino group. The "sulfamoyl alkyl group of 1 to 6 carbon atoms" in the general formula (I) shown above indicates a group wherein said "alkyl group of 1 to 6 carbon atoms" is substituted with sulfamoyl group (s), and can be, for example, a group sulfamoilmetilo 1 -sulfamoiletilo, 2-sulfamoiletilo, 1 -sulfamoyl-2-methylethyl, 2-sulfamoyl-2-methylethyl, 1 -sulfamoilpropilo, 2-sulfamoilpropilo, 3-sulfamoilpropilo, 1 -sulfamoilbutilo , 2-sulfamoylbutyl, 3-sulfamoylbutyl, 4-sulfamoylbutyl, 5-sulfamoylpentyl or 6-sulfamoylhexyl, and preferably is a sulfamoyl alkyl group having from 1 to 4 carbon atoms, more preferably a sulfamoyl alkyl group having from 1 to 3 carbon atoms. carbon, and most preferably a sulfamoylmethyl, 2-sulfamoylethyl or 3-sulfamoylpropyl group. The "heterocyclyl group" in the general formula (I) shown above can be, for example, a partially or fully reduced 4 to 7-membered heterocyclic group containing from 1 to 3 sulfur atom (s), atom (s) of oxygen and / or nitrogen atom (s) such as a morpholinyl, thiomorpholinyl, azetidinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrrazolidinyl, pyrrazolinyl, piperidyl, piperazinyl, homopiperazinyl or homopiperidinyl group, and preferably is a heterocyclyl group from 4 to 7 members containing at least one nitrogen atom, more preferably a morpholinyl, thiomorpholinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrrazolidinyl, pyrrazolinyl, piperidyl or piperazinyl group, and more preferably a pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl group or piperazinyl. The "heterocyclyl group (said heterocyclyl group may be substituted with from 1 to 4 groups or?)" In the general formula (I) shown above may be a group or? Opiperazinyl or dio? Opiperazinyl, in addition to said group heterocyclyl "; and preferably it is a 2-o? o-1-piperazino, 3-o? o-1-piperazino or 2,5-dio? o-1-piperazino group; and more preferably a 2-o? o-1-piperazino or 3-o? o-1-piperazino group. The substituent group a in the general formula (I) shown above is preferably a group consisting of a carboxy group, an alkoxycarbonyl group of 2 to 7 carbon atoms, and a group of the formula R 4 -CO-CR 5 R 6 - (CH2) m- (wherein R4 represents a hydroxy group, an amino group, an alkylamino group of 1 to 6 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) amino group, a hydro group? iamino, an alkoxy group of 1 to 6 carbon atoms or an alkoxy group of 1 to 6 carbon atoms, R5 and R6 each represent a hydrogen atom, and m represents an integer from 0 to 5), more preferably a group consisting of a carbo group, an alkoxycarbonyl group of 2 to 4 carbon atoms and a group of the formula R 4 -CO-CR 5 R 6 - (CH 2) m- (wherein R 4 represents a hydro group) ilo or an alkoxy group of 1 to 3 carbon atoms, R5 and R6 each represent a hydrogen atom, and m represents an integer from 0 to 2), and still more preferably a a group consisting of a carbo group, a methocarbonyl group, an ethocarbonyl group, a carboethylene group, a methocarbonylmethyl group, an ethocarbonylmethyl group, a 2- (carbo? i) ethyl group , a 2- (methidocarbonyl) ethyl group and a 2- (ethocarbonyl) ethyl group. The substituent group ß in the general formula (I) shown above is preferably a group consisting of a carbo group, an alkoxycarbonyl group of 2 to 7 carbon atoms, a cyano group, a hydro group, ilo, an alkoyl group of 1 to 6 carbon atoms and a group of the formula R9-CO- (CH2) kN (R1 0) - (wherein R9 represents a hydroyl group or an alkoyl group of 1 to 6 carbon atoms, R 1 0 represents an alkyl group of 1 to 6 carbon atoms, and k represents an integer from 1 to 5), more preferably a group consisting of a carbo group, an alkoxycarbonyl group of 2 to 4 carbon atoms, a hydroyl group and a group of the formula R9-CO- (CH2) kN (R10) - (wherein R9 represents a hydroxy group or an alkoxy group of 1 to 3 carbon atoms) carbon; R 1 0 represents an alkyl group of 1 to 3 carbon atoms and k represents an integer from 1 to 3), and more preferably a group consisting of a carboxy group and a group of the formula R 9 -CO- (CH 2) k - N (R1 0) - (wherein R9 represents a hydroxyl group, a methoxy group or an ethoxy group; R1 0 represents a methyl group, an ethyl group or an isopropyl group; and k represents an integer from 1 to 3). In the compounds (I) of the present invention, optical isomers may be present due to the asymmetric carbon atoms in their structures (including diastereomers), and additionally, geometric isomers may also be present due to the carbon-carbon double bond in the same compound. The present invention comprises all these isomers. Since some compounds (I) of the present invention have several groups, such as a sulfanyl group, a carboyl group, a hydroyl group or an amino group in its structure, the "prodrug thereof" means a derivative in the which any of these groups is modified by an appropriate functional group that can be segmented by a biological process such as in vivo hydrolysis. In these cases, it can be determined whether the derivative is "an appropriate functional group that can be cleaved by a biological process such as hydrolysis in vivo" or not, according to whether the original compound or a pharmacologically acceptable salt thereof can be detected , administering the derivative to an experimental animal such as a rat or a mouse by means of an intravenous injection, subcutaneous injection or oral administration, and measuring a body fluid of the animal thereafter. When the compounds (I) of the present invention contain a sulfanyl group in their structures, the functional group employed to form a prodrug thereof is not particularly restricted., and may be, for example, an "aliphatic acyl group", including an alkanoyl group such as a formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl, valeryl, isovaleryl, octanoyl, nonanoyl, decanoyl, 3-methylnonanoyl group , 8-methylnonanoyl, 3-ethylctanoyl, 3,7-dimethyloctanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, he? Adecanoyl, 1-methylpentadecanoyl, 14-methylpentadecanoyl, 13, 13-dimethyltetradecanoyl, heptadecanoyl, 15-methylhe? Adecanoyl , octadecanoyl, 1-methylheptadecanoyl, nonadecanoyl, icosanoyl or henicosanoyl; an alkylcarbonyl group substituted with a carbo group such as a succinoyl, glutaroyl or adipoyl group; a carbonyl group substituted with a halogenated lower alkyl group such as a chloroacetyl, dichloroacetyl, trichloroacetyl or trifluoroacetyl group; a saturated cyclic carbonyl hydrocarbon group such as a cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl or cyclooctylcarbonyl group; an alkylcarbonyl group substituted with lower alkoxy group (s) such as a methoxyacetyl group; and an unsaturated alkylcarbonyl group such as a (E) -2-methyl-2-butenoyl group (preferably an alkanoyl group of 1 to 6 carbon atoms); a "carbonyl? alkyl" group, including an oxodio? oleylmethyl group such as a group (5-methyl-2-o? o-1,3-dio? olen-4-yl) methyl or (5-phenyl-2-) o? o-1, 3-dio? olen-4-yl) methyl; an "aromatic acyl group", including an arylcarbonyl group such as a benzoyl, a-naphthoyl, b-naphthoyl, pyridoyl, thienoyl or furoyl group; a halogenated arylcarbonyl group such as a 2-bromobenzoyl or 4-chlorobenzoyl group; an arylcarbonyl group substituted with lower alkyl group (s) such as a 2,4,6-trimethylbenzoyl or 4-toluoyl group; a lower alkoxylated arylcarbonyl group such as a 4-anisoyl group; an arylcarbonyl group substituted with carboxy group (s) such as a 2-carbo? ibenzoyl, 3-carbo? ibenzoyl or 4-carbo? ibenzoyl group; a nitrated arylcarbonyl group such as a 4-nitrobenzoyl or 2-nitrobenzoyl group; an arylcarbonyl group substituted with lower alkoxycarbonyl group (s) such as a 2- (methocarbonyl) benzoyl group; and an arylcarbonyl group substituted with aryl group (s) such as a 4-phenylbenzoyl group (preferably an arylcarbonyl group); an "aralkylcarbonyl group", including a carbonyl group substituted with a lower alkyl group which is substituted with from 1 to 3 aryl groups such as a phenylacetyl, a-naphthylpropionyl, β-naphthylbutyryl, diphenylisobutyryl, triphenylacetyl, α-naphthyldiphenyl isobutyryl group or 9- anthrylpentanoyl; and a lower alkylcarbonyl group substituted with from 1 to 3 aryl groups, of which an aryl ring is substituted with lower alkyl group (s), lower alkoxy group (s), nitro group (s), atom (s) halogen or cyano group (s), such as a 4-methylphenylacetyl, 2,4,6-trimethylphenylformyl, 3,4,5-trimethylphenylbutyryl, 4-metho-phenyl-isobutyryl, 4-metho-ifnyldiphenylpivaloyl, 2-nitrophenylacetyl, 4- group nitrophenylpropionyl, 4-chlorophenylbutyryl, 4-bromophenylacetyl or 4-cyanophenyl pentanoyl; a "tetrahydropyranyl or tetrahydrothiopyranyl group" such as a tetrahydropyran-2-yl group, 3-bromotetrahydropyran-2-yl, 4-metho-tetrahydropyran-4-yl, tetrahydrothiopyran-2-yl or 4-methoxytetrahydrothiopyran-4-yl; a "tetrahydrofuranyl or tetrahydrothiofuranyl group" such as a tetrahydrofuran-2-yl or tetrahydrothiophan-2-yl group; an "alkoxymethyl group", including a lower alkoxymethyl group such as a metho-imethyl group, 1,1-dimethyl-1-metho-imethyl, etho-imethyl, propo-imethyl, isopropo-imethyl, buto-imethyl or -butoxymethyl; a lower alkoxymethyl group substituted with lower alkoxy group (s) such as a 2-methoxytoethyl group; and a halogenated lower alkoxymethyl group such as a 2,2,2-trichloroetho-imethyl or bis (2-chloroetho-i) methyl group; a "substituted ethyl group", including a lower alkoxylated ethyl group such as a 1-heptyethyl or 1 - (isopropoyl) ethyl group; and a halogenated ethyl group such as a 2,2,2-trichloroethyl group; an "aralkyl group", including a lower alkyl group substituted with from 1 to 3 aryl groups such as a benzyl, a-naphthylmethyl, b-naphthylmethyl, diphenylmethyl, triphenylmethyl, a-naphthyldiphenylmethyl or 9-anthrylmethyl group; and a lower alkyl group substituted with from 1 to 3 aryl groups, of which an aryl ring is substituted with lower alkyl group (s), lower alkoxy group (s), nitro group (s), halogen atom (s) or cyano group (s), such as a 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-metho-ifenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4- group chlorobenzyl, 4-bromobenzyl or 4-cyanobenzyl; an "alkoxycarbonyl group", including a lower alkoxycarbonyl group such as a methocarbonyl, ethocarbonyl, t-butocarbonyl or isobutocarbonyl group; and a lower alkoxycarbonyl group substituted with halogen atom (s) or tri-lower alkylsilyl group (s) such as a 2,2,2-trichloroethanecarbonyl or 2-trimethylsilylethylcarbonyl group; an "alkenyl? -carbonyl group" such as a vinyl? -carbonyl and allyl? -carbonyl group; an "aralkyl? -carbonyl group", of which an aryl ring may be substituted with 1 or 2 substituents selected from lower alkoxy group (s) or nitro group (s), such as a benzyl? -carbonyl group, 4-methoxy ? -benzyl? -carbonyl, 3,4-dimetho? -benzyl? -carbonyl, 2-nitrobenzyl? -carbonyl or 4-nitrobenzyloxycarbonyl; a straight or branched chain alkylsulfanyl group having from 1 to 6 carbon atoms such as a methylsulfanyl, ethylsulfanyl, n-propylsulfanyl, isopropylsulfanyl, n-butylsulfanyl, isobutylsulfanyl, s-butylsulfanyl, t-butylsulfanyl, n-pentylsulfanyl, isopentylsulfanyl group , 2-methylbutylsulfanyl, neopentylsulfanyl, 1-ethylpropylsulfanyl, n-hexylsulfanyl, 4-methylpentylsulfanyl, 3-methylpentylsulfanyl, 2-methylpentylsulfanyl, 1-methyl I penti I sulfanyl, 3,3-dimethylbutylsulfonyl, 2,2-dimethylbutylsuSynyl, 1, 1-dimethylbutylsulfanyl, 1,2-dimethylbutylsulfanyl, 1,3-dimethylbutylsulfanyl, 2,3-dimethylbutylsulfanyl or 2-ethylbutylsulfanyl; or an "aminoacyl group of an a-amino acid" such as a phenylalanine, and preferably is a group forming a pharmacologically acceptable ester such as an "aliphatic acyl group" or an "aromatic acyl group", or "alkylsulfanyl group of 1". to 6 carbon atoms "such as a methylisulfanyl, etiisulfanyl, n-propylsulfanyl, isopropylsulfanyl, n-butylsulfanyl, isobutylsulfanyl, s-butylsulfanyl or t-butylsulfanyl group; more preferably a pharmacologically acceptable ester forming group; even more preferably an "alkanoyl group of 1 to 6 carbon atoms" such as a formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl or pivaloyl group or an "arylcarbonyl group" such as a benzoyl group; in particular preferably an "alkanoyl group of 1 to 3 carbon atoms" or a benzoyl group; and much more preferably an acetyl group. When the compounds (I) of the present invention contain a carbo-i group in their structures, the functional group used to form a prodrug thereof can be, for example, a "lower alkyl group" such as a methyl, ethyl group, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, tert-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-heyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl or 2-ethylbutyl (preferably a alkyl group of 1 to 6 carbon atoms); an "lower alkyl alcool group", including a lower alkyl lower alkoxy group, such as a metho-imethyl, 1-isopropoxy, 1-methyl-1-metho-methyl, 1 - (isopropoxy) ethyl group , 2-methoxyethyl, 2-ethoxyethyl, 1,1-dimethyl-1-metho-imethyl, ethoxymethyl, n-propo-imethyl, isopropo-imethyl, n-buto-imethyl or tert-buto-imethyl; a lower alkoxy lower alkyl lower alkoxy group such as a 2-methoxytoethyl group; an "aryl'O" i "lower alkyl group" such as a phenoxymethyl group, and a halogenated lower alkyl lower alkoxy group such as a 2,2,2-trichloroethoxymethyl or bis (2-chloroethoxy) methyl group; a "lower alkoxy" "carbonyl" lower alkyl group "such as a methoxycarbonylmethyl group; a cyano" lower alkyl group "such as a cyanomethyl or 2-cyanoethyl group; a" lower alkyl "thiomethyl group such as a methylthiomethyl or ethylthiomethyl group; an" aryl "group thiomethyl such as a phenyltiomethyl or naphthythiomethyl group, a "lower alkyl" sulfonyl "lower alkyl group", which may be substituted with halogen atom (s), such as a 2-methanesulfonylethyl or 2-trifluoromethanesulfonylethyl group; an "aryl" sulfonyl "lower alkyl group" group such as a 2-benzenesulfonylethyl or 2-toluenesulfonylethyl group; an acyl? i "lower alkyl group", including an "aliphatic acyl" or "lower alkyl group" such as a formyl? imethyl, aceto? imethyl, propionyl? imethyl, butyryl? imethyl, pivaloyl? imethyl, valeryl? imethyl, isovaleryl, imethyl, heteroaryl, imethyl, 1-butyl, 1-butyl, 1-propionyl, 1-butyl, 1-butyryl, 1-pivaloyl, 1-butyl, 1-valeryloxyethyl, 1-isovaleryloxyethyl, 1 -hexanoyl? Ethyl, 2-formyl? -ethyl, 2-aceto-ethyl, 2-propionyl? -ethyl, 2-butyryl? -ethyl, 2-pivaloyl? -ethyl, 2-valeryl? -ethyl, 2-isovaleryl? -ethyl, 2- heteroaryl, 1-formyl, ipropyl, 1-acetoxypropyl, 1-propionyl, ipropyl, 1-butyryl, ipropyl, 1-pivaloyl, ipropyl, 1 -valeryl, ipropyl, 1 -isovaleryl, ipropyl, 1 -hex. anilyl? ipropyl, 1-aceto? ibutyl, 1-propionyl? ibutyl, 1-butyryl? ibutyl, 1-pivaloyloxybutyl, 1-acetoxypentyl, 1-propionyloxypentyl, 1-butyryloxypentyl, 1-pivaloyl? ipentyl or 1-pivaloyl? ihe? ilo; a "cycloalkyl" carbonyl? i "alkyl group in ferior "such as a cyclopentanoyl, imethyl, cyclohexanoyl, imethyl, 1-cyclopentanoyl, ethyl, 1-cyclohexanoyl, 1-cyclopentanoyloxypropyl, 1-cyclohexanoyl, ipropyl, 1-cyclopentanoyl, ibutyl or 1-cyclohene group; anilyl ibutyl; and an "aromatic acyl'Oxy" lower alkyl group "such as a benzoyloxymethyl group; a" (alkoxycarbonyl? i) alkyl "group such as a methocarbonyl, imethyl, ethocarbonyl, imethyl, propyl, carbon I put it in, I did it for coal, and I put it in, carbonatoxymethyl, isobutoxycarbonyl, imethyl, penti, carbon, and methyloxy, , carbon dioxide, carbon dioxide, methyl chloride, carbon dioxide (cyclohexyl) ethyl, 1- (methoxycarbonyl) i) ethyl, 1 - ( ethoxycarbonyloxy) ethyl, 1-propoxycarbonyloxyethyl, (isopropoxycarbonyl? i) ethyl, 1-buto? -carbonyl? ethyl, isobuto? icarbonyl? ethyl, 1- (tert-buto? -carbonyl? i) ethyl, pentyl? -carbonyl? ethyl, 1-hexyloxycarbonyl? Ethyl, cyclopentyl? Icarbon i lo? I ethyl, 1-cyclopentyl? -carbonyloxy propyl, cyclohexy lo? I carbon i lo? I propyl, 1-cyclopentyl? Icarbon i lo? I bu ti lo, cyclohe? I lo Coal i lo? i butyl, 1 - (cyclohexyloxycarbonyl? i) ethyl, (ethoxycarbonyl) i) propyl, 2-methoxycarbonyl, ethyl, 2-ethoxycarbonyl, ethyl, 2-propoxycarbonyl, ethyl, 2-isopropoxycarbonyl, ethyl, 2-buto-icarbonyl, ethyl, 2-isobute ? -carbonyl? -ethyl, 2-pentyl? -carbonyloxyethyl, 2-hexyl? -carbonyl? -ethyl, 1-methyl? -carbonyl? ipropyl, etho? -carbonyl, propyl, 1-propylcarbonyl, propyl, and sopropo? i coal and i propyl, 1 -buto carbon i i propyl, i sobuto i i carbon i i propilo, 1 -penti i i coal i i pro pilo, heiloilocarbonyloxypropyl, 1-methyl urea, butyl, ethoxycarbonyl, ibutyl, 1 -propoxycarbonyl, ibutyl, isopropocarbonyl, ibutyl, 1-buto-icarbonyl, ibutyl, 1-isobutoxycarbonyl, ibutyl, 1-methyl-carbonyl Ipentyl, 1-ethoxycarbonyl, ipentyl, 1-metho-icarbonyl-iheyl, or 1-ethoxycarbonyl-iheyl; a "carbonyl? alkyl group", including an oxodioxolenylmethyl group such as a group (5-phenyl-2-o? o-1,3-dio? olen-4-yl) methyl, [5- (4-methylphenyl) - 2-o? O-1, 3-dio? Olen-4-yl] methyl, [5- (4-metho? Ifenyl) -2-o? O-1,3-dio? Olen-4-yl] methyl , [5- (4-fluorophenyl) -2-o? O-1,3-dio? Olen-4-yl] methyl, [5- (4-chlorophenyl) -2-o? O-1,3-dio ? olen-4-yl] methyl, (2-o? o-1,3-dio? olen-4-yl) methyl, (5-methyl-2-o? o-1,3-dio? olen-4) -yl) methyl, (5-ethyl-2-o? o-1,3-dio? olen-4-yl) methyl, (5-propyl-2-o? o-1,3-dio? olen-4) -yl) methyl, (5-isopropyl-2-o? o-1,3-dio? olen-4-yl) methyl or (5-butyl-2-oxo-1,3-dioxolen-4-yl) methyl; a "phthalidyl group" such as a phthalidyl, dimethylphthalidyl or dimethoxy phthalidyl group; an "aryl group" such as a phenyl and indanyl group; a "carboalkyl group" such as a carboethylene group; or a "residual group that forms an amino acid amide" such as a phenylalanine, and preferably is a group that forms pharmacologically acceptable esters such as an "alkyl group", "alkoalkyl group", "carbonyl group" or "alkyl group" (alkoxycarbonyl? i) alkyl; more preferably an "alkyl group of 1 to 6 carbon atoms" such as a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, tert-butyl, n-pentyl, isopentyl, 2- group methylbutyl, neopentyl, 1-ethylpropyl, n-heyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl or 1-methylpentyl; and in particular preferably methyl or ethyl. When the compounds (I) of the present invention contain a hydrophilic group in their structures, the functional group employed to form a prodrug thereof can be, for example, an "aliphatic acyl group", including an alkylcarbonyl group such as a formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl, valeryl, isovaleryl, octanoyl, nonanoyl, decanoyl, 3-methylnonanoyl, 8-methylnonanoyl, 3-ethylhexanoyl, 3,7-dimethyloctanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl group , pentadecanoyl, he? adecanoyl, 1-methylpentadecanoyl, 14-methylpentadecanoyl, 13, 13-dimethyltetradecanoyl, heptadecanoilo, 15-methylhe? adecanoilo, octadecanoilo, 1-metilheptadecanoilo, nonadecanoilo, icosanoilo or henicosanoilo; a carboxylated alkylcarbonyl group such as a succinoyl, glutaroyl or adipoyl group; a halogenated lower alkylcarbonyl group such as a chloroacetyl, dichloroacetyl, trichloroacetyl or trifluoroacetyl group; a lower alkoxy lower alkylcarbonyl group such as a methoacetyl group; and an unsaturated alkylcarbonyl group such as a (E) -2-methyl-2-butenoyl group (preferably an alkanoyl group of 1 to 6 carbon atoms); an "aromatic acyl group", including an arylcarbonyl group such as a benzoyl, a-naphthoyl or a-naphthoyl group; a halogenated arylcarbonyl group such as a 2-bromobenzoyl or 4-chlorobenzoyl group; an alkylated lower arylcarbonyl group such as a 2,4,6-trimethylbenzoyl or 4-toluoyl group; a lower alkoxylated arylcarbonyl group such as a 4-anisoyl group; a carboarylated arylcarbonyl group such as a 2-carboxybenzoyl, 3-carbo? ibenzoyl or 4-carbo? ibenzoyl group; a nitro-arylcarbonyl group such as a 4-nitrobenzoyl or 2-nitrobenzoyl group; a lower alkoxycarbonyl arylcarbonyl group such as a 2- (methocarbonyl) benzoyl group; and an arylated arylcarbonyl group such as a 4-phenylbenzoyl group; a "carbonyloxyalkyl group", including an acyloxyalkyl group such as an ethylcarbonyl, imethyl, pivaloyl, imethyl, dimethylaminoacetyloxymethyl or 1-acetoxyethyl group; a 1- (alkoxycarbonyl) i) alkyl group such as a 1 - (methoxycarbonyl) group, 1 - (ethoxycarbonyl? i) ethyl, ethoxycarbonyl? imethyl, 1 - (isopropo-icarbonyl? i) ethyl, 1- (t-buto-dicarbonyl? i) ethyl, 1- (etho? -carbonyl? i) propyl or 1- (cyclohexyl? -carbonyloxy) ethyl; a phthalidyl group; and an oxodio-oleylmethyl group such as a 4-methyl-o? hate? oleylmethyl, 4-phenyl- or? hate? oleylmethyl or o? hate? oleylmethyl group; a "residual group of a salt of a succinic acid half ester"; a "residual group of a salt of a semi-ester of phosphoric acid"; a "residual group that forms an amino acid ester"; a carbamoyl group; a carbamoyl group substituted with 1 or 2 lower alkyl groups; or a "carbonyl? -alkyloxycarbonyl group" such as a pivaloyloxymethyl? -carbonyl group, and preferably is a pharmacologically acceptable ester forming group such as an "aliphatic acyl group" or an "aromatic acyl group", more preferably an "alkanoyl group" 1 to 6 carbon atoms "such as an acetyl, propionyl, butyryl, isobutyryl, pentanoyl or pivaloyl group; and in particular preferably an acetyl group.

When the compounds (I) of the present invention contain an amino group in their structures, the functional group used to form a prodrug thereof can be, for example, an aliphatic acyl group, including an alkanoyl group such as a formyl, acetyl group , propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl, valeryl, isovaleryl, octanoyl, lauroyl, palmitoyl or stearoyl; a halogenated lower alkylcarbonyl group such as a chloroacetyl, dichloroacetyl, trichloroacetyl or trifluoroacetyl group; a lower alkoxy lower alkylcarbonyl group such as a methoacetyl group; and an unsaturated alkylcarbonyl group such as a (E) -2-methyl-2-butenoyl group (preferably an alkanoyl group of 1 to 6 carbon atoms); an aromatic acyl group, including an arylcarbonyl group such as a benzoyl, a-naphthoyl or b-naphthoyl group, a halogenated arylcarbonyl group such as a 2-bromobenzoyl or 4-chlorobenzoyl group, an alkylated lower arylcarbonyl group such as a group 2, 4,6-trimethylbenzoyl or 4-toluoyl, a lower alkoxylated arylcarbonyl group such as a 4-anisoyl group, a nitrated arylcarbonyl group such as a 4-nitrobenzoyl or 2-nitrobenzoyl group, a lower alkoxycarbonyl arylcarbonyl group such as a 2- (methocarbaryl) benzoyl group, and an arylated arylcarbonyl group such as a 4-phenylbenzoyl group; an alkoxycarbonyl group, including a lower alkoxycarbonyl group such as a methocarbonyl, ethocarbonyl, t-butocarbonyl or isobutocarbonyl group, and a lower alkoxycarbonyl group substituted with a halogen atom (s) or tri-lower alkylsilyl group (s), such as a 2,2,2-trichloroethanecarbonyl or 2-trimethylsilylethylcarbonyl group; an alkenyl? -carbonyl group such as a vinyl? -carbonyl or allyloxycarbonyl group; or an aryl-icarbonyl group, of which an aryl ring may be substituted with 1 or 2 lower alkoxy group (s), nitro group (s) or halogen atom (s), such as a phenocarbonyl group, 4-metho? Ifene? Icarbonyl, 3,4-dimetho? Ifeno? Icarbonilo, 2-nitrofeno? Icarbonilo, 4-nitrofeno? Icarbonilo or 4-fluorofeno? Icarbonilo, and preferably is a alkanoilo group of 1 to 6 carbon atoms. The "prodrug" of the compounds of the formula (I) is preferably a pharmacologically acceptable ester thereof, which is prepared by converting the sulfanyl group, the carboxy group or the hydroxyl group contained in said compounds, respectively. "Pharmacologically acceptable salts thereof" means a salt that is prepared from the compounds (I) of the present invention. This salt is preferably a metal salt, including an alkali metal salt such as sodium salt, potassium salt or lithium salt, an alkaline earth metal salt such as calcium salt or magnesium salt, an aluminum salt, an iron salt, a zinc salt, a copper salt, a nickel salt and a cobalt salt; an amine salt, including an inorganic salt such as aluminum salt, an organic salt such as a t-octylamine salt, dibenzylamine salt, morpholine salt, glucosamine salt, phenylglycine alkyl ester salt, ethylenediamine salt, N-meitylglucamine salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt, N. N'-dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzyl salt phenethylamine, piperazine salt, tetramethylammonium salt or tris (hydro? imethyl) aminomethane salt; a salt of inorganic acid, including a hydrohalogen salt such as a fluorohydrate, hydrochloride, hydrobromide or hydroiodide, a nitrate, a perchlorate, a sulfate and a phosphate; a salt of organic acid, including a lower alkanesulfonate such as methanesulfonate, trifluoromethanesulfonate or ethanesulfonate, an arylsulfonate such as a benzenesulfonate or p-toluenesulfonate, an acetate, a malate, a fumarate, a succinate, a citrate, a tartrate, an o? alato, a maleate and a trifluoroacetate; or an amino acid salt such as glycine salt, Usin salt, arginine salt, ornithine salt, glutamate or aspartate, and more preferably an inorganic acid salt or an organic acid salt. In addition, the compounds (I) of the present invention can eεist as a hydrate or a solvate thereof. Preferred examples of the compounds of the general formula (I) may be those specifically shown in Tables 1-6, but the scope of the present invention should not be limited to these compounds. The meaning of the abbreviations in the following Tables is the one shown below. Ac: acetyl group, Me: methyl group, Et: ethyl group, iPr: isopropyl group, 1-Pyza: pyrazol-1-yl group, 3-Pyza: pyrazol-3-yl group, 4-Pyza: pyrazole-4 group -yl, 5-Pyza: pyrazol-5-yl group, 1-Triz: group 1, 2,3-triazol-1-yl, 2-Triz: group 1, 2,3-triazol-2-yl, 4- Triz: group 1, 2,3-triazol-4-yl, 5-Triz: group 1, 2,3-triazol-5-yl, 1-Tez: tetrazol-1-yl group, 2-Tez: tetrazol- group 2-yl, 5-Tez: tetrazol-5-yl group, 1-Pird: pyrrolidino group, 1-Pip: piperidino group, 4-Pip: piperidin-4-yl group, Mor: morpholino group, Thim: thiomorpholino group, 1-Piz: piperazino group, and 2,5-dioxo-1-Pip: 2,5-dio? O-1-piperidino group. (Table 11 Comp. No. P1 R2 X1 X2 X3 1-1 H H CH2-1-Pyza 2-F H H 1-2 Ac H CH2-1-Pyza 2-F H H 1-3 H H CH2-1-Pyza 2-F 4-F H 1-4 Ac H CH2-1-Pyza 2-F 4-F H 1-5 H H CH2- (3-C02H-1-Pyza) 2-F H H 1-6 Ac H CH2- (3-C02H-1-Pyza) 2-F H H 1-7 H H CH2- (3-C02H-1-Pyza) 2-F 4-F H 1-8 Ac H CH2- (3-C02H-1-Pyza) 2-F 4-F H 1-9 H H CH2- (3-C02Me-1-Pyza) 2-F H H 1-10 Ac H CH2- (3-C02Me-1-Pyza) 2-F H H 1-11 H H CH2- (3-C02Me-1-Pyza) 2-F 4-F H 1-12 Ac H CH2- (3-C02Me-1-Pyza) 2-F 4-F H 1-13 H H CH2- (3-C02Et-1-Pyza) 2-F H H 1-14 Ac H CH2- (3-C02Et-1-Pyza) 2-F H H 1-15 H H CH2- (3-C02Et-1-Pyza) 2-F 4-F H 1-16 Ac H CH2- (3-C02Et-1-Pyza) 2-F 4-F H 1-17 H H CH2- (4-C02H-1-Pyza) 2-F H H 1-18 Ac H CH2- (4-C02H-1-Pyza) 2-F H H 1-19 H H CH2- (4-C02H-1-Pyza) 2-F 4-F H 1-20 Ac H CH2- (4-C02H-1-Pyza) 2-F 4-F H 1-21 H H CH2- (4-C02Me-1-Pyza) 2-F H H 1-22 Ac H CH2- (4-C02Me-1-Pyza) 2-F H H 1-23 H H CH 2 - (4-C02Me-1-Pyza) 2-F 4-F H 1-24 Ac H CH2- (4-C02Me-1-Pyza) 2-F 4-F H 1-25 H H CH2- (4-C02Et-1-Pyza) 2-F H H 1-26 Ac H CH2- (4-C02Et-1-Pyza) 2-F H H 1-27 H H CH2- (4-C02Et-1-Pyza) 2-F 4-F H 1-28 Ac H CH2- (4-C02Et-1-Pyza) 2-F 4-F H 1-29 H H CH2- (5-C02H-1-Pyza) 2-F H H 1-30 Ac H CH2- (5-C02H-1-Pyza) 2-F H H 1-31 H H CH2- (5-C02H-1-Pyza) 2-F 4-F H 1-32 Ac H CH2- (5-C02H-1-Pyza) 2-F 4-F H 1-33 H H CH2- (5-C02Me-1-Pyza) 2-F H H 1-34 Ac H CH2- (5-C02Me-1-Pyza) 2-F H H 1-35 H H CH2- (5-C02Me-1-Pyza) 2-F 4-F H 1-36 Ac H CH2- (5-C02Me-1-Pyza) 2-F 4-F H 1-37 H H CH2- (5-C02Et-1-Pyza) 2-F H H 1-38 Ac H CH2- (5-C02Et-1-Pyza) 2-F H H 1-39 H H CH2- (5-C02Et-1-Pyza) 2-F 4-F H 1-40 Ac H CH2- (5-C02Et-1-Pyza) 2-F 4-F H 1-41 H H CH2- (3-CH2C02H-1-Pyza) 2-F H H 1-42 Ac H CH2- (3-CH2C02H-1-Pyza) 2-F H H 1-43 H H CH2- (3-CH2C02H-1-Pyza) 2-F 4-F H 1-44 Ac H CH2- (3-CH2C02H-1-Pyza) 2-F 4-F H 1-45 H H CH2- (3-CH2C02Me-1-Pyza) 2-F H H 1-46 Ac H CH2- (3-CH2C02Me-1-Pyza) 2-F H H 1-47 H H CH2- (3-CH2C02Me-1-Pyza) 2-F 4-F H 1-48 Ac H CH2- (v3-CH2C02Me-1-Pyza) 2-F 4-F H 1-49 H H CH2- (: 3-CH2C02Et-1-Pyza) 2-F H H 1-50 Ac H CH2- (; 3-CH2C02Et-1-Pyza) 2-F H H 1-51 H H CH2- (3-CH2C02Et-1-Pyza) 2-F 4-F H 1-52 Ac H CH2- (^ -CHzCOsEt-l-Pyza) 2-F 4-F H 1-53 H H CH2- (k4-CH2C02H-1-Pyza) 2-F H H 1-54 Ac H CH2- ([4-CH2C02H-1-Pyza) 2-F H H 1-55 H H CH2- ([4-CH2C02H-1-Pyza) 2-F 4-F H 1-56 Ac H CH2- ((4-CH2C02H-1-Pyza) 2-F 4-F H 1-57 H H CH2- ((4-CH2C02Me-1-Pyza) 2-F H H 1-58 Ac H CH2- ((4-CH2C02Me-1-Pyza) 2-F H H 1-59 H H CH2- ((4-CH2C02Me-1-Pyza) 2-F 4-F H 1-60 Ac H CH2- ((4-CH2C02Me-1-Pyza) 2-F 4-F H 1-61 H H CH2- ((4-CH2C02Et-1-Pyza) 2-F H H 1-62 Ac H CH2- ((4-CH2C02Et-1-Pyza) 2-F H H 1-63 H H CH- ((4-CH2C02Et-1-Pyza) 2-F 4-F H 1-64 Ac H CH2- ((4-CH2C02Et-1-Pyza) 2-F 4-F H 1-65 H H CH2- ((5-CH2C02H-1-Pyza) 2-F H H 1-66 Ac H CH2- ((5-CH2C02H-1-Pyza) 2-F H H 1-67 H H CH2- ((5-CH2C02H-1-Pyza) 2-F 4-F H 1-68 Ac H CH2- ((5-CH2C02H-1-Pyza) 2-F 4-F H 1-69 H H CH2- ((5-CH2C02Me-1-Pyza) 2-F H H 1-70 Ac H CH2- ((5-CH2C02Me-1-Pyza) 2-F H H 1-71 H H CH2- ((5-CH2C02Me-1-Pyza) 2-F 4-F H 1-72 Ac H CH2- ((5-CH2C02Me-1-Pyza) 2-F 4-F H 1-73 H H CH 2 - (Y 5 -CH 2 Cl 2 Et-1-Pyza) 2-F H H 1-74 Ac H CH2- (5 5-CH2C02Et-1-Pyza) 2-F H H 1-75 H H CH 2 - (Y 5 -CH 2 Cl 2 Et-1-Pyza) 2-F 4-F H 1-76 Ac H CH2- (! 5-CH2C02Et-1-Pyza) 2-F 4-F H 1-77 H H CH - (.3-CH2CH2C02H-1-Pyza) 2-F H H 1-78 Ac H Cp2"(> 3-CH2CH2C02H-1-Pyza) 2-F H H 1-79 H H CH2- (> 3-CH2CH2C02Me-1-Pyza) 2-F H H 1-80 Ac H CH2- (> 3-CH2CH2C02Me-1 -Pyza) 2-F H H 1-81 H H CH2- (.3-CH2CH2C02Et-1-Pyza) 2-F H H 1-82 Ac H CH2- (, 3-CH2CH2C02Et-1-Pyza) 2-F H H 1-83 H H CH2- (< 4-CH2CH2C02H-1-Pyza) 2-F H H 1-84 Ac H CH2 - (- 4-CH2CH2C02H-1-Pyza) 2-F H H 1-85 H H CH2- (< 4-CH2CH2C02Me-1 -Pyza) 2-F H H 1-86 Ac H CH2 - (- 4-CH2CH2C02Me-1 -Pyza) 2-F H H 1-87 H H CH2- ([4-CH2CH2C02Et-1-Pyza) 2-F H H 1-88 Ac H CH2- ([4-CH2CH2C02Et-1-Pyza) 2-F H H 1-89 H H CH2- ((5-CH2CH2C02H-1-Pyza) 2-F H H 1-90 Ac H CH2- ((5-CH2CH2C02H-1-Pyza) 2-F H H 1-91 H H CH2- ((5-CH2CH2C02Me-1-Pyza) 2-F H H 1-92 Ac H CH2- ((5-CH2CH2C02Me-1 -Pyza) 2-F H H 1-93 H H CH2- ((5-CH2CH2C02Et-1-Pyza) 2-F H H 1-94 Ac H CH2- ((5-CH2CH2C02Et-1-Pyza) 2-F H H 1-95 H H CH2- ((3-CH2CH2CH2CO2H-I -Pyza) 2-F H H 1-96 Ac H CH2- ((3-CH2CH2CH2C02H-1 -Pyza) 2-F H H 1-97 H H Cp 2_ ((3-CH 2 CH 2 CH 2 C 0 2 Me-1-Pyza) 2-F H H 1-98 Ac H CH 2 - (3-CH 2 CH 2 CH 2 C 0 2 Me-1 -Pyza) 2-F H H 1-99 H H CH2- (3-CH2CH2CH2C02Et-1 -Pyza) 2-F H H 1-100 Ac H CH2- (3-CH2CH2CH2C02Et-1 -Pyza) 2-F H H 1-101 H H CH2- (4-CH2CH2CH2C02H-1 -Pyza) 2-F H H 1-102 Ac H CH2- (4-CH2CH2CH2C02H-1 -Pyza) 2-F H H 1-103 H H CH2- (4-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 1-104 Ac H CH2- (4-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 1-105 H H CH2- (4-CH2CH2CH2C02Et-1 -Pyza) 2-F H H 1-106 Ac H CH2- (4-CH2CH2CH2C02Et-1 -Pyza) 2-F H H 1-107 H H CH2- (5-CH2CH2CH2C02H-1 -Pyza) 2-F H H 1-108 Ac H CH2- (5-CH2CH2CH2C02H-1 -Pyza) 2-F H H 1-109 H H CH2- (5-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 1-110 Ac H CH2- (5-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 1-111 H H CH2- (5-CH2CH2CH2C02Et-1 -Pyza) 2-F H H 1-112 Ac H CH2- (5-CH2CH2CH2C02Et-1 -Pyza) 2-F H H 1-113 H H CH2CH2-1-Pyza 2-F H H 1-114 Ac H CH2CH2-1-Pyza 2-F H H 1-115 H H CH2CH2- (3-C02H-1-Pyza) 2-F H H 1-116 Ac H CH2CH2- (3-C02H-1-Pyza) 2-F H H 1-117 H H CH2CH2- (3-C02Me-1 -Pyza) 2-F H H 1-118 Ac H CH2CH2- (3-C02Me-1 -Pyza) 2-F H H 1-119 H H CH2CH2- (3-C02Et-1-Pyza) 2-F H H 1-120 Ac H CH2CH2- (3-C02Et-1-Pyza) 2-F H H 1-121 H H CH2CH2- (4-C02H-1-Pyza) 2-F H H 1-122 Ac H CH2CH2- (4-C02H-1-Pyza) 2-F H H 1-123 H H CH 2 CH- ((4-C02Me-1-Pyza) 2-F H H 1-124 Ac H CH2CH2- ((4-C02Me-1-Pyza) 2-F H H 1-125 H H CH2CH2- ((4-C02Et-1-Pyza) 2-F H H 1-126 Ac H CH2CH2- ((4-C02Et-1-Pyza) 2-F H H 1-127 H H CH2CH2- ((5-C02H-1-Pyza) 2-F H H 1-128 Ac H CH2CH2- ((5-C02H-1-Pyza) 2-F H H 1-129 H H CH2CH2- ((5-C02Me-1-Pyza) 2-F H H 1-130 Ac H CH2CH2- ((5-C02Me-1-Pyza) 2-F H H 1-131 H H CH2CH2- ((5-C02Et-1-Pyza) 2-F H H 1-132 Ac H CH2CH2- ((5-C02Et-1-Pyza) 2-F H H 1-133 H H CH2CH2- ((3-CH2C02H-1-Pyza) 2-F H H 1-134 Ac H Cp2Cp2- ((3-CH2C02H-1-Pyza) 2-F H H 1-135 H H Cp2Cp2"((3-CH2C02Me-1-Pyza) 2-F H H 1-136 Ac H Cp2Cp- ((3-CH2C02Me-1-Pyza) 2-F H H 1-137 H H Cp2Cp2- ((3-CH2C02Et-1-Pyza) 2-F H H 1-138 Ac H CH2CH2- ((3-CH2C02Et-1-Pyza) 2-F H H 1-139 H H CH2CH2- ((4-CH2C02H-1-Pyza) 2-F H H 1-140 Ac H CH2CH2- ((4-CH2C02H-1-Pyza) 2-F H H 1-141 H H CH2CH2- ((4-CH2C02Me-1-Pyza) 2-F H H 1-142 Ac H CH2CH2- ((4-CH2C02Me-1-Pyza) 2-F H H 1-143 H H CH2CH2- ((4-CH2C02Et-1-Pyza) 2-F H H 1-144 Ac H CH2CH2- ((4-CH2C02Et-1-Pyza) 2-F H H 1-145 H H CH2CH2- ((5-CH2C02H-1-Pyza) 2-F H H 1-146 Ac H CH2CH2- ((5-CH2C02H-1-Pyza) 2-F H H 1-147 H H CH2CH2- ((5-CH2C02Me-1-Pyza) 2-F H H 1-148 Ac H CH 2 CH 2 5-CH 2 C0 2 Me-1-Pyza) 2-F H H 1-149 H H CH CH2- 5-CH2C02Et-1-Pyza) 2-F H H 1-150 Ac H CH2CH2-? 5-CH2C02Et-1-Pyza) 2-F H H 1-151 H H CH2CH 3-CH2CH2C02H-1-Pyza) 2-F H H 1-152 Ac H CH2CH2H 3-CH2CH2C02H-1-Pyza) 2-F H H 1-153 H H CH2CH2-? k3-CH2CH2C02Me-1 -Pyza) 2-F H H 1-154 Ac H CH2CH -? [3-CH2CH2C02Me-1 -Pyza) 2-F H H 1-155 H H CH2CH2 '; 3-CH2CH2C02Et-1-Pyza) 2-F H H 1-156 Ac H CH CH2 '; 3-CH2CH2C02Et-1-Pyza) 2-F H H 1-157 H H CH2CH2- [4-CH2CH2C02H-1-Pyza) 2-F H H 1-158 Ac H CH2CH2-? (4-CH2CH2C02H-1-Pyza) 2-F H H 1-159 H H CH2CH2-? (4-CH2CH2C02Me-1 -Pyza) 2-F H H 1-160 Ac H CH2CH2 (4-CH2CH2C02 e-1 -Pyza) 2-F H H 1-161 H H CH2CH2 (4-CH2CH2C02Et-1-Pyza) 2-F H H 1-162 Ac H CH2CH2- (4-CH2CH2C02Et-1-Pyza) 2-F H H 1-163 H H CH2CH2- (5-CH2CH2C02H-1-Pyza) 2-F H H 1-164 Ac H CH2CH2- (5-CH2CH2C02H-1-Pyza) 2-F H H 1-165 H H CH2CH2- (5-CH2CH2C02Me-1-Pyza) 2-F H H 1-166 Ac H CH2CH2- (5-CH2CH2C02Me-1 -Pyza) 2-F H H 1-167 H H CH2CH2- (5-CH2CH2C02Et-1-Pyza 2-F H H 1-168 Ac H CH2CH2- (5-CH2CH2C02Et-1-Pyza) 2-F H H 1-169 H H CH2CH2- (3-CH2CH2CH2C02H-1 -Pyza) 2-F H H 1-170 Ac H CH2CH2- (3-CH2CH2CH2C02H-1 -Pyza) 2-F H H 1-171 H H CH2CH2- (3-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 1-172 Ac H CH2CH2- (3-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 1-173 H H p2OH2- (33-CCHH22CCHH22CCpH22C02Et-1 -Pyza) 2-F H H 1-174 Ac H CH2CH2- (33-CCHH22CCHH22CCHH22C02Et-1 -Pyza) 2-F H H 1-175 H H CH2CH2- (44 - CCHH22CCHH22CCHH22C02H-1 -Pyza) 2-F H H 1-176 Ac H CH2CH2- (44-CCHH22CCHH22CCHH22C02H-1-Pyza) 2-F H H 1-177 H H CH2CH2- (44 - CCHH22CCHH22CCHH22C02Me-1 -Pyza) 2-F H H 1-178 Ac H CH2CH2- (44-CCHH2CCpH22CCHH22C02Me-1 -Pyza) 2-F H H 1-179 H H CH2CH2- (44-CCHH22CCHH2CCHH22C02Et-1 -Pyza) 2-F H H 1-180 Ac H CH2CH2- (44 - CCHH22CCHH22CCHH2C02Et-1 -Pyza) 2-F H H 1-181 H H CH CH2- (55 - CCHH2CCHH22CCHH22C02H-1 -Pyza) 2-F H H 1-182 Ac H CH2CH2- (55-CCHH22CCHH22CCHH22C02H-1 -Pyza) 2-F H H 1-183 H H CH2CH2- (55 - CCHH22CCHH22CCHH22C02Me-1 -Pyza) 2-F H H 1-184 Ac H CH2CH2- (55-CCHH22CCHH2CCHH2C02Me-1 -Pyza) 2-F H H 1-185 H H CH2CH2- (55 - CCHH22CCHH22CCHH22C02Et-1 -Pyza) 2-F H H 1-186 Ac H CH2CH2- (55 - CCHH22CCHH22CCHH22C02Et-1 -Pyza) 2-F H H 1-187 H H CH2-3-Pyza 2-F H H 1-188 Ac H CH2-3-Pyza 2-F H H 1-189 H H CH2-3-Pyza 2-F 4-F H 1-190 Ac H CH2-3-Pyza 2-F 4-F H 1-191 H H CH2- (1-C02Me-3-Pyza) 2-F H H 1-192 Ac H CH2- (1-C02Me-3-Pyza) 2-F H H 1-193 H H CH2- (1-C02Et-3-Pyza) 2-F H H 1-194 Ac H CH2- (1-C02Et-3-Pyza) 2-F H H 1-195 H H CH2- (4-C02H-3-Pyza) 2-F H H 1-196 Ac H CH2- (4-C02H-3-Pyza) 2-F H H 1-197 H H CH2- (4-C02Me-3-Pyza) 2-F H H 1-198 Ac H CH 2 - (4-C02Me-3-Pyza) 2-F H H 1-199 H H CH2- (4-C02Et-3-Pyza) 2-F H H 1-200 Ac H CH2- (4-C02Et-3-Pyza) 2-F H H 1-201 H H CH2- (5-C02H-3-Pyza) 2-F H H 1-202 Ac H CH2- (5-C02H-3-Pyza) 2-F H H 1-203 H H CH2- (5-C02Me-3-Pyza) 2-F H H 1-204 Ac H CH2- (5-C02Me-3-Pyza) 2-F H H 1-205 H H CH2- (5-C02Et-3-Pyza) 2-F H H 1-206 Ac H CH2- (5-C02Et-3-Pyza) 2-F H H 1-207 H H CH2- (1-CH2C02H-3-Pyza) 2-F H H 1-208 Ac H CH2- (1-CH2C02H-3-Pyza) 2-F H H 1-209 H H CH2- (1-CH2C02Me-3-Pyza) 2-F H H 1-210 Ac H CH2- (1-CH2C02Me-3-Pyza) 2-F H H 1-211 H H CH2- (1-CH2C02Et-3-Pyza) 2-F H H 1-212 Ac H CH2- (1-CH2C02Et-3-Pyza) 2-F H H 1-213 H H CH2- (4-CH2C02H-3-Pyza) 2-F H H 1-214 Ac H CH2- (4-CH2C02H-3-Pyza) 2-F H H 1-215 H H CH2- (4-CH2C02Me-3-Pyza) 2-F H H 1-216 Ac H CH2- (4-CH2C02Me-3-Pyza) 2-F H H 1-217 H H CH2- (4-CH2C02Et-3-Pyza) 2-F H H 1-218 Ac H CH2- (4-CH2C02Et-3-Pyza) 2-F H H 1-219 H H CH2- (5-CH2C02H-3-Pyza) 2-F H H 1-220 Ac H CH2- (5-CH2C02H-3-Pyza) 2-F H H 1-221 H H CH2- (5-CH2C02Me-3-Pyza) 2-F H H 1-222 Ac H CH2- (5-CH2C02Me-3-Pyza) 2-F H H 1-223 H H CH 2 - (Y 5 -CH 2 Cl 2 Et-3-Pyza) 2-F H H 1-224 Ac H CH2- (f 5 -CH2C02Et-3-Pyza) 2-F H H 1-225 H H CH2- (1-CH2CH2C02H-3-Pyza) 2-F H H 1-226 Ac H CH2- (1-CH2CH2C02H-3-Pyza) 2-F H H 1-227 H H CH2- (1 -CH2CH2C02Me-3-Pyza) 2-F H H 1-228 Ac H CH2- (1-CH2CH2C02 e-3-Pyza) 2-F H H 1-229 H H CH2- (1-CH2CH2C02Et-3-Pyza) 2-F H H 1-230 Ac H CH2- (1-CH2CH2C02Et-3-Pyza) 2-F H H 1-231 H H CH2- (< 4-CH2CH2C02H-3-Pyza) 2-F H H 1-232 Ac H CH2- (< 4-CH2CH2C02H-3-Pyza) 2-F H H 1-233 H H CH2- ('<4-CH2CH2C02Me-3-Pyza) 2-F H H 1-234 Ac H CH2- (v-4-CH2CH2C02Me-3-Pyza) 2-F H H 1-235 H H CH2- ('' 4-CH2CH2C02Et-3-Pyza) 2-F H H 1-236 Ac H CH2- ([4-CH2CH2C02Et-3-Pyza) 2-F H H 1-237 H H CH2- (; 5-CH2CH2C02H-3-Pyza) 2-F H H 1-238 Ac H CH2- ([5-CH2CH2C02H-3-Pyza) 2-F H H 1-239 H H CH2- ((5-CH2CH2C02Me-3-Pyza) 2-F H H 1-240 Ac H CH2- ((5-CH2CH2C02Me-3-Pyza) 2-F H H 1-241 H H CH2- ((5-CH2CH2C02Et-3-Pyza) 2-F H H 1-242 Ac H CH2- ((5-CH2CH2C02Et-3-Pyza) 2-F H H 1-245 H H CH2- ((1 -CH2CH2CH2C02H-3-Pyza) 2-F H H 1-246 Ac H CH2- ((1-CH2CH2CH2C02H-3-Pyza) 2-F H H 1-247 H H CH2- ((1-CH2CH2CH2C02Me-3-Pyza) 2-F H H 1-248 Ac H CH2- ((1-CH2CH2CH2C02Me-3-Pyza) 2-F H H 1-249 H H CH2- ((1-CH2CH2CH2C02Et-3-Pyza) 2-F H H 1-250 Ac H CH2- (1-CH2CH2CH2C02Et-3-Pyza) 2-F H H 1-251 H H CH2- (4-CH2CH2CH2C02H-3-Pyza) 2-F H H 1-252 Ac H CH2- (4-CH2CH2CH2C02H-3-Pyza) 2-F H H 1-253 H H CH2- (4-CH2CH2CH2C02Me-3-Pyza) 2-F H H 1-254 Ac H CH2- (4-CH2CH2CH2C02Me-3-Pyza) 2-F H H 1-255 H H CH2- (4-CH2CH2CH2C02Et-3-Pyza) 2-F H H 1-256 Ac H CH2- (4-CH2CH2CH2C? 2Et-3-Pyza) 2-F H H 1-257 H H CH2- (5-CH2CH2CH2C02H-3-Pyza) 2-F H H 1-258 Ac H CH2- (5-CH2CH2CH2C02H-3-Pyza) 2-F H H 1-259 H H CH2- (5-CH2CH2CH2C02 e-3-Pyza) 2-F H H 1-260 Ac H CH2- (5-CH2CH2CH2C02Me-3-Pyza) 2-F H H 1-261 H H CH2- (5-CH2CH2CH2C02Et-3-Pyza) 2-F H H 1-262 Ac H CH2- (5-CH2CH2CH2C02Et-3-Pyza) 2-F H H 1-263 H H CH2CH2-3-Pyza 2-F H H 1-264 Ac H CH2CH2-3-Pyza 2-F H H 1-265 H H CH2CH2-3-Pyza 2-F 4-F H 1-266 Ac H CH2CH2-3-Pyza 2-F 4-F H 1-267 H H CH2CH2- (1 -C02Me-3-Pyza) 2-F H H 1-268 Ac H CH2CH2- (1 -C02Me-3-Pyza) 2-F H H 1-269 H H CH2CH2- (1 -C02Et-3-Pyza) 2-F H H 1-270 Ac H CH2CH2- (1 -C02Et-3-Pyza) 2-F H H 1-271 H H CH2CH2- (4-C02H-3-Pyza) 2-F H H 1-272 Ac H CH2CH2- (4-C02H-3-Pyza) 2-F H H 1-273 H H CH2CH2- (4-C02Me-3-Pyza) 2-F H H 1-274 Ac H CH2CH2- (4-C02Me-3-Pyza) 2-F H H 1-275 H H CH2CH2- (('4-C02Et-3-Pyza) 2-F H H 1-276 Ac H OpCH2- (('4-C02Et-3-Pyza) 2-F H H 1-277 H H CH2CH- ((5-C02H-3-Pyza) 2-F H H 1-278 Ac H CH2CH2- ((5-C02H-3-Pyza) 2-F H H 1-279 H H CH2CH2- ((5-C02Me-3-Pyza) 2-F H H 1-280 Ac H CH2CH- ((5-C02Me-3-Pyza) 2-F H H 1-281 H H CH2CH2- ((5-C02Et-3-Pyza) 2-F H H 1-282 Ac H CH2CH2- ((5-C02Et-3-Pyza) 2-F H H 1-283 H H CH2CH2- ((1-CH2C02H-3-Pyza) 2-F H H 1-284 Ac H CH2CH2- ((1-CH2C02H-3-Pyza) 2-F H H 1-285 H H CH2CH2- ((1-CH2C02Me-3-Pyza) 2-F H H 1-286 Ac H CH2CH2- ((1-CH2C02 e-3-Pyza) 2-F H H 1-287 H H CH2CH- ((1-CH2C02Et-3-Pyza) 2-F H H 1-288 Ac H CH2CH2- ((1-CH2C02Et-3-Pyza) 2-F H H 1-289 H H CH2CH2- ((4-CH2C02H-3-Pyza) 2-F H H 1-290 Ac H Cp2CH2- ((4-CH2C02H-3-Pyza) 2-F H H 1-291 H H Cp2Cp2- ((4-CH2C02 e-3-Pyza) 2-F H H 1-292 Ac H CH2CH2- ((4-CH2C02Me-3-Pyza) 2-F H H 1-293 H H Cp2Cp2- ((4-CH2C02Et-3-Pyza) 2-F H H 1-294 Ac H CH2CH2- ((4-CH2C02Et-3-Pyza) 2-F H H 1-295 H H CH2CH2- ((5-CH2C02H-3-Pyza) 2-F H H 1-296 Ac H CH2CH2- ((5-CH2C02H-3-Pyza) 2-F H H 1-297 H H CH2CH2- ((5-CH2C02Me-3-Pyza) 2-F H H 1-298 Ac H CH2Cp2- ((5-CH2C02Me-3-Pyza) 2-F H H 1-299 H H CH2CH2- ((5-CH2C02Et-3-Pyza) 2-F H H 1-300 Ac H OH 2 H 2 -? 5-CH 2 C0 2 Et-3-Pyza) 2-F H H 1-301 H H Cp2CH2-? 1-CH2CH2C02H-3-Pyza) 2-F H H 1-302 Ac H CH2CH2- 1-CH2CH2C02H-3-Pyza) 2-F H H 1-303 H H CH2CH2- 1-CH2CH2C02Me-3-Pyza) 2-F H H 1-304 Ac H CH CH2- 1 -CH2CH2C02Me-3-Pyza 2-F H H 1-305 H H CH2CH ™ 1-CH2CH2C02Et-3-Pyza) 2-F H H 1-306 Ac H CH2CH2 ™ 1-CH2CH2C02Et-3-Pyza) 2-F H H 1-307 H H CH2CH2- (4-CH2CH2C02H-3-Pyza) 2-F H H 1-308 Ac H CH2CH2- 4-CH2CH2C02H-3-Pyza) 2-F H H 1-309 H H CH2CH2- k4-CH2CH2C? 2M? -3-Pyza) 2-F H H 1-310 Ac H CH2CH2- [4-CH2CH2C02Me-3-Pyza 2-F H H 1-311 H H CH2CH - [4-CH2CH2C02Et-3-Pyza) 2-F H H 1-312 Ac H CH2CH2- [4-CH2CH2C02Et-3-Pyza) 2-F H H 1-313 H H CH2CH2- [5-CH2CH2C02H-3-Pyza). 2-F H H 1-314 Ac H CH2CH2- [5-CH2CH2C02H-3-Pyza) 2-F H H 1-315 H H Cp2CH2- (5-CH2CH2C02Me-3-Pyza) 2-F H H 1-316 Ac H Cp2CH2- (5-CH2CH2C02Me-3-Pyza) 2-F H H 1-317 H H CH2Cp2- (5-CH2CH2C02Et-3-Pyza) 2-F H H 1-318 Ac H CH2CH2- [5-CH2CH2C02Et-3-Pyza) 2-F H H 1-319 H H CH2CH2- (1-CH2CH2CH2C? 2H-3-Pyza) 2-F H H 1-320 Ac H CH2CH2- (1-CH2CH2CH2C02H-3-Pyza) 2-F H H 1-321 H H CH2CH2- (1-CH2CH2CH2C02Me-3-Pyza) 2-F H H 1-322 Ac H CH2CH2- (1-CH2CH2CH2C02Me-3-Pyza) 2-F H H 1-323 H H CH2CH - (1-CH2CH2CH2C? 2Et-3-Pyza) 2-F H H 1-324 Ac H CH2CH2- (1 -CH2CH2CH2C? 2Et-3-Pyza) 2-F H H 1-325 H H CH2CH2- (4-CH2CH2CH2C02H-3-Pyza) 2-F H H 1-326 Ac H CH2CH2- (4-CH2CH2CH2C02H-3-Pyza) 2-F H H 1-327 H H CH2CH2- (4-CH2CH2CH2C02Me-3-Pyza) 2-F H H 1-328 Ac H CH2CH2- (4-CH2CH2CH2C02Me-3-Pyza) 2-F H H 1-329 H H CH2CH2- (4-CH2CH2CH2C02Et-3-Pyza) 2-F H H 1-330 Ac H CH2CH2- (4-CH2CH2CH2C02Et-3-Pyza) 2-F H H 1-331 H H CH2CH2- (5-CH2CH2CH2C02H-3-Pyza) 2-F H H 1-332 Ac H CH2CH2- (5-CH2CH2CH2C02H-3-Pyza) 2-F H H 1-333 H H CH2CH2- (5-CH2CH2CH2C02 e-3-Pyza) 2-F H H 1-334 Ac H CH2CH2- (5-CH2CH2CH2C02 e-3-Pyza) 2-F H H 1-335 H H CH2CH2- (5-CH2CH2CH2C02Et-3-Pyza) 2-F H H 1-336 Ac H CH2CH2- (5-CH2CH2CH2C02Et-3-Pyza) 2-F H H 1-337 H H CH2-4-Pyza 2-F H H 1-338 Ac H CH2-4-Pyza 2-F H H 1-339 H H CH2-4-Pyza 2-F 4-F H 1-340 Ac H CH2-4-Pyza 2-F 4-F H 1-341 H H CH2- (1-C02Me-4-Pyza) 2-F H H 1-342 Ac H CH2- (1-C02Me-4-Pyza) 2-F H H 1-343 H H CH2- (1-C02Et-4-Pyza) 2-F H H 1-344 Ac H CH2- (1-C02Et-4-Pyza) 2-F H H 1-345 H H CH2- (3-C02H-4-Pyza) 2-F H H 1-346 Ac H CH2- (3-C02H-4-Pyza) 2-F H H 1-347 H H CH2- (3-C02Me-4-Pyza) 2-F H H 1-348 Ac H CH2- (3-C02Me-4-Pyza) 2-F H H 1-349 H H CH2- (3-C02Et-4-Pyza) 2-F H H 1-350 Ac H CH- (v3-C02Et-4-Pyza) 2-F H H 1-351 H H CH2- ('1-CH2C02H-4-Pyza) 2-F H H 1-352 Ac H CH2- (1-CH2C02H-4-Pyza) 2-F H H 1-353 H H CH2- (1-CH2C02Me-4-Pyza) 2-F H H 1-354 Ac H CH2- (1-CH2C02Me-4-Pyza) 2-F H H 1-355 H H CH2- (1-CH2C02Et-4-Pyza) 2-F H H 1-356 Ac H CH2- (1-CH2C02Et-4-Pyza) 2-F H H 1-357 H H CH2- (, 3-CH2C02H-4-Pyza) 2-F H H 1-358 Ac H CH2- (, 3-CH2C02H-4-Pyza) 2-F H H 1-359 H H Cp2- (3-CH2C02Me-4-Pyza) 2-F H H 1-360 Ac H CH2- (, 3-CH2C02Me-4-Pyza) 2-F H H 1-361 H H Cp2- ((3-CH2C02Et-4-Pyza) 2-F H H 1-362 Ac H CH2- ((3-CH2C02Et-4-Pyza) 2-F H H 1-363 H H CH2- ((1-CH2CH2C02H-4-Pyza) 2-F H H 1-364 Ac H CH2- ((1-CH2CH2C02H-4-Pyza) 2-F H H 1-365 H H CH2- ((1-CH2CH2C02 e-4-Pyza) 2-F H H 1-366 Ac H CH2- ((1-CH2CH2C02Me-4-Pyza) 2-F H H 1-367 H H CH2- ((1-CH2CH2C02Et-4-Pyza) 2-F H H 1-368 Ac H CH2- ((1-CH2CH2C02Et-4-Pyza) 2-F H H 1-369 H H CH2- ((3-CH2CH2C02H-4-Pyza) 2-F H H 1-370 Ac H CH2- ((3-CH2CH2C02H-4-Pyza) 2-F H H 1-371 H H CH2- ((3-CH2CH2C02Me-4-Pyza) 2-F H H 1-372 Ac H CH2- ((3-CH2CH2C02Me-4-Pyza) 2-F H H 1-373 H H CH2- ((3-CH2CH2C02Et-4-Pyza) 2-F H H 1-374 Ac H CH2- ((3-CH2CH2C02Et-4-Pyza) 2-F H H 1-375 H H CH2- (1 -CH2CH2CH2C02H-4-Pyza) 2-F H H 1-376 Ac H CH2- (1-CH2CH2CH2C02H-4-Pyza) 2-F H H 1-377 H H CH2- (1-CH2CH2CH2C02i / e-4-Pyza) 2-F H H 1-378 Ac H CH2- (1 -CH2CH2CH2C02Me-4-Pyza) 2-F H H 1-379 H H CH2- (1-CH2CH2CH2C02Et-4-Pyza) 2-F H H 1-380 Ac H CH2- (1-CH2CH2CH2C02Et-4-Pyza) 2-F H H 1-381 H H CH2- (3-CH2CH2CH2C02H-4-Pyza) 2-F H H 1-382 Ac H CH2- (3-CH2CH2CH2C02H-4-Pyza) 2-F H H 1-383 H H CH2- (3-CH2CH2CH2C02Me-4-Pyza) 2-F H H 1-384 Ac H CH2- (3-CH2CH2CH2C02Me-4-Pyza) 2-F H H 1-385 H H CH2- (3-CH2CH2CH2C02Et-4-Pyza) 2-F H H 1-386 Ac H CH2- (3-CH2CH2CH2C02Et-4-Pyza) 2-F H H 1-387 H H CH2CH2-4-Pyza 2-F H H 1-388 Ac H CH2CH2-4-Pyza 2-F H H 1-389 H H CH2CH2-4-Pyza 2-F 4-F H 1-390 Ac H CH2CH2-4-Pyza 2-F 4-F H 1-391 H H CH2CH2- (1-C02Me-4-Pyza) 2-F H H 1-392 Ac H CH2CH2- (1-C02Me-4-Pyza) 2-F H H 1-393 H H CH2CH2- (1-C02Et-4-Pyza) 2-F H H 1-394 Ac H CH2CH2- (1-C02Et-4-Pyza) 2-F H H 1-395 H H CH2CH2- (3-C02H-4-Pyza) 2-F H H 1-396 Ac H CH2CH2- (3-C02H-4-Pyza) 2-F H H 1-397 H H CH2CH2- (3-C02Me-4-Pyza) 2-F H H 1-398 Ac H CH2CH2- (3-C02Me-4-Pyza) 2-F H H 1-399 H H CH2CH2- (3-C02Et-4-Pyza) 2-F H H 1-400 Ac H CH2CH2- (3-C02Et-4-Pyza) 2-F H H 1-401 H H CH2CH2- (1 -CH2C02H-4-Pyza) 2-F H H 1-402 Ac H CH2CH2- (1-CH2C02H-4-Pyza) 2-F H H 1-403 H H CH2CH2- (1-CH2C02Me-4-Pyza) 2-F H H 1-404 Ac H CH2CH2- (1-CH2C02Me-4-Pyza) 2-F H H 1-405 H H CH2CH2- (1-CH2C02Et-4-Pyza) 2-F H H 1-406 Ac H CH2CH2- (1-CH2C02Et-4-Pyza) 2-F H H 1-407 H H CH2CH2- (3-CH2C02H-4-Pyza) 2-F H H 1-408 Ac H CH2CH2- (3-CH2C02H-4-Pyza) 2-F H H 1-409 H H CH2CH2- (3-CH2C02 e-4-Pyza) 2-F H H 1-410 Ac H CH2CH2- (3-CH2C02Me-4-Pyza) 2-F H H 1-411 H H CH2CH2- (3-CH2C02Et-4-Pyza) 2-F H H 1-412 Ac H CH2CH2- (3-CH2C02Et-4-Pyza) 2-F H H 1-413 H H CH2CH2- (1-CH2CH2C02H-4-Pyza) 2-F H H 1-414 Ac H CH2CH2- (1-CH2CH2C02H-4-Pyza) 2-F H H 1-415 H H CH2CH2- (1-CH2CH2C02Me-4-Pyza) 2-F H H 1-416 Ac H CH2CH2- (1 -CH2CH2C02Me-4-Pyza) 2-F H H 1-417 H H CH2CH2- (1-CH2CH2C02Et-4-Pyza) 2-F H H 1-418 Ac H CH2CH2- (1-CH2CH2C02Et-4-Pyza) 2-F H H 1-419 H H CH2CH2- (3-CH2CH2C02H-4-Pyza) 2-F H H 1-420 Ac H CH2CH2- (3-CH2CH2C02H-4-Pyza) 2-F H H 1-421 H H CH2CH2- (3-CH2CH2C02 e-4-Pyza) 2-F H H 1-422 Ac H CH2CH2- (3-CH2CH2C02Me-4-Pyza) 2-F H H 1-423 H H CH2CH2- (3-CH2CH2C02Et-4-Pyza) 2-F H H 1-424 Ac H CH2CH2- (3-CH2CH2C02Et-4-Pyza) 2-F H H 1-425 H H CH2CH2- (1-CH2CH2CH2C02H-4-Pyza) 2-F H H 1-426 Ac H CH2CH2- (1-CH2CH2CH2C02H-4-Pyza) 2-F H H 1-427 H H CH2CH2- (1-CH2CH2CH2C02Me-4-Pyza) 2-F H H 1-428 Ac H CH2CH2- (1 -CH2CH2CH2C? 2Me-4-Pyza) 2-F H H 1-429 H H CH2CH2- (1-CH2CH2CH2C02Et-4-Pyza) 2-F H H 1-430 Ac H CH2CH2- (1-CH2CH2CH2C02Et-4-Pyza) 2-F H H 1-431 H H CH2CH2- (3-CH2CH2CH2C02H-4-Pyza) 2-F H H 1-432 Ac H CH2CH2- (3-CH2CH2CH2C02H-4-Pyza) 2-F H H 1-433 H H CH2CH2- (3-CH2CH2CH2C02Me-4-Pyza) 2-F H H 1-434 Ac H CH2CH2- (3-CH2CH2CH2C02Me-4-Pyza) 2-F H H 1-435 H H CH2CH2- (3-CH2CH2CH2C02Et-4-Pyza) 2-F H H 1-436 Ac H CH2CH2- (3-CH2CH2CH2C02Et-4-Pyza) 2-F H H 1-437 H H CH2- (1-C02Me-5-Pyza) 2-F 4-F H 1-438 Ac H CH2- (1-C02Me-5-Pyza) 2-F 4-F H 1-439 H H CH2- (1-C02Me-5-Pyza) 2-F H H 1-440 Ac H CH2- (1-C02Me-5-Pyza) 2-F H H 1-441 H H CH2- (1-C02Et-5-Pyza) 2-F H H 1-442 Ac H CH2- (1-C02Et-5-Pyza) 2-F H H 1-443 H H CH2- (1-CH2C02H-5-Pyza) 2-F H H 1-444 Ac H CH2- (1-CH2C02H-5-Pyza) 2-F H H 1-445 H H CH2- (1-CH2C02Me-5-Pyza) 2-F H H 1-446 Ac H CH2- (1-CH2C02Me-5-Pyza) 2-F H H 1-447 H H CH2- (1-CH2C02Et-5-Pyza) 2-F H H 1-448 Ac H CH2- (1-CH2C02Et-5-Pyza) 2-F H H 1-449 H H CH2- (1-CH2CH2C02H-5-Pyza) 2-F H H 1-450 Ac H CH2- (1 -CH2CH2C02H-5-Pyza) 2-F H H 1-451 H H CH2- (1 -CH2CH2C02Me-5-Pyza) 2-F H H 1-452 Ac H CH2- (1-CH2CH2C02Me-5-Pyza) 2-F H H 1-453 H H CH2- (1-CH2CH2C02Et-5-Pyza) 2-F H H 1-454 Ac H CH2- (1-CH2CH2C02Et-5-Pyza) 2-F H H 1-455 H H CH2- (1 -CH2CH2CH2C02H-5-Pyza) 2-F H H 1-456 Ac H CH2- (1-CH2CH2CH2C02H-5-Pyza) 2-F H H 1-457 H H CH2- (1-CH2CH2CH2C02Me-5-Pyza) 2-F H H 1-458 Ac H CH2- (1-CH2CH2CH2C02Me-5-Pyza) 2-F H H 1-459 H H CH2- (1 -CH2CH2CH2C02Et-5-Pyza) 2-F H H 1-460 Ac H CH2- (1 -CH2CH2CH2C02Et-5-Pyza) 2-F H H 1-461 H H CH2CH2- (1-C02Me-5-Pyza) 2-F 4-F H 1-462 Ac H CH2CH2- (1-C02Me-5-Pyza) 2-F 4-F H 1-463 H H CH2CH2- (1-C02Me-5-Pyza) 2-F H H 1-464 Ac H CH2CH2- (1 -C02lv1e-5-Pyza) 2-F H H 1-465 H H CH2CH2- (1 -C02Et-5-Pyza) 2-F H H 1-466 Ac H CH2CH2- (1-C02Et-5-Pyza) 2-F H H 1-467 H H CH2CH2- (1-CH2C02H-5-Pyza) 2-F H H 1-468 Ac H CH2CH2- (1-CH2C02H-5-Pyza) 2-F H H 1-469 H H CH2CH2- (1 -CH2C02Me-5-Pyza) 2-F H H 1-470 Ac H CH2CH2- (1-CH2C02 e-5-Pyza) 2-F H H 1-471 H H CH2CH2- (1 -CH2C02Et-5-Pyza) 2-F H H 1-472 Ac H CH2CH2- (1 -CH2C02Et-5-Pyza) 2-F H H 1-473 H H CH2CH2- (1-CH2CH2C02H-5-Pyza) 2-F H H 1-474 Ac H CH2CH2- (1 -CH2CH2C02H-5-Pyza) 2-F H H 1-475 H H CH2CH2- (1 -CH2CH2C02Me-5-Pyza) 2-F H H 1-476 Ac H CH2CH2- (1 -CH2CH2C02¡v1e-5-Pyza) 2-F H H 1-477 H H CH2CH2- (1-CH2CH2C02Et-5-Pyza) 2-F H H 1-478 Ac H CH2CH2- (1-CH2CH2C02Et-5-Pyza) 2-F H H 1-479 H H CH2CH2- (1 -CH2CH2CH2C02H-5-Pyza) 2-F H H 1-480 Ac H CH2CH2- (1 -CH2CH2CH2C02H-5-Pyza) 2-F H H 1-481 H H CH2CH2- (1-CH2CH2CH2C02 e-5-Pyza) 2-F H H 1-482 Ac H CH2CH2- (1-CH2CH2CH2C02Me-5-Pyza) 2-F H H 1-483 H H CH2CH2- (1-CH2CH2CH2C02Et-5-Pyza) 2-F H H 1-484 Ac H CH2CH2- (1-CH2CH2CH2C02Et-5-Pyza) 2-F H H 1-485 H H CH2-1-Triz 2-F H H 1-486 Ac H CH2-1-Triz 2-F H H 1-487 H H CH2- (4-C02H-1-Triz) 2-F H H 1-488 Ac H CH2- (4-C02H-1-Triz) 2-F H H 1-489 H H CH2- (4-C02Me-1-Triz) 2-F H H 1-490 Ac H CH2- (4-C02Me-1-Triz) 2-F H H 1-491 H H CH2- (4-C02Et-1-Triz) 2-F H H 1-492 Ac H CH2- (4-C02Et-1-Triz) 2-F H H 1-493 H H CH2- (5-C02H-1-Triz) 2-F H H 1-494 Ac H CH2- (5-C02H-1-Triz) 2-F H H 1-495 H H CH2- (5-C02Me-1-Triz) 2-F H H 1-496 Ac H CH2- (5-C02Me-1-Triz) 2-F H H 1-497 H H CH2- (5-C02Et-1-Triz) 2-F H H 1-498 Ac H CH2- (5-C02Et-1-Triz) 2-F H H 1-499 H H CH2- (4-CH2C02H-1-Triz) 2-F H H 1-500 Ac H CH2- (4-CH2C02H-1-Triz) 2-F H H 1-501 H H CH2- (4-CH2C02Me-1 -Triz) 2-F H H 1-502 Ac H CH2- (4-CH2C02Me-1 -Triz) 2-F H H 1-503 H H CH2- (4-CH2C02Et-1-Triz) 2-F H H 1-504 Ac H CH2- (4-CH2C02Et-1-Triz) 2-F H H 1-505 H H CH2- (5-CH2C02H-1-Triz) 2-F H H 1-506 Ac H CH2- (5-CH2C02H-1-Triz) 2-F H H 1-507 H H CH2- (5-CH2C02Me-1 -Triz) 2-F H H 1-508 Ac H CH2- (5-CH2C02Me-1 -Triz) 2-F H H 1-509 H H CH2- (5-CH2C02Et-1-Triz) 2-F H H 1-510 Ac H CH2- (5-CH2C02Et-1-Triz) 2-F H H 1-511 H H CH2- (4-CH2CH2C02H-1 -Triz) 2-F H H 1-512 Ac H CH2- (4-CH2CH2C02H-1 -Triz) 2-F H H 1-513 H H CH2- (4-CH2CH2C02Me-1 -Triz) 2-F H H 1-514 Ac H CH2- (4-CH2CH2C? 2Me-1 -Triz) 2-F H H 1-515 H H CH2- (4-CH2CH2C02Et-1 -Triz) 2-F H H 1-516 Ac H CH2- (4-CH2CH2C02Et-1 -Triz) 2-F H H 1-517 H H CH2- (5-CH2CH2C02H-1 -Triz) 2-F H H 1-518 Ac H CH2- (5-CH2CH2C02H-1 -Triz) 2-F H H 1-519 H H CH2- (5-CH2CH2C02Me-1 -Triz) 2-F H H 1-520 Ac H CH2- (5-CH2CH2C02Me-1 -Triz) 2-F H H 1-521 H H CH2- (5-CH2CH2C02Et-1 -Triz) 2-F H H 1-522 Ac H CH2- (5-CH2CH2C02Et-1 -Triz) 2-F H H 1-523 H H CH2- (4-CH2CH2CH2C02H-1 -Triz) 2-F H H 1-524 Ac H CH2- (4-CH2CH2CH2C02H-1 -Triz) 2-F H H 1-525 H H CH2- (4-CH2CH2CH2C02Me-1 -Triz) 2-F H H 1-526 Ac H CH2- (4-CH2CH2CH2C02Me-1 -Triz) 2-F H H 1-527 H H CH2- (4-CH2CH2CH2C02Et-1 -Triz) 2-F H H 1-528 Ac H CH2- (4-CH2CH2CH2C02Et-1 -Triz) 2-F H H 1-529 H H CH2- (5-CH2CH2CH2C02H-1-Triz) 2-F H H 1-530 Ac H CH2- (5-CH2CH2CH2C? 2H-1 -Triz) 2-F H H 1-531 H H CH2- (5-CH2CH2CH2C? 2Me-1 -Triz) 2-F H H 1-532 Ac H CH2- (5-CH2CH2CH2C02Me-1 -Triz) 2-F H H 1-533 H H CH2- (5-CH2CH2CH2C02Et-1 -Triz) 2-F H H 1-534 Ac H CH2- (5-CH2CH2CH2C02Et-1 -Triz) 2-F H H 1-535 H H CH2CH2-1-Triz 2-F H H 1-536 Ac H CH2CH2-1-Triz 2-F H H 1-537 H H CH2CH2- (4-C02H-1-Triz) 2-F H H 1-538 Ac H CH2CH2- (4-C02H-1-Triz) 2-F H H 1-539 H H CH2CH2- (4-C02Me-1-Triz) 2-F H H 1-540 Ac H CH2CH2- (4-C02Me-1 -Triz) 2-F H H 1-541 H H CH2CH2- (4-C02Et-1-Triz) 2-F H H 1-542 Ac H CH2CH2- (4-C02Et-1-Triz) 2-F H H 1-543 H H CH2CH2- (5-C02H-1-Triz) 2-F H H 1-544 Ac H CH2CH2- (5-C02H-1-Triz) 2-F H H 1-545 H H CH2CH2- (5-C02Me-1 -Triz) 2-F H H 1-546 Ac H CH2CH2- (5-C02Me-1-Triz) 2-F H H 1-547 H H CH2CH2- (5-C02Et-1-Triz) 2-F H H 1-548 Ac H CH2CH2- (5-C02Et-1-Triz) 2-F H H 1-549 H H CH2CH2- (4-CH2C02H-1 -Triz) 2-F H H 1-550 Ac H CH2CH2- (4-CH2C02H-1 -Triz) 2-F H H 1-551 H H CH2CH2- (4-CH2C02 e-1 -Triz) 2-F H H 1-552 Ac H CH2CH2- (4-CH2C02Me-1 -Triz) 2-F H H 1-553 H H CH2CH2- (4-CH2C02Et-1 -Triz) 2-F H H 1-554 Ac H CH2CH2- (4-CH2C02Et-1 -Triz) 2-F H H 1-555 H H CH2CH2- (5-CH2C02H-1 -Triz) 2-F H H 1-556 Ac H CH2CH2- (5-CH2C02H-1 -Triz) 2-F H H 1-557 H H CH2CH2- (5-CH2C02Me-1 -Triz) 2-F H H 1-558 Ac H CH2CH2- (5-CH2C02Me-1 -Triz) 2-F H H 1-559 H H CH2CH2- (5-CH2C02Et-1 -Triz) 2-F H H 1-560 Ac H CH2CH2- (5-CH2C02Et-1 -Triz) 2-F H H 1-561 H H CH2CH2- (4-CH2CH2C02H-1 -Triz) 2-F H H 1-562 Ac H CH2CH2- (4-CH2CH2C02H-1 -Triz) 2-F H H 1-563 H H CH2CH2- (4-CH2CH2C02 e-1 -Triz) 2-F H H 1-564 Ac H CH2CH2- (4-CH2CH2C02Me-1 -Triz) 2-F H H 1-565 H H CH2CH2- (4-CH2CH2C02Et-1 -Triz) 2-F H H 1-566 Ac H CH2CH2- (4-CH2CH2C02Et-1 -Triz) 2-F H H 1-567 H H CH2CH2- (5-CH2CH2C02H-1-Triz) 2-F H H 1-568 Ac H CH2CH2- (5-CH2CH2C02H-1-Triz) 2-F H H 1-569 H H CH2CH2- (5-CH2CH2C02Me-1 -Triz) 2-F H H 1-570 Ac H CH2CH2- (5-CH2CH2C02Me-1 -Triz) 2-F H H 1-571 H H CH2CH2- (5-CH2CH2C02Et-1 -Triz) 2-F H H 1-572 Ac H CH2CH2- (5-CH2CH2C02Et-1 -Triz) 2-F H H 1-573 H H CH2CH2- (4-CH2CH2CH2C02H-1 -Triz) 2-F H H 1-574 Ac H CH2CH2- (4-CH2CH2CH2C02H-1 -Triz) 2-F H H 1-575 H H CH2CH2- (4-CH2CH2CH2C? 2Me-1-Triz) 2-F H H 1-576 Ac H CH2CH2- (4-CH2CH2CH2C02Me-1-Triz) 2-F H H 1-577 H H CH2CH2- (4-CH2CH2CH2C02Et-1-Triz) 2-F H H 1-578 Ac H CH2CH2- (4-CH2CH2CH2C02Et-1-Triz) 2-F H H 1-579 H H CH2CH2- (5-CH2CH2CH2C02H-1-Triz) 2-F H H 1-580 Ac H CH2CH2- (5-CH2CH2CH2C02H-1-Triz) 2-F H H 1-581 H H CH2CH2- (5-CH2CH2CH2C02Me-1-Triz) 2-F H H 1-582 Ac H CH2CH2- (5-CH2CH2CH2C02Me-1-Triz) 2-F H H 1-583 H H CH2CH2- (5-CH2CH2CH2C02Et-1-Triz) 2-F H H 1-584 Ac H CH2CH2- (5-CH2CH2CH2C02Et-1-Triz) 2-F H H 1-585 H H CH2-2-Triz 2-F H H 1-586 Ac H CH2-2-Triz 2-F H H 1-587 H H CH2- (4-C02H-2-Triz) 2-F H H 1-588 Ac H CH2- (4-C02H-2-Triz) 2-F H H 1-589 H H CH2- (4-C02Me-2-Triz) 2-F H H 1-590 Ac H CH2- (4-C02Me-2-Triz) 2-F H H 1-591 H H CH2- (4-C02Et-2-Triz) 2-F H H 1-592 Ac H CH2- (4-C02Et-2-Triz) 2-F H H 1-593 H H CH2- (4-CH2C02H-2-Triz) 2-F H H 1-594 Ac H CH2- (4-CH2C02H-2-Triz) 2-F H H 1-595 H H CH2- (4-CH2C02Me-2-Triz) 2-F H H 1-596 Ac H CH2- (4-CH2C02Me-2-Triz) 2-F H H 1-597 H H CH2- (4-CH2C02Et-2-Tr yz) 2-F H H 1-598 Ac H CH2- (4-CH2C02Et-2-Triz) 2-FHH 1-599 HH CH2- (4-CH2CH2C02H-2-Triz) 2-FHH 1-600 Ac H CH2- (4-CH2CH2C02H-2 -Triz) 2-FHH 1-601 H H CH2- (4-CH2CH2C02Me-2-Triz) 2-F H H 1-602 Ac H CH2- (4-CH2CH2C02Me-2-Triz) 2-F H H 1-603 H H CH2- (4-CH2CH2C02Et-2-Triz) 2-F H H 1-604 Ac H CH2- (4-CH2CH2C02Et-2-Triz) 2-F H H 1-605 H H CH2- (4-CH2CH2CH2C02H-2-Triz) 2-F H H 1-606 Ac H CH2- (4-CH2CH2CH2C02H-2-Triz) 2-F H H 1-607 H H CH2- (4-CH2CH2CH2C? 2Me-2-Triz) 2-F H H 1-608 Ac H CH2- (4-CH2CH2CH2C02Me-2-Triz) 2-F H H 1-609 H H CH2- (4-CH2CH2CH2C02Et-2-Triz) 2-F H H 1-610 Ac H CH2- (4-CH2CH2CH2C02Et-2-Triz) 2-F H H 1-611 H H CH2CH2-2-Triz 2-F H H 1-612 Ac H CH2CH2-2-Triz 2-F H H 1-613 H H CH2CH2- (4-C02H-2-Triz) 2-F H H 1-614 Ac H CH2CH2- (4-C02H-2-Triz) 2-F H H 1-615 H H CH2CH2- (4-C02Me-2-Triz) 2-F H H 1-616 Ac H CH2CH2- (4-C02Me-2-Triz) 2-F H H 1-617 H H CH2CH2- (4-C? 2 Et-2-Triz) 2-F H H 1-618 Ac H CH2CH2- (4-C02Et-2-Triz) 2-F H H 1-619 H H CH2CH2- (4-CH2C02H-2-Triz) 2-F H H 1-620 Ac H CH2CH2- (4-CH2C02H-2-Triz) 2-F H H 1-621 H H CH2CH2- (4-CH2C02Me-2-Triz) 2-F H H 1-622 Ac H CH2CH2- (4-CH2C02Me-2-Triz) 2-F H H 1-623 HH CH2CH2- (4-CH2C02Et-2-Triz) 2-FHH 1-624 Ac H CH2CH2- (4-CH2C02Et-2-Triz) 2-FHH 1-625 HH CH2CH2- (4-CH2CH2C02H-2- Triz) 2-FHH 1-626 Ac H CH2CH2- (4-CH2CH2C02H-2-Triz) 2-F H H 1-627 H H CH2CH2- (4-CH2CH2C02Me-2-Triz) 2-F H H 1-628 Ac H CH2CH2- (4-CH2CH2C02Me-2-Triz) 2-F H H 1-629 H H CH2CH2- (4-CH2CH2C02Et-2-Triz) 2-F H H 1-630 Ac H CH2CH2- (4-CH2CH2C02Et-2-Triz) 2-F H H 1-631 H H CH2CH2- (4-CH2CH2CH2C02H-2-Triz) 2-F H H 1-632 Ac H CH2CH2- (4-CH2CH2CH2C02H-2-Triz) 2-F H H 1-633 H H CH2CH2- (4-CH2CH2CH2C02Me-2-Triz) 2-F H H 1-634 Ac H CH2CH2- (4-CH2CH2CH2C02Me-2-Triz) 2-F H H 1-635 H H CH2CH2- (4-CH2CH2CH2C02Et-2-Triz) 2-F H H 1-636 Ac H CH2CH2- (4-CH2CH2CH2C? 2Et-2-Triz) 2-F H H 1-637 H H CH2-4-Triz 2-F H H 1-638 Ac H CH2-4-Triz 2-F H H 1-639 H H CH2-4-Triz 2-F 4-F H 1-640 Ac H CH2-4-Triz 2-F 4-F H 1-641 H H CH2- (1-C02 e-4-Triz) 2-F H H 1-642 Ac H CH2- (1-C02Me-4-Triz) 2-F H H 1-643 H H CH2- (1-C02Et-4-Triz) 2-F H H 1-644 Ac H CH2- (1-C02Et-4-Triz) 2-F H H 1-645 H H CH2- (5-C02H-4-Triz) 2-F H H 1-646 Ac H CH2- (5-C02H-4-Triz) 2-F H H 1-647 H H CH2- (5-C02Me-4-Triz) 2-F H H 1-648 Ac H CH2- (5-C02Me-4-Triz) 2-F H H 1-649 H H CH2- (5-C02Et-4-Triz) 2-F H H 1-650 Ac H CH2 - ((! 5-C02Et-4-Triz) 2-F H H 1-651 H H CH2- ((1-CH2C02H-4-Triz) 2-F H H 1-652 Ac H CH2- ((1-CH2C02H-4-Triz) 2-F H H 1-653 H H CH2- ((1-CH2C? 2Me-4-Triz) 2-F H H 1-654 Ac H CH2- ((1-CH2C02Me-4-Triz) 2-F H H 1-655 H H CH2- ((1-CH2C02Et-4-Triz) 2-F H H 1-656 Ac H CH2- ((1-CH2C02Et-4-Triz) 2-F H H 1-657 H H CH2- ((.5-CH2C02H-4-Triz) 2-F H H 1-658 Ac H CH2- ((5-CH2C02H-4-Triz) 2-F H H 1-659 H H CH2- ((5-CH2C02lv1e-4-Triz) 2-F H H 1-660 Ac H CH2- ((5-CH2C02Me-4-Triz) 2-F H H 1-661 H H CH2- ((5-CH2C02Et-4-Triz) 2-F H H 1-662 Ac H CH2- ((5-CH2C02Et-4-Triz) 2-F H H 1-663 H H CH2- ((1-CH2CH2C02H-4-Triz) 2-F H H 1-664 Ac H CH2- ((1-CH2CH2C02H-4-Triz) 2-F H H 1-665 H H CH2- ((1 -CH2CH2C? 2Me-4-Triz) 2-F H H 1-666 Ac H CH2- ((1-CH2CH2C02Me-4-Triz) 2-F H H 1-667 H H CH2- ((1-CH2CH2C02Et-4-Triz) 2-F H H 1-668 Ac H CH2- ((1-CH2CH2C02Et-4-Triz) 2-F H H 1-669 H H CH2- ((5-CH2CH2C02H-4-Triz) 2-F H H 1-670 Ac H CH2- ((5-CH2CH2C02H-4-Triz) 2-F H H 1-671 H H CH2- ((5-CH2CH2C02Me-4-Triz) 2-F H H 1-672 Ac H CH2- ((5-CH2CH2C02 e-4-Triz) 2-F H H 1-673 H H CH2- ((5-CH2CH2C02Et-4-Triz) 2-F H H 1-674 Ac H CH2- ((5-CH2CH2C02Et-4-Triz) 2-F H H 1-675 H H CH2- (1 -CH2CH2CH2C02H-4-Triz) 2-F H H 1-676 Ac H CH2- (1 -CH2CH2CH2C02H-4-Triz) 2-F H H 1-677 H H CH2- (1 -CH2CH2CH2C02Me-4-Triz) 2-F H H 1-678 Ac H CH2- (1 -CH2CH2CH2C02Me-4-Triz) 2-F H H 1-679 H H CH2- (1-CH2CH2CH2C02Et-4-Tr yz) 2-F H H 1-680 Ac H CH2- (1-CH2CH2CH2C02Et-4-Triz) 2-F H H 1-681 H H CH2- (5-CH2CH2CH2C02H-4-Triz) 2-F H H 1-682 Ac H CH2- (5-CH2CH2CH2C02H-4-Triz) 2-F H H 1-683 H H CH2- (5-CH2CH2CH2C02Me-4-Triz) 2-F H H 1-684 Ac H CH2- (5-CH2CH2CH2C02Me-4-Triz) 2-F H H 1-685 H H CH2- (5-CH2CH2CH2C02Et-4-Triz) 2-F H H 1-686 Ac H CH2- (5-CH2CH2CH2C02Et-4-Triz) 2-F H H 1-687 H H CH2CH2-4-Triz 2-F H H 1-688 Ac H CH2CH2-4-Triz 2-F H H 1-689 H H CH2CH2-4-Triz 2-F 4-F H 1-690 Ac H CH2CH2-4-Triz 2-F 4-F H 1-691 H H CH2CH2- (1 -C02Me-4-Triz) 2-F H H 1-692 Ac H CH2CH2- (1 -C02Me-4-Triz) 2-F H H 1-693 H H CH2CH2- (1-C02Et-4-Triz) 2-F H H 1-694 Ac H CH2CH2- (1-C02Et-4-Triz) 2-F H H 1-695 H H CH2CH2- (5-C02H-4-Triz) 2-F H H 1-696 Ac H CH2CH2- (5-C02H-4-Triz) 2-F H H 1-697 H H CH2CH2- (5-C02Me-4-Triz) 2-F H H 1-698 Ac H CH2CH2- (5-C02Me-4-Triz) 2-F H H 1-699 H H CH2CH2- (5-C02Et-4-Triz) 2-F H H 1-700 Ac H CH2CH2 - ((5-C02Et-4-Triz) 2-F H H 1-701 H H CH2CH2- ((1-CH2C02H-4-Triz) 2-F H H 1-702 Ac H CH2CH - ((1-CH2C02H-4-Triz) 2-F H H 1-703 H H CH2CH - ((1-CH2C02Me-4-Triz) 2-F H H 1-704 Ac H CH2CH2- ((1-CH2C02Me-4-Triz) 2-F H H 1-705 H H CH2CH2- ((1-CH2C02Et-4-Triz) 2-F H H 1-706 Ac H CH2CH2- ((1-CH2C02Et-4-Triz) 2-F H H 1-707 H H CH2CH2- ((5-CH2C02H-4-Triz) 2-F H H 1-708 Ac H CH2CH2- ((5-CH2C02H-4-Triz) 2-F H H 1-709 H H CH2CH2- ((5-CH2C02Me-4-Triz) 2-F H H 1-710 Ac H CH2CH2- ((5-CH2C02Me-4-Triz) 2-F H H 1-711 H H CH2CH2- ((5-CH2C02Et-4-Triz) 2-F H H 1-712 Ac H CH2CH2- ((5-CH2C02Et-4-Triz) 2-F H H 1-713 H H CH2CH2- ((1-CH2CH2C? 2H-4-Triz) 2-F H H 1-714 Ac H CH2CH2- ((1-CH2CH2C02H-4-Triz) 2-F H H 1-715 H H CH2CH2- ((1-CH2CH2C02Me-4-Triz) 2-F H H 1-716 Ac H CH2CH2- ((1-CH2CH2C02Me-4-Triz) 2-F H H 1-717 H H CH2CH2- ((1-CH2CH2C02Et-4-Triz) 2-F H H 1-718 Ac H CH CH2- ((1-CH2CH2C02Et-4-Triz) 2-F H H 1-719 H H CH2CH2- ((5-CH2CH2C02H-4-Triz) 2-F H H 1-720 Ac H CH2CH2- ((5-CH2CH2C02H-4-Triz) 2-F H H 1-721 H H CH2CH2- ((5-CH2CH2C02Me-4-Triz) 2-F H H 1-722 Ac H CH2CH2- ((5-CH2CH2C02Me-4-Triz) 2-F H H 1-723 H H CH2CH2- ((5-CH2CH2C02Et-4-Triz) 2-F H H 1-724 Ac H CH2CH2- ((5-CH2CH2C02Et-4-Triz) 2-F H H 1-725 H H CH2CH2- (1 -CH2CH2CH2C02H-4-Triz) 2-F H H 1-726 Ac H CH2CH2- (1 -CH2CH2CH2C02H-4-Triz) 2-F H H 1-727 H H CH2CH2- (1 -CH2CH2CH2C02Me-4-Triz) 2-F H H 1-728 Ac H CH2CH2- (1 -CH2CH2CH2C02Me-4-Triz) 2-F H H 1-729 H H CH2CH2- (1 -CH2CH2CH2C02Et-4-Triz) 2-F H H 1-730 Ac H CH2CH2- (1 -CH2CH2CH2C02Et-4-Triz) 2-F H H 1-731 H H CH2CH2- (5-CH2CH2CH2C02H-4-Triz) 2-F H H 1-732 Ac H CH2CH2- (5-CH2CH2CH2C02H-4-Triz) 2-F H H 1-733 H H CH2CH2- (5-CH2CH2CH2C02Me-4-Triz) 2-F H H 1-734 Ac H CH2CH2- (5-CH2CH2CH2C02 e-4-Tr yz) 2-F H H 1-735 H H CH2CH2- (5-CH2CH2CH2C02Et-4-Triz) 2-F H H 1-736 Ac H CH2CH2- (5-CH2CH2CH2C02Et-4-Triz) 2-F H H 1-737 H H CH2- (1-C02Me-5-Triz) 2-F 4-F H 1-738 Ac H CH2- (1-C02Me-5-Triz) 2-F 4-F H 1-739 H H CH2- (1-C02Me-5-Triz) 2-F H H 1-740 Ac H CH2- (1-C02Me-5-Triz) 2-F H H 1-741 H H CH2- (1-C02Et-5-Triz) 2-F H H 1-742 Ac H CH2- (1-C02Et-5-Triz) 2-F H H 1-743 H H CH2- (1-CH2C02H-5-Triz) 2-F H H 1-744 Ac H CH2- (1-CH2C02H-5-Triz) 2-F H H 1-745 H H CH2- (1-CH2C02Me-5-Triz) 2-F H H 1-746 Ac H CH2- (1-CH2C02Me-5-Triz) 2-F H H 1-747 H H CH2- (1-CH2C02Et-5-Triz) 2-F H H 1-748 Ac H CH2- (1-CH2C02Et-5-Triz) 2-F H H 1-749 H H CH2- (1 -CH2CH2C02H-5-Triz) 2-F H H 1-750 Ac H CH 2 -C (1-CH 2 CH 2 -C0 2 H-5-Triz) 2-F H H 1-751 H H CH2- ((1-CH2CH2C02 e-5-Triz) 2-F H H 1-752 Ac H CH2- ((1-CH2CH2C02Me-5-Triz) 2-F H H 1-753 H H CH2- ((1-CH2CH2C02Et-5-Triz) 2-F H H 1-754 Ac H CH2- ((1-CH2CH2C02Et-5-Triz) 2-F H H 1-755 H H CH2- ((1 -CH2CH2CH2C02H-5-Triz) 2-F H H 1-756 Ac H CH2- ((1 -CH2CH2CH2C02H-5-Triz) 2-F H H 1-757 H H CH2- ((1-CH2CH2CH2C02Me-5-Triz) 2-F H H 1-758 Ac H CH2- ((1 -CH2CH2CH2C02 e-5-Triz) 2-F H H 1-759 H H CH2- ((1 -CH2CH2CH2C02Et-5-Triz) 2-F H H 1-760 Ac H CH2- ((1 -CH2CH2CH2C02Et-5-Triz) 2-F H H 1-761 H H CH2-1 1-Tez 2-F H H 1-762 Ac H CH2-I 1-Tez 2-F H H 1-763 H H CH2- ((.5-C02H-1-Tez) 2-F H H 1-764 Ac H CH2- ((5-C02H-1-Tez) 2-F H H 1-765 H H CH2- ((.5-C02Me-1-Tez) 2-F H H 1-766 Ac H CH2- ((.5-C02Me-1-Tez) 2-F H H 1-767 H H CH2- ((5-C02Et-1-Tez) 2-F H H 1-768 Ac H CH2- ((.5-C02Et-1-Tez) 2-F H H 1-769 H H CH2- ((5-CH2C02H-1-Tez) 2-F H H 1-770 Ac H CH2- ((5-CH2C02H-1-Tez) 2-F H H 1-771 H H CH2- ((5-CH2C02Me-1-Tez) 2-F H H 1-772 Ac H CH2- ((5-CH2C02Me-1-Tez) 2-F H H 1-773 H H CH2- ((5-CH2C02Et-1-Tez) 2-F H H 1-774 Ac H CH2- ((5-CH2C02Et-1-Tez) 2-F H H 1-775 H H CH2- (5-CH2CH2C02H-1 -Tez) 2-F H H 1-776 Ac H CH2- (5-CH2CH2C02H-1 -Tez) 2-F H H 1-777 H H CH2- (5-CH2CH2C02Me-1 -Tez) 2-F H H 1-778 Ac H CH2- (5-CH2CH2C02Me-1 -Tez) 2-F H H 1-779 H H CH2- (5-CH2CH2C02Et-1 -Tez) 2-F H H 1-780 Ac H CH2- (5-CH2CH2C02Et-1 -Tez) 2-F H H 1-781 H H CH2- (5-CH2CH2CH2C02H-1 -Tez) 2-F H H 1-782 Ac H CH2- (5-CH2CH2CH2C02H-1 -Tez) 2-F H H 1-783 H H CH2- (5-CH2CH2CH2C02Me-1 -Tez) 2-F H H 1-784 Ac H CH2- (5-CH2CH2CH2C02iv1e-1 -Tez) 2-F H H 1-785 H H CH2- (5-CH2CH2CH2C02Et-1 -Tez) 2-F H H 1-786 Ac H CH2- (5-CH2CH2CH2C02Et-1 -Tez) 2-F H H 1-787 H H CH2CH2-1-Tez 2-F H H 1-788 Ac H CH2CH2-1-Tez 2-F H H 1-789 H H CH2CH2- (5-C02H-1-Tez) 2-F H H 1-790 Ac H CH2CH2- (5-C02H-1-Tez) 2-F H H 1-791 H H CH2CH2- (5-C02Me-1-Tez) 2-F H H 1-792 Ac H CH2CH2- (5-C02Me-1-Tez) 2-F H H 1-793 H H CH2CH2- (5-C02Et-1-Tez) 2-F H H 1-794 Ac H CH2CH2- (5-C02Et-1-Tez) 2-F H H 1-795 H H CH2CH2- (5-CH2C02H-1 -Tez) 2-F H H 1-796 Ac H CH2CH2- (5-CH2C02H-1 -Tez) 2-F H H 1-797 H H CH2CH2- (5-CH2C02Me-1 -Tez) 2-F H H 1-798 Ac H CH2CH2- (5-CH2C02Me-1 -Tez) 2-F H H 1-799 H H CH2CH2- (5-CH2C02Et-1 -Tez) 2-F H H 1-800 Ac H CH2CH2- (5-CH2C02Et-1 -Tez) 2-F H H 1-801 H H CH2CH2- (5-CH2CH2C? 2H-1 -Tez) 2-F H H 1-802 Ac H CH2CH2- (5-CH2CH2C? 2H-1 -Tez) 2-F H H 1-803 H H CH2CH2- (5-CH2CH2C02Me-1 -Tez) 2-F H H 1-804 Ac H CH2CH2- (5-CH2CH2C02Me-1 -Tez) 2-F H H 1-805 H H CH2CH2- (5-CH2CH2C02Et-1 -Tez) 2-F H H 1-806 Ac H CH2CH2- (5-CH2CH2C02Et-1-Tez) 2-F H H 1-807 H H CH2CH2- (5-CH2CH2CH2C02H-1 -Tez) 2-F H H 1-808 Ac H CH2CH2- (5-CH2CH2CH2C02H-1 -Tez) 2-F H H 1-809 H H CH2CH2- (5-CH2CH2CH2C02Me-1 -Tez) 2-F H H 1-810 Ac H CH2CH2- (5-CH2CH2CH2C02 e-1 -Tez) 2-F H H 1-811 H H CH2CH2- (5-CH2CH2CH2C02Et-1 -Tez) 2-F H H 1-812 Ac H CH2CH2- (5-CH2CH2CH2C02Et-1 -Tez) 2-F H H 1-813 H H CH2-2-Tez 2-F H H 1-814 Ac H CH2-2-Tez 2-F H H 1-815 H H CH2- (5-C02H-2-Tez) 2-F H H 1-816 Ac H CH2- (5-C02H-2-Tez) 2-F H H 1-817 H H CH2- (5-C02Me-2-Tez) 2-F H H 1-818 Ac H CH2- (5-C02Me-2-Tez) 2-F H H 1-819 H H CH2- (5-C02Et-2-Tez) 2-F H H 1-820 Ac H CH2- (5-C02Et-2-Tez) 2-F H H 1-821 H H CH2- (5-CH2C02H-2-Tez) 2-F H H 1-822 Ac H CH2- (5-CH2C02H-2-Tez) 2-F H H 1-823 H H CH2- (5-CH2C02Me-2-Tez) 2-F H H 1-824 Ac H CH2- (5-CH2C02Me-2-Tez) 2-F H H 1-825 H H CH2- (5-CH2C02Et-2-Tez) 2-F H H 1-826 Ac H CH2- (5-CH2C02Et-2-Tez) 2-F H H 1-827 H H CH2- (5-CH2CH2C02H-2-Tez) 2-F H H 1-828 Ac H CH2- (5-CH2CH2C? 2H-2-Tez) 2-F H H 1-829 H H CH2- (5-CH2CH2C02Me-2-Tez) 2-F H H 1-830 Ac H CH2- (5-CH2CH2C02Me-2-Tez) 2-F H H 1-831 H H CH2- (5-CH2CH2C02Et-2-Tez) 2-F H H 1-832 Ac H CH2- (5-CH2CH2C02Et-2-Tez) 2-F H H 1-833 H H CH2- (5-CH2CH2CH2C02H-2-Tez) 2-F H H 1-834 Ac H CH2- (5-CH2CH2CH2C02H-2-Tez) 2-F H H 1-835 H H CH2- (5-CH2CH2CH2C02Me-2-Tez) 2-F H H 1-836 Ac H CH2- (5-CH2CH2CH2C02Me-2-Tez) 2-F H H 1-837 H H CH2- (5-CH2CH2CH2C02Et-2-Tez) 2-F H H 1-838 Ac H CH2- (5-CH2CH2CH2C02Et-2-Tez) 2-F H H 1-839 H H CH2CH2-2-Tez 2-F H H 1-840 Ac H CH2CH2-2-Tez 2-F H H 1-841 H H CH2CH2- (5-C02H-2-Tez) 2-F H H 1-842 Ac H CH2CH2- (5-C02H-2-Tez) 2-F H H 1-843 H H CH2CH2- (5-C02 e-2-Tez) 2-F H H 1-844 Ac H CH2CH2- (5-C02Me-2-Tez) 2-F H H 1-845 H H CH2CH2- (5-C02Et-2-Tez) 2-F H H 1-846 Ac H CH2CH2- (5-C02Et-2-Tez) 2-F H H 1-847 H H CH2CH2- (5-CH2C02H-2-Tez) 2-F H H 1-848 Ac H CH2CH2- (5-CH2C02H-2-Tez) 2-F H H 1-849 H H CH2CH2- (5-CH2C02Me-2-Tez) 2-F H H 1-850 Ac H CH2CH2- (5-CH2C02Me-2-Tez) 2-F H H 1-851 H H CH2CH2- (5-CH2C02Et-2-Tez) 2-F H H 1-852 Ac H CH2CH2- (5-CH2C02Et-2-Tez) 2-F H H 1-853 H H CH2CH2- (5-CH2CH2C02H-2-Tez) 2-F H H 1-854 Ac H CH2CH2- (5-CH2CH2C02H-2-Tez) 2-F H H 1-855 H H CH2CH2- (5-CH2CH2C02Me-2-Tez) 2-F H H 1-856 Ac H CH2CH2- (5-CH2CH2C02Me-2-Tez) 2-F H H 1-857 H H CH2CH2- (5-CH2CH2C02Et-2-Tez) 2-F H H 1-858 Ac H CH2CH2- (5-CH2CH2C02Et-2-Tez) 2-F H H 1-859 H H CH2CH2- (5-CH2CH2CH2C? 2H-2-Tez) 2-F H H 1-860 Ac H CH2CH2- (5-CH2CH2CH2C02H-2-Tez) 2-F H H 1-861 H H CH2CH2- (5-CH2CH2CH2C02Me-2-Tez) 2-F H H 1-862 Ac H CH2CH2- (5-CH2CH2CH2C02 e-2-Tez) 2-F H H 1-863 H H CH2CH2- (5-CH2CH2CH2C02Et-2-Tez) 2-F H H 1-864 Ac H CH2CH2- (5-CH2CH2CH2C02Et-2-Tez) 2-F H H 1-865 H H CH2-5-Tez 2-F H H 1-866 Ac H CH2-5-Tez 2-F H H 1-867 H H CH2-5-Tez 2-F 4-F H 1-868 Ac H CH2-5-Tez 2-F 4-F H 1-869 H H CH2- (1-C02Me-5-Tez) 2-F H H 1-870 Ac H CH2- (1-C02Me-5-Tez) 2-F H H 1-871 H H CH2- (1-C02Et-5-Tez) 2-F H H 1-872 Ac H CH2- (1-C02Et-5-Tez) 2-F H H 1-873 H H CH2- (2-C02Me-5-Tez) 2-F 4-F H 1-874 Ac H CH2- (2-C02Me-5-Tez) 2-F 4-F H 1-875 H H CH2- (2-C02Me-5-Tez) 2-F H H 1-876 Ac H CH2- (2-C02Me-5-Tez) 2-F H H 1-877 H H CH2- (2-C02Et-5-Tez) 2-F H H 1-878 Ac H CH2- (2-C02Et-5-Tez) 2-F H H 1-879 H H CH2- (1-CH2C02H-5-Tez) 2-F H H 1-880 Ac H CH2- (1-CH2C02H-5-Tez) 2-F H H 1-881 H H CH2- (1-CH2C02Me-5-Tez) 2-F H H 1-882 Ac H CH2- (1-CH2C02Me-5-Tez) 2-F H H 1-883 H H CH2- (1-CH2C02Et-5-Tez) 2-F H H 1-884 Ac H CH2- (1-CH2C02Et-5-Tez) 2-F H H 1-885 H H CH2- (2-CH2C02H-5-Tez) 2-F H H 1-886 Ac H CH2- (2-CH2C02H-5-Tez) 2-F H H 1-887 H H CH2- (2-CH2C02Me-5-Tez) 2-F H H 1-888 Ac H CH2- (2-CH2C02Me-5-Tez) 2-F H H 1-889 H H CH2- (2-CH2C02Et-5-Tez) 2-F H H 1-890 Ac H CH2- (2-CH2C02Et-5-Tez) 2-F H H 1-891 H H CH2- (1-CH2CH2C02H-5-Tez) 2-F H H 1-892 Ac H CH2- (1-CH2CH2C02H-5-Tez) 2-F H H 1-893 H H CH2- (1-CH2CH2C02Me-5-Tez) 2-F H H 1-894 Ac H CH2- (1-CH2CH2C02Me-5-Tez) 2-F H H 1-895 H H CH2- (1-CH2CH2C02Et-5-Tez) 2-F H H 1-896 Ac H CH2- (1-CH2CH2C02Et-5-Tez) 2-F H H 1-897 H H CH2- (2-CH2CH2C02H-5-Tez) 2-F H H 1-898 Ac H CH2- (2-CH2CH2C02H-5-Tez) 2-F H H 1-899 H H CH2- (2-CH2CH2C02Me-5-Tez) 2-F H H 1-900 Ac H CH2- (2-CH2CH2C02Me-5-Tez) 2-F H H 1-901 H H CH2- (2-CH2CH2C02Et-5-Tez) 2-F H H 1-902 Ac H CH2- (2-CH2CH2C02Et-5-Tez) 2-F H H 1-903 H H CH2- (1-CH2CH2CH2C02H-5-Tez) 2-F H H 1-904 Ac H CH2- (1 -CH2CH2CH2C02H-5-Tez) 2-F H H 1-905 H H CH2- (1 -CH2CH2CH2C02Me-5-Tez) 2-F H H 1-906 Ac H CH2- (1 -CH2CH2CH2C02Me-5-Tez) 2-F H H 1-907 H H CH2- (1 -CH2CH2CH2C02Et-5-Tez) 2-F H H 1-908 Ac H CH2- (1 -CH2CH2CH2C02Et-5-Tez) 2-F H H 1-909 H H CH2- (2-CH2CH2CH2C? 2H-5-Tez) 2-F H H 1-910 Ac H CH2- (2-CH2CH2CH2C02H-5-Tez) 2-F H H 1-911 H H CH2- (2-CH2CH2CH2C02Me-5-Tez) 2-F H H 1-912 Ac H CH2- (2-CH2CH2CH2C02Me-5-Tez) 2-F H H 1-913 H H CH2- (2-CH2CH2CH2C02Et-5-Tez) 2-F H H 1-914 Ac H CH2- (2-CH2CH2CH2C02Et-5-Tez) 2-F H H 1-915 H H CH2CH2-5-Tez 2-F H H 1-916 Ac H CH2CH2-5-Tez 2-F H H 1-917 H H CH2CH2-5-Tez 2-F 4-F H 1-918 Ac H CH2CH2-5-Tez 2-F 4-F H 1-919 H H CH2CH2- (1-C02Me-5-Tez) 2-F H H 1-920 Ac H CH2CH2- (1-C02Me-5-Tez) 2-F H H 1-921 H H CH2CH2- (1-C02Et-5-Tez) 2-F H H 1-922 Ac H CH2CH2- (1-C02Et-5-Tez) 2-F H H 1-923 H H CH2CH2- (2-C02Me-5-Tez) 2-F 4-F H 1-924 Ac H CH2CH2- (2-C02Me-5-Tez) 2-F 4-F H 1-925 H H CH2CH2- ((? 2-C02Me-5-Tez) 2-F H H 1-926 Ac H CH2CH- ((, 2-C02Me-5-Tez) 2-F H H 1-927 H H CH2CH2- ((2-C02Et-5-Tez) 2-F H H 1-928 Ac H CH2CH2- ((2-C02Et-5-Tez) 2-F H H 1-929 H H CH2CH2- ((1-CH2C02H-5-Tez) 2-F H H 1-930 Ac H CH2CH2- ((1-CH2C02H-5-Tez) 2-F H H 1-931 H H CH2CH2- ((1-CH2C02Me-5-Tez) 2-F H H 1-932 Ac H CH2CH2- ((1-CH2C02Me-5-Tez) 2-F H H 1-933 H H CHCH2- ((1-CH2C02Et-5-Tez) 2-F H H 1-934 Ac H CH2CH2- ((1-CH2C02Et-5-Tez) 2-F H H 1-935 H H CH2CH2- ((2-CH2C02H-5-Tez) 2-F H H 1-936 Ac H CH2CH2- ((2-CH2C02H-5-Tez) 2-F H H 1-937 H H CH2CH2- ((2-CH2C02Me-5-Tez) 2-F H H 1-938 Ac H CH2CH2- ((2-CH2C02Me-5-Tez) 2-F H H 1-939 H H CH2CH2- ((2-CH2C02Et-5-Tez) 2-F H H 1-940 Ac H CHCH2- ((2-CH2C02Et-5-Tez) 2-F H H 1-941 H H CHCH2- ((1-CH2CH2C02H-5-Tez) 2-F H H 1-942 Ac H CH2CH2- ((1-CH2CH2C02H-5-Tez) 2-F H H 1-943 H H CH2Cp2- ((1 -CH2CH2C02IV¡e-5-Tez) 2-F H H 1-944 Ac H Cp2Cp2- ((1-CH2CH2C02Me-5-Tez) 2-F H H 1-945 H H CH2CH2- ((1-CH2CH2C02Et-5-Tez) 2-F H H 1-946 Ac H CH2CH2- ((1-CH2CH2C02Et-5-Tez) 2-F H H 1-947 H H CH2CH2- ((2-CH2CH2C02H-5-Tez) 2-F H H 1-948 Ac H CH2CH2- ((2-CH2CH2C02H-5-Tez) 2-F H H 1-949 H H CH2CH2- ((2-CH2CH2C02Me-5-Tez) 2-F H H 1-950 Ac H CH2CH2- (2-CH2CH2C02Me-5-Tez) 2-F H H 1-951 H H CH2CH2- (2-CH2CH2C02Et-5-Tez) 2-F H H 1-952 Ac H CH2CH2- (2-CH2CH2C02Et-5-Tez) 2-F H H 1-953 H H CH2CH2- (1 -CH2CH2CH2C02H-5-Tez) 2-F H H 1-954 Ac H CH2CH2- (1 -CH2CH2CH2C02H-5-Tez) 2-F H H 1-955 H H CH2CH2- (1 -CH2CH2CH2C02Me-5-Tez) 2-F H H 1-956 Ac H CH2CH2- (1 -CH2CH2CH2C02Me-5-Tez) 2-F H H 1-957 H H CH2CH2- (1 -CH2CH2CH2C02Et-5-Tez) 2-F H H 1-958 Ac H CH2CH2- (1 -CH2CH2CH2C02Et-5-Tez) 2-F H H 1-959 H H CH2CH2- (2-CH2CH2CH2C02H-5-Tez) 2-F H H 1-960 Ac H CH2CH2- (2-CH2CH2CH2C02H-5-Tez) 2-F H H 1-961 H H CH2CH2- (2-CH2CH2CH2C02Me-5-Tez) 2-F H H 1-962 Ac H CH2CH2- (2-CH2CH2CH2C02Me-5-Tez) 2-F H H 1-963 H H CH2CH2- (2-CH2CH2CH2C02Et-5-Tez) 2-F H H 1-964 Ac H CH2CH2- (2-CH2CH2CH2C02Et-5-Tez) 2-F H H 1-965 H Me CH2-1-Pyza 2-F H H 1-966 Ac Me CH2-1-Pyza 2-F H H 1-967 H Me CH2- (3-C02H-1-Pyza) 2-F H H 1-968 Ac Me CH2- (3-C02H-1-Pyza) 2-F H H 1-969 H Me CH2- (3-C02Me-1-Pyza) 2-F H H 1-970 Ac Me CH2- (3-C02Me-1-Pyza) 2-F H H 1-971 H Me CH2- (3-C02Et-1-Pyza) 2-F H H 1-972 Ac Me CH2- (3-C02Et-1-Pyza) 2-F H H 1-973 H Me CH2- (4-C02H-1-Pyza) 2-F H H 1-974 Ac Me CH2- (4-C02H-1-Pyza) 2-F H H 1-975 H Me CH2- (4-C02Me-1-Pyza) 2-F H H 1-976 Ac Me CH2- (4-C02Me-1-Pyza) 2-F H H 1-977 H Me CH2- (4-C02Et-1-Pyza) 2-F H H 1-978 Ac Me CH2- (4-C02Et-1-Pyza) 2-F H H 1-979 H Me CH2- (3-CH2C02H-1 -Pyza) 2-F H H 1-980 Ac Me CH2- (3-CH2C02H-1-Pyza) 2-F H H 1-981 H Me CH2- (3-CH2C02Me-1 -Pyza) 2-F H H 1-982 Ac Me CH2- (3-CH2C02Me-1 -Pyza) 2-F H H 1-983 H Me CH2- (3-CH2C02Et-1 -Pyza) 2-F H H 1-984 Ac Me CH2- (3-CH2C02Et-1 -Pyza) 2-F H H 1-985 H Me CH2- (4-CH2C02H-1-Pyza) 2-F H H 1-986 Ac Me CH2- (4-CH2C02H-1 -Pyza) 2-F H H 1-987 H Me CH2- (4-CH2C02Me-1 -Pyza) 2-F H H 1-988 Ac Me CH2- (4-CH2C02Me-1 -Pyza) 2-F H H 1-989 H Me CH2- (4-CH2C02Et-1 -Pyza) 2-F H H 1-990 Ac Me CH2- (4-CH2C02Et-1 -Pyza) 2-F H H 1-991 H Me CH2- (3-CH2CH2C02H-1 -Pyza) 2-F H H 1-992 Ac Me CH2- (3-CH2CH2C02H-1 -Pyza) 2-F H H 1-993 H Me CH2- (3-CH2CH2C02Me-1 -Pyza) 2-F H H 1-994 Ac Me CH2- (3-CH2CH2C02Me-1 -Pyza) 2-F H H 1-995 H Me CH2- (3-CH2CH2C02Et-1 -Pyza) 2-F H H 1-996 Ac Me CH2- (3-CH2CH2C02Et-1 -Pyza) 2-F H H 1-997 H Me CH2- (4-CH2CH2C02H-1 -Pyza) 2-F H H 1-998 Ac Me CH2- (4-CH2CH2C02H-1 -Pyza) 2-FHH 1-999 H Me CH2- (4-CH2CH2C02Me-1 -Pyza) 2 -FHH 1-1000 Ac Me CH2- (4-CH2CH2C02Me- 1 -Pyza) 2-FHH 1-1001 H Me CH2- (4-CH2CH2C02Et-1-Pyza) 2-F H H 1-1002 Ac Me CH2- (4-CH2CH2C02Et-1 -Pyza) 2-F H H 1-1003 H Me CH2CH2-1-Pyza 2-F H H 1-1004 Ac Me CH2CH2-1-Pyza 2-F H H 1-1005 H Me CH2CH2- (3-C02H-1-Pyza) 2-F H H 1-1006 Ac Me CH2CH2- (3-C02H-1-Pyza) 2-F H H 1-1007 H Me CH2CH2- (3-C02Me-1 -Pyza) 2-F H H 1-1008 Ac Me CH2CH2- (3-C02Me-1 -Pyza) 2-F H H 1-1009 H Me CH2CH2- (3-C02Et-1 -Pyza) 2-F H H 1-1010 Ac Me CH2CH2- (3-C02Et-1 -Pyza) 2-F H H 1-1011 H Me CH2CH2- (4-C02H-1-Pyza) 2-F H H 1-1012 Ac Me CH2CH2- (4-C02H-1 -Pyza) 2-F H H 1-1013 H Me CH2CH2- (4-C02Me-1 -Pyza) 2-F H H 1-1014 Ac Me CH2CH2- (4-C02Me-1 -Pyza) 2-F H H 1-1015 H Me CH2CH2- (4-C02Et-1-Pyza) 2-F H H 1-1016 Ac Me CH2CH2- (4-C02Et-1 -Pyza) 2-F H H 1-1017 H Me CH2CH2- (3-CH2C02H-1 -Pyza) 2-F H H 1-1018 Ac Me CH2CH2- (3-CH2C02H-1 -Pyza) 2-F H H 1-1019 H Me CH2CH2- (3-CH2C02Me-1 -Pyza) 2-F H H 1-1020 Ac Me CH2CH2- (3-CH2C02Me-1 -Pyza) 2-F H H 1-1021 H Me CH2CH2- (3-CH2C02Et-1 -Pyza) 2-F H H 1-1022 Ac Me CH2CH2- (3-CH2C02Et-1 -Pyza) 2-F H H 1-1023 H Me CH2CH2- (4-CH2C02H-1-Pyza) 2-F H H 1-1024 Ac Me CH2CH2- (4-CH2C02H-1 -Pyza) 2-F H H 1-1025 H Me CH2CH2- (4-CH2C02Me-1 -Pyza) 2-F H H 1-1026 Ac Me CH2CH2- (4-CH2C02Me-1 -Pyza) 2-F H H 1-1027 H Me CH2CH2- (4-CH2C02Et-1 -Pyza) 2-F H H 1-1028 Ac Me CH2CH2- (4-CH2C02Et-1 -Pyza) 2-F H H 1-1029 H Me CH2CH2- (3-CH2CH2C02H-1 -Pyza) 2-F H H 1-1030 Ac Me CH2CH2- (3-CH2CH2C02H-1 -Pyza) 2-F H H 1-1031 H Me CH2CH2- (3-CH2CH2C02Me-1 -Pyza) 2-F H H 1-1032 Ac Me CH2CH2- (3-CH2CH2C02Me-1 -Pyza) 2-F H H 1-1033 H Me CH2CH2- (3-CH2CH2C02Et-1 -Pyza) 2-F H H 1-1034 Ac Me CH2CH2- (3-CH2CH2C02Et-1 -Pyza) 2-F H H 1-1035 H Me CH2CH2- (4-CH2CH2C02H-1-Pyza) 2-F H H 1-1036 Ac Me CH2CH2- (4-CH2CH2C02H-1 -Pyza) 2-F H H 1-1037 H Me CH2CH2- (4-CH2CH2C02Me-1 -Pyza) 2-F H H 1-1038 Ac Me CH2CH2- (4-CH2CH2C02Me-1 -Pyza) 2-F H H 1-1039 H Me CH2CH2- (4-CH2CH2C02Et-1-Pyza) 2-F H H 1-1040 Ac Me CH2CH2- (4-CH2CH2C02Et-1 -Pyza) 2-F H H 1-1041 H H CH2- (2-C02Me-4-Triz) 2-F H H 1-1042 Ac H CH2- (2-C02Me-4-Triz) 2-F H H 1-1043 H H CH2- (2-C02Et-4-Triz) 2-F H H 1-1044 Ac H CH2- (2-C02Et-4-Triz) 2-F H H 1-1045 H H CH2- (2-CH2C02H-4-Triz) 2-F H H 1-1046 Ac H CH2- (2-CH2C02H-4-Triz) 2-F H H 1-1047 H H CH2- (2-CH2C02Me-4-Triz) 2-F H H 1-1048 Ac H CH2- (2-CH2C02Me-4-Triz) 2-F H H 1-1049 H H CH2- (2-CH2C02Et-4-Triz) 2-F H H 1-1050 Ac H CH2- (2-CH2C02Et-4-Triz) 2-F H H 1-1051 H H CH2- (2-CH2CH2C02H-4-Triz) 2-F H H 1-1052 Ac H CH2- (2-CH2CH2C02H-4-Triz) 2-F H H 1-1053 H H CH2- (2-CH2CH2C02Me-4-Triz) 2-F H H 1-1054 Ac H CH2- (2-CH2CH2C02Me-4-Triz) 2-F H H 1-1055 H H CH2- (2-CH2CH2C02Et-4-Triz) 2-F H H 1-1056 Ac H CH2- (2-CH2CH2C02Et-4-Triz) 2-F H H 1-1057 H H CH2- (2-CH2CH2CH2C02H-4-Triz) 2-F H H 1-1058 Ac H CH2- (2-CH2CH2CH2C02H-4-Triz) 2-F H H 1-1059 H H CH2- (2-CH2CH2CH2C? 2Me-4-Triz) 2-F H H 1-1060 Ac H CH2- (2-CH2CH2CH2C? 2Me-4-Triz) 2-F H H 1-1061 H H CH2- (2-CH2CH2CH2C02Et-4-Triz) 2-F H H 1-1062 Ac H CH2- (2-CH2CH2CH2C02Et-4-Triz) 2-F H H 1-1063 H H CH2CH2- (2-C02Me-4-Triz) 2-F H H 1-1064 Ac H CH2CH2- (2-C02Me-4-Triz) 2-F H H 1-1065 H H CH2CH2- (2-C02Et-4-Triz) 2-F H H 1-1066 Ac H CH2CH2- (2-C02Et-4-Triz) 2-F H H 1-1067 H H CH2CH2- (2-CH2C02H-4-Triz) 2-F H H 1-1068 Ac H CH2CH2- (2-CH2C02H-4-Triz) 2-F H H 1-1069 H H CH2CH2- (2-CH2C02Me-4-Triz) 2-F H H 1-1070 Ac H CH2CH2- (2-CH2C02Me-4-Triz) 2-F H H 1-1071 H H CH2CH2- (2-CH2C02Et-4-Triz) 2-F H H 1-1072 Ac H CH2CH2- (2-CH2C02Et-4-Triz) 2-F H H 1-1073 H H CH2CH2- (2-CH2CH2C02H-4-Triz) 2-F H H 1-1074 Ac H CH2CH2- (2-CH2CH2C02H-4-Triz) 2-F H H 1-1075 H H CH2CH2- (2-CH2CH2C02Me-4-Triz) 2-F H H 1-1076 Ac H CH2CH2- (2-CH2CH2C02Me-4-Triz) 2-F H H 1-1077 H H CH2CH2- (2-CH2CH2C02Et-4-Triz) 2-F H H 1-1078 Ac H CH2CH2- (2-CH2CH2C02Et-4-Triz) 2-F H H 1-1079 H H CH2CH2- (2-CH2CH2CH2C02H-4-Triz) 2-F H H 1-1080 Ac H CH2CH2- (2-CH2CH2CH2C02H-4-Triz) 2-F H H 1-1081 H H CH2CH2- (2-CH2CH2CH2C02Me-4-Triz) 2-F H H 1-1082 Ac H CH2CH2- (2-CH2CH2CH2C02Me-4-Triz) 2-F H H 1-1083 H H CH2CH2- (2-CH2CH2CH2C02Et-4-Triz) 2-F H H 1-1084 Ac H CH2CH2- (2-CH2CH2CH2C02Et-4-Triz) 2-F H H (Table 2) Comp. No. P R2 R3 X1 X2 X3 2-1 HH CH2-1-Pyza 2-FHH 2-2 Ac H CH2-1-Pyza 2-FHH 2-3 HH CH2-1-Pyza 2-F 4-FH 2-4 Ac H CH2-1-Pyza 2-F 4-FH 2-5 HH CH2- (3-C02H-1-Pyza) 2-FHH 2-6 Ac H CH2- (3-C02H-1-Pyza) 2-FHH 2-7 H H CH2- (3-C02H-1-Pyza) 2-F 4-F H 2-8 Ac H CH2- (3-C02H-1-Pyza) 2-F 4-F H 2-9 H H CH2- (3-C02Me-1-Pyza) 2-F H H 2-10 Ac H CH2- (3-C02Me-1-Pyza) 2-F H H 2-11 H H CH2- (3-C02Me-1-Pyza) 2-F 4-F H 2-12 Ac H CH2- (3-C02Me-1-Pyza) 2-F 4-F H 2-13 H H CH2- (3-C02Et-1-Pyza) 2-F H H 2-14 Ac H CH2- (3-C02Et-1-Pyza) 2-F H H 2-15 H H CH2- (3-C02Et-1-Pyza) 2-F 4-F H 2-16 Ac H CH2- (3-C02Et-1-Pyza) 2-F 4-F H 2-17 H H CH2- (4-C02H-1-Pyza) 2-F H H 2-18 Ac H CH2- (4-C02H-1-Pyza) 2-F H H 2-19 H H CH2- (4-C02H-1-Pyza) 2-F 4-F H 2-20 Ac H CH2- (4-C02H-1-Pyza) 2-F 4-F H 2-21 H H CH2- (4-C02Me-1-Pyza) 2-F H H 2-22 Ac H CH2- (4-C02Me-1-Pyza) 2-F H H 2-23 H H CH2- (4-C02Me-1-Pyza) 2-F 4-F H 2-24 Ac H CH2- (4-C02Me-1-Pyza) 2-F 4-F H 2-25 H H CH2- (4-C02Et-1-Pyza) 2-F H H 2-26 Ac H CH2- (4-C02Et-1-Pyza) 2-F H H 2-27 H H CH2- (4-C02Et-1-Pyza) 2-F 4-F H 2-28 Ac H CH2- (4-C02Et-1-Pyza) 2-F 4-F H 2-29 H H CH2- (5-C02H-1-Pyza) 2-F H H 2-30 Ac H CH2- (5-C02H-1-Pyza) 2-F H H 2-31 H H CH2- (5-C02H-1-Pyza) 2-F 4-F H 2-32 Ac H CH2- (5-C02H-1-Pyza) 2-F 4-F H 2-33 H H CH2- (5-C02Me-1-Pyza) 2-F H H 2-34 Ac H CH2- (5-C02Me-1-Pyza) 2-F H H 2-35 H H CH2- (5-C02Me-1-Pyza) 2-F 4-F H 2-36 Ac H CH2- (5-C02Me-1-Pyza) 2-F 4-F H 2-37 H H CH2- (5-C02Et-1-Pyza) 2-F H H 2-38 Ac H CH2- (5-C02Et-1-Pyza) 2-F H H 2-39 H H CH2- (5-C02Et-1-Pyza) 2-F 4-F H 2-40 Ac H CH2- (5-C02Et-1-Pyza) 2-F 4-F H 2-41 H H CH2- (3-CH2C02H-1-Pyza) 2-F H H 2-42 Ac H CH2- (3-CH2C02H-1-Pyza) 2-F H H 2-43 H H CH2- (3-CH2C02H-1-Pyza) 2-F 4-F H 2-44 Ac H CH2- (3-CH2C02H-1-Pyza) 2-F 4-F H 2-45 H H CH2- (3-CH2C02Me-1-Pyza) 2-F H H 2-46 Ac H CH2- (3-CH2C02Me-1-Pyza) 2-F H H 2-47 H H CH2- (3-CH2C02Me-1-Pyza) 2-F 4-F H 2-48 Ac H CH2- (3-CH2C02Me-1-Pyza) 2-F 4-F H 2-49 H H CH2- (3-CH2C02Et-1-Pyza) 2-F H H 2-50 Ac H CH2- (3-CH2C02Et-1-Pyza) 2-F H H 2-51 H H CH2- (3-CH2C02Et-1-Pyza) 2-F 4-F H 2-52 Ac H CH2- (3-CH2C02Et-1-Pyza) 2-F 4-F H 2-53 H H CH2- (4-CH2C02H-1-Pyza) 2-F H H 2-54 Ac H CH2- (4-CH2C02H-1-Pyza) 2-F H H 2-55 H H CH2- (4-CH2C02H-1-Pyza) 2-F 4-F H 2-56 Ac H CH2- (4-CH2C02H-1-Pyza) 2-F 4-F H 2-57 H H CH2- (4-CH2C02Me-1 -Pyza) 2-F H H 2-58 Ac H CH2- (4-CH2C02Me-1 -Pyza) 2-F H H 2-59 H H CH2- (4-CH2C02Me-1 -Pyza) 2-F 4-F H 2-60 Ac H CH2- (4-CH2C02Me-1 -Pyza) 2-F 4-F H 2-61 H H CH2- (4-CH2C02Et-1 -Pyza) 2-F H H 2-62 Ac H CH2- (4-CH2C02Et-1-Pyza) 2-F H H 2-63 H H CH2- (4-CH2C02Et-1-Pyza) 2-F 4-F H 2-64 Ac H CH2- (4-CH2C02Et-1 -Pyza) 2-F 4-F H 2-65 H H CH2- (5-CH2C02H-1 -Pyza) 2-F H H 2-66 Ac H CH2- (5-CH2C02H-1 -Pyza) 2-F H H 2-67 H H CH2- (5-CH2C02H-1 -Pyza) 2-F 4-F H 2-68 Ac H CH2- (5-CH2C02H-1 -Pyza) 2-F 4-F H 2-69 H H CH2- (5-CH2C02Me-1 -Pyza) 2-F H H 2-70 Ac H CH2- (5-CH2C02Me-1 -Pyza) 2-F H H 2-71 H H CH2- (5-CH2C02Me-1 -Pyza) 2-F 4-F H 2-72 Ac H CH2- (5-CH2C02Me-1 -Pyza) 2-F 4-F H 2-73 H H CH2- (5-CH2C02Et-1 -Pyza) 2-F H H 2-74 Ac H CH2- (5-CH2C02Et-1 -Pyza) 2-F H H 2-75 H H CH2- (5-CH2C02Et-1 -Pyza) 2-F 4-F H 2-76 Ac H CH2- (5-CH2C02Et-1-Pyza) 2-F 4-F H 2-77 H H CH2- (3-CH2CH2C02H-1 -Pyza) 2-F H H 2-78 Ac H CH2- (3-CH2CH2C02H-1 -Pyza) 2-F H H 2-79 HH CH2- (3-CH2CH2C? 2Me-1 -Pyza) 2-FHH 2-80 Ac H CH2- (3-CH2CH2C02Me-1 -Pyza) 2 -FHH 2-81 HH CH2 - ((, 3- CH2CH2C02Et-1-Pyza) 2-FHH 2-82 Ac H CH2- ((, 3-CH2CH2C02Et-1-Pyza) 2-F H H 2-83 H H CH2- (4-CH2CH2C02H-1-Pyza) 2-F H H 2-84 Ac H CH2- ((< 4-CH2CH2C02H-1-Pyza) 2-F H H 2-85 H H CH2- ((-4-CH2CH2C02Me-1 -Pyza) 2-F H H 2-86 Ac H CH2- ((4-CH2CH2C02Me-1-Pyza) 2-F H H 2-87 H H CH2- ((4-CH2CH2C02Et-1-Pyza) 2-F H H 2-88 Ac H CH2- ((4-CH2CH2C02Et-1-Pyza) 2-F H H 2-89 H H CH2- ((5-CH2CH2C02H-1-Pyza) 2-F H H 2-90 Ac H CH2- ((5-CH2CH2C02H-1-Pyza) 2-F H H 2-91 H H CH2- ((5-CH2CH2C02Me-1 -Pyza) 2-F H H 2-92 Ac H CH2- ((5-CH2CH2C02Me-1 -Pyza) 2-F H H 2-93 H H CH2- ((5-CH2CH2C02Et-1 -Pyza) 2-F H H 2-94 Ac H CH2- ((5-CH2CH2C02Et-1 -Pyza) 2-F H H 2-95 H H Cp2_ ((3-CH2CH2CH2C02H-1 -Pyza) 2-F H H 2-96 Ac H CH2- ((3-CH2CH2CH2C02H-1 -Pyza) 2-F H H 2-97 H H CH2- ((3-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 2-98 Ac H CH - ((3-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 2-99 H H CH - ((3-CH2CH2CH2C02Et-1 -Pyza) 2-F H H 2-100 Ac H CH2- ((3-CH2CH2CH2C02Et-1 -Pyza) 2-F H H 2-101 H H Cp2- ((4-CH2CH2CH2CO2H-I -Pyza) 2-F H H 2-102 Ac H CH - ((4-CH2CH2CH2C? 2H-1-Pyza) 2-F H H 2-103 H H CH2- ((4-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 2-104 Ac H CH2- ((4-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 2-105 H H Cp2_ ((4-CH2CH2CH2C02Et-1-Pyza) 2-F H H 2-106 Ac H CH2- (4-CH2CH2CH2C02Et-1 -Pyza) 2-F H H 2-107 H H CH2- (5-CH2CH2CH2C02H-1 -Pyza) 2-F H H 2-108 Ac H CH2- (5-CH2CH2CH2C02H-1-Pyza) 2-F H H 2-109 H H CH2- (5-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 2-110 Ac H CH2- (5-CH2CH2CH2C02Me-1 -Pyza) 2-F H H 2-111 H H CH2- (5-CH2CH2CH2C02Et-1 -Pyza) 2-F H H 2-112 Ac H CH2- (5-CH2CH2CH2C02Et-1 -Pyza) 2-F H H 2-113 H H CH2CH2- -Pyza 2-F H H 2-114 Ac H CH2CH2- -Pyza 2-F H H 2-115 H H CH2CH2 3-C02H-1-Pyza) 2-F H H 2-116 Ac H CH CH2- 3-C02H-1-Pyza) 2-F H H 2-117 H H CH2CH2- 3-C02Me-1-Pyza) 2-F H H 2-118 Ac H CH2CH - 3-C02Me-1-Pyza) 2-F H H 2-119 H H CH2CH2- 3-C02Et-1-Pyza) 2-F H H 2-120 Ac H CH2CH2- 3-C02Et-1-Pyza) 2-F H H 2-121 H H CH2CH2- 4-C02H-1-Pyza) 2-F H H 2-122 Ac H CH2CH2- 4-C02H-1-Pyza) 2-F H H 2-123 H H CH2CH2-? 4-C02Me-1-Pyza) 2-F H H 2-124 Ac H CH2CH2p 4-C02Me-1-Pyza) 2-F H H 2-125 H H CH2CH2p 4-C02Et-1-Pyza) 2-F H H 2-126 Ac H CH CH -? 4-C02Et-1-Pyza) 2-F H H 2-127 H H L > H2CH '5-C02H-1-Pyza) 2-F H H 2-128 Ac H CH2CH2 '5-C02H-1-Pyza) 2-F H H 2-129 H H CH2CH2? 5-C02Me-1-Pyza) 2-F H H 2-130 Ac H CH CH 2 '5-C02Me-1-Pyza) 2-F H H 2-131 H H CH 2 CH 2 - (5-C02Et-1-Pyza) 2-F H H 2-132 Ac H CH2CH2- (5-C02Et-1 -Pyza) 2-F H H 2-133 H H CH2CH2- (3-CH2C02H-1 -Pyza) 2-F H H 2-134 Ac H CH2CH2- (3-CH2C02H-1 -Pyza) 2-F H H 2-135 H H CH2CH2- (3-CH2C02Me-1 -Pyza) 2-F H H 2-136 Ac H CH2CH2- (3-CH2C02Me-1 -Pyza) 2-F H H 2-137 H H CH2CH2- (3-CH2C? 2Et-1 -Pyza) 2-F H H 2-138 Ac H CH2CH2- (3-CH2C02Et-1 -Pyza) 2-F H H 2-139 H H CH2CH2- (4-CH2C02H-1 -Pyza) 2-F H H 2-140 Ac H CH2CH2- (4-CH2C02H-1 -Pyza) 2-F H H 2-141 H H CH2CH2- (4-CH2C02Me-1 -Pyza) 2-F H H 2-142 Ac H CH2CH2- (4-CH2C02Me-1 -Pyza) 2-F H H 2-143 H H CH2CH2- (4-CH2C02Et-1 -Pyza) 2-F H H 2-144 Ac H CH2CH2- (4-CH2C02Et-1 -Pyza) 2-F H H 2-145 H H CH2CH2- (5-CH2C02H-1 -Pyza) 2-F H H 2-146 Ac H CH2CH2- (5-CH2C02H-1 -Pyza) 2-F H H 2-147 H H CH2CH2- (5-CH2C02Me-1 -Pyza) 2-F H H 2-148 Ac H CH2CH2- (5-CH2C02Me-1 -Pyza) 2-F H H 2-149 H H CH2CH2- (5-CH2C02Et-1 -Pyza) 2-F H H 2-150 Ac H CH2CH2- (5-CH2C02Et-1-Pyza) 2-F H H 2-151 H H CH2CH2- (3-CH2CH2C02H-1 -Pyza) 2-F H H 2-152 Ac H CH2CH2- (3-CH2CH2C02H-1 -Pyza) 2-F H H 2-153 H H CH2CH2- (3-CH2CH2C02Me-1 -Pyza) 2-F H H 2-154 Ac H CH2CH2- (3-CH2CH2C02Me-1 -Pyza) 2 -FHH 2-155 HH CH2CH2- (3-CH2CH2C02Et-1-Pyza) 2 -FHH 2-156 Ac H Cp2Cp2"((> 3- CH2CH2C02Et-1-Pyza) 2-FHH 2-157 H H Cp2Cp2- (('4-CH2CH2C02H-1-Pyza) 2-F H H 2-158 Ac H Cp2CH2- (('4-CH2CH2C02H-1-Pyza) 2-F H H 2-159 H H CH2CH2- (('4-CH2CH2C02Me-1-Pyza) 2-F H H 2-160 Ac H CH2CH2- (('4-CH2CH2C02Me-1-Pyza) 2-F H H 2-161 H H CH2CH2- (('4-CH2CH2C02Et-1-Pyza) 2-F H H 2-162 Ac H CH2CH2- (('4-CH2CH2C02Et-1-Pyza) 2-F H H 2-163 H H CH2CH- ((5-CH2CH2C02H-1-Pyza) 2-F H H 2-164 Ac H CH2CH2- ((5-CH2CH2C02H-1-Pyza) 2-F H H 2-165 H H CH2CH2- ((5-CH2CH2C02Me-1-Pyza) 2-F H H 2-166 Ac H CH2CH- ((5-CH2CH2C02Me-1-Pyza) 2-F H H 2-167 H H CH2CH2- ((5-CH2CH2C02Et-1-Pyza) 2-F H H 2-168 Ac H CH2CH2- ((5-CH2CH2C02Et-1-Pyza) 2-F H H 2-169 H H CH2CH2- ((3-CH2CH2CH2C02H-1-Pyza) 2-F H H 2-170 Ac H CpCH2- ((3-CH2CH2CH2C02H-1-Pyza) 2-F H H 2-171 H H CHCH2- ((3-CH2CH2CH2C? 2Me-1-Pyza) 2-F H H 2-172 Ac H CHCp2- ((3-CH2CH2CH2C02Me-1-Pyza) 2-F H H 2-173 H H CH2CH2- ((3-CH2CH2CH2C02Et-1-Pyza) 2-F H H 2-174 Ac H CH2CH2- ((3-CH2CH2CH2C02Et-1-Pyza) 2-F H H 2-175 H H CHCH2- ((4-CH2CH2CH2C02H-1-Pyza) 2-F H H 2-176 Ac H Cp2Cp2"((4-CH2CH2CH2C02H-1-Pyza) 2-F H H 2-177 H H p H2- ((4-CH2CH2CH2C02Me-1-Pyza) 2-F H H 2-178 Ac H CH2Cp2"((4-CH2CH2CH2C02Me-1-Pyza) 2-F H H 2-179 H H CM2C 2- ((4-CH2CH2CH2C? 2Et-1-Pyza) 2-F H H 2-180 Ac H? 2CGI2- ((4-CH2CH2CH2C? 2Et-1-Pyza) 2 -FHH 2-181 HH CH2CH2- (5-CH2CH2CH2C02H-1-Pyza) 2 -FHH 2-182 Ac H CH2CH2- (5 -CH2CH2CH2C02H-1-Pyza) 2-FHH 2-183 HH CH2CH2- (5-CH2CH2CH2C02Me-1 -Pyza) 2 -FHH 2-184 Ac H CH2CH2- (5-CH2CH2CH2C02Me-1 -Pyza) 2 -FHH 2-185 HH CH2CH2- (5-CH2CH2CH2C02Et-1 -Pyza) 2 -FHH 2-186 Ac H CH2CH2- (5-CH2CH2CH2C02Et-1 -Pyza) 2 -FHH 2-187 HH CH2-, 3-Pyza 2 -FHH 2-188 Ac H CH2-> 3-Pyza 2-FHH 2-189 HH CH2- "3-Pyza 2-F 4 -FH 2-190 Ac H CH2-, 3-Pyza 2-F 4 -FH 2-191 HH CH2 - (1-C02Me-3-Pyza) 2-FHH 2-192 Ac H CH2- (1-C02Me-3-Pyza) 2-FHH 2-193 HH CH2- (1-C02Et-3-Pyza) 2-FHH 2-194 Ac H CH2- 1-C02Et-3-Pyza) 2-FHH 2-195 HH CH2- [4-C02H-3-Pyza) 2-FHH 2-196 Ac H CH2- f4-C02H-3-Pyza ) 2-FHH 2-197 HH CH2-; 4-C02Me-3-Pyza) 2-FHH 2-198 Ac H CH2- f4-C02Me-3-Pyza) 2-FHH 2-199 HH CH2- 4-C02Et- 3-Pyza) 2-FHH 2-200 Ac H CH2- 4-C02Et-3-Pyza) 2-FHH 2-201 HH CH2- [5-C02H-3-Pyza) 2-FHH 2-202 Ac H CH2 - 5-C02H-3-Pyza) 2-FHH 2-203 HH CH2- '5 -C02Me-3-Pyza) 2-FHH 2-204 Ac H CH2- 5-C02Me-3-Pyza) 2-FHH 2-205 HH CH2- [5-C02Et-3-Pyza) 2-FHH 2-206 Ac H CH2 - (! 5-C02Et-3-Pyza) 2-FHH 2-207 H H CH2- (1-CH2C02H-3-Pyza) 2-F H H 2-208 Ac H CH2- (1-CH2C02H-3-Pyza) 2-F H H 2-209 H H CH2- (1-CH2C02Me-3-Pyza) 2-F H H 2-210 Ac H CH2- (1-CH2C02Me-3-Pyza) 2-F H H 2-211 H H CH2- (1-CH2C02Et-3-Pyza) 2-F H H 2-212 Ac H CH2- (1-CH2C02Et-3-Pyza) 2-F H H 2-213 H H CH2 - (- 4-CH2C02H-3-Pyza) 2-F H H 2-214 Ac H CH2- (4-CH2C02H-3-Pyza) 2-F H H 2-215 H H CH2- (4-CH2C02Me-3-Pyza) 2-F H H 2-216 Ac H CH2 ~ (r4-CH2C02Me-3-Pyza) 2-F H H 2-217 H H CH2- (; 4-CH2C02Et-3-Pyza) 2-F H H 2-218 Ac H CH2- ([4-CH2C02Et-3-Pyza) 2-F H H 2-219 H H CH2- (; 5-CH2C02H-3-Pyza) 2-F H H 2-220 Ac H CH2- (; 5-CH2C02H-3-Pyza) 2-F H H 2-221 H H CH2- ([5-CH2C02Me-3-Pyza) 2-F H H 2-222 Ac H CH2- ([5-CH2C02Me-3-Pyza) 2-F H H 2-223 H H CH2- ((5-CH2C02Et-3-Pyza) 2-F H H 2-224 Ac H CH2- ([5-CH2C02Et-3-Pyza) 2-F H H 2-225 H H CH2- ((1-CH2CH2C02H-3-Pyza) 2-F H H 2-226 Ac H CH2- ((1-CH2CH2C02H-3-Pyza) 2-F H H 2-227 H H CH2- ((1-CH2CH2C02Me-3-Pyza) 2-F H H 2-228 Ac H CH2- ((1-CH2CH2C02Me-3-Pyza) 2-F H H 2-229 H H CH2- ((1-CH2CH2C02Et-3-Pyza) 2-F H H 2-230 Ac H CH2- ((1-CH2CH2C02Et-3-Pyza) 2-F H H 2-231 H H CH2- (4-CH2CH2C02H-3-Pyza) 2-F H H 2-232 Ac H CH2- (4-CH2CH2C02H-3-Pyza) 2-F H H 2-233 H H CH2- (4-CH2CH2C02Me-3-Pyza) 2-F H H 2-234 Ac H CH2- (4-CH2CH2C02Me-3-Pyza) 2-F H H 2-235 H H CH2- (4-CH2CH2C02Et-3-Pyza) 2-F H H 2-236 Ac H CH2- (4-CH2CH2C02Et-3-Pyza) 2-F H H 2-237 H H CH2- (5-CH2CH2C02H-3-Pyza) 2-F H H 2-238 Ac H CH2- (5-CH2CH2C02H-3-Pyza) 2-F H H 2-239 H H CH2- (5-CH2CH2C02Me-3-Pyza) 2-F H H 2-240 Ac H CH2- (5-CH2CH2C02Me-3-Pyza) 2-F H H 2-241 H H CH2- (5-CH2CH2C02Et-3-Pyza) 2-F H H 2-242 Ac H CH2- (5-CH2CH2C? 2Et-3-Pyza) 2-F H H 2-245 H H CH2- (1-CH2CH2CH2C02H-3-Pyza) 2-F H H 2-246 Ac H CH2- (1 -CH2CH2CH2C02H-3-Pyza) 2-F H H 2-247 H H CH2- (1-CH2CH2CH2C? 2Me-3-Pyza) 2-F H H 2-248 Ac H CH2- (1-CH2CH2CH2C02Me-3-Pyza) 2-F H H 2-249 H H CH2- (1 -CH2CH2CH2C02Et-3-Pyza) 2-F H H 2-250 Ac H CH2- (1 -CH2CH2CH2C02Et-3-Pyza) 2-F H H 2-251 H H CH2- (4-CH2CH2CH2C02H-3-Pyza) 2-F H H 2-252 Ac H CH2- (4-CH2CH2CH2C02H-3-Pyza) 2-F H H 2-253 H H CH2- (4-CH2CH2CH2C02Me-3-Pyza) 2-F H H 2-254 Ac H CH2- (4-CH2CH2CH2C02Me-3-Pyza) 2-F H H 2-255 H H CH2- (4-CH2CH2CH2C02Et-3-Pyza) 2-F H H 2-256 Ac H CH2- (4-CH2CH2CH2C02Et-3-Pyza) 2 -FHH 2-257 HH CH2- (5-CH2CH2CH2C02H-3-Pyza) 2 -FHH 2-258 Ac H CH2- (5-CH2CH2CH2C02H-3 -Pyza) 2-FHH 2-259 H H CH2- (5-CH2CH2CH2C02Me-3-Pyza) 2-F H H 2-260 Ac H CH2- (5-CH2CH2CH2C02Me-3-Pyza) 2-F H H 2-261 H H CH2- (5-CH2CH2CH2C02Et-3-Pyza) 2-F H H 2-262 Ac H CH2- (5-CH2CH2CH2C02Et-3-Pyza) 2-F H H 2-263 H H CH2CH2-3-Pyza 2-F H H 2-264 Ac H CH2CH2-3-Pyza 2-F H H 2-265 H H CH2CH2-3-Pyza 2-F 4-F H 2-266 Ac H CH2CH2-3-Pyza 2-F 4-F H 2-267 H H CH2CH2- (1 -C02Me-3-Pyza) 2-F H H 2-268 Ac H CH2CH2- (1 -C02Me-3-Pyza) 2-F H H 2-269 H H CH2CH2- (1 -C02Et-3-Pyza) 2-F H H 2-270 Ac H CH2CH2- (1-C02Et-3-Pyza) 2-F H H 2-271 H H CH2CH2- (4-C02H-3-Pyza) 2-F H H 2-272 Ac H CH2CH2- (4-C02H-3-Pyza) 2-F H H 2-273 H H CH2CH2- (4-C02Me-3-Pyza) 2-F H H 2-274 Ac H CH2CH2- (4-C02Me-3-Pyza) 2-F H H 2-275 H H CH2CH2- (4-C02Et-3-Pyza) 2-F H H 2-276 Ac H CH2CH2- (4-C02Et-3-Pyza) 2-F H H 2-277 H H CH2CH2- (5-C02H-3-Pyza) 2-F H H 2-278 Ac H CH2CH2- (5-C02H-3-Pyza) 2-F H H 2-279 H H CH2CH2- (5-C02Me-3-Pyza) 2-F H H 2-280 Ac H CH2CH2- (5-C02Me-3-Pyza) 2-F H H 2-281 HH CH2CH2- (5-C02Et-3-Pyza) 2-FHH 2-282 Ac H CH2CH2- (5-C02Et-3-Pyza) 2-FHH 2-283 HH CH2CH2- (1-CH2C02H-3- Pyza) 2-FHH 2-284 Ac H CH2CH2- (1-CH2C02H-3-Pyza) 2-F H H 2-285 H H CH2CH2- (1-CH2C02Me-3-Pyza) 2-F H H 2-286 Ac H CH2CH2- (1-CH2C02Me-3-Pyza) 2-F H H 2-287 H H CH2CH2- (1-CH2C02Et-3-Pyza) 2-F H H 2-288 Ac H CH2CH2- (1-CH2C02Et-3-Pyza) 2-F H H 2-289 H H CH2CH2- (4-CH2C02H-3-Pyza) 2-F H H 2-290 Ac H CH2CH2- (4-CH2C02H-3-Pyza) 2-F H H 2-291 H H CH2CH2- (4-CH2C02Me-3-Pyza) 2-F H H 2-292 Ac H CH2CH2- (4-CH2C02Me-3-Pyza) 2-F H H 2-293 H H CH2CH2- (4-CH2C02Et-3-Pyza) 2-F H H 2-294 Ac H CH2CH2- (4-CH2C02Et-3-Pyza) 2-F H H 2-295 H H CH2CH2- (5-CH2C02H-3-Pyza) 2-F H H 2-296 Ac H CH2CH2- (5-CH2C02H-3-Pyza) 2-F H H 2-297 H H CH2CH2- (5-CH2C02Me-3-Pyza) 2-F H H 2-298 Ac H CH2CH2- (5-CH2C02Me-3-Pyza) 2-F H H 2-299 H H CH2CH2- (5-CH2C02Et-3-Pyza) 2-F H H 2-300 Ac H CH2CH2- (5-CH2C02Et-3-Pyza) 2-F H H 2-301 H H CH2CH2- (1-CH2CH2C02H-3-Pyza) 2-F H H 2-302 Ac H CH2CH2- (1-CH2CH2C? 2H-3-Pyza) 2-F H H 2-303 H H CH2CH2- (1-CH2CH2C02Me-3-Pyza) 2-F H H 2-304 Ac H CH2CH2- (1-CH2CH2C02Me-3-Pyza) 2-F H H 2-305 H H CH2CH2- (1-CH2CH2C02Et-3-Pyza) 2-F H H 2-306 Ac H CH2CH2- (1-CH2CH2C02Et-3-Pyza) 2 -FHH 2-307 HH CH2CH2- (4-CH2CH2C02H-3-Pyza) 2 -FHH 2-308 Ac H CH2CH2- (('4-CH2CH2C02H -3-Pyza) 2-FHH 2-309 H H Cp2CH2- (('4-CH2CH2C02Me-3-Pyza) 2-F H H 2-310 Ac H p2CH2- (('4-CH2CH2C02Me-3-Pyza) 2-F H H 2-311 H H CH2CH2- (('4-CH2CH2C02Et-3-Pyza) 2-F H H 2-312 Ac H CHCH- ((4-CH2CH2C02Et-3-Pyza) 2-F H H 2-313 H H CH2CH2- ((5-CH2CH2C02H-3-Pyza) 2-F H H 2-314 Ac H CH2CH2- ((5-CH2CH2C02H-3-Pyza) 2-F H H 2-315 H H CH2CH2- ((5-CH2CH2C02Me-3-Pyza) 2-F H H 2-316 Ac H CH2CH- ((5-CH2CH2C02Me-3-Pyza) 2-F H H 2-317 H H CH2CH2- ((5-CH2CH2C02Et-3-Pyza) 2-F H H 2-318 Ac H CH2CH2- ((5-CH2CH2C02Et-3-Pyza) 2-F H H 2-319 H H CH2CH2- ((1-CH2CH2CH2C02H-3-Pyza) 2-F H H 2-320 Ac H CH2CH2- ((1-CH2CH2CH2C02H-3-Pyza) 2-F H H 2-321 H H CH2CH2- ((1-CH2CH2CH2C? 2Me-3-Pyza) 2-F H H 2-322 Ac H CH2CH2- ((1-CH2CH2CH2C? 2Me-3-Pyza) 2-F H H 2-323 H H CH2CH2- ((1-CH2CH2CH2C02Et-3-Pyza) 2-F H H 2-324 Ac H CH2CH2- ((1-CH2CH2CH2C02Et-3-Pyza) 2-F H H 2-325 H H CH2CH2- ((4-CH2CH2CH2C02H-3-Pyza) 2-F H H 2-326 Ac H CHCH- ((4-CH2CH2CH2C02H-3-Pyza) 2-F H H 2-327 H H Op2CH2- ((4-CH2CH2CH2C02Me-3-Pyza) 2-F H H 2-328 Ac H CH2CH2- ((4-CH2CH2CH2C02Me-3-Pyza) 2-F H H 2-329 H H CHCH- ((4-CH2CH2CH2C02Et-3-Pyza) 2-F H H 2-330 Ac H CH2CH2- ((4-CH2CH2CH2C02Et-3-Pyza) 2-F H H 2-331 H H CH2CH2- ((5-CH2CH2CH2C02H-3-Pyza) 2-F H H 2-332 Ac H CH2CH2- ((5-CH2CH2CH2C02H-3-Pyza) 2-F H H 2-333 H H CH2CH2- (5-CH2CH2CH2C02Me-3-Pyza) 2-F H H 2-334 Ac H CH2CH2- (5-CH2CH2CH2C02Me-3-Pyza) 2-F H H 2-335 H H CH2CH2- (5-CH2CH2CH2C02Et-3-Pyza) 2-F H H 2-336 Ac H CH2CH2- (5-CH2CH2CH2C02Et-3-Pyza) 2-F H H 2-337 H H CH2-4-Pyza 2-F H H 2-338 Ac H CH2-4-Pyza 2-F H H 2-339 H H CH2-4-Pyza 2-F 4-F H 2-340 Ac H CH2-4-Pyza 2-F 4-F H 2-341 H H CH2- (1-C02Me-4-Pyza) 2-F H H 2-342 Ac H CH2- (1-C02Me-4-Pyza) 2-F H H 2-343 H H CH2- (1-C02Et-4-Pyza) 2-F H H 2-344 Ac H CH2- (1-C02Et-4-Pyza) 2-F H H 2-345 H H CH2- (3-C02H-4-Pyza) 2-F H H 2-346 Ac H CH2- (3-C02H-4-Pyza) 2-F H H 2-347 H H CH2- (3-C02Me-4-Pyza) 2-F H H 2-348 Ac H CH2- (3-C02Me-4-Pyza) 2-F H H 2-349 H H CH2- (3-C02Et-4-Pyza) 2-F H H 2-350 Ac H CH2- (3-C02Et-4-Pyza) 2-F H H 2-351 H H CH2- (1-CH2C02H-4-Pyza) 2-F H H 2-352 Ac H CH2- (1 -CH2C02H-4-Pyza) 2-F H H 2-353 H H CH2- (1 -CH2C02Me-4-Pyza) 2-F H H 2-354 Ac H CH2- (1-CH2C02Me-4-Pyza) 2-F H H 2-355 H H CH2- (1 -CH2C02Et-4-Pyza) 2-F H H 2-356 Ac H CH2- (1-CH2C02Et-4-Pyza) 2-F H H 2-357 H H CH2- (3-CH2C02H-4-Pyza) 2-F H H 2-358 Ac H CH2-13-CH2C02H-4-Pyza) 2-F H H 2-359 H H CH2-? 3-CH2C02Me-4-Pyza) 2-F H H 2-360 Ac H CH2- 3-CH2C02Me-4-Pyza) 2-F H H 2-361 H H CH2 3-CH2C02Et-4-Pyza) 2-F H H 2-362 Ac H CH2 3-CH2C02Et-4-Pyza) 2-F H H 2-363 H H CH2 1-CH2CH2C02H-4-Pyza) 2-F H H 2-364 Ac H CH2 1-CH2CH2C02H-4-Pyza) 2-F H H 2-365 H H CH2-? 1-CH2CH2C02Me-4-Pyza) 2-F H H 2-366 Ac H CH2-? 1 -CH2CH2C02Me-4-Pyza) 2-F H H 2-367 H H CH2 1-CH2CH2C02Et-4-Pyza) 2-F H H 2-368 Ac H CH2- 1-CH2CH2C02Et-4-Pyza) 2-F H H 2-369 H H CH2- 3-CH2CH2C02H-4-Pyza) 2-F H H 2-370 Ac H CH2- 3-CH2CH2C02H-4-Pyza) 2-F H H 2-371 H H CH2- 3-CH2CH2C02Me-4-Pyza) 2-F H H 2-372 Ac H CH2- 3-CH2CH2C02Me-4-Pyza) 2-F H H 2-373 H H CH2-? 3-CH2CH2C02Et-4-Pyza) 2-F H H 2-374 Ac H CH2-? 3-CH2CH2C02Et-4-Pyza) 2-F H H 2-375 H H CH2-? '1-CH2CH2CH2C02H-4-Pyza) 2-F H H 2-376 Ac H CH2-?; i-CH2CH2CH2C02H-4-Pyza) 2-F H H 2-377 H H CH2 [1 -CH2CH2CH2C02Me-4-Pyza) 2-F H H 2-378 Ac H CH2 [1-CH2CH2CH2C02Me-4-Pyza) 2-F H H 2-379 H H CH2 (1-CH2CH2CH2C02Et-4-Pyza) 2-F H H 2-380 Ac H CH2-? (1-CH2CH2CH2C02Et-4-Pyza) 2-F H H 2-381 H H CH2-? (3-CH2CH2CH2C02H-4-Pyza) 2-F H H 2-382 Ac H CH2-? (3-CH2CH2CH2C02H-4-Pyza) 2-F H H 2-383 H H CH2- (3-CH2CH2CH2C02Me-4-Pyza) 2-F H H 2-384 Ac H CH2- (3-CH2CH2CH2C02Me-4-Pyza) 2-F H H 2-385 H H CH2- (3-CH2CH2CH2C02Et-4-Pyza) 2-F H H 2-386 Ac H CH2- (3-CH2CH2CH2C02Et-4-Pyza) 2-F H H 2-387 H H CH2CH2-4-Pyza 2-F H H 2-388 Ac H CH2CH2-4-Pyza 2-F H H 2-389 H H CH2CH2-4-Pyza 2-F 4-F H 2-390 Ac H CH2CH2-4-Pyza 2-F 4-F H 2-391 H H CH2CH2- (1-C02Me-4-Pyza) 2-F H H 2-392 Ac H CH2CH2- (1-C02Me-4-Pyza) 2-F H H 2-393 H H CH2CH2- (1-C02Et-4-Pyza) 2-F H H 2-394 Ac H CH2CH2- (1-C02Et-4-Pyza) 2-F H H 2-395 H H CH2CH2- (3-C02H-4-Pyza) 2-F H H 2-396 Ac H CH2CH2- (3-C02H-4-Pyza) 2-F H H 2-397 H H CH2CH2- (3-C02Me-4-Pyza) 2-F H H 2-398 Ac H CH2CH2- (3-C02Me-4-Pyza) 2-F H H 2-399 H H CH2CH2- (3-C02Et-4-Pyza) 2-F H H 2-400 Ac H CH2CH2- (3-C02Et-4-Pyza) 2-F H H 2-401 H H CH2CH2- (1-CH2C02H-4-Pyza) 2-F H H 2-402 Ac H CH2CH2- (1-CH2C02H-4-Pyza) 2-F H H 2-403 H H CH2CH2- (1-CH2C02Me-4-Pyza) 2-F H H 2-404 Ac H CH2CH2- (1-CH2C02Me-4-Pyza) 2-F H H 2-405 H H CH2CH2- (1-CH2C02Et-4-Pyza) 2-F H H 2-406 Ac H CH2CH2- (1-CH2C02Et-4-Pyza) 2 -FHH 2-407 HH CH2CH2- (3-CH2C02H-4-Pyza) 2 -FHH 2-408 Ac H CH2CH2- ((3-CH2C02H- 4-Pyza) 2-FHH 2-409 H H CH2CH2- ((3-CH2C02Me-4-Pyza) 2-F H H 2-410 Ac H Cp2Cp2- ((3-CH2C02Me-4-Pyza) 2-F H H 2-411 H H Cp2Cp2- ((3-CH2C02Et-4-Pyza) 2-F H H 2-412 Ac H Cp2CH2- ((3-CH2C02Et-4-Pyza) 2-F H H 2-413 H H CH2CH2- ((1-CH2CH2C02H-4-Pyza) 2-F H H 2-414 Ac H CH2CH2- ((1-CH2CH2C02H-4-Pyza) 2-F H H 2-415 H H CH2CH2- ((1-CH2CH2C02Me-4-Pyza) 2-F H H 2-416 Ac H CH2CH2- ((1-CH2CH2C02Me-4-Pyza) 2-F H H 2-417 H H CH2CH2- ((1-CH2CH2C02Et-4-Pyza) 2-F H H 2-418 Ac H CH2CH2- ((1-CH2CH2C02Et-4-Pyza) 2-F H H 2-419 H H CH2CH2- ((3-CH2CH2C02H-4-Pyza) 2-F H H 2-420 Ac H Cp CH2- ((3-CH2CH2C02H-4-Pyza) 2-F H H 2-421 H H H CH2- ((3-CH2CH2C02Me-4-Pyza) 2-F H H 2-422 Ac H Cp2CH2- ((3-CH2CH2C02Me-4-Pyza) 2-F H H 2-423 H H CH2CH2- ((3-CH2CH2C02Et-4-Pyza) 2-F H H 2-424 Ac H CH2CH2- ((3-CH2CH2C02Et-4-Pyza) 2-F H H 2-425 H H CH2CH2- ((1-CH2CH2CH2C02H-4-Pyza) 2-F H H 2-426 Ac H CH2CH2- ((1-CH2CH2CH2C02H-4-Pyza) 2-F H H 2-427 H H Cp CH2- ((1-CH2CH2CH2C02Me-4-Pyza) 2-F H H 2-428 Ac H CH2CH2- ((1-CH2CH2CH2C02Me-4-Pyza) 2-F H H 2-429 H H CH2CH2- ((1-CH2CH2CH2C02Et-4-Pyza) 2-F H H 2-430 Ac H CH2CH2- ((1-CH2CH2CH2C02Et-4-Pyza) 2-F H H 2-431 H H CH2CH2- ((3-CH2CH2CH2C02H-4-Pyza) 2-F H H 2-432 Ac H CH2CH2- ((3-CH2CH2CH2C02H-4-Pyza) 2-F H H 2-433 H H CH2CH2- (3-CH2CH2CH2C02Me-4-Pyza) 2-F H H 2-434 Ac H CH2CH2- (3-CH2CH2CH2C02Me-4-Pyza) 2-F H H 2-435 H H CH2CH2- (3-CH2CH2CH2C02Et-4-Pyza) 2-F H H 2-436 Ac H CH2CH2- (3-CH2CH2CH2C02Et-4-Pyza) 2-F H H 2-437 H H CH2- (1-C02Me-5-Pyza) 2-F 4-F H 2-438 Ac H CH2- (1-C02Me-5-Pyza) 2-F 4-F H 2-439 H H CH2- (1-C02Me-5-Pyza) 2-F H H 2-440 Ac H CH2- (1-C02Me-5-Pyza) 2-F H H 2-441 H H CH2- (1-C02Et-5-Pyza) 2-F H H 2-442 Ac H CH2- (1-C02Et-5-Pyza) 2-F H H 2-443 H H CH2- (1 -CH2C02H-5-Pyza) 2-F H H 2-444 Ac H CH2- (1 -CH2C02H-5-Pyza) 2-F H H 2-445 H H CH2- (1-CH2C02Me-5-Pyza) 2-F H H 2-446 Ac H CH2- (1-CH2C02Me-5-Pyza) 2-F H H 2-447 H H CH2- (1-CH2C02Et-5-Pyza) 2-F H H 2-448 Ac H CH2- (1-CH2C02Et-5-Pyza) 2-F H H 2-449 H H CH2- (1 -CH2CH2C02H-5-Pyza) 2-F H H 2-450 Ac H CH2- (1-CH2CH2C02H-5-Pyza) 2-F H H 2-451 H H CH2- (1-CH2CH2C02Me-5-Pyza) 2-F H H 2-452 Ac H CH2- (1-CH2CH2C02Me-5-Pyza) 2-F H H 2-453 H H CH2- (1-CH2CH2C02Et-5-Pyza) 2-F H H 2-454 Ac H CH2- (1-CH2CH2C02Et-5-Pyza) 2-F H H 2-455 H H CH2- (1-CH2CH2CH2C02H-5-Pyza) 2-F H H 2-456 Ac H CH2- (1-CH2CH2CH2C? 2H-5-Pyza) 2-FHH 2-457 HH CH2- (1 -CH2CH2CH2C02Me-5-Pyza) 2 -FHH 2-458 Ac H CH2- (1-CH2CH2CH2C02Me -5-Pyza) 2-FHH 2-459 H H CH2- (1-CH2CH2CH2C02Et-5-Pyza) 2-F H H 2-460 Ac H CH2- (1-CH2CH2CH2C02Et-5-Pyza) 2-F H H 2-461 H H CH2CH2- (1-C02Me-5-Pyza) 2-F 4-F H 2-462 Ac H CH2CH2- (1-C02Me-5-Pyza) 2-F 4-F H 2-463 H H CH2CH2- (1-C02Me-5-Pyza) 2-F H H 2-464 Ac H CH2CH2- (1-C02Me-5-Pyza) 2-F H H 2-465 H H CH2CH2- (1-C02Et-5-Pyza) 2-F H H 2-466 Ac H CH2CH2- (1-C02Et-5-Pyza) 2-F H H 2-467 H H CH2CH2- (1-CH2C02H-5-Pyza) 2-F H H 2-468 Ac H CH2CH2- (1-CH2C02H-5-Pyza) 2-F H H 2-469 H H CH2CH2- (1-CH2C02Me-5-Pyza) 2-F H H 2-470 Ac H CH2CH2- (1-CH2C02Me-5-Pyza) 2-F H H 2-471 H H CH2CH2- (1-CH2C02Et-5-Pyza) 2-F H H 2-472 Ac H CH2CH2- (1-CH2C02Et-5-Pyza) 2-F H H 2-473 H H CH2CH2- (1-CH2CH2C02H-5-Pyza) 2-F H H 2-474 Ac H CH2CH2- (1-CH2CH2C02H-5-Pyza) 2-F H H 2-475 H H CH2CH2- (1-CH2CH2C02Me-5-Pyza) 2-F H H 2-476 Ac H CH2CH2- (1 -CH2CH2C02Me-5-Pyza) 2-F H H 2-477 H H CH2CH2- (1 -CH2CH2C02Et-5-Pyza) 2-F H H 2-478 Ac H CH2CH2- (1 -CH2CH2C02Et-5-Pyza) 2-F H H 2-479 H H CH2CH2- (1-CH2CH2CH2C02H-5-Pyza) 2-F H H 2-480 Ac H CH2CH2- (1-CH2CH2CH2C02H-5-Pyza) 2-F H H 2-481 HH CH2CH2- (1-CH2CH2CH2C02Me-5-Pyza) 2-FHH 2-482 Ac H CH2CH2- (1 -CH2CH2CH2C02Me-5-Pyza) 2 -FHH 2-483 HH CH2CH2- (1-CH2CH2CH2C02Et-5- Pyza) 2-FHH 2-484 Ac H CH2CH2- (1 -CH2CH2CH2C02Et-5-Pyza) 2-F H H 2-485 H H CH2-1-Triz 2-F H H 2-486 Ac H CH2-1-Triz 2-F H H 2-487 H H CH2- (4-C02H-1-Triz) 2-F H H 2-488 Ac H CH2- (4-C02H-1-Triz) 2-F H H 2-489 H H CH2- (4-C02Me-1-Triz) 2-F H H 2-490 Ac H CH2- (4-C02Me-1-Triz) 2-F H H 2-491 H H CH2- (4-C02Et-1-Triz) 2-F H H 2-492 Ac H CH2- (4-C02Et-1-Triz) 2-F H H 2-493 H H CH2- (5-C02H-1-Triz) 2-F H H 2-494 Ac H CH2- (5-C02H-1-Triz) 2-F H H 2-495 H H CH2- (5-C02Me-1-Triz) 2-F H H 2-496 Ac H CH2- (5-C02Me-1-Triz) 2-F H H 2-497 H H CH2- (5-C02Et-1-Triz) 2-F H H 2-498 Ac H CH2- (5-C02Et-1-Triz) 2-F H H 2-499 H H CH2- (4-CH2C02H-1-Triz) 2-F H H 2-500 Ac H CH2- (4-CH2C02H-1-Triz) 2-F H H 2-501 H H CH2- (4-CH2C02Me-1 -Triz) 2-F H H 2-502 Ac H CH2- (4-CH2C02Me-1 -Triz) 2-F H H 2-503 H H CH2- (4-CH2C02Et-1-Triz) 2-F H H 2-504 Ac H CH2- (4-CH2C02Et-1-Triz) 2-F H H 2-505 H H CH2- (5-CH2C02H-1-Triz) 2-F H H 2-506 Ac H CH2- (5-CH2C02H-1-Triz) 2-F H H 2-507 H H CH2- (5-CH2C02Me-1 -Triz) 2-F H H 2-508 Ac H CH2- (5-CH2C02Me-1-Triz) 2-F H H 2-509 H H CH2- (5-CH2C02Et-1-Triz) 2-F H H 2-510 Ac H CH2- (5-CH2C02Et-1-Triz) 2-F H H 2-511 H H CH2- (4-CH2CH2C02H-1 -Triz) 2-F H H 2-512 Ac H CH2- (4-CH2CH2C02H-1 -Triz) 2-F H H 2-513 H H CH2- (4-CH2CH2C02Me-1 -Triz) 2-F H H 2-514 Ac H CH2- (4-CH2CH2C02Me-1 -Triz) 2-F H H 2-515 H H CH2- (4-CH2CH2C? 2Et-1 -Triz) 2-F H H 2-516 Ac H CH2- (4-CH2CH2C02Et-1 -Triz) 2-F H H 2-517 H H CH2- (5-CH2CH2C02H-1 -Triz) 2-F H H 2-518 Ac H CH2- (5-CH2CH2C02H-1 -Triz) 2-F H H 2-519 H H CH2- (5-CH2CH2C02Me-1 -Triz) 2-F H H 2-520 Ac H CH2- (5-CH2CH2C02Me-1 -Triz) 2-F H H 2-521 H H CH2- (5-CH2CH2C02Et-1 -Triz) 2-F H H 2-522 Ac H CH2- (5-CH2CH2C02Et-1 -Triz) 2-F H H 2-523 H H CH2- (4-CH2CH2CH2C02H-1 -Triz) 2-F H H 2-524 Ac H CH2- (4-CH2CH2CH2C02H-1 -Triz) 2-F H H 2-525 H H CH2- (4-CH2CH2CH2C02Me-1 -Triz) 2-F H H 2-526 Ac H CH2- (4-CH2CH2CH2C02Me-1 -Triz) 2-F H H 2-527 H H CH2- (4-CH2CH2CH2C02Et-1 -Triz) 2-F H H 2-528 Ac H CH2- (4-CH2CH2CH2C? 2Et-1 -Triz) 2-F H H 2-529 H H CH2- (5-CH2CH2CH2C02H-1 -Triz) 2-F H H 2-530 Ac H CH2- (5-CH2CH2CH2C02H-1 -Triz) 2-F H H 2-531 HH CH2- (5-CH2CH2CH2C02Me-1 -Triz) 2 -FHH 2-532 Ac H CH2- (5-CH2CH2CH2C02Me-1 -Triz) 2 -FHH 2-533 HH CH2- (5-CH2CH2CH2C02Et-1 - Tr 2-FHH 2-534 Ac H CH2- (5-CH2CH2CH2C02Et-1 -Tr 2-F H H 2-535 H H CH2CH2-1-Triz 2-F H H 2-536 Ac H CH2CH2-1-Triz 2-F H H 2-537 H H CH2CH2- (4-C02H-1-Triz) 2-F H H 2-538 Ac H CH2CH2- (4-C02H-1-Triz) 2-F H H 2-539 H H CH2CH2- (4-C02Me-1-Triz) 2-F H H 2-540 Ac H CH2CH2- (4-C02Me-1 -Triz) 2-F H H 2-541 H H CH2CH2- (4-C02Et-1-Triz) 2-F H H 2-542 Ac H CH2CH2- (4-C02Et-1-Triz) 2-F H H 2-543 H H CH2CH2- (5-C02H-1-Triz) 2-F H H 2-544 Ac H CH2CH2- (5-C02H-1-Triz) 2-F H H 2-545 H H CH2CH2- (5-C02Me-1 -Triz) 2-F H H 2-546 Ac H CH2CH2- (5-C02Me-1-Triz) 2-F H H 2-547 H H CH2CH2- (5-C02Et-1-Triz) 2-F H H 2-548 Ac H CH2CH2- (5-C? 2 Et-1-Triz) 2-F H H 2-549 H H CH2CH2- (4-CH2C02H-1-Triz) 2-F H H 2-550 Ac H CH2CH2- (4-CH2C02H-1 -Triz) 2-F H H 2-551 H H CH2CH2- (4-CH2C02Me-1 -Triz) 2-F H H 2-552 Ac H CH2CH2- (4-CH2C02Me-1 -Triz) 2-F H H 2-553 H H CH2CH2- (4-CH2C02Et-1 -Triz) 2-F H H 2-554 Ac H CH2CH2- (4-CH2C02Et-1 -Triz) 2-F H H 2-555 H H CH2CH2- (5-CH2C02H-1 -Triz) 2-F H H 2-556 Ac H CH2CH2- (5-CH2C02H-1 -Triz) 2 -FHH 2-557 HH CH2CH2- (5-CH2C02Me-1 -Triz) 2 -FHH 2-558 Ac H CH2CH2 - ((.5-CH2C02Me -1-Triz) 2-FHH 2-559 H H CH2CH2- ((5-CH2C02Et-1-Triz) 2-F H H 2-560 Ac H CH2CH2- ((5-CH2C02Et-1-Triz) 2-F H H 2-561 H H CH2CH2- ((4-CH2CH2C02H-1-Triz) 2-F H H 2-562 Ac H CH2CH2- ((4-CH2CH2C02H-1-Triz) 2-F H H 2-563 H H CH2CH2- ((4-CH2CH2C02Me-1-Triz) 2-F H H 2-564 Ac H CH2CH2- ((4-CH2CH2C02Me-1-Triz) 2-F H H 2-565 H H CH2CH2- ((4-CH2CH2C02Et-1-Triz) 2-F H H 2-566 Ac H CH2CH2- ((4-CH2CH2C02Et-1-Triz) 2-F H H 2-567 H H CH2CH2- ((5-CH2CH2C02H-1-Triz) 2-F H H 2-568 Ac H CH2CH2- ((5-CH2CH2C? 2H-1-Triz) 2-F H H 2-569 H H CH2CH2- ((5-CH2CH2C02Me-1-Triz) 2-F H H 2-570 Ac H CH2CH2- ((5-CH2CH2C02Me-1-Triz) 2-F H H 2-571 H H CH2CH2- ((5-CH2CH2C02Et-1-Triz) 2-F H H 2-572 Ac H CHCH2- ((5-CH2CH2C02Et-1-Triz) 2-F H H 2-573 H H CH2CH2- ((4-CH2CH2CH2C02H-1-Triz) 2-F H H 2-574 Ac H CH2CH2- ((4-CH2CH2CH2C02H-1-Triz) 2-F H H 2-575 H H CH2CH2- ((4-CH2CH2CH2C02Me-1-Triz) 2-F H H 2-576 Ac H CH2CH2- ((4-CH2CH2CH2C02Me-1-Triz) 2-F H H 2-577 H H CHCH2- ((4-CH2CH2CH2C? 2Et-1-Triz) 2-F H H 2-578 Ac H C? 2C? 2- ((4-CH2CH2CH2C? 2Et-1-Triz) 2-F H H 2-579 H H CH2CH2- ((d-CHzCHzCHzCOzH-l-Triz) 2-F H H 2-580 Ac H CH2CH2- ((5-CH2CH2CH2C02H-1-Triz) 2-F H H 2-581 HH CHCH- ((5-CH2CH2CH2C02Me-1-Triz) 2-FHH 2-582 Ac H Cp2CH2- ((5-CH2CH2CH2C02Me-1-Triz) 2 -FHH 2-583 HH CH2CH2- (5-CH2CH2CH2C02Et- 1-Triz) 2-FHH 2-584 Ac H CH2CH2- (5-CH2CH2CH2C02Et-1-Triz) 2-F H H 2-585 H H CH2-2-Triz 2-F H H 2-586 Ac H CH2-2-Triz 2-F H H 2-587 H H CH2- (4-C02H-2-Triz) 2-F H H 2-588 Ac H CH2- (4-C02H-2-Triz) 2-F H H 2-589 H H CH2- (4-C02Me-2-Triz) 2-F H H 2-590 Ac H CH2- (4-C02Me-2-Triz) 2-F H H 2-591 H H CH2- (4-C02Et-2-Triz) 2-F H H 2-592 Ac H CH2- (4-C02Et-2-Triz) 2-F H H 2-593 H H CH2- (4-CH2C02H-2-Triz) 2-F H H 2-594 Ac H CH2- (4-CH2C02H-2-Triz) 2-F H H 2-595 H H CH2- (4-CH2C? 2Me-2-Triz) 2-F H H 2-596 Ac H CH2- (4-CH2C02Me-2-Triz) 2-F H H 2-597 H H CH2- (4-CH2C? 2Et-2-Triz) 2-F H H 2-598 Ac H CH2- (4-CH2C02Et-2-Triz) 2-F H H 2-599 H H CH2- (4-CH2CH2C02H-2-Triz) 2-F H H 2-600 Ac H CH2- (4-CH2CH2C02H-2-Triz) 2-F H H 2-601 H H CH2- (4-CH2CH2C02Me-2-Triz) 2-F H H 2-602 Ac H CH2- (4-CH2CH2C02Me-2-Triz) 2-F H H 2-603 H H CH2- (4-CH2CH2C02Et-2-Triz) 2-F H H 2-604 Ac H CH2- (4-CH2CH2C02Et-2-Triz) 2-F H H 2-605 H H CH2- (4-CH2CH2CH2C02H-2-Triz) 2-F H H 2-606 Ac H CH2- (4-CH2CH2CH2C02H-2-Triz) 2-FHH 2-607 HH CH2- (4-CH2CH2CH2C02Me-2-Triz) 2 -FHH 2-608 Ac H CH2- (4-CH2CH2CH2C02Me-2 -Triz) 2-FHH 2-609 H H CH2- (4-CH2CH2CH2C02Et-2-Triz) 2-F H H 2-610 Ac H CH2- (4-CH2CH2CH2C02Et-2-Triz) 2-F H H 2-611 H H CH2CH2-2-Triz 2-F H H 2-612 Ac H CH2CH2-2-Triz 2-F H H 2-613 H H CH2CH2- (4-C02H-2-Triz) 2-F H H 2-614 Ac H CH2CH2- (4-C02H-2-Triz) 2-F H H 2-615 H H CH2CH2- (4-C02Me-2-Triz) 2-F H H 2-616 Ac H CH2CH2- (4-C02Me-2-Triz) 2-F H H 2-617 H H CH2CH2- (4-C02Et-2-Triz) 2-F H H 2-618 Ac H CH2CH2- (4-C02Et-2-Triz) 2-F H H 2-619 H H CH2CH2- (4-CH2C02H-2-Triz) 2-F H H 2-620 Ac H CH2CH2- (4-CH2C02H-2-Triz) 2-F H H 2-621 H H CH2CH2- (4-CH2C02Me-2-Triz) 2-F H H 2-622 Ac H CH2CH2- (4-CH2C02Me-2-Triz) 2-F H H 2-623 H H CH2CH2- (4-CH2C02Et-2-Triz) 2-F H H 2-624 Ac H CH2CH2- (4-CH2C02Et-2-Triz) 2-F H H 2-625 H H CH2CH2- (4-CH2CH2C02H-2-Triz) 2-F H H 2-626 Ac H CH2CH2- (4-CH2CH2C02H-2-Triz) 2-F H H 2-627 H H CH2CH2- (4-CH2CH2C02Me-2-Triz) 2-F H H 2-628 Ac H CH2CH2- (4-CH2CH2C02Me-2-Triz) 2-F H H 2-629 H H CH2CH2- (4-CH2CH2C02Et-2-Triz) 2-F H H 2-630 Ac H CH2CH2- (4-CH2CH2C02Et-2-Triz) 2-F H H 2-631 H H CH2CH2- (4-CH2CH2CH2C02H-2-Triz) 2-F H H 2-632 Ac H CH2CH2- (4-CH2CH2CH2C02H-2-Triz) 2-F H H 2-633 H H CH2CH2- (4-CH2CH2CH2C02Me-2-Triz) 2-F H H 2-634 Ac H CH2CH2- (4-CH2CH2CH2C02Me-2-Triz) 2-F H H 2-635 H H CH2CH2- (4-CH2CH2CH2C02Et-2-Triz) 2-F H H 2-636 Ac H CH2CH2- (4-CH2CH2CH2C02Et-2-Triz) 2-F H H 2-637 H H CH2-4-Triz 2-F H H 2-638 Ac H CH2-4-Triz 2-F H H 2-639 H H CH2-4-Triz 2-F 4-F H 2-640 Ac H CH2-4-Triz 2-F 4-F H 2-641 H H CH2- (1-C02Me-4-Triz) 2-F H H 2-642 Ac H CH2- (1-C02Me-4-Triz) 2-F H H 2-643 H H CH2- (1-C02Et-4-Triz) 2-F H H 2-644 Ac H CH2- (1-C02Et-4-Triz) 2-F H H 2-645 H H CH2- (5-C02H-4-Triz) 2-F H H 2-646 Ac H CH2- (5-C02H-4-Triz) 2-F H H 2-647 H H CH2- (5-C02Me-4-Triz) 2-F H H 2-648 Ac H CH2- (5-C02Me-4-Triz) 2-F H H 2-649 H H CH2- (5-C02Et-4-Triz) 2-F H H 2-650 Ac H CH2- (5-C02Et-4-Triz) 2-F H H 2-651 H H CH2- (1-CH2C02H-4-Triz) 2-F H H 2-652 Ac H CH2- (1-CH2C02H-4-Triz) 2-F H H 2-653 H H CH2- (1 -CH2C02Me-4-Triz) 2-F H H 2-654 Ac H CH2- (1-CH2C02Me-4-Triz) 2-F H H 2-655 H H CH2- (1-CH2C02Et-4-Tr yz) 2-F H H 2-656 Ac H CH2- (1-CH2C02Et-4-Triz) 2-F H H 2-657 H H CH2- (5-CH2C02H-4-Triz) 2-F H H 2-658 Ac H CH2- (5-CH2C02H-4-Triz) 2-F H H 2-659 H H CH2- (5-CH2C02Me-4-Triz) 2-F H H 2-660 Ac H CH2- (5-CH2C02Me-4-Triz) 2-F H H 2-661 H H CH2- (5-CH2C02Et-4-Triz) 2-F H H 2-662 Ac H CH2- (5-CH2C02Et-4-Triz) 2-F H H 2-663 H H CH2- (1 -CH2CH2C02H-4-Triz) 2-F H H 2-664 Ac H CH2- (1 -CH2CH2C02H-4-Triz) 2-F H H 2-665 H H CH2- (1 -CH2CH2C02Me-4-Triz) 2-F H H 2-666 Ac H CH2- (1 -CH2CH2C02Me-4-Triz) 2-F H H 2-667 H H CH2- (1 -CH2CH2C02Et-4-Triz) 2-F H H 2-668 Ac H CH2- (1 -CH2CH2C02Et-4-Triz) 2-F H H 2-669 H H CH2- (5-CH2CH2C02H-4-Triz) 2-F H H 2-670 Ac H CH2- (5-CH2CH2C02H-4-Triz) 2-F H H 2-671 H H CH2- (5-CH2CH2C02Me-4-Triz) 2-F H H 2-672 Ac H CH2- (5-CH2CH2C02Me-4-Triz) 2-F H H 2-673 H H CH2- (5-CH2CH2C02Et-4-Triz) 2-F H H 2-674 Ac H CH2- (5-CH2CH2C02Et-4-Triz) 2-F H H 2-675 H H CH2- (1 -CH2CH2CH2C02H-4-Triz) 2-F H H 2-676 Ac H CH2- (1 -CH2CH2CI-l2C02H-4-Triz) 2-F H H 2-677 H H CH2- (1 -CH2CH2CH2C02Me-4-Triz) 2-F H H 2-678 Ac H CH2- (1 -CH2CH2CH2C02Me-4-Triz) 2-F H H 2-679 H H CH2- (1 -CH2CH2CH2C? 2Et-4-Triz) 2-F H H 2-680 Ac H CH2- (1-CH2CH2CH2C02Et-4-Triz) 2-F H H 2-681 H H CH2- (5-CH2CH2CH2C02H-4-Triz) 2-F H H 2-682 Ac H CH2- (5-CH2CH2CH2C02H-4-Triz) 2-F H H 2-683 H H CH2- (5-CH2CH2CH2C02Me-4-Triz) 2-F H H 2-684 Ac H CH2- (5-CH2CH2CH2C02Me-4-Triz) 2-F H H 2-685 H H CH2- (5-CH2CH2CH2C02Et-4-Triz) 2-F H H 2-686 Ac H CH2- (5-CH2CH2CH2C02Et-4-Triz) 2-F H H 2-687 H H CH2CH2-4-Triz 2-F H H 2-688 Ac H CH2CH2-4-Triz 2-F H H 2-689 H H CH2CH2-4-Triz 2-F 4-F H 2-690 Ac H CH2CH2-4-Triz 2-F 4-F H 2-691 H H CH2CH2- (1 -C02Me-4-Triz) 2-F H H 2-692 Ac H CH2CH2- (1-C02Me-4-Triz) 2-F H H 2-693 H H CH2CH2- (1-C02Et-4-Triz) 2-F H H 2-694 Ac H CH2CH2- (1-C02Et-4-Triz) 2-F H H 2-695 H H CH2CH2- (5-C02H-4-Triz) 2-F H H 2-696 Ac H CH2CH2- (5-C02H-4-Triz) 2-F H H 2-697 H H CH2CH2- (5-C02Me-4-Triz) 2-F H H 2-698 Ac H CH2CH2- (5-C02Me-4-Triz) 2-F H H 2-699 H H CH2CH2- (5-C02Et-4-Triz) 2-F H H 2-700 Ac H CH2CH2- (5-C02Et-4-Triz) 2-F H H 2-701 H H CH2CH2- (1 -CH2C02H-4-Triz) 2-F H H 2-702 Ac H CH2CH2- (1 -CH2C02H-4-Triz) 2-F H H 2-703 H H CH2CH2- (1 -CH2C02Me-4-Triz) 2-F H H 2-704 Ac H CH2CH2- (1 -CH2C02Me-4-Triz) 2-F H H 2-705 H H CH2CH2- (1 -CH2C02Et-4-Triz) 2-F H H 2-706 Ac H CH2CH2- (1 -CH2C02Et-4-Triz) 2-F H H 2-707 H H CH2CH2- (5-CH2C02H-4-Triz) 2-F H H 2-708 Ac H CH2CH2-? 5-CH2C02H-4-Triz) 2-F H H 2-709 H H CH2CH2- (5-CH2C02Me-4-Triz) 2-F H H 2-710 Ac H CH2CH2- (5-CH2C02Me-4-Triz) 2-F H H 2-711 H H CH2CH2-? 5-CH2C02Et-4-Triz) 2-F H H 2-712 Ac H CH2CH2- 5-CH2C02Et-4-Triz) 2-F H H 2-713 H H CH2CH2H 1-CH2CH2C02H-4-Triz) 2-F H H 2-714 Ac H p2CH2- 1-CH2CH2C02H-4-Triz) 2-F H H 2-715 H H CH2CH2- (1-CH2CH2C02Me-4-Triz) 2-F H H 2-716 Ac H CH2CH2- 1-CH2CH2C02Me-4-Triz) 2-F H H 2-717 H H CH2CH2-; i-CH2CH2C02Et-4-Triz) 2-F H H 2-718 Ac H CH2CH2- '1-CH2CH2C02Et-4-Triz) 2-F H H 2-719 H H CH2CH2- [5-CH2CH2C02H-4-Triz) 2-F H H 2-720 Ac H CH2CH2-; 5-CH2CH2C02H-4-Triz) 2-F H H 2-721 H H CH2CH2- [5-CH2CH2C02Me-4-Triz) 2-F H H 2-722 Ac H CH2CH2-; 5-CH2CH2C02Me-4-Triz) 2-F H H 2-723 H H CH2CH2- [5-CH2CH2C02Et-4-Triz) 2-F H H 2-724 Ac H CH2CH2-; 5-CH2CH2C02Et-4-Triz) 2-F H H 2-725 H H CH CH2- [1-CH2CH2CH2C02H-4-Triz) 2-F H H 2-726 Ac H CH2CH2- (1 -CH2CH2CH2C02H-4-Triz) 2-F H H 2-727 H H CH2CH2- (1 -CH2CH2CH2C02Me-4-Triz) 2-F H H 2-728 Ac H CH2CH2- (1-CH2CH2CH2C02Me-4-Triz) 2-F H H 2-729 H H CH2CH2- (1-CH2CH2CH2C? 2Et-4-Triz) 2-F H H 2-730 Ac H CH2CH2- (1 -CH2CH2CH2C02Et-4-Triz) 2-F H H 2-731 HH Cp2CH - (5-CH2CH2CH2C02H-4-Triz) 2-FHH 2-732 Ac H CH2CH2- (5-CH2CH2CH2C02H-4-Triz) 2-FHH 2-733 HH CH2CH2- (5-CH2CH2CH2C02Me-4- Triz) 2-FHH 2-734 Ac H CH2CH2- (5-CH2CH2CH2C02Me-4-Triz) 2-F H H 2-735 H H CH2CH2- (5-CH2CH2CH2C02Et-4-Triz) 2-F H H 2-736 Ac H CH2CH2- (5-CH2CH2CH2C02Et-4-Triz) 2-F H H 2-737 H H CH2- (1-C02Me-5-Triz) 2-F 4-F H 2-738 Ac H CH2- (1-C02Me-5-Triz) 2-F 4-F H 2-739 H H CH2- (1-C02Me-5-Triz) 2-F H H 2-740 Ac H CH2- (1-C02Me-5-Triz) 2-F H H 2-741 H H CH2- (1-C02Et-5-Triz) 2-F H H 2-742 Ac H CH2- (1-C02Et-5-Triz) 2-F H H 2-743 H H CH2- (1-CH2C02H-5-Triz) 2-F H H 2-744 Ac H CH2- (1-CH2C02H-5-Triz) 2-F H H 2-745 H H CH2- (1 -CH2C02Me-5-Tr yz) 2-F H H 2-746 Ac H CH2- (1 -CH2C02Me-5-Triz) 2-F H H 2-747 H H CH2- (1-CH2C02Et-5-Triz) 2-F H H 2-748 Ac H CH2- (1-CH2C02Et-5-Triz) 2-F H H 2-749 H H CH2- (1 -CH2CH2C02H-5-Triz) 2-F H H 2-750 Ac H CH2- (1 -CH2CH2C02H-5-Triz) 2-F H H 2-751 H H CH2- (1-CH2CH2C02Me-5-Triz) 2-F H H 2-752 Ac H CH2- (1 -CH2CH2C02Me-5-Triz) 2-F H H 2-753 H H CH2- (1 -CH2CH2C02Et-5-Triz) 2-F H H 2-754 Ac H CH2- (1 -CH2CH2C02Et-5-Triz) 2-F H H 2-755 H H CH2- (1 -CH2CH2CH2C02H-5-Triz) 2-F H H 2-756 Ac H CH2- (1 -CH2CH2CH2C02H-5-Triz) 2-FHH 2-757 HH CH2- (1 -CH2CH2CH2C02Me-5-Triz) 2 -FHH 2-758 Ac H CH2- (1 -CH2CH2CH2C02Me-5 -Triz) 2-FHH 2-759 H H CH2- (1 -CH2CH2CH2C02Et-5-Triz) 2-F H H 2-760 Ac H CH2- (1 -CH2CH2CH2C02Et-5-Triz) 2-F H H 2-761 H H CH2-1-Tez 2-F H H 2-762 Ac H CH2-1-Tez 2-F H H 2-763 H H CH2- (5-C02H-1-Tez) 2-F H H 2-764 Ac H CH2- (5-C02H-1-Tez) 2-F H H 2-765 H H CH2- (5-C02Me-1-Tez) 2-F H H 2-766 Ac H CH2- (5-C02Me-1-Tez) 2-F H H 2-767 H H CH2- (5-C02Et-1-Tez) 2-F H H 2-768 Ac H CH2- (5-C02Et-1-Tez) 2-F H H 2-769 H H CH2- (5-CH2C02H-1 -Tez) 2-F H H 2-770 Ac H CH2- (5-CH2C02H-1-Tez) 2-F H H 2-771 H H CH2- (5-CH2C02Me-1 -Tez) 2-F H H 2-772 Ac H CH2- (5-CH2C02Me-1 -Tez) 2-F H H 2-773 H H CH2- (5-CH2C02Et-1-Tez) 2-F H H 2-774 Ac H CH2- (5-CH2C02Et-1-Tez) 2-F H H 2-775 H H CH2- (5-CH2CH2C02H-1 -Tez) 2-F H H 2-776 Ac H CH2- (5-CH2CH2C02H-1 -Tez) 2-F H H 2-777 H H CH2- (5-CH2CH2C02Me-1 -Tez) 2-F H H 2-778 Ac H CH2- (5-CH2CH2C02Me-1 -Tez) 2-F H H 2-779 H H CH2- (5-CH2CH2C02Et-1 -Tez) 2-F H H 2-780 Ac H CH2- (5-CH2CH2C02Et-1 -Tez) 2-F H H 2-781 HH CH2- (5-CH2CH2CH2C02H-1 -Tez) 2-FHH 2-782 Ac H CH2- (5-CH2CH2CH2C02H-1 -Tez) 2-FHH 2-783 HH CH2- (5-CH2CH2CH2C02Me-1 - Tez) 2-FHH 2-784 Ac H CH2- (5-CH2CH2CH2C02Me-1 -Tez) 2-F H H 2-785 H H CH2- (5-CH2CH2CH2C02Et-1 -Tez) 2-F H H 2-786 Ac H CH2- (5-CH2CH2CH2C02Et-1-Tez) 2-F H H 2-787 H H CH2CH2-1-Tez 2-F H H 2-788 Ac H CH2CH2-1-Tez 2-F H H 2-789 H H CH2CH2- (5-C02H-1-Tez) 2-F H H 2-790 Ac H CH2CH2- (5-C02H-1-Tez) 2-F H H 2-791 H H CH2CH2- (5-C02Me-1 -Tez) 2-F H H 2-792 Ac H CH2CH2- (5-C02Me-1 -Tez) 2-F H H 2-793 H H CH2CH2- (5-C02Et-1-Tez) 2-F H H 2-794 Ac H CH2CH2- (5-C02Et-1 -Tez) 2-F H H 2-795 H H CH2CH2- (5-CH2C02H-1 -Tez) 2-F H H 2-796 Ac H CH2CH2- (5-CH2C02H-1 -Tez) 2-F H H 2-797 H H CH2CH2- (5-CH2C02Me-1 -Tez) 2-F H H 2-798 Ac H CH2CH2- (5-CH2C02Me-1 -Tez) 2-F H H 2-799 H H CH2CH2- (5-CH2C02Et-1-Tez) 2-F H H 2-800 Ac H CH2CH2- (5-CH2C02Et-1-Tez) 2-F H H 2-801 H H CH2CH2- (5-CH2CH2C02H-1 -Tez) 2-F H H 2-802 Ac H CH2CH2- (5-CH2CH2C02H-1 -Tez) 2-F H H 2-803 H H CH2CH2- (5-CH2CH2C? 2Me-1 -Tez) 2-F H H 2-804 Ac H CH2CH2- (5-CH2CH2C02Me-1 -Tez) 2-F H H 2-805 H H CH2CH2- (5-CH2CH2C02Et-1 -Tez) 2-F H H 2-806 Ac H CH2CH2- (5-CH2CH2C02Et-1 -Tez) 2 -FHH 2-807 HH CH2CH2- (5-CH2CH2CH2C02H-1 -Tez) 2 -FHH 2-808 Ac H CH2CH2- (5-CH2CH2CH2C02H-1 - Tez) 2-FHH 2-809 H H CH2CH2- (5-CH2CH2CH2C02Me- I-Tez) 2-F H H 2-810 Ac H CH2CH2- (5-CH2CH2CH2C02Me-1 -Tez) 2-F H H 2-811 H H CH2CH2- (5-CH2CH2CH2C02Et-1 -Tez) 2-F H H 2-812 Ac H CH2CH2- (5-CH2CH2CH2C02Et-1 -Tez) 2-F H H 2-813 H H CH2-2-Tez 2-F H H 2-814 Ac H CH2-2-Tez 2-F H H 2-815 H H CH2- (5-C02H-2-Tez) 2-F H H 2-816 Ac H CH2- (5-C02H-2-Tez) 2-F H H 2-817 H H CH2- (5-C02Me-2-Tez) 2-F H H 2-818 Ac H CH2- (5-C02Me-2-Tez) 2-F H H 2-819 H H CH2- (5-C02Et-2-Tez) 2-F H H 2-820 Ac H CH2- (5-C02Et-2-Tez) 2-F H H 2-821 H H CH2- (5-CH2C02H-2-Tez) 2-F H H 2-822 Ac H CH2- (5-CH2C02H-2-Tez) 2-F H H 2-823 H H CH2- (5-CH2C02Me-2-Tez) 2-F H H 2-824 Ac H CH2- (5-CH2C02Me-2-Tez) 2-F H H 2-825 H H CH2- (5-CH2C02Et-2-Tez) 2-F H H 2-826 Ac H CH2- (5-CH2C02Et-2-Tez) 2-F H H 2-827 H H CH2- (5-CH2CH2C02H-2-Tez) 2-F H H 2-828 Ac H CH2- (5-CH2CH2C? 2H-2-Tez) 2-F H H 2-829 H H CH2- (5-CH2CH2C02Me-2-Tez) 2-F H H 2-830 Ac H CH2- (5-CH2CH2C02Me-2-Tez) 2-F H H 2-831 H H CH2- (5-CH2CH2C02Et-2-Tez) 2-F H H 2-832 Ac H CH2- (5-CH2CH2C02Et-2-Tez) 2-F H H 2-833 H H CH2- (5-CH2CH2CH2C02H-2-Tez) 2-F H H 2-834 Ac H CH2- (5-CH2CH2CH2C02H-2-Tez) 2-F H H 2-835 H H CH2- (5-CH2CH2CH2C02Me-2-Tez) 2-F H H 2-836 Ac H CH2- (5-CH2CH2CH2C02Me-2-Tez) 2-F H H 2-837 H H CH2- (5-CH2CH2CH2C02Et-2-Tez) 2-F H H 2-838 Ac H CH2- (5-CH2CH2CH2C02Et-2-Tez) 2-F H H 2-839 H H CH2CH2-2-Tez 2-F H H 2-840 Ac H CH2CH2-2-Tez 2-F H H 2-841 H H CH2CH2- (5-C02H-2-Tez) 2-F H H 2-842 Ac H CH2CH2- (5-C02H-2-Tez) 2-F H H 2-843 H H CH2CH2- (5-C02Me-2-Tez) 2-F H H 2-844 Ac H CH2CH2- (5-C02Me-2-Tez) 2-F H H 2-845 H H CH2CH2- (5-C02Et-2-Tez) 2-F H H 2-846 Ac H CH2CH2- (5-C02Et-2-Tez) 2-F H H 2-847 H H CH2CH2- (5-CH2C02H-2-Tez) 2-F H H 2-848 Ac H CH2CH2- (5-CH2C02H-2-Tez) 2-F H H 2-849 H H CH2CH2- (5-CH2C02Me-2-Tez) 2-F H H 2-850 Ac H CH2CH2- (5-CH2C02Me-2-Tez) 2-F H H 2-851 H H CH2CH2- (5-CH2C02Et-2-Tez) 2-F H H 2-852 Ac H CH2CH2- (5-CH2C02Et-2-Tez) 2-F H H 2-853 H H CH2CH2- (5-CH2CH2C02H-2-Tez) 2-F H H 2-854 Ac H CH2CH2- (5-CH2CH2C02H-2-Tez) 2-F H H 2-855 H H CH2CH2- (5-CH2CH2C? 2Me-2-Tez) 2-F H H 2-856 Ac H CH2CH2- (5-CH2CH2C02Me-2-Tez) 2-FHH 2-857 HH CH2CH2- (5-CH2CH2C02Et-2-Tez) 2-FHH 2-858 Ac H CH2CH2- (5-CH2CH2C02Et-2 -Tez) 2-FHH 2-859 H H CH2CH2- (5-CH2CH2CH2C02H-2-Tez) 2-F H H 2-860 Ac H CH2CH2- (5-CH2CH2CH2C02H-2-Tez) 2-F H H 2-861 H H CH2CH2- (5-CH2CH2CH2C02Me-2-Tez) 2-F H H 2-862 Ac H CH2CH2- (5-CH2CH2CH2C02Me-2-Tez) 2-F H H 2-863 H H CH2CH2- (5-CH2CH2CH2C02Et-2-Tez) 2-F H H 2-864 Ac H CH2CH2- (5-CH2CH2CH2C02Et-2-Tez) 2-F H H 2-865 H H CH2-5-Tez 2-F H H 2-866 Ac H CH2-5-Tez 2-F H H 2-867 H H CH2-5-Tez 2-F 4-F H 2-868 Ac H CH2-5-Tez 2-F 4-F H 2-869 H H CH2- (1-C02Me-5-Tez) 2-F H H 2-870 Ac H CH2- (1-C02Me-5-Tez) 2-F H H 2-871 H H CH2- (1-C02Et-5-Tez) 2-F H H 2-872 Ac H CH2- (1-C02Et-5-Tez) 2-F H H 2-873 H H CH2- (2-C02Me-5-Tez) 2-F 4-F H 2-874 Ac H CH2- (2-C02Me-5-Tez) 2-F 4-F H 2-875 H H CH2- (2-C02Me-5-Tez) 2-F H H 2-876 Ac H CH2- (2-C02Me-5-Tez) 2-F H H 2-877 H H CH2- (2-C02Et-5-Tez) 2-F H H 2-878 Ac H CH2- (2-C02Et-5-Tez) 2-F H H 2-879 H H CH2- (1-CH2C02H-5-Tez) 2-F H H 2-880 Ac H CH2- (1-CH2C02H-5-Tez) 2-F H H 2-881 HH CH2- (1-CH2C02Me-5-Tez) 2-FHH 2-882 Ac H CH2- (1-CH2C02Me-5-Tez) 2-FHH 2-883 HH CH2- (1-CH2C02Et-5- Tez) 2-FHH 2-884 Ac H CH2- (1-CH2C02Et-5-Tez) 2-F H H 2-885 H H CH2- (2-CH2C02H-5-Tez) 2-F H H 2-886 Ac H CH2- (2-CH2C02H-5-Tez) 2-F H H 2-887 H H CH2- (2-CH2C02Me-5-Tez) 2-F H H 2-888 Ac H CH2- (2-CH2C02Me-5-Tez) 2-F H H 2-889 H H CH2- (2-CH2C02Et-5-Tez) 2-F H H 2-890 Ac H CH2- (2-CH2C02Et-5-Tez) 2-F H H 2-891 H H CH2- (1 -CH2CH2C02H-5-Tez) 2-F H H 2-892 Ac H CH2- (1 -CH2CH2C02H-5-Tez) 2-F H H 2-893 H H CH2- (1 -CH2CH2C02Me-5-Tez) 2-F H H 2-894 Ac H CH2- (1 -CH2CH2C02Me-5-Tez) 2-F H H 2-895 H H CH2- (1 -CH2CH2C02Et-5-Tez) 2-F H H 2-896 Ac H CH2- (1 -CH2CH2C02Et-5-Tez) 2-F H H 2-897 H H CH2- (2-CH2CH2C? 2H-5-Tez) 2-F H H 2-898 Ac H CH2- (2-CH2CH2C02H-5-Tez) 2-F H H 2-899 H H CH2- (2-CH2CH2C02Me-5-Tez) 2-F H H 2-900 Ac H CH2- (2-CH2CH2C02Me-5-Tez) 2-F H H 2-901 H H CH2- (2-CH2CH2C02Et-5-Tez) 2-F H H 2-902 Ac H CH2- (2-CH2CH2C02Et-5-Tez) 2-F H H 2-903 H H CH2- (1 -CH2CH2CH2C02H-5-Tez) 2-F H H 2-904 Ac H CH2- (1 -CH2CH2CH2C02H-5-Tez) 2-F H H 2-905 H H CH2- (1 -CH2CH2CH2C02Me-5-Tez) 2-F H H 2-906 Ac H CH2- (1 -CH2CH2CH2C02Me-5-Tez) 2-FHH 2-907 HH CH2- (1 -CH2CH2CH2C02Et-5-Tez) 2 -FHH 2-908 Ac H CH2- (1-CH2CH2CH2C02Et-5 -Tez) 2-FHH 2-909 H H CH2- (2-CH2CH2CH2C02H-5-Tez) 2-F H H 2-910 Ac H CH2- (2-CH2CH2CH2C02H-5-Tez) 2-F H H 2-911 H H CH2- (2-CH2CH2CH2C02Me-5-Tez) 2-F H H 2-912 Ac H CH2- (2-CH2CH2CH2C02Me-5-Tez) 2-F H H 2-913 H H CH2- (2-CH2CH2CH2C02Et-5-Tez) 2-F H H 2-914 Ac H CH2- (2-CH2CH2CH2C02Et-5-Tez) 2-F H H 2-915 H H CH2CH2-5-Tez 2-F H H 2-916 Ac H CH2CH2-5-Tez 2-F H H 2-917 H H CH2CH2-5-Tez 2-F 4-F H 2-918 Ac H CH2CH2-5-Tez 2-F 4-F H 2-919 H H CH2CH2- (1 -C02Me-5-Tez) 2-F H H 2-920 Ac H CH2CH2- (1-C02Me-5-Tez) 2-F H H 2-921 H H CH2CH2- (1-C02Et-5-Tez) 2-F H H 2-922 Ac H CH2CH2- (1-C02Et-5-Tez) 2-F H H 2-923 H H CH2CH2- (2-C02Me-5-Tez) 2-F H H 2-924 Ac H CH2CH2- (2-C02Me-5-Tez) 2-F H H 2-925 H H CH2CH2- (2-C02Me-5-Tez) 2-F H H 2-926 Ac H CH2CH2- (2-C02Me-5-Tez) 2-F H H 2-927 H H CH2CH2- (2-C02Et-5-Tez) 2-F H H 2-928 Ac H CH2CH2- (2-C02Et-5-Tez) 2-F H H 2-929 H H CH2CH2- (1 -CH2C02H-5-Tez) 2-F H H 2-930 Ac H CH2CH2- (1 -CH2C02H-5-Tez) 2-F H H 2-931 HH CH2CH2- (1 -CH2C02Me-5-Tez) 2 -FHH 2-932 Ac H CH2CH2- (1 -CH2C02Me-5-Tez) 2 -FHH 2-933 HH Cp2Cp2- ((1-CH2C02Et-5 -Tez) 2-FHH 2-934 Ac H CH2CH- ((1-CH2C02Et-5-Tez) 2-F H H 2-935 H H CH2CH2- ((< 2-CH2C02H-5-Tez) 2-F H H 2-936 Ac H CH2CH2- ((2-CH2C02H-5-Tez) 2-F H H 2-937 H H CH2CH2- ((2-CH2C02Me-5-Tez) 2-F H H 2-938 Ac H CH2CH2- ((< 2-CH2C02Me-5-Tez) 2-F H H 2-939 H H CH2CH2- ((2-CH2C02Et-5-Tez) 2-F H H 2-940 Ac H CH2CH2- ((2-CH2C02Et-5-Tez) 2-F H H 2-941 H H CH2CH2- ((1-CH2CH2C02H-5-Tez) 2-F H H 2-942 Ac H CH2CH2- ((1-CH2CH2C02H-5-Tez) 2-F H H 2-943 H H CH2CH2- ((1 -CH2CH2C02Me-5-Tez) 2-F H H 2-944 Ac H Cp2CH2- ((1 -CH2CH2C02Me-5-Tez) 2-F H H 2-945 H H Cp2CH2- ((1-CH2CH2C02Et-5-Tez) 2-F H H 2-946 Ac H CH2CH2- ((1-CH2CH2C02Et-5-Tez) 2-F H H 2-947 H H CH2CH2- ((2-CH2CH2C02H-5-Tez) 2-F H H 2-948 Ac H CHCH- ((2-CH2CH2C02H-5-Tez) 2-F H H 2-949 H H CH2Cp2- ((2-CH2CH2C02Me-5-Tez) 2-F H H 2-950 Ac H Cp2CH2- ((2-CH2CH2C02Me-5-Tez) 2-F H H 2-951 H H CH2CH2- ((2-CH2CH2C02Et-5-Tez) 2-F H H 2-952 Ac H CH2CH2- ((2-CH2CH2C02Et-5-Tez) 2-F H H 2-953 H H CH2CH2- ((1 -CH2CH2CH2C02H-5-Tez) 2-F H H 2-954 Ac H CH2CH2- ((1-CH2CH2CH2C02H-5-Tez) 2-F H H 2-955 H H CH2CH2- ((1-CH2CH2CH2C02Me-5-Tez) 2 2 -FF H H 2-956 Ac H CH2CH2- ((1-CH2CH2CH2C02Me-5-Tez) 2 2 -FF H H 2-957 H H CH2CH2- ((1-CH2CH2CH2C02Et-5-Tez) 2 2 -FF H H 2-958 Ac H CH2CH2- (1-CH2CH2CH2C02Et-5-Tez) 2-F H H 2-959 H H CH2CH2- (2-CH2CH2CH2C02H-5-Tez) 2-F H H 2-960 Ac H CH2CH2- (2-CH2CH2CH2C02H-5-Tez) 2-F H H 2-961 H H CH2CH2- (2-CH2CH2CH2C02Me-5-Tez) 2-F H H 2-962 Ac H CH2CH2- (2-CH2CH2CH2C? 2Me-5-Tez) 2-F H H 2-963 H H CH2CH2- (2-CH2CH2CH2C02Et-5-Tez) 2-F H H 2-964 Ac H CH2CH2- (2-CH2CH2CH2C02Et-5-Tez) 2-F H H 2-965 H Me CH2-1-Pyza 2-F H H 2-966 Ac Me CH2-1-Pyza 2-F H H 2-967 H Me CH2- (3-C02H-1-Pyza) 2-F H H 2-968 Ac Me CH2- (3-C02H-1-Pyza) 2-F H H 2-969 H Me CH2- (3-C02Me-1-Pyza) 2-F H H 2-970 Ac Me CH2- (3-C02Me-1-Pyza) 2-F H H 2-971 H Me CH2- (3-C02Et-1-Pyza) 2-F H H 2-972 Ac Me CH2- (3-C02Et-1-Pyza) 2-F H H 2-973 H Me CH2- (4-C02H-1-Pyza) 2-F H H 2-974 Ac Me CH2- (4-C02H-1-Pyza) 2-F H H 2-975 H Me CH2- (4-C02Me-1-Pyza) 2-F H H 2-976 Ac Me CH2- (4-C02Me-1-Pyza) 2-F H H 2-977 H Me CH2- (4-C02Et-1-Pyza) 2-F H H 2-978 Ac Me CH2- (4-C02Et-1-Pyza) 2-F H H 2-979 H Me CH2- (3-CH2C02H-1-Pyza) 2-F H H 2-980 Ac Me CH2- (3-CH2C02H-1 -Pyza) 2-F H H 2-981 H Me CH2- (3-CH2C02Me-1-Pyza) 2-F H H 2-982 Ac Me CH2- (3-CH2C02Me-1-Pyza) 2-F H H 2-983 H Me CH2- (3-CH2C02Et-1 -Pyza) 2-F H H 2-984 Ac Me CH2- (3-CH2C02Et-1 -Pyza) 2-F H H 2-985 H Me CH2- (4-CH2C02H-1 -Pyza) 2-F H H 2-986 Ac Me CH2- (4-CH2C02H-1-Pyza) 2-F H H 2-987 H Me CH2- (4-CH2C02Me-1 -Pyza) 2-F H H 2-988 Ac Me CH2- (4-CH2C02Me-1 -Pyza) 2-F H H 2-989 H Me CH2- (4-CH2C02Et-1 -Pyza) 2-F H H 2-990 Ac Me CH2- (4-CH2C02Et-1 -Pyza) 2-F H H 2-991 H Me CH2- (3-CH2CH2C02H-1 -Pyza) 2-F H H 2-992 Ac Me CH2- (3-CH2CH2C02H-1 -Pyza) 2-F H H 2-993 H Me CH2- (3-CH2CH2C02Me-1 -Pyza) 2-F H H 2-994 Ac Me CH2- (3-CH2CH2C02Me-1 -Pyza) 2-F H H 2-995 H Me CH2- (3-CH2CH2C02Et-1 -Pyza) 2-F H H 2-996 Ac Me CH2- (3-CH2CH2C02Et-1-Pyza) 2-F H H 2-997 H Me CH2- (4-CH2CH2C02H-1 -Pyza) 2-F H H 2-998 Ac Me CH2- (4-CH2CH2C02H-1 -Pyza) 2-F H H 2-999 H Me CH2- (4-CH2CH2C02Me-1 -Pyza) 2-F H H 2-1000 Ac Me CH2- (4-CH2CH2C02Me-1 -Pyza) 2-F H H 2-1001 H Me CH2- (4-CH2CH2C02Et-1 -Pyza) 2-F H H 2-1002 Ac Me CH2- (4-CH2CH2C02Et-1 -Pyza) 2-F H H 2-1003 H Me CH2CH2-1-Pyza 2-F H H 2-1004 Ac Me CH2CH2-1-Pyza 2-F H H 2-1005 H Me CH2CH2- (3-C02H-1-Pyza) 2-F H H 2-1006 Ac Me CH2CH2- (3-C02H-1-Pyza) 2-FHH 2-1007 H Me CH2CH2- (3-C02Me-1 -Pyza) 2 -FHH 2-1008 Ac Me CH2CH2 '3-C02Me-1 -Pyza) 2-FHH 2-1009 H Me CH2CH2 3-C02Et-1-Pyza) 2-FHH 2-1010 Ac Me CH2CH2- 3-C02Et-1-Pyza) 2-FHH 2-1011 H Me CH2CH2 4-C02H -1-Pyza) 2-FHH 2-1012 Ac Me CH2CH2-? 4-C02H-1-Pyza) 2-F H H 2-1013 H Me CH2CH2-? 4-C02Me-1-Pyza) 2-FHH 2-1014 Ac Me CH CH 2 '4-C02Me-1-Pyza) 2-FHH 2-1015 H Me CH2CH2' 4-C02Et-1-Pyza) 2-FHH 2- 1016 Ac Me CH2CH2-? 4-C02Et-1-Pyza) 2-F H H 2-1017 H Me CH2CH2-? 3-CH2C02H-1-Pyza) 2-F H H 2-1018 Ac Me CH2CH2-? 3-CH2C02H-1-Pyza) 2-F H H 2-1019 H Me CH2CH2-? [3-CH2C02Me-1-Pyza) 2-F H H 2-1020 Ac Me CH2CH2-? r3-CH2C02Me-1-Pyza) 2-FHH 2-1021 H Me CH2CH2 '[3-CH2C02Et-1-Pyza) 2-FHH 2-1022 Ac Me CH2CH2- [3-CH2C02Et-1-Pyza) 2-FHH 2 -1023 H Me Cp2CH2 '[4-CH2C02H-1-Pyza) 2-FHH 2-1024 Ac Me Cp2CH2' [4-CH2C02H-1-Pyza) 2-FHH 2-1025 H Me CH2CH -? (4-CH2C02Me-1-Pyza) 2-F H H 2-1026 Ac Me CH2CH2-? (4-CH2C02Me-1-Pyza) 2-FHH 2-1027 H Me (4-CH2C02Et-1-Pyza) 2-FHH 2-1028 Ac Me C ^ CH ^ (4-CH2C02Et-1-Pyza) 2-FHH 2-1029 H Me CH2CH2- (3-CH2CH2C02H-1-Pyza) 2-FHH 2-1030 Ac Me CH2CH2- (3-CH2CH2C02H-1-Pyza) 2-FHH 2-1031 H Me CH2CH2- (3-CH2CH2C02Me- 1 -Pyza) 2-FHH 2-1032 Ac Me CH2CH2- (3-CH2CH2C02Me-1-Pyza) 2 -FHH 2-1033 H Me CH2CH2- (3-CH2CH2C02Et-1 -Pyza) 2-FHH 2-1034 Ac Me CH2CH2- (3-CH2CH2C02Et-1 -Pyza) 2-F H H 2-1035 H Me CH2CH2- (4-CH2CH2C02H-1 -Pyza) 2-F H H 2-1036 Ac Me CH2CH2- (4-CH2CH2C02H-1 -Pyza) 2-F H H 2-1037 H Me CH2CH2- (4-CH2CH2C02Me-1 -Pyza) 2-F H H 2-1038 Ac Me CH2CH2- (4-CH2CH2C02Me-1 -Pyza) 2-F H H 2-1039 H Me CH2CH2- (4-CH2CH2C02Et-1 -Pyza) 2-F H H 2-1040 Ac Me CH2CH2- (4-CH2CH2C02Et-1 -Pyza) 2-F H H 2-1041 H H CH2- (2-C02Me-4-Triz) 2-F H H 2-1042 Ac H CH2- (2-C02Me-4-Triz) 2-F H H 2-1043 H H CH2- (2-C02Et-4-Triz) 2-F H H 2-1044 Ac H CH2- (2-C02Et-4-Triz) 2-F H H 2-1045 H H CH2- (2-CH2C02H-4-Triz) 2-F H H 2-1046 Ac H CH2- (2-CH2C02H-4-Triz) 2-F H H 2-1047 H H CH2- (2-CH2C02Me-4-Triz) 2-F H H 2-1048 Ac H CH2- (2-CH2C02Me-4-Triz) 2-F H H 2-1049 H H CH2- (2-CH2C02Et-4-Triz) 2-F H H 2-1050 Ac H CH2- (2-CH2C02Et-4-Triz) 2-F H H 2-1051 H H CH2- (2-CH2CH2C02H-4-Triz) 2-F H H 2-1052 Ac H CH2- (2-CH2CH2C02H-4-Triz) 2-F H H 2-1053 H H CH2- (2-CH2CH2C02Me-4-Triz) 2-F H H 2-1054 Ac H CH2- (2-CH2CH2C02Me-4-Triz) 2-F H H 2-1055 H H CH2- (2-CH2CH2C02Et-4-Triz) 2-F H H 2-1056 Ac H CH2- (2-CH2CH2C02Et-4-Triz) 2-FHH 2-1057 HH CH2- (2-CH2CH2CH2C02H-4-Triz) 2-FHH 2-1058 Ac H CH2- (2-CH2CH2CH2C02H-4 -Triz) 2-FHH 2-1059 H H CH2- (2-CH2CH2CH2C02Me-4-Triz) 2-F H H 2-1060 Ac H CH2- (2-CH2CH2CH2C02Me-4-Triz) 2-F H H 2-1061 H H CH2- (2-CH2CH2CH2C02Et-4-Triz) 2-F H H 2-1062 Ac H CH2- (2-CH2CH2CH2C02Et-4-Triz) 2-F H H 2-1063 H H CH2CH2- (2-C02Me-4-Triz) 2-F H H 2-1064 Ac H CH2CH2- (2-C02Me-4-Triz) 2-F H H 2-1065 H H CH2CH2- (2-C02Et-4-Triz) 2-F H H 2-1066 Ac H CH2CH2- (2-C02Et-4-Triz) 2-F H H 2-1067 H H CH2CH2- (2-CH2C02H-4-Triz) 2-F H H 2-1068 Ac H CH2CH2- (2-CH2C02H-4-Triz) 2-F H H 2-1069 H H CH2CH2- (2-CH2C02Me-4-Triz) 2-F H H 2-1070 Ac H CH2CH2- (2-CH2C02Me-4-Triz) 2-F H H 2-1071 H H CH2CH2- (2-CH2C02Et-4-Triz) 2-F H H 2-1072 Ac H CH2CH2- (2-CH2C02Et-4-Triz) 2-F H H 2-1073 H H CH2CH2- (2-CH2CH2C02H-4-Triz) 2-F H H 2-1074 Ac H CH2CH2- (2-CH2CH2C02H-4-Triz) 2-F H H 2-1075 H H CH2CH2- (2-CH2CH2C? 2Me-4-Triz) 2-F H H 2-1076 Ac H CH2CH2- (2-CH2CH2C02Me-4-Triz) 2-F H H 2-1077 H H CH2CH2- (2-CH2CH2C02Et-4-Triz) 2-F H H 2-1078 Ac H CH2CH2- (2-CH2CH2C02Et-4-Triz) 2-F H H 2-1079 H H CH2CH2- (2-CH2CH2CH2C02H-4-Triz) 2-F H H 2-1080 Ac H CH2CH2- (2-CH2CH2CH2C02H-4-Triz) 2-F H H 2-1081 HH CH2CH2- (2-CH2CH2CH2C? 2 e-4-Triz) 2-FHH 2-1082 Ac H CH2CH2- (2-Triz CH2CH2CH2C02Me-4-) 2 2-1083 FHH HH CH2CH2- (2-CH2CH2CH2C02Et -4-Triz) 2-FHH 2-1084 Ac H CH2CH2- (2-CH2CH2CH2C02Et-4-Triz) 2-F H H (Table 2) Comp. No. P1 X1 X2 X3 3-1 H H CH2OH 2-F H H 3-2 Ac H CH2OH 2-F H H 3-3 H H CH2CH2OH 2-F H H 3-4 Ac H CH2CH2OH 2-F H H 3-5 H H CH2OMe 2-F H H 3-6 Ac H CH2OMe 2-F H H 3-7 H H CH2CH2OMe 2-F H H 3-8 Ac H CH2CH2OMe 2-F H H 3-9 H H CH2OEt 2-F H H 3-10 Ac H CH2OEt 2-F H H 3-11 H H CH2CH2OEt 2-F H H 3-12 Ac H CH2CH2OEt 2-F H H 3-13 H H CH2C02H 2-F H H 3-14 Ac H CH2C02H 2-F H H 3-15 H H CH2C02Me 2-F H H 3-16 Ac H CH2C02Me 2-F H H 3-17 H H CH2C02Et 2-F H H 3-18 Ac H CH2C02Et 2-F H H 3-19 H H 4-Pip 2-F H H 3-20 Ac H 4-Pip 2-F H H 3-21 H H 4-Pip 2-F 4-F H 3-22 Ac H 4-Pip 2-F 4-F H 3-23 H H 1-C02Me-4-Pip 2-F H H 3-24 Ac H 1-C02Me-4-Pip 2-F H H 3-25 H H 1-C02Et-4-Pip 2-F H H 3-26 Ac H 1-C02Et-4-Pip 2-F H H 3-27 H H 1 -CH2C02H-4-Pip 2-F H H 3-28 Ac H 1 -CH2C02H-4-Pip 2-F H H 3-29 H H 1 -CH2C02Me-4-Pip 2-F H H 3-30 Ac H 1 -CH2C02Me-4-Pip 2-F H H 3-31 H H 1 -CH2C02Et-4-Pip 2-F H H 3-32 Ac H 1 -CH2C02Et-4-Pip 2-F H H 3-33 H H 1 -CH2CH2C02H-4-Pip 2-F H H 3-34 Ac H 1 -CH2CH2C02H-4-Pip 2-F H H 3-35 H H 1 -CH2CH2C02Me-4-Pip 2-F H H 3-36 Ac H 1 -CH2CH2C02Me-4-Pip 2-F H H 3-37 H H 1 -CH2CH2C02Et-4-Pip 2-F H H 3-38 Ac H 1 -CH 2 CH 2 C 0 2 Et-4-Pip 2-F H H 3-39 Ac H 1 -CH2CH2C02Et-4-Pip 2-F 4-F H 3-40 H H 1 -CH2CH2CH2C02H-4-Pip 2-F H H 3-41 Ac H I-CH2CH2CH2CO2H-4-PIP 2-F H H 3-42 H H 1 -CH2CH2CH2C02Me-4-Pip 2-F H H 3-43 Ac H 1 -CH2CH2CH2C02Me-4-Pip 2-F H H 3-44 H H 1 -CH2CH2CH2C02Et-4-Pip 2-F H H 3-45 Ac H 1 -CH2CH2CH2C? 2Et-4-P¡p 2-F H H 3-46 H H CH2CN 2-F H H 3-47 Ac H CH2CN 2-F H H 3-48 H H CH2CH2CN 2-F H H 3-49 Ac H CH2CH2CN 2-F H H 3-50 H H CH2N (Me) CH2C02H 2-F H H 3-51 Ac H CH2N (Me) CH2C02H 2-F H H 3-52 H H CH2N (Me) CH2C02Me 2-F H H 3-53 Ac H CH2N (Me) CH2C02Me 2-F H H 3-54 H H CH2N (Me) CH2C02Et 2-F H H 3-55 Ac H CH2N (Me) CH2C02Et 2-F H H 3-56 H H CH2N (Me) CH2CH2C02H 2-F H H 3-57 Ac H CH2N (Me) CH2CH2C02H 2-F H H 3-58 H H CH2N (Me) CH2CH2C02Me 2-F H H 3-59 Ac H CH2N (Me) CH2CH2C02Me 2-F H H 3-60 H H CH2N (Me) CH2CH2C02Et 2-F H H 3-61 Ac H CH2N (Me) CH2CH2C02Et 2-F H H 3-62 H H CH2N (Me) CH2CH2CH2C02H 2-F H H 3-63 Ac H CH2N (Me) CH2CH2CH2C02H 2-F H H 3-64 H H CH2N (Me) CH2CH2CH2C02Me 2-F H H 3-65 Ac H CH2N (Me) CH2CH2CH2C02Me 2-F H H 3-66 H H CH2N (Me) 2-F H CH2CH2CH2C02Et H 3-67 Ac H CH2N (Me) 2-F H CH2CH2CH2C02Et H 3-68 H H CH2N (Et) CH2C02H 2-F H H 3-69 Ac H CH2N (Et) CH2C02H 2-F H H 3-70 H H CH2N (Et) CH2C02Me 2-F H H 3-71 Ac H CH2N (Et) CH2C02Me 2-F H H 3-72 H H CH2N (Et) CH2C02Et 2-F H H 3-73 Ac H CH2N (Et) CH2C02Et 2-F H H 3-74 H H CH2N (iPr) CH2C02H 2-F H H 3-75 Ac H CH2N (iPr) CH2C02H 2-F H H 3-76 H H CH2N (iPr) CH2C02Me 2-F H H 3-77 Ac H CH2N (Pr) CH2C02Me 2-F H H 3-78 H H CH2N (iPr) CH2C02Et 2-F H H 3-79 Ac H CH2N (iPr) CH2C02Et 2-F H H (Table 4) Comp. No. P R2 X1 X2 X3 4-1 H H CH2OH 2-F H H 4-2 Ac H CH2OH 2-F H H 4-3 H H CH2CH2OH 2-F H H 4-4 Ac H CH2CH2OH 2-F H H 4-5 H H CH2OMe 2-F H H 4-6 Ac H CH2OMe 2-F H H 4-7 H H CH2CH2OMe 2-F H H 4-8 Ac H CH2CH2OMe 2-F H H 4-9 H H CH2OEt 2-F H H 4-10 Ac H CH2OEt 2-F H H 4-11 H H CH2CH2OEt 2-F H H 4-12 Ac H CH2CH2OEt 2-F H H 4-13 H H CH2C02H 2-F H H 4-14 Ac H CH2C02H 2-F H H 4-15 H H CH2C02Me 2-F H H 4-16 Ac H CH2C02Me 2-F H H 4-17 H H CH2C02Et 2-F H H 4-18 Ac H CH2C02Et 2-F H H 4-19 H H 4-Pip 2-F H H 4-20 Ac H 4-Pip 2-F H H 4-21 H H 4-Pip 2-F 4-F H 4-22 Ac H 4-Pip 2-F 4-F H 4-23 H H 1-C02Me-4-Pip 2-F H H 4-24 Ac H 1-C02Me-4-Pip 2-F H H 4-25 H H 1-C02Et-4-Pip 2-F H H 4-26 Ac H 1-C02Et-4-Pip 2-F H H 4-27 H H 1 -CH2C02H-4-Pip 2-F H H 4-28 Ac H 1 -CH2C02H-4-Pip 2-F H H 4-29 H H 1 -CH2C02Me-4-Pip 2-F H H 4-30 Ac H 1 -CH 2 C0 2 Me-4-Pip 2-F H H 4-31 H H 1 -CH 2 C0 2 Et-4-Pip 2-F H H 4-32 Ac H 1 -CH2C02Et-4-Pip 2-F H H 4-33 H H 1 -CH2CH2C02H-4-Pip 2-F H H 4-34 Ac H 1 -CH2CH2C02H-4-Pip 2-F H H 4-35 H H 1 -CH 2 CH 2 C O 2 Me-4-Pip 2-F H H 4-36 Ac H 1 -CH 2 CH 2 C O 2 Me-4-Pip 2-F H H 4-37 H H 1 -CH2CH2C02Et-4-Pip 2-F H H 4-38 Ac H 1 -CH2CH2C02Et-4-Pip 2-F H H 4-39 Ac H 1 -CH2CH2C02Et-4-Pip 2-F 4-F H 4-40 H H 1 -CH2CH2CH2C02H-4-Pip 2-F H H 4-41 Ac H 1 -CH2CH2CH2C02H-4-Pip 2-F H H 4-42 H H 1 -CH2CH2CH2C02Me-4-Pip 2-F H H 4-43 Ac H 1 -CH2CH2CH2C02Me-4-Pip 2-F H H 4-44 H H 1 -CH2CH2CH2C02Et-4-Pip 2-F H H 4-45 Ac H 1 -CH2CH2CH2C02Et-4-Pip 2-F H H 4-46 H H CH2CN 2-F H H 4-47 Ac H CH2CN 2-F H H 4-48 H H CH2CH2CN 2-F H H 4-49 Ac H CH2CH2CN 2-F H H 4-50 H H CH2N (Me) CH2C02H 2-F H H 4-51 Ac H CH2N (Me) CH2C02H 2-F H H 4-52 H H CH2N (Me) CH2C02Me 2-F H H 4-53 Ac H CH2N (Me) CH2C02Me 2-F H H 4-54 H H CH2N (Me) CH2C02Et 2-F H H 4-55 Ac H CH2N (Me) CH2C02Et 2-F H H 4-56 H H CH2N (Me) CH2CH2C02H 2-F H H 4-57 Ac H CH2N (Me) CH2CH2C02H 2-F H H 4-58 H H CH2N (Me) CH2CH2C02Me 2-F H H 4-59 Ac H CH2N (Me) CH2CH2C02Me 2-F H H 4-60 H H CH2N (Me) CH2CH2C02Et 2-F H H 4-61 Ac H CH2N (Me) CH2CH2C02Et 2-F H H 4-62 H H CH2N (Me) CH2CH2CH2C02H 2-F H H 4-63 Ac H CH 2 N (Me) CH 2 CH 2 CH 2 C? 2 H 2 -F H H 4-64 H H CH2N (Me) CH2CH2CH2C02Me 2-F H H 4-65 Ac H CH2N (Me) CH2CH2CH2C02Me 2-F H H 4-66 H H CH2N (Me) CH2CH2CH2C02Et 2-F H H 4-67 Ac H CH2N (Me) CH2CH2CH2C02Et 2-F H H 4-68 H H CH2N (Et) CH2C02H 2-F H H 4-69 Ac H CH2N (Et) CH2C02H 2-F H H 4-70 HH CH2N (Et) CH2C02Me 2 -FHH 4-71 Ac H CH2N (Et) CH2C02Me 2 -FHH 4-72 HH CH2N (Et) CH2C02Et 2 -FHH 4-73 Ac H CH2N (Et) CH2C02Et 2 -FHH 4-74 HH CH2N (iPr) CH2C02H 2 -FHH 4-75 Ac H CH2N (iPr) CH2C02H 2 -FHH 4-76 HH CH2N (iPr) CH2C02Me 2 -FHH 4-77 Ac H CH2N (iPr) CH2C02Me 2 -FHH 4-78 HH CH2N (iPr) CH2C02Et 2-FHH 4-79 Ac H CH2N (iPr) CH2C02Et 2-FHH (Table 51 Comp. No. P1 D R2¿ D R3 X1 X2 X3 5-1 HH CH2-1-Pip 2-FHH 5-2 Ac H CH2-1-Pip 2 -FHH 5-3 HH CH2- (4-C02H-1-Pip) 2 -FHH 5-4 Ac H CH2- (4-C02H-1-Pip) 2-FHH 5-5 HH CH2- (4-C02Me-1-Pip) 2-FHH 5-6 Ac H CH2- (4-C02Me-1-Pip) 2-FHH 5 -7 HH CH2- (4-C02Et-1-Pip) 2-FHH 5-8 Ac H CH2- (4-C02Et-1-Pip) 2-F H H 5-9 H H CH2- (4-CH2C02H-1-Pip) 2-F H H 5-10 Ac H CH2- (4-CH2C02H-1-Pip) 2-F H H 5-11 H H CH2- (4-CH2C02Me-1-Pip) 2-F H H 5-12 Ac H CH2- (4-CH2C02Me-1-Pip) 2-F H H 5-13 H H CH2- (4-CH2C02Et-1-Pip) 2-F H H 5-14 Ac H CH2- (4-CH2C02Et-1-Pip) 2-F H H 5-15 H H CH2- (4-CH2CH2C02H-1 -Pip) 2-F H H 5-16 Ac H CH2- (4-CH2CH2C02H-1 -Pip) 2-F H H 5-17 H H CH2- (4-CH2CH2C? 2Me-1 -Pip) 2-F H H 5-18 Ac H CH2- (4-CH2CH2C02Me-1 -Pip) 2-F H H 5-19 H H CH2- (4-CH2CH2C02Et-1-Pip) 2-F H H 5-20 Ac H CH2- (4-CH2CH2C02Et-1 -Pip) 2-F H H 5-21 H H CH2- (4-CH2CH2CH2C02H-1 -Pip) 2-F H H 5-22 Ac H CH2- (4-CH2CH2CH2C02H-1 -Pip) 2-F H H 5-23 H H CH2- (4-CH2CH2CH2C? 2Me-1 -Pip) 2-F H H 5-24 Ac H CH2- (4-CH2CH2CH2C02Me-1 -Pip) 2-F H H 5-25 H H CH2- (4-CH2CH2CH2C? 2Et-1 -Pip) 2-F H H 5-26 Ac H CH2- (4-CH2CH2CH2C02Et-1 -Pip) 2-F H H 5-27 H H CH2-Mor 2-F H H 5-28 Ac H CH2-Mor 2-F H H 5-29 H H CH2-Thm 2 -F H H 5-30 Ac H CH2-Thim 2-F H H 5-31 H H CH2-1-Piz 2-F H H 5-32 Ac H CH2-1-Piz 2-F H H 5-33 H H CH2- (4-Ac-1-Piz) 2-F H H 5-34 Ac H CH2- (4-Ac-1-Piz) 2-F H H 5-35 H H CH2- (4-Ac-1-Piz) 2-F 4-F H 5-36 Ac H CH2- (4-Ac-1-Piz) 2-F 4-F H 5-37 H H CH2- (4-C02Me-1-Piz) 2-F H H 5-38 Ac H CH2- (4-C02Me-1-Piz) 2-F H H 5-39 H H CH2- (4-C02Et-1-Piz) 2-F H H 5-40 Ac H CH2- (4-C02Et-1-Piz) 2-F H H 5-41 H H CH2- (4-CH2C02H-1-Piz) 2-F H H 5-42 Ac H CH2- (4-CH2C02H-1-Piz) 2-F H H 5-43 H H CH2- (4-CH2C02Me-1 -Piz) 2-F H H 5-44 Ac H CH2- (4-CH2C02Me-1-Piz) 2-F H H 5-45 H H CH2- (4-CH2C02Et-1-Piz) 2-F H H 5-46 Ac H CH2- (4-CH2C02Et-1-Piz) 2-F H H 5-47 H H CH2- (4-CH2CH2C? 2H-1 -Piz) 2-F H H 5-48 Ac H CH2- (4-CH2CH2C? 2H-1 -Piz) 2-F H H 5-49 H H CH2- (4-CH2CH2C02Me-1 -Piz) 2-F H H 5-50 Ac H CH2- (4-CH2CH2C02Me-1 -Piz) 2-F H H 5-51 H H CH2- (4-CH2CH2C02Et-1 -Piz) 2-F H H 5-52 Ac H CH2- (4-CH2CH2C02Et-1 -Piz) 2-F H H 5-53 H H CH2- (4-CH2CH2CH2C02H-1 -Piz) 2-F H H 5-54 Ac H CH2- (4-CH2CH2CH2C02H-1 -Piz) 2-F H H 5-55 H H CH2- (4-CH2CH2CH2C02Me-1 -Piz) 2-F H H 5-56 Ac H CH2- (4-CH2CH2CH2C02Me-1 -Piz) 2-F H H 5-57 H H CH2- (4-CH2CH2CH2C02Et-1-Piz) 2-F H H 5-58 Ac H CH2- (4-CH2CH2CH2C02Et-1-Piz) 2-F H H 5-59 H H CH2- (2-o? O-1-Piz) 2-F H H 5-60 Ac H CH2- (2-o? O-1-Piz) 2-F H H 5-61 H H CH2- (4-Ac-2-o? O-1-Piz) 2-F H H 5-62 Ac H CH2- (4-Ac-2-o? O-1-Piz) 2-F H H 5-63 H H CH2- (4-Ac-2-oxo-1-Piz) 2-F 4-F H 5-64 Ac H CH2- (4-Ac-2-oxo-1-Piz) 2-F 4-F H 5-65 H H CH2- (4-C02Me-2-o? O-1-Piz) 2-F H H 5-66 Ac H CH2- (4-C02Me-2-o? O-1-Piz) 2-F H H 5-67 H H CH2- (4-C02Et-2-o? O-1-Piz) 2-F H H 5-68 Ac H CH2- (4-C02Et-2-oxo-1-Piz) 2-F H H 5-69 H H CH2- (4-CH2C02H-2-o? O-1-Piz) 2-F H H 5-70 Ac H CH2- (4-CH2C02H-2-o? O-1-Piz) 2-F H H 5-71 H H CH2- (4-CH2C02Me-2-o? O-1-Piz) 2-F H H 5-72 Ac H CH2- (4-CH2C02Me-2-o? O-1-Piz) 2-F H H 5-73 H H CH2- (4-CH2C02Et-2-oxo-1-Piz) 2-F H H 5-74 Ac H CH2- (4-CH2C02Et-2-o? O-1-Piz) 2-F H H 5-75 H H CH2- (4-CH2CH2C02H-2-oxo-1-Piz) 2-F H H 5-76 Ac H CH2- (4-CH2CH2C02H-2-oxo-1-Piz) 2-F H H 5-77 H H CH2- (4-CH2CH2C02Me-2-oxo-1-Piz) 2-F H H 5-78 Ac H CH2- (4-CH2CH2C02Me-2-o? O-1-Piz) 2-F H H 5-79 H H CH2- (4-CH2CH2C? 2Et-2-o? O-1-Piz) 2-F H H 5-80 Ac H CH2- (4-CH2CH2C? 2Et-2-oxo-1-Piz) 2-F H H 5-81 H H CH2- (4-CH2CH2CH2C02H-2-oxo-1-Piz) 2-F H H 5-82 Ac H CH2- (4-CH2CH2CH2C02H-2-oxo-1-Piz) 2-F H H 5-83 H H CH2- (4-CH2CH2CH2C02Me-2-o? O-1-Piz) 2-F H H 5-84 Ac H CH2- (4-CH2CH2CH2C02Me-2-o? O-1-Piz) 2-F H H 5-85 H H CH2- (4-CH2CH2CH2C02Et-2-oxo-1-Piz) 2-F H H 5-86 Ac H CH2- (4-CH2CH2CH2C02Et-2-oxo-1-Piz) 2-F H H 5-87 H H CH2- (3-o? O-1-Piz) 2-F H H 5-88 Ac H CH2- (3-o? O-1-Piz) 2-F H H 5-89 H H CH2- (4-Ac-3-o? O-1-Piz) 2-F H H 5-90 Ac H CH 2 - (4-Ac-3-oxo-1-Piz) 2-F H H 5-91 H H CH2- (4-Ac-3-o? O-1-Piz) 2-F 4-F H 5-92 Ac H CH2- (4-Ac-3-oxo-1-Piz) 2-F 4-F H 5-93 H H CH2- (4-C02Me-3-o? O-1-Piz) 2-F H H 5-94 Ac H CH2- (4-C02Me-3-oxo-1-Piz) 2-F H H 5-95 H H CH2- (4-C02Et-3-o? O-1-Piz) 2-F H H 5-96 Ac H CH2- (4-C02Et-3-oxo-1-Piz) 2-F H H 5-97 H H CH2- (4-CH2C02H-3-oxo-1-Piz) 2-F H H 5-98 Ac H CH2- (4-CH2C02H-3-oxo-1-Piz) 2-F H H 5-99 H H CH2- (4-CH2C02Me-3-oxo-1-Piz) 2-F H H 5-100 Ac H CH2- (4-CH2C02Me-3-o? O-1-Piz) 2-F H H 5-101 H H CH2- (4-CH2C02Et-3-oxo-1-Piz) 2-F H H 5-102 Ac H CH2- (4-CH2C02Et-3-oxo-1-Piz) 2-F H H 5-103 H H CH2- (4-CH2CH2C02H-3-oxo-1-Piz) 2-F H H 5-104 Ac H CH2- (4-CH2CH2C? 2H-3-oxo-1-Piz) 2-F H H 5-105 H H CH2- (4-CH2CH2C? 2Me-3-oxo-1-Piz) 2-F H H 5-106 Ac H CH2- (4-CH2CH2C? 2Me-3-oxo-1-Piz) 2-F H H 5-107 H H CH2- (4-CH2CH2C02Et-3-oxo-1-Piz) 2-F H H 5-108 Ac H CH2- (4-CH2CH2C02Et-3-oxo-1-Piz) 2-F H H 5-109 H H CH2- (4-CH2CH2CH2C02H-3-oxo-1-Piz) 2-F H H 5-110 Ac H CH2- (4-CH2CH2CH2C02H-3-o? O-1-Piz) 2-F H H 5-111 H H CH2- (4-CH2CH2CH2C02Me-3-oxo-1-Piz) 2-F H H 5-112 Ac H CH2- (4-CH2CH2CH2C? 2Me-3-oxo-1-Piz) 2-F H H 5-113 H H CH2- (4-CH2CH2CH2C02Et-3-o? O-1-Piz) 2-F H H 5-114 Ac H CH2- (4-CH2CH2CH2C? 2Et-3-o? O-1-Piz) 2-F H H 5-115 H H CH 2 - (2,5-dioxo-1-Piz) 2-F H H 5-116 Ac H CH 2 - (2,5-dioxo-1-Piz) 2-F H H 5-117 H H CH2- (4-Ac-2,5-dioxo-1-Piz) 2-F H H 5-118 Ac H CH2- (4-Ac-2,5-dioxo-1-Piz) 2-F H H 5-119 H H CH2- (4-Ac-2,5-dioxo-1-P yz) 2-F 4-F H 5-120 Ac H CH 2 - (4-Ac-2,5-dioxo-1-Piz) 2-F 4 -FH 5-121 HH CH 2 - (4-C02Me-2,5-dioxo-1-Piz) 2 -FHH 5-122 Ac H CH2- (4-C02Me-2,5-dioxo-1-Piz) 2-F H H 5-123 H H CH2- (4-C02Et-2,5-dioxo-1-Piz) 2-F H H 5-124 Ac H CH2- (4-C02Et-2,5-dioxo-1-Piz) 2-F H H 5-125 HH CH2- (4-CH2C02H-2,5-di? Xo-1-Piz) 2-FHH 5-126 Ac H CHr (4-CH2C02H-2,5-d¡oxo-1-P¡z 2-FHH 5-127 H H CH2- (4-CH2C02Me-2,5-dioxo-1-Piz) 2-F H H 5-128 Ac H CH2- (4-CH2C02Me-2,5-dio? O-1-Piz) 2-F H H 5-129 H H CH2- (4-CH2C02Et-2,5-dioxo-1-Piz) 2-F H H 5-130 Ac H CH2- (4-CH2C02Et-2,5-dio? O-1-Piz) 2-FHH 5-131 HH CH2- (4-CH2CH2C02H-2,5-dio? O-1-Piz) 2-FHH 5-132 Ac H CH2- (4-CH2CH2C02H-2,5-dioxo-1-Piz) 2-FHH 5-133 H H CH2- (4-CH2CH2C02Me-2,5-dio? O-1-Piz) 2-F H H 5-134 Ac H CH2- (4-CH2CH2C02Me-2,5-dio? O-1-Piz) 2-F H H 5-135 H H CH2- (4-CH2CH2C02Et-2,5-dio? O-1-Piz) 2-F H H 5-136 Ac H CH2- (4-CH2CH2C02Et-2,5-dio? O-1-Piz) 2-F H H 5-137 H H CH2- (4-CH2CH2CH2C02H-2,5-dio? O-1-Piz) 2-F H H 5-138 Ac H CH2- (4-CH2CH2CH2C02H-2,5-dioxo-1-Piz) 2-F H H 5-139 H H CH2- (4-CH2CH2CH2C02Me-2,5-dioxo-1-Piz) 2-F H H 5-140 Ac H CH2- (4-CH2CH2CH2C02Me-2,5-dioxo-1-Piz) 2-F H H 5-141 H H CH2- (4-CH2CH2CH2C02Et-2,5-dio? O-1-Piz) 2-F H H 5-142 Ac H CH2- (4-CH2CH2CH2C02Et-2,5-dio? O-1-Piz) 2-F H H 5-143 H H CH2-1-Pyrd 2-F H H 5-144 Ac H CH2-1-Pyrd 2-F H H 5-145 H H CH2- (2-C02H-1-Pyrd) 2-F H H 5-146 Ac H CH2- (2-C02H-1-Pyrd) 2-F H H 5-147 H H CH2- (2-C02Me-1-Pyrd) 2-F H H 5-148 Ac H CH2- (2-C02Me-1-Pyrd) 2-F H H 5-149 H H CH2- (2-C02Et-1-Pyrd) 2-F H H 5-150 Ac H CH2- (2-C02Et-1-Pyrd) 2-F H H 5-151 H H CH2- (2-CH2C02H-1-Pyrd) 2-F H H 5-152 Ac H CH2- (2-CH2C02H-1-Pyrd) 2-F H H 5-153 H H CH2- (2-CH2C02Me-1-Pyrd) 2-F H H 5-154 Ac H CH2- (2-CH2C02Me-1-Pyrd) 2-F H H 5-155 H H CH2- (2-CH2C02Et-1-Pyrd) 2-F H H 5-156 Ac H CH2- (2-CH2C? 2Et-1-Pyrd) 2-F H H 5-157 H H CH2- (2-CH2CH2C02H-1-Pyrd) 2-F H H 5-158 Ac H CH2- (2-CH2CH2C02H-1-Pyrd) 2-F H H 5-159 H H CH2- (2-CH2CH2C02Me-1-Pyrd) 2-F H H 5-160 Ac H CH2- (2-CH2CH2C02Me-1-Pyrd) 2-F H H 5-161 H H CH2- (2-CH2CH2C02Et-1-Pyrd) 2-F H H 5-162 Ac H CH2- (2-CH2CH2C02Et-1-Pyrd) 2-F H H 5-163 H H CH2- (2-CH2CH2CH2C02H-1-Pyrd) 2-F H H 5-164 Ac H CH2- (2-CH2CH2CH2C02H-1-Pyrd) 2-F H H 5-165 H H CH2- (2-CH2CH2CH2C02Me-1-Pyrd) 2-F H H 5-166 Ac H CH2- (2-CH2CH2CH2C02Me-1-Pyrd) 2-F H H 5-167 H H CH2- (2-CH2CH2CH2C02Et-1-Pyrd) 2-F H H 5-168 Ac H CH2- (2-CH2CH2CH2C02Et-1-Pyrd) 2-F H H 5-169 H H CH2CH2-1-Pip 2-F H H 5-170 Ac H CH2CH2-1-Pip 2-F H H 5-171 H H CH2CH2- (4-C02H-1-PIP) 2-F H H 5-172 Ac H CH2CH2- (4-C02H-1-Pip) 2-F H H 5-173 H H CH2CH2- (4-C02Me-1-Pip) 2-F H H 5-174 Ac H CH2CH2- (4-C02Me-1-Pip) 2-F H H 5-175 H H CH2CH2- (4-C02Et-1-Pip) 2-F H H 5-176 Ac H CH2CH2- (4-C02Et-1-Pip) 2-F H H 5-177 H H CH2CH2- (4-CH2C02H-1-Pip) 2-F H H 5-178 Ac H CH2CH2- (4-CH2C02H-1-Pip) 2-F H H 5-179 H H CH2CH2- (4-CH2C02Me-1-Pip) 2-F H H 5-180 Ac H CH2CH2- (4-CH2C02Me-1-Pip) 2-F H H 5-181 H H CH2CH2- (4-CH2C02Et-1-Pip) 2-F H H 5-182 Ac H CH2CH (4-CH2C02Et-1-Pip) 2-F H H 5-183 H H CH2CH (4-CH2CH2C02H-1-Pip) 2-F H H 5-184 Ac H CH2CH (4-CH2CH2C02H-1-Pip) 2-F H H 5-185 H H CH2CH2- (4-CH2CH2C02Me-1-Pip) 2-F H H 5-186 Ac H Cp2Cp2 '(4-CH2CH2C02Me-1-Pip) 2-F H H 5-187 H H CH2CH2- (4-CH2CH2C02Et-1-Pip) 2-F H H 5-188 Ac H CH2CH2 (4-CH2CH2C02Et-1-Pip) 2-F H H 5-189 H H CH CH2- (4-CH2CH2CH2C02H-1 -Pip) 2-F H H 5-190 Ac H CH2CH2- (? 4-CH2CH2CH2C02H-1 -Pip) 2-F H H 5-191 H H CH CH2 (4-CH2CH2CH2C02Me-1 -Pip) 2-F H H 5-192 Ac H CH2CH2- (4-CH2CH2CH2C02Me-1 -Pip) 2-F H H 5-193 H H CH2CH2- (4-CH2CH2CH2C02Et-1 -Pip) 2-F H H 5-194 Ac H CH2CH2- (4-CH2CH2CH2C02Et-1 -Pip) 2-F H H 5-195 H H CH2CH2-Mor 2-F H H 5-196 Ac H CH2CH2-Mor 2-F H H 5-197 H H CH2CH2-Thim 2-F H H 5-198 Ac H CH2CH2-Thim 2-F H H 5-199 H H CH2CH2-1-Piz 2-F H H 5-200 Ac H CH2CH2-1-Piz 2-F H H 5-201 H H CH2CH2- (4-Ac-1-Piz) 2-F H H 5-202 Ac H CH2CH2- (4-Ac-1-Piz) 2-F H H 5-203 H H CH2CH2- (4-Ac-1-Piz) 2-F 4-F H 5-204 Ac H CH2CH2- (4-Ac-1-Piz) 2-F 4-F H 5-205 H H CH2CH2- (4-C02Me-1-Piz) 2-F H H 5-206 Ac H CH2CH2- (4-C02Me-1 -Piz) 2-F H H 5-207 H H CH2CH2- (4-C02Et-1-Piz) 2-F H H 5-208 Ac H CH2CH2- (4-C02Et-1-Piz) 2-F H H 5-209 H H CH2CH2- (4-CH2C02H-1 -Piz) 2-F H H 5-210 Ac H CH2CH2- (4-CH2C02H-1 -Piz) 2-F H H 5-211 H H CH2CH2- (4-CH2C02Me-1 -Piz) 2-F H H 5-212 Ac H CH2CH2- (4-CH2C02Me-1 -Piz) 2-F H H 5-213 H H CH2CH2- (4-CH2C02Et-1 -Piz) 2-F H H 5-214 Ac H CH2CH2- (4-CH2C02Et-1 -Piz) 2-F H H 5-215 H H CH2CH2- (4-CH2CH2C02H-1 -Piz) 2-F H H 5-216 Ac H CH2CH2- (4-CH2CH2C02H-1 -Piz) 2-F H H 5-217 H H CH2CH2- (4-CH2CH2C02Me-1 -Piz) 2-F H H 5-218 Ac H CH2CH2- (4-CH2CH2C02Me-1 -Piz) 2-F H H 5-219 H H CH2CH2- (4-CH2CH2C02Et-1 -Piz) 2-F H H 5-220 Ac H CH2CH2- (4-CH2CH2C02Et-1 -Piz) 2-F H H 5-221 H H CH2CH2- (4-CH2CH2CH2C02H-1 -Piz) 2-F H H 5-222 Ac H CH2CH2- (4-CH2CH2CH2C02H-1 -Piz) 2-F H H 5-223 H H CH2CH2- (4-CH2CH2CH2C02Me-1 -Piz) 2-F H H 5-224 Ac H CH2CH2- (4-CH2CH2CH2C02Me-1 -Piz) 2-F H H 5-225 H H CH2CH2- (4-CH2CH2CH2C02Et-1 -Piz) 2-F H H 5-226 Ac H CH2CH2- (4-CH2CH2CH2C02Et-1 -Piz) 2-F H H 5-227 H H CH2CH2- (2-oxo-1-Piz) 2-F H H 5-228 Ac H CH2CH2- (2-o? O-1-Piz) 2-F H H 5-229 H H CH2CH2- (4-Ac-2-oxo-1 -Piz) 2-F H H 5-230 Ac H CH2CH2- (4-Ac-2-oxo-1 -Piz) 2-F H H 5-231 HH CH2CH2- (4-Ac-2-oxo-1 -Piz) 2-F 4 -FH 5-232 Ac H CHCH2- ((4-Ac-2-oxo-1-Piz) 2-F 4 -FH 5-233 H H CH2CH2- ((4-C02Me-2-oxo-1-Piz) 2-F H H 5-234 Ac H CH2CH2- ((4-C02Me-2-oxo-1-Piz) 2-F H H 5-235 H H CH2CH2- ((4-C02Et-2-oxo-1-Piz) 2-F H H 5-236 Ac H CH2CH2- ((4-C02Et-2-o? O-1-Piz) 2-F H H 5-237 H H CH2CH2- ((4-CH2C02H-2-oxo-1 -Piz) 2-F H H 5-238 Ac H CH2CH2- ((4-CH2C02H-2-o? O-1-Piz) 2-F H H 5-239 H H Cp2CH- ((4-CH2C02Me-2-o? O-1 -Piz) 2-F H H 5-240 Ac H C? 2CH2- ((4-CH2C02Me-2-oxo-1 -Piz) 2-F H H 5-241 H H CH2CH2- ((4-CH2C02Et-2-o? O-1 -Piz) 2-F H H 5-242 Ac H CH2CH2- ((4-CH2C02Et-2-o? O-1 -Piz) 2-F H H 5-243 H H CH2CH2- ((4-CH2CH2C02H-2-o? O-1 -Piz) 2-F H H 5-244 Ac H CH2CH2- ((4-CH2CH2C02H-2-o? O-1 -Piz) 2-F H H 5-245 H H CHCH2- ((4-CH2CH2C02Me-2-o? O-1 -Piz) 2-F H H 5-246 Ac H CH2CH2- ((4-CH2CH2C02Me-2-oxo-1 -Piz) 2-F H H 5-247 H H CH2CH2- ((4-CH2CH2C02Et-2-oxo-1-P yz) 2-F H H 5-248 Ac H CHCH2- ((4-CH2CH2C02Et-2-oxo-1 -Piz) 2-F H H 5-249 H H CHCH2- ((4-CH2CH2CH2C02H-2-o? O-1 -Piz) 2-F H H 5-250 Ac H CH2CH2- ((4-CH2CH2CH2C02H-2-o? O-1 -Piz) 2-F H H 5-251 H H C? 2C? 2- ((4-CH2CH2CH2C? 2Me-2-o? O-1 -Piz) 2-F H H 5-252 Ac H C? 2C? 2"((4-CH2CH2CH2C02Me-2-oxo-1 -Piz) 2-F H H 5-253 H H CH2Cri2- ((4-CH2CH2CH2C02Et-2-o? O-1 -Piz) 2-F H H 5-254 Ac H CH2C? 2- ((4-CH2CH2CH2C02Et-2-o? O-1 -Piz) 2-F H H 5-255 H H C? 2C? 2- ((3-o? O-1-Piz) 2-F H H 5-256 Ac H Crl2CH2- ((3-o? O-1-Piz) 2-F H H 5-257 H H CH2CH2- (4-Ac-3-o? O-1-Piz) 2-F H H 5-258 Ac H CH2CH2- (4-Ac-3-oxo-1-Piz) 2-F H H 5-259 H H CH2CH2- (4-Ac-3-oxo-1-Piz) 2-F 4-F H 5-260 Ac H CH2CH2- (4-Ac-3-oxo-1-Piz) 2-F 4-F H 5-261 H H CH2CH2- (4-C02Me-3-o? O-1-Piz) 2-F H H 5-262 Ac H CH2CH2- (4-C02Me-3-oxo-1-Piz) 2-F H H 5-263 H H CH2CH2- (4-C02Et-3? Xo-1-Piz) 2-F H H 5-264 Ac H CH2CH2- (4-C02Et-3-oxo-1-Piz) 2-F H H 5-265 H H CH2CH2- (4-CH2C? 2H-3-oxo-1-Piz) 2-F H H 5-266 Ac H CH2CH2- (4-CH2C? 2H-3-oxo-1-Piz) 2-F H H 5-267 H H CH2CH2- (4-CH2C02Me-3-o? O-1-Piz) 2-F H H 5-268 Ac H CH2CH2- (4-CH2C? 2Me-3-o? O-1-Piz) 2-F H H 5-269 H H CH2CH2- (4-CH2C? 2Et-3-oxo-1-Piz) 2-F H H 5-270 Ac H CH2CH2- (4-CH2C? 2Et-3-oxo-1-Piz) 2-F H H 5-271 H H CH2CH2- (4-CH2CH2C02H-3-o? O-1-Piz) 2-F H H 5-272 Ac H CH2CH2- (4-CH2CH2C? 2H-3-o? O-1-Piz) 2-F H H 5-273 H H CH2CH2- (4-CH2CH2C? 2Me-3-oxo-1-Piz) 2-F H H 5-274 Ac H CH2CH2- (4-CH2CH2C? 2Me-3-oxo-1-Piz) 2-F H H 5-275 H H CH2CH2- (4-CH2CH2C02Et-3-o? O-1-Piz) 2-F H H 5-276 Ac H CH2CH2- (4-CH2CH2C? 2Et-3-oxo-1-Piz) 2-F H H 5-277 H H CH2CH2- (4-CH2CH2CH2C02H-3-o? O-1-Piz) 2-F H H 5-278 Ac H CH2CH2- (4-CH2CH2CH2C02H-3-o? O-1-P yz) 2-F H H 5-279 H H CH2CH2- (4-CH2CH2CH2C02Me-3-o? O-1-Piz) 2-F H H 5-280 Ac H CH2CH2- (4-CH2CH2CH2C02Me-3-o? O-1-Piz) 2-FHH 5-281 HH CH2CH2- (4-CH2CH2CH2C? 2Et-3? Xo-1-Piz) 2-FHH 5-282 Ac H CHCH2- (('4-CH2CH2CH2C02Et-3-oxo-1-Piz) 2-FHH 5-283 H H CH2CH2- ((, 2,5-dioxo-1-Piz) 2-F H H 5-284 Ac H Cp2Cp2- ((< 2,5-dio? O-1-Piz) 2-F H H 5-285 H H C? 2C? 2- (('4-Ac-2,5-dio? O-1-Piz) 2-F H H 5-286 Ac H C? 2C? 2- (('4-Ac-2,5-dioxo-1-Piz) 2-F H H 5-287 H H C? 2C? 2- ((4-Ac-2,5-dio? O-1-Piz) 2-F 4-F H 5-288 Ac H Cp2CH2- ((4-Ac-2,5-dio? O-1-Piz) 2-F 4-F H 5-289 H H C? 2C? 2- ((4-C02Me-2,5-dio? O-1-Piz) 2-F H H 5-290 Ac H C? 2C? 2"((4-C02Me-2,5-dio? O-1-Piz) 2-F H H 5-291 H H CH2C? 2_ ((4-C02Et-2,5-dio? O-1-Piz) 2-F H H 5-292 Ac H Cp2CH2- ((4-C02Et-2,5-dio? O-1-Piz) 2-F H H 5-293 H H C? 2C? 2- ((4-CH2C02H-2,5-dio? O-1-Piz) 2-F H H 5-294 Ac H C? 2C? 2"((4-CH2C02H-2,5-dio? O-1-Piz) 2-F H H 5-295 H H Cp2CH2- ((4-CH2C02Me-2,5-dio? O-1-Piz) 2-F H H 5-296 Ac H C? 2C? 2- ((4-CH 2 C? 2Me-2,5-dioxo-1-Piz) 2-F H H 5-297 H H C? C? 2- ((4-CH2C02Et-2,5-dioxo-1-Piz) 2-F H H 5-298 Ac H CH2C? 2- ((4-CH2C02Et-2,5-dioxo-1-Piz) 2-F H H 5-299 H H CH2C? 2- < (4-CH2CH2C02H-2,5-dioxo-1-Piz) 2-F H H 5-300 Ac H CH2CH2- ((4-CH2CH2C02H-2,5-dioxo-1-Piz) 2-F H H 5-301 H H C? 2C? 2- ((4-CH2CH2C02Me-2,5-dio? O-1-Piz) 2-F H H 5-302 Ac H C? 2C? 2"((4-CH2CH2C02Me-2,5-dio? O-1-Piz) 2-F H H 5-303 H H C? 2C? 2- ((4-CH2CH2C02Et-2,5-dio? O-1-Piz) 2-F H H 5-304 Ac H C? 2C? 2- ((4-CH2CH2C02Et-2,5-dio? O-1-Piz) 2-F H H 5-305 H H C? 2CH2- ((4-CH2CH2CH2C02H-2,5-dio? O-1-Piz) 2-F H H 5-306 Ac H CH2CH2- ((4-CH2CH2CH2C? 2H-2,5-dio? O-1-Piz) 2-FHH 5-307 HH CH2CH2- (4-CH2CH2CH2C02Me-2,5-dioxo-1-Piz 2-FHH 5-308 Ac H CH2CH2- (4-CH2CH2CH2C? 2Me-2,5-dio? O-1-Piz) 2-F H H 5-309 H H CH2CH2- (4-CH2CH2CH2C? 2Et-2,5-dio? O-1-Piz) 2-F H H 5-310 Ac H CH2CH2- (4-CH2CH2CH2C02Et-2,5-dio? O-1-Piz) 2-F H H 5-311 H H CH2CH2-1-Pyrd 2-F H H 5-312 Ac H CH2CH2-1-Pyrd 2-F H H 5-313 H H CH2CH2- (2-C02H-1-Pyrd) 2-F H H 5-314 Ac H CH2CH2- (2-C02H-1-Pyrd) 2-F H H 5-315 H H CH2CH2- (2-C02Me-1 -Pyrd) 2-F H H 5-316 Ac H CH2CH2- (2-C02Me-1 -Pyrd) 2-F H H 5-317 H H CH2CH2- (2-C02Et-1 -Pyrd) 2-F H H 5-318 Ac H CH2CH2- (2-C02Et-1 -Pyrd) 2-F H H 5-319 H H CH2CH2- (2-CH2C02H-1 -Pyrd) 2-F H H 5-320 Ac H CH2CH2- (2-CH2C02H-1 -Pyrd) 2-F H H 5-321 H H CH2CH2- (2-CH2C02Me-1 -Pyrd) 2-F H H 5-322 Ac H CH2CH2- (2-CH2C02Me-1 -Pyrd) 2-F H H 5-323 H H CH2CH2- (2-CH2C02Et-1 -Pyrd) 2-F H H 5-324 Ac H CH2CH2- (2-CH2C02Et-1 -Pyrd) 2-F H H 5-325 H H CH2CH2- (2-CH2CH2C02H-1 -Pyrd) 2-F H H 5-326 Ac H CH2CH2- (2-CH2CH2C02H-1 -Pyrd) 2-F H H 5-327 H H CH2CH2- (2-CH2CH2C02Me-1 -Pyrd) 2-F H H 5-328 Ac H CH2CH2- (2-CH2CH2C? 2Me-1 -Pyrd) 2-F H H 5-329 H H CH2CH2- (2-CH2CH2C? 2Et-1 -Pyrd) 2-F H H 5-330 Ac H CH2CH2- (2-CH2CH2C02Et-1-Pyrd) 2-F H H 5-331 H H CH2CH2- (2-CH2CH2CH2C? 2H-1 -Pyrd) 2-F H H 5-332 Ac H CH2CH2- (2-CH2CH2CH2C02H-1-Pyrd) 2-F H H 5-333 H H CH2CH2- (2-CH2CH2CH2C02Me-1-Pyrd) 2-F H H 5-334 Ac H CH2CH2- (2-CH2CH2CH2C02Me-1-Pyrd) 2-F H H 5-335 H H CH2CH2- (2-CH2CH2CH2C02Et-1-Pyrd) 2-F H H 5-336 Ac H CH2CH2- (2-CH2CH2CH2C02Et-1-Pyrd) 2-F H H 5-337 H H CH2- (3-C02H-1-Pip) 2-F H H 5-338 Ac H CH2- (3-C02H-1-Pip) 2-F H H 5-339 H H CH2- (3-C02Me-1-Pip) 2-F H H 5-340 Ac H CH2- (3-C02Me-1-Pip) 2-F H H 5-341 H H CH2- (3-C02Et-1-Pip) 2-F H H 5-342 Ac H CH2- (3-C02Et-1-Pip) 2-F H H 5-343 H H CH2- (3-CH2C02H-1-Pp) 2-F H H 5-344 Ac H CH2- (3-CH2C02H-1-Pip) 2-F H H 5-345 H H CH2- (3-CH2C02Me-1-Pip) 2-F H H 5-346 Ac H CH2- (3-CH2C02Me-1-Pip) 2-F H H 5-347 H H CH2- (3-CH2C02Et-1-Pip) 2-F H H 5-348 Ac H CH2- (3-CH2C02Et-1-Pip) 2-F H H 5-349 H H CH2- (3-CH2CH2C02H-1-Pip) 2-F H H 5-350 Ac H CH2- (3-CH2CH2C02H-1-Pip) 2-F H H 5-351 H H CH2- (3-CH2CH2C02Me-1-Pip) 2-F H H 5-352 Ac H CH2- (3-CH2CH2C02Me-1-Pip) 2-F H H 5-353 H H CH2- (3-CH2CH2C02Et-1-Pip) 2-F H H 5-354 Ac H CH2- (3-CH2CH2C02Et-1-Pip) 2-F H H 5-355 HH CH2- (3-CH2CH2CH2C02H-1-Pip) 2-FHH 5-356 Ac H CH2- (3-CH2CH2CH2C02H-1-Pip) 2-FHH 5-357 HH CH2- (3-CH2CH2CH2C02Me-1 - Pip) 2-FHH 5-358 Ac H CH2- (3-CH2CH2CH2C02Me-1 -Pip) 2-F H H 5-359 H H CH2- (3-CH2CH2CH2C02Et-1 -Pip) 2-F H H 5-360 Ac H CH2- (3-CH2CH2CH2C02Et-1 -Pip) 2-F H H 5-361 H H CH2CH2- (3-C02H-1-Pip) 2-F H H 5-362 Ac H CH2CH2- (3-C02H-1-Pip) 2-F H H 5-363 H H CH2CH2- (3-C02Me-1-Pip) 2-F H H 5-364 Ac H CH2CH2- (3-C02Me-1-Pip) 2-F H H 5-365 H H CH2CH2- (3-C02Et-1-Pip) 2-F H H 5-366 Ac H CH2CH2- (3-C02Et-1-Pip) 2-F H H 5-367 H H CH2CH2- (3-CH2C02H-1 -Pip) 2-F H H 5-368 Ac H CH2CH2- (3-CH2C02H-1 -Pip) 2-F H H 5-369 H H CH2CH2- (3-CH2C02Me-1 -Pip) 2-F H H 5-370 Ac H CH2CH2- (3-CH2C02Me-1 -Pip) 2-F H H 5-371 H H CH2CH2- (3-CH2C02Et-1 -Pip) 2-F H H 5-372 Ac H CH2CH2- (3-CH2C02Et-1 -Pip) 2-F H H 5-373 H H CH2CH2- (3-CH2CH2C02H-1 -Pip) 2-F H H 5-374 Ac H CH2CH2- (3-CH2CH2C02H-1 -Pip) 2-F H H 5-375 H H CH2CH2- (3-CH2CH2C02Me-1 -Pip) 2-F H H 5-376 Ac H CH2CH2- (3-CH2CH2C02Me-1-Pip) 2-F H H 5-377 H H CH2CH2- (3-CH2CH2C02Et-1 -Pip) 2-F H H 5-378 Ac H CH2CH2- (3-CH2CH2C02Et-1 -Pip) 2-F H H 5-379 H H CH2CH2- (3-CH2CH2CH2C02H-1 -Pip) 2-F H H 5-380 Ac H CH2CH2- (3-CH2CH2CH2C02H-1 -Pip) 2 -FHH 5-381 HH CH2CH2- (3-CH2CH2CH2C02 e-1 -Pip) 2 -FHH 5-382 Ac H CH2CH2- (3-CH2CH2CH2C02Me- 1-Pip) 2-FHH 5-383 H H CH2CH2- (3-CH2CH2CH2C02Et-1-Pip) 2-F H H 5-384 Ac H CH2CH2- (3-CH2CH2CH2C? 2Et-1-Pip) 2-F H H 5-385 H H CH2- (4-OH-2-C02H-1-Pyrd) 2-F H H 5-386 Ac H CH2- (4-OH-2-C02H-1-Pyrd) 2-F H H 5-387 H H CH2- (4-OH-2-C02Me-1-Pyrd) 2-F H H 5-388 Ac H CH2- (4-OH-2-C02Me-1-Pyrd) 2-F H H 5-389 H H CH2- (4-OH-2-C02Et-1-Pyrd) 2-F H H 5-390 Ac H CH2- (4-OH-2-C02Et-1-Pyrd) 2-F H H (Table 6) Comp No. P1 R2 R3 X1 X2 X3 6-1 H H CH2-1-Pip 2-F H H 6-2 Ac H CH2-1-Pip 2-F H H 6-3 H H CH2- (4-C02H-1-Pip) 2-F H H 6-4 Ac H CH2- (4-C02H-1-Pip) 2-F H H 6-5 H H CH2- (4-C02Me-1-Pip) 2-F H H 6-6 Ac H CH2- (4-C02Me-1-Pip) 2-F H H 6-7 H H CH2- (4-C02Et-1-Pip) 2-F H H 6-8 Ac H CH2- (4-C02Et-1-Pip) 2-F H H 6-9 H H CH2- (4-CH2C02H-1-Pip) 2-F H H 6-10 Ac H CH2- (4-CH2C02H-1-Pip) 2-F H H 6-11 H H CH2- (4-CH2C02Me-1-Pip) 2-F H H 6-12 Ac H CH2- (4-CH2C02Me-1 -Pip) 2-F H H 6-13 H H CH2- (4-CH2C02Et-1-Pip) 2-F H H 6-14 Ac H CH2- (4-CH2C? 2Et-1-Pip) 2-F H H 6-15 H H CH2- (4-CH2CH2C? 2H-1 -Pip) 2-F H H 6-16 Ac H CH2- (4-CH2CH2C? 2H-1 -Pip) 2-F H H 6-17 H H CH2- (4-CH2CH2C? 2Me-1 -Pip) 2-F H H 6-18 Ac H CH2- (4-CH2CH2C? 2Me-1 -Pip) 2-F H H 6-19 H H CH2- (4-CH2CH2C02Et-1 -Pip) 2-F H H 6-20 Ac H CH2- (4-CH2CH2C02Et-1 -Pip) 2-F H H 6-21 H H CH2- (4-CH2CH2CH2C02H-1 -Pip) 2-F H H 6-22 Ac H CH2- (4-CH2CH2CH2C02H-1 -Pip) 2-F H H 6-23 H H CH2- (4-CH2CH2CH2C02Me-1 -Pip) 2-F H H 6-24 Ac H CH2- (4-CH2CH2CH2C02Me-1 -Pip) 2-F H H 6-25 H H CH2- (4-CH2CH2CH2C02Et-1 -Pip) 2-F H H 6-26 Ac H CH2- (4-CH2CH2CH2C02Et-1 -Pip) 2-F H H 6-27 H H CH2-Mor 2-F H H 6-28 Ac H CH2-Mor 2-F H H 6-29 H H CH2-Thim 2-F H H 6-30 Ac H CH2-Thim 2-F H H 6-31 H H CH2-1-Piz 2-F H H 6-32 Ac H CH2-I-PÍZ 2-F H H 6-33 H H CH2- (4-Ac-1-P yz) 2-F H H 6-34 Ac H CH2- (4-Ac-1-Piz) 2-F H H 6-35 H H CH2- (4-Ac-1-Piz) 2-F 4-F H 6-36 Ac H CH2- (4-Ac-1-Piz) 2-F 4-F H 6-37 H H CH2- (4-C02Me-1-Piz) 2-F H H 6-38 Ac H CH2- (4-C02Me-1-Piz) 2-F H H 6-39 H H CH2- (4-C02Et-1-Piz) 2-F H H 6-40 Ac H CH2- (4-C02Et-1-Piz) 2-F H H 6-41 H H CH2- (4-CH2C02H-1-Piz) 2-F H H 6-42 Ac H CH2- (4-CH2C02H-1-Piz) 2-F H H 6-43 H H CH2- (4-CH2C02Me-1 -Piz) 2-F H H 6-44 Ac H CH2- (4-CH2C02Me-1 -Piz) 2-F H H 6-45 H H CH2- (4-CH2C02Et-1-Piz) 2-F H H 6-46 Ac H CH2- (4-CH2C02Et-1-Piz) 2-F H H 6-47 H H CH2- (4-CH2CH2C02H-1 -Piz) 2-F H H 6-48 Ac H CH2- (4-CH2CH2C02H-1 -Piz) 2-F H H 6-49 H H CH2- (4-CH2CH2C02Me-1 -Piz) 2-F H H 6-50 Ac H CH2- (4-CH2CH2C02Me-1 -Piz) 2-F H H 6-51 H H CH2- (4-CH2CH2C02Et-1 -Piz) 2-F H H 6-52 Ac H CH2- (4-CH2CH2C02Et-1 -Piz) 2-F H H 6-53 H H CH2- (4-CH2CH2CH2C02H-1 -Piz) 2-F H H 6-54 Ac H CH2- (4-CH2CH2CH2C02H-1 -Piz) 2-F H H 6-55 H H CH2- (4-CH2CH2CH2C? 2Me-1 -Piz) 2-F H H 6-56 Ac H CH2- (4-CH2CH2CH2C02Me-1 -Piz) 2-F H H 6-57 H H CH2- (4-CH2CH2CH2C? 2Et-1-P¡z) 2-F H H 6-58 Ac H CH2- (4-CH2CH2CH2C? 2Et-1 -Piz) 2-F H H 6-59 H H CH2- (2-oxo-1-Piz) 2-F H H 6-60 Ac H CH2- (2-oxo-1-Piz) 2-F H H 6-61 H H CH2- (4-Ac-2-oxo-1-Piz) 2-F H H 6-62 Ac H CH2- (4-Ac-2-oxo-1-Piz) 2-F H H 6-63 H H CH2- (4-Ac-2-oxo-1-Piz) 2-F 4-F H 6-64 Ac H CH2- (4-Ac-2-oxo-1-Piz) 2-F 4-F H 6-65 H H CH2- (4-C02Me-2-oxo-1 -Piz) 2-F H H 6-66 Ac H CH2- (4-C02Me-2-o? O-1 -Piz) 2-F H H 6-67 H H CH2- (4-C02Et-2-oxo-1 -Piz) 2-F H H 6-68 Ac H CH2- (4-C02Et-2-oxo-1 -Piz) 2-F H H 6-69 H H CH2- (4-CH2C02H-2-oxo-1 -Piz) 2-F H H 6-70 Ac H CH2- (4-CH2C02H-2-oxo-1-Piz) 2-F H H 6-71 H H CH2- (4-CH2C02Me-2-oxo-1 -Piz) 2-F H H 6-72 Ac H CH2- (4-CH2C02Me-2-o? O-1 -Piz) 2-F H H 6-73 H H CH2- (4-CH2C02Et-2-oxo-1 -Piz) 2-F H H 6-74 Ac H CH2- (4-CH2C02Et-2-oxo-1 -Piz) 2-F H H 6-75 H H CH2- (4-CH2CH2C02H-2-o? O-1 -Piz) 2-F H H 6-76 Ac H CH2- (4-CH2CH2C02H-2-o? O-1 -Piz) 2-F H H 6-77 H H CH2- (4-CH2CH2C? 2Me-2-o? O-1 -Piz) 2-F H H 6-78 Ac H CH2- (4-CH2CH2C? 2Me-2-o? O-1 -Piz) 2-F H H 6-79 H H CH2- (4-CH2CH2C? 2Et-2-o? O-1 -Piz) 2-F H H 6-80 Ac H CH2- (4-CH2CH2C02Et-2-o? O-1 -Piz) 2-F H H 6-81 H H CH2- (4-CH2CH2CH2C02H-2-oxo-1-Piz) 2-F H H 6-82 Ac H CH2- (4-CH2CH2CH2C02H-2-o? O-1-Piz) 2-F H H 6-83 H H CH2- (4-CH2CH2CH2C02Me-2-oxo- 'I-Piz) 2-F H H 6-84 Ac H CH2- (4-CH2CH2CH2C? 2Me-2-o? O- 'I-Piz) 2-F H H 6-85 H H CH2- (4-CH2CH2CH2C? 2Et-2-o? O-1 -Piz) 2-F H H 6-86 Ac H CH2- (4-CH2CH2CH2C? 2Et-2-oxo-1 -Piz) 2-F H H 6-87 H H CH2- (3-o? O-1-Piz) 2-F H H 6-88 Ac H CH2- (3-o? O-1-Piz) 2-F H H 6-89 H H CH2- (4-Ac-3-oxo-1-Piz) 2-F H H 6-90 Ac H CH2- (4-Ac-3-o? O-1-Piz) 2-F H H 6-91 H H CH2- (4-Ac-3-o? O-1-Piz) 2-F 4-F H 6-92 Ac H CH2- (4-Ac-3-oxo-1-Piz) 2-F 4-F H 6-93 H H CH2- (4-C0Me-3-oxo-1-Piz) 2-F H H 6-94 Ac H CH2- (4-C02Me-3-o? O-1-Piz) 2-F H H 6-95 H H CH2- (4-C02Et-3-oxo-1-Piz) 2-F H H 6-96 Ac H CH2- (4-C02Et-3-oxo-1-Piz) 2-F H H 6-97 H H CH2- (4-CH2C02H-3-o? O-1-Piz) 2-F H H 6-98 Ac H CH2- (4-CH2C02H-3-oxo-1-Piz) 2-F H H 6-99 H H CH2- (4-CH2C02Me-3-o? O-1-Piz) 2-F H H 6-100 Ac H CH2- (4-CH2C02Me-3-o? O-1-Piz) 2-F H H 6-101 H H CH2- (4-CH2C02Et-3-oxo-1-Piz) 2-F H H 6-102 Ac H CH2- (4-CH2C02Et-3-o? O-1-Piz) 2-F H H 6-103 H H CH2- (4-CH2CH2C? 2H-3-o? O-1-Piz) 2-F H H 6-104 Ac H CH2- (4-CH2CH2C? 2H-3-o? O-1-Piz) 2-F H H 6-105 H H CH2- (4-CH2CH2C? 2Me-3-o? O-1-Piz) 2-F H H 6-106 Ac H CH2- (4-CH2CH2C02Me-3-oxo-1-Piz) 2-F H H 6-107 H H CH2- (4-CH2CH2C02Et-3-oxo-1-Piz) 2-F H H 6-108 Ac H CH2- (4-CH2CH2C? 2Et-3-oxo-1-Piz) 2-F H H 6-109 H H CH2- (4-CH2CH2CH2C02H-3-oxo-1-Piz) 2-F H H 6-110 Ac H CH2- (4-CH2CH2CH2C? 2H-3-o? O-1-Piz) 2-F H H 6-111 H H CH2- (4-CH2CH2CH2C02Me-3-o? O-1-Piz) 2-F H H 6-112 Ac H CH2- (4-CH2CH2CH2C? 2Me-3-o? O-1-Piz) 2-F H H 6-113 H H CH2- (4-CH2CH2CH2C02Et-3-oxo-1-Piz) 2-F H H 6-114 Ac H CH2- (4-CH2CH2CH2C02Et-3-oxo-1-Piz) 2-F H H 6-115 H H CH2- (2,5-dio? O-1-Piz) 2-F H H 6-116 Ac H CH2- (2,5-dioxo-1-Piz) 2-F H H 6-117 H H CH2- (4-Ac-2,5-dioxo-1-Piz) 2-F H H 6-118 Ac H CH2- (4-Ac-2,5-dioxo-1-Piz) 2-F H H 6-119 H H CH2- (4-Ac-2,5-dioxo-1-Piz) 2-F 4-F H 6-120 Ac H CH2- (4-Ac-2,5-dioxo-1-Piz) 2-F 4-F H 6-121 H H CH2- (4-C02Me-2,5-dioxo-1-Piz) 2-F H H 6-122 Ac H CH2- (4-C02Me-2,5-dio? O-1-Piz) 2-F H H 6-123 H H CH2- (4-C02Et-2,5-dioxo-1-Piz) 2-F H H 6-124 Ac H CH2- (4-C02Et-2,5-dioxo-1-Piz) 2-F H H 6-125 H H CH2- (4-CH2C02H-2,5-dioxo-1-Piz) 2-F H H 6-126 Ac H CH2- (4-CH2C02H-2,5-dioxo-1-Piz) 2-F H H 6-127 H H CH2- (4-CH2C02Me-2,5-dioxo-1-Piz) 2-F H H 6-128 Ac H CH2- (4-CH2C02Me-2,5-dioxo-1-Piz 2-F H H 6-130 Ac H CH2- (4-CH2C02Et-2,5-dioxo-1-Piz) 2-F H H 6-131 HH CH2- (4-CH2CH2C02H-2,5-dioxo-1-Piz) 2-FHH 6-132 Ac H CH2- (4-CH2CH2C? 2H-2,5-dio? O-1-Piz) 2-FHH 6-133 H H CH2- (4-CH2CH2C? 2Me-2,5-dio? O-1-Piz) 2-F H H 6-134 Ac H CH2- (4-CH2CH2C? 2Me-2,5-dio? O-1-Piz) 2-F H H 6-135 H H CH2- (4-CH2CH2C? 2Et-2,5-dioxo-1-Piz) 2-F H H 6-136 Ac H CH2- (4-CH2CH2C02Et-2,5-dioxo-1-Piz) 2-F H H 6-137 H H CH2- (4-CH2CH2CH2C02H-2,5-dio? O-1-Piz) 2-F H H 6-138 Ac H CH2- (4-CH2CH2CH2C02H-2,5-dio? O-1-Piz) 2-F H H 6-139 H H CH2- (4-CH2CH2CH2C02Me-2,5-dio? O-1-Piz) 2-F H H 5-140 Ac H CH2- (4-CH2CH2CH2C02Me-2,5-dio? O-1-Piz) 2-F H H 6-141 H H CH2- (4-CH2CH2CH2C? 2Et-2,5-d¡o? O-1-Piz) 2-F H H 6-142 Ac H CH2- (4-CH2CH2CH2C? 2Et-2,5-dio? O-1-P¡z) 2-F H H 6-143 H H CH2-1-Pyrd 2-F H H 6-144 Ac H CH2-1-Pyrd 2-F H H 6-145 H H CH2- (2-C02H-1-Pyrd) 2-F H H 6-146 Ac H CH2- (2-C02H-1-Pyrd) 2-F H H 6-147 H H CH2- (2-C02Me-1-Pyrd) 2-F H H 6-148 Ac H CH2- (2-C02Me-1-Pyrd) 2-F H H 6-149 H H CH2- (2-C02Et-1-Pyrd) 2-F H H 6-150 Ac H CH2- (2-C02Et-1-Pyrd) 2-F H H 6-151 H H CH2- (2-CH2C02H-1-Pyrd) 2-F H H 6-152 Ac H CH2- (2-CH2C02H-1-Pyrd) 2-F H H 6-153 H H CH2- (2-CH2C02Me-1 -Pyrd) 2-F H H 6-154 Ac H CH2- (2-CH2C02Me-1 -Pyrd) 2-F H H 6-155 H H CH2- (2-CH2C02Et-1 -Pyrd) 2-F H H 6-156 Ac H CH2- (2-CH2C02Et-1 -Pyrd) 2-F H H 6-157 H H CH2- (2-CH2CH2C02H-1 -Pyrd) 2-F H H 6-158 Ac H CH2- (2-CH2CH2C02H-1 -Pyrd) 2-F H H 6-159 H H CH2- (2-CH2CH2C02Me-1 -Pyrd) 2-F H H 6-160 Ac H CH2- (2-CH2CH2C02Me-1 -Pyrd) 2-F H H 6-161 H H CH2- (2-CH2CH2C02Et-1 -Pyrd) 2-F H H 6-162 Ac H CH2- (2-CH2CH2C02Et-1 -Pyrd) 2-F H H 6-163 H H CH2- (2-CH2CH2CH2C? 2H-1 -Pyrd) 2-F H H 6-164 Ac H CH2- (2-CH2CH2CH2C? 2H-1 -Pyrd) 2-F H H 6-165 H H CH2- (2-CH2CH2CH2C02Me-1 -Pyrd) 2-F H H 6-166 Ac H CH2- (2-CH2CH2CH2C02Me-1 -Pyrd) 2-F H H 6-167 H H CH2- (2-CH2CH2CH2C02Et-1 -Pyrd) 2-F H H 6-168 Ac H CH2- (2-CH2CH2CH2C02Et-1 -Pyrd) 2-F H H 6-169 H H CH2CH2-1-Pip 2-F H H 6-170 Ac H CH2CH2-1-Pip 2-F H H 6-171 H H CH2CH2- (4-C02H-1-Pip) 2-F H H 6-172 Ac H CH2CH2- (4-C02H-1-Pip) 2-F H H 6-173 H H CH2CH2- (4-C02Me-1-Pip) 2-F H H 6-174 Ac H CH2CH2- (4-C02Me-1-Pip) 2-F H H 6-175 H H CH2CH2- (4-C02Et-1-Pip) 2-F H H 6-176 Ac H CH2CH2- (4-C02Et-1-Pip) 2-F H H 6-177 H H CH2CH2- (4-CH2C02H-1 -Pip) 2-F H H 6-178 Ac H CH2CH2- (4-CH2C02H-1 -Pip) 2-F H H 6-179 H H CH2CH2- (4-CH2C? 2Me-1 -Pip) 2-F H H 6-180 Ac H CH2CH2- (4-CH2C? 2Me-1 -Pip) 2-F H H 6-181 H H CH2CH2- (4-CH2C02Et-1 -Pip) 2-F H H 6-182 Ac H CH2CH2- (4-CH2C? 2Et-1 -Pip) 2-F H H 6-183 H H CH2CH2- (4-CH2CH2C02H-1 -Pip) 2-F H H 6-184 Ac H CH2CH2- (4-CH2CH2C02H-1 -Pip) 2-F H H 6-185 H H CH2CH2- (4-CH2CH2C02Me-1 -Pip) 2-F H H 6-186 Ac H CH2CH2- (4-CH2CH2C02Me-1 -Pip) 2-F H H 6-187 H H CH2CH2- (4-CH2CH2C02Et-1 -Pip) 2-F H H 6-188 Ac H CH2CH2- (4-CH2CH2C? 2Et-1 -Pip) 2-F H H 6-189 H H CH2CH2- (4-CH2CH2CH2C? 2H-1 -Pip) 2-F H H 6-190 Ac H CH2CH2- (4-CH2CH2CH2C? 2H-1 -Pip) 2-F H H 6-191 H H CH2CH2- (4-CH2CH2CH2C? 2Me-1 -Pip) 2-F H H 6-192 Ac H CH2CH2- (4-CH2CH2CH2C02Me-1 -Pip) 2-F H H 6-193 H H CH2CH2- (4-CH2CH2CH2C? 2Et-1 -Pip) 2-F H H 6-194 Ac H CH2CH2- (4-CH2CH2CH2C? 2Et-1 -Pip) 2-F H H 6-195 H H CH2CH2-Mor 2-F H H 6-196 Ac H CH2CH2-Mor 2-F H H 6-197 H H CH2CH2-Thm 2 -F H H 6-198 Ac H CH2CH2-Thim 2-F H H 6-199 H H CH2CH2-1-Piz 2-F H H 6-200 Ac H CH2CH2-1-Piz 2-F H H 6-201 H H CH2CH2- (4-Ac-1-Piz) 2-F H H 6-202 Ac H CH2CH2- (4-Ac-1-Piz) 2-F H H 6-203 H H CH2CH2- (4-Ac-1-Piz) 2-F 4-F H 6-204 Ac H CH2CH2- (4-Ac-1-Piz) 2-F 4-F H 6-205 H H CH2CH2- (4-C02Me-1-Piz) 2-F H H 6-206 Ac H CH2CH2- (4-C02Me-1-Piz) 2-F H H 6-207 H H CH2CH2- (4-C02Et-1-Piz) 2-F H H 6-208 Ac H CH2CH2- (4-C02Et-1-Piz) 2-F H H 6-209 H H CH2CH2- (4-CH2C02H-1 -Piz) 2-F H H 6-210 Ac H CH2CH2- (4-CH2C02H-1 -Piz) 2-F H H 6-211 H H CH2CH2- (4-CH2C02Me-1 -Piz) 2-F H H 6-212 Ac H CH2CH2- (4-CH2C02Me-1 -Piz) 2-F H H 6-213 H H CH2CH2- (4-CH2C? 2Et-1 -Piz) 2-F H H 6-214 Ac H CH2CH2- (4-CH2C? 2Et-1 -Piz) 2-F H H 6-215 H H CH2CH2- (4-CH2CH2C02H-1 -Piz) 2-F H H 6-216 Ac H CH2CH2- (4-CH2CH2C02H-1 -Piz) 2-F H H 6-217 H H CH2CH2- (4-CH2CH2C? 2Me-1 -Piz) 2-F H H 6-218 Ac H CH2CH2- (4-CH2CH2C02Me-1 -Piz) 2-F H H 6-219 H H CH2CH2- (4-CH2CH2C02Et-1 -Piz) 2-F H H 6-220 Ac H CH2CH2- (4-CH2CH2C02Et-1 -Piz) 2-F H H 6-221 H H CH2CH2- (4-CH2CH2CH2C02H-1 -Piz) 2-F H H 6-222 Ac H CH2CH2- (4-CH2CH2CH2C02H-1 -Piz) 2-F H H 6-223 H H CH2CH2- (4-CH2CH2CH2C02Me-1 -Piz) 2-F H H 6-224 Ac H CH2CH2- (4-CH2CH2CH2C? 2Me-1 -Piz) 2-F H H 6-225 H H CH2CH2- (4-CH2CH2CH2C02Et-1 -Piz) 2-F H H 6-226 Ac H CH2CH2- (4-CH2CH2CH2C02Et-1 -Piz) 2-F H H 6-227 H H CH2CH2- (2-o? O-1-Piz) 2-F H H 6-228 Ac H CH2CH2- (2-o? O-1-Piz) 2-F H H 6-229 H H CH2CH2- (4-Ac-2-oxo-1 -Piz) 2-F H H 6-230 Ac H CH2CH2- (4-Ac-2-oxo-1 -Piz) 2-FHH 6-231 HH CH2CH2- (4-Ac-2-oxo-1 -Piz) 2-F 4 -FH 6- 232 Ac H CH2CH2 - ((4'-Ac-2-o? O-1-Piz) 2-F 4-FH 6-233 H H CH2CH2- (('4-C02Me-2-oxo-1-Piz) 2-F H H 6-234 Ac H Cp2CH2- ((4-C02Me-2-o? O-1-Piz) 2-F H H 6-235 H H CH2CH2- (('4-C02Et-2-oxo-1-Piz) 2-F H H 6-236 Ac H CH2CH- (('4-C02Et-2-oxo-1-Piz) 2-F H H 6-237 H H CH2CH2- (('4-CH2C02H-2-oxo-1-Piz) 2-F H H 6-238 Ac H Cp2CH2- (('4-CH2C02H-2-o? O-1-Piz) 2-F H H 6-239 H H Cp2Cp2- (('4-CH2C02Me-2-oxo-1-Piz) 2-F H H 6-240 Ac H CH2CH2- (('4-CH2C02Me-2-oxo-1-Piz) 2-F H H 6-241 H H CH2CH2- (('4-CH2C02Et-2-0X0-1-Piz) 2-F H H 6-242 Ac H CH2CH2- ((4-CH2C02Et-2-oxo-1-Piz) 2-F H H 6-243 H H Cp2CH2- ((4-CH2CH2C02H-2-o? O-1-Piz) 2-F H H 6-244 Ac H CH2CH2- ((4-CH2CH2C02H-2-oxo-1-Piz) 2-F H H 6-245 H H Cp2CH2- ((4-CH2CH2C02Me-2-oxo-1-Piz) 2-F H H 6-246 Ac H CH2CH2- ((4-CH2CH2C02Me-2-oxo-1-Piz) 2-F H H 6-247 H H CH2CH2- ((4-CH2CH2C02Et-2-oxo-1-Piz) 2-F H H 6-248 Ac H CHCH2- ((4-CH2CH2C? 2Et-2-o? O-1-Piz) 2-F H H 6-249 H H CH2CH2- < (4-CH2CH2CH2C02H-2-oxo-1-Piz) 2-F H H 6-250 Ac H CH2CH2- ((4-CH2CH2CH2C? 2H-2-o? O-1-Piz) 2-F H H 6-251 H H CH2CH2- ((4-CH2CH2CH2C02Me-2-oxo-1-Piz) 2-F H H 6-252 Ac H CH2CH2- ((4-CH2CH2CH2C02Me-2-oxo-1-Piz) 2-F H H 6-253 H H CH2OH2- ((4-CH2CH2CH2C02Et-2-oxo-1-Piz) 2-F H H 6-254 Ac H CH2CH2- ((4-CH2CH2CH2C02Et-2-o? O-1-Piz) 2-F H H 6-255 H H CH2CH2- ((3-0X0-1 -Piz) 2-F H H 6-256 Ac H CH2CH2- ((3-o? O-1-Piz) 2-F H H 6-257 H H CH2CH2-1 (4-Ac-3-oxo-1-Piz) 2-F H H 6-258 Ac H CH2CH2 (4-Ac-3-oxo-1-Piz) 2-F H H 6-259 H H CH2CH2 (4-Ac-3-oxo-1-Piz) 2-F 4-F H 6-260 Ac H CH2CH2-? (4-Ac-3-o? O-1-Piz) 2-F 4-F H 6-261 H H CH2CH2 '(4-C02Me-3-oxo-1-Piz) 2-F H H 6-262 Ac H CH2CH2-? (4-C02Me-3-oxo-1-Piz) 2-F H H 6-263 H H CH2CH2 (4-C02Et-3-oxo-1-Piz) 2-F H H 6-264 Ac H CH2CH2-? (4-C02Et-3-oxo-1-Piz) 2-F H H 6-265 H H CH2CH2 '(4-CH2C02H-3-oxo-1-Piz) 2-F H H 6-266 Ac H CH2CH2? (4-CH2C02H-3-oxo-1-Piz) 2-F H H 6-267 H H CH2CH2- (4-CH2C02Me-3-oxo-1-Piz) 2-F H H 6-268 Ac H CH2CH2 '(4-CH2C02Me-3-oxo-1-Piz) 2-F H H 6-269 H H CH2CH2-? (4-CH2C02Et-3-o? O-1-Piz) 2-F H H 6-270 Ac H CH2CH2 (4-CH2C02Et-3-oxo-1-Piz) 2-F H H 6-271 H H CH2CH2-? (4-CH2CH2CO2H-3-OXO-I-PÍZ) 2-F H H 6-272 Ac H CH2CH2 '(4-CH2CH2C02H-3-o? O-1-Piz) 2-F H H 6-273 H H CH2Cp2 '(4-CH2CH2C02Me-3-oxo-1-Piz) 2-F H H 6-274 Ac H CH2CH2- (4-CH2CH2C02Me-3-oxo-1-Piz) 2-F H H 6-275 H H CH2CH2 '(4-CH2CH2C02Et-3-oxo-1-P yz) 2-F H H 6-276 Ac H CH2CH2H (4-CH2CH2C? 2Et-3-o? O-1-P yz) 2-F H H 6-277 H H CH2CH2- (? 4-CH2CH2CH2C? 2H-3-o? O-1-P¡z) 2-F H H 6-278 Ac H CH2CH2-? (4-CH2CH2CH2CO2H-3-OXO-I-PÍZ) 2-F H H 6-279 H H CH2CH2 (4-CH2CH2CH2C? 2Me-3-o? O-1-Piz) 2-F H H 6-280 Ac H CH CH2-? (4-CH2CH2CH2C02Me-3-o? O-1-Piz) 2-F H H 6-281 H H CH2CH2 '(4-CH2CH2CH2C02Et-3-oxo-1-Piz) 2-F H H 6-282 Ac H CH2CH2- (4-CH2CH2CH2C02Et-3-oxo-1-Piz) 2-F H H 6-283 H H CH2CH2- (2,5-dioxo-1-Piz) 2-F H H 6-284 Ac H CH2CH2- (2,5-dioxo-1-Piz) 2-F H H 6-285 H H CH2CH2- (4-Ac-2,5-dioxo-1-Piz) 2-F H H 6-286 Ac H CH2CH2- (4-Ac-2,5-dioxo-1-Piz) 2-F H H 6-287 H H CH2CH2- (4-Ac-2,5-dioxo-1-Piz) 2-F 4-F H 6-288 Ac H CH2CH2- (4-Ac-2,5-dioxo-1-Piz) 2-F 4-F H 6-289 H H CH2CH2- (4-C02Me-2,5-dioxo-1-Piz) 2-F H H 6-290 Ac H CH2CH2- (4-C02Me-2,5-dioxo-1-Piz) 2-F H H 6-291 H H CH2CH2- (4-C02Et-2,5-dioxo-1-Piz) 2-F H H 6-292 Ac H CH2CH2- (4-C02Et-2,5-dio? O-1-Piz) 2-F H H 6-293 H H CH2CH2- (4-CH2C02H-2,5-dio? O-1-Piz) 2-F H H 6-294 Ac H CH2CH2- (4-CH2C02H-2,5-dio? O-1-Piz) 2-F H H 6-295 HH CH2CH2- (4-CH2C? 2Me-2,5-dioxo-1-Piz) 2 -FHH 6-296 Ac H CH2CH2- (4-CH2C? 2Me-2,5-dioxo-1-Piz) 2-FHH 6-297 H H CH2CH2- (4-CH2C02Et-2,5-d¡oxo-1-P¡z) 2-F H H 6-298 Ac H CH2CH2- (4-CH2C? 2Et-2,5-dioxo-1-Piz) 2-F H H 6-299 H H CH2CH2- (4-CH2CH2C02H-2,5-d -oxo-1-P yz) 2-F H H 6-300 Ac H CH2CH2- (4-CH2CH2C? 2H-2,5-dioxo-1-Piz) 2-FHH 6-301 HH CH2CH2- (4-CH2CH2C02Me-2,5-dio? O-1-Piz) 2-FHH 6-302 Ac H CH2CH2- (4-CH2CH2C? 2Me-2,5-dioxo-1-Piz) 2-F H H 6-303 H H CH2CH2- (4-CH2CH2C02Et-2,5-dÍ0X0-1-Piz) 2-F H H 6-304 Ac H CH2CH2- (4-CH2CH2C? 2Et-2,5-dioxo-1-P yz) 2-F H H 6-305 HH CH2CH2- (4-CH2CH2CH2C? 2H-2,5-di? Xo-1-P¡z) 2-FHH 6-306 Ac H CH2CH2- (4-CH2CH2CH2C02H-2,5-d -oxo- 1-Pi) 2-FHH 6-307 HH CH2CH2- (4-CH2CH2CH2C? 2Me-2,5-d -oxo-1 -Piz) 2-FHH 6-308 Ac H CH2CH2- (4-CH2CH2CH2C? 2Me-2,5-dio? O-1 -Piz) 2-F H H 6-309 H H CH2CH2- (4-CH2CH2CH2C? 2Et-2,5-dioxo-1-Piz) 2-F H H 6-310 Ac H CH2CH2- (4-CH2CH2CH2C02Et-2,5-dioxo-1- Piz) 2-F H H 6-311 H H CH2CH2-1-Pyrd 2-F H H 6-312 Ac H CH2CH2-1-Pyrd 2-F H H 6-313 H H CH2CH2- (2-C02H-1-Pyrd) 2-F H H 6-314 Ac H CH2CH2- (2-C02H-1-Pyrd) 2-F H H 6-315 H H CH2CH2- (2-C02Me-1 -Pyrd) 2-F H H 6-316 Ac H CH2CH2- (2-C02Me-1 -Pyrd) 2-F H H 6-317 H H CH2CH2- (2-C02Et-1-Pyrd) 2-F H H 6-318 Ac H CH2CH2- (2-C02Et-1 -Pyrd) 2-F H H 6-319 H H CH2CH2- (2-CH2C02H-1 -Pyrd) 2-F H H 6-320 Ac H CH2CH2- (2-CH2C02H-1-Pyrd) 2-F H H 6-321 H H CH2CH2- (2-CH2C02Me-1 -Pyrd) 2-F H H 6-322 Ac H CH2CH2- (2-CH2C02Me-1 -Pyrd) 2-F H H 6-323 H H CH2CH2- (2-CH2C02Et-1-Pyrd) 2-F H H 6-324 Ac H CH2CH2- (2-CH2C02Et-1-Pyrd) 2-F H H 6-325 H H CH2CH2- (2-CH2CH2C? 2H-1 -Pyrd) 2-F H H 6-326 Ac H CH2CH2- (2-CH2CH2C02H-1 -Pyrd) 2-F H H 6-327 H H CH2CH2- (2-CH2CH2C02Me-1-Pyrd) 2-F H H 6-328 Ac H CH2CH2- (2-CH2CH2C? 2Me-1 -Pyrd) 2-F H H 6-329 H H CH2CH2- (2-CH2CH2C02Et-1 -Pyrd) 2-F H H 6-330 Ac H CH2CH2- (2-CH2CH2C02Et-1 -Pyrd) 2-F H H 6-331 H H CH2CH2- (2-CH2CH2CH2C02H-1 -Pyrd) 2-F H H 6-332 Ac H CH2CH2- (2-CH2CH2CH2C02H-1 -Pyrd) 2-F H H 6-333 H H CH2CH2- (2-CH2CH2CH2C? 2Me-1 -Pyrd) 2-F H H 6-334 Ac H CH2CH2- (2-CH2CH2CH2C02Me-1-Pyrd) 2-F H H 6-335 H H CH2CH2- (2-CH2CH2CH2C? 2Et-1-Pyrd) 2-F H H 6-336 Ac H CH2CH2- (2-CH2CH2CH2C02Et-1-Pyrd) 2-F H H 6-337 H H CH2- (3-C02H-1-Pip) 2-F H H 6-338 Ac H CH2- (3-C02H-1-Pip) 2-F H H 6-339 H H CH2- (3-C02Me-1-Pip) 2-F H H 6-340 Ac H CH2- (3-C02Me-1-Pip) 2-F H H 6-341 H H CH2- (3-C02Et-1-Pip) 2-F H H 6-342 Ac H CH2- (3-C02Et-1-Pip) 2-F H H 6-343 H H CH2- (3-CH2C02H-1-Pp) 2-F H H 6-344 Ac H CH2- (3-CH2C02H-1-Pp) 2-F H H 6-345 H H CH2- (3-CH2C02Me-1-Pip) 2-F H H 6-346 Ac H CH2- (3-CH2C02Me-1-Pip) 2-F H H 6-347 H H CH2- (3-CH2C02Et-1-Pip) 2-F H H 6-348 Ac H CH2- (3-CH2C02Et-1-Pp) 2-F H H 6-349 H H CH2- (3-CH2CH2C02H-1 -Pip) 2-F H H 6-350 Ac H CH2- (3-CH2CH2C02H-1 -Pip) 2-F H H 6-351 H H CH2- (3-CH2CH2C02Me-1 -Pip) 2-F H H 6-352 Ac H CH2- (3-CH2CH2C02Me-1 -Pip) 2-F H H 6-353 H H CH2- (3-CH2CH2C02Et-1 -Pip) 2-F H H 6-354 Ac H CH2- (3-CH2CH2C02Et-1 -Pip) 2-F H H 6-355 H H CH2- (3-CH2CH2CH2C02H-1 -Pip) 2-F H H 6-356 Ac H CH2- (3-CH2CH2CH2C02H-1 -Pip) 2-F H H 6-357 H H CH2- (3-CH2CH2CH2C02Me-1 -Pip) 2-F H H 6-358 Ac H CH2- (3-CH2CH2CH2C02Me-1 -Pip) 2-F H H 6-359 H H CH2- (3-CH2CH2CH2C? 2Et-1 -Pip) 2-F H H 6-360 Ac H CH2- (3-CH2CH2CH2C02Et-1 -Pip) 2-F H H 6-361 H H CH2CH2- (3-C02H-1-Pp) 2-F H H 6-362 Ac H CH2CH2- (3-C02H-1-Pip) 2-F H H 6-363 H H CH2CH2- (3-C02Me-1-Pip) 2-F H H 6-364 Ac H CH2CH2- (3-C02Me-1-Pip) 2-F H H 6-365 H H CH2CH2- (3-C02Et-1-Pip) 2-F H H 6-366 Ac H CH2CH2- (3-C02Et-1-Pip) 2-F H H 6-367 H H CH2CH2- (3-CH2C02H-1 -Pip) 2-F H H 6-368 Ac H CH2CH2- (3-CH2C02H-1 -Pip) 2-F H H 6-369 H H CH2CH2- (3-CH2C02Me-1 -Pip) 2-F H H 6-370 Ac H CH2CH2- (3-CH2C02Me-1 -Pip) 2-F H H 6-371 H H CH2CH2- (3-CH2C02Et-1 -Pip) 2-F H H 6-372 Ac H CH2CH2- (3-CH2C02Et-1 -Pip) 2-F H H 6-373 H H CH2CH2- (3-CH2CH2C02H-1 -Pip) 2-F H H 6-374 Ac H CH2CH2- (3-CH2CH2C02H-1 -Pip) 2-F H H 6-375 H H CH2CH2- (3-CH2CH2C? 2Me-1 -Pip) 2-F H H 6-376 Ac H CH2CH2- (3-CH2CH2C02Me-1 -Pip) 2-F H H 6-377 H H CH2CH2- (3-CH2CH2C02Et-1 -Pip) 2-F H H 6-378 Ac H CH2CH2- (3-CH2CH2C02Et-1 -Pip) 2-F H H 6-379 H H CH2CH2- (3-CH2CH2CH2C02H-1 -Pip) 2-F H H 6-380 Ac H CH2CH2- (3-CH2CH2CH2C02H-1 -Pip) 2 -FHH 6-381 HH CH2CH2- (3-CH2CH2CH2C? 2Me-1 -Pip) 2 -FHH 6-382 Ac H CH2CH2- (3-CH2CH2CH2C 2Me-1-Pip) 2-FHH 6-383 H H CH2CH2- (3-CH2CH2CH2C? 2Et-1-Pip) 2-F H H 6-384 Ac H CH2CH2- (3-CH2CH2CH2C02Et-1-Pip) 2-F H H 6-385 H H CH2- (4-OH-2-C02H-1-Pyrd) 2-F H H 6-386 Ac H CH2- (4-OH-2-C02H-1-Pyrd) 2-F H H 6-387 H H CH2- (4-OH-2-C02Me-1-Pyrd) 2-F H H 6-388 Ac H CH2- (4-OH-2-C02Me-1-Pyrd) 2-F H H 6-389 H H CH2- (4-OH-2-C02Et-1-Pyrd) 2-F H H 6-390 Ac H CH2- (4-OH-2-C02Et-1-Pyrd) 2-F H H The numbers of the compounds, of the example compounds obtained by substituting a cyclopropyl group of the example compounds numbers 1-1 to 1-1084, 2-1 to 2-1084, 3-1 to 3-79, 4-1 to 4-79, 5-1 to 5-390 and 6-1 to 6-390 in Tables 1 to 6 with a Metho? I group, are respectively 7-1 to 7-1084, 8-1 to 8-1084, 9-1 to 9-79, 10-1 to 10-79, 11-1 to 11-390 and 12-1 to 12-390. For example, a compound obtained by substituting a cyclopropyl group of the example compound No. 5-103 in Table 7 with a methoi group, is an example compound No. 11-103. Among the above compounds, preferred compounds are the example compounds numbers 1-1, 1-2, 1-5, 1-6, 1-9, 1-10, 1-13, 1-14, 1-17, 1-18, 1-21, 1-22, 1-25, 1-26, 1-29, 1-30, 1-33, 1-34, 1 -37, 1-38, 1-41, 1-42, 1-45, 1-46, 1-49, 1-50, 1-53, 1-54, 1-57, 1-58, 1-61 , 1-62, 1-87, 1-88, 1-115, 1-116, 1-121, 1-122, 1-127, 1-128, 1-133, 1-134, 1-139, 1 -140, 1-187, 1-188, 1-207, 1-208, 1-209, 1-210, 1-211, 1-212, 1-337, 1-338, 1-351, 1-352 , 1-353, 1-354, 1-355, 1-356, 1-443, 1-444, 1-445, 1-446, 1-447, 1-448, 1-485, 1-486, 1 -487, 1-488, 1-489, 1-490, 1-491, 1-492, 1-493, 1-494, 1-495, 1-496, 1-497, 1-498, 1-499 , 1-500, 1-501, 1-502, 1-503, 1-504, 1-537, 1-538, 1-549, 1-550, 1-585, 1-586, 1-587, 1 -588, 1-589, 1-590, 1-591, 1-592, 1-593, 1-594, 1-595, 1-596, 1-597, 1-598, 1-613, 1-614 , 1-619, 1-620, 1-637, 1-638, 1-651, 1-652, 1-653, 1-654, 1-655, 1-656, 1-663, 1-664, 1 -665, 1-666, 1-667, 1-668, 1-743, 1-744, 1-745, 1-746, 1-747, 1-748, 1-749, 1-750, 1-751 , 1-752, 1-753, 1-754, 1-761, 1-762, 1-763, 1-764, 1-765, 1-766, 1-767, 1-768, 1-789, 1 -790, 1-813, 1-814, 1-815, 1-816, 1-817, 1-818, 1-819, 1-820, 1-84 1, 1-842, 1-865, 1-866, 1-879, 1-880, 1-881, 1-882, 1-883, 1-884, 1-885, 1-886, 1-887, 1-888, 1-889, 1-890, 1-965, 1-966, 1-967, 1-968, 1-969, 1-970, 1-971, 1-972, 1-973, 1- 974, 1-975, 1-976, 1-977, 1-978, 1-979, 1-980, 1-981, 1-982, 1-983, 1-984, 1-985, 1-986, 1-987, 1-988, 1-989, 1-990, 1-1005, 1-1006, 1-1011, 1-1012, 1-1017, 1-1018, 1-1023, 1-1024, 1- 1045, 1-1046, 1-1047, 1-1048, 1-1049, 1-1050, 2-1, 2-2, 2-5, 2-6, 2-9, 2-10, 2-13, 2-14, 2-17, 2-18, 2-21, 2-22, 2-25, 2-26, 2-29, 2-30, 2-33, 2-34, 2-37, 2- 38, 2-41, 2-42, 2-45, 2-46, 2-49, 2-50, 2-53, 2-54, 2-57, 2-58, 2-61, 2-62, 2-87, 2-88, 2-115, 2-116, 2-121, 2-122, 2-127, 2-128, 2-133, 2-134, 2-139, 2-140, 2- 187, 2-188, 2-207, 2-208, 2-209, 2-210, 2-211, 2-212, 2-337, 2-338, 2-351, 2-352, 2-353, 2-354, 2-355, 2-356, 2-443, 2-444, 2-445, 2-446, 2-447, 2-448, 2-485, 2-486, 2-487, 2- 488, 2-489, 2-490, 2-491, 2-492, 2-493, 2-494, 2-495, 2-496, 2-497, 2-498, 2-499, 2-500, 2-501, 2-502, 2-503, 2-504, 2-537, 2-538, 2-549, 2-550, 2-585, 2-586, 2-587, 2-588, 2-589, 2-590, 2-591, 2-592, 2-593, 2-594, 2-595, 2-596, 2-597, 2- 598, 2-613, 2-614, 2-619, 2-620, 2-637, 2-638, 2-651, 2-652, 2-653, 2-654, 2-655, 2-656, 2-663, 2-664, 2-665, 2-666, 2-667, 2-668, 2-743, 2-744, 2-745, 2-746, 2-747, 2-748, 2- 749, 2-750, 2-751, 2-752, 2-753, 2-754, 2-761, 2-762, 2-763, 2-764, 2-765, 2-766, 2-767, 2-768, 2-789, 2-790, 2-813, 2-814, 2-815, 2-816, 2-817, 2-818, 2-819, 2-820, 2-841, 2- 842, 2-865, 2-866, 2-879, 2-880, 2-881, 2-882, 2-883, 2-884, 2-885, 2-886, 2-887, 2-888, 2-889, 2-890, 2-965, 2-966, 2-967, 2-968, 2-969, 2-970, 2-971, 2-972, 2-973, 2-974, 2- 975, 2-976, 2-977, 2-978, 2-979, 2-980, 2-981, 2-982, 2-983, 2-984, 2-985, 2-986, 2-987, 2-988, 2-989, 2-990, 2-1005, 2-1006, 2-1011, 2-1012, 2-1017, 2-1018, 2-1023, 2-1024, 2-1045, 2- 1046, 2-1047, 2-1048, 2-1049, 2-1050, 3-1, 3-2, 3-5, 3-6, 3-13, 3-14, 3-15, 3-16, 3-17, 3-18, 3-27, 3-28, 3-29, 3-30, 3-31, 3-32, 3-33, 3-34, 3-35, 3-36, 3- 37, 3-38, 3-39, 3-46, 3-47, 3-50, 3-51, 3-52, 3-5 3, 3-54, 3-55, 3-56, 3-57, 3-58, 3-59, 3-60, 3-61, 3-62, 3-63, 3-64, 3-65, 3-66, 3-67, 3-68, 3-69, 3-70, 3-71, 3-72, 3-73, 3-74, 3-75, 3-76, 3-77, 3- 78, 3-79, 4-1, 4-2, 4-5, 4-6, 4-13, 4-14, 4-15, 4-16, 4-17, 4-18, 4-27, 4-28, 4-29, 4-30, 4-31, 4-32, 4-33, 4-34, 4-35, 4-36, 4-37, 4-38, 4-39, 4- 46, 4-47, 4-50, 4-51, 4-52, 4-53, 4-54, 4-55, 4-56, 4-57, 4-58, 4-59, 4-60, 4-61, 4-62, 4-63, 4-64, 4-65, 4-66, 4-67, 4-68, 4-69, 4-70, 4-71, 4-72, 4- 73, 4-74, 4-75, 4-76, 4-77, 4-78, 4-79, 5-1, 5-2, 5-3, 5-4, 5-5, 5-6, 5-7, 5-8, 5-9, 5-10, 5-11, 5-12, 5-13, 5-14, 5-27, 5-28, 5-29, 5-30, 5- 31, 5-32, 5-33, 5-34, 5-41, 5-42, 5-43, 5-44, 5-45, 5-46, 5-59, 5-60, 5-61, 5-62, 5-69, 5-70, 5-71, 5-72, 5-73, 5-74, 5-75, 5-76, 5-77, 5-78, 5-79, 5- 80, 5-81, 5-82, 5-85, 5-86, 5-87, 5-88, 5-89, 5-90, 5-93, 5-94, 5-95, 5-96, 5-97, 5-98, 5-99, 5-100, 5-101, 5-102, 5-103, 5-104, 5-105, 5-106, 5-107, 5-108, 5- 115, 5-116, 5-117, 5-118, 5-125, 5-126, 5-127, 5-128, 5-129, 5-130, 5-131, 5-132, 5-133, 5-134, 5-135, 5 -136, 5-143, 5-144, 5-145, 5-146, 5-147, 5-148, 5-149, 5-150, 5-151, 5-152, 5-153, 5-154, 5 -155, 5-156, 5-171, 5-172, 5-177, 5-178, 5-209, 5-210, 5-237, 5-238, 5-265, 5-266, 5-293 , 5-294, 5-313, 5-314, 5-319, 5-320, 5-337, 5-338, 5-339, 5-340, 5-341, 5-342, 5-343, 5 -344, 5-345, 5-346, 5-347, 5-348, 5-361, 5-362, 5-367, 5-368, 5-385, 5-386, 5-387, 5-388 , 6-1, 6-2, 6-3, 6-4, 6-5, 6-6, 6-7, 6-8, 6-9, 6-10, 6-11, 6-12, 6 -13, 6-14, 6-27, 6-28, 6-29, 6-30, 6-31, 6-32, 6-33, 6-34, 6-41, 6-42, 6-43 , 6-44, 6-45, 6-46, 6-59, 6-60, 6-61, 6-62, 6-69, 6-70, 6-71, 6-72, 6-73, 6 -74, 6-75, 6-76, 6-77, 6-78, 6-79, 6-80, 6-81, 6-82, 6-85, 6-86, 6-87, 6-88 , 6-89, 6-90, 6-93, 6-94, 6-95, 6-96, 6-97, 6-98, 6-99, 6-100, 6-101, 6-102, 6 -103, 6-104, 6-105, 6-106, 6-107, 6-108, 6-115, 6-116, 6-117, 6-118, 6-125, 6-126, 6-127 , 6-128, 6-129, 6-130, 6-131, 6-132, 6-133, 6-134, 6-135, 6-136, 6-143, 6-144, 6-145, 6 -146, 6-147, 6-148, 6-149, 6-150, 6-151, 6-152, 6-153, 6-154, 6-155, 6-156, 6-171, 6-172 , 6-177, 6-178, 6- 209, 6-210, 6-237, 6-238, 6-265, 6-266, 6-293, 6-294, 6-313, 6-314, 6-319, 6-320, 6-337, 6-338, 6-339, 6-340, 6-341, 6-342, 6-343, 6-344, 6-345, 6-346, 6-347, 6-348, 6-361, 6- 362, 6-367, 6-368, 6-385, 6-386, 6-387 and 6-388, The most preferred compounds are the example compounds numbers 1-1, 1-2, 1-5, 1- 6, 1-17, 1-18, 1-21, 1-22, 1-25, 1-26, 1-53, 1-54, 1-207, 1-208, 1-351, 1-352, 1-443, 1-444, 1-485, 1-486, 1-487, 1-488, 1-489, 1-490, 1-491, 1-492, 1-493, 1-494, 1- 587, 1-588, 1-589, 1-590, 1-591, 1-592, 1-651, 1-652, 1-743, 1-744, 1-763, 1-764, 1-815, 1-816, 1-967, 1-968, 1-973, 1-974, 1-975, 1-976, 1-977, 1-978, 2-1, 2-2, 2-5, 2- 6, 2-17, 2-18, 2-21, 2-22, 2-25, 2-26, 2-53, 2-54, 2-207, 2-208, 2-351, 2-352, 2-443, 2-444, 2-485, 2-486, 2-487, 2-488, 2-489, 2-490, 2-491, 2-492, 2-493, 2-494, 2- 587, 2-588, 2-589, 2-590, 2-591, 2-592, 2-651, 2-652, 2-743, 2-744, 2-763, 2-764, 2-815, 2-816, 2-967, 2-968, 2-973, 2-974, 2-975, 2-976, 2-977, 2-978, 3-1, 3-2, 3-13, 3- 14, 3-15, 3-16, 3-1 7, 3-18, 3-27, 3-28, 3-29, 3-30, 3-31, 3-32, 3-50, 3-51, 3-54, 3-55, 3-62, 3-63, 3-66, 3-67, 4-1, 4-2, 4-13, 4-14, 4-15, 4-16, 4-17, 4-18, 4-27, 4- 28, 4-29, 4-30, 4-31, 4-32, 4-50, 4-51, 4-54, 4-55, 4-62, 4-63, 4-66, 4-67, 5-3, 5-4, 5-5, 5-6, 5-7, 5-8, 5-9, 5-10, 5-11, 5-12, 5-13, 5-14, 5- 27, 5-28, 5-29, 5-30, 5-33, 5-34, 5-69, 5-70, 5-71, 5-72, 5-73, 5-74, 5-75, 5-76, 5-77, 5-78, 5-79, 5-80, 5-81, 5-82, 5-85, 5-86, 5-87, 5-88, 5-89, 5- 90, 5-93, 5-94, 5-95, 5-96, 5-97, 5-98, 5-99, 5-100, 5-101, 5-102, 5-103, 5-104, 5-105, 5-106, 5-107, 5-108, 5-145, 5-146, 5-147, 5-148, 5-149, 5-150, 5-151, 5-152, 5- 153, 5-154, 5-155, 5-156, 5-337, 5-338, 5-339, 5-340, 5-341, 5-342, 5-343, 5-344, 5-345, 5-346, 5-347, 5-348, 5-387, 5-388, 6-3, 6-4, 6-5, 6-6, 6-7, 6-8, 6-9, 6- 10, 6-11, 6-12, 6-13, 6-14, 6-27, 6-28, 6-29, 6-30, 6-33, 6-34, 6-69, 6-70, 6-71, 6-72, 6-73, 6-74, 6-75, 6-76, 6-77, 6-78, 6-79, 6-80, 6-81, 6-82, 6- 85, 6-86, 6-87, 6-88, 6-89, 6-90, 6-93, 6-94, 6-95, 6-96, 6-97, 6-98, 6-99, 6-100, 6-101, 6-102, 6-103, 6-104, 6-105, 6-106, 6-107, 6-108, 6-145, 6-146, 6-147, 6-148, 6- 149, 6-150, 6-151, 6-152, 6-153, 6-154, 6-155, 6-156, 6-337, 6-338, 6-339, 6-340, 6-341, 6-342, 6-343, 6-344, 6-345, 6-346, 6-347, 6-348, 6-387 and 6-388, The compounds still more preferred are the exemplary compounds numbers 1-17 , 1-18, 1-53, 1-54, 1-487, 1-488, 1-489, 1-490, 1-491, 1-492, 1-587, 1-588, 1-589, 1 -590, 1-591, 1-592, 1-973, 1-974, 2-17, 2-18, 2-53, 2-54, 2-487, 2-488, 2-489, 2-490 , 2-491, 2-492, 2-587, 2-588, 2-589, 2-590, 2-591, 2-592, 2-973, 2-974, 3-1, 3-2, 3 -13, 3-14, 3-31, 3-32, 3-50, 3-51, 3-54, 3-55, 3-62, 3-63, 3-66, 3-67, 4-1 , 4-2, 4-13, 4-14, 4-31, 4-32, 4-50, 4-51, 4-54, 4-55, 4-62, 4-63, 4-66, 4 -67, 5-3, 5-4, 5-5, 5-6, 5-7, 5-8, 5-75, 5-76, 5-77, 5-78, 5-79, 5-80 , 5-81, 5-82, 5-89, 5-90, 5-93, 5-94, 5-95, 5-96, 5-97, 5-98, 5-99, 5-100, 5 -101, 5-102, 5-103, 5-104, 5-105, 5-106, 5-107, 5-108, 5-145, 5-146, 5-147, 5-148, 5-149 , 5-150, 5-151, 5-152, 5-153, 5-155, 5-155 , 5-156, 5-337, 5-338, 5-339, 5-340, 5-341, 5-342, 5-387, 5-388, 6-3, 6-4, 6-5, 6-6, 6 -7, 6-8, 6-75, 6-76, 6-77, 6-78, 6-79, 6-80, 6-81, 6-82, 6-89, 6-90, 6-93 , 6-94, 6-95, 6-96, 6-97, 6-98, 6-99, 6-100, 6-101, 6-102, 6-103, 6-104, 6-105, 6 -106, 6-107, 6-108, 6-145, 6-146, 6-147, 6-148, 6-149, 6-150, 6-151, 6-152, 6-153, 6-154 , 6-155, 6-156, 6-337, 6-338, 6-339, 6-340, 6-341, 6-342, 6-387 and 6-388, and the particularly preferred compounds are Compound of Example No. 1-17: (E) -3- [2- (4-carbo? I-1H-pyrazol-1-yl) ethylidene] -1- [2-cyclopropyl-1- (2-fluorophenyl) -2- o? oethyl] -4-sulfanylpiperidine, Compound of Example No.1-53: (E) -3-. { 2- [4- (carbo] imethyl) -1H-pyrazol-1-yl] ethylidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine, Compound of Example No. 1-487: (E) -3- [2- (4-carbo? i-1 H-1, 2,3-triazol-1-yl) ethylidene] -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oethyl] -4-sulfanylpiperidine, Compound of Example No 1-587: (E) -3- [2- (4-carbo? I-2H-1,2,3-triazol-2-yl) ethylidene] -1- [2-cyclopropyl-1- (2- fluorophenyl) -2-o? oethyl] -4-sulfanylpiperidine Compound of Example No. 1-973: (E) -3-. { [2- (4-carbo? I-1H-pyrazol-1-yl) -1-methyl] etlidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine, Compound of Example No.3-1: (E) -1- [2-cyclopropyl-1- ( 2-fluorophenyl) -2-o? Oethyl] -3- (2-hydroxyethylidene) -4-sulfanylpiperidine, Compound of Example No.3-13: (E) -3- (2-carboethylstyide) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine, Compound of Example No.3-31: (E) -1- [2-cyclopropyl-1- (2- fluorophenyl) -2-oxoethyl] -3-. { [1- (Eto? Icarbonylmethyl) piperidin-4-yl] methylidene} -4-Sulfanylpiperidine, Compound of Example No.3-50: (E) -3-. { 2- [N- (carbo-imethyl) -N-methylamino] ethylidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine, Compound of Example No. 3-54: (E) -1 - [2-cyclopropyl-1 - ( 2-fluorophenyl) -2-o? Oethyl] -3-. { 2- [N- (etho? -carbonylmethyl) -N-methylamino] ethylidene} 4-Sulfanylpiperidine, Compound of Example No. 3-62: (E) -3- (2- { N- [3- (carbo? I) propyl] -N-methylamino.} Ethylidene) -1- [2-Cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -4-sulfanylpiperidine, Compound of Example No. 3-66: (E) -1 - [2-cyclopropyl-1- (2-fluorophenyl) ) -2-o? Oethyl] -3- (2- { N- [3- (etho? -carbonyl) propyl] -N-methylamino.} Ethylidene) -4-sulfanylpiperidine, Compound of Example No. 5- 3: (E) -3-. { 2- [4- (carbo? Ipiperidin) -1 -yl] ethylidene} -1 - [2-cyclopropyl-1 - (2-fluorophenyl) -2-oxoethyl] -4-sulfanylpiperidine, Compound of Example No. 5-7: (E) -1 - [2-cyclopropyl-1 - (2- fluorophenyl) -2-oxoethyl] -3-. { 2- [4- (ethocarbonyl) piperidin-1-yl] ethylidene} 4-Sulfanylpiperidine, Compound of Example No. 5-75: (E) -3- (2- {4- [2- (carboxyethyl)] -2-oxopiperazin-1-yl} ethylidene) -1 - [2-cyclopropyl-1 - (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine, Compound of Example No. 5-79: (E) -1 - [2-cyclopropyl-1 - (2- fluorophenyl) -2-o? oethyl] -3- (2- {4- [2- (etho? -carbonyl) ethyl] -2-o? opiperazin-1-yl} ethylidene) -4-sulfanylpiperidine, Compound of Example No. 5-81: (E) -3- (2- { 4- [3- (carbo? Ipropyl)] - 2-o? Opiperazin-1-yl.} Ethylidene) -1- [2-cyclopropyl-1 - (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine, Compound of Example No. 5-97: (E) -3-. { 2- [4- (carbo? Imethyl) -3-o? Opiperazin-1-yl] ethylidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperi ina, Compound of Example No.5-101: (E) -1- [2-cyclopropyl-1-] (2-fluorophenyl) -2-o? Oethyl] -3-. { 2- [4- (Etho? -carbonylmethyl) -3-o? Opiperazin-1-yl] ethylidene} 4-Sulfanylpiperidine, Compound of Example No.5-103: (E) -3- (2-. {4- [2- (carboethyl)] - 3-o? Opiperazin-1-yl.}. ethylidene) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -4-sulfanylpiperidine, Compound of Example No.5-105: (E) -1- [2-cyclopropyl-1 - (2-fluorophenyl) -2-o? Oethyl] -3- (2- {4- [2- (methoxycarbonyl) ethyl] -3-oxopiperazin-1-yl} ethylidene) -4-sulfanylpiperidine, Compound of Example No.5-107: (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3- (2- { 4- [2- (eto icarbonyl) ethyl] -3-o? opiperazin-1-yl.} ethylidene) -4-sulfanylpiperidine, Compound of Example No.5-147: (E) -1- [2-cyclopropyl-1- (2- fluorophenyl) -2-o? oethyl] -3-. { 2 - [(2S) - (methoxycarbonyl) pyrrolidin-1-yl] ethylidene} -4-Sulfanylpiperidine, Compound of Example No.5-151: (E) -3-. { 2 - [(2S) - (carboxymethyl) pyrrolidin-1-yl] ethylidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine, Compound of Example No.5-153: (E) -1- [2-cyclopropyl-1- ( 2-fluorophenyl) -2-o? Oethyl] -3-. { 2 - [(2S) - (methoxycarbonylmethyl) pyrrolidin-1-yl] ethylidene} -4-Sulfanylpiperidine, Compound of Example No.5-337: (E) -3-. { 2- [3- (carboxypiperidin) -1-yl] ethylidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -4-sulfanylpiperidine, Compound of Example No. 5-387: (E) -1 - [2-cyclopropyl-1 - ( 2-fluorophenyl) -2-o? Oethyl] -3-. { 2 - [(2S, 4R) -4-hydro? I-2- (methocarbyl) pyrrolidin-1-yl] ethylidene} -4-Sulfanylpiperidine, and its S-acetyl derivatives (Compounds No .: 1 -18, 1 -54, 1 -488, 1 - 588, 1 -974, 3-2, 3-14, 3-32, 3- 51, 3-55, 3-63, 3-67, 5-4, 5-8, 5-76, 5-80, 5-82, 5-98, 5-102, 5-104, 5-106, 5-108, 5-148, 5-152, 5-154, 5-338 and 5-388) or geometric isomers thereof (isomers (Z), Compounds No.: 2-17, 2-18, 2-53 , 2-54, 2-487, 2-488, 2-587, 2-588, 2-973, 2-974, 4-1, 4-2, 4-1 3, 4-1 4, 4-31 , 4-32, 4-50, 4-51, 4-54, 4-55, 4-62, 4-63, 4-66, 4-67, 6-3, 6-4, 6-7, 6 -8, 6-75, 6-76, 6-79, 6-80, 6-81, 6-82, 6-97, 6-98, 6-101, 6-1 02, 6-1 03, 6 -1 04, 6-1 05, 6-1 06, 6-1 07, 6-1 08, 6-147, 6-1 48, 6-1 51, 6-1 52, 6-1 53, 6- 1 54, 6-337, 6-338, 6-387 and 6-388). Effect of the invention) The compounds of the present invention are chemically stable and exert energetic platelet anticoagulant activities and inhibitory action against the formation of thrombosis. In addition, the compounds of the present invention exert said actions with short waiting times for onset and show low degree of tocidity. Thus, the compounds of the present invention can be useful for establishing prophylactic measures, preventing recurrence and establishing therapeutic measures (particularly the latter) against diseases induced by platelet activation, such as thrombosis formation and platelet coagulation and platelet release responses. , for example in percutaneous coronary intervention (PCI), angioplasty, endarterectomy, restenosis after stent placement; acute coronary syndrome, stable or unstable angina, myocardial infarction, atrial fibrillation, cerebral ischemic attack, cerebral infarction, and atherosclerosis and diseases induced by formation of thrombosis or embolus formation that are associated with diabetes mellitus, peripheral arterial disease, thrombocytopenia induced by heparin (HIT), thrombotic thrombocytopenic purpura (TTP), antiphospholipid antibody syndrome, venous thrombosis, and icoremia. BEST MODE FOR CARRYING OUT THE INVENTION The compound (I) in the present invention can be obtained by Process A or Process B described below. (li) (III) (i) In the above, from R1 to R3 and X1 to X5 have the same meanings defined above; R2a and R3a represent R2 and R3 described above or a group by which an amino group or a hydroxyl group in R2 and R3 can be protected, if necessary, by a protecting group for an amino group or a hydroxyl group; Pro1 represents a protecting group for a sulfanyl group; and Lv represents a suppressible group. The protecting group for a sulfanyl group such as Pro1 may be the same group as that described as the protecting group for a sulfanyl group of the above "prodrug", and preferably is an acetyl group. The protecting group for an amino group of R2a and R3a is not particularly restricted as long as it can usually protect an amino group in chemical reactions, and specifically indicates a protecting group that can be cleaved by a chemical process such as hydrogenolysis, hydrolysis, electrolysis and photolysis. This protecting group can be, for example, the "aliphatic acyl group" above; the "aromatic acyl group" above; the "alkoxycarbonyl group" above; the "aralkyl? -carbonyl group" above; the "silyl group" above; the "aralkyl group" above; a "substituted methylene group" which can form a Schiff base such as a N, N-dimethylaminomethylene, benzylidene, 4-methoxybenzylidene, 4-nitrobenzylidene, salicylidene, 5-chlorosalicylidene, diphenylmethylene or (5-chloro-2-hydro? ifenyl) group ) phenylmethylene; an "aromatic sulfonyl group" consisting of: an arylsulfonyl group such as a benzenesulfonyl group, and an arylsulfonyl group substituted with lower alkyl or with lower alkoxy group (s) such as a p-toluenesulfonyl group, pentamethylbenzenesulfonyl, p-meto ? -benzenesulfonyl, 2,4,6-trimetho? -benzenesulfonyl or 3-metho? i-4-t-butylbenzenesulfonyl; and an "aliphatic sulfonyl group", including an alkylsulfonyl group such as a methanesulfonyl or t-butylsulfonyl group, and an alkylsulfonyl group substituted with halogen atom (s), silyl group (s), or aryl group (s) such as a trifluoromethylsulfonyl, trisilylethanesulfonyl or benzylsulfonyl group. The protecting group for a hydrophilic group of R2a and R3a is not particularly restricted as long as it can usually protect a hydrophilic group in chemical reactions, and specifically indicates a protective group that can be cleaved by a chemical process such as hydrogenolysis, hydrolysis, electrolysis and photolysis. This protecting group can be, for example, the "aliphatic acyl group" above; the "aromatic acyl group" above; the "carbonyl-ialkyl group" above; the "residual group of a salt of a semi ester of succinic acid" above; the "residual group of a salt of a semi-ester of phosphoric acid" above; the "residual group that forms an amino acid ester"; a carbamoyl group; a carbamoyl group substituted with 1 or 2 lower alkyl groups; the "carbonyl? ialkyl? -carbonyl group" above; or the "silyl group" above, and preferably is a pharmacologically acceptable ester forming group such as an "aliphatic acyl group", an "aromatic acyl group" or a "silyl group", more preferably an "alkanoyl group of 1 to 6 carbon atoms "such as an acetyl group, propionyl, butyryl, isobutyryl, pentanoyl, or pivaloyl, or a" silyl group "such as t-butyldimethylsilyl or t-butyldiphenylsilyl, and particularly preferably an acetyl group, a t-group -butyldimethylsilyl or a t-butyldiphenylsilyl group. The cleavable group of Lv is not particularly restricted as long as this group is a functional group that can achieve a displacement reaction by reacting with a nucleophilic substituent, and can be, for example, the "halogen atom" above; a "lower alkylsulfonyl group" such as a methanesulfonyl group or ethanesulfonyl group; and a "halogenated lower alkylsulfonyl group" such as a trifluoromethanesulfonyloxy group.; or an "aromatic sulfonyloxy group" including an arylsulfonyl group, such as a benzenesulfonyl group, a lower alkylated arylsulfonyl group such as a p-toluenesulfonyl group, a halogenated arylsulfonyl group, such as a p-group; chlorobenzenesulfonyloxy and a nitrated arylsulfonyloxy group such as a p-nitrobenzenesulfonyl group? i. Each step of Process A and Process B is described here in detail in the following. (Process A) Process A is a step for the preparation of compound (I) by performing a nucleophilic displacement reaction in the presence of a base using compound (II), which is obtained by Process C and a compound (III) which is well known or easily prepared from the known compounds (A-1). In addition, if necessary, it is also possible to carry out various reactions, such as deprotection of a protecting group of a sulfanyl group (A-2), introduction of a substituent into a sulfanyl group (A-3), hydrolysis of a group ester (A-4), conversion of a carbo-i group to an amide group (A-5), conversion of a carbo-i group into an ester group (A-6), deprotection of a protecting group for an amino group (A-7), conversion of a carboi group into a hydroxyamino group (A-8) and conversion of a R3 group including a hydrophilic group into a group R3 (A-9). The steps from A-2 to A-9 can be performed before or after step A-1, and the order of these steps can be easily selected according to the circumstances by a person with ordinary skill in the art. (A-1) The solvent employed may be, for example, an aromatic hydrocarbon such as benzene, toluene or γ-ylene; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or dimethyl ether of di (ethylene glycol); a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cycloheanone; a nitrile, such as acetonitrile or isobutyronitrile; an amide, such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hemiamethylphosphoric triamide; or a sulphonated, such as sulphonated dimethyl or sulfolane, and preferably is a halogenated hydrocarbon, a nitrile or an amide, and more preferably N, N-dimethylformamide, N, N-dimethylacetamide, acetonitrile or dichloromethane. The base employed may be, for example, an inorganic base, including an alkali metal carbonate such as sodium carbonate, potassium carbonate or lithium carbonate; a hydrogenated alkali metal carbonate such as hydrogenated sodium carbonate, hydrogenated potassium carbonate or hydrogenated lithium carbonate; an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride; a hydroxide of alkali metal such as hydrated sodium, hydrogenated potassium or lithium hydroxide; and an alkali metal fluoride such as sodium fluoride or potassium fluoride; an alkali metal alkoxide such as sodium methoxide, sodium ethoxide, potassium mixed, potassium ethoxide, potassium t-butylated or lithium methoxide; an alkali metal mercaptan such as sodium mercaptan or sodium ethyl mercaptan; or an organic base such as N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di (t-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [2.2 .2] octane (DABCO) or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), and preferably is an alkali metal carbonate or an organic base, and more preferably potassium carbonate or triethylamine. The temperature of the reaction varies depending on the initial material and the reagent, and is between -50 ° C and 100 ° C, and preferably between 0 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 30 minutes to 48 hours, and preferably from 1 hour to 24 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separating the organic layer containing the desired compound, drying the organic layer over anhydrous magnesium sulfate or the like, and then evaporating the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. A-2? This step is a step for the deprotection of a protecting group for a sulfanyl group, and can be easily accomplished according to procedures that are well known to a person skilled in the art (e.g., the procedure described in Protective Groups in Organic Synthesis , Third Edition, TW Green, et al., John Wiley & amp;; Sons, Inc. (1999)), and preferably is carried out by a method for deprotection in the presence of an acid (A-2a) or a method for deprotection in the presence of a base (A-2b). ! A-2a) The solvent employed can be, for example, an aromatic hydrocarbon such as benzene, toluene or? Ylene; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; an alcohol such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cycloheanol or 2-metho-ethanol; an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hemiamethylphosphoric triamide; a sulphonated such as dimethyl sulfoxide or sulfolane; or a mixture of the above solvents, and preferably is an alcohol or a mixed solvent of a halogenated hydrocarbon and an alcohol, and more preferably methanol, ethanol or a solvent mixture of dichloromethane and methanol or ethanol. The acid employed is not particularly restricted so long as it can be used in general reactions, and may preferably be an inorganic acid such as hydrochloric acid, hydrogen chloride, hydrobromic acid, sulfuric acid, perchloric acid or phosphoric acid; or an organic acid such as acetic acid, formic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, camphor sulfonic acid, trifluoroacetic acid or trifluoromethanesulfonic acid, and preferably is an inorganic acid, and more preferably hydrogen chloride or hydrochloric acid. The temperature of the reaction varies depending on the starting material and the reagent, and is between -50 ° C and 1 00 ° C, and preferably between 0 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 30 minutes to 48 hours, and preferably from 1 hour to 24 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture; addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water, separating the organic layer containing the desired compound, drying the organic layer over anhydrous magnesium sulfate or the like, and then evaporating the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. Í? Z2h? The solvent employed can be, for example, an aromatic hydrocarbon such as benzene, toluene or iole; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; an alcohol such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol or 2-methoxyethanol; an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hemiamethylphosphoric triamide; a sulphonate such as sulphonated dimethyl or sulfolane; Water; or a mixture of the above solvents, and preferably it is an alcohol or a mixed solvent of an alcohol and water, and more preferably methanol, ethanol, methanol containing water or ethanol containing water. The base employed can be, for example, an inorganic base, including an alkali metal carbonate such as sodium carbonate, potassium carbonate or lithium carbonate.; a hydrogenated alkali metal carbonate such as hydrogenated sodium carbonate, hydrogenated potassium carbonate or hydrogenated lithium carbonate; an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride; a hydroxide of alkali metal such as hydrated sodium, hydrated potassium or hydrated lithium; and an alkali metal fluoride such as sodium fluoride or potassium fluoride; a mixture of alkali metal such as sodium, sodium ethoxide, potassium methoxide, potassium ethoxide, potassium t-butoxide or lithium methoxide; an alkali metal mercaptan such as sodium mercaptan or sodium ethyl mercaptan; or an organic base such as N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di (t-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [2.2 .2] octane (DABCO) or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), and preferably is an alkali metal carbonate or an alkali metal hydrate, and more preferably potassium carbonate or sodium hydroxide. The temperature of the reaction varies depending on the starting material and the reagent, and is between -50 ° C and 1 00 ° C, and preferably between -20 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 1 minute to 24 hours, and preferably from 5 minutes to 5 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separating the organic layer containing the desired compound, drying the organic layer over anhydrous magnesium sulfate or the like, and then evaporating the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. (A-3) This step is a step to introduce a substituent into a sulfanyl group in the presence of a base or the like. When an acid chloride, an acid anhydride, a sulfanyl halide or an active ester is used as a reagent, this step is carried out in the presence of a base (A-3a), when a carbohydric acid is used, this step is carried out in the presence of a condensing agent (A-3b), and when a thiol is employed, this step is carried out in the presence of iodine or a base (A-3c). (A-3a) The solvent employed may be, for example, an aromatic hydrocarbon such as benzene, toluene or γ-ylene; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cyclohexanone; an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hexamethylphosphoric triamide; or a sulphonated such as sulphonated dimethyl or sulfolane, and preferably is a halogenated hydrocarbon, a ketone or an amide, and more preferably N, N-dimethylformamide, N, N-dimethylacetamide, dichloromethane or acetone. The base employed can be, for example, an inorganic base, including an alkali metal carbonate such as sodium carbonate, potassium carbonate or lithium carbonate.; a hydrogenated alkali metal carbonate such as hydrogenated sodium carbonate, hydrogenated potassium carbonate or hydrogenated lithium carbonate; an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride; a hydroxide of alkali metal such as hydrated sodium, hydrated potassium or hydrated lithium; and an alkali metal fluoride such as sodium fluoride or potassium fluoride; a mixture of alkali metal such as sodium methoxide, sodium ethoxide, potassium, potassium ethoxide, potassium t-butoxide or lithium methoxide; an alkali metal mercaptan such as sodium mercaptan or sodium ethyl mercaptan; or an organic base such as N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di (t-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [2.2 .2] octane (DABCO) or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), and preferably is an alkali metal carbonate, an alkali metal hydride or an organic base, and more preferably hydride of sodium, potassium carbonate or triethylamine. The temperature of the reaction varies depending on the starting material and the reagent, and is between -30 ° C and 1 00 ° C, and preferably between -1 0 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 5 minutes to 24 hours, and preferably from 1 5 minutes to 10 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separating the organic layer containing the desired compound, drying the organic layer over anhydrous magnesium sulfate or the like, and then evaporating the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. ÍA-3b? The solvent employed may be, for example, an aromatic hydrocarbon such as benzene, toluene or xylene; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cyclohexanone; an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hexamethylphosphoric triamide; or a sulphonated such as sulphonated dimethyl or sulfolane, and preferably is a halogenated hydrocarbon or an amide, and more preferably N, N-dimethylformamide, N, N-dimethylacetamide or dichloromethane. The "condensing agent" employed may be, (i) a combination of a phosphated ester such as diethylphosphoryl cyanide, diphenylphosphoryl azide or diethyl cyanophosphonate and a base shown below; (ii) a carbodiimide, such as 1,3-dicyclohexylcarbodiimide (DCC), 1,3-diisopropylcarbodiimide or 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide (WSC); a combination of said carbodiimide and a base shown below; a combination of said carbodiimide and an N-hydroxyimide such as N-hydroisuccinimide, 1 -hydro? ibenzotriazole or N-hydro? i-5-norbornene-2,3-dicarboxyimide; and a combination of said carbodiimide, said N-hydro? iimide and a base shown below; (iii) a combination of a disulfide such as 2,2'-dipyridyl disulfide or 2,2'-dibenzothiazolyl disulfide and a phosphine such as triphenylphosphine or tributylphosphine; (iv) a carbonate such as N. N'-disuccinimidyl carbonate, diethyl pyrocarbonate (DEPC), di-2-pyridyl carbonate or S, S'-bis (1-phenyl-1 H-tetrazole-5-dithiocarbonate) carbonate. -ilo); (v) a phosphinic chloride such as N, N'-bis (2-o? o-3-o? azolidinyl) phosphinic chloride; (vi) an olato such as o? alato of N.N'-disuccinimidilo, or? alato of N. N'-diftalimida, or? alato of N, N'-bis (5-norborneno-2,3- dicarbo-iimidyl), or 1, 1'-bis (benzotriazolyl) alato, or 1, 1'-bis (6-chlorobenzotriazolyl) uo-alato 1,1-bis (6-trifluoromethylbenzotriazolyl) α1-alato; (vii) a combination of said phosphine and azodicarbo-ilato or an azodicarbo-iamide such as azodicarbo-diethyl ilate or 1, 1 '- (azodicarbonyl) dipiperidine; (viii) an N-lower alkyl-5-aryl iso? azole-3'-sulfonate such as N-ethyl-5-phenyl iso? azole-3'-sulfonate; (i?) a di-heteroaryl diselenide such as di-2-pyridyl diselenide; (?) an arylsulfonyl triazolide such as p-nitrobenzenesulfonyl friazolide; (? i) a lower 2-halo-l-alkylpyridinium halide such as 2-chloro-1-methylpyridinium iodide; (ii) an imidazole such as 1,1'-o-allyldiimidazole or N, N'-carbonyldiimidazole (CDI); (iii) a 3-lower alkyl-2-halogeno-benzothiazolium fluoroborate such as 3-ethyl-2-chloro-benzothiazolium fluoroborate; (iv) a 3-lower alkyl-benzothiazole-2-selone such as 3-methyl-benzothiazole-2-selone; (v) a phosphate such as phenyl dichlorophosphate or polyphosphate ester; (? vi) a halogensulfonyl isocyanate such as chlorosulfonyl isocyanate; (? vii) a halogensilane such as trimethylsilyl chloride or friethylsilyl chloride; (xviii) a combination of a lower alkanesulfonyl halide such as methanesulfonyl chloride and a base shown below; (xi?) a N, N, N ', N'-tetra-lower alkyl chloride halogenoformamide such as N, N, N', N'-tetramethylchloroformamido chloride; or (??) a combination of a pyridinium salt (Mukaiyama Reagent) such as 1-methyl-2-chloropyridinium chloride or 1-ethyl-2-bromopyridinium chloride and a base shown below, and preferably is a carbodiimide , and more preferably 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide or 1,3-dicyclohexylcarbodiimide. The base used can be, for example, an organic base such as pyrrolidine, piperidine, morpholene, N-methylmorpholine, triethylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N , N-dimethylamino) pyridine, 2,6-di (t-butyl) -4-methylpridine, quinoline, N, N-dimethylaniline or N, N-diethylaniline. The temperature of the reaction varies depending on the starting material and the reagent, and is between -30 ° C and 1 00 ° C, and preferably between -1 0 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 5 minutes to 24 hours, and preferably from 30 minutes to 10 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture; addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water, separating the organic layer containing the desired compound, drying the organic layer over anhydrous magnesium sulfate or the like, and then evaporating the organic solvent to give the desired product. The compound obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. A-3ct The solvent employed may be, for example, an aromatic hydrocarbon such as benzene, toluene or iolet; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cyclohexanone; an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hexamethylphosphoric triamide; or a sulphonated such as sulphonated dimethyl or sulfolane, and preferably is an ether, and more preferably tetrahydrofuran. The temperature of the reaction varies depending on the starting material and the reagent, and is between -30 ° C and 100 ° C, and preferably between -10 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 1 minute to 5 hours, and preferably from 5 minutes to 1 hour. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture.; addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water, separating the organic layer containing the desired compound, drying the organic layer over anhydrous magnesium sulfate or the like, and then evaporating the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. (A-4) This step is achieved by hydrolysis of an ester group (A-4). This step is carried out in a manner similar to that indicated hereinabove (A-2). (A-5) This step is achieved by converting a carbo group obtained in step A-4 into an active ester, followed by reacting said active ester with a desired amino compound. The solvent employed can be, for example, an aromatic hydrocarbon such as benzene, toluene or iole; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cyclohexanone; an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hexamethylphosphoric triamide; or a sulphonated such as sulphonated dimethyl or sulfolane, and preferably is a halogenated hydrocarbon or an amide, and more preferably N, N-dimethylformamide, N, N-dimethylacetamide or dichloromethane. The reagent employed is not particularly restricted as long as it is used for the formation of an active ester, and, for example, it can be isobutyl chloroformate. The base employed may be, for example, an inorganic base, including an alkali metal carbonate such as sodium carbonate, potassium carbonate or lithium carbonate; a hydrogenated alkali metal carbonate such as hydrogenated sodium carbonate, hydrogenated potassium carbonate or hydrogenated lithium carbonate; an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride; a hydroxide of alkali metal such as hydrated sodium, hydrated potassium or hydrated lithium; and an alkali metal fluoride such as sodium fluoride or potassium fluoride; a mixture of alkali metal such as sodium methoxide, sodium ethoxide, potassium, potassium ethoxide, potassium t-butoxide or lithium methoxide; an alkali metal mercaptan such as sodium mercaptan or sodium ethyl mercaptan; or an organic base such as N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di (t-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [2.2 .2] octane (DABCO) or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), and is preferably an alkali metal carbonate or an organic base, and more preferably potassium carbonate or triethylamine. The temperature of the reaction varies depending on the starting material and the reagent, and is between -30 ° C and 1 00 ° C, and preferably between -1 0 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 10 minutes to 24 hours, and preferably from 30 minutes to 10 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separation of the organic layer containing the desired compound; drying the organic layer over anhydrous magnesium sulfate or the like; and then evaporating the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like.

(A-ß) This step is carried out by performing a condensation-dehydration reaction between a carboalic acid obtained in step A-4 and an alcohol (A-6a) or by performing an ester exchange reaction using an ester in the presence of an acid or a base directly without performing the process of step A-4 (A-6b). A-6a) The solvent employed may be, for example, an aromatic hydrocarbon such as benzene, toluene or iole; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or dimethyl ether of di (ethylene glycol); an alcohol such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cycloheanol or 2-metho-ethanol; an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hexamethylphosphorotriamide; a sulfoxide such as dimethyl sulfoxide or sulfolane; or a mixed solvent of an alcohol and the above solvent. However, when an alcohol is used as a solvent in the above reaction, the addition of the alcohol as reagent is not necessary. The acid employed can be, for example, an inorganic acid such as hydrochloric acid, hydrogen chloride, hydrobromic acid, sulfuric acid, perchloric acid or phosphoric acid; or a sulfonic acid such as methanesulfonic acid, p-toluenesulfonic acid or camphorsulfonic acid, and preferably is an inorganic acid, and more preferably hydrogen chloride. The temperature of the reaction varies depending on the starting material and the reagent, is between -30 ° C and 100 ° C, and preferably between -10 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 10 minutes to 24 hours, and preferably from 30 minutes to 10 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separation of the organic layer containing the desired compound; drying the organic layer over anhydrous magnesium sulfate or the like; and then evaporating the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. This step is carried out in a manner similar to that indicated here above in (A-3b). (A-6b) In this step, an alcohol corresponding to the desired alkoxy group is used as solvent When an acid is used, this acid used can be, for example, an inorganic acid such as hydrochloric acid, hydrogen chloride, hydrobromic acid, sulfuric acid, perchloric acid or phosphoric acid, or a sulphonic acid such as methanesulfonic acid, p-toluenesulfonic acid or camphor sulfonic acid, and preferably is an inorganic acid, and more preferably hydrogen chloride.When a base is employed, this base employed can to be, for example, an inorganic base, including an alkali metal carbonate such as sodium carbonate, potassium carbonate or lithium carbonate, a hydrogenated alkali metal carbonate such as sodium hydrogenated carbonate, hydrogenated potassium carbonate or hydrogenated carbonate of lithium, an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride; such alkaline as sodium hydroxide, potassium hydroxide or lithium hydroxide; or an alkali metal fluoride such as sodium fluoride or potassium fluoride, and preferably is an alkali metal carbonate, and more preferably potassium carbonate. The temperature of the reaction varies depending on the starting material and the reagent, and is between -30 ° C and 100 ° C, and preferably between -10 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 10 minutes to 24 hours, and preferably from 30 minutes to 10 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separating the organic layer containing the desired compound, drying the organic layer over anhydrous magnesium sulfate or the like, and then evaporating the organic solvent to give the desired product. The compound obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. (A-7) This step is carried out in a manner similar to that indicated hereinabove in step A-2. When an acid is employed, trifluoroacetic acid or hydrogen chloride is used as a particularly preferred reagent. When the desired compound is obtained as its geometric isomer, the desired compound can be obtained by performing the photoisomerization reaction shown below. The solvent employed may be, for example, an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate.; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; an alcohol such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cycloheanol or methyl cellosolve; a nitrile such as acetonitrile or isobutyronitrile; an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, N-methylpyrrolidinone or he? amethylphosphorotriamide; a sulphonate such as sulphonated dimethyl or sulfolane; Water; or a mixture of these solvents, and preferably it is water, an alcohol, a nitrile or a mixture of these solvents. The light source used is a low pressure mercury lamp (which has from 20 W to 1 00 W, preferably 32 W). The sensitizer used can be, for example, benzophenone, fluorenone or anthraquinone. This reaction can also be carried out by the addition of an organic sulfur compound such as dimethyl disulfide, diethyl disulfide or diphenyl disulfide in order to accelerate the reaction. The temperature of the reaction varies depending on the starting material and the reagent, and is between -20 ° C and 1 00 ° C, and preferably between 0 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 5 minutes to 8 hours, and preferably from 10 minutes to 3 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separating the organic layer containing the desired compound, drying the organic layer over anhydrous magnesium sulfate or the like, and then evaporating the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. (A-8) This step is a step for the conversion of a carboi group into a hydroylamino group, and can be carried out easily according to procedures that are well known to a person with ordinary skill in the art. (for example, the methods described in A. Sekar Reddy, M. Suresh Kumar and G. Rabindra Reddy: Tetrahedron Letters, (2000), 41, 6285-6288). * A-9? This step can be carried out in accordance with a Mitsunobu reaction using an amine in an inert solvent or by conversion of a hydrophilic group into a suppressible group then performing a displacement reaction using an amine, and carried out in a similar manner. to which is indicated here below (C-2e). (Process B) Process B is constituted by the steps comprising the preparation of compound (V) carrying out a nucleophilic displacement reaction in the presence of a base using a compound (III) which is well known or is easily prepared from the known compounds and the compounds (IV) obtained by the process C described below (B-1) and the preparation of the compound (I) by conversion of a hydrophilic group of the compound (V) (B-2). In addition, if necessary, in process B, the deprotection of the protecting group for a sulfanyl group (B-3), the introduction of a substituent in a sulfanyl group (B-4), the hydrolysis of an ester group (B-5), the conversion of a carbo-i group into an amide group (B-6), the conversion of a carbo-i group into an ester group (B-7), the deprotection of a group protective for an amino group (B-8) and the conversion of a carbo-i group to a hydro-amino group (B-9). Steps from B-3 to B-9 can be performed before or after steps B-1 and B-2, and the order of these steps can be selected according to circumstances by a person with ordinary skill in the art. Í -? The solvent employed can be, for example, an aromatic hydrocarbon such as benzene, toluene or?; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cycloheanone; an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hemiamethylphosphoric triamide; or a sulphonated such as sulphonated dimethyl or sulfolane, and preferably is a halogenated hydrocarbon or an amide, and more preferably N, N-dimethylformamide, N, N-dimethylacetamide or dichloromethane. The base employed may be, for example, an inorganic base, including an alkali metal carbonate such as sodium carbonate, potassium carbonate or lithium carbonate; a hydrogenated alkali metal carbonate such as hydrogenated sodium carbonate, hydrogenated potassium carbonate or hydrogenated lithium carbonate; an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride; a hydroxide of alkali metal such as hydrated sodium, hydrogenated potassium or lithium hydroxide; and an alkali metal fluoride such as sodium fluoride or potassium fluoride; an alkali metal alkoxide such as sodium methoxide, sodium ethoxide, potassium added, ethanol potassium, potassium t-butylated or lithium methoxide; an alkali metal mercaptan such as sodium mercaptan or sodium ethyl mercaptan; or an organic base such as N-methylmorpholine, triethylamine, fripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di - (t-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [ 2.2.2] octane (DABCO) or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), and is preferably an alkali metal carbonate or an organic base, and more preferably potassium carbonate or triethylamine. The temperature of the reaction varies depending on the starting material and the reagent, and is between -30 ° C and 1 00 ° C, and preferably between -1 0 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 10 minutes to 48 hours, and preferably from 30 minutes to 24 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separation of the organic layer containing the desired compound, drying of the organic layer over anhydrous magnesium sulfate or the like, and then evaporation of the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. (B-2) This step is carried out by the Mitsunobu reaction in an inert solvent (B-2a), by a reaction in the presence of an amide-acetal reagent (B-2b), converting a hydrophilic group into a suppressible group and carrying out a substitution reaction using Pro1-SM (M represents an alkali metal, preferably potassium) (B-2c) or converting a hydrophilic group into a suppressible group and performing a substitution reaction using Pro1-SM in the presence of a palladium catalyst and a phosphine (B-2d). B-2aD The solvent used can be, for example, an aromatic hydrocarbon such as benzene, toluene or?; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; or an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether, and preferably it is a halogenated hydrocarbon or an ether, and more preferably dichloromethane or tetrahydrofuran. The reagent employed in the Mitsunobu reaction is not particularly restricted so long as it can be used in general for the Mitsunobu reaction, and, for example, preferably it is a combination of an azo compound, including a di-lower alkyl-azodicarbo-ylate such as azodicarboxylate of diethyl or azodicarbo-diisopropyl ilate or a heterocyclyl azodicarbonyl such as 1,1 '- (azodicarbonyl) dipiperidine, and a phosphine, including a triarylphosphine such as triphenylphosphine or a tri-lower alkyl-phosphine such as tri-n-butylphosphine, and more preferably a combination of a di-lower alkyl-azodicarbo-ylate and a triarylphosphine, and most preferably a combination of diethylazodicarboxylate or diisopropyl azodicarboxylate and triphenylphosphine. The temperature of the reaction varies depending on the starting material and the reagent, and is between -50 ° C and 100 ° C, and preferably between -10 ° C and 60 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 10 minutes to 48 hours, and preferably from 30 minutes to 24 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separation of the organic layer containing the desired compound, drying of the organic layer over anhydrous magnesium sulfate or the like, and then evaporation of the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. IB-2b) The solvent employed may be, for example, an aromatic hydrocarbon such as benzene, toluene or γ-ylene; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; or an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hexamethylphosphoric triamide, and preferably is an aromatic hydrocarbon, and more preferably toluene. The acetal amide reagent employed can be, for example, a group of the general formula (CH3) 2NCH (OR ') 2 (wherein R' represents an alkyl group of 1 to 6 carbon atoms or an aralkyl group of 7 to 1 5 carbon atoms), and preferably it is N, N-dimethylformamide acetal dyneopentyl. The temperature of the reaction varies depending on the starting material and the reagent, and is between -50 ° C and 1 50 ° C, and preferably between -1 0 ° C and 1 20 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 1 minute to 24 hours, and preferably from 5 minutes to 5 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separation of the organic layer containing the desired compound, drying of the organic layer over anhydrous magnesium sulfate or the like, and then evaporation of the organic solvent to give the desired product. The product obtained, if necessary, it is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. ÍB-2ci The solvent used for the conversion reaction of a hydroxyl group to a suppressible group can be, for example, a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; or an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane or di (ethylene glycol) dimethyl ether, and preferably is a halogenated hydrocarbon, and more preferably dichloromethane. The base used can be, for example, an organic base such as pyrrolidine, piperidine, morpholine, N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di (t-butyl) -4-methyl pyridine, quinoline, N. N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [2.2.2] octane (DABCO) or 1,8-diazabicyclo [ 5.4.0] undec-7-ene (DBU), and preferably is 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU). The reagent employed is not particularly restricted as long as it forms a suppressible group by reacting with a hydroyl group, and the conversion to the suppressible group is achieved by the addition of a halogenating agent, a sulfonylating agent or an acylating agent. The halogenation agent employed can be a carbon tetrahalide such as carbon tetrabromide or carbon tetrachloride, and in these cases, a phosphine is used as the reagent. This phosphine can be, for example, a trialkylphosphine having 1 to 6 carbon atoms such as trimethylphosphine, triethylphosphine, tripropylphosphine, tributylphosphine, tripentylphosphine or trihe? Ilphosphine; a triarylphosphine of 6 to 10 carbon atoms such as triphenylphosphine, triindenylphosphine or trinaphthylphosphine; or a triarylphosphine of 6 to 10 carbon atoms which may have alkyl group (s) of 1 to 4 carbon atoms as a substituent (s), such as tolyldiphenylphosphine, tritolylphosphine, trimestylphosphine, tributylphinephosphine or tri-6-ethyl-2- naphthylphosphine, and preferably is a trialkylphosphine of 1 to 6 carbon atoms (particularly trimethylphosphine, triethylphosphine, tripropylphosphine or tributylphosphine) or a triarylphosphine of 6 to 10 carbon atoms (particularly triphenylphosphine, triindenophosphine or trinaphthylphosphine), and more preferably a triarylphosphine of 6 to 10 carbon atoms (particularly triphenylphosphine). The sulfonylating agent employed can be, for example, a sulfonyl halide such as methanesulfonyl chloride, ethanesulfonyl chloride or tosyl chloride, and preferably is methanesulfonyl chloride. The acylating agent used can be, for example, acetyl chloride, acetic anhydride, trifluoroacetic anhydride or the like. The temperature of the reaction varies depending on the starting material and the reagent, and is between -50 ° C and 100 ° C, and preferably between -20 ° C and 80 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 30 minutes to 24 hours, and preferably from 1 hour to 10 hours. The solvent employed in the substitution reaction of Pro1-SM may be, for example, an aromatic hydrocarbon such as benzene, toluene or γ-ylene; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cycloheanone; a nitro compound such as nitroethane or nitrobenzene; a nitrile such as acetonitrile or isobutyronitrile; an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hemiamethylphosphoric triamide; or a sulphonated such as sulphonated sulphonyl or sulfolane, and preferably is a halogenated hydrocarbon, an amide or a sulfoxide, and more preferably N, N-dimethylformamide, N, N-dimethylacetamide, dichloromethane or dimethyl sulfoxide. The base employed may be, for example, an inorganic base containing an alkali metal carbonate such as sodium carbonate, potassium carbonate or lithium carbonate.; a hydrogenated alkali metal carbonate such as hydrogenated sodium carbonate, hydrogenated potassium carbonate or hydrogenated lithium carbonate; an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride; an alkali metal hydroxide such as sodium hydroxide, potassium hydroxide or lithium hydroxide; and an alkali metal fluoride such as sodium fluoride or potassium fluoride; an alkali metal alkoxide such as sodium, sodium ethoxide, potassium methoxide, potassium ethoxide, potassium t-butoxide or lithium methoxide; an alkali metal mercaptan such as sodium mercaptan or sodium ethyl mercaptan; or an organic base such as N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di- ( t-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N. N -diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [2.2. 2] octane (DABCO) or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), and preferably is an alkali metal carbonate or an organic base, and more preferably potassium carbonate or triethylamine. The temperature of the reaction varies depending on the starting material and the reagent, and is between -50 ° C and 100 ° C, and preferably between -20 ° C and 80 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 30 minutes to 24 hours, and preferably from 1 hour to 10 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separation of the organic layer containing the desired compound, drying of the organic layer over anhydrous magnesium sulfate or the like, and then evaporation of the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. (B-2d The reaction for converting a hydroxyl group to a suppressible group can be carried out in a manner similar to (B-2c) The solvent of the subsequent substitution reaction employed can be, for example, an aliphatic hydrocarbon such as a halo, cyclohexane, heptane, ligroin, or petroleum ether, an aromatic hydrocarbon such as benzene, toluene, or urea, a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, or dichlorobenzene an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane, or dimethyl ether of di (ethylene glycol), a nitrile such as acetonitrile or isobutyronitrile, or a mixture of water and the solvents mentioned above, and preferably it is a mixture of water and dioxane The palladium catalyst employed can be, for example, palladium chloride, palladium acetate, tris (dibenzylidene ketone) dipalladium-chloroform adduc, fris (dibenzyl) idenacetone) dipalladium, bis (dibenzylidenacefonone) palladium, p-allyl palladium chloride dimer, tetracis (triphenylphosphine) palladium, 1,1'-bis (diphenylphosphino) ferrocene palladium dichloride, bis (triphenylphosphine) palladium chloride, bis acetate (triphenylphosphine) palladium, dichloro (1,5-cyclooctadiene) palladium, dichlorobis (acetonitrile) palladium, bis (tricyclohexylphosphine) palladium dichloride, bis (tricyclohexylphosphine) palladium, or bis (tri-0-tolylphosphine) palladium dichloride, and preferably it is palladium chloride, palladium acetate, adduct of tris (dibenzylidene ketone) dipalladium-chloroform or tri s (di benzyl acetone) di palladium. The phosphine used can be, for example, a trialkylphosphine of 1 to 6 carbon atoms such as trimethylphosphine, triethylphosphine, tripropylphosphine, tributylphosphine, tripentylphosphine or trihe? Ilphosphine; a triarylphosphine of 6 to 10 carbon atoms such as triphenylphosphine, triindenylphosphine or trinaphthylphosphine; a triarylphosphine of 6 to 10 carbon atoms which may be substituted with an alkyl group of 1 to 4 carbon atoms such as tolyldiphenylphosphine, tritolylphosphine, trimestylphosphine, tributylphenylphosphine or tri-6-ethyl-2-naphthylphosphine; a bis (diphenylphosphino) alkane of 1 to 6 carbon atoms such as bis (diphenylphosphino) methane, 1,2-bis (diphenylphosphino) ethane, 1,3-bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) butane, 1, 5-bis (diphenylphosphino) pentane or 1,6-bis (diphenylphosphino) henigene; or bis (diphenylphosphino) acetylene, 1,2-bis (diphenylphosphino) benzene, (R) - (+) - 2,2'-bis (diphenylphosphino) -1, 1'-biphenyl, 2,2'-bis (diphenylphosphino) ) -1, 1'-biphenyl, (S) - (-) - 2,2'-bis (diphenylphosphino) -1,1-biphenyl, 1,1 '-bis (diphenylphosphino) ferrocene, 1, 1-bis (diphenylphosphino) ethylene or 4,5-bis (diphenylphosphino) -9,9-dimethyl-antenn, and preferably is 1,1 '-bis (diphenylphosphino) ferrocene, (R) - (+) - 2,2'-bis (diphenylphosphino) -1, 1'-biphenyl, 2,2'-bis (diphenylphosphino) -1, 1'-biphenyl or (S) - (-) - 2,2'-bis (diphenylphosphino) -1, 1 ' -bubble. The temperature of the reaction varies depending on the starting material and the reagent, and is between 0 ° C and 1 50 ° C, and preferably between 50 ° C and 120 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 1 hour to 24 hours, and preferably from 6 hours to 20 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separation of the organic layer containing the desired compound, drying of the organic layer over anhydrous magnesium sulfate or the like, and then evaporation of the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. From (B-3) to (B-9D) Each of these steps is carried out in a manner similar to that indicated in (A-2) to (A-8) here in the foregoing, respectively. (Process 0) In the foregoing, Pro1, R2a, R3a and, n have the same meanings as those indicated herein above; R2b and R3b represent the same groups as those indicated for R2a and R3a described hereinbefore; and Pro2 represents a protecting group for an amino group. The protecting group for an amino group shown as Pro2 is the same as that indicated for R2a and R3a. Process C is described here in detail below. (C-11 This step is a step for the preparation of the compound (Vi l) by reacting the compound (VI) which is well known or is easily prepared from known compounds with a compound having the formula R2b-C (= 0) -R3b which is well known or can be easily prepared from known compounds, and is carried out by a route by means of enamination (C-1 a) or by cross-reaction with aldol (C-1) b). < C-1 a) The base employed may be, for example, an organic base such as pyrrolidine, piperidine, morpholine, N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di- (t-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N, N-dietlan Lina, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [2.2.2] octane (DABCO) or 1,8-diazabicyclo [5.4.0] undec-7 -eno (DBU), and preferable mind is pyrrolidine, piperidine or morpholine. The solvent employed can be, for example, an aromatic hydrocarbon such as benzene, toluene or iole; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an alcohol such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cycloheanol or 2-metho-ethanol; or an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; and preferably it is benzene, toluene or ethanol. The temperature of the reaction varies depending on the starting material and the reagent, and is between 0 ° C and 200 ° C, and preferably between 50 ° C and 1 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 30 minutes to 24 hours, and preferably from 1 hour to 1 0 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separation of the organic layer containing the desired compound, drying of the organic layer over anhydrous magnesium sulfate or the like, and then evaporation of the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. When the compound having a hydrophilic group which is an intermediate product of the reaction remains and the reaction is not completed, the desired product can be obtained by further carrying out a dehydration reaction in the presence of a base.

The solvent employed can be, for example, a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; or an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether, and preferably is a halogenated hydrocarbon, and more preferably dichloromethane. The base employed can be an organic base such as pyrrolidine, piperidine, morpholine, N-methylmorpholine, triethylamine, tripropylamine, tributylamine., diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di- (t-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [2.2.2] octane (DABCO) or 1,8-diazabicyclo [ 5.4.0] undec-7-ene (DBU), and preferably it is 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU). The reagent employed is not particularly restricted as long as it forms a suppressible group by reacting with a hydrophilic group, and the conversion to the suppressible group is achieved by the addition of a halogenating agent, sulfonylating agent or acylating agent. The halogenation agent employed can be, for example, a carbon tetrahalide such as carbon tetrabromide or carbon tetrachloride, and in these cases, a phosphine is used as the reagent. This phosphine can be, for example, a trialkylphosphine of 1 to 6 carbon atoms such as trimethylphosphine, triethylphosphine, tripropylphosphine, tributylphosphine, tripentylphosphine or trihexylphosphine.; a triarylphosphine of 6 to 10 carbon atoms such as triphenylphosphine, triindenylphosphine or trinaphthylphosphine; or triarylphosphine of 6 to 10 carbon atoms which may have alkyl group (s) of 1 to 4 carbon atoms as a substituent (s), such as tolyldiphenylphosphine, tritolylphosphine, trimestylphosphine, tributylphenylphosphine or tri-6-ethyl-2-naphthylphosphine , and preferably is a trialkylphosphine of 1 to 6 carbon atoms (particularly trimethylphosphine, triethylphosphine, tripropylphosphine or tributylphosphine) or a triarylphosphine of 6 to 10 carbon atoms (particularly triphenylphosphine, triindenylphosphine or trinaphthylphosphine), and more preferably a triarylphosphine of 6 to 10 carbon atoms (particularly triphenylphosphine). The sulfonylating agent employed can be, for example, a sulfonyl halide such as methanesulfonyl chloride, ethanesulfonyl chloride or tosyl chloride, and preferably is methanesulfonyl chloride. The acylating agent used can be, for example, acetyl chloride, acetic anhydride, trifluoroacetic anhydride or the like. The temperature of the reaction varies depending on the starting material and the reagent, and is between -50 ° C and 100 ° C, and preferably between -20 ° C and 80 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 30 minutes to 24 hours, and preferably from 1 hour to 10 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separation of the organic layer containing the desired compound, drying of the organic layer over anhydrous magnesium sulfate or the like, and then evaporation of the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. (C-1 b) The base employed can be, for example, an organic base such as pyrrolidine, piperidine, morpholine, N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di- (t-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N. N -diethylaniline, 1,5-diazabicyclo [4.3 .0] non-5-ene (DBN), 1,4-diazabicyclo [2.2.2] octane (DABCO) or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU); or an organometallic base such as butylthio, lithium diisopropylamide, lithium bis (trimethylsilyl) amide, sodium bis (trimethylsilyl) amide or potassium bis (trimethylsilyl) amide, and preferably is lithium diisopropylamide, lithium bis (frimethylsilyl) amide , sodium bis (trimethylsilyl) amide or potassium bis (trimethylsilyl) amide. The solvent employed can be, for example, an aromatic hydrocarbon such as benzene, toluene or iole; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an alcohol such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cycloheanol or 2-metho-ethanol; or an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or dimethyl ether of di (ethylene glycol), and preferably is tetrahydrofuran. The temperature of the reaction varies depending on the starting material and the reagent, and is between -1 00 ° C and 20 ° C, and preferably between -78 ° C and 0 ° C. The reaction time varies depending on the temperature of the reaction, the initial material, the reagent and the type of solvent used, and generally it is from 30 minutes up to 24 hours, and preferably from 1 hour to 5 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, by adding to the mixture an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water, by separation of the organic layer containing the desired compound, by drying the organic layer over anhydrous magnesium sulfate or the like, and then evaporating the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. When the compound having a hydrophilic group which is an intermediate product of the reaction remains, a dehydration reaction can be carried out in a manner similar to that indicated in (C-1 a). <; C-2) This step is a step for the reduction reaction by conversion of a carbonyl group of the compound (Vi 1) obtained in (C-1) to a hydrophilic group (C-2a). Further, when R2b is a hydrogen atom, R2a is not a hydrogen atom and R3b is an alkocarbonyl group, a reaction can be carried out to introduce a R2a group (C-2b). Further, when the R3b group contains an ester group, if necessary, a reaction can be carried out to introduce an appropriate protecting group for the hydro-yl group (C-2c), a reduction reaction to convert the ester group to a hydro-imethyl group (C-2d), a reaction for converting the R3b group containing the hydro-yl group to a R3a group (C-2e) and a reaction to remove the protecting group for the hydro-yl group (C -2f). Steps from C-2c to C-2f can be performed before or after steps C-2a and C-2b, and it is easy for a person skilled in the art to determine an appropriate order of these steps. (C-2a) The solvent employed may be, for example, an aromatic hydrocarbon such as benzene, toluene or γ-ylene; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; an alcohol such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol or 2-metho-ethanol; or a mixture of an alcohol and a halogenated hydrocarbon, and preferably it is an alcohol, a mixture of an alcohol and a halogenated hydrocarbon, or an ether, and more preferably methanol, ethanol, tetrahydrofuran or a mixture of said alcohol and dichloromethane. The reagent employed is not particularly restricted as long as it can be used for a reduction reaction of a carbonyl group in a hydroxyl group, and can be, for example, an aluminum hydride reagent or boron compound such as sodium borohydride or diborane , and preferably is sodium borohydride. The temperature of the reaction varies depending on the starting material and the reagent, and is between -78 ° C and 1 00 ° C, and preferably between 0 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 10 minutes to 1 2 hours, and preferably from 30 minutes to 5 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separation of the organic layer containing the desired compound, drying of the organic layer over anhydrous magnesium sulfate or the like, and then evaporation of the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. When R3b is different from R3a, it may be possible to introduce a substituent into an amino group, if necessary. In this case, after removing a protecting group for the amino group in a manner similar to that described in (A-7), the introduction of the substituent can be carried out as described below. The solvent employed can be, for example, an aromatic hydrocarbon such as benzene, toluene or iole; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate or diethyl carbonate; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or di (ethylene glycol) dimethyl ether; a ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone or cycloheanone; an amide such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone or hemiamethylphosphoric triamide; or a sulphonated such as sulphonated dimethyl or sulfolane, and preferably is a halogenated hydrocarbon or an amide, and more preferably N, N-dimethylformamide, N, N-dimethylacetamide or dichloromethane. The reagent employed is not particularly restricted as long as it can be used in the displacement reaction by an amino group, and can be, for example, a reagent in which a suppressible group such as a halogen atom or a sulfonyl group is attached to a desired functional group. The base employed may be, for example, an inorganic base, including an alkali metal carbonate such as sodium carbonate, potassium carbonate or lithium carbonate; a hydrogenated alkali metal carbonate such as hydrogenated sodium carbonate, hydrogenated potassium carbonate or hydrogenated lithium carbonate; an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride; an alkali metal hydroxide such as hydroxide of sodium, potassium hydroxide or lithium hydroxide; and an alkali metal fluoride such as sodium fluoride or potassium fluoride; an alkali metal alkoxide such as sodium methoxide, sodium ethoxide, potassium added, ethanol potassium, potassium t-butoxide or lithium methoxide; an alkali metal mercaptan such as sodium mercaptan or sodium ethyl mercaptan; or an organic base such as N-methylmorpholine, triethylamine, fripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di - (t-butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [ 2.2.2] octane (DABCO) or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), and preferably it is potassium carbonate, sodium hydride or DBU. The temperature of the reaction varies depending on the starting material and the reagent, and is between -30 ° C and 1 50 ° C, and preferably between 0 ° C and 100 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 5 minutes to 48 hours, and preferably from 10 minutes to 1 5 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separation of the organic layer containing the desired compound, drying of the organic layer over anhydrous magnesium sulfate or the like, and then evaporation of the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. C-2bi This step can be achieved by using an R2a-Lv or an aldehyde or ketone which forms a group R2a in an inert solvent in the presence of a base to give a compound of the general formula (Vi l). The solvent employed may be, for example, an aliphatic hydrocarbon such as hennium, cyclohexane, heptane, ligroin or petroleum ether; an aromatic hydrocarbon such as benzene, toluene or? ileum; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxide, dimethoxyethane or dimethyl ether of di (ethylene glycol); or a nitrile such as acetonitrile or isobutyronitrile, and preferably is tetrahydrofuran. The base used can be, for example, lithium diisopropylamide, lithium benzyl (frimethylsilyl) amide, lithium dimethylamide, lithium diethylamide, lithium bis (t-mephilesilyl) amide or lithium dicyclohexylamide, and preferably is lithium diisopropylamide. The reagent employed can be, for example, an alkyl halide of 1 to 6 carbon atoms such as methyl iodide, ethyl iodide or propyl iodide.; an alkyl mesylate of 1 to 6 carbon atoms; an alkyl tosylate of 1 to 6 carbon atoms; an aralkyl halide of 7 to 15 carbon atoms such as benzyl bromide, 1-naphthylmethyl bromide, 2-naphthylmethyl bromide or phenethyl bromide; an aralkyl mesylate of 7 to 1 5 carbon atoms; an aralkyl tosylate of 7 to 1 5 carbon atoms; an alkyl aldehyde of 1 to 6 carbon atoms such as formaldehyde or acetaldehyde; or an alkyl ketone of 1 to 6 carbon atoms such as acetone. The temperature of the reaction varies depending on the starting material and the reagent, and is between -100 ° C and 1 50 ° C, and preferably between -80 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reagent and the type of solvent employed, and is generally from 1 hour to 48 hours, and preferably from 1 hour to 1 0 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture, addition to the mixture of an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water , separating the organic layer containing the desired compound, drying the organic layer over anhydrous magnesium sulfate or the like, and then evaporating the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. fC-2c) This step is a step for the protection of a hydroxyl group, and can be easily accomplished according to procedures that are well known to a person skilled in the art (e.g., the procedure described in Protective Groups in Organic Synthesis, Third Edition, TW Green, et al., John Wiley &Sons, I nc. (1 999)), and preferably is silyl protection (particularly t-bufildimethylsilyl group). (C-2d) This step is achieved by reducing the compound (Vi l) in an inert solvent in the presence of a reducing agent. The solvent employed may be, for example, an aliphatic hydrocarbon such as hexane, cyclohexane, heptane, ligroin or petroleum ether; an aromatic hydrocarbon such as benzene, toluene or xylene; a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimetho-ietane or dimethyl ether of di (ethylene glycol); or an alcohol such as methanol, ethanol, propanol or isobutanol. When the reducing agent is lithium aluminum hydride, aluminum hydride and diisobutyl or diborane, the solvent employed may be an aliphatic hydrocarbon (particularly water or cyclohexane), an aromatic hydrocarbon (particularly benzene or toluene), a hydrocarbon halogenated (particularly dichloromethane) or an ether (particularly diethyl ether or tetrahydrofuran). When the reducing agent is sodium borohydride, the solvent employed may be an alcohol (particularly methanol or ethanol). The reducing agent employed can be, for example, an aluminum hydride compound such as aluminum lithium hydride or aluminum hydride and diisobutyl; sodium borohydride; or diborane, and preferably it is aluminum hydride and diisobutyl. The temperature of the reaction varies depending on the starting material and the reagent, and is between -100 ° C and 100 ° C, and preferably between -80 ° C and 50 ° C. The reaction time varies depending on the temperature of the reaction, the starting material, the reaction reagent and the type of solvent employed, and is generally from 10 minutes to 24 hours, and preferably from 30 minutes to 5 hours. After completion of the reaction, the desired compound of this reaction can be obtained, for example, by concentration of the reaction mixture., by adding to the mixture an organic solvent immiscible with water such as ethyl acetate, washing the mixture with water, by separating the organic layer containing the desired compound, drying the organic layer over anhydrous magnesium sulfate or the like, and then evaporation of the organic solvent to give the desired product. The product obtained, if necessary, is further purified by conventional treatments, for example, by recrystallization, reprecipitation, column chromatography on silica gel or the like. (C-2e) This step is carried out by the Mitsunobu reaction in an inert solvent using an amine or the like (C-2e1) or by a substitution reaction using an amine or the like after converting a hydrophilic group into a suppressible group (C-2e2). Step (C-2e1) can be carried out in a manner similar to that indicated in (B-2a) eceptic because an amine or the like is used in place of Pro1-SM. Step (C-2e2) can be carried out in a manner similar to that indicated in (B-2c) except that an amine or the like is used in place of Pro1 -SM. <; C-2fl This step is a step for the deprotection of a protecting group for a hydroxyl group, and can be easily accomplished according to procedures that are well known to a person skilled in the art (e.g., the procedure described in Protective Groups in Organic Synthesis, Third Edition, TW Green, et al. , John Wiley & Sons, Inc. (1 999)). (C-Z) This step is carried out in a manner similar to that indicated in A-7, and is carried out much more preferably using trifluoroacetic acid or acetic acid. (C-4) This step is carried out in a manner similar to that indicated in B-2 (C-5) This step is carried out in a manner similar to that indicated in C-3 The compound (I) of the present invention, salts thereof or prodrugs thereof pharmacologically acceptable exerts inhibitory activity in the inhibition of platelet aggregation. In addition, the compound (I) of the present invention, pharmacologically acceptable salts thereof or prodrugs thereof exhibit excellent pharmacokinetic properties such as absorption, distribution, permanence in plasma, and the like, and low toxicities in organs such as the kidney, the and similar. Thus, the compound (I) of the present invention, pharmacologically acceptable salts thereof or prodrugs thereof are useful, for example as drugs, and particularly useful as therapeutic or prophylactic agents for various thrombotic diseases. When a compound of the present invention is used as a prophylactic or therapeutic agent for diseases as described above, said compound having the general formula (I), or pharmacologically acceptable salts thereof or prodrugs thereof, may be administered alone or as a mixture with pharmaceutically acceptable excipients, diluents and the like, in various dosage forms such as tablets, capsules, granules, powders, syrups or the like for oral administration; and injections, suppositories, patches, external application or the like for parenteral administration. Each of the above formulations can be prepared by well-known methods using additives for the formulation such as excipients (e.g., organic excipients, including sugar derivatives such as lactose, sucrose, glucose, mannitol or sorbitol; starch derivatives such as starch of corn, potato starch, α-starch or trine; cellulose derivatives such as crystalline cellulose; acacia; pulp; and inorganic yeasts including silicate derivatives such as light silicic acid anhydride, aluminum silicate synthetic, calcium silicate, or magnesium aluminum metasilicate, phosphate derivatives such as hydrogenated calcium phosphate, carbonate derivatives such as calcium carbonate, or sulfate derivatives such as calcium sulfate), lubricants (e.g., stearic acid) metal stearate derivatives such as calcium stearate or magnesium stearate; talcum; colloidal silica; waxes such as wax d e bees or spermaceti; boric acid; adipic acid; sulfate derivatives such as sodium sulfate; glycol; fumaric acid; sodium benzoate; DL-leucine; lauryl sulfate derivatives such as sodium lauryl sulfate or magnesium lauryl sulfate; silicic acid derivatives such as silicic anhydride or silicic acid hydrate; or starch derivatives described above), binders (eg, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, macrogol, such as those described above), disintegrants (eg, cellulose derivatives such as substituted hydropropylcellulose, carbohydrate, carbohydrate, carbohydrate) calcium mesoimethylcellulose or internally crosslinked sodium carboethylmethylcellulose, or chemically modified starch or cellulose derivatives such as carboxymethylstarch, sodium carboxymethyl starch, or crosslinked polyvinylpyrrolidone), emulsifiers (eg, colloidal clay such as bentonite or veegum; metals such as magnesium hydroxide or aluminum hydroxide, anionic surfactants such as sodium lauryl sulfate or calcium stearate, cationic surfactants such as benzalkonium chloride, and nonionic surfactants such as polyoxyethylene alkyl ethers, fatty acid esters polyoyethylene sorbitan or fatty acid esters of sucrose), stabilizers (eg, para-hydro-ibenzoic acid ester derivatives such as methylparaben or propylparaben; alcohol derivatives such as chlorobutanol, benzyl alcohol or phenylethyl alcohol; benzalkonium chloride; phenol derivatives such as phenol or cresol; thimerosal; dehydroacetic acid; or sorbic acid), corrective agents (for example, sweeteners, acidifying agents, flavoring agents or the like that are conventionally used) and diluents. The specific dose of a compound of the present invention will vary according to the severity of the patient's symptoms, age and the like. For oral administration to a human adult the amount of active ingredient in a unit dose may be in the range from 0.01 6 mg / kg (preferably 0.5 mg / kg) to 33.3 mg / kg (preferably 25 mg / kg). A dose unit for intravenous administration may be in the range of 0.008 mg / kg (preferably 0.08 mg / kg) to 8.3 mg / kg (preferably 4.2 mg / kg) of a compound of the present invention. The dose unit can be administered to a human adult from 1 to 6 times per day depending on the severity of the patient's symptoms. Examples Hereinafter, the present invention will be described in greater detail by means of Examples, test examples and formulation examples. When CDCI3 is used as the solvent for the measurement of hydrochloride compounds in the Examples, the NM N data for the corresponding free bases are shown. The free bases can be obtained by treating a small amount of a hydrochloride compound with an aqueous solution of hydrogenated sodium carbonate and performing the extraction with ethyl acetate or dichloromethane. (Example 1) dihydrochloride of (E) ° 4 ° (AcetilsuBfapiBi) ° 1 f2-cyll?) P? Ropi 1- (2-fluorofen-2-oxoethyl-3-3- (morpholin-4-inethylide1pi pendo ipia ( Hydrochloride of compound of Compound No.5-28) (a) (E) -4- (t-Butyldimethylsilyloxy) -3-f (ethoxycarbo? p? 8)? and ill lep? 1 ° 1l ° (triphenylmethyl) piperi ina To a solution of (E) -3 - [(ethoxycarbonyl) methylidene] -1- (triphenylmethyl) piperidin-4-ol (14.97 g) in N, N-dimethylformamide (130 mL) was added t-butyldimethylsilyl chloride (6.86 g), imidazole (3.34 g) and 4-dimethylaminopyridine (0.43 g) under ice-cooling, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/19) to obtain the title compound (16.38 g, 86% yield) as a colorless amorphous solid. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.01 (3H, s), 0.02 (3H, s), 0.90 (9H, s), 1.12 (3H, t, J = 7.0), 1.59-1.74 (1H, m), 1.83-2.01 (3H, m), 3.00-3.12 (1H, m), 3.90 (1H, t, J = 9.0), 3.96-4.15 (2H, m), 4.73 (1H, m), 6.06 ( 1H, s), 7.11-7.18 (3H, m), 7.20-7.28 (6H, m), 7.36-7.54 (6H, m). (b) (E) -4- (t ° ButyldimethylsipoxyD-3 ° (2-had [rox5et5Bid®? p] D "1" (triphenylmetippiperidine To a solution of (E) -4- (t-butyldimethylsilyloxy) -3- [(ethocarbonyl) methylidene] -1- (triphenylmethyl) piperidine (15.14 g) obtained in (a) above, in dichloromethane (110 mi) was added a solution of 1.01N diisobutylaluminum hydride in toluene (66.40 ml) at -70 ° C, and the resulting mixture was stirred at the same temperature for 3 hours.The reaction mixture was charged with an aqueous solution of ammonium chloride and then it was brought with ethyl acetate.The extract was washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate.The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/3) to obtain the title compound (13.22 g, 95% yield) as a colorless amorphous solid. (400 MHz, CDCl 3) d ppm: 0.01 (6H, s), 0.88 (9H, s), 1.62-2.00 (4H, m), 2.88-3.05 (1H, m), 3.51-3.71 (1H, m ), 3.86 (1H, m), 4.07-4.24 (2H, m), 5.79 (1H, t, J = 7.0), 7.11-7.33 (9H, m), 7.36-7.58 (6H, m). (cj (Eμ4- (ft-Butyldimethylsilyloxyμ3-í2- (tosinoxB) etiBi] e? nM ° (triphenylmethyl) piperidine To a solution of (E) -4- (t-butyldimethylsilyl) i) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine (1.11 g) obtained in (b) above, and p-toluenesulfonic anhydride (0.90 g) in dichloromethane (25 ml), triethylamine (0.37 ml) was added under cooling with ice, and the resulting mixture was stirred at room temperature for 2.5 hours. The reaction mixture was charged with a saturated aqueous solution of sodium chloride and then brought with ethyl acetate. The tract was washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo to obtain the title compound (1.64 g, quantitative yield) as a light yellow oil. 1 H NMR (400 MHz, CDCl 3) d ppm: -0.04 (3H, s), -0.01 (3H, s), 0.86 (9H, s), 1.60-1.92 (4H, m), 2.47 (3H, s) , 2.96 (1H, bs), 3.47 (1H, m), 3.79 (1H, m), 4.61 (2H, m), 5.65 (1H, t, J = 7.5), 7.13-7.48 (17H, m), 7.73 (2H, d, J = 9.0). id} (E) -4-ft-Butyldim? TlsiMloxy) -3-r2- (morpholin-4-yl) ethillic.Tn1-1l- (triphen i I meti I) piperidine To a solution of (E ) -4- (t-butyldimethylsilyloxy) -3- [2- (tosyl? I) ethylidene] -1- (triphenylmethyl) piperidine (1.64 g) obtained in (c) above, and morpholine (0.29 ml) in a mixed solvent of N, N-dimethylformamide (25 ml) and dichloromethane (50 ml) was added potassium carbonate (0.34 g) under ice-cooling, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was charged with a saturated aqueous solution of sodium chloride and then brought with ethyl acetate. The tract was washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / hexane = 2/3) to obtain the title compound (1.01 g, yield: 80%) as an oil colorless. 1 H NMR (400 MHz, CDCl 3) d ppm: -0.03 (3H, s), -0.02 (3H, s), 0.84 (9H, s), 1.74-2.06 (4H, m), 2.42 (4H, bs) , 2.77-2.93 (1H, m), 2.99 (1H, dd, J = 13.5, 6.5), 3.07 (1H, dd, J = 13.5, 6.5), 3.38-3.56 (1H, m), 3.71 (4H, t , J = 4.5), 3.87 (1H, m), 5.62 (1H, t, J = 6.5), 7.11-7.30 (9H, m), 7.38-7.55 (6H, m). . { eg (E -4-HydroxB-3 ° r2 ° (morfoy? p ° 4-inetiaid®p? 1 ° 1l ° (triphenylmethyl) piperidine To a solution of (E) -4- (t-butyldimethylsilyloxy) -3- [2- (morpholin-4-yl) ethylidene] -1 - (triphenylmethyl) piperidine (1.00 g) obtained in (d) In tetrahydrofuran (20 mL), tetrabutylammonium fluoride (0.99 g) was added under cooling with ice, and the resulting mixture was stirred at room temperature for 14 hours. The reaction mixture was charged with water and then extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (methanol / dichloromethane = 9/91) to obtain the title compound (0.80 g, quantitative yield) as a colorless oil. 1 H NMR (400 MHz, CDCl 3) d ppm: 1.74-1.86 (1H, m), 1.96-2.14 (2H, m), 2.45 (5H, bs), 2.59-2.69 (1H, m), 3.01 (2H, m), 3.10- 3.34 (1 H, m), 3.72 (4H, t, J = 4.5), 3.98 (1 H, m), 5.61 (1 H, t, J = 6.5), 7.1 1 -7.32 (9H , m), 7.39-7.57 (6H, m). Hydrochloride (E-Hydroxy-3-IT2- (mo? rfollii) -4- -Detilidenlpiperidirsa To a solution of (E) -4-hydro? i-3- [2- (morpholin-4 -yl) ethylidene] -1- (triphenylmethyl) piperidine (1.08 g) obtained in (e) above in dioxide (9 ml) was added a solution of 4N hydrogen chloride in dioxide (3 ml). under cooling with ice, and the resulting mixture was stirred at room temperature for 15 minutes.The reaction mixture was evaporated in vacuo, and the residue was partitioned with water and ethyl acetate.The aqueous layer was removed in vacuo to obtain the compound of the title (0.69 g, quantitative yield) as a light yellow amorphous solid.1 NMR with 1 H (400 MHz, DMSO-d6) d ppm: 1.66-1.77 (1 H, m), 1.95- 2.07 (1 H, m), 3.10 (4H, m), 3.21 -3.65 (3H, m), 3.73-4.02 (6H, m), 4.06 (1H, d, J = 13.5), 4.19 (1H, m), 5.90 (1 H, t, J = 8.0) a (E -1 -f2-Cyclopropyl-1 - (2-fluorophenyl)> 2-QxoTtini ° 4-hndr? ^ i ° 3-í2- ( morpholin-4-yl) ethylidene piperidine To a solution of di (E) -4-hydro? i -3- [2- (morpholin-4-yl) ethylidene] piperidine hydrochloride (0.65 g) obtained in (f) above and 2-bromo-2- (2-fluorophenyl) - 1-Cyclopropyletanone (0.73 g) in N, N-dimethylformamide (12 mL) was added triethylamine (1.16 mL) under ice-cooling, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (methanol / dichloromethane = 3/17) to obtain the title compound (0.65 g, yield 74%) as a light yellow amorphous solid. . 1 H NMR (500 MHz, CDCl 3) d ppm: 0.78-0.90 (2H, m), 0.96-1.09 (2H, m), 1.66-1.78 (1H, m), 1.95-2.04 (1H, m), 2.15- 2.25 (1H, m), 2.42 (4H, bs), 2.45-2.55 (1H, m), 2.78 and 3.00 (total 1H, each d, J = 12.5), 2.79-2.88 (1H, m), 2.95 (2H , d, J = 6.5), 3.31 and 3.45 (total 1H, each d, J = 12.5), 3.70 (4H, t, J = 4.5), 4.09 and 4.13 (total 1H, each m), 4.69 and 4.71 (total 1H, each s), 5.59 and 5.61 (total 1H, each t, J = 6.5), 7.11 (1H, m), 7.17 (1H, m), 7.29-7.36 (1H, m), 7.38-7.45 (1H, m). Ib) dihydrochloride of (E -4- (AcetylsulfaniB) ° 1 ° 2 ° C-chloropoly H- (2-fluorophenyl) -2-oxoetill-3-f2 ° (morpholin-4-yl) etiBideBi1p? Erndna To a solution of ( E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-hydro? I -3- [2- (morpholin-4-yl) ethylidene] piperidine (890 mg) obtained in (g) above in toluene (15 ml) was added thioacetic acid (0.33 ml) and dyneopentyl acetal of N, N-dimethylformamide (1.92 ml) under cooling with ice, and the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate, the solvent was removed in vacuo, and the residue was purified. by chromatography on a column of silica gel (methanol / dichloromethane = 1/19) to produce the free form (393 mg, yield 38%) of the title compound as a colorless amorphous solid. To a solution of a portion of this compound (88 mg) in dioe (4 ml) was added a solution of hydrogen chloride in 4N dioxide (0.25 ml) at room temperature, and the solvent was removed in vacuo. to obtain the title compound (11.1 mg, quantitative yield) as a colorless amorphous solid. NMR with H (400 MHz, CDCl 3) d ppm: 0.76-0.90 (2H, m), 0.95-1.10 (2H, m), 1.74-1.85 (1 H, m), 2.06-2.24 ( 2H, m), 2.28 and 2.29 (total 3H, each s), 2.38 (4H, bs), 2.47-2.79 (2H, m), 2.80 and 3.06 (total 1 H, each d, J = 12.5), 2.88 and 2.94 (total 2H, each d, J = 6.5), 3.29 and 3.37 (total 1 H, each d, J = 12.5), 3.69 (4H, m), 4.30 and 4.33 (total 1 H, each t, J = 4.5 ), 4.68 and 4.70 (total 1 H, each s), 5.64 (1 H, t, J = 6.5), 7.07-7.20 (2H, m), 7.29-7.43 (2H, m); IR (KBr, cm "1): 1700, 1494. (Example 2) dihydrochloride of (E-r2-C-cyclopropyl-, 2-f.uo-rof8o? Il) -2-oxoetiH-3-r2- (morpholin-4 ° il) etiiidenl-4-suifa? pilpiperidium (Compound Hydrochloride of Compound No. 5-27) To a solution of (E) -4- (acetylsulfanyl) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3- [2- (morpholin-4-yl) ethylidene] piperidine (180 mg) obtained in example 1 (h) in methanol (4 ml) was added potassium carbonate (48 mg) under cooling with ice, and the resulting mixture was stirred at room temperature for 15 minutes. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified using a preparative HPLC (YMC-Pack ODS-A; YMC, eluent: acetonitrile / 0.024N hydrochloric acid = 15/85) to obtain the title compound (83 mg, yield 50%) as a colorless amorphous solid. NMR with 1H (400 MHz, CDCl 3) d ppm: 0.77-0.91 (2H, m), 0.95-1.10 (2H, m), 1.67-1.77 (1H, m), 2.12-2.26 (2H, m), 2.39 ( 4H, bs), 2.46-2.95 (3H, m), 2.88 and 3.20 (total 2H, each d, J = 7.0), 3.13 and 3.37 (total 1H, each d, J = 12.5), 3.69 (4H, m) , 3.80 (1H, m), 4.71 and 4.73 (total 1H, each s), 5.59 and 5.62 (total 1H, each t, J = 7.0), 7.07-7.21 (2H, m), 7.28-7.37 (1H, m ), 7.39-7.45 (1H, m); IR (KBr, crn 1): 2556, 1712, 1494. (Example 3.}. (E) -4- (Acetylsulfanyl) -1 ° f2-cyclopropyl-1 ° (2 ° fluorofep? Ñü-2 ° oxo®t5B1 ° 3 ° f2- (pi perid i n-1 -i heti I idenl piperidine (Compound Bel eos aesto No.5-2D (a) (E) -4- (t-ButyldimethylsilyloxyB) -3-f2 ° (piperBdip ° 1 -inet5Bid®g? 1 ° 'a (triphenylmethyl) piperidine The title compound was synthesized in a yield of 67% as a colorless oil using piperidine in place of morpholine performing a reaction similar to that mentioned in Example 1 (d). 1 H NMR (400 MHz, CDCl 3) d ppm: -0.01 (6H, s), 0.81 (9H, s) ), 1.37-1.61 (8H, m), 1.74-1.93 (2H, m), 2.31-2.39 (4H, m), 2.75-3.07 (4H, m), 3.86 (1H, m), 5.63 (1H, t , J = 6.5), 7.11-7.18 (3H, m), 7.21-7.28 (6H, m), 7.41-7.51 (6H, m). Ib) (E) -4-Hydroxy-3-r2-phiP? Ri < .in-1-benzyldenM "(trifeinyl) phenyl) piperidine The title compound was synthesized in a quantitative yield as a colorless oil using (E) -4- (t-butyldimethylsilyl) -3- [2 - (piperidin-1-yl) ethylidene] -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e). 1 H NMR (500 MHz, CDCl 3) d ppm: 1.48-2.11 (14H, m), 2. 69-3.46 (4H, m), 4.01 (1H, m), 5.89 (1H, t, J = 5.0), 7.15-7.21 (3H, m), 7.24-7.31 (6H, m), 7.40-7.51 (6H , m). ic) bis (hydrogenated trifluoroacetate of (ED-4-Hn'dro) 3-f2 ° (pi perid i n-1 -i Deti I idenl piperidine To a solution of (E) -4-hydro? i-3- [2- (piperidin-1-yl) ethylidene] -1- (triphenylmethyl) piperidine (412 mg) obtained in (b) above in dichloromethane (10 ml) was added trifluoroacetic acid (0.21 ml) under cooling with ice, and The resulting mixture was stirred at room temperature for 3 hours, and trifluoroacetic acid (0.21 ml) was added to the reaction mixture, and the resulting mixture was stirred at room temperature for additional 1 hour. methanol (5 ml) was added, and the resulting mixture was evaporated in vacuo.The residue was partitioned with water and ethyl acetate, and the aqueous layer was removed in vacuo to obtain the title compound (403 mg, quantitative yield) as a light yellow amorphous solid. NMR with 1H (400 MHz, CDCl 3) d ppm: 1.35-1.49 (2H, m), 1.82-2.21 (6H, m), 2.73-2.82 (2H, m), 3.45-3.88 (7H, m ), 4.12 (1H, d, J = 13.0), 4.31-4.36 (1H, m), 6.01 (1H, t, J = 8.0). (d) (E »-1 2-CyclopropiB" 1 ° (2-fBuorofeniiμ2-oxoetBni ° 4-hydro? i "3-f2" (piperid i n-1 -i Deti I idenl piperidine The title compound was synthesized in a 60% yield as a light yellow oil using bis (hydrogenated trifluoroacetate) of (E) -4-hydro? i-3- [2 - (piperidin-1-yl) ethylidene] piperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.79-1.10 (4H, m), 1.38- 1.84 (8H, m), 1.93-2.03 (1H, m), 2.21-2.55 (6H, m), 2.78-3.01 (3H, m), 3.32 and 3.41 (total 1H, each d, J = 12.5), 4.08-4.14 (1H, m), 4.67 and 4.69 (total 1H, each s), 5.63 and 5.64 (total 1H, each t, J = 7.0), 7.07- 7.19 (2H, m), 7.28-7.46 (2H, m). le) (E) -4- (AcetBlsulfanyl) -1-r2-cyclopropy »H ° (2 ° foruoff®o? B ° 2 ° oxoetip-3-r2- (pi eridin-1-yl) etiBide? t) 1-piperidine To a solution of triphenylphosphine (290 mg) in tetrahydrofuran (4.5 ml) under a stream of nitrogen gas was added a 40% solution of diisopropyl azodicarboxylate in toluene (0.59 ml) at -10 ° C, and The resulting mixture was stirred at the same temperature for 1 hour. Then, a solution of (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -4-hydro? I-3 was added dropwise to a reaction mixture. - [2- (piperidin-1-yl) ethylidene] piperidine (211 mg) in tetrahydrofuran (1.5 ml) obtained in (d) above and thioacetic acid (0.14 ml), and additionally the resulting mixture was stirred at room temperature for 22 hours. hours. The reaction mixture was evaporated in vacuo, and the residue was purified by chromatography on a silica gel column (methanol / dichloromethane = 1/49) to obtain the title compound (138 mg, 57% yield) as an oil light yellow. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.78-0.90 (2H, m), 0.96-1.08 (2H, m), 1.41-1.50 (2H, m), 1.59-1.71 (4H, m), 1.75- 1.84 (1H, m), 2.07-2.23 (2H, m), 2.28 and 2.29 (total 3H, each s), 2.40-3.10 (9H, m), 3.16-3.39 (1H, m), 4.29 and 4.33 (total 1H, each t, J = 4.5), 4.68 and 4.72 (total 1H, each s), 5.69 (1H, t, J = 6.5), 7.08-7.21 (2H, m), 7.29-7.41 (2H, m); IR (liquid film, cm "1): 1696, 1488. (Example 4) hydrogenated bisftrifBuoroacetate]) of El) ° 1l-f2 ° Cyclopropyl-1- (2-fluorofenBl) -2-oxoetiB1-3 2 ° (piperidine) 1l ° Bl) ethylidene-4-sulfanylpBperidine (Trifluoroacetate leB cooTpipyte of B Compound No.5-1) The title compound was synthesized in an 11% yield as a colorless oil using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3 - [2- (piperidin-1-yl) ethylidene] piperidine obtained in Example 3 (e) by performing a reaction similar to that mentioned in Example 2. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.76-0.93 ( 2H, m), 0.99-1.10 (2H, m), 1.31-1.47 (2H, m), 1.63-2.07 (7H, m), 2.22-2.32 (1H, m), 2.56-3.87 (10H, m), 4.93 and 4.98 (total 1H, each s), 5.74 (1H, t, J = 6.5), 7.15-7.31 (3H, m), 7.36-7.46 (1H, m); MS (FAB) m / z: 403 (M + H) +. (Example 5) dicl orhidrate of leE) -4- (Acetyl-sulfa nill-H 42- • cid loiairopyD- 1- (2-fluorophenyl) • 2-oxoetii 3 2-ithi omorfoli-n-4- iUetiD odeiDl piperidine (Clor - O -hydrate of compound I Compound No. 5-30) (a) (E) -4- (ft-ButBldimethylsiloBoxi) -3-r2- (thiomorpholBir8 ° 4 -inet? nñl®p1 ° 1l- (triphenyl methyl I) piperidine The title compound was synthesized in a yield of 62%. % as a colorless oil using thiomorpholine in place of morpholine performing a reaction similar to that mentioned in Example 1 (d). 1 H NMR (500 MHz, CDCl 3) d ppm: -0.03 (3H, s), -0.02 (3H , s), 0.84 (9H, s), 1.76-1.95 (4H, m), 2.61-2.72 (7H, m), 2.77-2.91 (1H, m), 2.98-3.10 (2H, m), 3.31-3.66 (2H, m), 3.87 (1H, m), 5.56-5.63 (1H, m), 7.10-7.19 (3H, m), 7.21-7.35 (6H, m), 7.38-7.53 (6H, m). (b) (E) ° 4-Hydroxy-3- 2- (thiomorpholin-4-yl) ethylideraM- (triferaranimethyl B) piperidine The title compound was synthesized in 99% yield as a pale yellow amorphous solid using (E) ) -4- (t-butyldimethylsilyloxy) -3- [2- (thiomorpholin-4-yl) ethylidene] -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e) ). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.61-1.87 (2H, m), 1.98-2.14 (2H, m), 2.60-2.80 (8H, m), 2.98-3.06 (2H, m), 3.35- 3.46 (2H, m), 3.93-4.02 (1H, m), 5.58 (1H, t, J = 6.0), 7.12-7.20 (3H, m), 7.22-7.32 (6H, m), 7.38-7.56 (6H , m). (c) bis (hydrogenated acetate) of (E) -4 ° Hydro B-3 ° ¡2 ° (tiomo? rf @ CñBi ° 4-BPetilidenlpiperidina To a solution of (E) -4-hydro? i-3- [ 2- (thiomorpholin-4-yl) ethylidene] -1- (triphenylmethyl) piperidine (4.91 g) obtained in (b) above in dichloromethane (100 ml) was added acetic acid (44 ml) at room temperature, and the mixture The resulting mixture was refluxed for 1 hour.The reaction mixture was evaporated in vacuo, and the residue was purified by chromatography on a column of silica gel on a column of silica gel (methanol / dichloromethane = 1/4) obtain the title compound (3.56 g, 98% yield) as a light brown crystal.1 H NMR (400 MHz, CDCl 3) d ppm: 1.61-1.70 (1H, m), 1.97-2.02 (1H, m), 2.62 -2.77 (8H, m), 2.82-2.90 (1H, m), 3.02-3.08 (2H, m), 3.17-3.23 (2H, m), 3.74-3.78 (1H, m), 4.15-4.20 (1H, m), 5.58 (1H, t, J = 6.0). (d) (E) -1-f2-Cyclopropyl-1 ° (2-fBuorofeni¡) ° 2-oxoetiB1 ° 4-hBdro ^ i ° 3 -i2 ° (thiomorph i n-4-yl) ethylidene piperidine The title compound was synthesized in 65% yield as a light brown amorphous solid using (E) -4-hydro? i-3- [2] hydrogenated bis (hydrogenated acetate). - (thiomorpholin-4-yl) ethylidene] piperidine obtained in (c) above performing a reaction similar to the one mentioned in Example 1 (g). 1 H NMR (500 MHz, CDCl 3) d ppm: 0.76-1.12 (4H, m), 1.61-1.82 (1H, m), 1.94-2.04 (1H, m), 2.14-2.24 (1H, m), 2.44- 2.54 (1H, m), 2.59-2.73 (8H, m), 2.76 and 2.98 (total 1H, each d, J = 12.5), 2.77- 2.89 (1H, m), 2.96 (2H, d, J = 7.0) , 3.30 and 3.45 (total 1H, each d, J = 12.5), 4.05-4.16 (1H, m), 4.69 and 4.70 (total 1H, each s), 5.54-5.62 (1H, m), 7.06-7.22 (2H, m), 7.28-7.46 (2H, m). (e) (E) -4- (AcetylsulfanBB) dihydrochloride 1 2 ° c5cBoprop5B ° 1 ° (2 ° fluorophenyl) -2-oxoetiH-3-r2- (thiomorpholin-4 ° B8) ethylBdenTpiperid5? pg) was synthesized Title compound in a 26% yield as a light yellow powder crystal using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -4-hydro? i-3- [ 2- (thiomorpholin-4-yl) ethylidene] piperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (h). NMR with 1H (500 MHz, CDCl 3) d ppm: 0.74-1.12 (4H, m), 1.50-1.62 (1H, m), 1.74-1.85 (1H, m), 2.06-2.27 (2H, m), 2.29 and 2.30 (total 3H, each s), 2.44-2.72 (9H, m), 2.77 and 3.04 (total 1H, each d, J = 12.5), 2.84-2.98 (2H, m), 3.27 and 3.35 (total 1H, each d, J = 12.5), 4.26-4.36 (1H, m), 4.67 and 4.70 (total 1H, each s), 5.57-5.64 (1H, m), 7.07-7.22 (2H, m), 7.28-2.45 (2H , m); MS (FAB) m / z: 463 (M + H) +. (Example 6) dihydrochloride of (E) "1-r 2-CicDopropsl 1N (2" fluoc 2-oxoetH-4-sulfanyl-3 2 (iomorpholin-4-yl) etISISEELE 5peridip; (Hydrochloride of the Compound No.5-28) The title compound was synthesized in a 94% yield as a light yellow powder crystal using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl ] -3- [2- (thiomorpholin-4-yl) ethylidene] piperidine obtained in Example 5 (e) by performing a reaction similar to that mentioned in Example 2. 1 H NMR (500 MHz, CDCl 3) d ppm: 0.77 -1.12 (4H, m), 1.68-1.77 (1H, m), 2.11-2.27 (2H, m), 2.55-2.71 (9H, m), 2.72-2.85 (1H, m), 2.86-2.97 (2H, m), 3.13-3.24 (1H, m), 3.11 and 3.36 (total 1H, each d, J = 12.5), 3.70-3.82 (1H, m), 4.72 and 4.70 (total 1H, each s), 5.51-5.63 (1H, m), 7.07-7.21 (2H, m), 7.29-7.45 (2H, m); MS (FAB) m / z: 418 (M + H) +. (Example 7) (E) -4- (Acetylsuifanl) -1 2-cicBop? Rop5B ° 1l (2-fB or? Roife? N? In 2-oxoetill-342- (3 ° oxopiperazim-1 ° il ) ethylidenepiperi 5? p? a (Compound of compound No.5-88) (a) (E) ° 4- (t ° Butyldimethylsilyloxy) -342- (3 ° oxopiperazim-14B) eftiD5 of αm1l "1- (triphenylmethyl) piperidBna The title compound was synthesized in a yield of 66. % as a light brown oil using 2-oxopiperazine in place of morpholine performing a reaction similar to that mentioned in Example 1 (d). RMN with 1H (500 MHz, CDCl 3) d ppm: 0.02 (6H, s), 0.85 ( 9H, s), 1.72-1.95 (4H, m), 2.60-2.66 (2H, m), 2.80-3.19 (5H, m), 3.25-3.47 (3H, m), 3.82-3.90 (1H, m), 5.57-5.64 (1H, m), 7.13-7.21 (3H, m), 7.22-7.32 (6H, m), 7.39-7.57 (6H, m). (B) (E) -4-Hydroxy-3-r2 - (3 ° oxopiperazin-14l) etiideEi1 1l- (trifferiflnmetiB) piperidine The title compound was synthesized in a 96% yield as a light yellow oil using (E) -4- (t-butyldimethylsilyl i) - 3- [2- (3-oxopiperazin-1-yl) ethylidene] -1- (triphenylmethyl) piperidine obtained in (a) above performing a reaction similar to that mentioned in Example 1 (e) 1 H NMR (400 MHz, CDCl 3) d ppm: 1.75-2.12 (4H, m), 2.62-2.69 (2H, m), 3.02- 3.16 (2H, m), 3.32-3.42 (6H, m), 3.92-4.01 (1H, m), 5.57-5.62 (1H, m), 7.12-7.20 (3H, m), 7.22-7.31 (6H, m ), 7.38-7.56 (6H, m). (c) bis (hydrogenated acetate) of (E) ° H-hydroxy-3-y2- (3 ° oxopiperazin-1-yl) eti I idenl piperidine The title compound was synthesized in an 85% yield as a light brown glass using (E) -4-hydro? I -3- [2- (3-o? Opiperazin-1-yl) ethylidene] -1- (triphenylmethyl) piperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 5 (c). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.59-1.73 (2H, m), 2.57-2.61 (1H, m), 2.64-2.70 (2H, m), 3.08-3.25 (5H, m), 3.29- 3.39 (3H, m), 3.73-3.78 (1H, m), 4.16-4.22 (1H, m), 5.56-5.63 (1H, m). (d) (E) -142-Cyclopropyl B- 1- (2-fluorophenyl) ° 2 ° oxoeft5D1"4 ° h5dro 5 ° 342 ° (3-oxopiperazine-1 -i Deti i idenl piperidine The compound was synthesized of the title in a yield of 63% as a light brown amorphous solid using (E) -4-hydroxy-3- [2- (3-o? opiperazin-1-yl) ethylidene] piperidine bis (hydrogenated acetate) obtained in ( c) above, performing a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.76-1.10 (4H, m), 1.62-1.80 (2H, m), 1.94 -2.05 (1H, m), 2.12-2.23 (1H, m), 2.43-2.53 (1H, m), 2.57-2.68 (2H, m), 2.73 and 2.98 (total 1H, each d, J = 12.5), 2.78- 2.92 (1H, m), 2.94-3.08 (2H, m), 3.28-3.42 (3H, m), 3.45-3.52 (1H, m), 4.05-4.19 (1H, m), 4.67-4.74 (1H , m), 5.53-5.65 (1H, m), 7.06- 7.23 (2H, m), 7.28-7.48 (2H, m). (e) (E) -4- (Acetylsulfanyl) -142 ° cicBopropBB ° 142 ° flyoroif®? P5B) ° 2"oxoetiH-3-r2- (3-oxopiperazin-1-yl) ethylidenlpiperS ip? A The title compound was synthesized in a yield of 22% as a yellow amorphous solid. or clear using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oethyl] -4-hydro? i-3- [2- (3-o? opiperazin-1-yl ethylidene] piperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (h). NMR with 1H (500 MHz, CDCl 3) d ppm: 0.69-1.10 (4H, m), 1.73-1.86 (1H, m), 2.06-2.26 (2H, m), 2.29 and 2.30 (total 3H, each s), 2.44-2.72 (4H, m), 2.74-2.85 (1H, m), 2.95 and 3.01 (total 2H, each d, J = 7.0), 3.03-3.10 (2H, m), 3.28 and 3.38 (total 1H, each d, J = 12.5), 3.29-3.38 (2H, m), 4.26-4.36 (1H, m), 4.69 and 4.71 (total 1H, each s), 5.62 (1H, t, J = 7.0), 5.78 (1H , bs), 7.07-7.24 (2H, m), 7.28-7.48 (2H, m); MS (FAB) m / z: 460 (M + H) +. (Example 8) Dihydrochloride of (E) ° 142-Cyclopropene-1 2 BuoF @ f © B i ° 2-oxoetin-3-f2- (3-oxopBperazin-1-yi) ethylidene 4-suBfa8iilp8pe? Rn 5 ? p? a (Compound Hydrochloride of Compound No.5-87) The title compound was synthesized in a 91% yield as a light yellow powder crystal using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl ] -3- [2- (3-o? Opiperazin-1-yl) ethylidene] piperidine obtained in Example 7 (e) by performing a reaction similar to that mentioned in Example 2. 1 H NMR (500 MHz, CDCl 3) d ppm: 0.75-1.10 (4H, m), 1.69-1.78 (1H, m), 2.11-2.28 (2H, m), 2.53-2.70 (3H, m), 2.73-2.86 (1H, m), 2.92- 3.22 (4H, m), 3.30-3.45 (3H, m), 3.66-3.82 (1H, m), 4.72 and 4.73 (total 1H, each s), 5.52-5.64 (1H, m), 7.07-7.22 (2H , m), 7.29-7.44 (2H, m); MS (FAB) m / z: 418 (M + H) +. (Example 9) (E) -4- (Aceft5BsuCfamiB [l) ° 1] 42 ° cycloBopropyl-1- (2-fluorofeniB) -2-oxoethyl-3424 piperaz5n ° 1] "ΔDethylidenepiperidine (B-chlorohydrate Compound of Coppipyesto No. 5-32) (a) (E) -3- (2444t43utoxycarbonyl) piperazin ° 14B1ethylBd @ BTiμ44ft ° butyldimethyisilnloxy) -1- (triphenylmethyl) piperidBna The title compound was synthesized in a 61% yield as a colorless amorphous solid using 1- ( t-butoxycarbonyl) piperazine in place of morpholine performing a reaction similar to that mentioned in Example 1 (d). 1 H NMR (500 MHz, CDCl 3) d ppm: -0.03 (3H, s), -0.02 (3H, s), 0.84 (9H, s), 1.46 (9H, s), 1.73-1.96 (3H, m) , 2.30-2.41 (4H, m), 2.74-3.12 (4H, m), 3.36-3.46 (4H, m), 3.47-3.52 (1H, m), 3.81-3.92 (1H, m), 5.66 (1H, t, J = 6.0), 7.10-7.19 (3H, m), 7.20-7.32 (6H, m), 7. 34-7.57 (6H, m). (b) (E) -3 244- (t ° ButoxDcarbonil) pdperazin ° 14petiDDden} 4-Ra-5-hydroxy-1- (triphenylmethyl) piperidyl? The title compound was synthesized in a 99% yield as a colorless amorphous solid using (E) -3-. {2- [4- (t- buto? icarbonyl) piperazin-1-yl] ethylene] -4- (t-butyldimethylsilyl? i) -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e) NMR with 1H (400 MHz, CDCl 3) d ppm: 1.47 (9H, s), 1.57-1.84 (4H, m), 2.32-2.45 (4H, m), 2.92-3.08 (2H, m), 3.36-3.52 (6H, m), 3. 93-4.03 (1H, m), 5.61 (1H, t, J = 6.0), 7.11-7.20 (3H, m), 7.21-7.33 (6H, m), 7.40-7.55 (6H, m). £ cj bis (hydrogenated acetate) of (E) -3-y2-IT4- (t-Butoxycarboni8) piperazine-H-Bnetiiiden > -4-h id roxa piperi ina The title compound was synthesized in a 99% yield as a light brown crystal using (E) -3-. { 2- [4- (t-Buto? Icarbonyl) piperazin-1-yl] ethylidene} -4-hydroxy-1- (triphenylmethyl) piperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 5 (c). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.45 (9H, s), 1.56-1.73 (1H, m), 1.86-2.04 (1H, m), 2.32-2.46 (4H, m), 2.80-2.91 (1H, m), 2. 94-3.07 (2H, m), 3.17-3.29 (2H, m), 3.35-3.46 (4H, m), 3.51 and 3.74 (total 1H, each d, J = 13.5), 4.03-4.11 (1H, m) , 5.57-5.66 (1H, m). (d) (E) ° 3- 244- (t ° ButoxycarbonBl) pperazin-14D1ethylidene] 42 ° cyclopropyl 1- (2-fluoropheni8) -2-oxoetyl "4-hydroxypipyridine The title compound was synthesized in a 64% yield as a light brown amorphous solid using bis (hydrogenated acetate) of (E) -3-. {2- 2- [4- (t-butoxycarbonyl) piperazin-1-yl] ethylidene} -4 -hydro? ipiperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.76-1.11 (4H, m), 1.46 (9H, s), 1.64-1.81 (2H, m), 1.93-2.04 (1H, m), 2.13-2.25 (1H, m), 2.28-2.40 (4H, m), 2.44-2.55 (1H, m) , 2.76 and 2.99 (total 1H, each d, J = 13.0), 2.78-2.90 (1H, m), 2.90-2.98 (1H, m), 3.31 and 3.45 (total 1H, each d, J = 13.0), 3.37-3.45 (4H, m), 4.04-4.18 (1H, m), 4.69 and 4.70 (total 1H, each s), 5.55-5.64 (1H, m), 7.06-7.21 (2H, m), 7.27-7.36 (1H, m), 7.37-7.45 (1H, m). £ e (E) ° 44Aceti¡suBfani¡) ° 3- (244- (t ° butoxñcarboniB) pipera2 ?? p? ° 1l clletiliden ° 1 2-cyclopropyl-1 ° (2-fluorofens8) ° 2 ° oxoeftil ? pdi epidi? a? The title compound was synthesized in a 36% yield as a brown oil using (E) -3-. {2- 2- [4- (t-butoxycarbonyl) piperazin-1-yl] ethylidene .} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-hydro? Ipiperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (h) ). NMR with 1H (400 MHz, CDCl 3) d ppm: 0.76-1.10 (4H, m), 1.46. (9H, s), 1.75-1.84 (1H, m), 2.07-2.28 (2H, m), 2.22-2.37 (4H, m), 2.28 and 2.29 (total 3H, each s), 2.47-2.62 (1H, m), 2.65-2.80 (1H, m), 2.79 and 3.05 (total 1H, each d, J = 13.0), 2.84-2.90 (1H, m), 2.91-2.96 (1H, m), 3.29 and 3.36 (total 1H, every d, J = 13.0), 3.36-3.45 (4H, m), 4.27-4.36 (1H, m), 4.67 and 4.69 (total 1H, each s), 5.63 (1H, t, J = 6.5), 7.08-7.20 (2H, m), 7.28-7.36 (1H, m), 7.40 (1H, m). (f) (E) -4 ° (AcetylsulphaneB) trichlorohydrate ° H42 ° C-Chlopropyl-1l- (2-fluorophenyl) -2-oxoetin-3-r2- (piperazin-1-yl) ethylidene] p5periodide? a solution of (E) -4- (acetylsulfanyl) -3-. { 2- [4- (t-Butoxycarbonyl) piperazin-1-yl] ethylidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] piperidine (1.06 g) obtained in (e) above in dioxane (21 ml) was added a solution of hydrogen chloride in dioxane 4N (24 mL) under cooling with ice, and the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was evaporated in vacuo to obtain the title compound (1.25 g, quantitative yield) as a light yellow crystal. NMR with H (500 MHz, CDCl 3) d ppm: 0.76-1.10 (4H, m), 1.62- 1.85 (2H, m), 2.09-2.25 (2H, m), 2.28 (3H, s), 2.31-2.45 ( 4H, m), 2.47-2.62 (1H, m), 2.64-2.81 (1H, m), 2.80 and 3.05 (total 1H, each d, J = 12.5), 2.84-2.97 (4H, m), 3.29 and 3.35 (total 1H, every d, J = 12.5), 3.40-3.67 (1H, m), 4.26-4.36 (1H, m), 4.67 and 4.69 (total 1H, each s), 5.64 (1H, t, J = 7.0 ), 7.07-7.21 (2H, m), 7.28-7.45 (2H, m); MS (FAB) m / z: 446 (M + H) +. (Example 10) fE) -1-r2-Cyclopropyl-1- (2-fluoropheniH 2-oxoel..m-3-f2- (piperazin-1-yl) ethylidene-1-4-sulfanylpiperidine (Compound compound No. 5-31) and (E) -342- (4 ° acetBlpiperazñri ° 1-Bl) etiBid®pT] ° H ° | [2-cyclopropyl-1 ° (2-fluorofert? il) -2-oxoetin- 4-sulfart? ÑBpiperidóraa (Compound of compound No.5 ° 33) Both title compounds were synthesized using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- [2- (piperazin-1-yl ethylidene] piperidine obtained in Example 9 (f) by carrying out a reaction similar to that mentioned in Example 2. (E) -1- [2-Cyclopropyl-1- (2-fluorophenyl) -2-o? oethyl] - 3- [2- (piperazin-1-yl) ethylidene] -4-sulfanylpiperidine with a high degree of polarity: a light yellow oil, yield 12%. 1 H NMR (500 MHz, CDCl 3) d ppm: 0.77-1.09 (4H, m), 1.67-1.76 (2H, m), 2.12-2.26 (2H, m), 2.29-2.43 (4H, m), 2.55- 2.67 (1H, m), 2.70-2.82 (1H, m), 2.83-2.89 (4H, m), 2.90-2.95 (1H, m), 3.14 and 3. 35 (total 1H, each d, J = 12.5), 3.43-3.68 (1H, m), 3.72-3.83 (1H, m), 4.70 and 4.71 (total 1H, each s), 5.56-5.66 (1H, m) , 7.06-7.21 (2H, m), 7.27-7.46 (2H, m); MS (FAB) m / z: 404 (M + H) \ (E) -3- [2- (4-Acetylpiperazin-1-yl) ethylidene] -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine with a low degree of polarity: a colorless oil, yield 46%. 1 H NMR (500 MHz, CDCl 3) d ppm: 0.75-1.09 (4H, m), 1.69-1.77 (1H, m), 2.08 (3H, s), 2.12-2.26 (2H, m), 2.27-2.43 ( 4H, m), 2.54-2.69 (1H, m), 2.73-2.85 (1H, m), 2.87-2.97 (2H, m), 3.08 and 3.37 (total 1 H, each d, J = 12.5), 3.13- 3.24 (1 H, m), 3.41 -3.67 (4H, m), 3.69-3.82 (1 H, m), 4.71 and 4.73 (total 1 H, each s), 5.53-5.64 (1 H, m), 7.08 -7.20 (2H, m), 7.28-7.44 (2H, m); MS (FAB) m / z: 446 (M + H) +. (Example 1 t) (E) -4 ° (AcetylsulfaniB) -142 ° c3clopropyl ° 1l (2 ° fluorophenyl) -2-oxoetill-3- (244- (ethoxycarbonylmetnB) pperazin-1D-1-illethylidenepiperidine (Compound of Compound No. 5-46) (a) (E) -1-f2-Cyclopropyl 1,1-chlorohydrate (2 ° fByorolf®? p? ñi) 2-oxoetin-4-hydroxy-3-f2- (piperazin ° 1 il) eti8Bdenlp5peridim The title compound was synthesized in a 99% yield as a light yellow powder crystal using (E) -3-. { 2- [4- (t-Buto? Icarbonyl) piperazin-1-yl] ethylidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-hydro? Ipiperidine obtained in Example 9 (d) performing a reaction similar to that mentioned in Example 9 (f) . NMR with 1 H (400 MHz, DMSO-d6) d ppm: 0.89-1.15 (4H, m), 1.74-1.96 (2H, m), 2.00-2.1 5 (1 H, m), 2.82-4.25 (15H, m), 5.94-6.19 (2H, m), 7.40-7.54 (2H, m), 7.64-7.84 (2H, m). (b) (E) -1-r2-Cyclopropyl-1-f2-fluorophysi-2-oxoetin-3-l2-ir4- (ethoxycarbonylmethyl) piperazin-1-iHTethylidene-4-hydrox5p5periddp) a A a suspension of trichlorhydrate of (E) -1 - [2-cyclopropyl-1 - (2-fluorophenyl) -2-oxoethyl] -4-hydro? i -3- [2- (piperazin-1 -yl) ethylidene] piperidine (1.14) g) obtained in (a) above in acetonitrile (35 ml) was added ethyl bromoacetate (0.31 ml) and triethylamine (1.92 ml) under cooling with ice, and the resulting mixture was stirred at room temperature for 1 hour. After the reaction mixture was evaporated in vacuo, water was poured in and the mixture was brought with a combined dichloromethane and isopropanol solvent. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (methanol / dichloromethane = 1/9) to obtain the title compound (0.71 g, 66% yield) as a light yellow oil. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.77-0.90 (2H, m), 0.95-1.08 (2H, m), 1.28 (3H, t, J = 7.0), 1.65- 1.80 (2H, m), 1.94-2.03 (1 H, m), 2.16-2.25 (1 H, m), 2.41 -2.70 (8H, m), 2.75-2.88 (2H, m), 2.96 -3.02 (2H, m), 3.20 (2H, s), 3.30 and 3.44 (total 1 H, each d, J = 12.5), 4.06-4.1 5 (1 H, m), 4.19 (2H, q, J = 7.0), 4.68 and 4.70 (total 1 H, each s), 5.58-5.66 (1 H, m), 7.07-7.21 (2H, m), 7.28-7.45 (2H, m). £ cj (E) -4- (Acetylsufanyl) -142-cyclopropiB "142 loorotf®niD) ° 2-oxoetin-3- (2-f4- (ethoxycarboniBmetii) pBperazira ° 1 ° B-ethylidene) piperidine The compound of title in a yield of 23% as a light brown oil using (E) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3-. {2- 2- [4- ( eto? icarbonylmethyl) piperazin-1-yl] ethylidene} -4-hydro? ipiperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 1 (h). 1 H NMR (500 MHz, CDCl 3) d ppm: 0.77-1.09 (4H, m), 1.27 (3H, t, J = 7.0), 1.75-1.83 (1H, m), 2.06-2.24 (2H, m), 2.28 (3H, s), 2.37- 2.64 (8H, m), 2.65-2.81 (2H, m), 2.79 and 3.03 (total 1H, each d, J = 12.5), 2.85-2.90 (1H, m), 2.92-2.98 (1H, m), 3.19 (2H, s), 3.28 and 3.34 (total 1H, each d, J = 12.5), 4.19 (2H, q, J = 7.0), 4.26-4.35 (1H, m), 4.66 and 4.68 (total 1H, each s ), 5.61-5.67 (1H, m), 7.06-7.20 (2H, m), 7.29-7.43 (2H, m); MS (FAB) m / z: 532 (M + H) +. (Example 12) (E) -1-r2-Cyclopropyl-1- (2-ffluorophen-H-2-oxoettim-3-f2-r4- (ethoxycarbonylmethyl) piperazine-1-inethylidene 4 ° s llfanBlpi e? rand (Compound of compound No.5-45) To a solution of (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3-. { 2- [4- (Ethoxycarbonyl methyl) piperazin-1-yl] ethylidene} piperidine (111 mg) obtained in example 11 (c) in ethanol (3 ml) was added potassium carbonate (289 mg) under ice-cooling, and the resulting mixture was stirred at room temperature for 2 hours. After the reaction mixture was poured into water and extracted with dichloromethane, the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo to obtain the title compound (77 mg, 75% yield) as a light yellow oil. NMR with 1H (400 MHz, CDCl 3) d ppm: 0.75-1.09 (4H, m), 1.27 (3H, t, J = 7.0), 1.66-1.76 (1H, m), 2.09-2.26 (2H, m), 2.35-2.67 (8H, m), 2.69-2.84 (1H, m), 2.86-2.91 (1H, m), 2.91-2.98 (1H, m), 3.11 and 3.35 (total 1H, each d, J = 12.5) , 3.18 (2H, s), 3.48 (2H, s), 3.68-3.81 (1H, m), 4.17 (2H, q, J = 7.0), 4.68 and 4.69 (total 1H, each s), 5.52-5.64 ( 1H, m), 7.02-7.19 (2H, m), 7.23-7.43 (2H, m); MS (FAB) m / z: 490 (M + H) +. (Example 13.}. (E) -4 ° (AcetylsulfanBB) ° 142 ° cñcBoprop ?8 ° 1l ° (2 ° ffluorophenyl) ° 2-oxoetiB1"3" {244- (ethoxycarbonBÍmetBB) -3-oxopBp®razi ? pi "1-iBlethylidenepiperidine (Compound of compound No.5-102) (ai (E) -4- (t-ButyldBmethylsilyloxy) -3- (244- (etoxBcarbon5Bpp) @ t5n) "3-oxopiperazin-1-inetidemide ° 1 (triphenylmethyl) piper? ñ? p) a It was synthesized the title compound in a yield of 13% as a pale yellow amorphous solid using 1- (ethocarbarylmethyl) -2-o? o-piperazine hydrochloride in place of morpholine performing a reaction similar to that mentioned in Example 1 (d NMR with 1H (500 MHz, CDCl 3) d ppm: -0.01 (3H, s), -0.02 (3H, s), 0.85 (9H, s), 1.28 (3H, t, J = 7.0), 1.69- 2.08 (2H, m), 2.67-2.74 (2H, m), 3.00-3.20 (2H, m), 3.17 (2H, s), 3.34-3.42 (2H, m), 3.61-3.67 (2H, m), 3.73-3.81 (2H, m), 3.82-3.91 (1H, m), 4.11 (2H, s), 4.21 (2H, q, J = 7.0), 5.56-5.65 (1H, m), 7.1 1 -7.20 (3H, m), 7.21 -7.32 (6H, m), 7.36-7.56 (6H, m). (B) (E) -3-f2-r4- (Ethoxycarbonylmethyl) ° 3-oxopBPerazi? P? 1l - BBlethylide [p? V4-hydroxy-1 - (triphenylmethyl) piperidine The title compound was synthesized in 80% yield as a pale yellow amorphous solid using (E) -4- (t-butyldimethylsil i lo? i) -3- { 2- [4- (Etho? -carbonyl methyl) -3-o? Opiperazin-1-yl] ethylidene} -1 - (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.28 (3H, t, J = 7.0), 1 .76-1 .86 (1 H, m), 2.02-2.12 (1 H, m), 2.70-2.78 (2H, m), 3.02-3.14 (2H, m), 3.20 (2H, s), 3.37 -3.44 (2H, m), 3.60-3.68 (2H, m), 3.73-3.81 (2H, m), 3.93-4.02 (1H, m), 4.12 (2H, s), 4.21 (2H, q, J = 7.0), 5.60 (1 H, t, J = 7.0), 7.1 1 -7.20 (3H, m), 7.21 -7.31 (6H, m), 7.38-7.53 (6H, m). (c) (E) -3- (244- (Ethoxycarbonylmethyl) -3-oxopiperazine "H ° iB1etiBideot ?.}." 4-Hydroxypiperidine bis (hydrogenated acetate) The title compound was synthesized in a yield of 99% as a clear coffee crystal using (E) -3- { 2- [4- (ethoxycarbonylmethyl) -3-o? opiperazin-1 -yl] ethylidene} -4-hydroxy-1- (triphenylmethyl) piperidine obtained in b) above carrying out a reaction similar to that mentioned in Example 5 (c). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.28 (3H, t, J = 7.0), 1 .56-1 .69 (1 H, m), 1 .94-2.06 (2H, m), 2.70-2.88 (4H, m), 3.20 (2H, s), 3.37-3.49 (2H, m), 3.70-3.79 (2H, m), 4.10 (2H, s), 4.14-4.20 (2H, m), 4.20 (2H, q, J = 7.0), 5.60 (1H, t, J = 7.0). (d) (E) -1-r2-Cyclopropin-1 ° (2-fluorofenBÍ) -2 ° oxoeftil1"3-f2 4 ° (ethoxycarbonylmethyl) -3 ° oxopiperazin-1-yllethylidene} -4-hydroxypiperidine The title compound was synthesized in a 68% yield as a light brown amorphous solid using bis (hydrogenated acetate) of (E) -3-. { 2- [4- (Etho? -carbonylmethyl) -3-o? Opiperazin-1-yl] ethylidene} -4-hydro? Ipiperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.76-1.09 (4H, m), 1.28 (3H, t, J = 7.0), 1.60-1.77 (2H, m), 1.94-2.04 (1H, m), 2.13-2.23 (1H, m), 2.43-2.53 (1H, m), 2.65-2.77 (2H, m), 2.79-2.90 (1H, m), 2.93-3.07 (2H, m), 3.16 (2H, s), 3.33 and 3.47 (total 1H, each d, J = 12.5), 3.35-3.42 (2H, m), 4.04-4.14 (1H, m), 4.11 (2H, s), 4.21 (2H, q, J = 7.0), 4.70 and 4.71 (total 1H, each s), 5.54-5.63 (1H, m), 7.05-7.21 (2H, m), 7.28-7.36 (1H, m), 7.37-7.45 (1H , m). (e) (E) -4- (Acetylsulfanyl) -142 ° eielopr © pil "1" (2 ° flyoro1f®? p? in) ° 2 ° oxoetin ° 3-f2-r4- (ethoxycarboniBmeti8) -3-oxopiperazi? p? -1? B-ethylidene piperidane The title compound was synthesized in a yield of 34% as a yellow oil using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oethyl] -3 -. { 2- [4- (Ethoxycarbonylmethyl) -3-o? Opiperazin-1-yl] ethylidene} -4-hydro? Ipiperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (h). 1 H NMR (500 MHz, CDCl 3) d ppm: 0.76-1.09 (4H, m), 1.28 (3H, t, J = 7.0), 1.75-1.84 (1H, m), 2.09-2.25 (2H, m), 2.29 and 2.30 (total 3H, each s), 2.48-2.59 (1H, m), 2.60-2.74 (2H, m), 2.75-2.83 (1H, m), 2.92-2.97 (1H, m), 2.99-3.03 (1H, m), 3.07 and 3.28 (total 1H, each d, J = 12.5), 3.09-3.17 (2H, m), 3.34-3.41 (2H, m), 3.46-3.52 (1H, m), 4.11 ( 2H, s), 4.21 (2H, q, J = 7.0), 4.26-4.34 (1H, m), 4.69 and 4.70 (total 1H, each s), 5.61 (1H, t, J = 7.0), 7.07-7.21 (2H, m), 7.29-7.44 (2H, m); MS (FAB) m / z: 546 (M + H) +. (Example 14) (E) -1-f2-CicBopropy6 ° 1-f2 ° fBuoroferaBB) -2 ° oxoe6iC1 ° 3 ° (2-í4- (methoxycarboniimetii) -3"? Xopiperazin-1" ipeti8ide? P)} -4-Sulfanylpiperidine (Compound of compound No.5-99) The title compound was synthesized in a 93% yield as a yellow oil using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3 -. { 2- [4- (Etho? -carbonylmethyl) -3-oxopiperazin-1-yl] ethylidene} piperidine obtained in example 13 (e) carrying out a reaction similar to that mentioned in Example 2. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.76-1.09 (4H, m), 1.69-1.77 (1H, m) , 2.12-2.26 (2H, m), 2.53-2.73 (3H, m), 2.74-2.85 (1H, m), 2.93-3.04 (2H, m), 3.07 and 3.38 (total 1H, each d, J = 12.5 ), 3.12-3.22 (3H, m), 3.35-3.44 (2H, m), 3.68-3.81 (1H, m), 3.75 (3H, s), 4.13 (2H, s), 4.72 and 4.73 (total 1H, each s), 5.57 and 5.61 (total 1H, each t, J = 7.0), 7.07-7.21 (2H, m), 7.29-7.44 (2H, m); MS (FAB) m / z: 490 (M + H) +. (Example 15) (E) -3-t2-r4-fCarboxipn < Btin-3-oxopiperazin-1-yl1etiBiden} - 2-cyclopropyO-142-iFBuorofenii) -2-oxoetill-4-sulfanylpiperidirúa (Hydrochloride of O compound Compound No.5-97) a solution of (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oethyl] -3-. { 2- [4- (Methoxycarbonylmethyl) -3-o? Opiperazin-1-yl] ethylidene} -4-Sulfanylpiperidine (280 mg) obtained in Example 14 in water (1 mL) was added 3N hydrochloric acid (5 mL) at room temperature, and the resulting mixture was stirred at 50 ° C for 2.5 hours. The reaction mixture was evaporated in vacuo, and the residue was purified using a preparative HPLC (YMC-Pack ODS-A; YMC, eluent: acetonitrile / 0.024N hydrochloric acid = 15/85) to obtain the title compound (203 mg, 65% yield) as a colorless crystal. NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.78-0.88 (2H, m), 0. 94-1.18 (2H, m), 1.74-1.86 (1H, m), 2.14-2.28 (1H, m), 2.40-2.60 (1H, m), 2.60-2.80 (3H, m), 2.86-3.02 (1H , m), 3.02-3.15 (2H, m), 3.30-3.46 (3H, m), 3.50-3.66 (3H, m), 3.88 (1H, bs), 4.50 (2H, s), 4.94 (1H, s) ), 5.80 (1H, t, J = 7.0), 7.18-7.36 (3H, m), 7.70-7.78 (1H, m); MS (FAB) m / z: 476 (M + H) +. (For example, 1 16 (3)) ddiicclDrehydrate of EE) -4-ÍA cetii syBfarDÜ) '> 3 =. { 244 = (carb ooxxBimmeettiill)) - 33 - ooxxoot pipe ratio - 1 - illeti iiiden > -1 - [2 = ci cBopropi 0-H-2 2 -fluoro offeenniill)) - 22 - ooxoxethetiiBDlpsperidine (Chlorohydrate of compound cflei Compound No. 5-98) To a suspension of (E) -3- dihydrochloride. { 2- [4- (carboxymethyl) -3-o? Opiperazin-1-yl] ethylidene} -1- [2-Cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -4-sulfanylpiperidine (100 mg) obtained in Example 15 in dichloromethane (5 mL) was added acetic anhydride (259 μL) and pyridine (514 μl) under cooling with ice, and the resulting mixture was stirred at room temperature for 4 hours. The reaction mixture was evaporated in vacuo, and the residue was purified by chromatography on a silica gel column (methanol / dichloromethane = 3/17) to yield the free form (85 mg, 90% yield) of the title compound like a solid coffee. To a solution of this compound in dichloromethane (3 mL) was added a solution of hydrogen chloride in 4N dioxide (82 μL) at room temperature, and the reaction mixture was evaporated in vacuo. The residue was crystallized from ether to obtain the title compound (44 mg, 45% yield) as a pale yellow amorphous solid.

NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.72-0.85 (2H, m), 0.98-1.05 (1H, m), 1.06-1.16 (1H, m), 1.79-1.90 (1H, m), 2.15-2.26 (1H, m), 2.23 and 2.24 (total 3H, each s), 2.35-2.49 (1H, m), 2.53-2.75 (3H, m), 2.75-2.91 (1H, m), 2.97-3.22 (3H, m), 3.30-3.38 (2H, m), 3.47-3.55 (2H, m), 3.56-3.65 (1H, m), 4.44-4.47 (2H, m), 4.51-4.55 (1H, m) , 4.93 and 4.94 (total 1H, each s), 5.81 and 5.83 (total 1H, each t, J = 7.0), 7.16-7.36 (3H, m), 7.64-7.72 (1H, m); MS (FAB) m / z: 518 (M + H) +. (Example 17) (E) -4- (Acetylsulfanyl) -1-IT2-CDClopropyl-1- (2-fluorophenyl) 2-oxoetip 342-4442- (ethoxycarbonBl) etiBTl "3 ° oxopiperazine- 1-yl> ethylidene) piperidine (Compound of B compound No.5-108) [a] _ (E) -4- (t-ButyldimethyBsilyBloxy) -3- (2-442- (ethoxycarboxy n-3-oxopiperazin-1-yl ethylidene) 1- (triphenylmetBl) pBper? da? p) a The title compound was synthesized in a 44% yield as a light yellow oil using 1- [2- (ethocarbonyl) -ethyl] -2- or? -opiperazine hydrochloride in place of morpholine performing a reaction similar to mentioned in Example 1 (d). NMR with 1H (500 MHz, CDCI3) d ppm: -0.01 (3H, s), -0.02 (3H, s), 0.86 (9H, s), 1.27 (3H, t, J = 7.0), 1.70-1.95 (4H, m), 2.59 -2.6, (2H, m), 2.63 (2H, t, J = 7.0), 2.84-2.97 (2H, m), 2.99-3.17 (2H, m), 3.1 1 (2H, s), 3.34-3.42 (2H , m), 3.64 (2H, t, J = 7.0), 3.83-3.92 (1H, m), 4.14 (2H, q, J = 7.0), 5.57-5.64 (1H, m), 7.10-7.21 ( 3H, m), 7.22-7.33 (6H, m), 7.37-7.57 (6H, m). ib) (E) -3- (2- (4-r2- (Ethoxycarbonyl) etha1-3-oxopiperazin-1-in.}. et? nidem?) 4-hydroxy-1 - (triphenylmet-58) p-peridine synthesized the title compound in a 96% yield as a pale yellow amorphous solid using (E) -4- (t-butyldimethylsilyl) i) -3- (2-. {4- [2- (ethocarbonyl)) ethyl] -3-o? opiperazin-1-yl.} ethylidene) -1 - (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e). 1 H NMR ( 500 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 1 .64-1 .87 (4H, m), 2.62 (2H, t, J = 7.0), 2.64-2.71 (2H, m), 2.98-3.17 (2H, m), 3.12 (2H, s), 3.35-3.43 (4H, m), 3.63 (2H, t, J = 7.0), 3.91 - 4.01 (1 H, m), 4.14 (2H, q, J = 7.0), 5.58 (1 H, t, J = 7.0), 7.10-7.20 (3H, m), 7.21 -7.33 (6H, m), 7.37-7.57 (6H, m). (c) bis (hydrogenated acetate) of (E) ° 3 ° (2-i4424EtoxBcarbop? in) etini ° 3 oxopiperazin-1-ethylidene) -4-hydroxypropyl 5a The title compound was synthesized in a 98% yield as a light brown oil using (E) -3- (2-. {4- [2 - (ethylocarbonyl) ethyl] -3-o? opiperazin-1-yl.} ethylidene) -4-hydro? i-1 - (triphenylmethyl) piperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 5 (c). 1 H NMR (500 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 1 .63-1 .73 (2H, m), 2.61 (2H, t, J = 7.0), 2.65-2.72 (2H, m), 3.07-3.15 (4H, m), 3.17-3.41 (6H, m) , 3.62 (2H, t, J = 7.0), 4.13 (2H, q, J = 7.0), 4.17-4.22 (1H, m), 5.61 (1H, t, J = 7.0). (d) (E) -142-CBClopropi! -142 ° fluorofemBn) ° 2-oxoetip-3- [2 = (ethoxycarbonyl) ethiH-3-oxopiperazin-1-yl} etBladenl "4 ° DiidroxypiperidBna The title compound was synthesized in a 77% yield as a light brown oil using (E) -3- (2. {4- [2- (ethocarbonyl) bis (hydrogenated acetate)) ) ethyl] -3-o? opiperazin-1-yl.} ethylidene) -4-hydro? ipiperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 1 (g). MHz, CDCI3) d ppm: 0.78-0.90 (2H, m), 0.95- 1.09 (2H, m), 1.26 (3H, t, J = 7.0), 1.52-1.65 (2H, m), 1.67-1.78 (1H , m), 1.95-2.04 (1H, m), 2.13-2.22 (1H, m), 2.44-2.52 (1H, m), 2.56-2.68 (4H, m), 2.72 and 2.96 (total 1H, each d, J = 13.0), 2.79-2.90 (1H, m), 2.93-3.02 (2H, m), 3.32 and 3.47 (total 1H, each d, J = 13.0), 3.35-3.41 (2H, m), 3.63 (2H , t, J = 7.0), 4.05-4.12 (1H, m), 4.14 (2H, q, J = 7.0), 4.70 and 4.71 (total 1H, each s), 5.53-5.60 (1H, m), 7.08- 7.21 (2H, m), 7.29-7.44 (2H, m). (E) (E) ° 4- (Acetylsulfa? I) -142 ° cyclopropyl ° 1 (2 ° fiyoroff®mñl) -2-oxoet p "3- (2-442- (ethoxycarbonyl) etBp-3-oxopBperazim-1" i Bleti I of n) piperidine The title compound was synthesized in a 22% yield as a light brown oil using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- ( 2-. { 4- [2- (etho? -carbonyl) ethyl] -3-o? Opiperazin-1-yl} ethylidene) -4-hydro? ipiperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (h). 1 H NMR (500 MHz, CDCl 3) d ppm: 0.77-1.08 (4H, m), 1.26 (3H, t, J = 7.0), 1.76-1.84 (1H, m), 2.08-2.24 (2H, m), 2.29 and 2.30 (total 3H, each s), 2.46-2.72 (6H, m), 2.74-2.82 (1H, m), 2.89-3.00 (2H, m), 3.01-3.09 (2H, m), 3.05 and 3.27 (total 1H, each d, J = 13.0), 3.33-3.40 (2H, m), 3.63 (2H, t, J = 7.0), 4.14 (2H, q, J = 7.0), 4.26-4.35 (1H, m ), 4.68 and 4.70 (total 1H, each s), 5.60 (1H, t, J = 7.0), 7.08-7.20 (2H, m), 7.29-7.43 (2H, m); MS (FAB) m / z: 560 (M + H) +. (Example 18) dichlorhodrate of EI) -142 = Gdc! Or ropit = 1] -i2 = phorophenyl) -2-oxoetill-3-f2" {442- (methoxycarbonyl) etDlll-3-oxopiperazin-1- il.} ethylidene) < -4-sulfanylpiperidBrta (CD-Dihydrate d @ D composed of Compound No.5-105) The title compound was synthesized in a 71% yield as a white powder crystal using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- (2- {4- [2- (ethocarbonyl) ethyl] -3-o? Opiperazin-1-yl} ethylidene) piperidine obtained in Example 17 (e) carrying out a reaction similar to the one mentioned in Example 2. 1 H NMR (500 MHz, CDCl 3) d ppm: 0.78-0.90 (2H, m), 0.96-1.08 (2H, m), 1.68-1.78 (1H, m), 2.12-2.26 ( 2H, m), 2.53-2.68 (5H, m), 2.74-2.85 (1H, m), 2.90-3.01 (2H, m), 3.03-3.10 (3H, m), 3.19 (1H, s), 3.34- 3.43 (2H, m), 3.63 (2H, t, J = 7.0), 3.67-3.81 (1H, m), 3.69 (3H, s), 4.71 and 4.73 (total 1H, each s), 5.55 and 5.59 (total 1H, each t, J = 7.0), 7.08-7.21 (2H, m), 7.30-7.36 (1H, m), 7.38-7.43 (1H, m); MS (FAB) m / z: 504 (M + H) +. (Example 19) dihydrochloride of (E) -342 ° i4424Carbox5®tBl) 1-3-oxopiperazBn-1-ii) ethylidene) "142-cyclopropyl" 1 ° (2-ff yorophenyl) oxoetiH-4-su8fanylpiperidiraa (Hydrochloride defl. composed of Compound No.5-103) The title compound was synthesized in a 48% yield as a white powder crystal using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- (2-. { 4- [2- (methocarbonyl) ethyl] -3-o? Opiperazin-1-yl.} Ethylidene) -4-sulfanylpiperidine obtained in Example 18 carrying out a reaction similar to that mentioned in Example 15. NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.77-1.11 (4H, m), 1.76-1.87 (1H, m), 2.14-2.27 (1H, m), 2.40-2.48 (1H, m), 2.64 -2.73 (3H, m), 2.87-2.99 (3H, m), 3.04-3.13 (2H, m), 3.28-3.34 (3H, m), 3.44-3.47 (2H, m), 3.50 and 3.59 (total 1H , each d, J = 12.5), 3.85-3.93 (3H, m), 4.95 (1H, s), 5.77-5.82 (1H, m), 7.21-7.37 (3H, m), 7.69-7.75 (1H, m ); MS (FAB) m / z: 490 (M + H) +. (Example 20) (E) ° 4- (AcetylsuBfaniB) ° 3- (2 ° i442 carbox5 @ tiB) 1-3 ° oxopiperazin-1-yl ethylidene) ° 1-f2-cycloprop5B ° 1 ° (2 ° fBuofoffen8l) ° 2 ° oxoetillpiperidina dichlorhydrate (CBorhydrate of compound of Compound No.5-104) The title compound was synthesized in a 35% yield as a light yellow powder crystal using (E) -3- (2- {4- [2- (carboxyethyl)] - 3-o-opiperazine dihydrochloride. 1-yl.} Ethylidene) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -4-sulfanylpiperidine obtained in the example 19 performing a reaction similar to that mentioned in Example 16.

NMR with 1H (500 MHz, CDCl 3) d ppm: 0.78-1.17 (4H, m), 1.84-1.90 (1H, m), 2.21-2.29 (1H, m), 2.25 and 2.26 (total 3H, each s), 2.39-2.46 (1H, m), 2.57-2.88 (3H, m), 2.90-2.94 (3H, m), 2.98-3.01 (2H, m), 3.19-3.28 (2H, m), 3.33-3.38 (2H , m), 3.41-3.44 (2H, m), 3.88-3.93 (2H, m), 4.54-4.55 (1H, m), 4.95 and 4.96 (total 1H, each s), 5.82-5.86 (1H, m) , 7.21-7.38 (3H, m), 7.66-7.73 (1H, m); MS (FAB) m / z: 532 (M + H) +. (Example 21) (E) -4- dihydrochloride (Ac @ ftalsu »fap) iD) ° H42 ° cyclopropyl-1- (2-fluorophenyl) -2-oxoetiM ° 3- (2-γ 442 ° (ethoxycarbonyl) ethyl 1- 2 ° oxopiperazine ° 1 ° et5lidene) piperidine (CB-hydrochloride of compound of Compound No.5-80) (a) (E) -4- (t-Butyldimethylsilyloxy) "3- (2 ° 442- (ethoxyarboniB ® tG 1" 2"oxopiperazin-1-yl) ethylidene) 1- (triphenylmethyl) piperdipBip? a To one solution of sodium hydride (1.94 g) in N, N-dimethylformamide (430 ml) was added a solution of (E) -4- (t-butyldimethylsilyloxy) -3- [2- (tosyloxy) ethylidene] -1- ( triphenylmethyl) piperidine (27.37 g) obtained in example 1 (c) and 1- [2- (ethocarbonyl) ethyl] -3-o? opiperazine (9.70 g) in N, N-dimethylformamide (100 ml) under cooling with ice, and the resulting mixture was stirred at room temperature for 3 hours.The reaction mixture was charged with a saturated aqueous solution of sodium chloride and then it was brought with ethyl acetate. a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate, the solvent was removed in vacuo, and the residue was purified by chromatography on a column of silica gel (ethyl acetate / he? = 2/3 - 1/1) to obtain the compound of the title (14.79 g, yield 54%) as a pale yellow amorphous solid. 1 H NMR (500 MHz, CDCl 3) d ppm: -0.05 (3H, s), -0.02 (3H, s), 0.83 (9H, s), 1.26 (3H, t, J = 7.5), 1.73-1.94 ( 2H, m), 2.48 (2H, t, J = 7.5), 2.65-2.76 (4H, m), 2.84-2.93 (1H, m), 3.16 (2H, s), 3.20-3.27 (2H, m), 3.40-3.55 (1H, m), 3.81-4.18 (7H, m), 5.41-5.48 (1H, m), 7.11-7.29 (9H, m), 7.41-7.52 (6H, m). (b) (E) -3- (2-4-r2- (Ethoxycarbonyl) etiBl-2 ° oxopyperazin-1-yl eiflderide) -4-idroxy-1 ° (triphenylmethi) piperidine The title compound was synthesized in a yield 99% as a pale yellow amorphous solid using (E) -4- (t-butyldimethylsilyl) -3- (2-. {4- [2- (ethocarbonyl) ethyl] -2-o? opiperazine -1-yl.} Ethylidene) -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 1.60-1.86 (2H, m), 1.98-2.11 (1H, m), 2.49 (2H, t, J = 7.0 ), 2.65-2.77 (4H, m), 3.16 (2H, s), 3.21-3.44 (3H, m), 3.88-4.20 (7H, m), 5.44 (1H, t, J = 6.5), 7.10-7.31 (9H, m), 7.39-7.53 (6H, m). (c) bis (hydrogenated acetate) of (E) ° 3 ° (2- {4 ° r2- (EtoxBcarbomci) etñB1 ° 2-oxopiperazin-1-il >; etiBiden) -4- idroxypiperidone The title compound was synthesized in a 99% yield as a light brown oil using (E) -3- (2-. {4- [2- (ethocarbonyl) ethyl) ] -2-oxopiperazin-1-yl.} Ethylidene) -4-hydroxy-1- (triphenylmethyl) piperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 5 (c). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 1.62-1.83 (2H, m), 2.01-2.12 (1H, m), 2.49 (2H, t, J = 7.0 ), 2.66-2.77 (4H, m), 2.90-3.01 (1H, m), 3.15 (2H, s), 3.23-3.45 (3H, m), 3.83-4.27 (6H, m), 5.57 (1H, t , J = 7.5). (d) (E) -1-r2-Cyclopropyl-1- (2-fluorophenBn) -2 ° or? oetiB1-3 ° (f2-l4-t2 ° (ethoxycarbonyl) ethyl1-2 ° oxopiperazin-1-yl) etBlBden ) ° 4 ° hydroxypiperidine The title compound was synthesized in a 93% yield as a light yellow oil using (E) -3- (2-. {4- [2- (ethocarbonyl) ethyl] -2- or? opiperazin-1-yl.} ethylidene) -4-hydro? ipiperidine bis (hydrogenated acetate) obtained in (c) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (500 MHz, CDCl 3) d ppm: 0.78-0.91 (2H, m), 0.97-1.10 (2H, m), 1.26 (3H, t, J = 7.5), 1.62-1.77 (2H, m), 1.95-2.03 (1H, m), 2.09-2.16 (1H, m), 2.43-2.54 (2H, m), 2.65-2.77 (4H, m), 2.78-2.89 (1H, m), 3.00 and 3.33 (total 1H, every d, J = 12.5), 3.15 (2H, s), 3.22-3.30 (2H, m), 3.47-3.55 (1H, m), 3.88-4.19 (5H, m), 4.73 and 4.75 (total 1H , each s), 5.42-5.49 (1H, m), 7.08-7.20 (2H, m), 7.29-7.41 (2H, m). (e) (E) -4 ° (AcetylsulfanB) dihydrochloride ° il ° r2 ° cchloclopropSl ° l- (2-ffluorophenyl) -2-oxoetip-342- (442- (ethoxycarboniB) etiD] l "2" oxopiperazin 1-il > eti i-den) piperidine The title compound was synthesized in a 4% yield as a light yellow powder crystal using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3- (2- { 4- [2- (ethoxycarbonyl) ethyl] -2-o? Opiperazin-1-yl}. Ethylidene) -4-hydro? Ipiperidine obtained in ( d) above performing a reaction similar to that mentioned in Example 1 (h). NMR with 1H (400 MHz, CDCl 3) d ppm: 0.75-1.09 (4H, m), 1.27 (3H, t, J = 7.0), 1.72-1.84 (1H, m), 2.05-2.32 (6H, m), 2.43-2.83 (7H, m), 3.04-3.42 (6H, m), 3.77-4.35 (5H, m), 4.71 and 4.74 (total 1H, each s), 5.43-5.52 (1H, m), 7.06-7.22 (2H, m), 7.29-7.41 (2H, m); MS (FAB) m / z: 560 (M + H) +. (Example 22) (E) -1-IT2-C'clopropyl-1- (2-fluorophenyl) -2-oxoeti8-3- (2-4- (ethoxycarbonBl) etiD1-2 ° oxopiperazine-1-dihydrochloride -yl> ethylidene) ° 4-sulfanylpiperidine (GBorhydrat® of compound of Compound No.5-79) The title compound was synthesized in an 80% yield as a white powder crystal using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- (2- { 4- [2- (etho? -carbonyl) ethyl] -2-o? Opiperazin-1-yl.} Ethylidene) piperidine obtained in Example 21 (e) carrying out a reaction similar to the one mentioned in Example 12. NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.76-0.89 (2H, m), 0.99-1.08 (2H, m), 1.13 (3H, t, J = 7.5), 1.72-1.85 (1H, m), 2.12-2.26 (1H, m), 2.38-3.00 (9H, m), 3.21-3.42 (5H, m), 3.51-3.68 (1H, m), 3.81 (1H, bs ), 4.06-4.21 (4H, m), 4.96 (1H, s), 5.62-5.71 (1H, m), 7.19-7.40 (3H, m), 7.66-7.76 (1H, m); MS (FAB) m / z: 518 (M + H) +. (Example 23) dihydrochloride (E) -3 2-442 Carboxy (tiB) T ° 2 ° oxopiperazBn-1-yl > etBlidene) -1-f2-cyclopropyl-1- (2-fBy @ rof @ nBB) -2-oxoetip-4-sulfanylpiperodime (Hydrochloride of B compound of B Compound No.5-75) The title compound was synthesized in an 88% yield as a white powder crystal using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- (2- . {4- [2- (Ethocarbonyl) ethyl] -2-o? Opiperazin-1-yl} ethylidene) -4-sulfanylpiperidine obtained in Example 22 by carrying out a reaction similar to that mentioned in Example 15 NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.77-0.89 (2H, m), 0. 98-1.19 (2H, m), 1.71-1.84 (1H, m), 2.10-2.28 (1H, m), 2.38-3.01 (9H, m), 3.23-3.69 (6H, m), 3.81 (1H, bs ), 4.05-4.29 (2H, m), 4.96 (1H, s), 5.63-5.72 (1H, m), 7.16-7.40 (3H, m), 7.67-7.78 (1H, m); MS (FAB) m / z: 490 (M + H) +. (Example 24) (E) "4- (AcetBlsulfanyl) -3- (2-442 carbox5®tB?) 1 ° 2 ° oxopiperazin-1-yl> ethylidene) ° 142-cicDopropiB-1- (2" fD oroferaB¡ ° 2 ° oxoetippiperidina dihydrochloride (eompuest® Hydrochloride of B Compound No.5-76) The title compound was synthesized in a 44% yield as a light yellow powder crystal using (E) -3- (2- {4- [2- (carboxyethyl)] -2- or [beta] -opiperazine dihydrochloride. 1-yl.} Ethylidene) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine obtained in Example 23 carrying out a reaction similar to that mentioned in Example 16 . 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.76-0.91 (2H, m), 1 .01 -1 .20 (2H, m), 1.81 -1.90 (1 H, m) , 2.14-2.29 (4H, m), 2.34-2.48 (1 H, m), 2.53-2.92 (8H, m), 3.17-3.72 (6H, m), 4.00-4.31 (2H, m), 4.46-4.56 (1 H, m), 4.95 and 4.97 (total 1 H, each s), 5.69-5.80 (1 H, m), 7.18-7.40 (3H, m), 7.62-7.75 (1 H, m); MS (FAB) m / z: 532 (M + H) +. (Example 25) dihydrochloride of (E ° 4- (Acetyl-sulfate pB) 142-cyclopropyl-1- (2-fluorophenifl) 2-oxoethyl-1 -3- (24 (2S) ° (methoxycarbonyl) pyrroBidin ° 1 -inethylidene piperidyrae (CBorhydc compound of Compound No. 5-148) [E) -4- (t-Butyldimethylsilyloxy) -3 ° (24 (2S) 4-methoxy) [r_3Qr l) pyrrolidin-1-ylethylidene 1 - (trifhenylmethyl) piperidine To a solution of (E) -4- (t-butyldimethylsilyl i) -3- [2- (tosyloxy) ethylidene] -1- (triphenylmethyl) piperidine (4.50 g) obtained in example 1 (c) in N. N -dimethylformamide (60 ml) was added with (2S) hydrochloride ) - (methocarbaryl) pyrrolidine (1 .14 g) and triethylamine (2.1 ml) under cooling with ice, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was charged with a saturated aqueous solution of sodium chloride and then brought with ethyl acetate. The tract was washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/9) to obtain the title compound (1.46 g, 35% yield) as a colorless amorphous solid. 1 H NMR (500 MHz, CDCl 3) d ppm: -0.04 (3H, s), -0.02 (3H, s), 0.84 (9H, s), 1.69-1.98 (7H, m), 2.03-2.13 (1H, m), 2.31-2.54 (1H, m), 2.71-2.98 (1H, m), 3.03-3.29 (3H, m), 3.37-3.48 (2H, m), 3.59 and 3.62 (total 3H, each s), 3.80-3.93 (1H, m) , 5.63-5.73 (1H, m), 7.08-7.19 (3H, m), 7.20-7.30 (6H, m), 7.36-7.56 (6H, m). (b) (E) -4-Hydrox? -3-f2-r (2S) - (methoxycarbo? p? il) irronfl Din-1-ñ Heti liden) -1- (triphen i I meti H piperidine was synthesized Compound of the title in 99% yield as a pale yellow amorphous solid using (E) -4- (t-butyldimethylsilyl? i) -3- {2 - [(2S) - (methocarbonyl) pyrrolidin-1 -yl] ethylidene} -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e). 1 H NMR (500 MHz, CDCl 3) d ppm: 1.73-1.85 (2H, m), 1.87- 1.98 (2H, m), 2.01-2.18 (3H, m), 2.33-2.43 (2H, m), 2.53-2.75 (1H, m), 3.05-3.23 (4H, m) , 3.26-3.37 (1H, m), 3.64 and 3.66 (total 3H, each s), 3.92-4.04 (1H, m), 5.60-5.70 (1H, m), 7.10-7.20 (3H, m), 7.21- 7.32 (6H, m), 7.37-7.57 (6H, m). (C) hydrogenated bisíacetatc) of (E) -44 ^? Droxi ° 3- 2 ° (2S) - (methoxycarboniQpirroli in-l-ipietilBdenlpiperídipa It was synthesized the title compound in a quantitative yield as a light brown oil using (E) -4-hydro? i -3 {2 - [(2S) - (methocarbyl) pyr rolidin-1-yl] ethylidene} -1- (triphenylmethyl) piperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 5 (c). 1 H NMR (500 MHz, CDCl 3) d ppm: 1.71-1.81 (2H, m), 1.87-2.05 (3H, m), 2.09-2.19 (2H, m), 2.34-2.43 (1H, m), 2.90- 2.98 (1H, m), 3.09-3.33 (4H, m), 3.37-3.45 (1H, m), 3.73 and 3.74 (total 3H, each s), 3.78 (1H, d, J = 14.0), 4.18-4.25 (1H, m), 5.70 (1H, t, J = 7.5). (d) (E) -1-r2-Cyclopropyl ° 1 ° (2-fluorophenyl) ° 2-oxoetBB1 ° 4-hSdro? i ° 3-í2 ° í (2S) - (methoxycarbonyl) pyrrolidin-1-B-ethylidene ) pipep ina The title compound was synthesized in a 54% yield as a light brown oil using (E) -4-hydroxy-3-. { 2 - [(2S) - (methocarbyl) pyrrolidin-1-yl] ethylidene} piperidine bis (hydrogenated acetate) obtained in (c) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (500 MHz, CDCl 3) d ppm: 0.79-0.90 (2H, m), 0.96-1.09 (2H, m), 1.66-1.84 (2H, m), 1.87-2.02 (3H, m), 2.06- 2.16 (1H, m), 2.20-2.29 (1H, m), 2.31-2.39 (1H, m), 2.42-2.56 (1H, m), 2.74-2.86 (1H, m), 2.85 and 2.95 (total 1H, each d, J = 12.5), 2.98 and 3.06 (total 1H, each d, J = 12.5), 3.08-3.19 (2H, m), 3.21-3.45 (2H, m), 3.70 and 3.71 (total 3H, each s ), 4.06-4.16 (1H, m), 4.68 and 4.69 and 4.70 (total 1H, each s), 5.61-5.70 (1H, m), 7.06-7.21 (2H, m), 7.28-7.35 (1H, m) , 7.39-7.47 (1H, m). (e) (E) -4 ° dihydrochloride (AcetylsulfaniB) ° 1-í2 ° eaclopropylene-1] - (2-fluorophenyl) -2-oxoetin-3- (2S) - (methoxycarbonaB) PBB-lidin-1 ] ° illethylidenepiperidine The title compound was synthesized in a 22% yield as a light brown powder crystal using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -4 -hydro? i-3-. { 2 - [(2S) - (methocarbyl) pyrrolidin-1-yl] ethylidene} piperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (h). NMR with 1H (500 MHz, CDCl 3) d ppm: 0.78-0.90 (2H, m), 0.95-1.09 (2H, m), 1.72-1.82 (2H, m), 1.84-1.97 (2H, m), 2.04- 2.40 (4H, m), 2.28 and 2.29 (total 3H, each s), 2.43-2.63 (1H, m), 2.65-2.78 (1H, m), 2.81-3.35 (6H, m), 3.69 and 3.70 and 3.71 and 3.72 (total 3H, each s), 4.26-4.32 (1H, m), 4.65 and 4.67 and 4.68 and 4.69 (total 1H, each s), 5.67-5.73 (1H, m), 7.07-7.19 (2H, m ), 7.29-7.35 (1H, m), 7.39-7.45 (1H, m); MS (FAB) m / z: 489 (M + H) +. (Example 26) dicE hydrochloride). '142 = Cycl? 0r © pdfl = 1 - (2-fluorophenyl) -2-oxoetill-3 =. { 2-r (2S) - (m etox; icarbonal) parroli Dip? = 1] -illetiliden} - 4-Sulfanylpipepdine (Cl lorhi drato deB corrapuesio d @ D Compound No.5-147) The title compound was synthesized in a 46% yield as a light pink powder crystal using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl ]-3-. { 2 - [(2S) - (methocarbyl) pyrrolidin-1-yl] ethylidene} piperidine obtained in Example 25 (e) by performing a reaction similar to that mentioned in Example 2. 1 H NMR (500 MHz, CDCl 3) d ppm: 0.78-0.90 (2H, m), 0.95-1.08 (2H, m) , 1.66-1.99 (4H, m), 2.05-2.38 (4H, m), 2.53-2.66 (1H, m), 2.67-2.86 (1H, m), 3.01-3.39 (6H, m), 3.65-3.79 ( 1H, m), 3.71 and 3.72 (total 3H, each s), 4.69 and 4.71 (total 1H, each s), 5.63-5.71 (1H, m), 7.07-7.19 (2H, m), 7.28-7.35 (1H , m), 7.40-7.46 (1H, m); MS (FAB) m / z: 447 (M + H) +. (Example 27) (E) -3-f2-dic (2S) dihydrochloride ° Carboxyparnon5dan ° 1 inethylidene) -1-r2-cyclopropin-1- (2-fluorophenBl) -2-oxo®tan-4"sulfanylpiperidine ( Hydrochloride of the compound of Gompipyesto B 5-145) The title compound was synthesized in a 76% yield as a light yellow powder crystal using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3-. { 2 - [(2S) - (methocarbyl) pyrrolidin-1-yl] ethylidene} -4-Sulfanylpiperidine obtained in Example 26 carrying out a reaction similar to that mentioned in Example 15. NMR with H (400 MHz, pyridine-d5) d ppm: 0.72-0.90 (2H, m), 0.95-1.20 (2H, m), 1.67-2.26 (4H, m), 2.28-2.53 (3H, m), 2.55-3.21 (3H, m), 3.37-4.38 (7H, m), 4.94-5.09 (1H, m), 6.10- 6.31 (1H, m), 7.11-7.37 (3H, m), 7.62-7.83 (1H, m); MS (FAB) m / z: 433 (M + H) +. (Ex emp ll loo 2 288)) ddii icclloorrhha? Ddrraattoo dde «9 (E) - 4-ÍAcetils uBfan i¡). • 3-Í2- • ÍÍ2S) -carbox ii ippiirrrroolliiddiinn-- -11-- -iilllleett¡i8Siiddeenn} } --11- 42 -cic lopropal-il 424B? uorofeira .01-2-oxoetillpiperidina (Hydrochloride of B compound of B Compound No. 5-146) To a suspension of (E) -3- dihydrochloride. { 2 - [(2S) -carbo? Ipyrrolidin-1-yl] ethylidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine (100 mg) obtained in Example 27 in dichloromethane (5 mL) was added acetic anhydride (28 μL) and triethylamine (97 μl) under cooling with ice, and the resulting mixture was stirred at room temperature for 2 hours. The solvent was removed in vacuo, and the residue was purified using a preparative HPLC (YMC-Pack ODS-A; YMC, eluent: acetonitrile / water containing triethylamine (0.2%) and acetic acid (0.2%) = 3/7) to produce the free form (57 mg, 61% yield) of the title compound as a light brown oil. To a solution of this compound in dichloromethane (1 mL) was added a solution of hydrogen chloride in 4N dioxide (60 μL) at room temperature, and the reaction mixture was evaporated in vacuo. The residue was crystallized from ether to obtain the title compound (41 mg, 62% yield) as a light brown powder crystal. NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.72-0.92 (2H, m), 0.99-1.21 (2H, m), 1.71-2.00 (3H, m), 2.12-2.35 (2H, m), 2.25 and 2.26 and 2.27 (total 3H, each s), 2.38-2.89 (4H, m), 3.17-3.50 (3H, m), 3.55-4.06 (4H, m), 4.53 (1H, m), 4.94 and 4.97 and 4.99 (total 1H, each s), 6.10-6.21 (1H, m), 7.16-7.39 (3H, m), 7.63-7.77 (1H, m); MS (FAB) m / z: 475 (M + H) +. (Eg, ipplloo 2 299)) ddihydrochloride of (E) -4- (AcTtD! SuDfapa0l < -1 42-cycle pprrooppiill- -11-4 (22-- -fflluuoo? RofeniD) -2-oxoetl l | 3 42 -f4-íttoxBcar oraaD) piper ¡iddiinn - 1I ° illlleettiiliiiddeen} piperidine (Cl lorh idrato of B compound of 8 Compound No.5-8) (a) (E) -4- (t-ButyBdmethyl-8-oxyloxy) -34244- (ethoxycarbonyl) pipep in 1 ° I ilet I iden) -14-triphenyl methi H piperidine The title compound was synthesized in a yield of 37%. % as a colorless amorphous solid using 4- (ethoxycarbonyl) piperidine in place of morpholine performing a reaction similar to that mentioned in Example 1 (d). NMR with 1H (500 MHz, CDCl 3) d ppm: -0.04 (3H, s), -0.02 (3H, s), 0.83 (9H, s), 1.25 (3H, t, J = 7.0), 1.68-2.07 ( 10H, m), 2.20-2.30 (1H, m), 2.77-2.91 (3H, m), 2.93-3.10 (2H, m), 3.27-3.65 (1H, m), 3.82-3.92 (1H, m), 4.13 (2H, q, J = 7.0), 5.57-5.66 (1H, m), 7.06-7.19 (3H, m), 7.20-7.30 (6H, m), 7.36-7.58 (6H, m). (b) (E) -342444 EthoxycarboniD) p.peridin-1-B Tet5iid © n > -4-hyd [roxy ° 1"(triphenylmethyl) piperidine The title compound was synthesized in a 99% yield as a colorless oil using (E) -4- (t-butyldimethylsilyloxy) -3-. 4- (ethocarbonyl) piperidin-1-yl] ethylidene} -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e). MHz, CDCl 3) d ppm: 1.25 (3H, t, J = 7.0), 1. 64-2.11 (10H, m), 2.24-2.35 (1H, m), 2.83-2.94 (2H, m), 2.94-3.07 (2H, m), 3.35-3.44 (2H, m), 3.95-4.01 (1H , m), 4.14 (2H, q, J = 7.0), 5.62 (1H, t, J = 6.0), 7.13-7.21 (3H, m), 7.23-7.33 (6H, m), 7.41-7.55 (6H, m). (c) hydrogenated bisiacetate) of (E) ° 3-24244 ° (Etoxycarbonyl) piperidine 1-ethylidene-4 ° h5droxip5 epidine The title compound was synthesized in a 99% yield as a brown crystal using (E) -3-. { 2- [4- (ethoxycarbonyl) piperidin-1-yl] ethylidene} -4-hydro? I-1- (triphenylmethyl) piperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 5 (c). 1 H NMR (500 MHz, CDCl 3) d ppm: 1.25 (3H, t, J = 7.0), 1.41-1.50 (1H, m), 1.60-2.12 (6H, m), 2.23-2.34 (1H, m), 2.83-3.09 (5H, m), 3.30 (2H, q, J = 7.0), 3.39-3.51 (1H, m), 3.75-3.82 (1H, m), 4.13 (2H, q, J = 7.0), 4.19 -4.25 (1H, m), 5.58-5.75 (1H, m). dj (E) -142-Cyclopropyl-1- (2-chloropheniD) "2"? xoetiB1"3 ° 244- (ethoxycarbonyl) piper5din ° 1" petiliden} -4-Hadroxipipepdime The title compound was synthesized in a 63% yield as a light brown oil using (E) -3-. { 2- [4- (ethoxycarbonyl) piperidin-1-yl] ethylidene} -4-hydro? Ipiperidine bis (hydrogenated acetate) obtained in (c) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (500 MHz, CDCl 3) d ppm: 0.76-1.10 (4H, m), 1.25 (3H, t, J = 7.0), 1.42-1.51 (1H, m), 1.65-2.04 (8H, m), 2.08-2.23 (2H, m), 2.27-2.37 (1H, m), 2.42-2.53 (1H, m), 2.76 and 2.96 (total 1H, each d, J = 12.5), 2.77-2.95 (1H, m) , 3.00-3.07 (2H, m), 3.32 and 3.45 (total 1H, each d, J = 12.5), 4.06-4.11 (1H, m), 4.13 (2H, q, J = 7.0), 4.69 and 4.72 (total 1H, each s), 5.61-5.70 (1H, m), 7.07-7.21 (2H, m), 7.28-7.45 (2H, m). (e) (E) -4- (AcetylsulfanBn) dihydrochloride ° 1 ° 2 ° cyc8opropion 1 (2 ° fluorophenyl) -2-oxoetin-34244- (ethoxycarbonyl) pipepdan-1 ° illethylidene) piperidine was synthesized Compound the title in a 17% yield as a yellow powder crystal using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3-. { 2- [4- (ethoxycarbonyl) piperidin-1-yl] ethylidene} -4-hydro? Ipiperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (h). 1 H NMR (500 MHz, CDCl 3) d ppm: 0.77-1.11 (4H, m), 1.25 (3H, t, J = 7.0), 1.67-1.98 (7H, m), 2.07-2.29 (3H, m), 2.28 and 2.29 (total 3H, each s), 2.47-2.62 (1H, m), 2.65-2.96 (5H, m), 2.81 and 3.02 (total 1H, each d, J = 12.5), 3.26-3.39 (1H, m), 4.13 (2H, q, J = 7.0), 4.27-4.36 (1 H, m), 4.66 and 4.69 (total 1 H, each s), 5.64 (1 H, t, J = 7.0), 7.07-7.20 (2H , m), 7.28-7.45 (2H, m); MS (FAB) m / z: 517 (M + H) +. (Example 30) dicBordádrato de (E) ° 142 ° GBClopropiD ° 'B 42-fluorophenyl) ° 2-oxoetip-3-f2-r4- (ethoxycarbonyl) piperñdñn ° 1 ° Blletiliden} -4-Sulfanylpiperidine (CBorhydrate of Compound B Compound No. 5-7) The title compound was synthesized in a 97% yield as a light yellow powder crystal using (E) -4- (acetylsulfanyl) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl ]-3-. { 2- [4- (ethocarbonyl) piperidin-1-yl] ethylidene} piperidine obtained in Example 29 (e) by performing a reaction similar to that mentioned in Example 12. NMR with H (500 MHz, CDCI3) d ppm: 0.75-1.10 (4H, m), 1.25 (3H, t, J = 7.0), 1.667-1.80 (3H, m), 1 .82-1 .99 (4H, m), 2.10-2.31 (3H, m), 2.54-2.68 (1 H, m), 2.69-2.97 (5H, m), 3.14 and 3.35 (total 1 H, each d, J = 12.5), 3.16-3.23 (1 H, m), 3.72-3.83 (1 H, m), 4.13 (2 H, q, J = 7.0), 4.69 and 4.71 (total 1 H, each s), 5.61 (1 H, m) , 7.05-7.21 (2H, m), 7.23-7.46 (2H, m); MS (FAB) m / z: 475 (M + H) +. (Example 31) (E) -3-f2444Carboxipiperid5-na) dihydrochloride] 1] -inethylidene > -142-cyclopropiB-142-fluorofenBl) "2-oxoeti8] -4-sulfanylpiperadine (Hydrochloride of compound of Compound No. 5-3) The title compound was synthesized in a 90% yield as a light yellow powder crystal using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- dihydrochloride. . { 2- [4- (Ethoxycarbonyl) piperidin-1-yl] ethylidene} -4-Sulfanylpiperidine obtained in Example 30 performing a reaction similar to that mentioned in Example 15. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.73-0.83 (2H, m), 1.03-1.13 (2H, m), 1.73-1.81 (1H, m), 2.13-2.31 (2H, m), 2.47 (2H, br), 2.59-2.98 (7H, m), 3.04-3.27 (1H, m), 3.39 and 3.45 ( total 1H, each d, J = 12.0), 3.51-3.68 (2H, m), 3.80-3.89 (3H, m), 5.00 and 5.01 (total 1H, each s), 6.41 (1H, t, J = 7.5) , 7.22-7.25 (2H, m), 7.27-7.35 (1H, m), 7.58-7.60 (1H, m); MS (FAB) m / z: 447 (M + H) +. (Example 32.}. (E) -44 AcetylsulfanaB) -142-cic8oprop5B "H42 ° fluorophenol) -2-oxoetin ° 3 ° (2-hydroxyethylidene) piperidane (Compound of compound No.3-2) (a) (E) -4- (Acetalsu8fani8) ° 3-r (ethoxycarbo? p? ol)? m? etñB5 l®? r? l ° 1 ° (traphenyl methyl I) piperidine To a solution of (E) -3 - [(ethocarbonyl) methylidene] -1- (triphenylmethyl) piperidin-4-ol (23.06 g) in dichloromethane (200 ml) was added methanesulfonyl (4.60 ml) and triethylamine (9.77 ml) under cooling with ice, and the resulting mixture was stirred at room temperature for 1 hour. After a saturated aqueous solution of sodium hydrogenated carbonate was poured into the reaction mixture and the resulting mixture was extracted with dichloromethane, the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to obtain a crude product of (E) -3 - [(ethocarbonyl) methylidene] -4-mesyl? I-1 - (triphenylmethyl) piperidine as a pale yellow amorphous solid. To a solution of this compound in ethanol (250 ml) was added potassium thioacetate (1.32 g) at room temperature, and the resulting mixture was stirred at 70 ° C for 1 hour. The reaction mixture was evaporated in vacuo. The residue was diluted with ethyl acetate and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/5) to obtain the title compound (1 8.35 g, yield 70%) as a light yellow amorphous solid. 1 H NMR (400 MHz, CDCl 3) d ppm: 1.1 (314, t, J = 7.0), 1.89-1.99 (1 H, m), 2.1 0-2.24 (1 H, m ), 2.27 (3H, s), 2.30-2.40 (2H, m), 2.51-2.65 (1H, m), 3.83 (1H, m), 3.98-4.08 (2H, m), 4.30-4.37 (1H, m ), 5.98 (1H, s), 7.12-7.51 (15H, m). (b) (E) -3- (2-Hydroxyethylidene) -4-sulfanyl-14-triphenylmethoxypropionate [p? a To a solution of (E) -4- (acetylsulfanyl) -3 - [(ethoxycarbonyl) methylidene] -1- (triphenylmethyl) piperidine (18.35 g) obtained in (a) above in dichloromethane (300 ml) was added dropwise a 1.01N solution of diisobutylaluminum hydride in toluene (151 ml) at -78 ° C, and the The resulting mixture was stirred at the same temperature for 1 hour. A saturated aqueous tetrahydrated solution of sodium potassium tartrate was added to the reaction mixture, and the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was extracted with ethyl acetate and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water / dichloromethane = 1/2/1) to obtain the title compound (10.00 g, yield 66). %) as a light yellow amorphous solid. 1 H NMR (400 MHz, CDCl 3) d ppm: 1.75-1.92 (1H, m), 2.25-2.57 (3H, m), 2.74-3.13 (2H, m), 3.53-3.72 (1H, m), 4.03- 4.22 (2H, m), 5.71-5.85 (1H, m), 7.10-7.60 (15H, m). (c) (E) -3-f2- (t-ButyldimethylsilyBBoxi) et5ladenl-4 ° sunifa? nBB ° 1l ° (triphenylmethi) piperidine To a solution of (E) -3- (2-hydroxyethylidene) -4-sulfanyl-1- (triphenylmethyl) piperidine (10.00 g) obtained in (b) above in dichloromethane (100 ml) was added chloride of t-butyldimethylsilyl (5.63 g), triethylamine (5.23 ml) and 4-dimethylaminopyridine (0.15 g) under cooling with ice, and the resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was evaporated in vacuo. The residue was diluted with dichloromethane and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/10) to obtain the title compound (10.66 g, 83% yield) as a colorless amorphous solid. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.01-0.05 (6H, m), 0.85-0.90 (9H, m), 1.73-1.85 (1H, m), 2.20-2.51 (3H, m), 2.86- 3.20 (2H, m), 3.60-3.64 (1H, m), 4.11-4.19 (2H, m), 5.64-5.71 (1H, m), 7.12-7.53 (15H, m). (d) (E) -4- (AcetilsuBfanl) -3424t-butiidirneti8siBa oxy) etaDide [p? Tl-1] ° (trifen i I meti I) piperi ina To a solution of (E) -3- [2- (t-butyldimethylsilyloxy) ethylidene] -4-sulfanyl-1- (triphenylmethyl) piperidine (10.66 g) obtained in (c) above in dichloromethane (100 mL) was added acetic anhydride (2.93 mL), pyridine (5.00 mL) and 4-dimethylaminopyridine (0.13 g) under ice cooling, and the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was evaporated in vacuo. The residue was diluted with ethyl acetate and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / hexane = 1/10) to obtain the title compound (10.95 g, 95% yield) as an amorphous solid. colorless. NMR with H (400 MHz, CDCl 3) d ppm: 0.04-0.07 (6H, m), 0.83-0.92 (9H, m), 1.75-1.92 (1H, m), 2.19-2.34 (5H, m), 2.41- 2.70 (1H, m), 2.90-3.13 (2H, m), 4.06-4.21 (2H, m), 4.21-4.34 (1H, m), 5.66 (1H, t, J = 6.0), 7.11-7.54 (15H , m). (e) Hydrogenated trifluoroacetate of (E) -44AceSDlsulfan) -342-hydroxyethylidene) piperidine To a solution of (E) -4- (acetylsulfanyl) -3- [2- (t-butyldimethylsilyl) i) ethylidene] -1 - (triphenylmethyl) piperidine (10.95 g) obtained in (d) above in dichloromethane (10 ml) was added trifluoroacetic acid (15 ml) under cooling with ice, and the resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was evaporated in vacuo, and the residue was purified by chromatography on a silica gel column (methanol / dichloromethane = 1/10 - 1/1) to obtain the title compound (6.90 g, quantitative yield) like a brown oil. 1 H NMR (400 MHz, CDCl 3) d ppm: 1.96-2.10 (1H, m), 2.26-2.43 (4H, m), 3.13-3.28 (1H, m), 3.29-3.41 (1H, m), 3.57- 3.67 (1H, m), 4.02-4.11 (1H, m), 4.14-4.28 (2H, m), 4.40-4.45 (1H, m), 6.04-6.11 (1H, m). £ f] (E) -44 AcetylsulfaniB) -142-cycloBropyl ° 1424luorof®? P) iD) -2"Oxoetin ° 3- (2-hdroxietiBiden) piperi ina The title compound was synthesized in a yield of 74% as an oil yellow using hydrogenated trifluoroacetate of (E) -4- (acetylsulfanyl) -3- (2-hydroxyethylidene) piperidine (6.90 g) obtained in (e) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.75-0.92 (2H, m), 0.96-1.11 (2H, m), 1.59-1.87 (2H, m), 2.07-2.19 (1H, m), 2.19- 2.34 (3H, m), 2.44-2.63 (1H, m), 2.64-2.79 (1H, m), 2.82 and 3.09 (total 1H, each d, J = 12.5), 3.26 and 3.41 (total 1H, each d, J = 12.5), 3.97-4.18 (2H, m), 4.23-4.37 (1H, m), 4.73 and 4.78 (total 1H, each s), 5.75-5.87 (1H, m), 7.70-7.24 (2H, m ), 7.29-7.41 (2H, m). (Example 33.} (E) -44-Acetylsulfan-B) ° 1 2-cyclopropaland H-4-fluorophenyl) -2-oxoetyl-3-f2-r4- (ethoxycarbonyl et58) paperidira ° H -yltilylidene piperidine (Compound of compound Mo .5-14) To a solution of (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- (2-hydroxyethylidene) piperidine (500 mg) obtained in the example 32 (f) and p-toluenesulfonic anhydride (580 mg) in acetonitrile (5 ml) was added triethylamine (0.22 ml) under cooling with ice, the resulting mixture was stirred at room temperature for 5.5 hours. To the reaction mixture was added 4- (ethoxycarbonylmethyl) piperidine (450 mg) and triethylamine (0.37 ml), and the resulting mixture was stirred at room temperature for 3 hours and then allowed to stand for 3 days. The reaction mixture was diluted with ethyl acetate and washed with water, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (methanol / dichloromethane = 1/10) and then purified using a preparative HPLC (YMC-Pack ODS-A; YMC , eluent: acetonitrile / water with triethylamine (0.2%) and acetic acid (0.2%) = 13/7). The eluted fraction was brought with ethyl acetate and washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to obtain the title compound (204 mg, 29% yield) as a yellow oil. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.77-0.92 (2H, m), 0.94-1.10 (2H, m), 1.26 (3H, t, J = 7.0), 1.55-1.89 (7H, m), 2.08-2.19 (2H, m), 2.21-2.26 (2H, m), 2.27-2.32 (3H, m), 2.48-2.61 (1H, m), 2.62-2.72 (1H, m), 2.72-3.40 (7H , m), 4.07-4.17 (2H, m), 4.24-4.36 (1H, m), 4.65-4.75 (1H, m), 5.69 (1H, bs), 7.08-7.22 (2H, m), 7.29-7.42 (2H, m). (Example 34) dihydrochloride of (E) ° 1"42" Cg 8opropon-H42 ° fluorophenyl) -2-oxoetip ° 3 ° 244- (ethoxycarbo il? Methy) p5perid.RTM. 1i -Hethylidene -4-sulfanylpperapera (Hydrochloride of B compound DEB Compound No.5-13) To a solution of (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3-. { 2- [4- (Etho-icarbonylmethyl) piperidin-1-yl] ethylidene} Piperidine (204 mg) obtained in Example 33 in ethanol (10 ml) was bubbled with hydrogen chloride under cooling with ice, and the resulting mixture was stirred at room temperature under hermetic conditions overnight. The reaction mixture was evaporated in vacuo to obtain the title compound (201 mg, 93% yield) as a colorless amorphous solid. NMR with 1H (400 MHz, CDCl 3) d ppm: 0.71-0.86 (2H, m), 1.03-1.12 (2H, m), 1.14 (3H, t, J = 7.0), 1.71-1.82 (1H, m), 1.94-2.08 (2H, m), 2.09-2.49 (6H, m), 2.57-3.02 (4H, m), 3.33-3.48 (1H, m), 3.49-3.71 (4H, m), 3.76-3.83 (2H , m), 3.83-3.92 (1H, m), 4.11 (2H, q, J = 7.0), 5.03 and 5.04 (total 1H, each s), 6.31-6.43 (1H, m), 7.13-7.31 (2H, m), 7.31-7.42 (1H, m), 7.54-7.65 (1H, m). (Example 35) dihydrochloride of (E) -34244-Carboxn? Pp®tBlpip®pdB? -1] -yl) ethylidene-42-cyclopropyl-1- (2-fluorofenfll) -2-oxo tall-4 ° sulfanylpiperidine (Hydrochloride of B compound deB Compound No. 5-9) • 2HCl The title compound was synthesized in a 57% yield as a colorless amorphous solid using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3-. { 2- [4- (Etho-icarbonylmethyl) piperidin-1-yl] ethylidene} -4-Sulfanylpiperidine dihydrochloride obtained in Example 34 carrying out a reaction similar to that mentioned in Example 15. 1 H NMR (500 MHz, CDCl 3) d ppm: 0.72-0.88 (2H, m), 1.04-1.17 (2H, m ), 1.71-1.83 (1H, m), 1.94-2.11 (2H, m), 2.11-2.34 (5H, m), 2.46 (2H, bs), 2.65-2.76 (1H, m), 2.76-3.07 (4H , m), 3.46 (1H, d, J = 12.5), 3.59 (1H, d, J = 12.5), 3.62-3.75 (2H, m), 3.83-3.96 (2H, m), 5.08 (1H, s) , 6.40 (1H, m), 7.22-7.31 (2H, m), 7.34-7.41 (1H, m), 7.61-7.67 (1H, m); IR (KBr, cm "1): 2556, 1714, 1493. (Example 36) dihydrochloride of (E) ° 4- (Acet5lsuBfap5l) ° 1-r2 ° cyclopropyl ° 1- (2-fluorofeniB) ° 2-oxoetin-3 - {1 1 (((ethoxycarbonyl? ppiTtñB) piperidin-4-ylmethylidene.}. piperidine (Hydrochloride of B compound of B Compound No.3-32) (a) 3-. { H Etoxycarbonylmethyl) pfperfldin-4-i8lfoidrox5m @ ft¡8} 1) - (triphenylmethyl) piperidin-4-one To a solution of 1- (triphenylmethyl) piperidin-4-one (22.99 g) in tetrahydrofuran (250 ml) was added dropwise a 1.0N solution of bis (trimethylsilyl) sodium amide in tetrahydrofuran (68 ml) at -78 ° C, and the resulting mixture was stirred at the same temperature for 20 minutes. To the reaction mixture was added dropwise a solution of 1- (ethocarbarylmethyl) piperidin-4-carbaldehyde (13.43 g) in tetrahydrofuran (35 ml) at -78 ° C, and the resulting mixture was stirred to the Same temperature for 2 hours. The reaction mixture was charged with a saturated aqueous solution of ammonium chloride and then was brought with a mixed solvent of ethyl acetate and diethyl ether. The tract was washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/4 - 1/0) to obtain the title compound (12.32 g, yield 34). %) as a light yellow amorphous solid. NMR with 1H (400 MHz, CDCl 3) d ppm: 1.27 (3H, t, J = 7.0), 1.41-2.18 (8H, m), 2.30-2.51 (1H, m), 2.67-3.25 (8H, m), 3.45-3.71 (2H, m), 4.18 (2H, q, J = 7.0), 7.11-7.60 (15H, m). £ b} (E) -3 ° ai4 EthoxycarbonylmethoB) piperBdnn-44l? MetiBBd®o) 1] - (triphenylmethyl) piperidine 4-one To a solution of 3-. { [1- (Ethylcarbonylmethyl) piperidin-4-yl] hydroxymethyl} -1- (triphenylmethyl) -piperidin-4-one (9.87 g) obtained in (a) above in tetrahydrofuran (150 ml) was added methanesulfonyl chloride (7.0 ml), 1,8-diazabicyclo [5.4.0] undec. -7-ene (19 ml) and 4-dimethylaminopyridine (0.23 g) under ice-cooling, and the resulting mixture was stirred at room temperature for 17 hours. The reaction mixture was diluted with a mixed solvent of ethyl acetate and diethyl ether and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/4 - 4/1) to obtain the title compound (3.92 g, yield 41 %) as a yellow amorphous solid. 1 H NMR (400 MHz, CDCl 3) d ppm: 1.27 (3H, t, J = 7.0), 1.50-1.66 (4H, m), 1.89-2.01 (1H, m), 2.10-2.21 (2H, m), 2.50-2.69 (4H, m), 2.83-2.93 (2H, m), 3.08-3.23 (4H, m), 4.18 (2H, q, J = 7.0), 6.49 (1H, d, J = 10.0), 7.14 -7.33 (9H, m), 7.46-7.56 (6H, m). £ cj (E) -34ri- (EthoxycarbonylmetB) piperidin "44llmet8D5 ®ct) >;1 (trifhenylmethyl) piperidin-4 ° ol To a solution of (E) -3-. { [1- (ethoxycarbonylmethyl) piperidin-4-yl] methylidene} -1- (triphenylmethyl) piperidin-4-one (6.14 g) obtained in (b) above in a mixed solvent of ethanol (40 ml) and dichloromethane (40 ml) was added sodium borohydride (0.55 g) under cooling with ice, and the resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of hydrogenated sodium carbonate and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / hexane = 2/3) to obtain the title compound (4.17 g, 68% yield) as an amorphous solid. colorless. NMR with 1H (400 MHz, CDCl 3) d ppm: 1.29 (3H, t, J = 7.5), 1. 44-2.18 (7H, m), 2.77-3.22 (10H, m), 3.91-4.02 (1H, m), 4.20 (2H, q, J = 7.5), 5.31 (1H, d, J = 10.0), 7.09 -7.30 (9H, m), 7.38-7.56 (6H, m). (d) bis (hydrogenated trifluoroacetate) of (E) -4- (Aceti-suB1Fa? p? an) ° 3'- (ethoxycarbonylmethyl) piperidin-4-inmethylidene > pñp®ri Braa To a solution of (E) -3-. { [1- (ethoxycarbonylmethyl) piperidin-4-yl] methylidene} -1- (triphenylmethyl) piperidin-4-ol (2.98 g) obtained in (c) above in toluene (50 ml) was added thioacetic acid (1.20 ml) and dyneopentyl acetal of N, N-dimethylformamide (4.80 ml) under ice cooling, and the resulting mixture was stirred at room temperature for 1.5 hours. The reaction mixture was diluted with ethyl acetate and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 2/3) to obtain (E) -4- (acetylsulfanyl) -3-. { [1- (Eto? Icarbonylmethyl) piperidin-4-yl] methylidene} -1- (triphenylmethyl) piperidine (1.97 g, with impurities) as a pale yellow amorphous solid. To a solution of the above mixture (1.97 g) in dichloromethane (30 ml) was added trifluoroacetic acid (0.60 ml) under cooling with ice, and the resulting mixture was stirred at room temperature for 30 minutes. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethanol / dichloromethane = 1/4 - 2/3) to obtain the title compound (1.53 g, 48% yield) as a yellow amorphous solid. NMR with 1H (400 MHz, CDCl 3) d ppm: 1.29 (3H, t, J = 7.0), 1.67-2.61 (10H, m), 3.00-4.03 (10H, m), 4.25 (2H, q, J = 7.0 ), 4.39 (1H, t, J = 4.5), 5.71 (1H, d, J = 10.0). (e) (E) -44-Acetylsulfana8) -H-4-cyclopropyl-1,442-fluorophenyl) -2-oxoetip-34-dihydrochloride (ethoxycarbonyl-ethyl) pip® rbdBn-4"5H-methylidene) piperidine The title compound was synthesized in a yield of 81% as a colorless amorphous solid using bis (hydrogenated trifluoroacetate) of (E) -4- (acetylsulfanyl) -3-. { [1- (ethoxycarbonylmethyl) piperidin-4-yl] methylidene} piperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (g). NMR with 1H (400 MHz, CDCl 3) d ppm: 0.76-0.89 (2H, m), 0.90-1.12 (2H, m), 1.28 (3H, t, J = 7.0), 1.39-2.34 (11H, m), 2.41-2.98 (7H, m), 3.18 and 3.19 (total 2H, each s), 3.28-3.39 (1H, m), 4.13-4.33 (3H, m), 4.63 and 4.70 (total 1H, each s), 5.38 (1H, d, J = 9.0), 7.05-7.21 (2H, m), 7.27-7.37 (1H, m), 7.39-7.51 (1H, m); IR (KBr, cm "1): 2614, 1697. (Example 37) (E) -3-yp- (Carboxim®tiB) pip® dihydrochloride] rdinin 4-inmethylidene-1-r2-cyclopropyl-1- ( 2-fluorofeniB) ° 2 ° oxoetBn ° 4 ° sulfanylpiperidine (Hydrochloride of Compound B Compound No. 3-27) To a solution of (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3-. { [1- (Eto? Icarbonylmethyl) piperidin-4-yl] methylidene} piperidine (1.13 g) obtained in example 36 (e) in ethanol (20 ml) was bubbled with hydrogen chloride under cooling with ice, and the resulting mixture was stirred at room temperature under airtight condition for 3 hours. After the reaction mixture was evaporated in vacuo, the residue obtained was dissolved in 3N hydrochloric acid (20 ml) and the resulting mixture was stirred at 50 ° C for 12.5 hours. The reaction mixture was stirred in vacuo, and the residue was purified using a preparative HPLC (YMC-Pack ODS-A; YMC, eluent: acetonitrile / 0.024N hydrochloric acid = 10/90) to obtain the title compound (0.38 g, 34% yield) as a colorless amorphous solid. NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.75-0.87 (2H, m), 0. 96-1.19 (2H, m), 1.62-2.54 (8H, m), 2.62-3.19 (4H, m), 3.31-3.87 (5H, m), 4.10 and 4.11 (total 2H, each s), 4.94 and 4.95 (total 1H, each s), 5.49 and 5.50 (total 1H, each d, J = 9.0), 7.18-7.39 (3H, m), 7.70-7.78 (1H, m); IR (KBr, cnT1): 2659, 1713, 1494. fluorophenyl!) -2-oxoetill-34p- (ethoxycarbonyl) Dethyl) piperidyl? -4-? llmethylide n) -4-his Ifanilpaperidine (Hydrochloride of D compound) Compound No.3-31) To a solution of (E) -3- dihydrochloride. { [1- (carbo? Imethyl) piperidin-4-yl] methylidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine (0.17 g) obtained in Example 37 in ethanol (4 mL) was bubbled with hydrogen chloride under cooling with ice, and the resulting mixture was stirred at room temperature under sealed conditions for 7 hours. The reaction mixture was allowed to stand still at -20 ° C for 3 days and then stirred at room temperature for a further 7 hours. The reaction mixture was evaporated in vacuo, and the residue was purified by chromatography on a silica gel column (ethanol / dichloromethane = 1 / 99-1 / 4) to obtain the title compound (0.16 g, 89% yield). ) as a colorless amorphous solid. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.77-1.12 (4H, m), 1.28 (3H, t, J = 7.0), 1.41-2.36 (8H, m), 2.55-3.36 (10H, m), 3.68-3.81 (1H, m), 4.19 (2H, q, J = 7.0), 4.66 and 4.72 (total 1H, each s), 5.32 and 5.34 (total 1H, each d, J = 9.0), 7.03-7.55 ( 4H, m); IR (KBr, cnrT1): 2617, 1713, 1494.

(Example 39) dihydrochloride of (E) -44Aceta sulfan5ll) -3 '._! __. carboxymethyl) piperidin-4-ylmethylidene-1-f2-chloclopropyl-1- (2-fluorophenyl) -2-oxoetiH ppependine (Hydrochloride of Compound Compound No.3-28) The compound was synthesized in a 52% yield as a colorless amorphous solid using (E) -3- dihydrochloride. { [1- (carbo? Imethyl) piperidin-4-yl] methylidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-sulfanylpiperidine obtained in Example 37 performing a reaction similar to that mentioned in Example 28. 1 H NMR (400 MHz, CDCI3) d ppm: 0.73-0.89 (2H, m), 0.95-1.07 (2H, m), 1.67-2.34 (11H, m), 2.47-3.42 (10H, m), 4.21 and 4.27 (total 1H, each t , J = 4.5), 4.73 and 4.75 (total 1H, each s), 5.37-5.45 (1H, m), 7.09-7.20 (2H, m), 7.31-7.39 (2H, m); IR (KBr, cm-1): 2627, 1698. (EiempBo 40.}. (E) ° 4- (AcetilsulfaraBB) ° 1 ° r2 ° echlopropionl 1l ° (2-fluorofeni8) -2-oxoetin-3-r2 - (1H-pirazoS-1-B ») etB8iden1p¡pepd? Cna (Compound of compound No. H-2) (a) (E) "4- (t-Butyldim®tiBsilyloxy) -34241H-pyrazop-'fl 4l) etBBid® rcl-1 - (triphen I I meti) piperidine To a solution of (E) -4- ( t-butyldimethylsilyl) i) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine (14.7 g) obtained in Example 1 (b), 1H-pyrazole (2.0 g) and 1.1 '- ( azodicarbonyl) dipiperidine (8.9 g) in toluene (150 ml) under a stream of nitrogen gas was added tributylphosphine (8.8 ml) under cooling with ice, and the resulting mixture was stirred at room temperature for 1 hour. evaporated in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/6) to obtain the title compound (9.78 g, 57% yield) as an amorphous solid colorless NMR with 1H (400 MHz, CDCl 3) d ppm: 0.04 (3H, s), 0.06 (3H, s), 0.89 (9H, s), 1.82 (1H, bs), 1.90-2.03 (3H, m) , 3.04 (1H, bs), 3.74 (1H, bs), 3.97 (1H, m), 4.78-4.90 (2H, m), 5.86 (1H, t, J = 7.0), 6.33-6.34 (1H, m) , 7.22-7.23 (5H, m), 7.28-7.32 (4H, m), 7.48-7.68 (8H, m). (b) (E) ° 4-Hydroxy-3-r2 ° (1H-pyrazoB-1-DB) etiBid® 1- (trife? p? oBpp? ethan) piperidine The title compound was synthesized in a yield of 77% as a colorless crystal using (E) -4- (t-butyldimethylsilyloxy) -3- [2- (1 H -pyrazol-1-yl) ethylidene] -1- (triphenylmethyl) piperidine obtained in (a) above by performing a reaction similar to that mentioned in Example 1 (e). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.44-1.50 (1H, m), 1.65-1.70 (1H, m), 1.82-1.89 (1H, m), 2.08-2.12 (1H, m), 2.85 ( 1H, bs), 3.38-3.41 (1H, m), 4.01 (1H, bs), 4.73-4.82 (2H, m), 5.79 (1H, t, J = 6.5), 6.28 (1H, m), 7.15-7.17 (5H, m), 7.24-7.27 (4H, m), 7.42 (1H, m), 7.49 (6H , bs), 7.53 (1H, m). (c) (E) -4- (Acetylsulfanyl) -3- [2- (1H-pyrazol-1-yl) ethylidene] -1- (triphenylmethyl) piperidine The title compound was synthesized in a 56% yield as a yellow amorphous solid using (E) -4-hydro? -3- [2- (1 H-pyrazol-1-yl) ethylidene] -1- (triphenylmethyl) piperidine obtained in (b) above carrying out a reaction similar to mentioned in Example 1 (h). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.85-1.92 (1H, m), 2.24 (3H, s), 2.26-2.34 (1H, m), 2.64-2.67 (1H, m), 2.79-2.83 (1H, m), 4.21-4.36 (3H, m), 4.65-4.78 (2H, m) , 5.79 (1H, t, J = 7.0), 6.26 (1H, m), 7.11-7.15 (5H, m), 7.22-7.27 (4H, m), 7.42 (1H, m), 7.45 (6H, bs) 7.62 (1H, m). (d) hydrogenated trifluoroacetate of (E) -44Ac®t5lsulfap? iD) ° 342 ° (1 H-pi razo 1-1 -i Qetilidenl piperidine The title compound was synthesized in a yield of 32% as a brown oil using ( E) -4- (Acetylsulfanyl) -3- [2- (1 H -pyrazol-1-yl) ethylidene] -1- (triphenylmethyl) piperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 3 (c). 1 H NMR (400 MHz, CDCl 3) d ppm: 2.03-2.07 (1H, m), 2.35 (3H, s), 2.38-2.45 (1H, m), 3.23-3.30 (1H, m), 3.38-3.43 (1H, m), 3.73 (1H, d, J = 14.0), 4.12 (1H, d, J = 14.0), 4.43-4.45 (1H, m), 4.68-4.84 (2H, m), 6.03 (1H, t, J = 7.0), 6.23-6.24 (1H, m), 7.39-7.40 (1H, m), 7.46 (1H, bs). (e) (E) -4- (AcetylsulfaniB) -142"CyclopropaB" 1424! uorotF®pál) -2-oxoetin-34241H-pyrazoB-148) ethylidenepiperidine The title compound was synthesized in 75% yield as a yellow oil using hydrogenated trifluoroacetate of (E) -4- (acetylsulfanyl) -3- [2- (1 H-pyrazol-1-yl) ethylidene] piperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.75-0.88 (2H, m), 0.97-1.06 (2H, m), 1.79-1.86 (1H, m), 2.10-2.21 (1H, m), 2.22- 2.31 (1H, m), 2.28 and 2.29 (total 3H, each s), 2.49-2.62 (1H, m), 2.68-2.73 and 2.76-2.81 (total 1H, each m), 2.89 and 3.16 (total 1H, each d, J = 12.5), 3.32 and 3.43 (total 1H, each d, J = 12.5), 4.28-4.35 (1H, m), 4.67-4.75 (3H, m), 5.80 (1H, t, J = 7.0) , 6.22-6.24 (1H, m), 7.08-7.17 (2H, m), 7.28-7.38 (3H, m), 7.47-7.48 (1H, m). (Example 41) (E) -142-C5clopropBB ° H424Dyoroff®niiD) hydrochloride) "2-oxoetiH-34241H-pyrazole" 1-yl) ethylidene-1,4-suptha) BBp5pen (Compound H-Hydrochloride -HI The title compound was synthesized in a 27% yield as a colorless amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- [2- (1H-pyrazol-1-yl) ethylidene] piperidine obtained in Example 40 (e) by performing a reaction similar to that mentioned in Example 2. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.77-0.80 (2H, m), 0.98-1.03 (1H, m), 1.06-1.13 (1H, m), 1.74-1.81 (1H, m), 2.13-2.24 (1H, m), 2.39-2.47 (1H, m) , 2.51-2.54 (1H, m), 2.83-2.88 and 2.91-2.97 (total 1H, each m), 3.33-3.38 (1H, m), 3.75-3.80 (1H, m), 4.90-4.96 (3H, m ), 5.94-5.98 (1H, m), 6.33 (1H, t, J = 2.0), 7.17-7.22 (1H, m), 7.26-7.32 (1H, m), 7.63-7.66 (3H, m), 7.70 -7.71 (2H, m); IR (KBr, cm "1): 1712, 1495. (Example 42) (E) -4- (AcetylsuDfanal) -1] 42-cyclopropne" 142-fluorophenyl) -2-oxoetin-342- (4-ethoxycarbonB8 hydrochloride. ° 1H "Pirazofl ° 1-ñDetilidenlpiperidina (B-hydrochloride of compound of Compound No. 1-26) (a) (E) -44t-ButyldimetBflsi8llox!) -34244-etox -earb @ mll 1H-porg) gol ° 11 -yl) ethylidene-1-triphenyl-ethyl) piperidine The title compound was synthesized in a yield 83% as a colorless amorphous solid using (E) -4- (t-butyldimethylsilyloxy) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine obtained in Example 1 (b) and 4-ethoxycarbonyl-1H-pyrazole performing a reaction similar to that mentioned in Example 40 (a). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.04 (6H, s), 0.88 (9H, s), 1.36-1.49 (2H, m), 1.40 (3H, t, J = 7.0), 1.71-1.82 ( 1H, m), 1.90-2.00 (2H, m), 2.40 (1H, bs), 3.93-3.97 (1H, m), 4.34 (2H, q, J = 7.0), 4. 73-4.86 (2H, m), 5.84 (1H, t, J = 7.0), 7.19-7.23 (5H, m), 7.27-7.32 (5H, m), 7.52 (5H, bs), 7.95 (1H, s), 7.97 (1H, s). (b) (E) -342- (4-Ethoxycarbonyl-1H-pyrazoB-1 ° B) et? 8id®n1-4-hydroxy "1- (triphenylmethyl) piperidine The title compound was synthesized in a quantitative yield as a colorless amorphous solid using (E) -4- (t-butyldimethylsilyl) i) -3- [2- (4-ethoxycarbonyl-1H-pyrazol-1-yl) ethylidene-3-1- (triphenylmethyl) piperidine obtained in (a) ) above performing a reaction similar to that mentioned in Example 1 (e). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.34 (3 H, t, J = 7.0), 1. 81-1.90 (1H, m), 2.07-2.12 (1H, m), 2.87 (2H, bs), 3.46 (2H, bs), 3. 98 (1H, bs), 4.28 (2H, q, J = 7.0), 4.68-4.79 (2H, m), 5.76 (1H, t, J = 7.0), 7.12-7.15 (3H, m), 7.21-7.25 (6H, m), 7.45 (6H, bs), 7.89 (2H, s). (c) (E) -44 AcetylsulfanBl) -34244-ethoxycarboniD "1H-pyrazo8" 1"iD) ethylidene-1- (triphenylmethyl) piperidine The title compound was synthesized in 88% yield as a yellow amorphous solid using (E) ) -3- [2- (4-ethoxycarbonyl-1 H -pyrazol-1-yl) ethylidene] -4-hydro? I-1- (triphenylmethyl) piperidine obtained in (b) above performing a reaction similar to that mentioned in Example 1 (h). NMR with 1H (400 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 1. 86-1.94 (1H, m), 2.21-2.24 (1H, m), 2.24 (3H, s), 3.80-3.83 (1H, m), 4.11 (2H, q, J = 7.0), 4.19-4.27 (6H , m), 5.77 (1H, t, J = 7.0), 7.12-7.17 (5H, m), 7.22-7.26 (5H, m), 7.43-7.45 (5H, m), 7.85 (1H, s), 7.91 (1H, s). (d) Hydrogenated trifluoroacetate of (E) -44AcetaDsylfanil) -34244-ethoxycarbon and 1-1 H-pyrazoi-1 -i Detylidene piperidine The title compound was synthesized in a 23% yield as an amorphous coffee solid using (E) ) -4- (acetylsulfanyl) -3- [2- (4-ethoxycarbon and 1-1H-pyrazol-1-yl) ethylidene] -1- (triphenylmethyl) piperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 3 (c). NMR with 1H (400 MHz, CDCl 3) d ppm: 1.33 (3H, t, J = 7.0), 2. 07-2.10 (1H, m), 2.36 (3H, s), 2.38-2.46 (1H, m), 3.22-3.28 (1H, m), 3. 36-3.42 (1H, m), 3.73 (1H, d, J = 14.0), 4.11 (1H, d, J = 14.0), 4.27 (2H, q, J = 7.0), 4.44-4.46 (1H, m), 4.72-4.84 (2H, m), 6.04-6.07 (1H, m), 7.85 (1H, s), 7.88 (1H, s) . (e) hydrochloride (E) -44Acetdlsulfan8D) "142" eicoropDD ° H42-fluorophenyl) -2-oxoetin-34244-ethoxycarbonBB-1H-p5razo ° Detylidenepiperidine The title compound was synthesized in a yield of 74. % as a yellow amorphous solid using hydrogenated trifluoroacetate of (E) -4- (acetylsulfanyl) -3- [2- (4-ethoxycarbonyl-1 H -pyrazol-1-yl) ethylidene] piperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (g). NMR with 1H (400 MHz, CDCl 3) d ppm: 0.75-0.88 (2H, m), 1.00-1.07 (2H, m), 1.34 (3H, t, J = 7.0), 1.80-1.87 (1H, m), 2.08-2.26 (2H, m), 2.28 and 2.30 (total 3H, each s), 2.50-2.60 (1H, m), 2.67-2.72 and 2.78-2.82 (total 1H, each m), 2.87 and 3.18 (total 1H , every d, J = 12.5), 3. 29 and 3.44 (total 1H, each d, J = 12.5), 4.28 (2H, q, J = 7.0), 4.33-4.35 (1H, m), 4.67-4.76 (3H, m), 5.79 (1H, t, J = 7.0), 7.08-7.17 (2H, m), 7. 29-7.37 (2H, m), 7.85-7.87 (2H, m). (Example 43) hydrochloride of (E? -1-r2-Cycloprop.M4'2-fluo? Roff? Nl) -2-oxoet »n-342- (4-ethoxycarbonyl-1H-pyrazole-1 BD) etaBidenl -4 ° Sulfanylpiperidine (Hydrochloride of compound of Compound No. 1-25) The title compound was synthesized in a 46% yield as a yellow amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] - 3- [2- (4-etho-icarbonyl-1H-pyrazol-1-yl) ethylidene] piperidine obtained in Example 42 (e) by performing a reaction similar to that mentioned in Example 34. 1 H NMR (400 MHz , CDCl 3) d ppm: 0.76-0.88 (2H, m), 1.00-1.04 (2H, m), 1.35 (3H, t, J = 7.0), 1.73-1.79 (1H, m), 2.09-2.12 (1H, m), 2.17-2.28 (1H, m), 2.54-2.60 and 2.61-2.67 (total 1H, each m), 2.78-2.85 (1H, m), 3.04 and 3.24 (total 1H, each d, J = 12.5) , 3.31 and 3.54 (total 1H, each d, J = 12.5), 3.65-3.70 and 3.73-3.77 (total 1H, each m), 4.28 (2H, q, J = 7.0), 4.69-4.77 (3H, m) , 5.74-5.82 (1H, m), 7.09-7.17 (2H, m), 7.29-7.38 (2H, m), 7.87-7.90 (2H, m); IR (KBr, CI? T1): 2466, 1712, 1554.

(Example 44) (E) -34244-Carboxy-1H-pyrazole-1N-yl) ethylidene-14-cyclopropyl-1] -42-fluorophenyl) -2"xetin-4-sulfanylpiperadine hydrochloride (Compound Hydrochloride Compound B No. 1-17) The title compound was synthesized in a 14% yield as a colorless amorphous solid using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- [2- ( 4-ethoxycarbonyl-1 H-pyrazol-1-yl) ethylidene] -4-sulfanylpiperidine obtained in Example 43 by performing a reaction similar to that mentioned in Example 15. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.79-0.82 (2H, m), 1. 01-1.05 (1H, m), 1.09-1.13 (1H, m), 1.75-1.83 (1H, m), 2.16-2.25 (1H, m), 2.41-2.49 (1H, m), 2.62-2.68 (1H , m), 2.85-2.91 and 2.92-2.98 (total 1H, each m), 3.35 and 3.38 (total 1H, each d, J = 13.0), 3.63 and 3.70 (total 1H, each d, J = 13.0), 3.79 -3.82 (1H, m), 4.91-5.05 (3H, m), 5.99-6.03 (1H, m), 7.19-7.27 (2H, m), 7.29-7.35 (1H, m), 7.68-7.72 (1H, m), 8.43 (1H, s), 8.53 (1H, d, J = 1.5); IR (KBr, cm'1): 2546, 1709, 1555. (Example 45) Hydrogenated trifluoroacetate of (E) ° 4 ° (Acetylsulfani8) -142-cyclopropyl-142-fluorofeniB) -2 ° oxoetiB] l "342 ° methoxyethylidenepiperidine (Hydrogenated trifluoroacetate d @ B compound of8 Compound No. 3-6) £ a) (E) -4- (t-Butyl imetBlsiiiloxa) ° 3 ° (2 ° [? ®toxi®ti BBd®at?) ° 1 ° (triphenylmethyl) pi peridi na To a solution of (E) -4- (t-butyldimethylsilyloxy) -3- (2-hydroxyethylidene) -1 - (triphenylmethyl) piperidine (1.85 g) obtained in Example 1 (b) in N, N-dimethylformamide (20 ml) was added sodium hydride (0.23 g) under cooling with ice, and the resulting mixture was stirred at room temperature for 15 minutes. Methyl iodide (0.34 ml) was added to the reaction mixture at the same temperature, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with a mixed solvent of ethyl acetate and ether and washed with a saturated aqueous solution of hydrogenated sodium carbonate and a saturated aqueous solution of sodium chloride, and the organic layer was dried over sodium sulfate. anhydrous. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/24) to obtain the title compound (1.441 g, 74% yield) as a colorless oil. RM N with 1 H (400 M Hz, CDCl 3) d ppm: -0.02 (3H, s), -0.01 (3H, s), 0.86 (9H, s), 1 .69-2.00 (4H, m), 2.87 -2.96 (1 H, m), 3.31 (3H, s), 3.49-3.61 (1H, m), 3.83-4.02 (3H, m), 5.72 (1H, t, J = 8.0), 7.12-7.20 (3H, m), 7.22-7.28 (6H, m), 7.40-7.55 (6H, m). (b) (E) -4-Hydroxy ° 342-methoxyet? lidem) -14-methyl-B-methyl) pi erB ñ? p? a The title compound was synthesized in a quantitative yield as a colorless amorphous solid using (E) -4- ( t-butyldimethylsilyl) i) -3- (2-methoxyethylidene) -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e). NMR with 1H (400 MHz, CDCl 3) d ppm: 1.75-2.13 (4H, m), 2.66-2.81 (2H, m), 3.35 (3H, m), 3.88-4.02 (3H, m), 5.70 (1H, t, J = 7.0), 7.13-7.20 (3H, m), 7.23-7.30 (6H, m), 7.43-7.53 (6H, m). (c) bis (Hydrogenated trifluoroacetate) of (E) -4-H5dro 5 ° 3- (2-methoxyethylidene) piperidine The title compound was synthesized in a 95% yield as a colorless oil using (E) -4-hydroxy -3- (2-methoxyethylidene) -1- (triphenylmethyl) piperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 3 (c). 1 H NMR (400 MHz, CDCl 3 + DMSO-d 6) d ppm: 1.88-2.13 (2H, m), 3.11-3.19 (1H, m), 3.32 (3H, s), 3.39-3.48 (1H, m), 3.75 (1H, d, J = 13.5), 3.92 (1H, d, J = 13.5), 4.01 (2H, d, J = 6.0), 4.22-4.27 (1H, m), 5.87 (1H, t, J = 6.0). (d) (E) -142 ° CiclopropiD-1424luorophenyl) ° 2 ° oxoet5nTl ° 4"h5droxD-342" metoxieti I den) piperidine The title compound was synthesized in a yield of 78% as a brown oil using (E) -4-hydro? I -3- (2-methoxyethylidene) piperidine bis (hydrogenated trifluoroacetate) obtained in (c) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.78-1.09 (4H, m), 1.68-1.79 (1H, m), 1.96-2.05 (1H, m), 2.19-2.28 (1H, m), 2.42- 2.54 (1H, m), 2.76-3.00 (2H, m), 3.30 (3H, s), 3.36 and 3.47 (total 1H, each d, J = 12.0), 3.92 (2H, d, J = 6.0), 4.07-4.15 (1H, m), 4.69 and 4.71 (total 1H, each s), 5.68 and 5.69 (total 1H, each t, J = 6.0) , 7.07-7.20 (2H, m), 7. 28-7.46 (2H, m). (e) hydrogenated trifiuoroacetate of (E) ° 44Aceti¡suDfam) Bfl) "H42" cyclopropyl ° 1- (2-fluorophenyl) 2-oxoetin-3- (2-methoxyethyl) n) piperidine The title compound was synthesized in a yield of 30% as a light brown oil using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -4-hydro? i -3- (2-methoxyethylidene) piperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 3 (e). NMR with 1H (400 MHz, CDCI3) d ppm: 0.79-0.89 (2H, m), 0.95- 1.08 (2H, m), 1.77-1.85 (1H, m), 2.11-2.28 (2H, m), 2.29 and 2.30 (total 3H, each s), 2.46-3.08 (3H, m), 3.26 and 3.28 (total 3H, each s), 3.30- 3.56 (1H, m), 3.81-3.92 (2H, m), 4.28-4.36 (1H, m), 4.68 and 4.71 (total 1H, each s), 5.72 (1H, t, J = 6.5), 7.07-7.20 (2H, m), 7.29-7.35 (1H, m), 7.39-7.45 (1H, m); IR (liquid film, cm "1): 1711, 1495. (Example 46) Hydrogenated trifluoroacetate d © (E)" 142-Cyclopropyl-1- (2-fluorophenyl) -2-oxoetyl ° 3 ° (2-methoxyethyl). deri) -4 ° sulfanylpiperidine (Hydrogenated trifluoroacetate of B compound of Compound No.3-5) The title compound was synthesized in a 60% yield as a colorless oil using hydrogenated trifluoroacetate of (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] - 3- (2-methoxyethylidene) piperidine obtained in Example 45 (e) carrying out a reaction similar to that mentioned in Example 2. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.79-0.90 (2H, m) , 0.95-1.09 (2H, m), 1.69-1.78 (1H, m), 2.13-2.32 (2H, m), 2.51-2.87 (2H, m), 3.03-3.57 (2H, m), 3.27 and 3.29 ( total 3H, each s), 3.70-3.92 (3H, m), 4.70 and 4.73 (total 1H, each s), 5.68 and 5.71 (total 1H, each t, J = 6.5), 7.07-7.20 (2H, m) , 7.28-7.46 (2H, m); IR (liquid film, cm "1): 2564, 1714, 1495. (Example 47.). (E) -44 AcetylsulfarBBB)" 142 ° eaclopropo ° 1l 2-fluorophenyl) -2-oxoetill-34244-ethoxycarbonyl-2H -1] .2.3-tpazoD-2-iPetilidenlpiperidina (Compound of compound Mo. 1-592). (E) ° 44-acetylsulfanyl) -142"Cazopropyl-1- (2-fluorophenyl) 2-oxoetiD1 342" (4-ethoxycarbonyl-1H-1,2,3-triazole-1-yl) ethylidene-1-pyridine compound No. H-492) and (E) ° 4 ° (aeetilsyBfa? piBl ° 1 ° f2-cyclopropyl-142-fluorofeni!) - 2-oxoetip-3424§ ° ethoxycarb «-11 1 .2.3-triazo8- 14l) ethylidene p5peridine (Compound of B compound No. 1-498) To a solution of (E) -4- (acetylsulfanyl) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3- (2-hydro? Ylethylidene) piperidine (1000 mg ) obtained in Example 32 (f) and 4-etho-icarbonyl-1 H-1,2,3-triazole (449 mg) in toluene (10 mL) under a stream of nitrogen gas was added 1.1. - (azodicarbonyl) dipiperidine (802 mg) and tributylphosphine (0.79 ml) under cooling with ice, and the resulting mixture was stirred at room temperature for 1 8 hours. To the reaction mixture was added 4-ethoxycarbonyl-1 H-1, 2,3-triazole (224 mg), 1, 1 '- (azodicarbonyl) dipiperidine (802 mg) and tributylphosphine (0.79 ml), and the resulting mixture was stirred at room temperature for 4.5 hours. To the reaction mixture was added 4-ethoxycarbonyl-1 H-1,2,3-triazole (12 mg), 1,1 '- (azodicarbonyl) dipiperidine (200 mg) and tributylphosphine (0.20 ml), and The resulting mixture was further stirred at room temperature for 2 hours. The reaction mixture was evaporated in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1 / 2-1 / 1) and then purified using a Preparative HPLC (YMC-Pack ODS-A; YMC, eluent: acetonitrile / 0.024N hydrochloric acid = 1 5/85) to obtain the hydrochlorides of the three title compounds. Each of the hydrochlorides obtained was neutralized with a saturated aqueous solution of hydrogenated sodium carbonate and was brought with ethyl acetate. The tract was washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to obtain the three title compounds. (E) -4- (Acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3- [2- (4-ethoxycarbonyl-1 H-1, 2 , 3-triazol-1-yl) ethylidene] piperidine had the highest polarity: a colorless oil, amount produced 120 mg, yield 9% NMR with 1H (400 MHz, CDCl 3) d ppm: 0.76-0.90 (2H, m), 1.02-1.05 (2H, m), 1.42 (3H, t, J = 7.0), 1.80-1.86 (1H, m), 1.98-2.04 (1H, m), 2.09-2.19 and 2.20-2.28 (total 1H, each m), 2.29 and 2.31 (total 3H, each s), 2.53-2.59 (1H, m), 2.66-2.71 and 2.78-2.84 (total 1H, each m), 2.90 and 3.51 (total 1H, each d, J = 12.5), 3.28 (1H, bs), 4.25-4.27 and 4.32-4.34 (total 1H, each m), 4.44 (2H, q, J = 7.0), 4.80 and 4.81 (total 1H, each s), 4.98-5.04 (2H, m), 5.80 (1H, t, J = 7.5), 7.12-7.21 (2H, m), 7.31-7.39 (2H, m), 8.19 and 8.22 (total 1H, each s). (E) -4- (Acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3- [2- (5-ethoxycarbonyl-1H-1, 2,3-triazol-1-yl) ethylidene] piperidine the second highest polarity: a yellow oil, produced amount 219 mg, yield 17% NMR with 1H (400 MHz, CDCl 3) d ppm: 0.81-0.91 (2H, m), 1.00-1.11 (2H, m), 1.39 and 1.40 (total 3H, each t, J = 7.0), 1.77-1.84 (1H, m), 2.14-2.24 (2H, m), 2.25 (3H, s ), 2.44-2.51 and 2.57-2.63 (total 1H, each m), 2.68-2.77 (1H, m), 3.01 and 3.19 (total 1H, each d, J = 12.5), 3.48 and 3.53 (total 1H, each d , J = 12.5), 4.24-4.29 (1H, m), 4.37 and 4.38 (total 2H, each q, J = 7.0), 4.76 and 4.78 (total 1H, each s), 5.27-5.35 (2H, m), 5.72-5.77 (1H, m), 7.09-7.20 (2H, m), 7.28-7.44 (2H, m), 8.07 (1H, s). (E) -4- (Acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3- [2- (4-ethoxycarbonyl-2H-1, 2, 3-triazol-2-yl) ethylidene] piperidine had the lowest polarity: a colorless oil, produced amount 236 mg, yield 18% 1 H NMR (400 MHz, CDCl 3) d ppm: 0.82-0.89 (2H, m), 1.00 - 1.08 (2H, m), 1.41 (3H, t, J = 7.0), 1.79-1.86 (1H, m), 2.12-2.30 (2H, m), 2.27 and 2.28 (total 3H, each s), 2.50- 2.63 (1H, m), 2.68-2.80 (1H, m), 2.95 and 3.22 (total 1H, each d, J = 13.0), 3.34 and 3.68 (total 1H, each d, J = 13.0), 4.28-4.35 ( 1H, m), 4.43 (2H, q, J = 7.0), 4.75 and 4.78 (total 1H, each s), 5.05-5.13 (2H, m), 5.86 (1H, t, J = 7.0), 7.11-7.22 (2H, m), 7.32-7.43 (2H, m), 8.03 (1H, s). (Example 48) hydrochloride of (E) -1 ° F2-C¡BBoprop5B ° H ° (2 ° fiuor®1F®pil) -2-oxoetiM-34244-ethoxycarbonyl-2H-1.2.3-triazoB ° 248T) ®tBlidenT Sulfanylpiperidine (B-hydrochloride compound of B Compound No. 1-591) • HCl The title compound was synthesized in a quantitative yield as a light yellow oil using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] - 3- [2- (4-etho-icarbonyl-2H-1,2,3-triazol-2-yl) ethylidene] piperidine obtained in Example 47 carrying out a reaction similar to that mentioned in Example 34. 1 H NMR ( 400 MHz, pyridine-d5) d ppm: 0.84-0.91 (2H, m), 1.01-1.07 (1H, m), 1.14-1.18 (1H, m), 1.23 (3H, t, J = 7.0), 1.74- 1.84 (1H, m), 2.14-2.24 (1H, m), 2.48-2.64 (2H, m), 2.84-2.98 (1H, m), 3.35-3.41 (1H, m), 3.69 and 3.75 (total 1H, each d, J = 12.5), 3.79-3.82 (1H, m), 4.35 (2H, q, J = 7.0), 4.95 and 4.96 (total 1H, each s), 5.30-5.35 (2H, m), 6.10- 6.14 (1H, m), 7.23-7.35 (3H, m), 7.69-7.75 (1H, m), 8.37 (1H, s); IR (KBr, cm "1): 2914, 1717. (Example 49) hydrochloride of (E) -3-r2- (4-Carboxy-2H-1,2,3-traazoi-2-yl) ethylidene-42-cyclopropene-142- fluorofenBl) ° 2-oxQ @ t5p-4-sulfanylpiperidine (Compound hydrochloride of 14587) The title compound was synthesized in a 74% yield as a colorless amorphous solid using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- [2- ( 4-ethocarbonyl-2H-1,2,3-triazol-2-yl) ethylidene] -4-sulfanylpiperidine obtained in Example 48 carrying out a reaction similar to that mentioned in Example 15. 1 H NMR (400 MHz, pyridine-d5) d ppm: 0.80-0.94 (2H, m), 1.01-1.07 (1H, m), 1.14-1.19 (1H, m), 1.74-1.84 (1H, m), 2.14-2.25 (1H, m ), 2.52-2.66 (2H, m), 2.84-2.98 (1H, m), 3.38-3.42 (1H, m), 3.70 and 3.76 (total 1H, each d, J = 13.0), 3.79-3.84 (1H, m), 4.95-4.97 (1H, m), 5.31-5.38 (2H, m), 6.12-6.17 (1H, m), 7.24-7.36 (3H, m), 7.71-7.78 (1H, m), 8.51 ( 1H, s); IR (KBr, cm "1): 2927, 1712. (Example 50) hydrochloride of (E 42-C? Cloprop5l-l42-fliLio? Roffen-8) -2-oxoetip-342- (4-ethoxycarbonyl-1H-1.2 .3-tpazon "H n) ®tilidenTl" 4 ° sulfanylpiperidine (Hydrochloride of compound of Compound No. 1-491) The title compound was synthesized in a quantitative yield as a colorless oil using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- [2- (4-ethocarbonyl-1H-1, 2,3-triazol-1-yl) ethylidene] piperidine obtained in Example 47 carrying out a reaction similar to that mentioned in Example 34. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.77-0.90 (2H, m), 1.02-1.05 (2H, m), 1.42 (3H, t, J = 7.0), 1.54-1.58 (1H, m), 1.73-1.79 (1H, m), 1.99-2.03 (1H, m), 2.15-2.29 (1H, m), 2.53-2.58 and 2.62-2.67 (total 1H, each m), 2.78-2.85 (1H, m), 3.27-3.35 (1H, m) , 3.63-3.66 and 3.72-3.76 (total 1H, each m), 4.44 (2H, q, J = 7.0), 4.83 (1H, s), 5.01-5.06 (2H, m), 5.76-5.85 (1H, m ), 7.12-7.26 (3H, m), 7.33-7.36 (1H, m), 8.23 and 8.24 (total 1H, each s); MS (FAB) m / z: 459 (M + H) + (Example 51) (E) -3-r2- (4-CarboxMH-1.2.3-tr1a? .goll-1-BB) ethylidenehydrochloride -1-r2-cyclopropyl ° 1 ° (2-fluorophenyl) -2-oxoetB81-4 ° sulfanylpiperidine (Hydrochloride of Compound B Compound No. 1-487) The title compound was synthesized in a 71% yield as a colorless amorphous solid using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- [2] hydrochloride. - (4-ethoxycarbonyl-1H-1,2,3-triazol-1-yl) ethylidene] -4-sulfanylpiperidine obtained in Example 50 carrying out a reaction similar to that mentioned in Example 15. 1 H NMR (400 MHz, pyridine-d5) d ppm: 0.77-0.81 (2H, m), 0. 99-1.11 (2H, m), 1.73-1.81 (1H, m), 2.12-2.23 (1H, m), 2.29-2.36 (1H, m), 2.60-2.63 (1H, m), 2.82-2.96 (1H , m), 3.34 and 3.40 (total 1H, each d, J = 12.5), 3.65 and 3.73 (total 1H, each d, J = 12.5), 3.76-3.83 (1H, m), 4.96 and 4.97 (total 1H, each s), 5.21-5.27 (2H, m), 5.96-6.01 (1H, m), 7.20-7.32 (3H, m), 7.64-7.68 (1H, m), 8.88 (1H, s); IR (KBr, crn "1): 2927, 1711. (Example 52) (E) -142-CycloBopropBB" 1l42-fluoroff® [p? Nl) -2-oxoethyl-1-342- (5-ethoxycarbonyl-1H- hydrochloride 1.2.3-triazo8-H ° Bl) @tiliden] l-4"sulfanylpiperidine (CBorhydrate of Compound B Compound No. • 497) The title compound was synthesized in a 90% yield as a colorless amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] - 3- [2- (5-etho-icarbonyl-1H-1,2,3-triazol-1-yl) ethylidene] piperidine obtained in Example 47 carrying out a reaction similar to that mentioned in Example 34. 1 H NMR ( 400 MHz, pyridine-d5) d ppm: 0.84-0.91 (2H, m), 1. 03-1.09 (1H, m), 1.15-1.22 (1H, m), 1.21 (3H, t, J = 7.0), 1.75-1.83 (1H, m), 2.15-2.25 (1H, m), 2.50-2.57 (1H, m), 2.60-2.68 (1H, m), 2.84-2.89 and 2.93-2.99 (total 1H, each m), 3.46-3.54 (1H, m), 3.77-3.81 (2H, m), 4.28 ( 2H, q, J = 7.0), 4.98 (1H, s), 5.52-5.56 (2H, m), 6.04-6.09 (1H, m), 7.21-7.35 (3H, m), 7.69-7.76 (1H, m ), 8.39 (1H, s); MS (FAB) m / z: 459 (M + H) +. (Example 53) (E) -3-f2-f5-Carboxy-1IHI-1.2.3-t? Rlfflgol-1l-yl) ethylidene-142-cyclopropin-142-fluorophen? L) "2-oxo @ tiB1 hydrochloride -4"Sulfanylpiperidine (Compound Hydrochloride of Compound No. 1-493) The title compound was synthesized in a 68% yield as a colorless amorphous solid using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- [2] hydrochloride. - (5-ethoxycarbonyl-1H-1,2,3-triazol-1-yl) ethylidene] -4-sulfanylpiperidine obtained in Example 52 carrying out a reaction similar to that mentioned in Example 15. 1 H NMR (400 MHz, pyridine-d5) d ppm: 0.77-0.91 (2H, m), 0. 99-1.04 (1H, m), 1.13-1.19 (1H, m), 1.71-1.81 (1H, m), 2.10-2.21 (1H, m), 2.49-2.66 (2H, m), 2.78-2.96 (1H , m), 3.48-3.52 and 3.57-3.60 (total 1H, each m), 3.77-3.83 (2H, m), 4.95 (1H, s), 5.68-5.72 (2H, m), 6.14-6.22 (1H, m), 7.21-7.33 (3H, m), 7.70-7.78 (1H, m), 8.55 (1H, s); MS (FAB) m / z: 431 (M + H) \ (Example 54) dihydrochloride of (E) ° 4- (AcetBlsulfaraiD) -142-cic8opropii ° 142-fluorofenifl) -2-oxoetin-3424 (2S) - ( methoxycarbonylmethyl) pyrrolidin-1 ° inethylidene} piñññríñia (Hydrochloride of compound of Compound No.5-HS4) The title compound was synthesized in a 17% yield as a yellow oil using (E) -4- (acetylsulfanyl) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3 - (2-hydroxyethylidene) piperidine obtained in Example 32 (f) and (2S) - (methocarbylmethyl) pyrrolidine hydrochloride by performing a reaction similar to that mentioned in Example 33. 1 H NMR (500 MHz, pyridine-d5) d ppm: 0.71 -0.87 (2H, m), 1.02-1.15 (2H, m), 1.74-1.89 (2H, m), 1.89-2.04 (2H, m), 2.08-2.34 (5H, m), 2.54-2.81 (2H, m), 3.02-3.50 (5H, m), 3.53-3.69 (4H, m), 3.70-3.79 (1H, m), 3.79 -3.99 (2H, m), 4.03-4.19 (1 H, m), 4.42-4.51 (1 H, m), 4.99-5.06 (1 H, m), 6.29-6.41 (1 H, m), 7.20- 7.31 (2H, m), 7.32-7.41 (1 H, m), 7.54-7.64 (1 H, m); IR (KBr, cm-1): 2547, 1700, 1494. (Example 55) dichlorhadrate of (E) "142" Cicioprop5B-H - (2 ° fluorophenyl) -2-oxoetiH-3424 (2S) - (methoxycarbon8Brn®tBl ) p3rro8o 5? p) "1" allylidene-4-sulfanylpiperidBna (Hydrochloride of compound of Compound No. 5-153) To a solution of (E) -4- (acetylsulfanyl) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- dihydrochloride. { 2 - [(2S) - (methocarbarylmethyl) pyrrolidin-1-yl] ethylidene} piperidine (407 mg) obtained in example 54 in methanol (10 ml) was bubbled with hydrogen chloride under cooling with ice, and the resulting mixture was stirred at room temperature under hermetic conditions overnight. The reaction mixture was stirred in vacuo, and the residue was purified using preparative HPLC (YMC-Pack ODS-A; YMC, eluent: acetonitrile / water containing triethylamine (0.2%) and acetic acid (0.2%) = 1 / 1). The eluted fraction was extracted with ethyl acetate and washed with a saturated aqueous solution of hydrogenated sodium carbonate and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and to a solution of the residue in dichloromethane (10 ml) was added a solution of hydrogen chloride in 4N dioxane (0.26 ml) at room temperature. The reaction mixture was evaporated in vacuo to obtain the title compound (192 mg, 48% yield) as a pale yellow amorphous solid. NMR with 1H (500 MHz, pyridine-d5) d ppm: 0.73-0.89 (2H, m), 1.02-1.14 (2H, m), 1.69-1.82 (1H, m), 1.82-2.11 (3H, m), 2.12-2.28 (2H, m), 2.29-2.43 (1H, m), 2.59-2.73 (1H, m), 2.74-2.98 (1H, m), 3.11-3.42 (3H, m), 3.44-3.71 (5H , m), 3.76-4.02 (4H, m), 4.13-4.28 (1H, m), 5.00-5.07 (1H, m), 6.25-6.36 (1H, m), 7.22-7.32 (2H, m), 7.34 -7.44 (1H, m), 7.58-7.67 (1H, m); IR (KBr, cm "1): 2558, 1714, 1493. (Example 56.). D.hydrochloride d (E) -3 242S) ° (Carboxymethyl) pyrro8adin-1 ° inethylidene > -1-f2-caclopro Bl-1- (2 ° fSuorofenH) -2-oxoetii1-4 ° sulfanylpiperidine (Hydrochloride of B compound of Compound No.5-151) The title compound was synthesized in a 46% yield as a colorless amorphous solid using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- dihydrochloride. { 2 - [(2S) - (methocarbarylmethyl) pyrrolidin-1-yl] ethylidene} -4-Sulfanylpiperidine obtained in Example 55 performing a reaction similar to that mentioned in Example 15. 1 H NMR (500 MHz, pyridine-d 5) d ppm: 0.71-0.86 (2H, m), 0.98-1.15 (2H, m), 1.71-1.90 (2H, m), 1.93-2.09 (2H, m), 2.11-2.24 (1H, m), 2.25-2.45 (2H, m), 2.56-2.75 (2H, m), 2.77- 2.99 (1H, m), 3.26-4.05 (8H, m), 4.06-4.23 (1H, m), 4.95-5.02 (1H, m), 6.25-6.39 (1H, m), 7.19-7.29 (2H, m ), 7.30-7.38 (1H, m), 7.57-7.67 (1H, m); IR (KBr, cm "1): 2562, 1713, 1493. (Example 57) dicbohydrate of (E) ° 4- (Ace? Sulfart? Opl) ° 1l ° r2 ° ciciopropil ° 142-fluorofeniB)" 2-oxoetill- 342434etoxn'carbop5ll) piperidin-1-ethylidene > Piperidine (Compound Hydrochloride of Compound No.5-342) The title compound was synthesized in a 61% yield as an amorphous brown solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- (2-hydroxyethylidene) piperidine obtained in example 32 (f) and 3- (ethocarbonyl) piperidine carrying out a reaction similar to that mentioned in Example 33. 1 H NMR (400 MHz, pyridine-d 5) d ppm : 0.73-0.89 (2H, m), 1.02-1.14 (5H, m), 1.43-1.56 (1H, m), 1.65-1.76 (1H, m), 1.79-1.89 (1H, m), 1.98-2.09 ( 1H, m), 2.09-2.36 (6H, m), 2.54-2.84 (3H, m), 2.88-3.02 (1H, m), 3.17-3.66 (4H, m), 3.67-3.82 (3H, m), 4.02-4.11 (2H, m), 4.46-4.54 (1H, m), 4.99-5.05 (1H, m), 6.28-6.37 (1H, m), 7.18-7.42 (3H, m), 7.58-7.70 (1H , m); IR (KBr, cm "1): 2526, 1710, 1493. (Example 58) (E) -1-r2-Cycloproplyl-1l- (2-fluorophenyl) -2-oxoetiBTI" 342434etoxflcarbonBl) pBperidinium hydrochloride} -1] -ñlletiliden > -4-Sulfanylpiperdbd (Hydrochloride of the compound of Compound No.5-341) The title compound was synthesized in a 49% yield as a pale yellow amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oetil] -3-. { 2- [3- (ethoxycarbonyl) piperidin-1-yl] ethylidene} piperidine obtained in Example 57 carrying out a reaction similar to that mentioned in Example 34.

NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.74-0.86 (2H, m), 1.01-1.15 (5H, m), 1.45-1.56 (1H, m), 1.64-1.82 (2H, m), 1.98-2.38 (4H, m), 2.50-3.08 (5H, m), 3.27-3.92 (7H, m), 4.00-4.12 (2H, m), 4.97-5.03 (1H, m), 6.22-6.36 (1H , m), 7.20-7.38 (3H, m), 7.60-7.72 (1H, m); IR (KBr, cm-1): 2533, 1726, 1493. (Example 59) (E) -3-f2 ° f3- (Carboxipiper? DDip?) Daciorhydrate ° 1 ° Snetilidene > ° 142-cyclopropy! 142-fluorofenB!) -2-oxo®tiB1-4-sulfanylpiperidine (Hydrochloride of compound of Compound No. 5-337) The title compound was synthesized in a 72% yield as a colorless amorphous solid using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- dihydrochloride. { 2- [3- (ethocarbonyl) piperidin} -1-yl] ethylidene} -4-Sulfanylpiperidine obtained in Example 58 performing a reaction similar to that mentioned in Example 15. 1 H NMR (500 MHz, pyridine-d 5) d ppm: 0.75-0.92 (2H, m), 1. 02-1.17 (2H, m), 1.62-1.89 (3H, m), 2.11-2.38 (4H, m), 2.61-2.74 (1H, m), 2.74-3.00 (2H, m), 3.13-3.32 (1H , m), 3.37-3.54 (1H, m), 3. 54-3.69 (3H, m), 3.85-4.10 (4H, m), 5.01-5.08 (1H, m), 6.27-6.37 (1H, m), 7.22-7.46 (3H, m), 7.65-7.79 (1H, m); IR (KBr, cm-1): 2542, 1713, 1493. (Example 60.). (E) ° 4- (Acetalsulfanyl) ° 1 ° r 2 ° c5cBopropal-i] - (2 ° fluorophenyl) -2-oxoetin ° 34r244-ethoxycarbon5B-1H-parazoB ° 1-iB) ° 1 rnetipetilidene) piperidine (Compound of compound No. 1 -978) . { to} (E) -3-ri ° (Ethoxycarbonyl) etBliden1-4 ° hydroxy-1 ° (trife? PiBn? Pp? @ Tnn) piperidine To a solution of (E) -4- (t-butyldimethylsilyl? I) -3- [(ethocarbonyl) methylidene] -1- (triphenylmethyl) piperidine (1.6 g) obtained in example 1 (a) in tetrahydrofuran (20 ml) was added dropwise a standard 2.0 solution of lithium diisopropylamide in solution of heptane / tetrahydrofuran / ethyl benzene (2.30 ml) at -78 ° C, and the resulting mixture was stirred at the same temperature for 1 hour. To the reaction mixture was added dropwise methyl iodide (0.31 ml) at -78 ° C, and then the resulting mixture was stirred for 2 hours while gradually warming to room temperature. The reaction mixture was charged with a saturated aqueous solution of ammonium chloride and then extracted with ethyl acetate. The tract was washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 3/97) to obtain a 1: 2 mixture (1.1 g, 69% yield). ) of (E) -4- (t-butyldimethylsilyl) i) -3 - [(1-ethocarbonyl) ethylidene] -1- (triphenylmethyl) piperidine and the (Z) isomer thereof as a pale yellow amorphous solid. To a solution of this mixture (0.97 g) in tetrahydrofuran (15 mL) was added a 75% solution of tetrabutylammonium fluoride (1.40 g) in water, and the resulting mixture was stirred at 60 ° C for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/19 - 1/1) to obtain the title compound (292 mg, yield 38). %) as a light yellow oil. 1 H NMR (400 MHz, CDCl 3) d ppm: 1.03 (3H, t, J = 7.0), 1.78-2.50 (6H, m), 2.74-2.83 (1H, m), 3.20-3.28 (1H, m), 3.84-4.03 (3H, m), 4.79 (1H, bs), 7.08-7.32 (9H, m), 7.37-7.50 (6H, m). (b) (E) -4- (t-Butyldimethylsilyloxy) -3-p- (etoxBcarb? Bi? il) ®tinñdep? 1 ° 1 ° (triphenylmethyl) piperidine To a solution of (E) -3- [1- (ethoxycarbonyl) ethylidene] -4-hydroxy-1- (triphenylmethyl) piperidine (1.05 g) obtained in (a) above in dichloromethane (20 ml) was Trifluoromethanesulfonate of t-butyldimethylsilyl (0.60 ml) and 2,6-lutidine (0.83 ml) were added dropwise under cooling with ice, and the resulting mixture was stirred at the same temperature for 10 minutes. The reaction mixture was charged with a saturated aqueous solution of hydrogenated sodium carbonate and then brought with ethyl acetate. The tract was washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium. The solvent was removed in vacuo, and the residue was purified by chromatography on a column of silica gel (toluene / water = 1/9 - 1/4, then ethyl acetate / water = 1/9 - 1). 4) to obtain the title compound (1.05 g, yield 79%) as a light yellow oil. 1 H NMR (400 MHz, CDCl 3) d ppm: -0.16 (3H, s), -0.06 (3H, s), 0.63 (9H, s), 0.99 (3H, t, J = 7.5), 1.64-2.32 ( 7H, m), 2.75-2.83 (1H, m), 3.83-4.02 (3H, m), 4.68 (1H, bs), 7.07-7.34 (9H, m), 7.38-7.52 (6H, m). (c) (E) -4- (t-But-8-dimethylsilyloxy) -3 ° r (2-hydroxa-1-methyl) etDlñd®? p? 1-1- (t rifen i I meti I) piperidine A suspension of (E) -4- (t-butyldimethylsilyloxy) -3- [1- (ethocarbonyl) ethylidene] -1- (triphenylmethyl) piperidine (1.05 g) obtained in (b) above in dichloromethane (15 ml) is drip added a 1.01N solution of diisobutylaluminum hydride in toluene (5.7 ml) at -78 ° C, and the resulting mixture was stirred at the same temperature for 30 minutes. An aqueous solution of sodium potassium tartrate was added to the reaction mixture, and then the resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/19 - 1/4) to obtain the title compound (0.72 g, yield 74). %) as a colorless amorphous solid. NMR with 1H (400 MHz, CDCl 3) d ppm: -0.20 (3H, s), -0.07 (3H, s), 0.61 (9H, s), 1.62-2.20 (7H, m), 2.76-2.84 (1H, m), 3.57 (1H, d, J = 12.0), 4.03-4.08 (2H, m), 4.70 (1H, bs), 7.08-7.28 (9H, m), 7.40-7.54 (6H, m). (d) (E) -4- (t-ButyldimethylsiBiBoxi) -3 ° 2- (4-ethoxacarbo? p? il-1HIHI p. p. 1ol-1-yl) -1-methyl-1-ylidene (triphenylmethyl) piperidine The title compound was synthesized in a 94% yield as a pale yellow amorphous solid using (E) -4- (t-butyldimethylsilyl) i) -3 - [(2-hydro? I-1-methyl) ethylidene] - 1- (Triphenylmethyl) piperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 40 (a). NMR with 1H (400 MHz, CDCl 3) d ppm: -0.20 (3H, s), -0.08 (3H, s), 0.62 (9H, s), 1.34 (3H, t, J = 7.5), 1.62-2.08 ( 6H, m), 2.30-2.36 (1H, m), 2.83-2.90 (1H, m), 3.60-3.67 (1H, m), 4.22-4.35 (2H, m), 4. 67-4.75 (3H, m), 7.07-7.33 (9H, m), 7.43-7.57 (6H, m), 7.77 (1H, s), 7. 92 (1H, s). (e) (E) -3-fr2- (4-EthoxycarboniB-1H-pramzoB ° 1 ° Bl) ° 1-metim® tBflderadera ° 4-hydroxy-1- (triphenylmethyl) piperidine The compound of the invention was synthesized. title in a 69% yield as a yellow amorphous solid using (E) -4- (t-butyldimethylsilyl? i) -3-. { [2- (4-ethocarboxyl-1-1 H-pi-razol-1-yl) -1-methyl] ethylidene} -1 - (triphenylmethyl) piperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (e). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.36 (3H, t, J = 7.5), 1.69 (3H, s), 1.86-2.35 (4H, m), 2.88-2.97 (1H, m), 3.75 ( 1H, d, J = 13.5), 4. 31 (2H, q, J = 7.5), 4.62-4.73 (2H, m), 4.83 (1H, bs), 7.10-7.30 (9H, m), 7.40-7.56 (6H, m), 7.80 (1H, s) ), 7.92 (1H, s). (f) Hydrogenated trifluoroacetate of (E) -44AcetylsuD! fanBi) ° 3"íl244" ethoxycarbonyl ° 1H-pyrazole ° 1 il) -1-methyethylBdenyl pipernane The title compound was synthesized in a 67% yield as an oil colorless using (E) -3-. { [2- (4-ethoxycarbonyl-1 H -pyrazol-1-yl) -1-methyl] ethylidene} -4-hydro? I-1- (triphenylmethyl) piperidine obtained in (e) above performing a reaction similar to that mentioned in Example 36 (d). NMR with H (400 MHz, CDCl 3) d ppm: 1.33 (3H, t, J = 7.0), 1.80 (3H, s), 2.01-2.12 (1H, m), 2.37 (3H, s), 3.16-3.56 (4H, m), 4.28 (2H, q, J = 7.0), 4.47 (1H, d, J = 13.5), 4.72 (2H, s), 4.89 (1H, bs), 7.86 (1H, s), 7.88 (1H, s). (P (E) -4- (Acet¡lsulfanil) -142"CicBopropiB" 1424iuoroif®¡p) iB) "2-oxoetil1" 34ir244-etox¡carbonifl-1H-pirazo8-14D) " 'i" metiiletiliden piperidine Synthesized the title compound in a 78% yield as a colorless amorphous solid using hydrogenated trifluoroacetate of (E) -4- (acetylsulfanyl) -3-. { [2- (4-ethoxycarbonyl-1H-pyrazol-1-yl) -1-methyl] ethylidene} piperidine obtained in (f) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.65-1.08 (4H, m), 1.35 (3H, t, J = 7.0), 1.70 and 1.73 (total 3H, each s), 1.76-1.91 (1H, m), 2.02-2.99 (7H, m), 3.80-3.93 (1H, m), 4.24- 4.34 (2H, m), 4.56-4.88 (5H, m), 7.08-7.23 (2H, m), 7.27-7.47 (2H, m), 7.77-7.91 (2H, m). (Example 61) Methyl (E) -142-C8clopropñB-142 ° iFByorof®piD) "2-oxoetin-3 ° r2- (4-ethoxycarbonyl-1H ° pyrazole ° 1-nb) ° 1 ííta®tinetBni] ® [p? -4-Sulfanylpiperidine (Hydrochloride of Compound Compound No. 1-977) The title compound was synthesized in a 64% yield as a colorless amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] - 3-. { [2- (4-etho-icarbonyl-1H-pyrazol-1-yl) -1-methyl] ethylidene} piperidine obtained in example 60 (g) above carrying out a reaction similar to that mentioned in Example 34. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.69-0.87 (2H, m), 0.96-1.16 (2H , m), 1.22 (3H, t, J = 7.0), 1.70-2.80 (7H, m), 2.89-3.00 (1H, m), 3.19 and 3.36 (total 1H, each d, J = 13.5), 4.01- 4.48 (4H, m), 4.75-5.04 (3H, m), 7.14-7.37 (3H, m), 7.71-7.81 (1H, m), 8.25 (1H, s), 8.38 and 8.48 (total 1H, each s ); IR (KBr, CPV1): 2611, 1713, 1494. (Example 62) Methyl (E) -34r244-Carbox5"1JHl ° pyrazo [] ° H4D) -1-metipetiliden} -142-cicBopropil-1- (.. 2-fluorophenol) "2nd oxoetB81¡-4-sulfanilpiperidina (deB hydrochloride compound No. 1-973 compound deB) the title compound was synthesized in a yield of 75% as a colorless amorphous solid using hydrochloride (E) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3-. { [2- (4-ethoxycarbonyl-1H-pyrazol-1-yl) -1-methyl] ethylidene} -4-Sulfanylpiperidine obtained in Example 61 carrying out a reaction similar to that mentioned in Example 15. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.72-0.88 (2H, m), 0.97-1.17 (2H, m), 1.57-3.03 (8H, m), 3.20 and 3.37 (total 1H, each d, J = 12.5), 4.06 and 4.18 (total 1H, each d, J = 12.5), 4.37-4.47 (1H, m) , 4.77-5.04 (3H, m), 7.16-7.35 (3H, m), 7.74-7.84 (1H, m), 8.41 (1H, s), 8.47 and 8.57 (total 1H, each s); IR (KBr, cm "1): 2630, 1711, 1494. (Example 83) Methyl (E) -4 ° (Aceta8syBfarañn) ° 3- (2 ° cianoetiliden) -142-c¡c¡opropil-142-fluorofeniB ) ° 2"? XoetiB1 piperidine (Compound Hydrochloride of Compound No.3-47) (A) (E) -44t-ButildimetB8s¡iiloxi) -342-c¡anoetiBBd®p) ° H4trífe nmetBD) piperidine To a solution of sodium cyanide (13.7 g) in a mixed solvent of N, N-dimethylformamide (250 mi) and water (25 ml) was added (E) -4- (t-butyldimethylsilyloxy) -3- [2- (tosyl? i) ethylidene] -1- (triphenylmethyl) piperidine (34.4 g) obtained in the example 1 (c) at room temperature, and the resulting mixture was stirred for 30 minutes. The reaction mixture was charged with water and then brought with ethyl acetate. The tract was washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to obtain the title compound (26.8 g, quantitative yield) as a brown oil. 1 H NMR (500 MHz, CDCl 3) d ppm: 0.01 (3H, s), 0.02 (3H, s), 0.88 (9H, s), 1.64-1.98 (4H, m), 2.94-3.16 (3H, m) , 3.45-3.61 (1H, m), 3.82-3.89 (1H, m), 5.57 (1H, t, J = 7.5), 7.12-7.36 (9H, m), 7.39-7.56 (6H, m). (b) (E) -342-Cyanoethylidene) "14trifendBmet®B) piperidBet) ° 4-oD The title compound was synthesized in a 65% yield as a pale yellow amorphous solid using (E) -4- (t- butyldimethylsilyl i) -3- (2-cyanoethylidene) -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e). 1 H NMR (400 MHz, CDCI3) d ppm: 1.75-2.28 (4H, m), 2.75-2.95 (1H, m), 3.07 (2H, m), 3.19-3.41 (1H, m), 3.91-4.02 (1H, m), 5.58 (1H, t, J = 7.5), 7.14-7.35 (9H, m), 7.39-7.55 (6H, m). (c) Hydrogenated trifiuoroacetate of (E) -4- (Ac®tBlsulfa? p? n)) 3 ° (2 ° cyanoeti ii den) piperidi a The title compound was synthesized in a yield of 12% as a colorless solid using (E) -3- (2-cyanoethylidene) -1- (triphenylmethyl) piperidin-4-ol obtained in (b) above carrying out a reaction similar to that mentioned in Example 36 (d). NMR with 1H (400 MHz, DMSO-d6) d ppm: 1.82-1.93 (1H, m), 2. 11-2.23 (1H, m), 2.37 (3H, s), 3.05-3.17 (1H, m), 3.25-3.43 (1H, m), 3. 47 (2H, d, J = 7.0), 3.60-3.68 (1H, m), 3.90-3.97 (1H, m), 4.40 (1H, m), 5.77 (1H, t, J = 7.0). (d) (E) -44-Acetylsulfanyl) -342"CIPA) ethyl ether) -H-4-cyclopropi8-142-fBuorofeniB) -2-oxoetappiperBdina hydrochloride The title compound was synthesized in 58% yield as a yellow oil using (E) -4- (Acetylsulfanyl) -3- (2-cyanoethylidene) piperidine trifluoroacetate hydrogenated obtained in (c) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (500 MHz, CDCl 3) d ppm: 0.79-0.92 (2H, m), 0.99-1.09 (2H, m), 1.77-1.85 (1H, m), 2.05-2.27 (2H, m), 2.29 and 2.31 (total 3H, each s), 2.46-2.58 (1H, m), 2.64-2.71 and 2.75-2.81 (total 1H, each m), 2.76 and 3.08 (total 1H, each d, J = 12.5), 3.02-3.11 (2H, m), 3.15 and 3.33 (total 1H, every d, J = 12.5), 4.27 and 4.32 (total 1H, each m), 4.74 and 4.77 (total 1H, each s), 5.57 (1H, t, J = 7.0), 7.11-7.23 ( 2H, m), 7.32-7.39 (2H, m). (Example 64) hydrochloride of (E) ° 3 ° (2 ° Carbo iet8id ©? P?) - il ° 2 ° cyclopropyl ° 1- (2-fluorophenyl) ° 2-oxoetiH ° 4-suifanñlpB ®radBna [Hydrochloride of compound of Compound No. 3-11: The title compound was synthesized in a yield of 39% as a colorless amorphous solid using (E) -4- (acetylsulfanyl) -3- (2-cyanoethylidene) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] pi pendin obtained in Example 63 (d) carrying out a reaction similar to that mentioned in Example 37. 1 H NMR (500 MHz, pyridine-d 5) d ppm: 0.77-0.94 (2H, m), 0.97-1.04 (1H, m), 1.10-1.20 (1H, m), 1.75-1.85 (1H, m), 2.17-2.29 (1H, m), 2.51-2.60 (1H, m), 2.62- 2.69 (1H, m), 2.87 and 2.97 (total 1H, each m), 3.32-3.44 (3H, m), 3.59 (1H, m), 3.88-3.95 (1H, m), 4.91 and 4.93 (total 1H, each s), 6.18-6.24 (1H, m), 7.17-7.26 (2H, m), 7.27-7.34 (1H, m), 7.70-7.75 (1H, m). MS (FAB) m / z: 364 (M + H) +. (Example 65) (E) -1-r2-CycloBoproPBB ° 1 (2 ° fluoro1!???? B) 2-oxoetiH-342- (ethoBarbonal) ethylidene-4-sulfanBBpn ®ridine hydrochloride (Compound hydrochloride of Compound No.3-17) The title compound was synthesized in an 81% yield as a colorless amorphous solid using (E) -3- (2-carboxyethylidene) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl hydrochloride. ] -4-Sulfanylpiperidine obtained in Example 64 carrying out a reaction similar to that mentioned in Example 38. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.76-0.88 (2H, m), 0.97-1.04 (1H , m), 1.11-1.17 (1H, m), 1.11 (3H, t, J = 7.0), 1.73-1.84 (1H, m), 2.12-2.26 (1H, m), 2.44-2.53 (1H, m) , 2.60-2.69 (1H, m), 2.80-2.99 (1H, m), 3.20-3.35 (3H, m), 3.53 (1H, m), 3.87 (1H, m), 4.10 (2H, q, J = 7.0), 4.91 and 4.92 (total 1H, each s), 5.98-6.05 (1H, m), 7.17-7.26 (2H, m), 7.28-7.36 (1H, m), 7.66-7.72 (1H, m). MS (FAB) m / z: 392 (M + H) +. (Example 66) (Z) -4- (AcetiBsuhfanal) hydrochloride ° 1l ° 2 ° CBclopropyl-1- (2-fluorophenyl) -2-oxoetin ° 3- (2-hi roxietiBiden) pBp®rBdirt? A ( Hydrochloride of compound of Compound No.4-2) (a) (E) -3- (2-Hydroxyethyl) -1- (triphenylmethyl) piperidn-4-oB The title compound was synthesized in a 86% yield as a colorless amorphous solid using (E) -4 - (t-butyldimethylsilyloxy) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine obtained in Example 1 (b) performing a reaction similar to that mentioned in Example 1 (e). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.75-1.87 (2H, m), 2.02-2.04 (2H, m), 2.78 (1H, bs), 3.33 (1H, bs), 3.97 (1H, bs) , 4.10-4.22 (2H, m), 5.74 (1H, t, J = 7.0), 7.13-7.31 (15H, m). (b) (E) -342- (t ° ButBdiphenylsilyloxy) etBBiden1-'34tripefmttiD) piperidin-4-ol To a solution of (E) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine- 4-ol (5.50 g) obtained in (a) above in dichloromethane (120 ml) was added t-butyldiphenylsilyl chloride (6.30 g), triethylamine (4.00 ml) and 4-dimethylaminopyridine (0.35 g) under cooling with ice, and the resulting mixture was stirred at room temperature for 24 hours. The reaction mixture was evaporated in vacuo and then diluted with dichloromethane. The resulting mixture was washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/4) to obtain the title compound (7.54 g, 85% yield) as a colorless amorphous solid. 1 H NMR (400 MHz, CDCl 3) d ppm: 1.03 (9H, s), 1.68-1.81 (2H, m), 1.97-2.09 (2H, m), 2.64 (1H, bs), 3.03 (1H, bs) , 3.89 (1H, bs), 4.22-4.35 (2H, m), 5.66 (1H, t, J = 7.0), 7.04-7.50 (20H, m), 7.60-7.75 (5H, m). C} _ (E) -4-Acetoxy-3424t-butyldipheniBsaBaDox¡) etiDid®p? M " (triphenylmethyl) piperidine To a solution of (E) -3- [2- (t-butyldiphenylsilyl) i) ethylidene] -1- (triphenylmethyl) piperidin-4-ol (512 mg) obtained in (b) above in dichloromethane ( 8 ml) was added acetic anhydride (0.10 ml), triethylamine (0.17 ml) and 4-dimethylaminopyridine (10 mg) under cooling with ice, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / liver = 1/19 - 3/17) to obtain the title compound (527 mg, yield 96 %) as a colorless amorphous solid. 1 H NMR (500 MHz, CDCl 3) d ppm: 1.03 (9H, s), 1.76-1.89 (1H, m), 1.94-2.10 (4H, m), 2.40-2.76 (2H, m), 2.80-3.18 ( 1H, m), 3.39-3.64 (1H, m), 4.26 (2H, t, J = 6.0), 4.99-5.11 (1H, m), 5.61 (1H, t, J = 6.0), 7.03-7.48 (21H , m), 7.59-7.70 (4H, m). £ d} (Z) -44-Acetylsuifanil) -342-hydroxyethylidep) "14tr8feraiflBip®taD) piperidine y_ (E) -4- (acetylsulfaniB) -3- (2 hdroxB @ tiBñd © [p?) ° il ° (triphenylmethyl) piperidine Was dissolved palladium chloride (7 mg) and 1,1'-bis (diphenylphosphino) ferrocene (44 mg) in 1,4-dioxane (4 ml) under a stream of nitrogen gas, and the resulting mixture was stirred at room temperature for 30 minutes. minutes To the resulting mixture was added a solution of (E) -4-aceto? i-3- [2- (t-butyldiphenylsilyl? i) ethylidene] -1- (triphenylmethyl) piperidine (527 mg) obtained in c) above in 1,4-dioxide (2 ml) and a solution of potassium thioacetate (283 mg) in water (1.5 ml), and the resulting mixture was stirred at 100 ° C for 6 hours. the reaction was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate.The solvent was removed in vacuo, and the residue was purified by chromatography on a column of gel of síl ice (ethyl acetate / water = 1/19 - 3/17) to obtain a 1: 7 mixture (479 mg, 89% yield) of (Z) -4- (acetylsulfanyl) -3- [2- ( t-butyldiphenylsilyl i) ethylidene] -1- (triphenylmethyl) piperidine and its (E) isomer as a colorless oil. To a solution of this mixture 1: 7 (374 mg) in tetrahydrofuran (5 ml) was added acetic acid (0.12 ml) and a 75% solution of tetrabutylammonium fluoride (750 mg) in water at room temperature, and The resulting mixture was stirred at the same temperature for 3 hours and at 50 ° C for another 2 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / liver = 1/19 - 1/3) to obtain the (Z) form of the title compound ( 25 mg, yield 11%) as a colorless amorphous solid and form (E) (178 mg, yield 74%) as a white crystal. (Z) -4- (Acetylsulfanyl) -3- (2-hydroxyethylidene) -1 - (triphenylmethyl) piperidine: NMR with 1H (400 MHz, CDCl 3) d ppm: 1.60 (1H, dd, J = 12.0, 2.0 ), 1.77-1.83 (1H, m), 2.13 (1H, d, J = 12.0), 2.20 (3H, s), 2.31-2.42 (1H, m), 3.03-3.10 (1H, m), 3.37 (1H , dd, J = 12.0, 2.0), 4.19-4.28 (1H, m), 4.40-4.48 (1H, m), 4.86 (1H, d, J = 4.0), 5.51 (1H, t, J = 7.0), 7.11-7.54 (15H, m). (E) -4- (Acetylsulfani I) -3- (2-Hydro-εethylidene) -1 - (triphenylmethyl) piperidine: NMR with 1H (400 MHz, CDCl 3) d ppm: 1.83-1.96 (1H, m), 2.21 - 2.42 (1H, m), 2.37 (3H, s), 2.95-3.16 (2H, m), 3.36-3.48 (1H, m), 3.60-3.79 (3H, m), 4.40 (1H, m), 5.98 (1H, t, J = 6.0), 7.19-7.31 (9H, m), 7.36-7.40 (6H, m). (e) (Z) -4- (AcetiBsulfanyl) hydrochloride-1l-r2 ° C? cloprop? B-1l ° (2 ° fluorophenyl) -2-oxoetipy-342 ° hydroxyethylidene) piperid?? a To a solution of ( Z) -4- (acetylsulfanyl) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine (130 mg) obtained in (d) above in dichloromethane (5 ml) was added trifluoroacetic acid (0.30 ml) under cooling with ice, and the resulting mixture was stirred at room temperature for 1 hour. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (methanol / dichloromethane = 1/5) to obtain hydrogenated trifluoroacetate of (Z) -4- (acetylsulfanyl) -3- (2- hydro-ethylidene) piperidine as a colorless amorphous solid. To a solution of the above amorphous solid and 2-bromo-2- (2-fluorophenyl) -1-cyclopropyletanone (150 mg) in acetonitrile (2 mL) was added triethylamine (0.10 mL) under ice-cooling, and the resulting mixture it was stirred at room temperature for 15 minutes. The reaction mixture was diluted with ethyl acetate and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / hexane = 1/1) to yield the free form (54 mg, 49% yield) of the title compound as a colorless amorphous solid. To a solution of this compound in dioe (3 mL) was added a solution of hydrogen chloride in 4N dioxide (0.11 mL) at room temperature, and the solvent was removed in vacuo to obtain the title compound ( 61 mg, quantitative yield) as a colorless amorphous solid. NMR with 1H (500 MHz, pyridine-d5) d ppm: 0.70-0.84 (2H, m), 0. 94-1.13 (2H, m), 1.75-1.89 (1H, m), 2.13-2.61 (3H, m), 2.19 (3H, s), 2.87-3.11 (1H, m), 2.91 and 3.07 (total 1H, each d, J = 12.0), 3.37 and 3.54 (total 1H, each d, J = 12.0), 4.54-4.64 (1H, m), 4.71-4.81 (1H, m), 4.83 and 4.88 (total 1H, each s ), 5.12 (1H, bs), 5.81 and 5.91 (total 1H, each t, J = 6.5), 7.17-7.24 (2H, m), 7.27-7.33 (1H, m), 7.61-7.68 (1H, m) . MS (FAB) m / z: 378 (M + H) +. (Example 67.). (Z) -4 ° (Acetylsu8fa? PiB) ° 1 ° r2 ° CBc8opropane ° 1 ° 2 ° fluorophenyl) ° 2-oxoetip-34244424etoxicarbonBl) etiD11"3" oxopiperazin-14l) ethylidene) piperidine (Compound Compound No.6-108) The title compound was synthesized in a 50% yield as a colorless amorphous solid using (Z) -4- (acetylsulfanyl) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- (2-hydroxyethylidene) piperidine obtained in Example 66 (e) and 1 - [2- (ethocarbonyl) ethyl] -2-o? Opiperazine hydrochloride performing a reaction similar to that mentioned in Example 33. NMR with 1 H (400 MHz, CDCl 3) d ppm: 0.79-0.90 (2H, m), 0.94-1.07 (2H, m), 1.26 and 1.27 (total 3H, each t, J = 7.0), 1 .71 -1 .84 (1 H, m), 2.06-2.50 (3H, m), 2.30 (3H, s), 2.57-2.72 (6H, m), 2.77-3.33 (5H, m), 3.34- 3.42 (2H, m), 3.58-3.66 (2H, m), 4.13 and 4.15 (total 2H, each q, J = 7.0), 4.63 and 4.67 (total 1 H, each s), 4.78 (1 H, bs) , 5.27 and 5.36 (total 1 H, each t, J = 7.0), 7.07-7.20 (2H, m), 7.28-7.44 (2H, m). MS (FAB) m / z: 560 (M + H) +. (EgempBo 68) dicbohydrate (Z) -142 ° C5cBoproiB) 58 ° 1l 42-fluorophenyl) -2-oxoetipy "3424442- (ethoxycarbonBl) etiD1-3" oxopiperazin-1 -i B > ethylidene-4-sulfanyl piperi ina (CBor ñd ato d®D composed of Compound No. 6-107] The title compound was synthesized in a 66% yield as a colorless amorphous solid using (Z) -4- (acetylsulfanyl) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- (2- {4- [2- (ethocarbonyl) ethyl] -3-o? Opiperazin-1-yl} ethylidene) piperidine obtained in Example 67 by performing a reaction similar to that mentioned in Example 34 .

NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.71-0.83 (2H, m), 0.95-1.02 (1H, m), 1.05-1.11 (4H, m), 1.69-1.80 (1H, m), 2.15-2.30 (1H, m), 2.40-2.48 (1H, m), 2.64-3.00 (6H, m), 3.10-3.18 (2H, m), 3.19-3.51 (6H, m), 3.72-3.78 (2H , m), 4.07 and 4.08 (total 2H, each q, J = 7.0), 4.43 (1H, bs), 4.90 and 4.92 (total 1H, each s), 5.35 and 5.43 (total 1H, each t, J = 7.0 ), 7.16-7.23 (2H, m), 7.27-7.33 (2H, m). MS (FAB) m / z: 518 (M + H) +. (Example 69) (Z) -34244424-dihydrochloride-carboxyethyl T-3 ° oxopiperazin-1-yl > ethylidene) -142-cyclopropiB "42-fiuorofeniß) -2-oxoetiH-4-sulfanylpiperidine (Hydrochloride of the compound of B Compound No. 6-103) The title compound was synthesized in a 95% yield as a colorless amorphous solid using (Z) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- (2-dihydrochloride. - { 4- [2- (ethocarbonyl) ethyl] -3-o? Opiperazin-1-yl} ethylidene) -4-sulfanylpiperidine obtained in Example 68 by performing a reaction similar to that mentioned in Example fifteen.

NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.69-0.85 (2H, m), 0. 94-1.13 (2H, m), 1.66-1.82 (1H, m), 2.12-2.33 (1H, m), 2.39-2.50 (1H, m), 2.60-3.04 (6H, m), 3.08-3.43 (6H, m), 3.43-3.54 (2H, m), 3. 83-3.94 (2H, m), 4.44 (1H, bs), 4.90 and 4.92 (total 1H, each s), 5.33 and 5.44 (total 1H, each t, J = 7.0), 7.16-7.33 (3H, m) 7.64-7.72 (1H, m).

MS (FAB) m / z: 490 (M + H) +. (EXAMPLE 70) (E) -4- (Acetonisulfan-8]) -hydrochloride) -cyclopropyl-142-fluorophenyl) -2-oxoetyl-34244434-ethoxycarbora [l propip-2-oxopiperazine ° 1-il > ethylidene) piperidine (CBorhadrate d (compound of Compound No.5-86) (a) (E) -4- (t-ButyldimethylsilBlox!) -3- (2 ° H -3 ° (ethoxycarboraa8) prop? ni ° 2 ° oxopiperazin-1-yl> etiBiden) ° 1- (triphenylmethyl) piperidyra The title compound was synthesized in a 62% yield as a yellow oil using (E) -4- (t-butyldimethylsilyloxy) -3- [2- (tosyloxy) ethylidene] -1- (triphenylmethyl) piperidine obtained in the example 1 (c) and 1- [3- (ethocarbonyl) propyl] -3-o? Opiperazine performing a reaction similar to that mentioned in Example 21 (a). NMR with 1H (400 MHz, CDCl 3) d ppm: -0.05 (3H, s), -0.02 (3H, s), 0.83 (9H, s), 1.25 (3H, t, J = 7.0), 1.75-1.94 (3H, m), 1.81 (2H, t, J = 7.0), 2.35 (2H, t, J = 7.0), 2.41 (2H, t, J = 7.0), 2.63 (2H, t, J = 5.5), 2.80-2.95 (1H, m ), 3.12 (2H, s), 3.18-3.27 (2H, m), 3.50 (1H, m), 3.81-3.89 (1H, m), 3.94-4.10 (3H, m), 4.12 (2H, q, J = 7.0), 5.44 (1H, t, J = 6.5), 7.10-7.19 (3H, m), 7.21-7.31 (6H, m), 7.37-7.56 (6H, m). (b) EI) -34244434 Ethoxycarbonyl) propy] 2"? xopip®ras5 [p? -1- 5l.}. ethylidene)" 4-idroxB-14-triphenylmethyl) pipepdine The title compound was synthesized in a yield of 98% as a yellow amorphous solid using (E) -4- (t-butyldimethylsilyl) i) -3- (2- {4- [3- (ethocarbonyl) propyl] -2-o? opiperazin-1-yl} ethylidene) -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e). NMR with 1H (400 MHz, CDCl 3) d ppm: 1.24 (3H, t, J = 7.0), 1. 74-1.84 (1H, m), 1.80 (2H, t, J = 7.0), 1.91-2.11 (3H, m), 2.34 (2H, t, J = 7.0), 2.40 (2H, t, J = 7.0) , 2.65 (2H, t, J = 6.0), 2.74 (1H, m), 3.12 (2H, s), 3.19-3.40 (1H, m), 3.25 (2H, t, J = 5.5), 3.90-4.01 ( 2H, m), 4.02-4.09 (1H, m), 4.11 (2H, q, J = 7.0), 5.43 (1H, t, J = 6.5), 7.06-7.32 (9H, m), 7.35-7.58 (6H , m). (c) (E) -44Acetylsulfanyl) -34244434etoxDcarlboniD) propiDTl-2 ° oxopiperazin-1-yl} ethylidene) 1- (trifenaBmethyl) piperidyra The title compound was synthesized in a yield of 10% as a yellow amorphous solid using (E) -3- (2-. {4- [3- (ethoxycarbonyl) propyl] - 2-o? Opiperazin-1-yl.} Ethylidene) -4-hydro? I-1- (triphenylmethyl) piperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 1 (h). NMR with 1H (500 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 1.74-1.88 (1H, m), 1.82 (2H, t, J = 7.0), 2.15-2.39 (2H, m ), 2.24 (3H, s), 2.36 (2H, t, J = 7.5), 2.41 (2H, t, J = 7.0), 2.49-2.70 (4H, m), 2.98-3.33 (1H, m), 3.13 (2H, s), 3.20 (2H, t, J = 5.5), 3.92-4.07 (2H, m), 4.11 (2H, q, J = 7.0), 4.25 (1H, bs), 5.44 (1H, t, J = 6.5), 7.12-7.21 (3H, m), 7.23-7.32 (6H, m), 7.38-7.56 (6H, m). (d) bis (hydrogenated trifluoroacetate) of (E) ° 4 ° (AcetylsyBffa? p? ñB) ° 3 ° (2- (4-r3- (ethoxycarbonyl) propyl-2-oxopiperazine-1 ° 5B. @tilBde? p?) piperidine The title compound was synthesized in a quantitative yield as a light orange amorphous solid using (E) -4- (acetylsulfanyl) -3- (2-. {4- [3- (eto ? -carbonyl) propyl] -2-oxopiperazin-1-yl.} ethylidene) -1- (triphenylmethyl) piperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 3 (c). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 1.93-2.05 (3H, m), 2.32-2.44 (1H, m), 2.35 (3H, s), 2.41 ( 2H, t, J = 7.0), 2.99 (2H, t, J = 7.5), 3.16-3.42 (4H, m), 3.50-3.82 (4H, m), 3.79 (2H, t, J = 7.5), 4.13 (2H, q, J = 7.0), 4.26-4.36 (2H, m), 4.42 (1H, m), 5.92 (1H, t, J = 7.5). (e) dicbohydrate of (E) ° 44AcetylsulfanDB) -142 ° c5clopropp -142 ° fluorophenyl) "2-oxoetin-34244434ethoxycarbonyl) prop50" 2"oxopiperazine ° 1 -yl eti Iden) iperidine The compound was synthesized of the title in a yield of 70% as a light brown amorphous solid using bis (hydrogenated trifluoroacetate) of (E) -4- (acetylsulfanyl) -3- (2-. {4- [3- (ethoxycarbonyl) propyl] - 2-oxopiperazin-1-yl.} Ethylidene) piperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (g). NMR with H (500 MHz, pyridine-d5) d ppm: 0.76- 0.88 (2H, m), 1. 04-1.09 (1H, m), 1.10-1.18 (1H, m), 1.15 (3H, t, J = 7.0), 1.77-1.91 (1H, m), 1.81 (2H, t, J = 7.0), 2.15 -2.35 (3H, m), 2.24 and 2.26 (total 3H, each s), 2.38 (2H, t, J = 7.0), 2.40-2.47 (1H, m), 2.48-2.75 (3H, m), 2.77- 2.83 and 2.85-2.91 (total 1H, each m), 3.06-3.32 (3H, m), 3.24 (2H, s), 3.64-3.70 (1H, m), 4.06-4.22 (1H, m), 4.13 (2H , q, J = 7.0), 4.24-4.31 (1H, m), 4.52 (1H, m), 4.96 and 4.98 (total 1H, each s), 5.73-5.81 (1H, m), 7.20-7.39 (3H, m), 7.65-7.73 (1H, m). IR (KBr, cm-1): 1727, 1662, 1495. (Example 71) dihydrochloride of (E) ° 142-Cccloprop-B-1] 42 ° fluorophenyl) -2-oxoetin-3 ° (244434etoxicarboniB) propiB1-2 ° oxopiperazin -1-il} ethylidene) -4-sulfanylpiperidine (CB time of the compound of Compound No.5-85) The title compound was synthesized in a 35% yield as a pale yellow amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oethyl] -3- (2- {4- [3- (ethocarbonyl) propyl] -2-o? opiperazin-1-yl} ethylidene) piperidine obtained in Example 70 (e) carrying out a reaction similar to that mentioned in Example 34. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.79-0.88 (2H, m), 1.00-1.08 (1H, m), 1.10-1.19 (1H, m), 1.15 (3H, t, J = 7.0), 1.74-1.88 (1H, m), 1.83 (2H, t, J = 7.0), 2.14-2.27 (1H, m), 2.29-2.57 (3H, m), 2.33 (2H, t, J = 7.0), 2.39 (2H, t, J = 7.0), 2.61-2.74 (1H, m), 2.85-3.04 (1H, m), 3.24-3.32 (2H, m), 3.27 ( 2H, s), 3.39 (1H, dd, J = 12.0, 3.5), 3.53-3.68 (1H, m), 3.80-3.86 (1H, m), 4.13 (2H, q, J = 7.0), 4.17-4.29 (2H, m), 4.97 (1H, s), 5.68-5.75 (1H, m), 7.21-7.42 (3H, m), 7.68-7.75 (1H, m).

IR (KBr, crn-1): 2536, 1727, 1661, 1495. (Example 72) (E) -3- (2 44434C ^ arboxipropy1) 1-2-oxopiperazin-1-yl dihydrochloride} ethylidene) -1 ° [2-ci clopropi B-142-fl? uorofeniD-2-oxoetill-4-sulfa nylpiperodine (Cl orhydrate <3 ofO compound of D Compound No.5-81) The title compound was synthesized in a 57% yield as a colorless amorphous solid using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- (2-dihydrochloride. - { 4- [3- (ethoxycarbonyl) propyl] -2-o? Opiperazin-1-yl}. Ethylidene) -4-sulfanylpiperidine obtained in Example 71 carrying out a reaction similar to that mentioned in Example 15. NMR with 1H (500 MHz, pyridine-d5) d ppm: 0.76-0.88 (2H, m), 1.01-1.08 (1H, m), 1.10-1.18 (1H, m), 1.74-1.84 (1H, m), 1.96 (2H, t, J = 7.0), 2.13-2.28 (1H, m), 2.38-2.60 (5H, m), 2.42 (2H, t, J = 7.0), 2.61-2.74 (1H, m), 2.84 -3.00 (1H, m), 3.27 (2H, t, J = 5.5), 3.30 (2H, s), 3.34-3.42 (1H, m), 3.55 and 3.64 (total 1H, each d, J = 12.5), 3.79-3.86 (1H, m), 4.10-4.28 (2H, m), 4.96 (1H, s), 5.67-5.74 (1H, m), 7.19-7.37 (3H, m), 7.68-7.76 (1H, m ). IR (KBr, cm "1): 2576, 1713, 1659, 1495. (Example 73.). (E) -44 Acetylsulfanyl) -tl42- < e? Cloprop88-1 2 ° fluorophenyl) -2-oxoetip-342444 ethoxycarboniBmetiD) ° H-p 5 -razol-1-ethylhexide) piperidine (Compound of B compound No. 1-62) [(E) -4 ° (t-Butyldimethylsilyloxy) -3 ° i2-r4- (ethoxycarbonBBmet-5-pyrazol-1-inethylidene-1- (triphenylmethyl) piperidi a The title compound was synthesized in 45% yield as a solid colorless amorphous using (E) -4- (t-butyldimethylsilyloxy) -3- [2- (tosyl? i) ethylidene] -1- (triphenylmethyl) piperidine obtained in the example 1 (c) and 4- (ethoxycarbonylmethyl) -1H-pyrazole performing a reaction similar to that mentioned in Example 21 (a). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.06 (6H, s), 0.88 (9H, s), 1.29 (3H, t, J = 7.0), 1.89-2.04 (4H, m), 3.03 (1H, bs), 3.55 (2H, s), 3.69 (1H, bs), 3.93-3.98 (1H, m), 4.19 (2H, q, J = 7.0), 4.73-4.84 (2H, m), 5.84 (1H, t, J = 7.5), 7.17-7.37 (15H, m), 7.44 (1H, s), 7.49 (1H, s). (b) (E) -3-242444 Ethoxycarbonylmethyl) 1H-pyroD ° H4Dlet®Did®ot? 4-Hydroxy-1- (triphenylmethyl) piperidine The title compound was synthesized in a 63% yield as a colorless amorphous solid using (E) -4- (t-butyldimethylsilyl) i -3-. [4- (Ethocarbonylmethyl) -1H-pi-razol-1-yl] ethylidene} -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e) NMR with 1H (400 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 1.58-1.61 (1H, m), 1.81-1.89 (1H, m), 2.00 (1H, bs), 2.08-2.14 (1H, m), 2.84 (1H, bs), 3.45 (1H, bs), 3.50 (2H, s), 4.00 (1H, bs), 4.16 (2H, q, J = 7.0), 4.68- 4.79 (2H, m), 5.77 (1H, t, J = 7.0), 7.14-7.18 (3H, m), 7.24-7.28 (12H, m), 7.41 (1H, s), 7.44 (1H, s). (c) (E) -4- (AcetylsulfaniB) ° 3 ° (2-r4- (ethoxycarboraylnp? etnn) ° 1H ° py2? B-1 ° Het i I iden > -1- (triphenylmethyl) piperidine It was synthesized the title compound in a 60% yield as a yellow oil using (E) -3-. {2- 2- [4- (ethoxycarbonylmethyl) -1 H -pyrazol-1-yl] ethylidene} -4-hydro ? i-1- (trife nylmethyl) piperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 1 (h). NMR with H (400 MHz, CDCl 3) d ppm: 1.25 (3H, t, J = 7.0), 1.79-1.92 (1H, m), 2.24 (3H, s), 2.29-2.33 (2H, m), 3.10- 3.14 (1H, m), 3.41 (2H, s), 3.98 (1H, bs), 4.13 (2H, q, J = 7.0), 4.25-4.36 (2H, m), 4.61-4.73 (2H, m), 5.78 (1H, t, J = 7.0), 7.12-7.20 (3H, m), 7.21-7.31 (6H, m), 7.40-7.56 (8H, m). (d) Hydrogenated trifluoroacetate of (E) -4- (Acetylsylphaa?!) -3-f244- (ethoxycarbonyl methyl) -1 H-pi razol-1 -i netiliden pi nated The title compound was synthesized in a yield 20% as a colorless oil using (E) -4- (acetylsulfanyl) -3-. { 2- [4- (Etho? -carbonylmethyl) -l H-pyrazol-1-yl] ethylidene} -1- (triphenylmethyl) piperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 3 (c). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.28 (3H, t, J = 7.0), 2.03-2.08 (1H, m), 2.36 (3H, s), 2.37-2.41 (1H, m), 3.24- 3.31 (1H, m), 3.39-3.44 (1H, m), 3.47 (2H, s), 3.73 (1H, d, J = 14.0), 4.10 (1H, d, J = 14.0), 4.16 (2H, q, J = 7.0), 4.44 (1H, t, J = 4.0), 4.63-4.68 (1H, m), 4.73-4.80 (1H, m), 6.05 (1H, t, J = 7.0), 7.41 (2H, s). . { and} (E) -4- (Acetylsulfanii) -1-y2-cic8opropiB 1- (2-fBuoroiF®it? N) ° 2o oxoetin-3-f2-r4- (ethoxycarboniBmetiB) -1H-PBrazol ° 1-ñB1etñBidera ^ piperidine The title compound was synthesized in a 57% yield as a light yellow oil using hydrogenated trifluoroacetate of (E) -4- (acetylsulfanyl) -3-. { 2- [4- (Ethoxycarbonylmethyl) -1H-pyrazol-1-yl] ethylidene} piperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.75-0.88 (2H, m), 0.97-1.07 (2H, m), 1.27 (3H, t, J = 7.0), 1.78-1.86 (1H, m), 2.12-2.22 (2H, m), 2.28 and 2.29 (total 3H, each s), 2.49-2.62 (1H, m), 2.68-2.73 and 2.76-2.81 (total 1H, each m), 2.88 and 3.15 (total 1H , each d, J = 12.5), 3.30 and 3.41 (total 1H, each d, J = 12.5), 3.46 (2H, s), 4.15 (2H, q, J = 7.0), 4.28-4.34 (1H, m) , 4.62-4.64 and 4.67-4.70 (total 2H, each m), 4.71 and 4.74 (total 1H, each s), 5.78 (1H, t, J = 7.0), 7.07-7.17 (2H, m), 7.19-7.27 (1H, m), 7.28-7.37 (1H, m), 7.33 and 7.34 (total 1H, each s), 7.39 (1H, s). (Example 74) hydrochloride of (E:) - 3 -f2-y4-ÍCarboxam®ti I) -1H = • P-razoB-1-yl-1-ethylidene-142-cyclopropyl-1- (2-fluorophenyl) -2-oxoet 111 -4-Sulfanylpiperi dine (Chlorohydrate of Compound of Cornpuc? SttO No. 1-53) The title compound was synthesized in a 28% yield as a colorless amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] - 3-. { 2- [4- (Ethoxycarbonylmethyl) -1H-pyrazol-1-yl] ethylidene} piperidine obtained in Example 73 (e) by performing a reaction similar to that mentioned in Example 15. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.78-0.83 (2H, m), 0. 98-1.04 (1H, m), 1.09-1.15 (1H, m), 1.74-1.83 (1H, m), 2.14-2.24 (1H, m), 2.46-2.55 (1H, m), 2.61-2.67 (1H , m), 2.82-2.98 (1H, m), 3.36 and 3.67 (total 2H, each d, J = 12.5), 3.79 (3H, bs), 4.85-4.93 (3H, m), 5.98 (1H, t, J = 7.0), 7.23-7.26 (2H, m), 7.29-7.35 (1H, m), 7.69-7.74 (1H, m), 7.81 (1H, s), 7.84 (1H, s). MS (FAB) m / z: 444 (M + H) +. (Example 75.). (E) -4- (AcetylsulfanB) ° 1-r2 ° c-Chlorpropylene-1- (2-fluorophenyl) -2-oxoethyl- -34243 ° ethoxycarbonyl-1H-prazzoi-1"aB ) ethylidenepiperidine (Compound of compound No.1-14) The 12% yield was synthesized as a yellow oil using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- (2-hydro) ? ethyl) piperidine obtained in Example 32 (f) and 3-ethoxycarbonyl-1 H-pyrazole in place of 4-ethocarbonyl-1 H-1, 2,3-triazole carrying out a reaction similar to that mentioned in Example 47. NMR with 1H (400 MHz, CDCl 3) d ppm: 0.80-0.91 (2H, m), 0.99-1.11 (2H, m), 1.37 (3H, t, J = 7.0), 1.76-1.84 (1H , m), 2.12-2.35 (2H, m), 2.26 (3H, s), 2.47 and 2.62 (total 1H, each m), 2.73 (1H, m), 3.01 and 3.11 (total 1H, each d, J = 12.5), 3.48 and 3.51 (total 1H, each d, J = 12.5), 4.28-4.36 (3H, m), 4.75 and 4.77 (total 1H, each s), 5.13-5.21 (2H, m), 5.70-5.74 (1H, m), 6.81-6.82 (1H, m), 7.09-7.21 (2H, m), 7.33 (1H, m), 7.43-7.49 (2H, m). (Example 76) hydrochloride of (E) -1 ° 2-CaclopropBl ° 1l (2-iFByoroff®? P? IB) ° 2-oxoetip-34243-ethoxycarbonyl-1H-pyrazole "1 l) eti5in1 ° 4" Sulfanylpiperidine (Hydrochloride of compound of Compound No. 1-13) The 39% strength was synthesized as a colorless amorphous solid using (E) -4- (acetylsulfani!) - 1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- [2- (3 -eto? icarbonyl-1 H-pyrazol-1-yl) ethylidene] piperidine obtained in Example 75 carrying out a reaction similar to that mentioned in Example 34. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.84- 0.92 (2H, m), 1.03-1.09 (1H, m), 1.16-1.24 (1H, m), 1.20 and 1.21 (total 3H, each t, J = 7.0), 1.74-1.82 (1H, m), 2.14 -2.24 (1H, m), 2.55-2.68 (2H, m), 2.83-2.90 and 2.93-2.99 (total 1H, each m), 3.46 and 3.54 (total 1H, each t, d = 12.0), 3.69-3.82 (2H, m), 4.26 (2H, q, J = 7.0), 4.97 (1H, s), 5.43-5.46 (2H, m), 6.08 (1H, m), 6.99-7.00 (1H, m), 7.23 -7.36 (3H, m), 7.68-7.69 (1H, m), 7.74-7.80 (1H, m). MS (FAB) m / z: 458 (M + H) +. (Example 77) hydrochloride of (E) -34243-Carboxy ° 1H-pyg) S? D-1 ° Dl) ethylidene-1-r2-c5-chloropropyl-1- (2-fluorofeniB) -2 ° oxoetap ° 4"sulfanylpiperidine ( Compound Hydrochloride of Compound No. B -L51 The title compound was synthesized in a 34% yield as a colorless amorphous solid using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- [2] hydrochloride. - (3-ethoxycarbonyl-1H-pyrazol-1-yl) ethylidene] -4-sulfanylpiperidine obtained in Example 76 carrying out a reaction similar to that mentioned in Example 15. 1 H NMR (400 MHz, pyridine-d 5 ) d ppm: 0.81-0.95 (2H, m), 1.02-1.06 (1H, m), 1.16-1.21 (1H, m), 1.74-1.81 (1H, m), 2.14-2.22 (1H, m), 2.59 -2.67 (2H, m), 2.85 and 2.95 (total 1H, each m), 3.50 and 3.61 (total 1H, each d, J = 12.5), 3.77-3.84 (2H, m), 4.96 (1H, s), 5.59-5.63 (2H, m), 6.17-6.21 (1H, m), 7.19-7.34 (4H, m), 7.73 (1H, s), 7.75-7.81 (1H, m). MS (FAB) m / z: 430 (M + H) \ (EjempBo 78) dici lorh? Drato de ÍE) -4- (Ac @ tBlsulfa 5l) - -12-ciclopropii I-1-Í24 jorofen? L) - 2-oxoetill -3- -24 (2S.4R) -4. -hydro? u-2 (metoxicar bonil l) p irroB idin-1 -alleti liden > P iperidone (Hydrochloride d®0 composed of Compound No.5-388) The title compound was synthesized in a 57% yield as a yellow amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] - 3- (2-hydroxyethylidene) piperidine obtained in example 32 (f) and (2S, 4R) -4-hydroxy-2- (methocarbonyl) pyrrolidine in place of 4- (ethoxycarbonylmethyl) piperidine performing a reaction similar to that mentioned in Example 33. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.79-0.88 (2H, m), 1.00-1.07 (1H, m), 1.10-1.21 (1H, m), 1.82-1.93 (1H, m), 2.17-2.27 (1H, m), 2.25 and 2.26 (total 3H, each s), 2.31-2.60 (4H, m), 2.67-2.92 (3H, m), 3.14-3.25 (1H, m), 3.36-3.53 (2H, m), 3.58-3.75 (1H , m), 3.69 and 3.71 (total 3H, each s), 3.80-3.90 (1H, m), 4.53-4.58 (1H, m), 4.71-4.77 (1H, m), 4.92 and 4.95 (total 1H, each s), 6.01-6.08 (1H, m), 7.20-7.34 (3H, m), 7.67-7.78 (1H, m). IR (KBr, cm "1): 1747, 1702, 1494. (EiempBo 79) dicbohydrate of (E) -142-GicBopro? E) iil-142-fluoroyl) -2-oxoetS1-3424 (2S, 4R) "4-hydroxy ° 24m © toxicarbonaB) pyrrolidin-1-inethylidene 4 ° sulfanylpiperi ina (Hydrochloride composed of Compound No.5-387) The title compound was synthesized in a 58% yield as a pale yellow amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oetil] -3-. { 2 - [(2S, 4R) -4-hydro? I-2- (methocarbyl) pyrrolidin-1-yl] ethylidene} piperidine obtained in Example 78 carrying out a reaction similar to that mentioned in Example 55. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.77-0.97 (2H, m), 0.98-1.08 (1H, m), 1.09-1.21 (1H, m), 1.74-1.85 (1H, m), 2.13-2.29 (1H, m), 2.35-2.60 (4H, m), 2.61-2.71 (1H, m), 2.81-3.04 (2H , m), 3.34-3.61 (3H, m), 3.65-3.80 (1H, m), 3.72 and 3.73 and 3.74 (total 3H, each s), 3.82-4.06 (2H, m), 4.72-4.80 (1H, m), 4.94 and 4.95 and 4.96 (total 1H, each s), 5.95-6.06 (1H, m), 7.19-7.37 (3H, m), 7.71-7.81 (1H, m). IR (KBr, cm "1): 2545, 1746, 1712, 1494. (Example 80) dichlorhydride of (E) -3424 (2S.4R) ° 2-Carboxy-4-hydroxypyridine ° 1 iB1etBliden 42- cicBopropil ° 142 ° luorof® [ri) B [l) "2 ° oxoetill-4-sulfanylpipepdine (Hydrochloride of B compound of] Compound No.5-385) The title compound was synthesized in a 75% yield as a colorless amorphous solid using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oetil] -3-. { 2 - [(2S, 4R) -4-hydro? I-2- (methocarbyl) pyrrolidin-1-yl] ethylidene} -4-Sulfanylpiperidine obtained in Example 79 carrying out a reaction similar to that mentioned in Example 15. 1 H NMR (500 MHz, pyridine-d 5) d ppm: 0.76-0.95 (2H, m), 0.99-1.06 (1H, m), 1.11-1.20 (1H, m), 1.73-1.84 (1H, m), 2.15-2.26 (1H, m), 2.45-2.55 (1H, m), 2.56-2.86 (3H, m), 2.93- 3.03 (1H, m), 3.34-4.03 (4H, m), 4.05-4.35 (3H, m), 4.53-4.66 (1H, m), 4.84-4.90 (1H, m), 4.97 and 4.99 and 5.00 and 5.02 (total 1H, each s), 6.18-6.29 (1H, m), 7.16-7.34 (3H, m), 7.70-7.80 (1H, m). IR (KBr, cm "1): 2559, 1738, 1711, 1494. (Example 81) dihydrochloride of (E)" 44Ac®talsulfa? P? 5l]) ° 142 ° cyclopropyl-42-fluorophenyl) -2-oxoeti n ° 3-f24N- (ethoxycarbonylmethyl) -N ° methylaminoethylidene > piperñdñ? p? a (C lord id time of the compound of Compound No.3-55) • 2HCl The title compound was synthesized in a 56% yield as a pale yellow amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oethyl] -3- (2-hydroxyethylidene) piperidine obtained in example 32 (f) and N- (etho-icarbonylmethyl) -N-methylamine hydrochloride in place of 4- (eto-icarbonylmethyl) piperidine carrying out a similar reaction to that mentioned in Example 33. NMR with H (500 MHz, pyridine-d5) d ppm: 0.76-0.92 (2H, m), 0.99-1.06 (1H, m), 1.11-1.22 (1H, m), 1.13 and 1.14 (total 3H, each t, J = 7.0), 1.81-1.93 (1H, m), 2.16-2.30 (1H, m), 2.25 and 2.26 (total 3H, each s), 2.39-2.51 (1H, m ), 2.45 and 2.47 (total 3H, each s), 2.52-2.60 and 2.67-2.75 (total 1H, each m), 2.77-2.90 (1H, m), 3.13 and 3.22 (total 1H, each d, J = 13.0 ), 3.27-3.51 (4H, m), 3.56-3.72 (1H, m), 4.13 (2H, q, J = 7.0), 4.52-4.58 (1H, m), 4.94 and 4.96 (total 1H, each s) , 5.90-6.00 (1H, m), 7.20-7.30 (2H, m), 7.31-7.39 (1H, m), 7.66-7.74 (1H, m). IR (KBr, cm "1): 1745, 1700, 1494. (Example 82) dicBorhydrate d (E) -142 ° C? C) oprop.n ° 1 ° (2 ° fluorophenyl) -2-oxoetip-3424N- (ethoxycarbon) i BmetiB) -M ° meti lamino! etiliden) -4-sulfanylpiperadsna (Hydrochloride of B compound of B Compound No.3-54) The title compound was synthesized in a 63% yield as a pale yellow amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3-. { 2- [N- (etho? -carbonylmethyl) -N-methylamino] ethylidene} piperidine dihydrochloride obtained in Example 81 carrying out a reaction similar to that mentioned in Example 34. 1 H NMR (500 MHz, pyridine-d 5) d ppm: 0.79-0.88 (2H, m), 1. 01-1.07 (1H, m), 1.11-1.20 (1H, m), 1.14 and 1.15 (total 3H, each t, J = 7.0), 1.74-1.83 (1H, m), 2.16-2.27 (1H, m) , 2.43-2.54 (1H, m), 2.47 and 2.49 (total 3H, each s), 2.63-2.72 (1H, m), 2.81-2.90 and 2.93-3.00 (total 1H, each m), 3.30-3.61 (6H , m), 3.84-3.89 (1H, m), 4.14 and 4.15 (total 2H, each q, J = 7.0), 4.94 and 4.95 (total 1H, each s), 5.86-5.91 (1H, m), 7.21- 7.28 (2H, m), 7.31-7.37 (1H, m), 7.70-7.75 (1H, m). IR (KBr, cm "1): 2536, 1745, 1713, 1494. (Example 83) dihydrochloride of (E) -3424N4Garboxipp? ®táB) -N-methylamino-1-ethylidene-1-f2-cyclopropyl-1- (2-fBuoroferai8) -2-oxo®t? L1 ° 4 ° sulfanylpiperidine (Hydrochloride of Compound B Compound No. 3-50) The title compound was synthesized in a 17% yield as a colorless amorphous solid using (E) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- dihydrochloride. { 2- [N- (etho? -carbonylmethyl) -N-methylamino] ethylidene} -4-Sulfanylpiperidine obtained in Example 82 carrying out a reaction similar to that mentioned in Example 15.

NMR with 1H (500 MHz, pyridine-d5) d ppm: 0.79-0.92 (2H, m), 1.00-1.08 (1H, m), 1.12-1.21 (1H, m), 1.74-1.86 (1H, m), 2.15-2.28 (1H, m), 2.44-2.60 (1H, m), 2.63-2.75 (1H, m), 2.71 and 2.73 (total 3H, each s), 2.80-2.89 and 2.93-3.02 (total 1H, each m), 3.38-3.69 (4H, m), 3.72-3.93 (3H, m), 4.94 and 4.96 (total 1H, each s), 5.99-6.06 (1H, m), 7.17-7.35 (3H, m), 7.69-7.76 (1H, m). IR (KBr, cm-1): 2630, 1741, 1712, 1494. (Example 84) dihydrochloride of (Z) -44Acet5BsuDfa? P) i []) ° 142 ° cyclopropi8-1- (2-fluorofeniB) -2 ° oxoetBn-3424N "(ethoxycarbonylmethyl) -N-methylamino-ethylidene> piperidimenide (Clo time of Compound B Compound No.4-55) (ai (Z) ° 44Acetilsulfanii) "3424N4etoxBcarboraBBrip? © t? l methylaminolethylidene > -1- (triphenylmethyl) piperidBine The title compound was synthesized in a 38% yield as a colorless amorphous solid using (Z) -4- ( acetylsulfanyl) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine obtained in example 66 (d) in place of (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- ( 2-fluorophenyl) -2-o? Oethyl] -3- (2-hydro? Ylethylidene) piperidine and N- (etho? -carbonylmethyl) -N-methylamine hydrochloride instead of 4- (etho? -carbonylmethyl) piperidine carrying out a reaction similar to that mentioned in Example 33.

NMR with 1H (400 MHz, CDCl 3) d ppm: 1.29 (3H, t, J = 7.0), 1.73-1.85 (1H, m), 1.94-2.05 (1H, m), 2.15-2.52 (4H, m), 2.20 (3H, s), 2.41 (3H, s), 3.00-3.47 (4H, m), 4.21 (2H, q, J = 7.0), 4.82 (1H, bs), 5.39 (1H, t, J = 6.5 ), 7.03-7.75 (15H, m). (b) bis (hydrogenated trifluoroacetate) of (Z) -44-AcetylsuBffa? p? ñ8? -3" { 24N- (ethoxycarbonylmethyl) -N-methylamino-1-ethylidene} pip.ridane The title compound was synthesized in a yield of 90% as a colorless amorphous solid using (Z) -4- (acetylsulfanyl) -3-. {2- [N- (etho-icarbonylmethyl) -N-methylamino] ethylidene} - 1 - (triphenylmethyl) piperidine obtained in (a) above performing a reaction similar to that mentioned in Example 3 (c). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.30 (3H, t, J = 7.0), 1.99-2.10 (1H, m ), 2.35 (3H, s), 2.35-2.50 (1H, m), 2.88 (3H, s), 3.07-3.20 (1H, m), 3.36-3.49 (1H, m), 3.65-3.98 (5H, m) ), 4.25 (2H, q, J = 7.0), 4.28-4.38 (1H, m), 4.78 (1H, bs), 5.78-5.86 (1H, m). (C) (Z) -4 ° dihydrochloride ( Acetylsulfanal) 1 1 r 2 -chlorocpropyl 1 (2-fluoro-phenyl) -2-oxoeti ^ 3424 N 4 -ethoxycarboniflmetin) "N-methylamine p) 1-ethylidenepiperidine The title compound was synthesized in 50% yield as a solid Colorless amorphous using bis (trifluoroacetate hydroge swimming) of (Z) -4- (acetylsulfanyl) -3-. { 2- [N- (ethoxycarbonylmethyl) -N-methylamino] ethylidene} piperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.75-0.92 (2H, m), 0.93-1.09 (2H, m), 1.23-1.35 (3H, m), 1.70-1.87 (1H, m), 2.06- 2.56 (2H, m), 2.29 (3H, s), 2.35 and 2.36 (total 3H, each s), 2.65-3.00 (2H, m), 3.08-3.36 (6H, m), 4.14-4.25 (2H, m ), 4.62 and 4.67 (total 1H, each s), 4.79 (1H, bs), 5.35 and 5.45 (total 1H, each t, J = 6.5), 7.04-7.22 (2H, m), 7.26-7.48 (2H, m). IR (KBr, cm "1): 1745, 1699, 1494. (Ex. Pp. 8855)) ddiic <(Z) -1-C-clopropal-1- (2-fluoro pffeenn ¡ihl) hydrochloride # 22 - ooxoxoethetyln-3424N4ethoxycarbonylmethyl] 1-N-methylBaotp? I myol et. Lead.) - 4 4 - ssuullffaannii llppiipp < eridine (Cl orhydrate of compound d®D Compound No.4-54) The title compound was synthesized in a 90% yield as a colorless amorphous solid using (Z) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] dihydrochloride] - 3-. { 2- [N- (etho? -carbonylmethyl) -N-methylamino] ethylidene} piperidine obtained in Example 84 performing a reaction similar to that mentioned in Example 34. NMR with 1H (400 MHz, CDCl 3) d ppm: 0.75-0.91 (2H, m), 0.94-1.09 (2H, m), 1.22-1.33 (3H, m), 1.65-1.79 (1H, m) , 2.07-2.28 (2H, m), 2.37 and 2.39 (total 3H, each s), 2.44-3.35 (8H, m), 4.12-4.24 (2H, m), 4.30 (1H, bs), 4.68 and 4.73 ( total 1H, each s), 5.23 and 5.33 (total 1H, each t, J = 7.0), 7.05-7.21 (2H, m), 7.26-7.48 (2H, m). IR (KBr, cm-1): 2626, 2560, 1745, 1712, 1494. (Example 86) (Z) -3424N4CarbQXBCtp®t5D dihydrochloride) "N-methylaminolethylidene 42-cycloprop-1-y2-1-fluorophene BHDl ) -2 '-oxoetiDll-4-sulfan ilpiperid ina (Clorhi drato of Compound Compound No. 4-50) The title compound was synthesized in a 50% yield as a colorless amorphous solid using (Z) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- dihydrochloride. { 2- [N- (etho? -carbonylmethyl) -N-methylamino] ethylidene} -4-Sulfanylpiperidine obtained in Example 85 performing a reaction similar to that mentioned in Example 15. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.71-0.94 (2H, m), 0. 96-1.17 (2H, m), 1.71-1.87 (1H, m), 2.21-2.42 (1H, m), 2.43-2.56 (1H, m), 2.60-3.07 (2H, m), 2.98 and 3.02 (total 3H, each s), 3.25-3.62 (2H, m), 4.00-4.26 (4H, m), 4.71 (1H, bs) , 4.90 and 4.96 (total 1H, each s), 5.76 and 5.87 (total 1H, each t, J = 7.0), 7.10-7.36 (3H, m), 7.62-7.72 (1H, m). IR (KBr, cm-1): 2558, 1740, 1712, 1494. (Example 87) (4S) 4Z hydrochloride) 44Ac® tñ8su Dfarcn) -142-cyclopropyl 1- (2-fluorophenyl) -2- oxoetip-342-hydroxB @ tal? defiT)) piperidine (Hydrochloride of the form (4S) deB composed of B Compound No.4-2) • HCl (a) (4S) - (Z) -4- (Acetylsunfanyl) ° 3- (2-hydroxyethylBBBden) ° H- (triphenBm @ tán) piperidine v (4R) - (Z) -4- (aceti > sulfanyl) -3- (2 ° hydroxyethyl? dB) ° 1 ° (triphenylmethyl) piperidine (Z) -4- (Acetylsulfanyl) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine (102 mg) obtained in example 66 (d) using a preparative HPLC (Daicel, Chiralcel OD-H, eluent: heineum / ethanol / diethylamine = 90/10 / 0.1) to obtain (4S) - (Z) -4- (acetylsulfanyl) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine (1 mg) with a shorter retention time and (4R) - (Z) -4- (acetylsulfanyl) -3- (2- hydroxyethylidene) -1- (triphenylmethyl) piperidine (43 mg) with a longer retention time, as colorless amorphous solids, respectively. The 1 H NMR was the same as that of the (Z) -4- (acetylsulfanyl) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine of Example 66 (d). [a] D of the form (4S): -15.2 ° (c = 1.00, MeOH) [a] D of the form (4R): + 11.5 ° (c = 0.50, MeOH) (b) hydrochloride of (4S) ° (Z) ° 4- (AcetñlsuBfanBl) ° 1 ° í2 ° cicBopropñB ° 1- (2 ° fluorofenii) -2-oxoetill-342 ° hidroxietiliden) PBperíd ??? na The title compound was synthesized in a yield of 67% as a colorless amorphous solid using (4S) - (Z) -4- (acetylsulfanyl) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 66 (and). The 1 H NMR was the same as in Example 66 (e). IR (KBr, cm "1): 3345, 1696, 1494. (Example 88) hydrochloride of (4R) 4Z) -44Ac®tinsulfam) 5B)" H42 ° ecyclopropyl-142-fluorofeni I) -2-oxoetin-342- hydroxylethenyl) pi peridine (8th Form hydrochloride (4R) of compound of Compound No. 4-2) The title compound was synthesized in a 70% yield as a colorless amorphous solid using (4R) - (Z) -4- (acetylsulfanyl) -3- (2-hydroxyethylidene) -1 - (triphenylmethyl) piperidine obtained in Example 87 (a) performing a reaction similar to that mentioned in Example 66 (and). The 1 H NMR was the same as in Example 66 (e). IR (KBr, cm-1): 3350, 1 696, 1494. (Example 89) (Z) -dialhydrochloride 44Acet? 8su8faBT) Bn) -142 ° cyclopropyl-142-fluorofeni I) -2-oxoetip-3424N434®toxicarbo ? p? l) propyl1-N-methylamino) ethylidene) piperidine (B-hydrochloride compound of B Compound No. 4-67) The title compound was synthesized in a 43% yield as a light orange amorphous solid using (Z) -4- (acetylsulfanyl) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- (2-hydroxyethylidene) piperidine obtained in example 66 (e) in place of (E) -4- (acetylsulfanyl) -1 - [2-cyclopropyl-1 - (2-fluorophenyl) -2- or ? oethyl] -3- (2-hydroxyethylidene) piperidine and N- [3- (etho? -carbonyl) propyl] -N-methylamine hydrochloride in place of 4- (etho? -carbonylmethyl) piperidine carrying out a reaction similar to that mentioned in Example 33. NMR with H (500 MHz, pyridine-d5) d ppm: 0.76-0.85 (1H, m), 0.99-1.08 (2H, m), 1.09-1.18 (1H, m), 1.11 and 1.12 (total 3H, each t, J = 7.0), 1.81-1.89 (1H, m), 2.23-2.42 (3H, m), 2.25 and 2.26 (total 3H, each s), 2.47-2.61 (1H, m), 2.51 (2H, t, J = 7.0), 2.77 and 2.78 (total 3H, each s), 2.96-3.13 (2H, m), 3.15-3.26 (2H, m), 3.35 and 3.55 (total 1H, each d, J = 12.0), 3.60-3.67 (1H, m ), 3.98-4.12 (1H, m), 4.08 and 4.09 (total 2H, each q, J = 7.0), 4.13-4.23 (1H, m), 4.86 and 4.96 (total 1H, each s), 4.89-4.94 ( 1H, m), 6.10 and 6.21 (total 1H, each t, J = 7.0), 7.19-7.38 (3H, m), 7.57-7.66 (1H, m). IR (KBr, cm-1): 1725, 1712, 1495. (Example 90) (Z) -142 dihydrochloride "CñcBopropol-1- (2 ° phorophenyl) -2-oxoetiH-3424N434ethoxycarbonol) propiB) 11-N "methylane and not) ethylidene) -4-sulfan i piperidine (Hydrochloride of compound of Compound No.4-66) The title compound was synthesized in a 76% yield as a yellow amorphous solid using (Z) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-o-ethyl dichlorohydrate. ] -3- (2- {N- [3- (ethocarbonyl) propyl] -N-methylamino.} Ethylidene) piperidine obtained in example 89 carrying out a reaction similar to that mentioned in Example 34. NMR with 1H (500 MHz, pyridine-d5) d ppm: 0.74-0.85 (1H, m), 0.87-0.96 (1H, m), 0.99-1.06 (1H, m), 1.07-1.15 (1H, m), 1.10 and 1.11 (total 3H, each t, J = 7.0), 1.74-1.85 (1H, m), 2.25-2.40 (3H, m), 2.43-2.54 (3H, m), 2.65-2.72 (1H, m), 2.81 and 2.83 (total 3H, each s), 2.93-2.98 (1H, m), 3.19-3.64 (4H, m), 3.89-4.00 (2H, m), 4.07 and 4.09 (total 2H, each q, J = 7.0), 4.54-4.59 (1H, m), 4.89 and 4.95 (total 1H, each s), 5.85 and 5.96 (total 1H, each t, J = 7.0), 7.17-7.25 (2H, m), 7.26-7.34 (1H, m), 7.57-7.68 (1H, m). IR (KBr, cm "1): 2550, 1728, 1495. (Example plate 91) dic lorhi idrato of IZ) -342-ÍN434Carboxi) propBlll-N = methylamino > ethyl liden) -1 42-cyclone Iopropi0-14240uorofe? nBB) -2-oxo®taD1-4-sulfanylpiperidine (Hydrochloride of Compound Compound No. 4-62) The title compound was synthesized in a 50% yield as a colorless amorphous solid using (Z) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- (2-. {N- [3- (Ethocarbonyl) propyl] -N-methylamino} ethylidene) -4-sulfanylpiperidine obtained in Example 90 carrying out a reaction similar to that mentioned in Example 15. NMR with 1H (500 MHz, pyridine-d5) d ppm: 0.73-0.83 (1H, m), 0.86-0.97 (1H, m), 0.98-1.06 (1H, m), 1.07-1.17 (1H, m), 1.71-1.85 (1H, m), 2.25-2.54 (4H, m), 2.58-2.89 (3H, m), 2.81 and 2.83 (total 3H, each s), 2.90-3.01 (1H, m), 3.21-3.37 (2H, m), 3.39-3.48 (1H, m), 3.50-3.56 (1H, m), 3.86-4.00 (2H, m), 4.53-4.60 (1H, m), 4.89 and 4.97 (total 1H, each s), 5.86 and 5.97 (total 1H, each t, J = 7.0), 7.16-7.24 (2H, m), 7.25-7.34 (1H, m), 7.62-7.68 (1H, m). IR (KBr, cm "1): 2553, 1713, 1494. (Using 92) IZD-dihydrate) -44Ac®t? Bsulfan? D) = 142» cyclopropyl-1. (2Buorofeni D-2-oxoetiIl -3424N- (etoxica rbon? Dm®t? Í) -N- isopropi lami noletilider? Hydrochloride (Compound Hydrochloride of Compound No.4-79) The title compound was synthesized in a 33% yield as an amorphous brown solid using (Z) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] - 3- (2-hydroxyethyl) piperidine obtained in example 66 (e) in place of (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oethyl] -3- (2-hydroxyethylidene) piperidine and N- (eto-icarbonylmethyl) -N-isopropylamine in place of 4- (eto-icarbonylmethyl) piperidine performing a reaction similar to that mentioned in Example 33. NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.74-0.86 (2H, m), 0.98-1.13 (2H, m), 1.04 and 1.06 (total 3H, each d, J = 6.5), 1.07 and 1.09 (total 3H, every d, J = 6.5), 1.17 and 1.19 (total 3H, each t, J = 7.0), 1.85-1.96 (1H, m), 2.28 (3H, s), 2.30-2.41 (1H, m), 2.42-2.52 (1H, m), 2.59-2.68 (1H, m), 2.90-3.01 (1H, m), 3.03-3.12 (1H, m), 3.13-3.22 (1H, m), 3.36-3.70 (5H , m), 4.18 and 4.20 (total 2H, each q, J = 7.0), 4.87 and 4.92 (total 1H, each s), 5.14 (1H, bs), 5.63 and 5.72 (total 1H, each t, J = 7.0 ), 7.19-7 .27 (2H, m), 7.29-7.36 (1H, m), 7.64-7.70 (1H, m). IR (KBr, cm "1): 1745, 1696, 1495. (Ejex ippploo 9933)) ddiicclloorrhhiaddrraattoo dde (Z) -142-C? Clopropo'0 -1- (2-fluoro pffeenniill)) - 22 - ooxxooeettiinll -33442244NN44eettooxxiiccarbonilmet? L) -N-? Sopr ooppylamaminoinnoo 11eettiilliiddeenn.}...). -44"-Suuilffaanniillppéa? Perid? Na (CD-Hydrate d®D composed of Compound No. 4-78) The title compound was synthesized in a 41% yield as a colorless amorphous solid using (Z) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-o-ethyl dichlorohydrate. ]-3-. { 2- [N- (ethoxycarbonylmethyl) -N-isopropylamino] ethylidene} piperidine obtained in Example 92 carrying out a reaction similar to that mentioned in Example 34. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.75-0.83 (2H, m), 0.97-1.13 (2H, m), 1.03 (3H, d, J = 6.5), 1.06 (3H, d, J = 6.5), 1.16 and 1.18 (total 3H, each t, J = 7.0), 1.73-1.85 (1H, m), 2.22-2.37 (1H, m), 2.45-2.54 (1H, m), 2.66-2.75 (1H, m), 2.81-3.27 (3H, m), 3.36-3.55 (5H, m), 4.17 and 4.18 (total 2H, each q, J = 7.0) , 4.61 (1H, bs), 4.89 and 4.93 (total 1H, each s), 5.44 and 5.55 (total 1H, each t, J = 7.0), 7.18- 7.24 (2H, m), 7.27-7.34 (1H, m ), 7.67-7.74 (1H, m). IR (KBr, crn 1): 2545, 1745, 1712, 1494. asopropylaminol leylideneV 142-cyclopropyl-1- (2-fluorophenyl) -2-oxoetill-4-sulpha nylpipepdine (Hydrochloride of compound d®D Compound No.4-74) The title compound was synthesized in a 40% yield as a colorless amorphous solid using (Z) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- dihydrochloride. { 2- [N- (etho? -carbonylmethyl) -N-isopropylamino] ethylidene} -4-Sulfanylpiperidine obtained in Example 93 carrying out a reaction similar to that mentioned in Example 15.

NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.70-0.87 (2H, m), 0.94-1.04 (1H, m), 1.05-1.19 (1H, m), 1.13 and 1.14 (total 3H, each d , J = 6.5), 1.15 and 1.16 (total 3H, each d, J = 6.5), 1.71-1.84 (1H, m), 2.22-2.41 (1H, m), 2.48-2.57 (1H, m), 2.64- 3.02 (2H, m), 3.21-3.44 (2H, m), 3.49-3.69 (5H, m), 4.67 (1H, bs), 4.87 and 4.92 (total 1H, each s), 5.55 and 5.67 (total 1H, each t, J = 7.0), 7.16-7.23 (2H, m), 7.25-7.32 (1H, m), 7.66-7.73 (1H, m). IR (KBr, cm "1): 2554, 1740, 1712, 1494. (Example 95) dihydrochloride (Z) -44Ace) tD8suBfaníDT) -1 42-cicBopropi 11-142-fluorophenyl-2-oxo-till-3 -í2-ÍN-íetoxacarbo? piDD? r¡p? ® DB) -N-ethylami nolethyl liden) piper «dina (Clorhi drato of the compound ofO Compound No.4-73) The title compound was synthesized in a 38% yield as an amorphous brown solid using (Z) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] - 3- (2-hydroxyethylidene) piperidine obtained in example 66 (e) in place of (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oethyl] -3- (2-hydroxyethylidene) piperidine and N- (eto-icarbonylmethyl) -N-ethylamine in place of 4- (ethoxycarbonylmethyl) piperidine carrying out a reaction similar to that mentioned in Example 33. 1H NMR ( 500 MHz, pyridine-d5) d ppm: 0.74-0.88 (2H, m), 0.99-1.05 (1H, m), 1.07-1.15 (1H, m), 1.10 and 1.12 (total 3H, each t, J = 7.5 ), 1.17 and 1.18 (total 3H, each t, J = 7.0), 1.84-1.94 (1H, m), 2.27 (3H, s), 2.30-2.68 (3H, m), 2.83 and 2.86 (total 2H, each d, J = 7.5), 2.92-3.01 (1H, m), 3.05-3.12 (1H, m), 3.40 and 3.55 (total 1H, each d, J = 13.0), 3.52-3.67 (3H, m), 3.72 -3.81 (1H, m), 4.15-4.22 (2H, m), 4.89 and 4.94 (total 1H, each s), 5.12 (1H, bs), 5.63 and 5.73 (total 1H, each t, J = 7.0), 7.20-7.26 (2 H, m), 7.30-7.36 (1H, m), 7.64-7.69 (1H, m). IR (KBr, cm "1): 1745, 1697, 1494. (Example 96) (Z) -142-Cyclopropylo-142-fluorophenyl) -2-oxoetiH-3424N- (ethoxycarbonylmethyl) dihydrochloride" M-etiiam? ' [ethylidene-4-sulfanylpiperidane pO (Compound Hydrochloride Compound No.4-72) The title compound was synthesized in a 64% yield as a colorless amorphous solid using (Z) -4- (acetylsulfanyl) dihydrochloride -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -3-. { 2- [N- (etho? -carbonylmethyl) -N-ethylamino] ethylidene} piperidine obtained in Example 95 carrying out a reaction similar to that mentioned in Example 34. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.71-0.86 (2H, m), 0.96-1.04 (1H, m ), 1.06-1.20 (1H, m), 1.09 (3H, t, J = 7.0), 1.15 and 1.16 (total 3H, each t, J = 7.0), 1.70-1.85 (1H, m), 2.17-2.36 ( 1H, m), 2.44-2.54 (1H, m), 2.64-3.04 (4H, m), 3.25 and 3.40 (total 1H, each d, J = 12.5), 3.37-3.62 (5H, m), 4.16 and 4.17 (total 2H, each q, J = 7.0), 4.57 (1H, bs), 4.90 and 4.94 (total 1H, each s), 5.46 and 5.57 (total 1H, each t, J = 7.0), 7.16-7.26 (2H , m), 7.27-7.36 (1H, m), 7.64-7.76 (1H, m). IR (KBr, cm "1): 2558, 1744, 1712, 1494. (Example 97) dihydrochloride of (Z? -3- (2-rN4Ca? Rboxirn? Till? -N-ethylaminolethylidene.). -142 ° cicBopropil ° 142- fluorofenSn) "2-oxoetinyl ° 4 ° sulfanylpiperidine (Hydrochloride of compound of Compound No. 4-68) • 2HCl The title compound was synthesized in a 53% yield as a colorless amorphous solid using (Z) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- dihydrochloride. . { 2- [N- (etho? -carbonylmethyl) -N-ethylamino] ethylidene} -4-Sulfanylpiperidine obtained in Example 96 performing a reaction similar to that mentioned in Example 15. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.72-0.92 (2H, m), 0.97-1.05 (1H, m), 1.06-1.15 (1H, m), 1.33 and 1.35 (total 3H, each t, J = 7.0), 1.72-1.84 (1H, m), 2.23-2.41 (1H, m), 2.46-2.56 (1H , m), 2.62-2.98 (2H, m), 3.22-3.58 (4H, m), 3.71-4.12 (4H, m), 4.68 (1H, bs), 4.89 and 4.95 (total 1H, each s), 5.17 and 5.89 (total 1H, each t, J = 7.0), 7.16-7.24 (2H, m), 7.25-7.34 (1H, m), 7.64-7.72 (1H, m). IR (KBr, cm "1): 2556, 1740, 1713, 1494. (Example 98) dihydrochloride of (E) -44 Acetylsulfinyl-342-f4-r2- (ethoxycarbonyl) etin-3-oxopnperazine 1 -ethyl ethylidene) ° 1 ° H ° (2 ° fluoro-phenyl) ° 2-methoxy ° 2 ° oxoetyl piperidi a (Hydrochloride d © B composed of Compound No.11-108) _ (E) -4- (Acetylsulfanyl) -3- (24442-Fetox5carbonaB) ®tfl oxopiperazine ° 1-iB ethylidene) 1- (triphenylmethyl) piperale a? Pa The title compound was synthesized in a yield of 40% as a yellow powder crystal using (E) -3- (2- {4- [2- (ethocarbonyl) ethyl] -3-o? opiperazin-1-yl} ethylidene) -4-hydro? i-1- (triphenylmethyl) piperidine obtained in example 17 (b) carrying out a reaction similar to that mentioned in Example 1 (h). NMR with 1H (400 MHz, CDCl 3) d ppm: 1.27 (3H, t, J = 7.0), 1.79-1.91 (1H, m), 2.14-2.32 (2H, m), 2.24 (3H, s), 2.51- 2.66 (6H, m), 2.93-3.06 (3H, m), 3.09 (2H, s), 3.38 (2H, t, J = 5.0), 3.63 (2H, t, J = 7.0), 4.15 (2H, q , J = 7.0), 4.25 (1H, m), 5.59 (1H, t, J = 7.0), 7.13-7.22 (3H, m), 7.23-7.34 (6H, m), 7.40-7.54 (6H, m) . (b) bis (hydrogenated trifluoroacetate) of (E) ° 4- (AcetñlsuliFanñB) ° 3 ° (2-. {4-f2- (ethoxycarbonyl) etin-3-oxopiperazin-1-il etiBaden) pip @? BNA The title compound was synthesized in an 81% yield as a brown oil using (E) -4- (acetylsulfanyl) -3- (2-. {4- [2- (ethocarbon I) ethyl) ] -3-o? Opiperazin-1 -i l.} Eti Iden) -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 3 (c). NMR with 1H (400 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 2. 00-2.09 (1H, m), 2.36 (3H, s), 2.38-2.45 (1H, m), 2.62 (2H, t, J = 6.5), 2.86-2.95 (1H, m), 2.97-3.06 (1H , m), 3.17-3.26 (1H, m), 3.28-3.45 (5H, m), 3.50-3.54 (2H, m), 3.63 (2H, t, J = 7.0), 3.67 (1H, d, J = 13.0), 4.13 (2H, q, J = 7.0), 4.16 (1H, d, J = 13.0), 4.43-4.47 (1H, m), 5.59 (1H, t, J = 7.0). (c) dihydrochloride of (E) ° 44AcetylsuBfanyl) ° 3424442- (ethoxycarbonyl) etiM-3-oxopiperazin-1-yl) etiBden) "1 ° n42 ° fluorofen il) ° 2-methoxy-2 ° oxoetin piperidi a A a solution of hydrogenated bis (trifluoroacetate) of (E) -4- (acetylsulfanyl) -3- (2- {4- [2- (ethocarbonyl) ethyl] -3- o? opiperazin-1-yl} ethylidene) piperidine (0.76 g) obtained in (b) above and methyl bromine (2-fluorophenyl) acetate (0.45 g) in acetonitrile (10 ml) was added triethylamine (0.51 ml) under ice-cooling, and the The resulting mixture was stirred at room temperature for 30 minutes The reaction mixture was diluted with ethyl acetate and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (methanol / dichloromethane = 1/20) to give the free form (0.50 g, yield 74%) of the title compound as a light yellow oil. To a solution of this compound in dichloromethane (8 ml) was added a solution of hydrogen chloride in 4N dioxide (0.69 ml) at room temperature, and the reaction mixture was evaporated in vacuo to obtain the title compound (0.66 g, quantitative yield) as a light brown amorphous solid. NMR with 1H (400 MHz, pyridine-d5) d ppm: 1.12 (3H, t, J = 7.0), 1.80-1.89 (1H, m), 2.14-2.24 (1H, m), 2.25 and 2.27 (total 3H, each s), 2.45-2.65 (2H, m), 2.73 (2H, t, J = 7.0), 2.77-3.02 (5H, m), 3.19 and 3.37 (total 1H, each d, J = 12.5), 3.23 and 3.25 (total 2H, each s), 3.29-3.36 (2H, m), 3.68 (3H, s), 3.76 (2H, t, J = 7.0), 4.10 (2H, q, J = 7.0), 4.50-4.57 (1H, m), 4.95 and 4.97 (total 1H, each s), 5.81 (1H, t, J = 7.0), 7.20-7.28 (2H, m), 7.31-7.38 (1H, m), 7.73-7.80 ( 1H, m). IR (KBr, cm "1): 1752, 1730, 1697, 1664, 1497. (EiempBo 99) dihydrochloride of (E? -342-M-r24 Ethoxycarbonifl ett.ITl-3-oxopiperazin-1- 8). iiden) - 141424Duo rofeni l.}. -2- -m @ toxi i-2-oxo®tiD1 = 4- Sulfani Ipiperi dina (Clorh idrato del comp ues lo d®l Compyesto No. 11-107) The title compound was synthesized in a 65% yield as a colorless amorphous solid using (E) -4- (acetylsulfanyl) -3- (2- {4- [2- (ethocarbonyl) ethyl] dihydrochloride] -3-o? Opiperazin-1-yl.} Ethylidene) -1- [1- (2-fluorophenyl) -2-metho? I-2-o? Oethyl] piperidine obtained in example 98 carrying out a reaction similar to the one mentioned in Example 34. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 1.12 (3 H, t, J = 7.0), 1. 71-1.83 (1H, m), 2.11-2.24 (1H, m), 2.54-2.65 (2H, m), 2.67-2.82 (1H, m), 2.74 (2H, t, J = 7.0), 2.96-3.09 (1H, m), 3.01 (2H, t, J = 6.5), 3.26 (2H, s), 3.34 (2H, t, J = 5.0), 3.37 and 3.48 (total 1H, each d, J = 12.5), 3.60 and 3.73 (total 1H, each d, J = 12.5), 3.67 (3H, s), 3.77 (2H, t, J = 7.0), 3.80-3.89 (1H, m), 4.10 (2H, q, J = 7.0), 4.94 and 4.95 (total 1H, each s), 5.69-5.78 (1H, m), 7.18-7.28 (2H, m), 7.30-7.38 (1H, m), 7.75-7.83 (1H, m). IR (KBr, cm-1): 2522, 1752, 1730, 1661, 1496. (EiempBo 100) dihydrochloride of (E) -342-f4424Garboxñ®t? B) H "3" oxopiperazin-1-iB ethylidene) -1 -f1- (2nd fluorofenBl) -2-rra®toxi-2 ° © ^ o®tBl1 ° 4-sulfanylpiperidine (Hydrochloride of Compound B Compound No.11-103) The title compound was synthesized in a quantitative yield as a colorless amorphous solid using (E) -3- (2- {4- [2- (ethocarbonyl) ethyl] -3-o-opiperazin-1-dihydrochloride] ethyl) -1- [1- (2-fluorophenyl) -2-metho? i-2-o? oethyl] -4-sulfanylpiperidine obtained in example 99 carrying out a reaction similar to that mentioned in Example 15. NMR with 1H (400 MHz, pyridine-d5) d ppm: 1.71-1.83 (1H, m), 2.12-2.24 (1H, m), 2.53-2.64 (2H, m), 2.67-2.84 (1H, m) ), 2.92 (2H, t, J = 7.0), 2.95-3.09 (1H, m), 2.99 (2H, t, J = 6.5), 3.26 and 3.27 (total 2H, each s), 3.34-3.46 (2H, m), 3.37 and 3.47 (total 1H, each d, J = 12.5), 3.60 and 3.72 (total 1H, each d, J = 12.5), 3.67 (3H, s), 3.80-3.88 (1H, m), 3.91 (2H, t, J = 7.0), 4.94 and 4.95 (total 1H, each s), 5.69-5.78 (1H, m), 7.18-7.26 (2H, m), 7.29-7.36 (1H, m), 7.75- 7.82 (1H, m). IR (KBr, cm "1): 2570, 1750, 1659, 1496. (Example 101) dicbohydrate of (E) -44Ac @ tiisuBfaBT) ón) ° 142" cyclopropyl-1- (2-fluorophenal) -2-oxoetin- 3- 3-RiH ° pyrazole ° 3 (5) ° inpropiliden piperidi? P? A (Hydrochloride of compound of Compound No.1-264) (a) (E) -3-np ° (t-Butoxycarbonyl) - H- parazoi-3-i8l-1l ° hBdroxipropin ° 1 (triphenylmethyl) piperidi-4-one The title compound was synthesized in a 45% yield as a colorless amorphous solid using 3- [1- (t-butoxycarbonyl) -1H-pyrazol-3-yl] propanal in place of 1- (etho-icarbonylmethyl) piperidin-4-carbaldehyde by performing a reaction similar to that mentioned in Example 36 (a). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.63 (9H, s), 1.66-1.80 (2H, m), 1.84-2.01 (1H, m), 2.37-2.45 (1H, m), 2.68-2.95 ( 4H, m), 3.11-3.32 (2H, m), 3.73-3.84 (2H, m), 6.16 (1H, d, J = 2.5), 7.14-7.21 (3H, m), 7.23-7.34 (6H, m ), 7.41-7.59 (6H, m), 7.94 (1H, d, J = 2.5). (b) (E) ° 3-f3-ri- (t-Butoxycarbonin) -1H-p? razol ° 3-anilpropyl? d®p- (triphenylmethyl) piperidine ° 4 ° ona To a solution of (E) -3 -. { 3- [1- (t-Butoxycarbonyl) -1 H -pyrazol-3-yl] -1-hydro? Ipropyl} -1- (triphenylmethyl) piperidin-4-one (1.92 g) obtained in (a) above in dichloromethane (45 ml) was added methanesulfonyl chloride (0.29 ml) and triethylamine (0.61 ml) under cooling with ice, and The resulting mixture was stirred at the same temperature for 2.5 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo to obtain a mesyl compound (2.14 g) as a colorless amorphous solid. To a solution of this compound in tetrahydrofuran (50 ml) was added 1,8-diazabicyclo [5.4.0] undeca-7-ene (0.98 ml), the resulting mixture was refluxed for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of ammonia and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / hexane = 7/13) to obtain the title compound (1.20 g, 65% yield) as an amorphous solid. colorless. 1 H NMR (400 MHz, CDCl 3) d ppm: 1.64 (9H, s), 2.28-2.35 (2H, m), 2.58 (2H, bs), 2.66 (2H, t, J = 6.0), 2.79 (2H, t, J = 7.5), 3.12 (2H, bs), 6.12 (1H, d, J = 2.5), 6.68 (1H, t, J = 7.5), 7.12-7.21 (3H, m), 7.22-7.32 (6H, m), 7.41-7.56 (6H, m), 7.94 (1H, d, J = 2.5). (c) (E) -343-M4t-Butoxycarbonyl) -1H-pyrazole "3 gnipropyrid® p) -4 ° hydroxy-1- (triphenylmethyl) piperidine The title compound was synthesized in a yield of 68 g. % as a colorless solid using (E) -3-. {3- [1- (t-butoxycarbonyl) -1 H -pyrazol-3-yl] propylidene} -1- (triphenylmethyl) piperidin-4-one obtained in (b) above carrying out a reaction similar to that mentioned in Example 36 (c). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.63 (9H, s), 1.72-1.83 (1H, m), 2.01 -2.25 (2H, m), 2.31-2.42 (2H, m), 2.59 (2H, bs), 2.78 (2H, t, J = 7.5), 3.06 (1H, bs), 3.98 (1H, bs), 5.52 (1H, t, J = 7.5), 6.15 (1H, d, J = 2.5), 7.09-7.19 (3H, m), 7.20-7.31 (6H, m), 7.36-7.56 (6H, m), 7.97 ( 1H, d, J = 2.5). (D) Hydrogenated trifluoroacetate of (E) ° 3 ° (3 ° F1l ° (t-Butoxycarboxyla5B) ° 1H ° pyrazole-3-yl-propylidene >; "4-hydroxypiperidium? The title compound was synthesized in a 65% yield as a colorless oil using (E) -3-. {3- [1- (t-butoxycarbonyl) -1 H-pyrazole -3-yl] propylidene.} - 4-hydroxy-1- (triphenylmethyl) piperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 3 (c). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.60 (9H, s), 1.91-2.05 (2H, m), 2.39-2.50 (1H, m), 2.53-2.65 (1H, m), 2.75-2.92 (2H, m), 3.27-3.38 ( 1H, m), 3.58-3.70 (1H, m), 3.88-3.96 (1H, m), 3.97-4.06 (1H, m), 4.37 (1H, m), 5.73 (1H, t, J = 8.0), 6.18 (1H, d, J = 2.5), 7.85 (1H, d, J = 2.5). (E) (E) -343-M- (t-Butoxycarbonyl) -1H-pyrazole ° 34llpropiDide? P). "142-cyclopropi-1-142-fluorophen-yl) -2-oxoetill-4-h idroxy piperidine The title compound was synthesized in a 93% yield as a colorless amorphous solid using hydrogenated trifluoroacetate of (E) -3-. { 3- [1- (t-Butoxycarbonyl) -1H-pyrazol-3-yl] propylidene} -4-hydro? Ipiperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (g). NMR with 1H (400 MHz, CDCl 3 + DzO) d ppm: 0.77-0.89 (2H, m), 0.92-1.08 (2H, m), 1.64 (9H, s), 1.66-1.77 (1H, m), 1.89- 2.10 (1H, m), 2.17-2.27 (1H, m), 2.29-2.39 (2H, m), 2.41-2.55 (1H, m), 2.69-2.82 (3H, m), 2.84 and 2.93 (total 1H, each d, J = 12.5), 3.16 and 3.26 (total 1H, each d, J = 12.5), 4.08 (1H, m), 4.67 and 4.68 (total 1H, each s), 5.52 (1H, m), 6.18 and 6.19 (total 1H, each d, J = 2.5), 7.06-7.22 (2H, m), 7.25-7.34 (1H, m), 7.38-7.46 (1H, m), 7.95 and 7.96 (total 1H, each d, J = 2.5). (f) (E) -44-Acetylsulfanyl) -3-0-p4t-butoxBcarbo? raiB) -1H-Pcrg) zol "3 ° inpropiliden > -142-cicDopropyl-142-ffluorofeni!) - 2-oxoethyl-1-piperidine was synthesized Compound the title in a yield of 17% as a colorless oil using (E) -3-. {3- [1- (t-butoxycarbonyl) -1 H -pyrazol-3-yl] propylidene}. [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] -4-hydro? Ipiperidine obtained in (e) above carrying out a reaction similar to that mentioned in Example 1 (h). RMN with 1H ( 400 MHz, CDCl 3) d ppm: 0.77-0.91 (2H, m), 0.92-1.09 (2H, m), 1.65 (9H, s), 1.71-1.84 (1H, m), 2.06-2.62 (5H, m) , 2.28 and 2.29 (total 3H, each s), 2.65-2.92 (4H, m), 3.28-3.39 (1H, m), 4.32 (1H, m), 4.63 and 4.69 (total 1H, each s), 5.59 ( 1H, m), 6.15 and 6.19 (total 1H, each d, J = 2.5), 7.06-7.22 (2H, m), 7.25-7.47 (2H, m), 7.95 and 7.96 (total 1H, each d, J = 2.5). (Q) (E) -4- (AcetylsulfaniB) 142"(5-ChlorpropBl-1 (2-fluorophenyl) -2-oxoetin-34341H-pyrazole ° 3 (5) ° inpropBBideft.} Piperidine dihydrochloride. It was synthesized the title compound in a quantitative yield as a colorless amorphous solid using (E) -4- (acetylsulfanyl) -3-. { 3- [1- (t-Butoxycarbonyl) -1H-pyrazol-3-yl] propylidene} -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? Oethyl] piperidine obtained in (f) above carrying out a reaction similar to that mentioned in Example 9 (f). NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.75-0.90 (2H, m), 0.95-1.05 (1H, m), 1.08-1.17 (1H, m), 1.81-1.92 (1H, m), 2.17-2.32 (1H, m), 2.25 and 2.27 (total 3H, each s), 2.42-2.74 (4H, m), 2.76-2.95 (3H, m), 3.00 and 3.07 (total 1H, each d, J = 12.5), 3.58 and 3.67 (total 1H, each d, J = 12.5), 4.56 (1H, m), 4.87 and 4.92 (total 1H, each s), 5.85 (1H, m), 6.30 and 6.31 (total 1H, each d, J = 2.0), 7.18-7.36 (3H, m), 7.64-7.74 (1H, m), 7.81 and 7.82 (total 1H, each d, J = 2.0). MS (FAB) m / z: 442 (M + H) +. fluorophenyl) • 2-oxo-till-343-MH-pyrazole-3 (5) -lpid Diden > -4-Sulfanylpiperidine (Compound Hydrochloride of Compound No. 1-263) The title compound was synthesized in an 82% yield as a colorless amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-o-ethyl dichlorohydrate. ]-3-. { 3- [1 H -pyrazol-3 (5) -yl] propylidene} piperidine obtained in Example 101 (g) carrying out a reaction similar to that mentioned in Example 34. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.73-0.89 (2H, m), 0.94-1.04 (1H, m), 1.06-1.17 (1H, m), 1.71-1.82 (1H, m), 2.13-2.28 (1H, m), 2.44-2.61 (3H, m), 2.62-2.72 (1H, m), 2.79- 3.01 (1H, m), 2. 91 and 2.92 (total 2H, each t, J = 7.5), 3.32 and 3.41 (total 1H, each d, J = 12.5), 3.48 and 3.49 (total 1H, each d, J = 12.5), 3.85 (1H, m ), 4.90 and 4. 92 (total 1H, each s), 5.75 and 5.76 (total 1H, each t, J = 7.5), 6.31 and 6.32 (total 1H, each d, J = 2.0), 7.16-7.35 (3H, m), 7.69- 7.76 (1H, m), 7.82 and 7.83 (total 1H, each d, J = 2.0). MS (FAB) m / z: 400 (M + H) +. Example 103) daclorh dactyl of IE) -44Acetyl Isulfa? P? Ifl) -1-r2-cie ilopropyl-? 142-fl uoropheni I) -2-oxoetill -342-. { N424etßxDcarbooDiD) eti ll-N-methylaminc > } ethylidene) pyrrolidine (Dihydrochloride compound of Compound No. 3-61) The title compound was synthesized in a 35% yield as a colorless amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] - 3- (2-hydroxyethylidene) piperidine obtained in example 32 (f) and N- [2- (ethocarbonyl) ethyl] -N-methylamine instead of 4- (ethocarbarylmethyl) piperidine carrying out a similar reaction to that mentioned in Example 33. 1 H NMR (500 MHz, pyridine-d 5 + D 20) d ppm: 0.79-0.96 (2H, m), 1.06-1.16 (2H, m), 1.16 (3H, t, J = 7.0), 1.81-1.90 (1H, m), 2.17-2.37 (2H, m), 2.31 and 2.34 (total 3H , each s), 2.50-2.57 and 2.67-2.74 (total 1H, each m), 2.73 and 2.75 (total 3H, each s), 2.79-2.89 (1H, m), 2.94-3.02 (2H, m), 3.11 and 3.24 (total 1H, each d, J = 12.5), 3.26-3.41 (2H, m), 3.62-3.68 (2H, m), 3.70-3.75 (1H, m), 4.14 (2H, q, J = 7.0 ), 4.46-4.51 (1H, m), 5.03 and 5.04 (total 1H, each s), 6.07 and 6.09 (total 1H, each t, J = 7.5), 7.28-7.40 (2H, m), 7.45-7.52 ( 1H, m), 7.67-7.73 (1H, m). IR (KBr, cm "1): 1730, 1709, 1495. (Example 104) dihydrochloride of (E) ° 1 ° r 2 ° CyclopropiB ° 1l ° (2 ° fluorophenyl) -2-oxoetin ° 3 ° (2 ° (N) -r2- (ethoxycarbonyl) etiB11 ° N-methylamino) ethylidene) -4 ° sulfanylpipepdine (Hydrochloride d @ D composed of B Compound No.3-60) The title compound was synthesized in a 31% yield as a colorless amorphous solid using (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-o-ethyl dichlorohydrate. ] -3- (2- {N- [2- (ethocarbonyl) ethyl) -N-methylamino} ethylidene) piperidine obtained in Example 103 carrying out a reaction similar to that mentioned in Example 34. 1 H NMR (400 MHz, pyridine-d 5 + D 20) d ppm: 0.79-0.98 (2H, m), 1.05-1.17 (2H , m), 1.17 (3H, t, J = 7.0), 1.75-1.86 (1H, m), 2.19-2.34 (2H, m), 2.63-2.73 (1H, m), 2.80 and 2.83 (total 3H, each s), 2.76-2.84 and 2.89-2.97 (total 1H, each m), 3.01 and 3.03 (total 2H, each t, J = 7.0), 3.35-3.47 (3H, m), 3.52 and 3.60 (total 1H, each d, J = 12.5), 3.66-3.80 (2H, m), 3.89-3.95 (1H, m), 4.15 (2H, q, J = 7.0), 5.01 and 5.03 (total 1H, each s), 6.05-6.12 (1H, m), 7.29-7.39 (2H, m), 7.45-7.53 (1H, m), 7.67-7.73 (1H, m). IR (KBr, cm "1): 2463, 1730, 1495. Eiemple 105) d (E) -3424N42- '(Carboxy-D-t-1-N-methylamino) ethylidene) 2-cyclohydrate ? prop il-142-f¡uorofe r¡5D) -2-ox @@ ttB] -4-sulfanyl piperidine (Hydrochloride of Compound 1 Compound No. 3-56) (E) -4- (Acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- (2- {N- [2- (ethoxycarbonyl) ethyl)) -N-methylamino} ethylidene) piperidine (365 mg) obtained in Example 103 with 3N hydrochloric acid (10 ml) and then the resulting mixture was stirred at 60 ° C for 3 hours. The reaction mixture was evaporated in vacuo, and the residue was purified using a preparative HPLC (YMC-Pack ODS-A; YMC, eluent: acetonitrile / 0.012N hydrochloric acid = 15/85) to obtain the title compound (271 mg, 74% yield) as a colorless amorphous solid. 1 H NMR (500 MHz, pyridine-d 5 + D 20) d ppm: 0.77-0.86 (1H, m), 0.87-0.94 (1H, m), 1.07-1.15 (2H, m), 1.75-1.84 (1H, m), 2.20-2.31 (2H, m), 2.64-2.71 (1H, m) , 2.76-2.83 and 2.89-2.96 (total 1H, each m), 2.98 and 2.99 (total 3H, each s), 3.21 and 3.22 (total 2H, each t, J = 7.0), 3.44 and 3.45 (total 1H, each d, J = 12.0), 3.55 and 3.62 (total 1H, each d, J = 12.0), 3.59-3.68 (2H, m), 3.88-3.94 (2H, m), 3.93-4.02 (1H, m), 5.03 and 5.05 (total 1H, each s), 6.15 (1H, t, J = 7.5), 7.27-7.38 (2H, m), 7.43-7.50 (1H, m), 7.66-7.72 (1H, m). IR (KBr, cm "1): 2553, 1713, 1494. (Example 106) dichlorhadrate of (Z) ° 4- (Acet? Lsulfan? Ñn) ° i] -i2-cyclopropiB-142-fluorofenifl) ° 2 -oxoetip ° 3424N424etoxicarfooo? L) etiB1-N-methalamino) ethylidene) piperidine (Hydrochloride of B compound of Compound No.4-61) The title compound was synthesized in a 36% yield as a colorless amorphous solid using (Z) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] - 3- (2-hydroxyethylidene) piperidine obtained in example 66 (e) in place of (E) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o? oethyl] -3- (2-hydroxyethylidene) piperidine and N- [2- (ethocarbonyl) ethyl) -N-methylamine in place of 4- (ethocarbonylmethyl) piperidine by carrying out a reaction similar to that mentioned in Example 33. NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.76-0.84 (1H, m), 0.96-1.18 (3H, m), 1.07 and 1.08 (total 3H, each t, J = 7.0), 1.80-1.91 (1H, m), 2.23-2.42 (1H, m), 2.26 and 2.27 (total 3H, each s), 2.46-2.65 (2H, m), 2.77 and 2.79 (total 3H, each s), 2.95 -3.13 (2H, m), 3.22-3.32 (2H, m), 3.40-3.57 (3H, m), 3.93-4.20 (2H, m), 4.07 and 4.08 (total 2H, each q, J = 7.0), 4.87 and 4.95 (total 1H, each s), 4.93-4.99 (1H, m), 6.02 and 6.13 (total 1H, each t, J = 7.0), 7.20-7.39 (3H, m), 7.58-7.67 (1H, m). IR (KBr, cm-1): 1731, 1711, 1494. (Example 107) dichlorhadrate of (Z? -1-r2-Cyclop? Ropill-142-fluorophenyl) -2-oxoetin-3424N42- (ethoxycarbort) il). tiBl "[N" meti lam i no > ethylidene) -4 ° sulfanyl piperidine (CBorhdrate of compound of Compound No.4-60) The title compound was synthesized in a 60% yield as a colorless amorphous solid using (Z) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-o-ethyl dichlorohydrate. ] -3- (2- {N- [2- (etho? -carbonyl) ethyl] -N-methylamino.} Ethylidene) piperidine obtained in Example 106 performing a reaction similar to that mentioned in Example 34. NMR with 1H (400 MHz, pyridine-d5 + DzO) d ppm: 0.77-0.89 (1H, m), 0.90-0.98 (1H, m), 0.99-1.06 (1H, m), 1.07-1.15 (1H, m), 1.12 and 1.13 (total 3H, each t, J = 7.0), 1.75- 1.88 (1H, m), 2.25-2.50 (2H, m), 2.58-3.01 (2H, m), 2.86 and 2.90 (total 3H, each s), 3.08-3.18 (2H, m), 3.31 and 3.37 (total 1H, each d, J = 12.5), 3.42-3.57 (3H, m), 3.86-4.02 (2H, m), 4.10 and 4.12 (total 2H, each q, J = 7.0), 4.61-4.66 (1H, m ), 4.87 and 4.94 (total 1H, each s), 5.71 and 5.84 (total 1H, each t, J = 7.5), 7.22-7.30 (2H, m), 7.34-7.43 (1H, m), 7.63-7.70 ( 1H, m). IR (KBr, cm-1): 2550, 1730, 1714, 1494. (Example iplo) dihydrochloride of IZ) -3424N42- (Carboxy) eti il) -N-methylaminolethyl iden) -142-cycloi prop il-1- (2-Fluorophe nDD) -2-oxo-t-yl-4-sulfanylpip ißridi na (Chloride of Compound B Compound No. 4-56) The title compound was synthesized in a 42% yield as a colorless amorphous solid using (Z) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- (2-dihydrochloride. - { N- [2- (Ethocarbonyl) ethyl] -N-methylamino} ethylidene) -4-sulfanylpiperidine obtained in Example 107 carrying out a reaction similar to that mentioned in Example 15. 1H NMR ( 500 MHz, pyridine-d5 + D20) d ppm: 0.79-0.96 (2H, m), 0.99-1.05 (1H, m), 1.06-1.13 (1H, m), 1.76-1.87 (1H, m), 2.28- 2.48 (2H, m), 2.60-2.99 (2H, m), 2.83 and 2.87 (total 3H, each s), 3.13 and 3.16 (total 2H, each t, J = 7.0), 3.30 and 3.36 (total 1H, each d, J = 12.0), 3.42-3.56 (3H, m), 3.80-3.97 (2H, m), 4.60-4.64 (1H, m), 4.87 and 4.93 (total 1H, each s), 5.65 and 5.78 (total 1H, each t, J = 7.0), 7.23-7.30 (2H, m), 7.36-7.44 (1H, m), 7.64-7.70 (1H, m). MS (FAB) m / z: 421 (M + H) +. (Example 109) (Z) 4-hydrochloride (Ac © t »lsuBfa? P) Bn) ° 142-cyclopropyl-1- (2-fluorofeniB) ° 2-oxoetip-34244-ethoxycarbonyl-1H] pyrazol-1 -yl) ethylidene piperidine (B-hydrochloride compound of Compound No.2-26) The title compound was synthesized in an 11% yield as a light yellow amorphous solid using (Z) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- (2-hydroxyethylidene) piperidine obtained in example 66 (e) and 4-etho-icarbonyl-1 H-pyrazole performing a reaction similar to that mentioned in Example 40 (to). NMR with 1H (400 MHz, CDCl 3) d ppm: 0.77-0.89 (2H, m), 0.96-1.06 (2H, m), 1.33 and 1.34 (total 3H, each t, J = 7.0), 1.81-1.89 (1H , m), 2.10-2.21 (2H, m), 2.30-2.38 (1H, m), 2.32 (3H, s), 2.79 and 2.97 (total 1H, each d, J = 12.0), 2.83-2.85 and 2.98- 3.00 (total 1H, each m), 3.15 and 3.30 (total 1H, each d, J = 12.0), 4.28 and 4.29 (total 2H, each q, J = 7.0), 4.67 and 4.71 (total 1H, each s), 4.83 (1H, bs), 4.90-5.05 (2H, m), 5.47 and 5.56 (total 1H, each t, J = 7.0), 7.09-7.18 (2H, m), 7.30-7.39 (2H, m), 7.86 and 7.87 (total 1H, each s), 7.88 and 7.90 (total 1H, each s). IR (KBr, cm "1): 1713, 1495. (Example 110) (Z) -142-Cycloprop H-142-fluorophenyl)" 2-oxoeti [] 1 342 ° (4-ethoxycarbonyl-1H-pyrazole- 1 ° il) ethylidene-4-sulfan-1-piperidine hydrochloride (Hydrochloride of compound of Compound No.2-25) • HCl The title compound was synthesized in 88% yield as a colorless amorphous solid using (Z) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-hydrochloride ? oethyl] -3- [2- (4-etho? -carbonyl-1 H-pyrazol-1-yl) ethylidene] piperidine obtained in Example 109 performing a similar reaction to that mentioned in Example 34. 1 H NMR (400 MHz, pyridine-d5) d ppm: 0.73-0.83 (2H, m), 0.97-1.04 (1H, m), 1.06-1.13 (1H, m), 1.18-1.25 (3H, m), 1.75-1.84 (1H , m), 2.20-2.36 (1H, m), 2.65-2.71 and 2.97-3.01 (total 1H, each m), 2.82-2.93 (2H, m), 3.23 and 3.40 (total 1H, each d, J = 12.0 ), 3.37 and 3.53 (total 1H, each d, J = 12.0), 4.25-4.34 (2H, m), 4.68 (1H, bs), 4.91 and 4.93 (total 1H, each s), 5.02 and 5.05 (total 2H) , each d, J = 7.0), 5.52 and 5.63 (total 1H, each t, J = 7.0), 7.17-7.25 (2H, m), 7.29-7.34 (1H, m), 7.64-7.68 (1H, m) , 8.28 and 8.29 (total 1H, each s), 8.41 and 8.44 (total 1H, each s). IR (KBr, cm "1): 2541, 1713, 1494. (Example 111) (Z) -3 ° F2- hydrochloride (4 ° Carbo-1-H-pdrazole ° 1 il) ethylidene-1-r 2- Cyclopropyl B 1- (2-fluorophenyl) -2-oxoethep 4-sulfanylpiperadine (Hydrochloride of compound of Compound No. 2-17) The title compound was synthesized in a 49% yield as a colorless amorphous solid using (Z) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] -3- [2- ( 4-etho-icarbonyl-1H-pyrazol-1-yl) ethylidene] -4-sulfanylpiperidine hydrochloride obtained in Example 110 carrying out a reaction similar to that mentioned in Example 15. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.71-0.84 (2H, m), 0.96-1.04 (1H, m), 1.06-1.15 (1H, m), 1.72-1.89 (1H, m), 2.17-2.36 (1H, m), 2.62-3.02 (3H, m), 3.22 and 3.39 (total 1H, each d, J = 12.0), 3.37 and 3.53 (total 1H, each d, J = 12.5), 4.68 (1H, bs), 4.90 and 4.92 (total 1H, each s), 4.98-5.09 (2H, m), 5.52 and 5.63 (total 1H, each t, J = 7.0), 7.16-7.35 (3H, m), 7.66 (1H, m), 8.43 and 8.45 (total 1H , each s), 8.52 and 8.55 (total 1H, each s). IR (KBr, cm'1): 3399, 2547, 1710, 1494. (Ejem ípplloo 1 11122)) cclloorrhhi ídrat or de (Z) -44 Aceta lsulffaiDiu 1 2-cid or pprrooppiiBB- -11 - ((22- -ffBluuoorrooffeenni il) -2- -oxoetill- 34244-íet oxDcarborDDDmetaD) -1H-p? Iirraazzooll - 11 - iilllleettiilliiddeenn ^ lpp iperi di na (C lhydrate of compound of Compound No.2-62) (a) (Z) -4 ° Acetoxy-3-r2- (t-butyldifeni8saniBoxi) ®tiBid®p? l ° 1 (triphenylmethyl) piperidine To a solution of (E) -4-acetoxy-3- [2- (t-butyldiphenylsilyl) i) ethylidene] -1- (triphenylmethyl) piperidine (200 mg) obtained in Example 66 (c) and 1, 1'-bis (diphenylphosphino) ferrocene (33 mg) in toluene (2 ml) was added a solution of potassium acetate (147 mg) in water (1 ml) at room temperature and then palladium acetate (7 mg). ) at 50 ° C, and the resulting mixture was stirred at the same temperature for 1.5 hours. The reaction mixture was diluted with ethyl acetate and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/19 - 1/9) to obtain 1:11 ml? Ture (143 mg. ) of the title compound and its (E) isomer as a colorless amorphous solid. This mixture was further purified using a preparative HPLC (YMC-Pack ODS-A; YMC, eluent: acetonitrile / water = 19/1) to obtain the title compound (3 mg, yield 2%) and the form (E) (73 mg, yield 37%) thereof as a colorless amorphous solid, respectively. NMR with 1H (400 MHz CDC | 3) d ppm. 1 10 (9H? S) (1.67-1.80 (1H, m), 1.77 (3H, s), 1.84-1.96 (2H, m), 2.25-2.37 (1H, m), 2.69-2.81 (1H, m), 3.07-3.16 (1H, m), 4.38 (1H, dd, J = 14.0, 4.5), 4.54 (1H, dd, J = 14.0, 7.0), 5.42 (1H, bs), 5.55 (1H, dd, J = 7.0, 4.5), 7.14-7.20 (3H , m), 7.23-7.30 (6H, m), 7.37-7.50 (12H, m), 7.71-7.77 (4H, m). . { b} (Z) -3-r2- (t-ButBldifeniisilyloxy) etBliden1 ° < a- (trifenBflm © tBa) piperidin-4-oB To a solution of (Z) -4-acetoxy-3- [2- (t-butyldiphenylsilyloxy) ethylidene] -1- (triphenylmethyl) piperidine (3.00 g) obtained in ( a) above in methanol (60 ml) was added potassium carbonate (2.00 g) under cooling with ice, and the resulting mixture was stirred at room temperature for 4 hours. The insoluble particles in the reaction mixture were removed by filtration, and the solvent was evaporated in vacuo. The residue obtained was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / hexane = 1/10) to obtain the title compound (2.02 g, 72% yield) as an amorphous solid. colorless. 1 H NMR (400 MHz, CDCl 3) d ppm: 1.06 (9H, s), 1.72-1.83 (1H, m), 1.89-2.01 (1H, m), 2.06-2.27 (1H, m), 2.40-2.65 (2H, m), 2.77-2.95 (1H, m), 4.30-4.41 (3H, m) , 5.50 (1H, t, J = 6.5), 7.12-7.20 (3H, m), 7.22-7.31 (6H, m), 7.34-7.53 (12H, m), 7.64-7.77 (4H, m). (c) (Z) -3- (2-Hydroxyethylidene) -1 ° (triphenylmetBl) piperidi? p? -4-oB The title compound was synthesized in a 96% yield as a colorless amorphous solid using (Z) - 3- [2- (t-butyldiphenylsilyl) i) ethylidene] -1- (triphenylmethyl) piperidin-4-ol obtained in (b) above carrying out a reaction similar to that mentioned in Example 1 (e). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.78-1.89 (1H, m), 1.97-2.09 (1H, m), 2.11-2.67 (3H, m), 2.79-2.95 (1H, m), 4.21 ( 1H, dd, J = 12.5, 6.5), 4.31 (1H, dd, J = 12.5, 7.5), 4.55 (1H, bs), 5.52 (1H, dd, J = 7.5, 6.5), 7.11-7.18 (3H, m), 7.21-7.30 (6H, m), 7.41-7.55 (6H, m). (d) (Z) -3- (2-Acetoxyethylidene) -14-triphenylmethane) P8Pepdon-4-oB To a suspension of (Z) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidin-4-ol (33.0 g) obtained in (c) above in dichloromethane (500 ml) was added a solution of acetic anhydride (8.0 ml) in dichloromethane (60 ml) and triethylamine (24.0 ml) under cooling with ice, and the resulting mixture was stirred at room temperature for 20 hours. The reaction mixture was diluted with dichloromethane and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/2) to obtain the title compound (30.9 g, yield 84%) as a colorless amorphous solid. 1 H NMR (400 MHz, CDCl 3) d ppm: 1.85-2.17 (5H, m), 2.36-2.45 (1H, m), 2.50-2.59 (1H, m), 2.62-2.74 (1H, m), 2.97- 3.09 (1H, m), 4.53 (1H, dd, J = 12.0, 6.0), 4.74 (1H, bs), 5.05 (1H, dd, J = 12.0, 9.0), 5.35 (1H, dd, J = 9.0, 6.0), 7.11-7.19 (3H, m), 7.21-7.29 (6H, m), 7.40-7.52 (6H, m). (e) (Z) -44t ° Butyldi? rnetinsilyloxy) -342 ° ae®toxietiB? d®p?) "1- (triphenylmethyl) piperidine The title compound was synthesized in a 68% yield as a colorless amorphous solid using (Z) -3- (2-acetoxyethylidene) -1- (triphenylmethyl) piperidin-4-ol obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (a). RMN with 1H (500 MHz, CDCl 3) d ppm: -0.13 (3H, s), -0.05 (3H, s), 0.67 (9H, s), 1.69-1.78 (1H, m), 1.84-1.93 (1H, m), 2.08 (3H, s), 2.12-2.30 (1H, m), 2.43-2.68 (2H, m), 2.79-2.98 (1H, m), 4.40 (1H, bs), 4.66-4.85 (2H, m), 5.35 (1H, t, J = 7.5), 7.08-7.18 (3H, m), 7.20-7.29 (6H, m), 7.39-7.54 (6H, m) { fj (Z) -4- (t ° ButildimetilsiBi8oxñ) - 3- (2 ° hydroxB @ tiBñd®? P?) ° 1] ° (triphenylmethyl) piperidine The title compound was synthesized in a 94% yield as a colorless amorphous solid using (Z) -4- (t-butyldimethylsilyl) i) -3- (2-aceto-ylethylidene) -1- (triphenylmethyl) ) piperidine obtained in (e) above carrying out a reaction similar to that mentioned in Example 112 (b). NMR with 1H (500 MHz, CDCl 3) d ppm: -0.09 (3H, s), -0.03 (3H, s), 0.72 (9H, s), 1.71-1.94 (2H, m), 2.21-2.85 (4H, m), 4.16-4.36 (2H, m), 4.46 (1H, bs), 5.50 (1H, t, J = 7.0), 7.09-7.18 (3H, m), 7.20-7.29 (6H, m), 7.39-7.56 (6H, m) . (a) (Z) -4- (t-Butyldimethylsilyloxy) -3-f2-r4- (etoxacarbonylm®tB) - E-α pyrazol-1-ipetiBiden} -1- (triffenylmethyl) piperidium To a solution of (Z) -4- (t-butyldimethylsilyloxy) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine (5.80 g) obtained in (f) above and p-toluenesulfonic anhydride (3.80 g) in acetonitrile (60 ml) was added tritylamine (1.94 ml) at room temperature, and the resulting mixture was stirred at the same temperature for 2.5 hours. The reaction mixture was diluted with ethyl acetate and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo to obtain (Z) -4- (t-butyldimethylsilyloxy) -3- [2- (tosyl? I) ethylidene] -1- (triphenylmethyl) piperidine (9.08 g, quantitative yield) as a brown oil . To a solution of 4- (etho? -carbonylmethyl) -1H-pyrazole (1.80 g) in N, N-dimethylformamide (40 ml) was added sodium hydride (0.56 g) under ice-cooling, and the resulting mixture was stirred at the same temperature for 20 minutes. To the reaction mixture was added a solution of (Z) -4- (t-butyldimethylsilyloxy) -3- [2- (tosyloxy) ethylidene] -1- (triphenylmethyl) piperidine obtained above in N, N-dimethylformamide ( 10 ml), and then the resulting mixture was stirred at room temperature for 1.5 hours and at 60 ° C for additionally 30 minutes. The reaction mixture was diluted with ethyl acetate and washed with water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/5 - 1/4) to obtain the title compound (3.83 g, yield 52). %) as a yellow oil. NMR with 1H (400 MHz, CDCl 3) d ppm: -0.11 (3H, s), -0.04 (3H, s), 0.70 (9H, s), 1.22-1.31 (3H, m), 1.72-1.99 (4H, m), 2.15-2.40 (1H, m), 2.53-2.79 (1H, m), 3.51 (2H, s), 4.16 (2H, q, J = 7.5), 4.51-4.57 (1H, m), 4.88- 4.98 (2H, m), 5.46 (1H, t, J = 7.0), 7.09-7.28 (15H, m), 7.42 (1H, s), 7.45 (1H, s). £ h} (Z) -342444 EthoxycarbonylrnetiB) -1H-pyrazoB "1-iMetiDid® [p ^ ° 4 hr idroxy 1- (triphen i I met i) piperidine The title compound was synthesized in a 67% yield as an amorphous solid colorless using (Z) -4- (t-butyldimethylsilyl) i) -3- { 2- [4- (etho? -carbonylmethyl) -1 H-pi-razol-1 -yl] ethylidene} -1- ( triphenylmethyl) piperidine obtained in (g) above carrying out a reaction similar to that mentioned in Example 1 (e) NMR with 1H (400 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 1.92-2.00 (1H, m), 2.08-2.23 (2H, m), 2.57-2.69 (2H, m), 2.91-3.03 (1H, m), 3.44 (2H, s), 4.14 (2H, q, J = 7.0) , 4.59-4.68 (1H, m), 4.75 (1H, m), 4.97-5.06 (1H, m), 5.48 (1H, t, J = 8.0), 7.10-7.29 (15H, m), 7.36 (1H, s), 7.37 (1H, s). (i) (Z) -44 Acetylsulfanyl) -342444 ethoxycarbonylmetBB) "1H-parazoD-1" Bpethylidene - "8 ° (triphenylmethyl) piperidine The title compound was synthesized in a yield of 88% as an amorphous coffee solid using (Z) -3-. { 2- [4- (Etho? -carbonylmethyl) -1 H -pyrazol-1-yl] ethylidene} -4-hydro? I-1- (triphenylmethyl) piperidine obtained in (h) above carrying out a reaction similar to that mentioned in Example 1 (h). NMR with 1H (400 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 1.62-1.69 (1H, m), 1.80-1.87 (1H, m), 2.06-2.12 (1H, m), 2.23 (3H, s), 2.36-2.49 (1H, m), 3.06-3.14 (1H, m), 3.38-3.44 (1H, m), 3.47 (2H, s), 4.15 (2H, q, J = 7.0 ), 4.85-4.89 (1H, m), 4.95 (2H, d, J = 6.5), 5.50 (1H, t, J = 6.5), 7.12-7.30 (15H, m), 7.37 (1H, s), 7.42 (1H, s). (S) Hydrogenated trifluoroacetate of (Z) -4- (Acetin-kaolin) -3- 244-ethoxycarbonylmethyl) -1H-pyrazole-1-yl-ethylidene paperidBE a The title compound was synthesized in an 87% yield as a brown oil using (Z) -4- (acetylsulfanyl) -3-. { 2- [4- (etho? -carbonylmethyl) -l H-pi-razol-1-yl] ethylidene} -1- (triphenyl methyl) piperidine obtained in (i) above carrying out a reaction similar to that mentioned in Example 3 (c). NMR with 1H (400 MHz, CDCl 3) d ppm: 1.26 (3H, t, J = 7.0), 2. 06-2.10 (1H, m), 2.39 (3H, s), 2.39-2.51 (1H, m), 3.10-3.21 (1H, m), 3.38-3.46 (1H, m), 3.47 (2H, s), 3.62-3.77 (2H, m), 4.12 (2H, q, J = 7.0), 4.86 (1H, m), 4.89-5.04 (2H, m), 5.80 (1H, t, J = 6.5), 7.42 (1H, s), 7.43 (1H, s). (k) IZ hydrochloride) -44AcetylsulfaniB) ° 142"Cyclopropyl ° 142" fluorophenyl) -2-oxoetin-342444etoxycarbonylmethyl) "HH-pira.goi" 1"illethylidenepiperidine The title compound was synthesized in 80% yield as a light yellow amorphous solid using hydrogenated trifluoroacetate of (Z) -4- (acetylsulfanyl) -3-. {2- 2- [4- (ethoxycarbonylmethyl) -1 H -pyrazol-1-yl] ethylidene} piperidine obtained in ) above performing a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.70-0.83 (2H, m), 0.96-1.12 (2H, m), 1.11 and 1.12 (total 3H, each t, J = 7.0), 1.81-1.93 (1H, m), 2.04-2.15 (1H, m), 2.26-2.44 (2H, m), 2.26 (3H, s), 2.48- 2.59 (1H, m), 2.90-2.98 and 3.04-3.12 (total 1H, each m), 3.31 and 3.46 (total 1H, each d, J = 12.0), 3.61 (2H, s), 4.11 and 4.12 (total 2H , each q, J = 7.0), 4.87 and 4.90 (total 1H, each s), 5.05-5.23 (3H, m), 5.65 and 5.74 (total 1H, each t, J = 6.5), 7.16-7.27 (2H, m), 7.28-7.36 (1H, m), 7.57-7.65 (1H, m), 7.69 and 7.72 (total 1H , each s), 7.73 and 7.75 (total 1H, each s). MS (FAB) m / z: 514 (M + H) +.

(Eiemol or 113) (Z) -142-Cic lopropaB-11 - (2-fl uor®1F®raiS) -2-oxoet ill-342444 ethoxycarbonylmethyl) -1H- -pyrazol-1-jeti lód® hydrochloride? p ?} = 4 = suifanil piperidine (Compound hydrochloride of Compound No. 2-61) The title compound was synthesized in a 45% yield as a colorless amorphous solid using (Z) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl ]-3-. { 2- [4- (Etho-icarbonylmethyl) -l H-pyrazol-1-yl] ethylidene} piperidine obtained in Example 112 (k) carrying out a reaction similar to that mentioned in Example 34. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.71-0.81 (2H, m), 0. 95-1.13 (2H, m), 1.11 and 1.12 (total 3H, each t, J = 7.0), 1.71-1.83 (1H, m), 2.16-2.36 (1H, m), 2.38-2.47 (1H, m) , 2.61-3.02 (3H, m), 3.18 and 3.36 (total 1H, each d, J = 12.5), 3.51 and 3.61 (total 1H, each d, J = 12.5), 3.64 (2H, s), 4.11 and 4.12 (total 2H, each q, J = 7.0), 4.63 (1H, m), 4.87-4.97 (2H, m), 5.46 and 5.58 (total 1H, each t, J = 6.5), 7.15-7.35 (3H, m ), 7.56-7.78 (3H, m). MS (FAB) m / z: 472 (M + H) +. (EiempBo 114) (Z) -3-y2-f4- (Carboxymethyl) hydrochloride (1H-yl) irazon-1-yleleideniden > -142-cyclopropyl-142-fluorofeniB) -2-oxoetin-4-sulfanylpiperidine (Hydrochloride of Compound B Compound No.

The title compound was synthesized in a 23% yield as a colorless amorphous solid using (Z) -4- (acetylsulfanyl) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl ]-3-. { 2- [4- (Etho-icarbonylmethyl) -l H-pyrazol-1-yl] ethylidene} piperidine obtained in Example 112 (k) carrying out a reaction similar to that mentioned in Example 105. 1 H NMR (400 MHz, pyridine-d 5) d ppm: 0.71-0.83 (2H, m), 0.96-1.12 (2H, m), 1.73-1.82 (1H, m), 2.19-2.35 (1H, m), 2.40-2.48 (1H, m), 2.80-3.00 (2H, m), 3.18 and 3.35 (total 1H, each d, J = 11.5), 3.35 and 3.51 (total 1H, each d, J = 11.5), 3.79 and 3.80 (total 2H, each s), 4.64 (1H, bs), 4.86-5.01 (2H, m), 4.88 and 4.91 ( total 1H, each s), 5.47 and 5.59 (total 1H, each t, J = 7.0), 7.16-7.33 (3H, m), 7.65 (1H, m), 7.78 and 7.81 (total 1H, each s), 7.83 and 7.85 (total 1H, each s). MS (FAB) m / z: 444 (M + H) +. (Example 115) (E) -44 Acetylsulfanyl) -1 ° r 2 ° C 1 cyclopropyl 2-fluorophenyl) -2-oxoetin-34244424-ethoxycarbonyl) ethyl 1 H-pirason "1" yl ethylidene) piperidine (Compound of compound No.1 -88) (a) (E) -44t-ButyldimethylsB8iyoxy) ° 3424442- (etoxacarborai!) ®tiB1 ° 1H-pyrazole-1-ii > etiBiden) ° 1- (triphenylmethyl) piperadi a The title compound was synthesized in a 64% yield as a colorless oil using (E) -4- (t-butyldimethylsilyloxy) -3- [2- (tosyloxy) ethypide] - 1- (Triphenylmethyl) piperidine obtained in Example 1 (c) and 4- [2- (ethocarbonyl) ethyl] -1H-pyrazole performing a reaction similar to that mentioned in Example 21 (a). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.06 (6H, s), 0.88 (9H, s), 1.27 (3H, t, J = 7.0), 1.82 (1H, m), 1.90-2.03 (3H, m), 2.60 (2H, t, J = 7.0), 2.86 (2H, t, J = 7.0), 3.03 (1H, bs), 3.70 (1H, bs), 3.91-3.98 (1H, m), 4.16 (2H, q, J = 7.0), 4.71-4.81 (2H, m), 5.81-5.84 (1H, m), 7. 21 (3H, m), 7.28-7.33 (9H, m), 7.40 (1H, s), 7.53 (4H, m). (b) (E) -3424442- (Ethoxycarbonyl) etip-1H-pyrazo D-1-B (tiBid (R) p)) 4-hydroxy-1- (triphenylmethi) piperidine The title compound was synthesized in a yield of 58%. % in a colorless amorphous solid using (E) -4- (t-butyldimethylsilyl] i) -3- (2- { 4- [2- (ethocarbonyl) ethyl] -1 H -pyrazole-1-yl ethylide) -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e) NMR with 1H (400 MHz, CDCl 3) d ppm: 1.23 (3H, t , J = 7.0), 1. 57-1.63 (1H, m), 1.81-1.90 (1H, m), 2.10-2.14 (1H, m), 2.34 (1H, bs), 2.56 (2H, t, J = 7.0), 2.80 (2H, t , J = 7.0), 2.84 (1H, bs), 3.42 (1H, bs), 4.01 (1H, m), 4.12 (2H, q, J = 7.0), 4.65-4.76 (2H, m), 5.75 (1H , t, J = 7.0), 7.14-7.27 (10H, m), 7.35 (1H, s), 7.48 (6H, m). (c) (E) -4- (AcetylsuifaniB) -3- (2-4-r2- (ethoxycarboniB) ethyl 1-H-pramzoB ° 1 -yl ethylidene) 1- (triphenylmethyl) piperidi a The compound was synthesized of the title in a 65% yield as a colorless oil using (E) -3- (2- {4- [2- (ethocarbonyl) ethyl] -1H-pyrazole-1-yl}. ethylidene) -4-hydro? i-1 - (triphenylmethyl) piperidine obtained in (b) above carrying out a reaction similar to that mentioned in Example 1 (h). NMR with 1H (400 MHz, CDCl 3) d ppm: 1.24 (3H, t, J = 7.0), 1. 86-1.94 (1H, m), 2.25 (3H, s), 2.31 (2H, m), 2.56 (2H, t, J = 7.0), 2. 81 (2H, t, J = 7.0), 2.86 (1H, m), 4.12 (2H, q, J = 7.0), 4.16-4.34 (3H, m), 4.58-4.71 (2H, m), 5.77 (1H , t, J = 7.0), 7.15-7.29 (10H, m), 7.36 (1H, s), 7.60 (6H, m). (d) Hydrogenated trifluoroacetate of (E) -4- (Ac (t-Bisulfanyl) -342-f4-r-ethoxycarbonyl) ethip-1H-pyrazole-1-Bl) ethylidene) pap-nino The title compound was synthesized in a yield of 23%. % as a colorless oil using (E) -4- (acetylsulfanyl) -3- (2- {4- [2- (ethocarbonyl) ethyl] -1H-pyrazol-1-yl} ethylidene) -1- (triphenylmethyl) piperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 3 (c). NMR with 1H (400 MHz, CDCl 3) d ppm: 1.25 (3H, t, J = 7.0), 2.03-2.09 (1H, m), 2.36 (3H, s), 2.39-2.47 (1H, m), 2.55 ( 2H, t, J = 7.0), 2.79 (2H, t, J = 7.0), 3.24-3.31 (1H, m), 3.41-3.49 (1H, m), 3.75 (1H, d, J = 14.0), 4.11 -4.17 (3H, m), 4.44 (1H, m), 4.63 (1H, dd, J = 15.5, 5.5), 4.83 (1H, dd, J = 15.5, 9.0), 5.93-5.96 (1H, m), 7.31 (1H, s), 7.39 (1H, s). (e) (E) -44-Acetylsulfanyl) -142-cyclopropyS 142-f8uorotr®? p) il) -2 ° oxoetin-3- (2- ^ 4-f2- (ethoxycarbonyl) ethyl- H-pirazon ° 1 -ñ eti8id®ra) piperidine The title compound was synthesized in a 67% yield as a colorless oil using hydrogenated trifluoroacetate of (E) -4- (acetylsulfani I) -3- (2-. {4- [2- ( eto? icarboni I) ethyl] -1H-pyrazol-1-yl.} ethylidene) piperidine obtained in (d) above carrying out a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.77-0.89 (2H, m), 0.99-1.07 (2H, m), 1.25 (3H, t, J = 7.0), 1.83 ( 1 H, m), 2.15 (2H, m), 2.29 and 2.30 (total 3H, each s), 2.54 (2H, t, J = 7.0), 2.55-2.64 (1 H, m), 2.68-2.76 (1 H, m), 2.78 (2H, t, J = 7.0), 2.84-2.92 and 3.12-3.18 (total 1 H, each m), 3.26-3.35 and 3.39-3.46 (total 1 H, each m), 4.14 ( 2H, q, J = 7.0), 4.28-4.35 (1H, m), 4.60-4.76 (3H, m), 5.77 (1H, m), 7.09-7.22 (2H, m), 7.27-7.42 (4H , m). (Example 116) hydrochloride of (E) ° 1 ° r 2-CicBopropin ° 1 ° (2 ° FBuor © f®naB) ° 2-oxoetip-3424442- (ethoxycarbonyl) ethylpi-1 H-pyrazoB "1 sulfanylpiperidine (Compound Hydrochloride of Compound No. B 1 - . 1 -87) The title compound was synthesized in a 74% yield as a colorless amorphous solid using (E) -4- (acetylsulfanyl) -1 - [2-cyclopropyl-1- (2-fluorophenyl) -2-oxoethyl] -3- (2- {4- [2- (ethoxycarbonyl) ethyl] -1H-pyrazol-1-yl} ethylidene) piperidine obtained in Example 115 (e) by performing a reaction similar to that mentioned in Example 34 NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.77-0.83 (2H, m), 0.99-1.06 (1H, m), 1.09-1.16 (1H, m), 1.12 (3H, t, J = 7.0), 1.74-1.83 (1H, m), 2.14-2.24 (1H, m), 2.47-2.52 (1H, m), 2.62 (2H, t, J = 7.0), 2.65 (1H, m), 2.86 (2H, t, J = 7.0), 2.83-2.99 (1H, m), 3.34 and 3.36 (total 1H, each d, J = 12.5), 3.77-3.81 (1H, m), 4.12 (2H, q, J = 7.0), 4.84-4.92 (3H, m), 4.93 and 4.95 (total 1H, each s), 5.95-5.99 (1H, m), 7.19-7.27 (2H, m), 7.28-7.36 (1H, m), 7.58 (1H, s), 7.62 (1H, s), 7.66-7.73 (1H, m). MS (FAB) m / z: 486 (M + H) +. (Example 117) hydrochloride of (Z) ° 4- (Ac.t.sub.Bu.sub.Bu.fan) 3- (2-cyanoethylidene-142-cyclopropyl-142 ° fluoroffenii) -2 ° oxoetinyl piperidine (Hydrochloride of compound Compound No.4-47 ) (a) (Z) -4- (t ° Butyldimethylsiloxy) -3- (2-cyanoethylidene) -1- (trife? p? aam®t? 8) piperidine To a solution of (Z) -4- (t-butyldimethylsilyl? !) -3- (2-hydroxyethylidene) -1- (triphenylmethyl) piperidine (10.00 g) obtained in example 112 (f) in benzene (500 ml) was added tributylphosphine (6.10 g), acetone cyanohydrin (3.60 g) ) and 1,1'-azobis (N, N-dimethylformamide) (5.20 g), and the resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium chloride, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and the residue was purified by chromatography on a silica gel column (ethyl acetate / water = 1/6) to obtain the title compound (9.27 g, 91% yield) as a colorless amorphous solid. 1 H NMR (400 MHz, CDCl 3) d ppm: 0.00-0.10 (6H, m), 0.81 (9H, s), 1.82-2.01 (2H, m), 2.15-3.02 (4H, m), 3.35-3.60 ( 2H, m), 4.40 (1H, bs), 5.29 (1H, t, J = 7.5), 7.18-7.25 (3H, m), 7.28-7.36 (5H, m), 7.46-7.59 (7H, m). (b) (Z) -342-Cyanoethylidene) -14-triphenylmethyl) piperidnm ° 4-oB The title compound was synthesized in a quantitative yield as a colorless amorphous solid using (Z) -4- (t-butyldimethylsilyl? i) -3 - (2-cyanoethylidene) -1- (triphenylmethyl) piperidine obtained in (a) above carrying out a reaction similar to that mentioned in Example 1 (e). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.86-1.97 (1H, m), 1.99-2.10 (1H, m), 2.23-2.54 (2H, m), 2.64-2.88 (2H, m), 3.37 ( 2H, d, J = 7.5), 4.50 (1H, bs), 5.30 (1H, t, J = 7.5), 7.13-7.20 (1H, m), 7.23-7.31 (7H, m), 7.42-7.52 (7H , m). (c) (Z) -4- (Acetylsulfanyl) ° 342"Cyanoetilad®)" 14trif®nBH [pp) ®tfli) piperidine The title compound was synthesized in 83% yield as a colorless amorphous solid using (Z) ) -3- (2-cyanoethylidene) -1- (triphenylmethyl) piperidin-4-ol obtained in (b) above carrying out a reaction similar to that mentioned in Example 1 (h). 1 H NMR (400 MHz, CDCl 3) d ppm: 1.54-1.64 (1H, m), 1.78- 1.85 (1H, m), 2.08 (1H, d, J = 13.0), 2.22 (3H, s), 2.34- 2.45 (1H, m), 3. 06-3.13 (1H, m), 3.28 (1H, dd, J = 18.0, 7.0), 3.41 (1H, d, J = 13.0), 3.47 (1H, dd, J = 18.0, 7.0), 4.68 (1H, m), 5.24 (1H, t, J = 7.0), 7.13-7.32 (7H, m), 7.39-7.53 (8H, m). (d) Hydrogenated trifiuoroacetate of (Z) ° 4- (AcetñBsulfanñn) -3- (2 ° cyanoethylidene) piperidine The title compound was synthesized in a 54% yield as a colorless amorphous solid using (Z) -4- (acetylsulfanil ) -3- (2-cyanoethylidene) -1- (triphenylmethyl) piperidine obtained in (c) above carrying out a reaction similar to that mentioned in Example 3 (c). 1 H NMR (400 MHz, CDCl 3) d ppm: 2.02-2.12 (1H, m), 2.36-2.47 (1H, m), 2.39 (3H, s), 3.04-3.17 (1H, m), 3.33-3.77 ( 5H, m), 4.70 (1H, bs), 5.59 (1H, t, J = 7.0). (e) (Z) -4- (Acetylsulfanyl) -342-ciapoetBid®p) "142 ° Eicotropyl" 1- (2-fluoropheni8) ° 2-oxoetiH piperidane hydrochloride The title compound was synthesized in a yield of 80% as a colorless amorphous solid using hydrogenated trifluoroacetate of (Z) -4- (acetylsulfanyl) -3- (2-cyanoethylidene) piperidine obtained in (d) above by performing a reaction similar to that mentioned in Example 1 (g). 1 H NMR (400 MHz, CDCl 3) d ppm: 0.75-0.88 (2H, m), 0.97-1.07 (2H, m), 1.27 (3H, t, J = 7.0), 1.78-1.86 (1H, m), 2.12-2.22 (2H, m), 2.28 and 2.29 (total 3H, each s), 2.49-2.62 (1H, m), 2.68-2.73 and 2.76-2.81 (total 1H, each m), 2.88 and 3.15 (total 1H , each d, J = 12.5), 3.30 and 3.41 (total 1H, each d, J = 12.5), 3.46 (2H, s), 4.15 (2H, q, J = 7.0), 4.28-4.34 (1H, m) , 4.62-4.64 and 4.67-4.70 (total 2H, each m), 4.71 and 4.74 (total 1H, each s), 5.78 (1H, t, J = 7.0), 7.07-7.17 (2H, m), 7.19-7.27 (1H, m), 7.28-7.37 (1H, m), 7.33 and 7.34 (total 1H, each s), 7.39 (1H, s). MS (FAB) m / z: 387 (M + H) +. (Example 118) (Z) -342"Carboxyethylidene) -142-CBClopro @ BD ° 142 ° fluorophenyl) -2-oxoetill-4-sulfanylpiperidine (Compound of compound No.4-13) (Z) -4- (Acetylsulfanyl) -3- (2-cyanoethylidene) -1- [2-cyclopropyl-1- (2-fluorophenyl) -2-o-oethyl] piperidine hydrochloride (48 mg) obtained in Example 117 (e) with 6N hydrochloric acid (6 ml) at room temperature and then the resulting mixture was stirred at 60 ° C for 3 hours. The reaction mixture was evaporated in vacuo, and the residue was purified using a preparative HPLC (YMC-Pack ODS-A; YMC, eluent: acetonitrile / water / acetic acid / triethylamine = 1/1 / 0.05 / 0.05) to obtain the title compound (22 mg, 56% yield) as a colorless oil. NMR with 1H (400 MHz, pyridine-d5) d ppm: 0.72-0.86 (2H, m), 0.96-1.04 (1H, m), 1.07-1.15 (1H, m), 1.70-1.84 (1H, m), 2.19-2.38 (1H, m), 2.46-2.54 (1H, m), 2.61-3.09 (2H, m), 3.30 and 3.39 (total 1H, each d, J = 14.0), 3.41-3.58 (3H, m) , 4.55 (1H, bs), 4.89 and 4.93 (total 1H, each s), 5.72 and 5.83 (total 1H, each t, J = 7.5), 7.15-7.25 (2H, m), 7.26-7.34 (1H, m ), 7.67-7.73 (1H, m). MS (FAB) m / z: 364 (M + H) +. (Test example 1) Test to confirm ®B © fecto iph? Bidor of aggregation of plaguetas in vitro Sprague-Dawley male rats (8 weeks old, Japan SLC, Inc.), 3 to 4 animals per group, were used to the proof. Platelet aggregation was measured with an automatic platelet aggregometer (MCM Hema Tracer 313M, MC Medical, Inc.) by a partially modified method of Born et al., The Journal of Physiology, Vol. 168, Section 178 (1963). A 6.3 ml sample of blood was taken from the ventral aorta of a ramus anesthetized with pentobarbital (40 mg / kg) using 3.8% (w / v) sodium citrate solution (0.7 ml) as an anticoagulant. The obtained blood containing citrate was centrifuged (230 g, 15 minutes, room temperature) to separate a platelet-rich plasma (hereinafter abbreviated as PRP). The blood after separation of PRP was further centrifuged (2,000 g, 10 minutes, room temperature) to separate a low platelet plasma (hereinafter abbreviated as PPP). After the number of blood platelets in PRP was measured with a multi-element automatic blood corpuscle counter (KX-21N, Sysme? Corporation), PPP was added to adjust the blood platelet count to 5? 1 08 / ml. After the PRP (239 μl) was pipetted in cuvettes, test compounds (1 μl) dissolved in sulphonated dimethyl (DMSO) were added to the PRP and the cuvettes were placed in the automatic platelet aggregometer. DMSO (1 μl) was added in place of the test compounds for the control group. After preliminary heating (37 ° C) for 1.5 minutes, 1 μl of adenosine 5'-diphosphate (ADP) solution (final concentration at 10 μM) was added to produce platelet aggregation. Platelet aggregation was measured for 5 minutes and the maximum platelet aggregation rate was determined. The results are shown in Table 7. (Table 7) Test compound Test example 1 (% inhibition) 10 μg / ml Compound of example 15 90 Compound of example 18 73 Compound of example 19 77 Compound of example 22 67 Compound of example 23 77 Compound of example 44 81 Compound of example 50 79 Compound of example 51 81 Compound of example 74 80 Compound of example 83 68 Compound of Example 86 82 Compound of Example 91 74 Compound of Example 111 82 The compounds of the present invention showed a considerable inhibitory effect of platelet aggregation. The compounds of the present invention are useful as an antithrombotic drug. (Test example 2) Test to confirm ®B affect to platelet aggregation ra erger ex vivo Male Sprague-Dawley rats (8 weeks old, Japan SLC, Inc.), 3 to 4 animals per group were used , for the test. Platelet aggregation was measured with an automatic platelet aggregometer (MCM Hema Tracer 31 3M, MC Medical, Inc.) by a partially modified method of Born et al. , The Journal of Physiology, Vol. 1 68, Section 1 78 (1 963). The test compounds were suspended orally in 5% gum arabic solution or in 10% dimethylacetamide / 64% polyethylene glycol 400/1 6% Tween 80 solution at a dose rate of 1 mL / kg 4 hours before taking the blood sample. Vehicle was administered 4 hours at a dose rate of 1 mL / kg before taking the blood sample for the control group. A sample of 6.3 ml of blood was taken from the ventral aorta of an anesthetized rat with pentobarbital (40 mg / kg) using 3.8% (w / v) sodium citrate solution (0.7 ml) as an anticoagulant. The citrated blood obtained was centrifuged (230 g, 15 minutes, room temperature) to separate the PRP. The blood after separation of PRP was further centrifuged (2,000 g, 10 minutes, room temperature) to separate the PPP. After the amount of blood platelets in the PRP was measured with a multi-element automatic blood corpuscle counter (KX-21N, Sysmex Corporation), PPP was added to adjust the blood platelets to 5? 108 / ml . After the PRP (240 μl) was pipetted in cuvettes, the cuvettes were placed in the automatic platelet aggregometer. After preliminary heating (37 ° C) for 1.5 minutes, 10 μl of ADP solution (final concentration 3 μM) was added to produce platelet aggregation. Platelet aggregation was measured for 5 minutes and the maximum platelet aggregation rate was determined. The results are shown in Table 8. (Table 8) Test compound Test example 1 (% inhibition) 3 mg / kg 10 mg / kg Compound of Example 13-63 Compound of Example 17-92 Compound of Example 18-74 Compound of I Example 1 9 Compound of Example I 90 Compound of I Example 22 Compound of Example I 23 Compound of I Example 24 Compound Example I 25 Compound of I Example 26 Compound of I Example 29 Compound of I Example 30 Compound of I Example 31 Compound of I Example 32 Compound of I Example 36 Compound of I Example 38 Compound of I EXAMPLE 44 61 Example I Compound 62 94 Compound of I Example 64 94 Example I Compound 66 87 Example I Compound 72 76 Compound of I Example 74 100 Compound of I Example 78 75 Compound of I Example 81 83 Compound of EXAMPLE 82 81 Compound of Example I 84 82 Compound of Example I 85 82 Compound of I Example 89 83 Example Compound 1 1 1 - 82 The compounds of the present invention showed a considerable inhibitory effect of platelet aggregation. The compounds of the present invention are useful as an antithrombotic drug. (Preparation example 1) hard capsules Each standard two-part hard gelatin capsule is filled with 1 00 mg of powdered compound of Example 1, 1 50 mg of lactose, 50 mg of cellulose and 6 mg of magnesium stearate to prepare capsules in simple unit, which are washed and then dried. (Preparation Example 2) Soft capsules A mixture of the compound of Example 2 is prepared in digestible oil, such as soybean oil, cottonseed oil and olive oil and injected into gelatin with a direct exchange pump to obtain soft capsules capsules containing 1 00 mg of an active substance, which are washed and then dried. (Preparation example 3) Tablets Tablets are prepared according to a common method using 100 mg of the compound of Example 3, 0.2 mg of colloidal silicon dioxide, 5 mg of magnesium stearate, 275 mg of crystalline microcellulose, 1 mg of starch and 98.8 mg of lactose. If desired, a coating is applied to the tablet. (Preparation example 4) Suspension A suspension is prepared in such a way that 5 ml of the suspension contains 1 00 mg of compound of finely pulverized Example 4, 1 00 mg of sodium carboxymethyl cellulose, 5 mg of sodium benzoate, 1.0 g of sorbitol solution (Japanese Pharmacopoeia) and 0.025 ml of vanillin. (Preparation Example 5) Cream A cream is prepared by mixing 1 00 mg of the compound of Example 5 finely pulverized in 5 g of a cream containing 40% white petrolatum, 3% microcrystalline wax, 1% lanolin, 5% of Span 20, 0.3% of Tween 20 and 41 .7% of water. (Preparation example 6) Mixture agent 1.5% by weight of the compound of Example 6 was the resulting mixture, stirred at 10% by weight of propylene glycol and then the volume was adjusted to a predetermined volume with water to injection, the mixture was sterilized to prepare an injectable preparation. Industrial applicability The compounds according to the present invention are chemically stable and have excellent platelet activation inhibiting activity and thrombosis inhibiting activity, and also their responses are rapid and their tocices are low. Therefore, the compounds are useful as drugs for prophylaxis, to prevent recurrence or for therapy (in particular, for therapy) of thromboembolism or diseases induced by platelet activation, such as platelet aggregation or platelet release reaction, for example, restenosis after percutaneous coronary intervention (PCI), angioplasty, endarterectomy, or stent placement; acute coronary syndromes; stable or unstable angina; myocardial infarction; atrial fibrillation; cerebral ischemic attack; cerebral stroke; atherosclerosis; cardiovascular and cerebrovascular diseases associated with diabetes mellitus, such as thromboembolism; peripheral arterial diseases; heparin-induced thrombocytopenia (HIT); thrombotic thrombocytopenic purpura (TTP); antiphospholipid antibody syndromes; venous thrombosis; and septicemia.

Claims (10)

ND1CATIONS

1 . A compound having the general formula (I) shown below, [Wherein R1 represents a hydrogen atom, an alkyl group of 1 to 6 carbon atoms which may be substituted (said substituent group represents a halogen atom or an alco? I group of 1 to 6 carbon atoms), a group cycloalkyl of 3 to 6 carbon atoms which may be substituted (said substituent group represents a halogen atom or an alkoyl group of 1 to 6 carbon atoms), an alkoxy group of 1 to 6 carbon atoms which may be substituted (said substituent group represents a halogen atom or an alkoyl group of 1 to 6 carbon atoms), or an aryl group of 6 to 10 carbon atoms which may be substituted (said substituent group represents a halogen atom, a alkyl group of 1 to 6 carbon atoms, an alkoyl group of 1 to 6 carbon atoms, a cyano group, or a nitro group); R 2 represents a hydrogen atom, a halogen atom, a carbo group, an alkoxycarbonyl group of 2 to 7 carbon atoms, a carbamoyl group, a cyano group, an alkyl group of 1 to 6 carbon atoms, a halogenated alkyl group of 1 to 6 carbon atoms, an alkyl group of 1 to 6 carbon atoms substituted by a heteroaryl group, an alkoyl group of 1 to 6 carbon atoms, a halogenated alkoxy group of 1 to 6 carbon atoms, a hydroxyl group of 1 to 6 carbon atoms, an alkoxyalkyl group of 2 to 12 carbon atoms, a formyl group, an alkanoyl group of 2 to 7 carbon atoms, a cycloalkylcarbonyl group from 4 to 7 carbon atoms, an alkylcarbamoyl group of 2 to 7 carbon atoms, a di (C 1-6) alkyl group, carbamoyl, a group of the formula R 4 -CO-CR 5 R 6 - (CH 2) m. { wherein R 4 represents a hydroxy group, an amino group, an alkyl group of 1 to 6 carbon atoms, an alkylamino group of 1 to 6 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) amino group , a hydroxyamino group, an alkoxyamino group of 1 to 6 carbon atoms or an alkoyl group of 1 to 6 carbon atoms; R5 and R6 are the same or different and each represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms; and m represents an integer from 0 to 5.}. , a group of the formula R7-CO- (CH2) rN (R8). { wherein R7 represents a hydroxy group, an amino group, an alkyl group of 1 to 6 carbon atoms, an alkylamino group of 1 to 6 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) amino group , a hydroxyamino group, an alkoxyamino group of 1 to 6 carbon atoms or an alkoyl group of 1 to 6 carbon atoms; R8 represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms; and I represents an integer from 0 to 5.}. or a sulfamoyl alkyl group of 1 to 6 carbon atoms; R3 represents a substituted alkyl group of 1 to 6 carbon atoms. { said substituent group represents an aryl group of 6 to 10 carbon atoms or an aryl group of 6 to 10 carbon atoms substituted with from 1 to 5 substituents selected from < Substituent group a >; a heterocyclyl group or a heterocyclyl group substituted with from 1 to 5 substituents selected from < Substituent group a > (said heterocyclyl groups can be substituted with from 1 to 4 o? o groups); a heteroaryl group or a heteroaryl group substituted with from 1 to 5 substituents selected from < Substituent group a >; or a substituent selected from < Substituent group ß > } , or a heterocyclyl group or a heterocyclyl group substituted with from 1 to 5 substituents selected from < Substituent group a > (said heterocyclyl groups can be substituted with from 1 to 4 o? o groups); X1, X2, X3, X4 and X5 each independently represent a hydrogen atom, a halogen atom, an amino group, a carboi group, a carbamoyl group, a cyano group, a nitro group, an alkyl group of 1 to 6 carbon atoms, a halogenated alkyl group of 1 to 6 carbon atoms, an alkoyl group of 1 to 6 carbon atoms or a halogenated alkoxy group of 1 to 6 carbon atoms; n represents an integer from 0 to 2, the < Substituent group a > is defined by a halogen atom, an amino group, a carboi group, an alkoxycarbonyl group of 2 to 7 carbon atoms, a carbamoyl group, a cyano group, a hydroyl group, a nitro group, a alkyl group of 1 to 6 carbon atoms, a halogenated alkyl group of 1 to 6 carbon atoms, an alkyl group of 1 to 6 carbon atoms substituted with heteroaryl group (s), an alkoyl group of 1 to 6 atoms of carbon, a halogenated alkoxy group of 1 to 6 carbon atoms, a hydroxyl group of 1 to 6 carbon atoms, an alkoxyalkyl group of 2 to 1 2 carbon atoms, a formyl group, an alkanoyl group of 2 to 7 carbon atoms, a cycloalkylcarbonyl group of 4 to 7 carbon atoms, an alkylamino group of 1 to 6 carbon atoms, a di (alkyl group of 1 to 6 carbon atoms) amino, an alkylcarbamoyl group from 2 to 7 carbon atoms, a carbamoyl di (alkyl of 1 to 6 carbon atoms), a group of the formula R 4 -CO-CR 5 R 6 - (CH 2) m-. { wherein R 4 represents a hydroxy group, an amino group, an alkyl group of 1 to 6 carbon atoms, an alkylamino group of 1 to 6 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) amino group , a hydroxyamino group, an alkoxyamino group of 1 to 6 carbon atoms or an alkoyl group of 1 to 6 carbon atoms; R5 and R6 are the same or different and each represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms; and m represents an integer from 0 to 5.}. and a sulfamoyl alkyl group of 1 to 6 carbon atoms; and The < Substituent group ß > is defined by a halogen atom, an amino group, a carboi group, an alkoxycarbonyl group of 2 to 7 carbon atoms, a carbamoyl group, a cyano group, a hydroyl group, a nitro group, a Alcoa group of 1 to 6 carbon atoms, a halogenoalkyl group of 1 to 6 carbon atoms, a formyl group, an alkanoyl group of 2 to 7 carbon atoms, a cycloalkylcarbonyl group of 4 to 7 carbon atoms carbon, an alkylamino group of 1 to 6 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) amino group, an alkylcarbamoyl group of 2 to 7 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) group carbon) carbamoyl, a hydroxyaminocarbonyl group, a (C1 to C6 alkoxy) aminocarbonyl group, a group of the formula R9-CO- (CH2) kN (R10) -. { wherein R 9 represents a hydroxy group, an amino group, an alkyl group of 1 to 6 carbon atoms, an alkylamino group of 1 to 6 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) amino group , a hydroxyamino group, an alkoxyamino group of 1 to 6 carbon atoms or an alkoyl group of 1 to 6 carbon atoms; R 1 0 represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms; and k represents an integer from 0 to 5.}. and a sulfamoyl alkyl group of 1 to 6 carbon atoms], salts thereof or prodrugs thereof pharmacologically acceptable.

2. A compound according to claim 1, wherein R1 represents an alkyl group of 1 to 6 carbon atoms, a halogenated alkyl group of 1 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, halogenated cycloalkyl group of 3 to 6 carbon atoms or an alkoyl group of 1 to 6 carbon atoms, salts thereof or prodrugs thereof pharmacologically acceptable.

3. A compound according to claim 1, wherein R1 represents a cycloalkyl group of 3 to 6 carbon atoms, a halogenated cycloalkyl group of 3 to 6 carbon atoms or an alco? I group of 1 to 6 carbon atoms , salts of it or prodrugs of it pharmacologically acceptable.

4. A compound according to claim 1 wherein R1 represents a cycloalkyl group of 3 to 6 carbon atoms or an alkoyl group of 1 to 6 carbon atoms, salts thereof or prodrugs thereof pharmacologically acceptable.

5. A compound according to claim 1, wherein R1 represents a cyclopropyl group or a methoi group., salts of it or prodrugs of it pharmacologically acceptable.

6. A compound according to claim 1, wherein R1 is a cyclopropyl group, prodrug salts thereof or prodrugs thereof pharmacologically acceptable.

7. A compound according to any of claims 1 to 6, wherein R2 represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms, salts thereof or prodrugs thereof pharmacologically acceptable.

8. A compound according to any of claims 1 to 6, wherein R2 represents a hydrogen atom or a methyl group, salts thereof or pharmacologically acceptable prodrugs thereof.

9. A compound according to any of claims 1 to 6, wherein R2 represents a hydrogen atom, salts thereof or prodrugs thereof pharmacologically acceptable.

10. A compound according to any of claims 1 to 9, wherein R3 represents a substituted alkyl group of 1 to 6 carbon atoms. { said substituent group represents a heterocyclyl group or a heterocyclyl group substituted with 1 or 2 substituents selected from <Substituent group a > (said heterocyclyl groups may be substituted by 1 or 2 o? o groups), a heteroaryl group or a heteroaryl group substituted with 1 or 2 substituents selected from < Substituent group a > or a substituent selected from < Substituent group ß > } , or a heterocyclyl group or a heterocyclyl group substituted with 1 or 2 substituents selected from < Substituent group > (said heterocyclyl groups may be substituted by 1 or 2 groups or?), salts thereof or pharmacologically acceptable prodrugs thereof. eleven . A compound according to any of claims 1 to 9, wherein R 3 represents a substituted alkyl group of 1 to 6 carbon atoms. { said substituent group represents a 4- to 7-membered heterocyclyl group containing at least one nitrogen atom which may be substituted with 1 or 2 substituents selected from < Substituent group a1 > (said heterocyclyl group may be substituted by a group or?), a heteroaryl group containing at least one nitrogen atom which may be substituted with 1 or 2 substituents selected from < Substituent group a1 > , a carbonyl group, an alkoxycarbonyl group of 2 to 7 carbon atoms, a cyano group, a hydroyl group, an alkoxy group of 1 to 6 carbon atoms or a group of the formula R9-CO- (CH2) kN (R10) - (wherein R9 represents a hydroyl group or an alkoyl group of 1 to 6 carbon atoms, R 0 represents an alkyl group of 1 to 6 carbon atoms, and k represents an integer from 1 to 5)} , or a 4- to 7-membered heterocyclyl group containing at least one nitrogen atom which may be substituted with a substituent selected from < Substituent group a1 > (said heterocyclyl group may be substituted by an oxo group), and The < Substituent group a1 > is a group consisting of a carbo group, an alkoxycarbonyl group of 2 to 7 carbon atoms and a group of the formula R 4 -CO-CR 5 R 6 - (CH 2) m- (wherein R 4 represents a hydro group) ilo, an amino group, an alkylamino group of 1 to 6 carbon atoms, a di (alkyl of 1 to 6 carbon atoms) amino group, a hydroxyamino group, an alkoxyamino group of 1 to 6 carbon atoms or an alco-i group of 1 to 6 carbon atoms, R5 and R6 each represent a hydrogen atom, and m represents an integer from 0 to 5), salts thereof or pharmacologically acceptable prodrugs thereof. 2. A compound according to any of claims 1 to 9, wherein R 3 represents an alkyl group substituted by 1 to 3 carbon atoms. { said substituent group represents a pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, pyrazolyl, triazolyl or fetrazolyl group which may be substituted with 1 or 2 substituents selected from < Substituent group a2 > (said pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl or piperazinyl group can be substituted by a group or?), a carbo? i group, an alkoxycarbonyl group of 2 to 4 carbon atoms, a hydrophilic group or a group of the formula R9-CO- (CH2) kN (R10) - (wherein R9 represents a hydroyl group or an alkoyl group of 1 to 3 carbon atoms, R1 0 represents an alkyl group of 1 to 3 atoms of carbon and k represents an integer from 1 to 3)} , or a pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl or piperazinyl group which may be substituted by a substituent selected from < Substituent group a2 > (said pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl or piperazinyl group may be substituted by a group or?), and The < Substituent group a2 > is a group consisting of a carbo group, an alkoxycarbonyl group of 2 to 4 carbon atoms and a group of the formula R 4 -CO-CR 5 R 6 - (CH 2) m- (wherein R 4 represents a hydro group) ilo or an alkoxy group of 1 to 3 carbon atoms, R5 and R6 each represent a hydrogen atom, and m represents an integer from 0 to 2), salts thereof or pharmacologically acceptable prodrugs thereof. 1 3. A compound according to any of claims 1 to 9, wherein R3 represents a substituted methyl or ethyl group. { said substituent group represents a pyrrolidinyl, piperidinyl, piperazinyl or pyrazolyl group which may be substituted with 1 or 2 substituents selected from <Substituent group a3 > (said pyrrolidinyl, piperidinyl or piperazinyl group may be substituted by a group or?), a carbon group or a group of the formula R9-CO- (CH2) kN (R1 0) - (wherein R9 represents a hydro group) ilo, a metho group, an etho group, R 1 0 represents a methyl group, an ethyl group or an isopropyl group, and k represents an integer from 1 to 3), and The < Substituent group a3 > is a group consisting of a carboi group, a methocarbonyl group, an ethocarbonyl group, a carboethylene group, a methocarbonylmethyl group, an ethocarbonylmethyl group, a 2- (carbohydrate) group, ethyl), a 2- (methocarbonyl) ethyl group and a 2- (ethoxycarbonyl) ethyl group, pharmacologically acceptable salts thereof or prodrugs thereof. 14. A compound according to any one of claims 1 to 1 wherein X1, X2, X3, X4 and X5 independently represent a hydrogen atom or a halogen atom, salts thereof or prodrugs thereof pharmacologically acceptable. 5. A compound according to claim 1, wherein X1 and X2 independently represent a hydrogen atom or a halogen atom; and X3, X4 and X5 represent a hydrogen atom, salts thereof or prodrugs thereof pharmacologically acceptable. 1 6. A compound according to any of claims 1 to 13 wherein X 1 represents a halogen atom; and X2, X3, X4 and X5 represent a hydrogen atom, salts thereof or prodrugs thereof pharmacologically acceptable. 7. A compound according to claim 1, wherein X1 represents a fluorine atom; and X2, X3, X4 and X5 represent a hydrogen atom, salts thereof or prodrugs thereof pharmacologically acceptable. 18. A compound according to any of claims 1 to 1 7 wherein n represents 0 or 1, salts thereof 0 prodrugs of it pharmacologically acceptable. 9. A compound according to any one of claims 1 to 17 wherein n represents 1, pharmacologically acceptable salts thereof or prodrugs thereof. 20. A compound according to any one of claims 1 to 1 wherein a prodrug which is a pharmacologically acceptable ester is formed in the sulfanyl moiety, salts thereof or prodrugs thereof pharmacologically acceptable. twenty-one . The compound according to claim 20 wherein a functional group that forms the pharmacologically acceptable ester with a sulfanyl group is an alkanoyl group of 1 to 6 carbon atoms or an arylcarbonyl group, salts thereof or prodrugs thereof pharmacologically acceptable. 22. The compound according to claim 20 wherein a functional group that forms the pharmacologically acceptable ester with a sulfanyl group is an alkanoyl group of 1 to 3 carbon atoms or a benzoyl group, salts thereof or prodrugs thereof pharmacologically acceptable. . 23. The compound according to claim 20, wherein a functional group which forms the pharmacologically acceptable ester with a sulfanyl group is an ester formed with an acetyl group, pharmacologically acceptable salts thereof or prodrugs thereof. 24. A pharmaceutical composition containing a compound according to any of claims 1 to 23, salts thereof or prodrugs thereof pharmacologically acceptable as an active ingredient. 25. A pharmaceutical composition according to claim 24, wherein the pharmaceutical composition is a composition for prophylactic or therapeutic agents for diseases related to thrombus or embolus formation. 26. Use of a compound according to any one of claims 1 to 23, pharmaceutically acceptable salts thereof or prodrugs thereof to manufacture a pharmaceutical composition. 27. Use according to claim 26, wherein the pharmaceutical composition is a composition for prophylactic or therapeutic agents for diseases related to thrombus or embolus formation. 28. Use of a compound according to any one of claims 1 to 23, salts thereof or prodrugs thereof pharmacologically acceptable for prophylactic or therapeutic agents for diseases related to thrombus or embolus formation. 29. A prophylactic or therapeutic method for diseases by administering a compound according to any one of claims 1 to 23, salts thereof or prodrugs thereof pharmacologically acceptable to warm-blooded animals in pharmacologically effective doses. 30. A method according to claim 29 wherein the diseases are diseases related to thrombus or embolus formation. 31 A method according to claim 29 or 30 wherein the warm-blooded animals are human. SUMMARY A compound represented by the following general formula (I), a pharmacologically acceptable salt thereof, or a prodrug thereof is described. (I) (In the formula, R1 represents a hydrogen atom, an optionally substituted alkyl group of 1 to 6 carbon atoms, optionally substituted cycloalkyl group of 3 to 6 carbon atoms or the like, R2 represents a hydrogen atom, a halogen atom, a carbo group, an alkoxycarbonyl group of 2 to 7 carbon atoms, a carbamoyl group, a cyano group, an alkyl group of 1 to 6 carbon atoms, a halogenated alkyl group of 1 to 6 carbon atoms; an alkyl group of 1 to 6 carbon atoms substituted with a heteroaryl group or the like; R3 represents a substituted alkyl group of 1 to 6 carbon atoms, a heterocyclyl group, or a mono- to penta-substituted heterocyclyl group; X1, X2, X3, X4 and X5 independently represent a hydrogen atom, a halogen atom, an amino group, a carboi group, a carbamoyl group, a cyano group, a nitro group, an alkyl group of 1 to 6. carbon atoms or similar; and n represents an integer of 0-2. )