MXPA06007357A

MXPA06007357A - Thiazole derivative

Info

Publication number: MXPA06007357A
Application number: MXPA/A/2006/007357A
Authority: MX
Inventors: Ohno Tetsuji; Nakasato Yoshisuke; Nakajima Takao; Sugawara Masamori; Uchida Shinichi; Nomoto Yuji; Uesaka Noriaki
Original assignee: Kyowa Hakko Kogyo Co Ltd
Priority date: 2003-12-26
Filing date: 2006-06-23
Publication date: 2006-12-13

Abstract

An adenosine A2A receptor antagonist which contains as an active ingredient either a thiazole derivative represented by the following general formula (I):(I) (wherein n is an integer of 0 to 3;R1 represents (un)substituted cycloalkyl, (un)substituted aryl, (un)substituted alicyclic heterocyclic group, or (un)substituted aromatic heterocyclic group;R2 represents halogeno, (un)substituted lower alkyl, (un)substituted aryl, (un)substituted alicyclic heterocyclic group, (un)substituted aromatic heterocyclic group, -COR8, etc.;and R3 and R4 are the same or different and each represents hydrogen, (un)substituted lower alkyl, (un)substituted aralkyl, -COR12, etc.) or a pharmacologically acceptable salt of the derivative.

Description

DERIVATIVES OF TIAZOL Field of the Invention The present invention relates to, for example, A2A adenosine receptor antagonists comprising a thiazole derivative or a pharmaceutically acceptable salt thereof as the active ingredient, etc. Background of the Invention It is known that adenosine is in broad ranges in the living body and exhibits various physiological actions in the central nervous system, cardiac muscle, kidney, lung, stomach muscle and the like by means of its receptor. . Four subtypes of adenosine receptors, Ai, A2a, A2B and A3 are known up to now. The respective selective subtype receptor antagonists and agonists are expected to exhibit their pharmaceutical effects based on the physiological meanings of the subtype and the biological distribution thereof. Among these, A2A receptors are located in the brain, especially in the striatium body thereof, and as one of its functions, the inhibition of neurotransmitter release is reported (European Journal of Pharmacology, Vol. 168, p.285, 1989). Consequently, A2A adenosine receptor antagonists can be expected as agents to prevent and / or Ref.: 173164 treat diseases associated with the A2A adenosine receptor, such as Parkinson's disease, Alzheimer's disease, progressive supranuclear palsy, AIDS encephalopathy, transmissible spongiform encephalopathy, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's chorea, multiple system atrophy, cerebral ischemia , attention deficit hyperactivity disorder, sleep disorder, ischemic heart disease, intermittent claudication, diabetes, anxiety disorders (eg, panic attack and panic disorder, phobia, obsessive-compulsive disorder, post-traumatic stress disorder, disorder of acute tension, generalized anxiety disorder, physical symptoms of anxiety or caused by substances), mood disorders (eg, depression, dysthymic disorder, circulatory mood disorder), restless legs syndrome (RLS, for its acronym in English) , drug dependence (for example, dependence on lcohol), eating disorder, epilepsy, migraine and pain of the chronic musculoskeletal system. On the other hand, a large number of compounds having thiazole backbone are known (for example, see U.S. Patents 5,314,889 and 5,189,049; Japanese Patent Application No. 335680/2003, Patent Application.

Not Examined Published Japanese No. 53566/2002, Japanese Patent Application Nos. 209284/1999 and 087490/1998; W093 / 21168, WO96 / 16650, O97 / 03058, WO01 / 52847, WO01 / 53267, WO01 / 74811, WO02 / 053156, O02 / 053161, WO02 / 094798, WO03 / 000257, WO03 / 062215, O03 / 062233, WO03 / 072554, WO03 / 075923, WO2004 / 002481, WO2004 / 014884, W02004 / 041813 and the like); and as thiazole derivatives having adenosine receptor antagonism, thiazole derivatives having adenosine A3 receptor antagonism are known (see 099/21555 and Japanese Published Unexamined Patent Application No. 114779/2001), thiazole derivatives having A2B adenosine receptor antagonism and A3 adenosine receptor antagonism (see W099 / 64418 and Patent Application Publication E.Ü.A. No. 2004-0053982), and thiazole derivatives having Al receptor antagonism adenosine and A2A adenosine receptor antagonism (see O03 / 039451). In addition, the thiazole derivatives having the furyl group in the 4-position thereof are known (see US Patent No. 6,489,476, WO02 / 03978, WO01 / 47935, WO00 / 38666, WO00 / 14095; Heterocyclic Compounds, 2002, Vol. 38, p.883; Khimiko-Farmatsevticheskii Zhurnal, 1974, Vol. 8, p.25; Journal of Medicinal Chemistry, 1970, Vol. 13, p. 638; Khimiya Geterotsiklicheskikh Soedinenii, 1969, Vol. 3, p. 498; Journal of Organic Chemistry, 1962, Vol. 27, p.

(A) (where R represents phenylmethyl, 2-furyl, 4-fluorophenyl), 2-fluorophenyl, 2,4-dichlorophenyl, 4-nitrophenyl, 2-nitrophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 2-chlorophenyl, 3-bromo-2-methoxyphenyl, 4-tert-butylphenyl, 3 methylphenyl, 4-methylphenyl, 4-methoxyphenyl, 2-methoxyphenyl or phenyl). Also, the thiazole derivatives represented by the general formula described above (A) are registered as a chemical collection in the CAS REGISTRY database (Registers Nos. 341929-13-3, 341929-11-1, 341929-09-7 , 341929-07-5, 341929-05-3, 341929-04-2, 341929-02-0, 341929-00-8, 341928-98-1, 341928-96-9, 341928-94-7, 341928 -92-5, 341928-90-3, 341928-88-9, 341928-86-7, 341928-84-5, 341928-82-3 and 341928-80-1). Description of the Invention An object of the present invention is to provide, for example, A2A adenosine receptor antagonists comprising a thiazole derivative or a pharmaceutically salt acceptable thereof as the active ingredient, and thiazole derivatives or pharmaceutically acceptable salts thereof having an A2A adenosine receptor antagonism and are useful for preventing and / or treating diseases associated with the adenosine A 2 receptor. The invention relates to the following (1) to (118): (1) An adenosine A 2 receptor antagonist comprising, as the active ingredient, a thiazole derivative represented by a general formula (I): (O.) Wherein n represents an integer from 0 to 3, Ra represents substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted heterocyclic aromatic group; R2 represents a halogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted aryl or unsubstituted, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted heterocyclic aromatic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl, -NR5R6 (wherein R5 and R6 may be the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted lower alkanoyl, substituted or unsubstituted cycloalkyl substituted, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted heterocyclic aromatic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted heterocyclic aromatic alkyl), -OR7 (in d R7 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkanoyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted heterocyclic alicyclic group, an aromatic heterocyclic group substituted or unsubstituted, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl), or -COR8 [wherein R8 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted heterocyclic aromatic group, unsubstituted or substituted alicyclic heterocyclic alkyl , substituted or unsubstituted aromatic heterocyclic alkyl -NR9R10 (wherein R9 and R10 may be the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted lower alkynyl or unsubstituted, alkanoyl substituted or unsubstituted lower alkoxy, substituted or unsubstituted lower alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted alicyclic heterocyclic group, substituted or unsubstituted heterocyclic aromatic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted heterocyclic aromatic alkyl), or -OR11 (wherein R11 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl , substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted heterocyclic aromatic group, substituted or unsubstituted substituted heterocyclic alkyl, or substituted aromatic heterocyclic alkyl or not replaced)]; and R3 and R4 may be the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted aralkyl, alicyclic heterocyclic alkyl substituted or unsubstituted, substituted or unsubstituted aromatic heterocyclic alkyl, -COR12 [wherein R12 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted lower alkynyl or not substituted, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted heterocyclic aromatic group, substituted or unsubstituted substituted heterocyclic alkyl, substituted aromatic heterocyclic alkyl or unsubstituted, -NR13R14 (wherein R13 and R14 may be the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, alkanoyl substituted or unsubstituted lower alkoxy, substituted or unsubstituted lower alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted heterocyclic aromatic group, alkyl heterozyme substituted or unsubstituted alicyclic alkyl, substituted or unsubstituted heterocyclic aromatic alkyl), or -OR15 (wherein R15 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, lower alkynyl substituted or unsubstituted, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted heterocyclic aromatic group, substituted or unsubstituted, substituted or unsubstituted heterocyclic alkyl, alkyl substituted or unsubstituted aromatic heterocyclic)]; with the proviso that, when R1 is substituted or unsubstituted phenyl and n is 0, then R2 is not 6-oxo-l, 6-dihydropyridazin-3-yl} substituted or unsubstituted, or a pharmaceutically acceptable salt thereof. (2) The A2A adenosine receptor antagonist according to the preceding (1), wherein R1 is substituted or unsubstituted aryl, or a substituted or unsubstituted heterocyclic aromatic group. (3) The A2A adenosine receptor antagonist according to the preceding (1), wherein R1 is substituted or unsubstituted aryl or a substituted or unsubstituted heterocyclic aromatic group. (4) The A2A adenosine receptor antagonist according to the preceding (1), wherein R1 is a substituted or unsubstituted monocyclic aromatic heterocyclic group. (5) The A2A adenosine receptor antagonist according to the preceding (1), wherein R1 is a substituted or unsubstituted 5-membered aromatic heterocyclic group. (6) The A2A adenosine receptor antagonist according to the preceding (1), wherein R1 is a substituted or unsubstituted 5-membered aromatic heterocyclic group containing at least one oxygen atom. (7) The A2A adenosine receptor antagonist according to the preceding (1), wherein R1 is substituted or unsubstituted furyl. (8) The A2A adenosine receptor antagonist according to any of the above (1) to (7), wherein n is 0. (9) The adenosine A2A receptor antagonist in accordance with any of the foregoing (1) ) until (8), wherein R2 is substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted heterocyclic aromatic group, substituted or unsubstituted substituted heterocyclic alkyl, aromatic heterocyclic alkyl substituted or unsubstituted, or -COR8 (wherein R8 has the same meaning as defined above). (10) The A2A adenosine receptor antagonist according to any of the above (1) to (8), wherein R2 is substituted or unsubstituted aryl. (11) The A2A adenosine receptor antagonist according to any of the above (1) to (8), wherein R2 is a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted heterocyclic aromatic group. (12) The A2A adenosine receptor antagonist according to any of the above (1) to (8), wherein R2 is a substituted or unsubstituted alicyclic heterocyclic group. (13) The A2A adenosine receptor antagonist according to any of the above (1) to (8), wherein R2 is a substituted or unsubstituted heterocyclic aromatic group. (14) The A2A adenosine receptor antagonist according to any of the above (1) to (8), wherein R2 is -COR8 (wherein R8 has the same meaning as defined above). (15) The A2A adenosine receptor antagonist according to any of the above (1) to (9) and (14), wherein R8 is a hydrogen atom, substituted or unsubstituted lower alkyl, substituted lower alkenyl or non-substituted substituted, substituted lower alkynyl or not substituted, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, "substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted heterocyclic aromatic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or heterocyclic alkyl substituted or unsubstituted aromatic (16) The A2A adenosine receptor antagonist according to any of the above (1) to (9) and (14), wherein R8 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl , a substituted or unsubstituted heterocyclic heterocyclic group, or a substituted or unsubstituted heterocyclic aromatic group (17) The A2A adenosine receptor antagonist according to any of the foregoing (1) to (9) and (14), in wherein R 8 is substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclic or substituted heterocyclic group, or a heterocyclic group substituted or unsubstituted mático. (18) The adenosine A2__ receptor antagonist according to any of the above (1) to (9) and (14), wherein R8 is substituted or unsubstituted aryl. (19) The A2A adenosine receptor antagonist according to any of the foregoing (1) to (9) and (14), wherein R is a substituted or unsubstituted heterocyclic aromatic group. (20) The A2A adenosine receptor antagonist according to any of the above (1) to (9) and (14), wherein R8 is a substituted or unsubstituted alicyclic heterocyclic group. (21) The A2A adenosine receptor antagonist according to any of the above (1) to (9) and (14), wherein R8 is a substituted or unsubstituted alicyclic heterocyclic group, containing at least one oxygen atom . (22) The A2A adenosine receptor antagonist according to any of the above (1) to (21), wherein R3 is a hydrogen atom. (23) The A2A adenosine receptor antagonist according to any of the above (1) to (21), wherein R3 is lower alkyl or aralkyl. (24) The A2A adenosine receptor antagonist according to the above (22) or (23), wherein R4 is -COR12 (wherein R12 has the same meaning as defined above). (25) The A2A adenosine receptor antagonist according to the above (22) or (23), wherein R4 is -COR12a (wherein R12a is substituted or unsubstituted lower alkyl, substituted lower alkoxy or not substituted, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic-substituted heterocyclic group, a substituted or unsubstituted heterocyclic aromatic group, substituted or unsubstituted substituted heterocyclic alkyl, or heterocyclic alkyl aromatic substituted or unsubstituted). (26) The A2A adenosine receptor antagonist according to the above (22) or (23), wherein R4 is -CHR12b (wherein R12b is substituted or unsubstituted phenyl, or a substituted or unsubstituted heterocyclic aromatic group) . (27) The A2A adenosine receptor antagonist according to the above (22) or (23), wherein R 4 is -CHR 12c (wherein R 12c is substituted or unsubstituted alicyclic heterocyclic methyl, or substituted or unsubstituted heterocyclic aromatic methyl ). (28) The A2A adenosine receptor antagonist according to the above (27), wherein R12c is substituted or unsubstituted alicyclic heterocyclic methyl. (29) The A2A adenosine receptor antagonist according to the above (22) or (23), wherein R4 is -COR12d (wherein R12d is substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclic alicyclic group, or a substituted or unsubstituted heterocyclic aromatic group). (30) The A2A adenosine receptor antagonist in accordance with the above (29), wherein R12d is a substituted or unsubstituted alicyclic heterocyclic group. (31) The A2A adenosine receptor antagonist according to the above (22) or (23), wherein R4 is -COR12e (wherein R12e is substituted or unsubstituted lower alkoxy). (32) The A2A adenosine receptor antagonist according to the above (22) or (23), wherein R4 is -COR12f [wherein R12f is -NR13R14 (wherein R13 and R14 have the same meanings as defined above , respectively)]. (33) The A2A adenosine receptor antagonist according to the above (32), wherein R13 is a hydrogen atom. (34) The A2A adenosine receptor antagonist according to the above (22) or (23), wherein R4 is -COR12g [wherein R12g is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted cycloalkyl or unsubstituted, substituted or unsubstituted aryl (with the proviso that the "site to be substituted by the substituent on the substituted aryl" which is not close to the "site to which -CO- binds to R12g in -COR12g"), aralkyl substituted or unsubstituted (with the proviso that the "site to be replaced by the substituent on the aryl portion of the substituted aralkyl" is not close to "the site to which the alkyl portion of the aralkyl links to the aryl portion thereto"), a substituted or unsubstituted heterocyclic heterocyclic group, a substituted or unsubstituted heterocyclic aromatic group (with the proviso that the "site to be substituted by the substituent on the substituted aromatic heterocyclic group" is not close to the "site to which -CO- is linked to R12g in -COR12g '), or substituted or unsubstituted aromatic heterocyclic alkyl (with the proviso that the "site to be substituted for the substituent on the aromatic heterocyclic portion of the substituted aromatic heterocyclic alkyl" is not close to the "site to which the alkyl portion of the aromatic heterocyclic alkyl is bonded to the aromatic heterocyclic portion thereof ")] (35) The A2A receptor antagonist of adenosine according to any of the foregoing (1) to (21), wherein R3 and R4 may be the same or different, and each represents -COR12 (wherein R12 has the same meaning as defined above). (36) The A2A adenosine receptor antagonist according to any of the above (1) to (21), wherein R3 and R4 may be the same or different, and each represents -C0R12a (wherein R12a has the same meaning as defined above). (37) The A2A adenosine receptor antagonist according to any of the foregoing (1) to (21), wherein R3 and R4 may be the same or different, and each represents -COR12b (wherein R12 has the same meaning as defined above). (38) The A2A adenosine receptor antagonist according to any of the above (1) to (21), wherein R3 and R4 may be the same or different, and each represents -C0R12c (wherein R12c has the same meaning as defined above). (39) The A2A adenosine receptor antagonist according to any of the above (1) to (21), wherein R3 and R4 may be the same or different, and each represents -C0R12d (wherein R12d has the same meaning as defined above). (40) The A2A adenosine receptor antagonist according to any of the foregoing (1) to (21), wherein R3 and R4 may be the same or different, and each represents -COR12e (wherein R12e has the same meaning as defined above). (41) The A2A adenosine receptor antagonist according to any of the above (1) to (21), wherein R3 and R4 may be the same or different, and each represents -COR12f (wherein R12f has the same meaning as defined above). (42) The A2A adenosine receptor antagonist according to any of the above (1) to (21), wherein R3 and R4 may be the same or different, and each represents -COR12g (wherein R12g has the same meaning as defined above). (43) The A2A adenosine receptor antagonist according to the above (1), wherein n is 0; R1 is a substituted or unsubstituted 5-membered aromatic heterocyclic group containing at least one oxygen atom; and R2 is -COR8a (wherein R8 represents a substituted or unsubstituted alicyclic heterocyclic group). (44) The A2A adenosine receptor antagonist according to the above (43), wherein R1 is substituted or unsubstituted furyl. (45) The A2A adenosine receptor antagonist according to the above (43) or (44), wherein R8a is a substituted or unsubstituted heterocyclic alicyclic group containing at least one oxygen atom. (46) The A2A adenosine receptor antagonist according to any of the above (1) to (21) and (43) to (45), wherein R3 is a hydrogen atom; and R 4 is substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted heterocyclic aromatic alkyl. (47) The A2A adenosine receptor antagonist according to any of the above (1) to (21) and (43) to (45), wherein R3 is a hydrogen atom; and R 4 is lower alkyl, aralkyl, or aromatic heterocyclic alkyl. (48) The A2A adenosine receptor antagonist according to any of the above (1) to (21) and (43) to (45), wherein R3 is a hydrogen atom; and R 4 is lower alkyl, or aralkyl. (49) The A2__ adenosine receptor antagonist according to any of the above (1) up (21) and (43) to (45), wherein R3 and R4 may be the same or different, and each represents substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted aromatic heterocyclic alkyl. (50) an agent for treating and / or preventing diseases associated with the A2A adenosine receptor comprising, as the active ingredient, a thiazole derivative according to any of the foregoing (1) to (49), or a pharmaceutically salt acceptable of it. (51) The agent for treating and / or preventing diseases according to the above (50), wherein the disease associated with the A2A adenosine receptor is Parkinson's disease. (52) A thiazole derivative represented by l. Formula (IA): (IA) [wherein R1A represents a substituted or unsubstituted 5-membered aromatic heterocyclic group containing at least one oxygen atom (excluding a group selected from 5-phosphonofuran-2-yl and 5-nitrofuran-2-yl); R12 and n have the same meanings as defined above, respectively; R3? represents a hydrogen atom; substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl, -C0R12A (where R12A has the same meaning as that of R12); and R2A represents substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group (excluding 2-furyl), alkyl substituted or unsubstituted alicyclic heterocyclic, substituted or unsubstituted aromatic heterocyclic alkyl, -NR5R6 (wherein R5 and R6 have the same meaning as defined above, respectively), -OR7 (wherein R7 has the same meaning as defined above) , or -COR8 (wherein R8 has the same meaning as defined above)], or a pharmaceutically acceptable salt thereof. (53) The thiazole derivative according to the preceding (52), wherein R1A is substituted or unsubstituted furyl, or a pharmaceutically acceptable salt thereof. (54) The thiazole derivative according to the above (52) or (53), wherein n is 0, or a pharmaceutically acceptable salt thereof. (55) The thiazole derivative according to any of the above (52) to (54), wherein R2A is substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, a substituted alicyclic heterocyclic group or unsubstituted, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl, or -COR8 (wherein R8 has the same meaning as defined above), or a pharmaceutically acceptable salt of the same. (56) The thiazole derivative according to any of the foregoing (52) through (54), wherein R2A is substituted or unsubstituted aryl, or a pharmaceutically acceptable salt thereof. (57) The thiazole derivative according to any of the foregoing (52) up to (54), wherein R2A is a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. (58) The thiazole derivative according to any of the foregoing (52) through (54), wherein R2A is a substituted or unsubstituted alicyclic heterocyclic group, or a pharmaceutically acceptable salt thereof. (59) The thiazole derivative according to any of the foregoing (52) through (54), wherein R2A is a substituted or unsubstituted aromatic heterocyclic group or a pharmaceutically acceptable salt thereof. (60) The thiazole derivative according to any of the foregoing (52) to (54), wherein R2A is -COR8 (in wherein R8 has the same meaning as defined above), or a pharmaceutically acceptable salt thereof. (61) The thiazole derivative according to the above (60), wherein R8 is a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl substituted, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl, or a pharmaceutically acceptable salt thereof. (62) The thiazole derivative according to the above (60), wherein R 8 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted aromatic heterocyclic group , or a pharmaceutically acceptable salt thereof. (63) The thiazole derivative according to the preceding (60), wherein R8 is a substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. (64) The thiazole derivative according to the previous (60), wherein R8 is a substituted or unsubstituted aryl, or a pharmaceutically acceptable salt thereof. (65) The thiazole derivative according to the preceding (60), wherein R8 is a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. (66) The thiazole derivative according to the preceding (60), wherein R8 is a substituted or unsubstituted alicyclic heterocyclic group, or a pharmaceutically acceptable salt thereof. (67) The thiazole derivative according to the preceding (60), wherein R8 is a substituted or unsubstituted alicyclic heterocyclic group containing at least one oxygen atom, or a pharmaceutically acceptable salt thereof. (68) The thiazole derivative according to the above (60), wherein R8 is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted aryl or unsubstituted, a substituted or unsubstituted alicyclic group, or a substituted or unsubstituted aromatic heterocyclic group (excluding a substituted or unsubstituted heterocyclic group having a nitrogen atom and linking to -CO- of -COR8 via the atom of nitrogen same), or a pharmaceutically acceptable salt thereof. (69) The thiazole derivative according to the preceding (68), wherein R8 is a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. (70) The thiazole derivative according to the preceding (68), wherein R8 is a substituted or unsubstituted alicyclic heterocyclic group, or a pharmaceutically acceptable salt thereof. (71) The thiazole derivative according to the preceding (68), wherein R8 is a substituted or unsubstituted alicyclic heterocyclic group containing at least one oxygen atom, or a pharmaceutically acceptable salt thereof. (72) The thiazole derivative according to any of the above (52) to (71), wherein R3A is a hydrogen atom, or a pharmaceutically acceptable salt thereof. (73) The thiazole derivative according to any of the foregoing (52) through (71), wherein R3A is lower alkyl or aralkyl, or a pharmaceutically acceptable salt thereof. (74) The thiazole derivative according to any of the above (52) to (71), wherein R3A is -COR12A (wherein R12A has the same meaning as defined above), or a pharmaceutically acceptable salt thereof. (75) The thiazole derivative according to the preceding (74), wherein R12A is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl substituted, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl, or a pharmaceutically acceptable salt thereof. (76) The thiazole derivative according to the preceding (74), wherein R12A is substituted or unsubstituted phenyl, or a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. (77) The thiazole derivative according to the previous (74), wherein R12A is substituted or unsubstituted alicyclic heterocyclic methyl, or substituted or unsubstituted aromatic heterocyclic methyl, or a pharmaceutically acceptable salt thereof. (78) The thiazole derivative according to the preceding (74), wherein R12A is substituted or unsubstituted alicyclic heterocyclic methyl, or a pharmaceutically acceptable salt thereof. (79) The thiazole derivative according to the previous (74), wherein R12A is a substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. (80) The thiazole derivative according to the preceding (74), wherein R12A is a substituted or unsubstituted alicyclic heterocyclic group, or a pharmaceutically acceptable salt thereof. (81) The thiazole derivative according to the preceding (74), wherein R12A is substituted or unsubstituted lower alkoxy, or a pharmaceutically acceptable salt thereof. (82) The thiazole derivative according to the preceding (74), wherein R12A is -NR13AR14A (wherein R13A and R14A have the same meaning as R13 and R14 defined above, respectively) or a pharmaceutically acceptable salt thereof. (83) The thiazole derivative according to the preceding (82), wherein R13A is a hydrogen atom, or a pharmaceutically acceptable salt thereof. (84) The thiazole derivative according to the previous (74), wherein R12A is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl (with the proviso that the "site to be substituted for the substituent in the aryl replaced "no is close to the "site to which -CO- is linked to R in -COR12A"), substituted or unsubstituted aralkyl (with the proviso that the "site to be substituted by the substituent on the aryl portion of the substituted aralkyl" is not close to "the site to which the alkyl portion of the aralkyl is attached to the aryl portion thereof"), a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group (with the proviso that the "site to be replaced by the substituent on the aromatic heterocyclic group "is not close to" the site to which -CO- is linked to R12A on -COR12A "), substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl (provided the that the "site to be replaced by the substituent on the aromatic heterocyclic portion of the substituted aromatic heterocyclic alkyl" is not close to the "site at which the the aromatic heterocyclic alkyl is linked to the aromatic heterocyclic portion thereof), or a pharmaceutically acceptable salt thereof. (85) The thiazole derivative according to any of the above (52) to (84), wherein R12 is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl substituted, substituted or unsubstituted aralkyl, a heterocyclic group substituted or unsubstituted alicyclic, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl, or a pharmaceutically acceptable salt thereof. (86) The thiazole derivative according to any of the foregoing (52) to (84), wherein R12 is substituted or unsubstituted phenyl, or a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof. (87) The thiazole derivative according to any of the above (52) to (84), wherein R12 is substituted or unsubstituted alicyclic heterocyclic methyl, or substituted or unsubstituted aromatic heterocyclic methyl, or a pharmaceutically acceptable salt thereof . (88) The thiazole derivative according to any of the foregoing (52) through (84), wherein R12 is substituted or unsubstituted alicyclic heterocyclic methyl, or a pharmaceutically acceptable salt thereof. (89) The thiazole derivative according to any of the above (52) to (84), wherein R12 is substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted aromatic heterocyclic group , or a pharmaceutically acceptable salt thereof. (90) The thiazole derivative according to any of the foregoing (52) through (84), wherein R12 is a substituted or unsubstituted alicyclic heterocyclic group, or a pharmaceutically acceptable salt thereof. (91) The thiazole derivative according to any of the foregoing (52) through (84), wherein R12 is substituted or unsubstituted lower alkoxy, or a pharmaceutically acceptable salt thereof. (92) The thiazole derivative according to any of the above (52) to (84), wherein R12 is -NR13R14 (wherein R13 and R14 have the same meaning as defined above, respectively), or a pharmaceutically salt acceptable of it. (93) The thiazole derivative according to the preceding (92), wherein R13 is a hydrogen atom, or a pharmaceutically acceptable salt thereof. (94) The thiazole derivative according to any of the above (52) to (84), wherein R12 is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted cycloalkyl, substituted aryl or not substituted (with the proviso that the "site to be replaced by the substituent on the substituted aryl" is not close to "the site to which -CO- is linked to R12 on -COR12"), substituted or unsubstituted aralkyl (with the condition that the "site to be substituted by the substituent on the aryl portion of the substituted aralkyl" is not close to the "site to which the alkyl portion of the aralkyl is attached to the aryl portion thereof"), a substituted or unsubstituted alicyclic heterocyclic group substituted, a substituted or unsubstituted aromatic heterocyclic group (with the proviso that the "site to be substituted by the substituent on the substituted aromatic heterocyclic group" is not close to the "site to which -CO- is linked to R12 on -COR12" ), substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl (with the proviso that the "site to be substituted for the substituent on the aromatic heterocyclic portion of the substituted aromatic heterocyclic alkyl" is not close to the which the alkyl portion of the aromatic heterocyclic alkyl is bonded to the aromatic heterocyclic portion thereof "), or a pharmaceutically acceptable salt thereof. (95) A thiazole derivative is represented by a formula (IB): (where ', B' n and R1 have the same meaning as defined above, respectively; R38 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl; R4B represents substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl; and R8B represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a heterocyclic group substituted or unsubstituted alicyclic, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl), or a pharmaceutically acceptable salt thereof. (96) The thiazole derivative according to the preceding (95), wherein R1 is substituted or unsubstituted furyl, or a pharmaceutically acceptable salt thereof. (97) The thiazole derivative according to the above (95) or (96), wherein n is 0, or a pharmaceutically acceptable salt thereof. (98) The thiazole derivative according to any of the above (95) to (97), wherein R8B is a substituted or unsubstituted alicyclic heterocyclic group, or a pharmaceutically acceptable salt thereof. (99) The thiazole derivative according to any of the above (95) to (97), wherein R8B is a substituted or unsubstituted alicyclic heterocyclic group containing at least one oxygen atom, or a pharmaceutically acceptable salt thereof . (100) The thiazole derivative according to any of the above (95) to (97), wherein R8B is substituted or unsubstituted tetrahydropyranyl, or a pharmaceutically acceptable salt thereof. (101) The thiazole derivative according to any of the above (95) to (100), wherein R3B is a hydrogen atom, or a pharmaceutically acceptable salt thereof. (102) The thiazole derivative according to the preceding (101), wherein R4B is lower alkyl, aralkyl or aromatic heterocyclic alkyl, or a pharmaceutically salt acceptable of it. (103) The thiazole derivative according to the preceding (101), wherein R4B is lower alkyl or aralkyl, or a pharmaceutically acceptable salt thereof. (104) A pharmaceutical composition comprising, as the active ingredient, a thiazole derivative according to any of the foregoing (52) through (103), or a pharmaceutically acceptable salt thereof. (105) An A2A adenosine receptor antagonist comprising, as the active ingredient, a thiazole derivative according to any of the foregoing (52) through (103), or a pharmaceutically acceptable salt thereof. (106) An agent for treating and / or preventing diseases associated with the A2A adenosine receptor comprising, as the active ingredient, a thiazole derivative according to any of the foregoing (52) through (103), or a pharmaceutically salt acceptable of it. (107) "An agent for treating and / or preventing diseases of the central nervous system comprising, as the active ingredient, a thiazole derivative according to any of the foregoing (52) through (103), or a pharmaceutically acceptable salt. (108) An agent for treating and / or preventing Parkinson's disease comprising, as the active ingredient, a thiazole derivative in accordance with any of the above (52) to (103), or a pharmaceutically acceptable salt thereof. (109) A method for treating and / or preventing diseases associated with the A2A adenosine receptor, which comprises administering an effective amount of a thiazole derivative represented by a general formula (I): (I) (wherein n, R1, R2, R3 and R4 have the same meaning as defined above, respectively), or a pharmaceutically acceptable salt thereof. (110) A method for treating and / or preventing Parkinson's disease, which comprises administering an effective amount of a thiazole derivative according to any of the foregoing (52) through (103), or a pharmaceutically acceptable salt thereof. . (111) A method for treating and / or preventing diseases associated with adenosine A2A receptor, which comprises administering an effective amount of a thiazole derivative according to any of the foregoing (52) to (103), or a pharmaceutically salt acceptable of it. (112) A method for treating and / or preventing diseases of the central nervous system, which comprises administering an effective amount of a thiazole derivative according to any of the foregoing (52) through (103), or a pharmaceutically acceptable salt of the same. (113) The use of a thiazole derivative represented by the general formula (I): (i) (wherein n, R1, R2, R3 and R4 have the same meaning as defined above, respectively) or a pharmaceutically acceptable salt thereof for the manufacture of an agent to treat and / or prevent diseases associated with the A2A adenosine receptor . (114) The use of a thiazole derivative represented by a general formula (I): (1) (wherein n, R1, R2, R3 and R4 have the same meanings as defined above, respectively) or a pharmaceutically acceptable salt thereof, for the manufacture of an A2A adenosine receptor antagonist. (115) The use of a thiazole derivative according to any of the foregoing (52) through (103) or a pharmaceutically acceptable salt thereof for the manufacture of an agent for treating and / or preventing Parkinson's disease. (116) The use of a thiazole derivative according to any of the foregoing (52) through (103) or a pharmaceutically acceptable salt thereof for the manufacture of an agent for treating and / or preventing diseases associated with the A2A receptor of adenosine (117) The use of a thiazole derivative according to any of the foregoing (52) through (103) or a pharmaceutically acceptable salt thereof for the manufacture of an agent for treating and / or preventing diseases of the central nervous system. (118) The use of a thiazole derivative according to any of the foregoing (52) through (103) or a pharmaceutically acceptable salt thereof for the manufacture of an A2A adenosine receptor antagonist. Hereinafter, the compounds represented by the general formula (I) are referred to as compounds (I), and apply the same to compounds of other formula numbers.

In the definition of each group in general formula (I), general formula (IA) and general formula (IB): (i) examples of the lower alkyl portion of lower alkyl, lower alkoxy and lower alkanoyl include linear alkyl or branched having 1 to 10 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl and decyl. (ü) Examples of the lower alkenyl include linear or branched alkenyl having 2 to 10 carbon atoms, such as vinyl, allyl, 1-propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl and decenyl. (ii) Examples of the lower alkynyl include linear or branched alkynyl having 2 to 10 carbon atoms, such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl and decynyl. (iv) Examples of the cycloalkyl include a cycloalkyl having 3 to 8 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. (v) Examples of the aryl portion of the aryl and the aralkyl include aryl having 6 to 10 carbon atoms, such as phenyl and naphthyl. (vi) Examples of the aromatic heterocyclic moiety of the aromatic heterocyclic group, the aromatic heterocyclic alkyl and the aromatic heterocyclic methyl include 5- or 6-membered monocyclic aromatic heterocyclic groups containing at least one atom selected from a nitrogen atom, an oxygen and a sulfur atom; or fused bicyclic or tricyclic ring aromatic heterocyclic groups containing at least one atom selected from a nitrogen atom, an oxygen atom and a sulfur atom in which rings of 4 to 8 members condense; such as include furyl, thienyl, pyrrolyl, pyridyl, N-oxopyridyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, benzothienyl, benzofuranyl, benzothiazolyl, benzimidazolyl. , benzothiadiazolyl, benzotriazolyl, quinolyl, isoquinolyl, quinazolinyl and furo [2, 3 ~ b] pyridyl. (vii) Examples of the monocyclic aromatic heterocyclic group include the 5- or 6-membered monocyclic aromatic heterocyclic groups described in the above examples of the aromatic heterocyclic group (vi), such as furyl, thienyl, pyrrolyl, pyridyl, N-oxopyridyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, pyrimidinyl and pyridazinyl. (viii) Examples of the 5-membered aromatic heterocyclic group include the 5-membered monocyclic aromatic heterocyclic groups described in the above examples of the monocyclic aromatic heterocyclic group (vii), such as furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, thiazolyl , isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl and oxadiazolyl. (ix) Examples of the 5-membered aromatic heterocyclic group containing at least one oxygen atom include the 5-membered monocyclic aromatic heterocyclic groups containing at least one oxygen atom of the 5-membered monocyclic aromatic heterocyclic groups in the above examples of the 5-membered aromatic heterocyclic group (viii), such as furyl, oxazolyl, isoxazolyl and oxadiazolyl. (x) Examples of the alicyclic heterocyclic moiety of the alicyclic heterocyclic group, the alicyclic heterocyclic alkyl and the alicyclic heterocyclic methyl include 3 to 6 membered monocyclic alicyclic heterocyclic groups containing at least one atom selected from a nitrogen atom, an oxygen and a sulfur atom; or bicyclic or tricyclic fused ring alicyclic heterocyclic groups containing at least one atom selected from a nitrogen atom, an oxygen atom and a sulfur atom in which the rings from 4 to 8 members are condensed; such as pyrrolidinyl, imidazolidinyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, piperidino, morpholino, thiomorpholino, oxazolinyl, dioxolanyl, dioxanyl, dioxepanyl, dihydropyridyl, tetrahydropyridyl, pyranyl, dihydropyrazyl, tetrahydropyranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, indolinyl, isoindolinyl, dihydropyridazinyl, oxyranyl, oxetanyl, oxolanyl, thiolanyl, thianyl, aziridinyl, azetidinyl, azolidinyl, perhydroxazepinyl, perhydrothiazepinyl, perhydroazepinyl, perhydroazocinyl, perhydrodiazepinyl, succinimido, phthalimido, glutarimido, 1,3-benzodioxolilo, 1,4-benzodioxanilo, 3,4-dihidro- 2H-1, 5-benzodio-xepinyl, 1,4-dioxaspiro [.5] decanyl, 1,4-dioxa-8-azaspiro [4.5] decanyl, octahydropyrrolo [1, 2-a] pyrazinyl, octahydropyrazino [2, 1 -c] [1,4] oxazinyl and octahydropyrazino [2, 1-c] [1,4] thiazinyl. (xi) Examples of the alicyclic heterocyclic group containing at least one oxygen atom include the alicyclic heterocyclic groups containing at least one oxygen atom described in the above examples of the alicyclic heterocyclic group (x), such as morpholinyl, morpholino, oxazolinyl , dioxolanil, dioxanil, dioxepanil, pyranyl, dihydropyranyl, tetrahydropyranyl, oxiranyl, oxetanyl, oxolanyl, perhydroxazepinyl, 1,3- benzodioxolyl, 1,4-benzodioxanyl, 3,4-dihydro-2H-1, 5-benzodioxepinyl, 1,4-dioxaspiro [4.5] decanyl, 1,4-dioxa-8-azaspiro [4.5] decanyl and octahydropyrazino [2] 1- c] [1,4] oxazinyl. (xii) Examples of the heterocyclic group having a nitrogen atom and linking to -CO- of -COR8 via the nitrogen atom include 5 or 6 membered monocyclic heterocyclic groups containing at least one nitrogen atom (the groups monocyclic heterocyclics can contain any other nitrogen atom, oxygen atom or sulfur atom); or bicyclic or tricyclic fused ring heterocyclic groups containing at least one nitrogen atom in which the 3 to 8 membered rings condense (the heterocyclic groups in the fused ring may contain any other nitrogen atom, oxygen atom or sulfur atom); such as 1-pyrrolyl, 1-pyrrolidinyl, morpholino, thiomorpholino, 1-pyrazolidinyl, piperidino, 1-piperazinyl, 1-ho or opiperazinyl, 1-aziridinyl, 1-azetidinyl, 1-azolidinyl, 1-perhydroazepinyl and 1-perhydroazocinyl. (xiii) Examples of the alkylene portion of the aralkyl, the aromatic heterocyclic alkyl and the alicyclic heterocyclic alkyl include linear or branched alkylene having 1 to 10 carbon atoms, such as a product by removing each hydrogen atom from the groups described in the above examples of lower alkyl (i) • (xiv) Halogen means each atom of fluorine, chlorine, bromine and iodine. (xv) Examples of the substituents (A) in the substituted lower alkyl include 1 to 3 substituents which may be the same or different, such as halogen, hydroxy, nitro, azido, amino, cyano, carboxy, formyl, lower alkoxy substituted or unsubstituted, substituted or unsubstituted lower alkanoyloxy, substituted or unsubstituted lower alkylsulphanyl, substituted or unsubstituted lower alkylamino, substituted or unsubstituted lower (alkyl) amino, substituted or unsubstituted adamantylamino, substituted or unsubstituted cycloalkyl, aryloxy substituted or unsubstituted and substituted or unsubstituted heterocyclic-oxy. In the examples of the substituents (A), the examples of the substituents (a), in the substituted lower alkoxy, the substituted lower alkanoyloxy, substituted lower alkylsulphanyl, the substituted lower alkylamino and the substituted lower (alkyl) amino include 1 to 3 substituents which may be the same or different, such as halogen, hydroxy, hydroxyimino, methoxyimino, nitro, azido, amino, cyano, carboxy, cycloalkyl, alkoxy substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkanoyloxy, substituted or unsubstituted lower alkylamino, substituted or unsubstituted lower (alkyl) amino, substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, an aromatic heterocyclic group substituted or unsubstituted, aryloxy and heterocyclic-oxy. In the examples of the substituents (a), examples of the substituents (b) in the substituted lower alkoxy, the substituted lower alkanoyloxy, the substituted lower alkylamino and the substituted lower di (alkyl) amino include 1 to 3 substituents which may be the same or different, such as halogen, hydroxy, amino, lower alkoxy, lower alkylamino, lower di (alkyl) amino, aryl, and an aromatic heterocyclic group. In the examples of the substituents (a), examples of the substituents (c) in the substituted aryl and the substituted aromatic heterocyclic group include 1 to 3 substituents which may be the same or different, such as the groups described in the examples of the substituents (b), and lower alkyl. In the examples of the substituents (a), examples of the substituents (d) in the substituted alicyclic heterocyclic group include 1 to 3 substituents which may be the same or different, such as the groups described in the examples of the substituents (b), lower alkyl and oxo. In the examples of the substituents (A), examples of the substituents (e) in the substituted adamantylamino include 1 to 3 substituents which may be the same or different, such as lower alkyl, lower alkoxy, hydroxy, oxo and formyl. In the examples of the substituents (A), examples of the substituents (f) in the substituted cycloalkyl include 1 to 3 substituents which may be the same or different such as the groups in the examples of the substituents (a), lower alkyl , oxo and formyl. In the examples of the substituents (A), examples of the substituents (g) on the substituted aryloxy and the substituted heterocyclic oxy include 1 to 3 substituents which may be the same or different, such as halogen, hydroxy, nitro, azido , amino, cyano, carboxy, formyl, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkanoyl, cycloalkyl, lower alkoxy, lower alkylsulphanyl, lower alkylsulfonyl, lower alkoxycarbonyl, lower alkylaminocarbonyl, lower di (alkyl) aminocarbonyl, lower alkylamino, lower di (alkyl) amino, aryl, an alicyclic heterocyclic group, a group heterocyclic aromatic, aryloxy and heterocyclic-oxy. In the examples of the substituents (g), examples of the substituents on the substituted lower alkyl and the substituted lower alkanoyl include 1 to 3 substituents which may be the same or different, such as the groups described in the examples of the substituents (b). In the examples of substituents (A), substituents (a), substituents (b), substituents (c), substituents (d), substituents (e), substituents (f) and substituents (g) ), examples of the lower alkyl portion of lower alkyl, lower alkoxy, lower alkanoyl, lower alkanoyloxy, lower alkylsulphanyl, lower alkylsulfonyl, lower alkoxycarbonyl, lower alkylaminocarbonyl, lower di (alkyl) aminocarbonyl, lower alkylamino and the lower di (alkyl) amino; the cycloalkyl; the aryl portion of the aryl and the aryloxy; the alicyclic heterocyclic group; the aromatic heterocyclic group; and the halogen has the same meaning as the lower alkyl (i), the cycloalkyl (iv), the aryl (v), the heterocyclic alicyclic group (x), the heterocyclic aromatic group (vi) and the halogen (xiv) are defined previously, respectively; the heterocyclic portion of the heterocyclic-oxy include groups described in the above examples of the "alicyclic heterocyclic group (x), aromatic heterocyclic group (vi) and the like, and the two lower alkyl portions of the lower di (alkyl) aminocarbonyl and the lower di (alkyl) amino can be the same or (xvi) Examples of the substituents (B) on the substituted lower alkanoyl, the substituted lower alkenyl, the substituted lower alkynyl and the substituted lower alkoxy include 1 to 3 substituents which may be the same or different, such as the groups described in the examples of the substituents (A), substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, and a substituted or unsubstituted aromatic heterocyclic group. In the examples of the substituents (B), examples of the substituents (h) in the substituted aryl and the substituted aromatic heterocyclic group include 1 to 3 substituents which may be the same or different, such as the groups described in the examples of the substituents (a) and lower alkyl. In the examples of the substituents (B), examples of the substituents (j) in the substituted alicyclic heterocyclic group include 1 to 3 substituents which may be the same or different, such as the groups described in the examples of substituents (a), lower alkyl, oxo and formyl. In the examples of the substituents (B), the substituents (h) and the substituents (j), the lower alkyl, the aryl, the heterocyclic alicyclic group and the aromatic heterocyclic group have the same meaning as the lower alkyl (i) , the aryl (v), the heterocyclic alicyclic group (x) and the aromatic heterocyclic group (vi) defined above, respectively. (xvii) Examples of the substituents (C) in the substituted cycloalkyl include 1 to 3 substituents which may be the same or different, such as the groups described in the examples of the substituents (A), lower alkyl or oxo. In the examples of the substituents (C), the lower alkyl has the same meaning as the lower alkyl (i) defined above. (xviii) Examples of the substituents (D) on the substituted aryl, the substituted phenyl, the substituted aralkyl, the substituted aromatic heterocyclic group, the substituted monocyclic aromatic heterocyclic group, the substituted 5-membered aromatic heterocyclic group, the aromatic heterocyclic group of 5 substituted members containing at least one atom of Oxygen, the substituted furyl, the substituted heterocyclic group having a nitrogen atom and is bonded to -CO- of -COR8 by means of the nitrogen atom, the substituted 6-oxo-1,6-dihydropyridazin-3-yl, the substituted aromatic heterocyclic alkyl and substituted aromatic heterocyclic methyl include 1 to 4 substituents which may be the same or different, such as halogen, hydroxy, nitro, azido, amino, cyano, carboxy, formyl, substituted or unsubstituted lower alkyl, alkanoyl substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted lower alkoxy cycloalkyl, substituted or unsubstituted lower alkanoyloxy, substituted or unsubstituted lower alkylamino, substituted lower (alkyl) amino or unsubstituted, substituted or unsubstituted lower alkylsulphanyl, substituted or unsubstituted lower alkylsulfonyl, sulfam oyl, substituted or unsubstituted lower alkylaminosulfonyl, substituted or unsubstituted lower (alkyl) aminosulfonyl, lower alkoxycarbonyl, substituted or unsubstituted lower alkylaminocarbonyl, substituted or unsubstituted lower (alkyl) aminocarbonyl, heterocyclic carbonyl, substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted aryloxy, substituted or unsubstituted heterocyclic-oxy and tri (lower) silyl. In the examples of the substituents (D), examples of the substituents on the substituted lower alkyl, the substituted lower alkenyl, the substituted lower alkynyl, the substituted lower alkanoyl, the substituted lower alkoxy, the substituted lower alkanoyloxy, the substituted lower alkylamino, lower substituted (alkyl) amino, substituted lower alkylsulfanyl, substituted lower alkylsulfonyl, substituted lower alkylaminosulfonyl, substituted lower (alkyl) aminosulfonyl, substituted lower alkoxycarbonyl, substituted lower alkylaminocarbonyl and lower di (alkyl) aminocarbonyl substituted include 1 to 3 substituents which may be the same or different, such as the groups described in the examples of substituents (a). In the examples of the substituents (D), examples of the substituents on the substituted aryl, the substituted aryloxy, the substituted aromatic heterocyclic group and the substituted heterocyclic oxy include 1 to 3 substituents which may be the same or different, such as the groups described in the examples of the substituents (g). In the examples of the substituents (D), examples of the substituents (k) on the substituted cycloalkyl and the substituted alicyclic heterocyclic group include 1 to 3 substituents which may be the same or different, such as the groups described in the examples of the substituents (a), lower alkyl and oxo. In the examples of the substituents (D) and the substituents (k), the lower alkyl portion of the lower alkyl, the lower alkanoyl, the lower alkoxy, the lower alkanoyloxy, the lower alkylamino, the lower di (alkyl) amino, the alkylsulfañyl lower, lower alkylsulfonyl, lower alkylaminosulfonyl, lower di (alkyl) aminosulfonyl, lower alkoxycarbonyl, lower alkylaminocarbonyl, lower di (alkyl) aminocarbonyl, and tri (lower) alkylsilyl; lower alkenyl; the lower alkynyl; the cycloalkyl; the aryl portion of the aryl and the aryloxy; the alicyclic heterocyclic group; the aromatic heterocyclic group and the halogen have the same meaning as the alkyl lower (i), lower alkenyl (ii), lower alkynyl (iii), cycloalkyl (iv), aryl (v), alicyclic heterocyclic group (x), aromatic heterocyclic group (vi) and halogen ( xiv), defined above, respectively; the heterocyclic portion of the heterocyclic carbonyl and the heterocyclic-oxy include the groups described in the above examples describe the heterocyclic alicyclic group (x) and aromatic heterocyclic group (vi), and the like; the two lower alkyl portions of the lower di (lower alkyl) amino, the lower di (alkyl) aminocarbonyl and the lower di (alkyl) aminosulfonyl can be the same or different; and the three lower alkyl portions of the lower tri (alkyl) silyl can be the same or different. (xix) Examples of the substituents (E) in the substituted alicyclic heterocyclic group, the substituted alicyclic heterocyclic group containing at least one oxygen atom, the substituted tetrahydropyranyl, the substituted alicyclic heterocyclic alkyl and the substituted alicyclic heterocyclic methyl include 1 to 3 substituents which may be the same or different, such as the groups described in the examples of the substituents (D) and oxo. Examples of the pharmaceutically acceptable salt of the compound (I) include pharmaceutically acceptable acid addition salts, metal salts, ammonium salts, amino acid addition salts. Examples of the pharmaceutically acceptable addition salts of the compounds (I) include inorganic acid addition salts such as chlorohydrate, sulfate, nitrate and phosphate and organic acid addition salts such as acetate, maleate, fumarate and citrate. Examples of the pharmaceutically acceptable metal salts include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts, such as magnesium salt and calcium salt, aluminum salt and zinc salt. Examples of pharmaceutically acceptable salts include ammonium and tetramethylammonium. Examples of the pharmaceutically acceptable organic amine addition salts include a morpholine or piperidine addition salt. Examples of the pharmaceutically acceptable amino acid addition salts include lysine addition salt, glycine, phenylalanine, aspartic acid or glutamic acid. Examples of diseases associated with the adenosine A2 receptor, which can be treated and / or prevented by the adenosine A2A receptor antagonist of the present invention, include Parkinson's disease, Alzheimer's disease, progressive supernuclear palsy, AIDS encephalopathy. , transmissible spondiform encephalopathy, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's chorea, multiple system atrophy, cerebral ischemia, hyperactive attention deficit disorder, sleeping disorders, ischemic heart disease, intermittent claudication, diabetes, anxiety disorders, (for example, panic disorder, panic, phobia, obsessive-compulsive disorder, post-traumatic stress disorder, acute tension disorder, generalized anxiety disorder, physical symptoms of anxiety or caused by substances), mood disorders (eg, depression, dysthymic disorder, circulatory disorder of humor), restless legs syndrome (RLS), dependence on drugs (for example, alcohol dependence), eating disorders, epilepsy, migraine, pain of the chronic musculoskeletal system and the like. The processes for preparing the compounds (I) are described below. In the following production processes, when the groups are defined under changes under the reaction conditions or are not available to carry out the processes, the desired compounds can be produced by the methods generally used in synthetic organic chemistry, such as protection of the functional groups, removal of protective groups and the like [e.g., T. Greene, Protective Groups in Organic Synthesis, third edition, John Wiley & Sons Inc. (1999)]. If necessary, the order of the reaction steps, such as the introduction of a substituent, can be changed. The compounds (I) can be produced according to the following processes. < Production Method 1 > Among the compounds (I), compounds (la) in which R3 and R4 are hydrogen atoms; the compounds (Ib) in which R3 is a hydrogen atom, and R4 is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted aralkyl, substituted aromatic heterocyclic alkyl or not replaced or -COR12 (where R12 has the same meaning as defined above); and the compounds (le) in which R3 and R4 may be the same or different, and each represents substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aromatic heterocyclic alkyl or -COR12 (wherein R12 has the same meaning as defined above) can be produced, for example, in accordance with the method described in Japanese Published Unexamined Patent Applications Nos. 155871/1993, 193281/1999 or the like, or methods similar to these. Briefly, these can be produced according to the following stages: (Ib) (le) [in the formulas, R1, R2 and n have the same meaning as defined above, respectively; x represents a chlorine atom, a bromine atom or an iodine atom; R3a and R4a may be the same or different in the definition of the above R3 and R4, and each represents substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted aralkyl, heterocyclic alkyl aromatic substituted or unsubstituted, or -COR12 (where R12 has the same meaning as defined above). ] Step 1: The compound (III) can be produced by reacting the compound (II), which is commercially available or which can be obtained, for example, in accordance with the method described in W003 / 35639, Unexamined Patent Application Published Japanese No. 193281/1999 or the like, or methods similar to these, with 1 to 200 equivalents, preferably 1 to 5 equivalents of a halogenating agent in the absence of a solvent or in a solvent inert to the reaction, at a temperature between - 30 ° C and 150 ° C, preferably at a temperature between 0 ° C and 100 ° C, for 5 minutes up to 48 hours. Examples of the halogenating agent include chlorine, bromine, iodine, N, N, N, N-tetra-n-butylammonium tribromide and pyridinium tribromide. The solvent inert to the reaction is not specifically limited, and examples thereof include acetone, 1,4-dioxane, acetonitrile, chloroform, dichloromethane, tetrahydrofuran (THF), ethyl acetate, N, N-dimethylformamide (DMF), acid acetic and water. These can be used in the present either alone or in a combination. Step 2: The compound (la) can be produced by reacting the compound (III) with 1 to 20 equivalents of thiourea in a solvent inert to the reaction at a temperature between - ° C and 150 ° C, preferably at a temperature between room temperature and 100 ° C, for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited and examples thereof include toluene, hexane, THF, DMF, ethanol and acetonitrile. These can also be used in the present either alone or in a combination. Step 3: The compound (Ib) can be produced by reacting the compound (III) with 1 to 100 equivalents of R ^ X1 (wherein Ra has the same meaning as defined above, X1 has the same meaning as X defined above), in the absence of a solvent or in a solvent inert to the reaction, optionally in the presence of 1 to 100 equivalents of a base, at a temperature between -30 ° C and 150 ° C for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited, and examples thereof include acetonitrile, dichloromethane, 1,2-dichloroethane, chloroform, 1,2-dimethoxyethane, DMF, N, N-dimethylacetamide (DMA), 1,4- dioxane, THF, diethyl ether, diisopropyl ether, benzene, toluene, xylene, pyridine, N, N-dimethylimidazolidinone (DMI), N-methylpyrrolidone (NMP) and sulforane. These can be used in the present either alone or in a combination.

Examples of the base include pyridine, triethylamine, diisopropylethylamine, N-methylmorpholine, N-methylpiperidine, 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), N, N-dimethylaminopyridine (DMAP), potassium acetate , potassium carbonate, cesium carbonate, sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, lithium hydroxide, potassium hydroxide and potassium phosphate. These can be used in the present either alone or in a combination of two or more. Step 4: The compound (le) can be produced by reacting the compound (Ib) with 1 to 100 equivalents of R3aX2 (wherein R3a has the same meaning as defined above, X2 has the same meaning as X defined above), in the absence of a solvent or in a solvent inert to the reaction, optionally in the presence of 1 to 100 equivalents of a base, at a temperature between -30 ° C and 150 ° C for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited and examples thereof include acetonitrile, dichloromethane, 1,2-dichloroethane, chloroform, 1,2-dimethoxyethane, DMF, DMA, 1,4-dioxane, THF, diethyl ether, diisopropyl. ether, benzene, toluene, xylene, pyridine, DMI, NMP and sulforane. These can also be used in the present either alone or in a combination.

Examples of the base include pyridine, triethylamine, diisopropylethylamine, N-methylmorpholine, N-methylpiperidine, DBU, DMAP, potassium acetate, potassium carbonate, cesium carbonate, sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, hydroxide of lithium, potassium hydroxide and potassium phosphate. These may also be used in the present either alone or in a combination of two or more. < Production Method 2 > Among Compounds (I), Compounds (Ib-i) in which R3 is a hydrogen atom and R4 is -COR12 (wherein R12 has the same meaning as defined above) can also be produced in accordance with the next step : (ta) (lb-) (in the formulas, R1, R2, R12 and n have the same meaning as defined above, respectively.) Step 5: The compound (Ib-i) can be produced by reacting the compound (s) with 1 to 100 equivalents of (R12CO) 20 (where R12 has the same meaning as defined above) or R12C0C1 (where R12 has the same meaning as defined above), in the absence of a solvent or in a solvent inert to the reaction, optionally in the presence of 1 to 100 equivalents of a base, at a temperature between -30 ° C and 150 ° C for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited, and examples thereof include acetonitrile, dichloromethane, 1,2-dichloroethane, chloroform, 1,2-dimethoxyethane, DMF, DMA, 1,4-dioxane, THF, diethyl ether, diisopropyl ether, benzene, toluene, xylene, pyridine, DMI, NMP and sulforane. These can also be used in the present either alone or in a combination. Examples of the base include pyridine, triethylamine, diisopropylethylamine, N-methylmorpholine, N-methylpiperidine, DBU, DMAP, potassium acetate, potassium carbonate, cesium carbonate, sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, hydroxide of lithium, potassium hydroxide and potassium phosphate. These can be used in the present either only in a combination of two or more. As another method for this, the compound (Ib-i) can also be produced by reacting the compound (la) with 1 to 50 equivalents of R12C00H (wherein R12 has the same meaning as defined above) in a solvent inert to the reaction, in the presence of 1 to 30 equivalents of a condensing agent, optionally in the presence of 1 to 30 equivalents of an appropriate additive, at a temperature between -30 ° C and 100 ° C for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited and examples thereof include acetonitrile, dichloromethane, 1,2-dichloroethane, chloroform, 1,2-dimethoxyethane, DMF, DMA, 1,4-dioxane, THF, diethyl ether, diisopropyl ether, benzene, toluene, xylene, pyridine, - DMI, NMP, sulforane and Water. These can be used in the present either alone or in a combination. Examples of the condensing agent include dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide, N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide (EDC), EDC chlorohydrate, benzotriazol-1-yltris (dimethylamino) phosphonium hexafluorophosphate (BOP), hexafluorophosphate of benzotriazol-1-yltripyrrolidinophosphonium (PyBOP) and diphenylphosphorylazide (DPPA). Examples of the additive include 1-hydroxybenzotriazole hydrate and triethylamine. These can also be used either alone or in a combination. <; Production Method 3 > Among the compounds (I), Compounds (Ib-ii) in which R3 is a hydrogen atom, and R4 is -C0R12h [wherein R12h is in the definition of the above R12 and represents a substituted or unsubstituted alicyclic heterocyclic group replaced having a nitrogen atom and linking to -CO- of -COR12 via the nitrogen atom, -NR13R14 (wherein R13 and R14 have the same meaning as defined above, respectively) or -OR15 (wherein R15 has the same meaning as defined above)] may be produced in accordance with the following steps: (in the formulas R1, R2, R12h and n have the same meaning as defined above, respectively.) Step 6: The compound (IV) can be prepared from the compound according to the method described in Lecture of Experimental Chemistry (4th. ed.). Vol. 20, pp. 473-483, by the Chemical Society of Japan, Maruzen, 1992, or methods similar to these. Briefly, the compound (IV) can be produced by reacting the compound (la) with 1 to 20 equivalents of phosphene or one equivalent of phosphene in the absence of a solvent or in a solvent inert to the reaction, optionally in the presence of up to 100 equivalents of a base, at a temperature of -30 ° C and 150 ° C for 5 minutes up to 72 hours.

The solvent inert to the reaction is not specifically limited, and examples thereof include acetonitrile, methanol, ethanol, dichloromethane, chloroform, 1,2-dichloroethane, 1,2-dimethoxyethane, DMF, DMA, 1,4-dioxane, THF, diethyl ether, diisopropyl ether, benzene, toluene, xylene, DMI, NMP, sulforane and water. These can be used in the present either alone or in a combination. Among these, DMF or DMA are preferred. Examples of the equivalent phosgene include triphosgene and 1,1 '-dicarbonylimidazole (CDl). Examples of the base include triethylamine, diisopropylethylamine, DBU, potassium carbonate and sodium hydroxide. Step 7: The compound (Ib-ii) can be produced by reacting the compound (IV) with 1 to 200 equivalents of HR12h (wherein R12h has the same meaning as defined above), in the absence of a solvent or in a solvent inert to the reaction, optionally in the presence of 1 to 100 equivalents of a base, at a temperature between -30 ° C and 150 ° C for 5 minutes up to 72 hours. The solvent inert to the reaction is not specifically limited and examples thereof include acetonitrile, dichloromethane, chloroform, 1,2-dichloroethane, 1,2-dimethoxyethane, DMF, DMA, 1,4-dioxane, THF, diethyl ether, diisopropyl ether, benzene, toluene, xylene, DMI, NMP, sulforane and water. These can be used in the present either alone or in a combination. Among these, DMF or DMA are preferred. Examples of the base include triethylamine, diisopropylethylamine and DBU. < Production Method 4 > The amount of the compounds (I), Compounds (Id) in which n is 0 and R2 is R2a [R2a is in the definition of the above R2, and represents a substituted or unsubstituted alicyclic heterocyclic group having a nitrogen atom and it is linked to the thiazole ring by means of the nitrogen atom, or -NR5R6 (wherein R5 and R6 have the same meaning as defined above, respectively)] can be produced according to the following steps: (V) (la-í) (| d-i) Stage 10 RR R22aaX 's sHH RR4433 EEttaappaa 1111. (l -i) (Id-iii) (In the formulas, R1, R2a, R3a and Ra have the same meaning as defined above, respectively.) Step 8: The compound (Ia-i) can be produced, for example, according to the method described in J. Chem. Soc., P. 114, 1947 or methods similar to these, by using the compound (V) which is commercially available or which can be obtained, for example, according to the method described in J. Am. Chem. Soc., Vol. 72, p. 3722, 1953 or method similar to these. Briefly, the compound (Ia-i) can be produced by reacting the compound (V) with 1 to 20 equivalents of a brominating agent in a solvent inert to the reaction at a temperature between -30 ° C and the boiling point of the solvent used, for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited, and examples thereof include dichloromethane, chloroform and 1,2-dichloroethane. These can be used in the present either alone or in a combination. Examples of the brominating agent include N-bromosuccinimide, bromine and N, N, N, N-tetra-n-butylammonium bromide. Step 9: Among the compounds (Id), the Compounds (Id-i) in which R3 and R4 are hydrogen atoms can be produced according to, for example, the method described in EP518731 or methods similar to these, by using the compound (Ia-i). Briefly, the compound (Id-i) can be produced by reacting the compound (Ia-i) with 1 to 200 equivalents of HR2a (wherein R2a has the same meaning as defined above) in the absence of a solvent or in a solvent inert to the reaction, optionally in the presence of 1 to 100 equivalents of a base, at a temperature between -30 ° C and 150 ° C for 5 minutes up to 72 hours. The solvent inert to the reaction is not specifically limited, and examples thereof include acetonitrile, methanol, ethanol, dichloromethane, chloroform, 1,2-dichloroethane, 1,2-dimethoxyethane, DMF, DMA, 1,4-dioxane, THF , diethyl ether, diisopropyl ether, benzene, toluene, xylene, DMI, NMP, sulforane and water. These can be used in the present either alone or in a combination. Among these, DMF or DMA are preferred. Examples of the base include triethylamine, diisopropylethylamine, DBU, potassium carbonate and sodium hydroxide. Step 10: Among the compounds (Id), the Compounds (Id-ii) in which R3 is a hydrogen atom and R4 is R4a (R4a has the same meaning as defined above) can be produced in a manner similar to that in Stage 3 of Production Method 1, by using the compound (Id-i). Step 11: Among the compounds (Id), the Compounds (Id-iii) in which R3 and R4 are R3a (R3a has the same meaning as defined above) and R4a (R4a has the same meaning as defined above), respectively, can produced in a manner similar to that in Step 4 of Production Method 1, by using the compound (Id-ii). < Production Method 5 > Among the compounds (I), the Compounds (le) in which n is 0 and R2 is formyl, and the compounds (If) in which n is 1 and R2 is -NR5R6 (wherein R5 and R6 have the same meaning as defined above, respectively) may be produced in accordance with the following steps: (la-i) (VI) (Vil) le-iii) (In the formulas, R1, R3, R4, R3a, R4a, R5 and R6 have the same meaning as defined above, respectively, P represents a protective group, and examples of the protective group include tert-butoxycarbonyl (Boc group), benzyloxycarbonyl (group Z), benzyl, acetyl or benzoyl. Step 12: The compound (VI) can be produced in a manner similar to methods for introducing a protecting group into an amino group, for example, as described in Protective Groups in Organic Synthesis, by TW Greene, John Wiley & Sons Inc., 1981, for using the compound (Ia-i) obtained in Step 8 of Production Method 4. For example, among the Compounds (VI), the Compounds (Vl-i) in which P is a group Boc can be produced by reacting the compound (Ia-i) with 1 to 30 equivalents of di-tert-butyl bicarbonate in a solvent inert to the reaction, optionally in the presence of 1 to 30 equivalents of a base, at a temperature between -30 ° C and boiling point of the solvent used, for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited, and examples thereof include 1,2-dimethoxyethane, DMF, dioxane, THF, diethyl. ether, diisopropyl ether, dichloromethane, chloroform, 1,2-dichloroethane, benzene, toluene, xylene, pyridine, NMP, DMI, sulforane and water. These can be used in the present either alone or in a combination. Examples of the base include pyridine, triethylamine, diisopropylethylamine, DBU, DMAP, N-methylmorphine, N-methylpiperidine, potassium acetate, potassium carbonate, cesium carbonate, sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, lithium hydroxide, potassium hydroxide and potassium phosphate. These can be used either alone or in a combination of two or more. Step 13: The compound (VII) can be produced by reacting the compound (VI) with 1 to 100 equivalents of a formylating agent in a solvent inert to the reaction in the presence of 1 to 20 equivalents of a base, at a temperature between -78 ° C and room temperature, for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited, and examples thereof include THF, diethyl ether, 1,4-dioxane, 1,2-dimethoxyethane and hexane. These can be used in the present either alone or in a combination. Examples of the formylating agent include DMF, N- methyl-N-phenylformamide, N-methyl-N- (2-pyridyl) formamide and morpholinformamide. Among these, DMF are preferred. Examples of the base include lithium diisopropylamide, lithium bis (trimethylsilyl) amide, methylthio, n-butylithium, lithium hydride, sodium hydride, potassium hydride, methylmagnesium bromide, ethylmagnesium bromide, and isopropylmagnesium chloride. These can be used either alone in a combination of two or more. Step 14: Among Compounds (le), Compounds (Ie-i) in which R3 and R4 are hydrogen atoms, can be produced in a manner similar to the methods for removing a protecting group, for example, as described in Protective Groups in Organic Synthesis, by TW Greene, John Wiley & Sons Inc., 1981, by using the compound (VII). For example, the compound (Ie-i) in which P is a Boc group can be produced by reacting the Compound (VII) with 1 equivalent to an excessive large amount of an acid in the absence of a solvent or in a solvent inert to the reaction, at a temperature between -30 ° C and 150 ° C for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited, and examples thereof include dichloromethane, chloroform, 1,2-dichloroethane, methanol, ethanol, THF, acetate of ethyl and water. These can be used in the present either alone or in a combination. Examples of the acid include trifluoroacetic acid, hydrochloric acid and sulfuric acid. Step 15: Among Compounds (le), Compounds (Ie-ii) in which R is a hydrogen atom and R is R 4a R 4a has the same meaning as defined above) can be produced in a manner similar to that in Step 3 of Production Method 1, by using the compound (Ie-i). Step 16: Among Compounds (le), Compounds (Ie-iii) in which R3 is R3a (R a has the same meaning as defined above) and R4 is R4a R 4a has the same meaning as defined above) can be produced in a manner similar to that in Step 4 of Production Method 1, by using the compound (Ie-ii). Step 17: Compound (If) can be produced by reacting Compound (Ie-i). Compound (Ie-ii) or Compound (Ie-iii) with 1 to 200 equivalents of HNR5R6 (where R5 and R6 have the same meaning) as defined above, respectively) in a solvent inert to the reaction in the presence of 1 to 50 equivalents of a reducing agent, at a temperature between -30 ° C and the boiling point of the solvent used, for 5 minutes up to 48 hours . Examples of the reducing agent include sodium triacetoxyborohydride, sodium borohydride and sodium cyanoborohydride. Among these, sodium triacetoxyborohydride is preferred. The solvent inert to the reaction is not specifically limited, and examples thereof include methanol, ethanol, dichloromethane, chloroform, 1,2-dichloroethane, THF, 1,4-dioxane, diethyl ether, diisopropyl ether, benzene, toluene, xylene, DMF and water. These can be used in the present either alone or in a combination. < Production Method 6 > Among Compounds (I), Compounds (Ih) in which R2 is -COOH, and Compounds (Ii) in which R2 is -C0R8b [wherein R8b in the definition of the above R8, and represents a heterocyclic group substituted or unsubstituted alicyclic having a nitrogen atom and linked to ~CO- of -COR8 via the nitrogen atom, or -NR9R10 (wherein R9 and R10 have the same meaning as defined above, respectively)] they can be produced according to the following stages: Cß) (lh) ... (») (In the formulas, R1, R3, R4, R8b and n have the same meaning as defined above, respectively; Rlla is in the definition of the above R11, and represents lower alkyl or benzyl.) Step 18: Compound (Ih) can be produced, for example, in a manner similar to the method for removing a protective group as described in Protective Groups in Organic Synthesis, by TW Greene, John Wiley & amp;; Sons Inc., 1981, by using Compound (Ig) in which R2 is -COORlla (wherein Rlla has the same meaning as defined above) the amount of the compounds (I) obtained in accordance with Production Method 1 For example, Compound (Ih) in which Rlla is methyl or ethyl can be produced by treating the compound (Ig) with 1 equivalent to an excessive large amount of a base in a solvent containing water, at a temperature between 0 ° C and the boiling point of the solvent used for 5 minutes up to 48 hours. The solvent is not specifically limited, and examples thereof include methanol, ethanol, propanol, THF, 1,4-dioxane, 1,2-dimethoxyethane, toluene, dichloromethane and DMF.

These can be used in the present either alone or in a combination. Examples of the base include sodium hydroxide, potassium hydroxide and lithium hydroxide. The compound (Ih) in which Rlla is tert-butyl, the compound (Ih) can be produced by treating the compound (Ig) with 1 equivalent to a large excess amount of an acid in the absence of a solvent or in an inert solvent to the reaction, at a temperature between -30 ° C and 100 ° C for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited, and examples thereof include methanol, ethanol, propanol, THF, 1,4-dioxane, 1,2-dimethoxyethane, toluene, ethyl acetate, dichloromethane, DMF and water. These can be used in the present either alone or in a combination. Examples of the acid include trifluoroacetic acid, hydrochloric acid and sulfuric acid.

Step 19: The compound (Ii) can be produced by reacting the compound (Ih) with 1 to 100 equivalents of HR8b (wherein R8b has the same meaning as defined above) in the absence of a solvent or in a solvent inert to the reaction in the presence of 1 to 30 equivalents of an appropriate condensed agent and optionally in the presence of 1 to 30 equivalents of an appropriate additive. at a temperature between -30 ° C and 100 ° C for 5 minutes up to 72 hours. The solvent is not specifically limited, and examples thereof include acetonitrile, dichloromethane, 1,2-dichloroethane, chloroform, 1,2-dimethoxyethane, DMF, DMA, 1,4-dioxane, THF, diethyl ether, diisopropyl ether, benzene , toluene, xylene, pyridine, DMI, NMP, sulforane and water. These can be used in the present either alone or in a combination. Examples of the condensed agent include DCC, diisopropylcarbodiimide, EDC, EDC chlorohydrate, BOP, PyBOP and DPPA. Examples of the additive include 1-hydroxybenzotriazole hydrate and triethylamine, and may also be used either alone or in a combination. < Production Method 7 > Among Compounds (I), Compounds (Ij) in which R2 is -C0R8c (wherein R8c is in the definition of the above R8, and represents substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted alicyclic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, a substituted or unsubstituted aromatic heterocyclic group, or substituted or unsubstituted aromatic heterocyclic alkyl) can be produced according to the following steps: (IH) ("i) (In the formulas, R1, R3, R4, R8c and n have the same meaning as defined above, respectively, R9a represents the same lower alkoxy as above, and R10a represents the same lower alkyl as defined above.) Step 20: The compound (Ij) can be produced by reacting the compound (Ii-i) obtained in the Production Method 6 with 1 to 50 equivalents of R8cM (wherein R8c has the same meaning as defined above; M represents a group metal of MgCl, MgBr, Mgl, Li, ZnCH3, ZnCH2CH3, Ti (OCH (CH3) 2) 2 or the like), in a solvent inert to the reaction at a temperature between -78 ° C and the boiling point of the solvent used for 5 minutes up to 48 hours. * The solvent inert to the reaction is not specifically limited, and examples thereof include diethyl ether, THF, 1,4-dioxane, 1,2-dimethoxyethane and toluene. These can be used in the present either alone or in a combination. < Production Method 8 > Among Compounds (I), Compounds (Ij-i) in which n is 0 and R2 is -COR8c (wherein R8c has the same meaning -as defined above) can be produced in accordance with the following steps: [In the formulas, R1, R3, R4, R8c and M have the same meaning as defined above, respectively; Ra has same lower alkoxy as defined above, or represents -NRblRb2 (wherein Rbl and Rb2 may be the same or different, and each represents the same lower alkyl as defined above or the same lower alkoxy as defined above) .] Step 21: The compound (Ij-i) can be produced by reacting the compound (Ik) with 1 to 100 equivalents of R8c-CORa in a solvent inert to the reaction in the presence of 1 to 20 equivalents of a base, to a temperature between -78 ° C and room temperature for 5 minutes up to 48 hours. The compounds (Ia-i) obtained in Step 8 of the production method 4; or the compounds obtained from the compound (Ia-i) in a manner similar to that in step 3 of Production Method 1 or in Step 3 and Step 4 of Production Method 1 are used as the starting compound (Ik). The solvent inert to the reaction is not specifically limited, and examples thereof include THF, diethyl ether, 1,4-dioxane, 1,2-dimethoxyethane and hexane. These they can be used in the present either alone or in a combination. Examples of the base include lithium diisopropylamide, lithium bis (trimethylsilyl) amide, methylthio, n-butylithium, lithium hydride, sodium hydride, potassium hydride, methylmagnesium bromide, ethylmagnesium bromide, and isopropylmagnesium chloride. These can be used either alone in a combination of two or more. Step 22: The compound (Im) can be produced by reacting the compound (Ik) with 1 to 100 equivalents of R8cCHO in a solvent inert to the reaction in the presence of 1 to 20 equivalents of a base at a temperature between -78 ° C and room temperature for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited, and examples thereof include THF, diethyl ether, 1,4-dioxane, 1,2-dimethoxyethane and hexane. These can be used in the present either alone or in a combination. Examples of the base include lithium diisopropylamide, lithium bis (trimethylsilyl) amide, methylthio, n-butylithium, lithium hydride, sodium hydride, potassium hydride, methylmagnesium bromide, ethylmagnesium bromide, and isopropylmagnesium chloride. These can be used either alone in a combination of two or more. A mixture with Step 23: The compound (Im) can also be produced by reacting the compound (le) obtained in Production Method 5, with 1 to 50 equivalents of R8cM (wherein R8c and M have the same meaning as defined above, respectively ) in a solvent inert to the reaction at a temperature between -78 ° C and the boiling point of the solvent used, for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited, and examples thereof include diethyl ether, .THF, 1,4-dioxane, 1,2-dimethoxyethane and toluene. These can be used in the present either alone or in a combination.

Step 24: The compound (Ij-i) can be produced by treating the compound (Im) with 1 to 100 equivalents of an oxidizing agent in the absence of a solvent or a solvent inert to the reaction at a temperature between -78 ° C and the boiling point of the solvent used, for 5 minutes up to 48 hours. The solvent inert to the reaction is not specifically limited, and examples thereof include acetonitrile, dichloromethane, 1,2- dichloroethane, chloroform, 1,2-dimethoxyethane, DMF, DMA, 1,4-dioxane, THF, diethyl ether, diisopropyl ether, benzene, toluene, xylene, pyridine, DMI, NMP, sulforane and water. These can also be used either alone or in a combination. Examples of the oxidizing agent include chromic acid, pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), dimethisulfoxide (DMSO), oxalyl chloride, DMSO-dicyclohexylimide (DCC), tetrapropylammonium perruthenate (TPAP), Dess-Martin reagent (DMP: 1, 1, 1-triacetoxy-l, 1-dihydro-l, 2-benziodoxol-3 (1H) -one. Lecture of Experimental Chemistry, 5th Ed., Vol. 15, p. 27, by the Chemical Society of Japan, Maruzen, 2003), 2-iodoxybenzoic acid (IBX), 2, 2, 6, 6-tetramethylpiperidine-N-oxide (TEMPO) and manganese dioxide. In addition, the transformation of the functional group contained in R1, R2, R3 or R4 into the compounds (I) can be carried out according to any other known method to those steps described above (for example, methods described in Comprehensive Organic Transormations, by RC Larock, 1989) or methods similar to these. By appropriately combining the processes described above and the like, the compounds (I) that have desired functional groups to desired positions can be obtained. The intermediates and compounds desired in the production processes described above can be isolated and purified by appropriately combining separation and purification methods conventionally used in synthetic organic chemistry, for example, filtration, extraction, washing, drying, concentration, re-crystallization and various types of chromatography. Intermediates can also undergo subsequent reactions without purification. For some of Compounds (I), stereoisomers such as regioisomers, geometric isomers, optical isomers and tautomers may exist, and all possible isomers including them and mixtures thereof may be used for the A2A adenosine receptor antagonists of the present invention. When it is desired to obtain a salt of the compound (I), in the case where the compound (I) is produced in the salt form, it can be purified in such a way that, where it is produced in the free state, it can become a salt by dissolving or suspending in an appropriate solvent and then adding an acid or base to it. In addition, the compounds (I) and pharmaceutically acceptable salts thereof may exist in the form of adducts with water or various solvents, and these adducts can also be used for the A2A adenosine receptor antagonist of the present invention. Specific examples of the compounds (I) obtained in the present invention are shown in Table 1 to Table 8. However, the compounds usable in the present invention or the compounds of the present invention should not limit these. Table 1 No. of R2 R4 Compound Br .__ £; _ / GN Table 2 Compound No. R2 R4 ^ 1 -- . 1 - 0 = 4 - . 4 - OR, -. --O 5 -O 8 * - -C- J 9 -. 9 -? -x 0 -. 10 - 11 - * - ° - \ J- ° H 13 -. 13 -O-CH2- ^ J Table 2 (continued) 16 -. 16 -O ^ - - ^^ 19 -. 19 -o - ~ cH2"1 twenty - . 20 - ** "° ~? V ~ CH2 ~ N ~ ° H 0 =. 21 -o 2. 3 - . 23 -CH * 0 O / ^ 24 - C-0CH2CH3 0 25 II - C-CH3 0 26 -CH3 II - C-CH3 Table 2 (continued) O 35 II N V - C- J -N NCH3 / - \ 36 V -C- - CH2CI Pl 39 -N p - ^ - CN Table 2 (continued) 47 -. 47 -N ^ O ^ K ~ ~ N ° 2 Table 2 (continued) 56 * -NQ? Q O 57"~ NN p -C- (-SQ2CH3 -o - ^ a 61 - "v ° - d-¿> -CH2 - N ~~ > -0H Table 2 (continued) No. of R Compound O 66 II -N NCH3 / - \ O O r = ^ 61 - N NCH2CH3 II N o / == N 74 - = 0 -Hy Table 2 (continued) or - ^ 76 - N (CH3) 2 79 o ^ _CH2O II - C-CH3 80 - N NH or II - C-CH3 81 P 0 II - C-CH3 or 82 -OO II - C-CH3 0 y = \ 85 -. 85 -CHO or - ^ 86 - CH2-N O Table 2 (continued) O o / == 97 - C-N (CH3) 2 O pCH. O? = 98 -C-N C-H3 O 7 = ^ 99 - Table 3 Compound No. R 'R * 100 r ~ \ o / - ^ -Br Table 4 No. of R¿R4 Compound 101"102 -O O -_- - £? RF 103 -C - ^ _ ^ - 0CH3 Table 4 (continued) = \ 115 -. 115 - 0 / Table 5 126 -. 126 -X ^ G-X ° O / == \ N C? 3 O 7 =; ^ 127 CH2CH3 ^ H_ 0, = \ 128 Table 5 (continued) Table 5 (continued) 140 ^ -o - ^ - CN Table 5 (continued) Table 5 (continued) Do not . of R is2 R is.4 Compound Table 5 (continued) Compound No. R2 R4 Table 5 (continued) 173 ?? > • ^ - 0 / = ^ 174 X-Ó Table 5 (continued) No. of R2 R4 Compound 183 -. 183 - -CN -H Table 5 (continued) Compound No. R2 R4 0 y ^ 184 -. 184 -K ~ ~ CN 9 N = \ 9 PH3 185 - C-0- (-CH3 CH3 9 / = v 186 -H O N = \ 0 191 -. 191 -K_7 '• and \ -c X¡ 0 192 -K_ > CH3 193 -co Table 5 (continued) No. of R2 R4 Compound 195 9, = \ or II /. - \ 0 II - C - ^^ N-C-0-C (CH3) 3 Table 5 (continued) Table 5 (continued) Table 5 (continued) Table 5 (continued) Do not . of Co-option R2 R4 0 N = \ 236? X ° / ° YN ° 2 Table 5 (continued) O 53 241 ^ - 242 + or -c? U H3C 245 »/ N = \ Table 5 (continued) or 249 H_ > -C-OCH3 O and 254 H_C-O- / N- > CH Table 5 (continued) Do not . of Compound O -OCH, 260 -. 260 - II -C-N- H Table 5 (continued) 266 9 -H_ - C-CH2-N r- \ V- CH3 267 -. 267 -H3 - C-CH2-N V-OCH3 0 N = 271 - 9 C-CH2-N r ~ V-N r ~ \ 0 272 9, N = \ - 9 C-CH2-N - \ N-CH3 2 \ f 3 273 CH2CH3.

Table 5 (continued) Co-pay No. R ^ 279 -. 279 - > - C-CH2-N H- O 280 -. 280 -Hy - 9 C-CH2-N - < N-CH3 281 -. 281 -HL / -C-CH2-N I Table 5 (continued) CH3 O y ==? 0 284 you PH3 O 286 -H tí PHa O, - 287 ll \ - c- - C-CH2-N p 2 \ __ / tí PHa O 288 - 9 C-CH2-N y- V_- OH tí PHa O 290 9 - C-CH2-N N-CH2CH3 2/2 3 Table 5 (continued) 298 OCH, -Hy Table 5 (continued) 303 -. 303 - * - 0 -H Table 5 (continued) Compound No. R2 R4 O y = N 9 PHs 311 - C-O- (-CH3 CH3 O y = N 315 ° _ ° ^? Table 5 (continued) Co-pay No. R * R4 O y ==? 328 -H o / = ^ 329 N 9 _ / = v Table 5 (continued) Table 5 (continued) 3. 4. 5 ?-? -H Table 5 (continued) Compound No. R2 R4 S O y ^ 351 xxp S CH33 ° -i__ (H3C) 2HC. , CH (CH3) 2 352 - C Q1 CHÍCHa), -H? Table 5 (continued) No. of R ^ R Co-set Table 5 (continued) O N = \ 0 y ^ 374 -. 374 -c- ^ -N 375 9 / N = -HD O and ^ 376 Table 5 (continued) Compound No. R2 R4 O 0 y ^ 377 II - C-CHg O 379 II -H - C-CFg O 381 • G "* ~ Crl2Cr_3 HD1 or - ^ 382 or 11 * C CH2CH CHg O 384 II -H ^ - C- CHCH CH3 Table 5 (continued) No. of R2 R K4 Compound 0 386 II * C GH2CH2CH3 ~ °? J 0 387 II • C GH GH CH - ° -__ > N 0 0 390 II II / / - \ v * C- CHCH2CH3 - C-CH2-N O Table 5 (continued) No. of R2 Compound R * 0 397 II -H * C- CH CHCH2CH3 9 Ha O ysrr 400 - C-SCH3 CH3 -Hv N Table 5 (continued) Do not . of Coimposed R4 O 403 II -H - C-CH2-0-CH3 O O = N 404 II n r r -C-CH2-0-CH3 -CS and I / -CI O 407 II -H -C-CH2-0-CH2CH3 O 410 II -H - C-CH2CH2-0-CH3 Table 5 (continued) Co-pay No. Rz R4 O 412 II -H - C-CH2CH2O-CH2CH3 O 413 II - C-C = C-CH2-OCH3 • ~ K ^ N Or 416 ti -C- CHCHCH_OCH3 -H 417 -. 417 -ß- -H N w 419 - * - < ] -H H3CO 420 -c-0 ~ & Table 5 (continued) No. of R2 Co-option R4 or 421 ^ ?? / - \ v - C »- < ] -C-CH2-N p 423 »_y \ -H Table 5 (continued) Do not . of R IS.2 i Rs.4 Compound 431 -. 431 - * o O y = -K_ 432 -. 432 - * or 9 PH3 - C-O- (-CH3 CH3 433 ~ * o -H Table 5 (continued) Compound No. R4 446 -. 446 -H Table 5 (continued) Do not . of Co-option R2 R4 447 _ 9 c- / - \ X = o -H 450 - 9 c- / - v X = o -C- 452 - 9 c- / - \ = 0 -KD ~ CN 0 / - 9 PHa 453 -. 453 -H_ - C-O- (-CH3 CH3 0 / - .454 -H 0 - 455 -Hy Table 5 (continued) Compound No. R2 R4 0 / - ^ or 456 -KD - 0 - - 0 p = 457 > Table 5 (continued) Do not . of Co-option R2 R4 Table 5 (continued) Compound No. R2 R4 474 -. 474 - D -MD ~ CN. 0 / - ^ 480 -0 - ^) 0 KD ~ cKD 481 - C- -CH2-N V-OH Table 5 (continued) Co-pay No. R2 R4 0 - ^ 489 -C- ^ O - * and Table 5 (continued) 496 -. 496 -? O - > 0 - ^ 497 -KD - you Table 5 (continued) J V / = N 501 -. 501 -KD C- \ Table 5 (continued) Co-pay No. R¿ R4 OR II 9, 507 -o -KD = O / -. O or -K > - ° 3 X -trCH3 Table 5 (continued) Co-pay No. R < 0 - * O CHO 513 II -K OR H = N-OH 514 O C - O KD II P-, -C- 4J 0 515 II K > O y - v O O < 5 517 -KD - o-O o 519 JO II - C Table 5 (continued) Do not . of Compound R2 R4 O 522 -? and - > -C ~ 527 -. 527 - ° kD > - C-CH2-CH2- _ 529 x? S > - 9 C-CH2-0- ^ / = Table 5 (continued) Do not . of Compound R2 R4 O 530 - C-CH2-0-CH3 or J - ^ O 532 -KD - C-CH2-0-CH2CH3 O - 9 PH3 533 -KD - C-CH2-N bH3 Table 5 (continued) Do not . of Compound R2 R4 543 -. 543 -KD - 9 C-CH2-N r- V-OH Table 5 (continued) Co-pay No. Rz O - > 548 - D - 9 C-CH2-N r- X-CH2-0H 0 - v 552 -KD 9 r ~ \ y - \ - C-CH2-N VN 556 Xr - C-CH2-N ^ ^ Table 5 (continued) Co-pay No. R4 O - v O 561 KD ?? Z i - \. - C-CH2-N NH 2 v_y Table 5 (continued) Co-pay No. R2 O y - v 571 KD II / - \ C-CH2-N: N- < DO 574 < s OR II - C-CH2-N r4 N-CH3 Table 5 (continued) No. of R2 R4 Co-deposited O / - v 578 KD - ° C-CHa-N _-PJvSL-OH Table 5 (continued) Compound No. R ' Table 5 (continued) Do not . of R K2 i R \ 4 Compound 594 -. 594 -kD -H O y = 597 -C-CH2 ^ -H -H3CO 9 PHa 598 -. 598-CH2- - C-O- (-CH3 CH3 H3CO 600 -C-CH2SQ -H Table 6 610 -. 610 -? J -H Tabl, to 6 (continued) Table 7 0 - 627 -KD -H -C (CH3) 3 Table 8 The pharmacological activities of the typical compounds (I) are illustrated below with reference to the test compounds.

Test Example 1. Adenosine receptor binding activity (adenosine A2A receptor binding test) This test was carried out in a manner similar to the method of Bruns et al., (Molecular Pharmacology, vol.29, p. 331, 1986). The corpus striatam of rats (rat SD, by Nippon SLC) was suspended in 50 mol / L of a buffer solution of an ice-cooled tris (hydroxymethyl) aminomethane (Tris-HC1) hydrochloride (pH 7.7) when using a polytron homogenizer (by Kinematica). The resulting homogenate was centrifuged (48,000 xg, 20 minutes), and the resulting precipitate was suspended again by adding the same amount of a 50 mmol / L Tris-HCl buffer, followed by centrifugation under the same condition. The resulting final precipitate was suspended by adding a Tris-HCl buffer of 50 mmol / L (containing 10 mmol / L of magnesium chloride, tissue in adenosine deaminase 0.02 units / mg (By Sigma), so that the concentration of the tissue was 5 mg (wet weight) / mL To 100 μL of the tissue suspension before purified was added 80 μL (final concentration 6.0 mmol / L) of CGS-21680 labeled with tritium { 3H-2- [ p- (2-carboxyethyl) phenethylamino] -5 '- (N-ethylcarboxamido) -adenosine: 40 curios / mmol; by New England Nuclear [The Journal of Pharmacology and Experminetal Therapeutics, Vol. 251, p. 888, 1989]} and 20 μL of a solution of a test compound (10 ~ 7 mol / L; a solution of a test compound in DMSO was diluted with Tris-HCl buffer). The resulting mixture was allowed to stand at 25 ° C for 120 minutes, followed by rapid suction filtration through a glass fiber paper filter (GF / C, by Whatman). The filter was washed immediately three times with 200μL of a 50 mM / L Tris-HCl buffer solution cooled on ice. The fiberglass paper filter was transferred to a vial, Microscinti (by Perkin Elmer) was added thereto, and the level of radioactivity was measured with Topcount (by Perkin Elmer). The rate of inhibition of the test compound for the binding of adenosine A2A receptor (3 H-CGS21680 linkage) was calculated according to the following formula.

Inhibition rate (%) = The total binding amount means the binding radioactivity content of 3H-CGS21680 in the absence of the test compound. The non-specific binding amount means the binding radioactivity content of 3H-CGS21680 in the presence of 100 μmol / L cyclopentyladenosine (CPA, by Sigma). The amount of binding in the presence of the test compound means the binding radioactivity content of 3H-CGS21680 in the presence of 10 ~ 7 mol / L of the test compound. The results are shown in Table 9.

Table 9 No. Inhibition Rate No. Compound Inhibition Rate (%) Linker Link (%) Linker A2a Receptor A2a Rat Adenosine Rat Receptor (10 ~ 7 mol / L) (10 ~ 7 mol / L) 1 90 187 86 4 95 191 98 5 100 206 95 100 228 84 9 100 234 100 11 100 249 85 19 90 348 100 23 85 431 98 24 88 455 100 41 92 456 94 46 95 462 99 87 100 468 93 94 100 502 90 99 98 504 100 131 99 511 88 149 91 515 95 170 87 558 92 Table 9 indicates that the compounds (I) have a strong antagonism to the adenosine A2A receptor. Therefore, it was suggested that the pharmaceutical composition comprising the compound (I) as the active ingredient, be effective for diseases associated with the adenosine A2 receptor (for example, central nervous system disorders such as Parkinson's disease, Alzheimer's disease, progressive supranuclear palsy, AIDS encephalopathy, transmissible spongiform encephalopathy, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's chorea, multiple system atrophy, cerebral ischemia, attention deficit hyperactivity disorder, sleep disorders, intermittent claudication, diabetes, anxiety disorders (for example, panic attack and panic disorder, phobia, obsessive-compulsive disorder, acute tension disorder, generalized anxiety disorder, physical symptoms of anxiety or substance-induced symptoms), mood disorders (for example, depression, dysthymic disorder, circulatory disturbance of the ani mo), legs syndrome without rest (RLS), drug dependence (eg, alcohol dependence), eating disorders, epilepsy, migraine and chronic pain of the musculoskeletal system; ischemic heart disease such as myocardial infarction and cerebral infarction).

Test Example 2. Effect on the Parkinson's Disease Model [common titi treated with l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)] Parkinson's disease is a disorder based on the 'eneration and lack of dopaminergic neurons in the nigro-striatal trajectory. In primates, treatment with a dopamine neurotoxin, which is MPTP, causes the selective degeneration and lack of dopaminergic neurons in the nigro-striatal trajectory and causes a symptom such as akinesia and body rigidity. The primate treated with MPTP is known as a model of Parkinson's disease (Proceedings of the National Academy of Science USA, Vol. 80, p 4546, 1983). Also the common tities belong to the Anthropoidea, and it is known that they have parkinsonism caused by MPTP like others of the Anthropidea (Neuroscience Letter, Vol. 57, p.37, 1985). The experiment was carried out using four common female and male tities of 2 or 3 years of age (body weight, 300 to 375 g, by Nippon Clea) per group. MPTP (by RBI) was dissolved in a physiological saline solution for injection (by Otsuka Pharmaceutical), and hypodermically administered to the common tities in a dose of 2.0 mg / kg, once a day for 5 days. Six weeks or more after administration, they were used in the test "the animals showing chronic parkinsonian symptoms." The test compound was used as a suspension in aqueous solution containing 0.3% Tween 80 and 10% sucrose.One hour before administration of the test compound, the animals to be tested in an observation cage (equipped with a spontaneous locomotor activity measuring device), to adapt them to the environment The motor disability of the animals was recorded before the administration of the test compound, and this was compared with the registration of motor disability after oral administration of the test compound (Compound 1) at a dose of 10 mg / kg As for parkinsonian symptoms, motor disabilities were recorded at 30 minute intervals for 8 hours, by observation through a one-way view window Spontaneous locomotor activity was measured at 30-minute intervals for 12 hours by an automatic device. and computer controlled measurement. Parkinsonian symptoms were recorded based on the rating scale of each observation item as shown below, and the total points were used as the record of each individual. Table 10 shows the relationship between the observation items and the record.

Table 10 The results were judged by comparing the average records of parkinsonian symptoms in 4 animals per group between before and after the administration of compound 1 (significance test: Wilcoxon Rank Sum test).

As a result, it was confirmed that compound 1 is effective for the remission of parkinsonian symptoms in the test described above, and indicates that the compounds (I) are effective in preventing and / or treating Parkinson's disease. Although the compounds (I) or pharmaceutically acceptable salts thereof can be administered as such, it is generally preferred to offer them in the form of various pharmaceutical preparations. Such pharmaceutical preparations will be used in animals and humans. The pharmaceutical preparations of the present invention may comprise Compounds (I) or pharmaceutically acceptable salts thereof as the active ingredient alone or in combination with any other active ingredients for therapy. These pharmaceutical preparations can be produced by some of the methods well known in the technical field of pharmaceuticals, by mixing the active ingredient with one or more pharmaceutically acceptable carriers. It is desirable to ct a route of administration that is more effective for therapy, examples of which are oral administration or parenteral administration such as intravenous administration. Examples of the dosage form include tablets and injections.

Preparations suitable for oral administration such as tablets can be produced by using for example, excipients (eg, lactose and mannitol), disintegrants (eg, starch), lubricants (eg, magnesium stearate), binders (eg. hydroxypropyl cellulose), surfactants (e.g., fatty acid esters) and plasticizers (e.g., glycerin). Preparations suitable for parenteral administration preferably comprise a sterile aqueous preparation containing an active compound which is isotonic to the blood of the recipient. In the case of an injection, for example, a solution for injection is prepared by using a carrier comprising a saline solution, a glucose solution, or a mixture of a saline solution and a glucose solution. Parenteral preparations can also comprise one or more auxiliary components cted from excipients, disintegrators, lubricants, binders, surfactants and plasticizers described in the above description of oral preparations and diluents, antiseptics, flavors, etc. In the case of the applications described above, in general, the compounds (I) or pharmaceutically acceptable salts thereof can be administered systemically or locally, and orally or parenterally. The dose and Frequency of administration may vary, depending on the form of administration, the age and body weight of the patient, and the property and seriousness of the symptom to be treated. In the case of oral administration in general, it can be administered once up to a few times a day in a dose of 0.01 to 1000 mg / adult, preferably 0.05 to 500 mg / adult. In the case of parenteral administration such as intravenous administration, in general, it may be administered once a few times a day or administered continuously in an intravenous administration mode for 1 to 24 hours a day, in a dose of 0.001 to 1000. mg / adult, preferably 0.01 to 300 mg / adult. However, the dose and frequency of administration may vary depending on various conditions mentioned above.

BEST MODE FOR CARRYING OUT THE INVENTION The invention is described in detail with reference to the following Examples, Reference Examples and Formulation Examples. The proton nuclear magnetic resonance spectrum ("" "H NMR) used in the examples is determined at 270 MHz or 300 MHz. Some compounds can not show an exchangeable proton under some conditions. The expression multiplicity of signal is ordinary, for which "it indicates an apparently broad signal.

[Example 1] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 1) The compound a (1.70 g, 7.00 mmol) obtained in the Reference example 1 was dissolved in DMA (14 mL), and isonicotinoyl chloride hydrochloride (2.49 g, 14.0 mmol) and triethylamine (1.95 mL, 14.0 mmol) were added thereto, followed by stirring at room temperature for 4 hours. Aqueous saturated sodium acid carbonate solution was added to the reaction mixture, and the precipitated solid was collected by filtration. The resulting solid was washed successively with water and ethanol, and the title compound 1 (2.19 g, 90%) is obtained as pale brown crystals. X H NMR (DMSO-d 6, d ppm): 6.61 (dd, J = 1.8, 3.3 Hz, 1H), 6.74 (dd, J = 0.7, 3.3 Hz, 1H), 7.46 (dd, J = 1.5, 4.6 Hz, 2H), 7. 67 (dd, J = 0.7, 1.8 Hz, 1H), 8.02 (dd, J = 1.5, 4.6 Hz, 2H), 8.63 (dd, J = 1.5, 4.6 Hz, 2H), 8.83 (dd, J = 1.5, 4.6 Hz, 2H). ESIMS m / z: [M + H] + 349.

[Example 2] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] acetamide (Compound 2) Compound a (729 mg, 3.00 mmol) obtained in the reference example 1 was dissolved in DMA (15 mL), and chloride of acetyl (0.43 mL, 6.00 mmol) was added thereto, followed by stirring at 80 ° C for 3 hours. Aqueous saturated sodium acid carbonate solution was added to the reaction mixture, and the precipitated solid was collected by filtration to provide the title compound 2 (620 mg, 72%). X H NMR (DMS0-d 6, d ppm): 2.20 (s, 3H), 6.58 (dd, J = 1.8, 3.3 Hz, 1H), 6.68 (dd, J = 0.7, 3.3 Hz, 1H), 7.42 (dd, J = 1.5, 4.5 Hz, 2H), 7.62 (dd, J = 0.7, 1.8 Hz, 1H), 8.58 (dd, J = 1.5, 4.5 Hz, 2H), 12.50 (br s, 1H). ESIMS m / z: [M + H] + 286.

[Example 3] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] methoxyacetamide (Compound 3) The compound a (300 mg, 1.23 mmol) obtained in reference example 1 was dissolved in DMF (17 mL), and methoxyacetic acid (0.19 mL, 2.46 mmol), EDC hydrochloride (472 mg, 2.46 mmol) and 1-hydroxybenzotriazole monohydrate (377 mg, 2.46 mmol) were added thereto, followed by stirring at 50 ° C for 3 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration to provide the title compound 3 (142 mg, 36%). H NMR (DMS0-d6, d ppm): 3.34 (s, 3H), 4.20 (s, 2H), 6.59 (dd, J = 1.8, 3.3 Hz, 1H), 6.70 (d, J = 3.3 Hz, 1H) , 7.43 (d, J = 6.1 Hz, 2H), 7.65 (d, J = 1.8 Hz, 1H), 8.61 (d, J = 6.1 Hz, 2H), 12.5 (br s, 1H). APCIMS m / z; [M + H] + 315.

[Example 4] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] cyclohexanecarboxamide (Compound 4) In a manner similar to that in Example 1, using, cyclohexanecarbonyl chloride (0.22 mL, 0.82 mmol) in place of isonicotinoyl chloride hydrochloride, the title compound 4 (261 mg, 90%) is obtained from compound a (200 mg, 0.82 mmol) obtained in reference example 1. XH NMR (DMSO-d6, d ppm): 1.24-1.86 (10H,), 2.50-2.56 (m, 1H), 6.58 (d, J = 1.8, 3.3 Hz, 1H), 6.69 (d, J = 3.3 Hz, 1H), 7.41 (d, J = 6.0 Hz, 2H), 7.64 (d, J = 1.8 Hz, 1H), 8.56 (d, J = 6.0 Hz, 2H), 12.4 (brs, 1H). ESIMS m / z: [M + H] + 354.

[Example 5] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] pyridine-3-carboxamide (Compound 5) In a manner similar to that in example 3, using nicotinic acid (303 mg, 2.46 mmol) in place of methoxyacetic acid, the title compound 5 (230 mg, 54%) was obtain compound a (300 mg, 1.23 mmol) obtained in reference example 1. 1 H NMR (DMS0-d 6, d ppm): 6.61 (dd, J = 1.8, 3.3 Hz, 1H), 6.75 (d, J = 3.3 Hz, 1H), 7.48 (d, J = 6.1 Hz, 2H), 7.59-7.63 (m, 1H), 7.67-7.68 (m, 1H), 8.44-8.48 (m, 1H), 8.64 (d, J = 6.1 Hz, 2H), 8.81-8.83 (m, 1H), 9.24-9.25 (m, 1H). APCIMS m / z: [M + H] + 349. [Example 6] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] pyridine-2-carboxamide (Compound 6) In a manner similar to that in Example 3, when using picolinic acid (303 mg, 2.46 mmol) instead of methoxyacetic acid, the title compound 6 (154 mg, 36%) is obtained from compound a (300 mg, 1.23 mmol) obtained in reference example 1. a H NMR (DMS0-d6, d ppm): 6.61 (dd, J = 1.8, 3.3 Hz, 1H), 6.77 (d, J = 3.3 Hz, 1H), 7.47 (dd, J = 1.7, 4.4 Hz, 2H), 7.68 (d, J = 1.8 Hz, 1H), 7.72-7.76 ( m, 1H), 8.09-8.21 (m, 2H), 8.63 (dd, J = 1.7, 4.4 Hz, 2H), 8.78-8.80 (m, 1H), 12.4 (br s, 1H). APCIMS m / z: [M + H] + 349. [Example 7] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] pyrazine-2-carboxamide (Compound 7) In a manner similar to that in Example 3, when using pyrazine-2-carboxylic acid (305 mg, 2.46 mmol) instead of methoxyacetic acid, the title compound 7 (182 mg, 42%) is obtained from compound a (300 mg, 1.23 mmol) obtained in reference example 1. X H NMR (DMSO-d 6, d ppm): 6.58 (dd, J = 1.8, 3.3 Hz, 1H), 6.74 (d, J = 3.3 Hz, 1H), 7.45 (d, J = 6.1 Hz, 2H), 7.66 (d, J = 1.8 Hz, 1H), 8.61 (d, J = 6.1 Hz, 2H), 8.83-8.84 (m, 1H), 8.94-8.95 (m, 1H), 9.30-9.31 (m, 1H), 12.85 (br s, 1H). APCIMS m / z: [M + H] + 350.

[Example 8] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] furan-2-carboxamide (Compound 8) In a manner similar to that in Example 3, using furan-2-carboxylic acid (276 mg, 2.46 mmol) in place of methoxyacetic acid, the title compound 8 (126 mg, 30%) is obtained from compound a (300 mg, 1.23 mmol) obtained in reference example 1 NMR (DMSO-d6, d ppm): 6.60 (dd, J = 1.8, 3.3 Hz, 1H), 6.74. (d, J = 3.3 Hz, 1H), 6.77 (dd, J = 1.7, 3.5 Hz, 1H), 7.45 (d, J = 6.0 Hz, 2H), 7.67 (d, J = 1.8 Hz, 1H), 7.76 (d, J = 3.5 Hz, 1H), 8.05 (d, J = 1.7 Hz, 1H), 8.62 (d, J = 6.0 Hz, 2H), 13. 02 (br s, 1H). APCIMS m / z: [M + H] + 338.

[Example 9] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] furan-3-carboxamide (Compound 9) In a manner similar to that in Example 3, using furan-3-carboxylic acid (276 mg, 2.46 mmol) in place of methoxyacetic acid, the title compound 9 (47.9 mg, 12 %) is obtained from compound a (300 mg, 1.23 mmol) obtained in reference example 1. X H NMR (DMSO-d 6, d ppm): 6.59 (dd, J = 1.8, 3.3 Hz, 1 H), 6.71 (d , J = 3.3 Hz, 1H), 7.12-7.13 (m, 1H), 7.42-7.44 (m, 2H), 7.65 (d, J = 1.8 Hz, 1H), 7.85-7.86 (m, 1H), 8.30- 8.62 (m, 3H), 12.84 (br s, 1H). APCIMS m / z: [M + H] + 338.

[Example 10] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -l-oxopyridine-3-carboxamide (Compound 10) In a manner similar to that in Example 3 , when using N-oxide of nicotinic acid (342 mg, 2.46 mmol) in place of methoxyacetic acid, the title compound 10 (60.1 mg, 13 %) is obtained from compound a (300 mg, 1.23 mmol) obtained in reference example 1. 2 H NMR (DMSO-d 6, d ppm): 6.62 (dd, J = 1.7, 3.5 Hz, 1 H), 6.77 (dd, J = 0.7, 3.5 Hz, 1H), 7.53 (dd, J = 1.7, 4.6 Hz, 2H), 7.58-7.63 (m, 1H), 7.68 (dd, J = 0.7, 1.7 Hz, 1H), 7.96-7.99 (m, 1H), 8.44-8.46 (m, 1H), 8.66 (dd, J = 1.7, 4.6 Hz, 2H), 8.83-8.84 (m, 1H). APCIMS m / z: [MtH] + 365.

[Example 11] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -2-hydroxypyridine-5-carboxamide (Compound 11) In a manner similar to that in Example 3 , when using 6-hydroxynicotinic acid (342 mg, 2.46 mmol) in place of methoxyacetic acid, the title compound 11 (38.2 mg, %) is obtained from compound a (300 mg, 1.23 mmol) obtained in reference example 1. X H NMR (DMSO-d 6, d ppm): 6.42 (d, J-9.7 Hz, 1 H), 6.58 (dd, J = 1.7, 3.3 Hz, 1H), 6.70 (d, J = 3.3 Hz, 1H), 7.42 (d, J = 6.1 Hz, 2H), 7.64 (d, J = 1.7 Hz, 1H), 8.03 (dd, J = 2.8, 9. 7 Hz, 1H), 8.42 (d, J = 2.8 Hz, 1H), 8.59 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M + H] + 365.

[Example 12] 2-Chloro-N- [4- (2-furyl) -5- (4-pyridyl) thiazol-2-yl] pyridine-3-carboxamide (Compound 12) In a manner similar to that in the example 3, by using 2-chloronicotinic acid (388 mg, 2.46 mmol) in place of methoxyacetic acid, the title compound 12 (60.3 mg, 13%) was obtain compound a (300 mg, 1.23 mmol) obtained in reference example 1. X H NMR (DMSO-d 6, d ppm): 6.58 (dd, J = 1.8, 3.3 Hz, 1 H) 6.71 (d, J = 3.3 Hz, 1H), 7.47 (d, J = 6.1 Hz, 2H), 7.58 (dd, J = 4.8, 7.5 Hz, 1H), 7.65 (d, J = 1.8 Hz, 1H), 8.17 (dd, J = 1.8 , 7.5 Hz, 1H), 8.57 (dd, J = 1.8, 4.8 Hz, 1H), 8.62 (d, J = 6.1 Hz, 2H), 13.28 (br s, 1H). APCIMS m / z; [M + H] + 383.

[Example 13] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -2- (3-pyridyl) acetamide (Compound 13) In a manner similar to that in the example 3, using 3-pyridylacetic acid hydrochloride (427 mg, 2.46 mmol) in place of methoxyacetic acid, the title compound 13 (20.2 mg, 4%) is obtained from compound a (300 mg, 1.23 mmol) obtained in the reference example 1. XH NMR (DMSO-d6, d ppm): 4.02 (s, 2H), 6.59 (dd, J = 1.8, 3.3 Hz, 1H), 6.71 (d, J = 3.3 Hz, 1H), 7.28 -7.32 (m, 1H), 7.42 (m, 3H), 7.65 (d, J = 1.8 Hz, 1H), 7.76-7.81 (m, 1H), 8.50- 8.52 (, 1H), 8.60 (dd, J = 1.8, 4.4 Hz, 2H), 12.8 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 363.

[Example 14] 1- (tert-Butoxycarbonyl) -N- [4- (2-furyl) -5- (4-pyridyl) thiazol-2-yl] piperidine-4-carboxamide (Compound 14) Compound a (2.00 g, 8.22 mmol) obtained "in reference example 1, 1- (tert-butoxycarbonyl) piperidine-4-carboxylic acid (5.94 g, 25.9 mmol) and PyBOP (14.1 g, 27.1 mmol) were dissolved in DMF (32 mL), and triethylamine (7.56 mL, 54.3 mmol) was added thereto, followed by stirring at 60 ° C for 4 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting solid is re-made in a thick mixture with ethanol to give the title compound 14 (1.88 g, 50%). NMR (DMS0-d6, d ppm): 1.41 (s, 9H), 1.41-1.57 (m, 2H), 1.81-1.85 (m, 2H), 2.65-2.80 (m, 3H), 3.94-3.99 ( m, 2H), 6.58 (dd, J = 1.7, 3.5 Hz, 1H), 6.69 (dd, J = 0.7, 3.5 Hz, 1H), 7.41 (dd, J = 1.6, 4.4 Hz, 2H), 7.64 (dd) , J = 0.7, 1.7 Hz, 1H), 8.60 (dd, J = 1.6, 4.4 Hz, 2H), 12.56 (br s, 1H). APCIMS m / z: [M + H] + 455.

[Example 15] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] piperidine-4-carboxy ida (Compound 15) Compound 14 (1.80 g, 3.96 mmol) was dissolved in dichloromethane (20 mL) and trifluoroacetic acid (20 mL) was added thereto, followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and water was added to the resulting residue, followed by adding a 10 mol / L aqueous solution of sodium hydroxide to adjust the pH to 12. The precipitated solid was collected by filtration to provide the compound of the title 15 (1.17 g, 84%). X H NMR (DMSO-d 5, d ppm): 1.46-1.60 (m, 2H), 1.74 (d, J = 10.2 Hz, 2H), 2.40-2.55 (m, 3H), 2.90 (d, J = 12.4 Hz, 2H), 6.58 (dd, J = 1.6, 3.2 Hz, 1H), 6.68 (dd, J = 0.8, 3.2 Hz , 1 HOUR) , 7. 40 (dd, J = 1.6, 4.6 Hz, 2H), 7.63 (d, J = 0.8, 1.6 Hz, 1H), 8.59 (dd, J = 1.6, 4.6 Hz, 2H). APCIMS m / z: [M + H] + 355.

[Example 16] 1- (5-Cyano-pyridin-2-yl) -N- [4- (2-furyl) -5- (4-pyridyl) thiazol-2-yl] piperidine-4-carboxamide (Compound 16) compound 15 (177 mg, 0.50 mmol), 2-chloro-5-cyanopyridine (104 mg, 0.75 mmol) and potassium carbonate (207 mg, 1.50 mmol) were dissolved in NMP (4 mL), followed by stirring overnight under heating and reflux. The reaction mixture was allowed to cool to room temperature, then it was poured into water, and the deposited precipitate was collected by filtration. The resulting precipitate was purified through silica gel column chromatography (chloroform: methanol = 17: 3) to give the title compound 16 (114 mg, 50%). a H NMR (DMSO-de, d ppm): 1.55-1.68 (m, 2H), 1.91-1.96 (m, 2H), 2.85-2.90 (m, 1H), 3.02-3.10 (m, 2H), 4.42-4.52 (m, 2H), 6.59 (dd, J = 1.9, 3.5 Hz, 1H), 6.69 (dd, J = 0.8, 3.5 Hz, 1H), 6.97 (d, J = 9.2 Hz, 1H), 7.41 (dd, J = 1.6, 4.6 Hz, 2H), 7.64 (dd, J = 0.8, 1.9 Hz, 1H), 7.84 (dd, J = 2.4, 9.2 Hz, 1H), 8.48 (d, J = 2.4 Hz, 1H), 8.59 (dd, J "= 1.6, 4.6 Hz, 2H), 12.60 (br s, 1H) APCIMS m / z: [M + H] + 457.

[Example 17] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -1- [5- (methanesulfonyl) pyridin-2-yl] piperidine-4-carboxamide (Compound 17) In a manner similar to that in Example 16, using 2-chloro-5- (methanesulfonyl) pyridine (144 mg, 0.75 mmol) obtained in accordance with the method described in W002 / 51836 in place of 2-chloro- 5-cyanopyridine, the title compound 17 (94.3 mg, 37%) is obtained from compound 15 (177 mg, 0.50 mmol). X H NMR (DMSO-d 6, d ppm): 1.55-1.69 (m, 2H), 1.91-1.97 (m, 2H), 2.86-2.91 (m, 1H), 3.03-3.21 (m, 2H), 3.23 (s) , 3H), 4.45-4.55 (m, 2H), 6.59 (dd, J = 1.6, 3.5 Hz, 1H), 6.70 (d, J = 0.8, 3.5 Hz, 1H), 7.01 (d, J = 9.2 Hz, 1H), 7.41 (dd, J = 1.6, 4.6 Hz, 2H), 7.64 (dd, J = 0.8, 1.6 Hz, 1H), 7.88 (dd, J = 3.0, 9.2 Hz, 1H), 8.50 (d, J = 3.0 Hz, 1H), 8.59 (dd, J = 1.6, 4.6 Hz, 2H), 12.61 (br s, 1H). APCIMS m / z: [M + H] + 510.

[Example 18] 4- (Bromomethyl) -N- [4- (2-furyl) -5- (4-pyridyl) thiazol-2-yl] benzamide (Compound 18) 4- (Bromomethyl) benzoic acid (1.12 g) , 5.20 mmol) was dissolved in toluene (80 mL) and thionyl chloride (7.59 mL, 104 mmol) was added thereto, followed by stirring under heating and refluxing for 5 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in THF (50 mL). Compound a (1.00 g, 4.11 mmol) obtained in Reference Example 1, triethylamine (0.86 mL, 6.17 mmol) and N, N-dimethylaminopyridine (97.6 mg, 0.800 mmol) were added thereto, followed by stirring under heating and reflux for 1 hour. The reaction mixture was allowed to cool to room temperature environment, and the precipitated solid was collected by filtration, followed by washing with diethyl ether to give the title compound 18 (2.28 g, 100%) - 1 H NMR (DMSO-d 6, d ppm): 4.8.6 (s, 2H), 6.60 (dd, J = 1.9, 3.5 Hz, 1H), 6.74 (dd, J = 0.5, 3.5 Hz, 1H), 7.46 (dd, J = 1.6, 4.3 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.67 (dd, J = 0.5, 1.9 Hz, 1H), 8.14 (dd, J = 1.6, 4.3 Hz, 2H), 8.62 (d, J = 8.4 Hz, 2H).

[Example 19] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -4- (imidazol-1-ylmethyl) benzamide (Compound 19) Compound 18 (880 mg, 2.00 mmol) was suspended in NMP (10 mL), and imidazole (408 mg, 6.00 mmol) was added thereto, followed by stirring at 65 ° C for 2 hours. The reaction mixture was allowed to cool to room temperature and then emptied into water, and the deposited precipitate was collected by filtration. The resulting precipitate was purified through silica gel column chromatography (chloroform: methanol = 17: 3) to give the title compound 19 (538 mg, 63%). X H NMR (DMSO-dg, d ppm): 5.23 (s, 2 H), 6.42 (dd, J = 1.9, 3.2 Hz, 1 H), 6.57 (dd, J = 0.8, 3.2 Hz, 1 H), 6. 93 (m, 1H), 7.17 (m, 1H), 7.28 (d, J = 8.4 Hz, 2H), 7.36 (dd, J = 0.8, 1.9 Hz, 1H), 7.42 (dd, J = 1.6, 4.6 Hz , 2H), 7.60 (m, 1H), 7.96 (d, J = 8.4 Hz, 2H), 8.65 (dd, J = 1.6, 4.6 Hz, 2H), 10.15 (br s, 1H). APCIMS m / z: [M + H] + 428.

[Example 20] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -4- [(4-hydroxypiperidino) methyl] benzamide dichlorohydrate (Compound 20). In a manner similar to that in Example 19, by using 4-hydroxypiperidine (607 mg, 6.00 mmol) in place of imidazole, a free form of the title compound is obtained. The resulting free form was treated with a solution of ethyl acetate of 4 mol / L hydrogen chloride to provide the title compound 20 (512 mg, 48%). 1E NMR (DMSO-d6, d ppm): 1.38-1.42 (m, 2H), 1.69-1.73 (m, 2H), 2.03-2.18 (m, 2H), 2.65-2.70 (m, 3H), 3.40-3.50 (m, 2H), 4.55 (d, J = 4.0 Hz, 1H), 6.60 (dd, J = 1.9, 3.5 Hz, 1H), 6.74 (dd, J = 0.8, 3.5 Hz, 1H), 7.45 (dd, J = 1.6, 4.6 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.67 (dd, J = 0.8, 1.9 Hz, 1H), 8.10 (d, J = 8.4 Hz, 2H), 8.62 ( dd, J = 1.6, 4.6 Hz, 2H), 12.97 (br s, 1H). APCIMS m / z: [M + H] + 461.

[Example 21] N- [4- (2-Furyl) -5- (2-pyridyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 21) In a manner similar to that in Example 1, the Compound of title 21 (157 mg, 90%) was obtained from compound b (122 mg, 0.50 mmol) obtained in reference example 2 in place of compound a. aH NMR (DMSO-d6, d ppm): 6.65 (dd, J = 1.8, 3.3 Hz, 1H), 6.84 (d, J = 3.3 Hz, 1H), 7.31-7.35 (m, 1H), 7.50-7.53 ( m, 1H), 7.74 (d, J = 1.8 Hz, 1H), 7.78-7.83 (m, 1H), 8.00 (d, J = 4.8 Hz, 2H), 8.60-8.62 (m, 1H), 8.81 (d , J = 4.8 Hz, 2H), 13.2 (br s, 1H). APCIMS m / z: [M + H] + 349.

[Example 22] N- [4- (2-Furyl) -5-phenylthiazol-2-yl] pyridine-4-carboxamide (Compound 22) In a manner similar to that in Example 1, using Compound c (300 mg , 1.24 mmol) obtained in reference example 3 instead of compound a, the title compound 22 (372 mg, 86%) is obtained. ^? NMR (DMSO-d6, d ppm): 6.53-6.55 (m, 2H), 7.43-7.46 (m, 5H), 7.61 (dd, J = 0.7, 1.8 Hz, 1H), 8.02 (dd, J = 1.7, 4.5 Hz, 2H), 8.82 (dd, J = 1.7, 4.5 Hz, 2H), 13.23 (br s, 1H). ESIMS m / z: [M + H] + 348.

[Example 23] N- [5-Benzyl-4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 23) In a manner similar to that in example 1, the title compound 23 ( 99.4 mg, 31%) is obtained from compound d (300 mg, 0.89 mmol) obtained in reference example 4 instead of compound a. 1 H NMR (DMSO-d 6, d ppm): 4.39 (s, 2 H), 6.34 (dd, J = 1.8, 3.5 Hz, 1 H), 6.50 (d, J = 3.5 Hz, 1 H), 7.26-7.36 (m, 6H), 7.63 (dd, J = 1.7, 4.5 Hz, 2H), 8.71 (dd, J = 1.7, 4.5 Hz, 2H), 10.90 (br s, 1H). ESIMS m / z: [M-H] "360.

[Example 24] N- (5- (Ethoxycarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 24) In a manner similar to that in Example 1, the title compound 24 (1.15 g, 53%) is obtained from compound e (2.00 g, 6.27 mmol) obtained in reference example 5 instead of compound a.XH NMR (DMSO-d6, d ppm): 1.41 (t, J = 7.2 Hz, 3H), 4.39 (q, J = 7.2 Hz, 2H), 6.52 (dd, J = 1.7, 3.5 Hz, 1H), 7.47 (d, J = 1.7 Hz, 1H), 7.73 (dd, J = 1.5, 4.4 Hz, 2H), 7.79 (d, J = 3.5 Hz, 1H), 8.71 (dd, J = 1.5, 4.4 Hz, 2H) ESIMS m / z: [MH] "342.

[Example 25] N- [4- (2-Furyl) -5- (l-oxopyridin-4-yl) thiazol-2-yl] acetamide (Compound 25) Compound 2 (550 mg, 1.92 mmol) was suspended in dichloromethane (30 mL), and m-chloroperbenzoic acid (531 mg, 2.51 mmol) was added thereto, followed by stirring at room temperature for 1 hour. An aqueous solution of sodium thiosulfate was added to the reaction mixture, followed by stirring for 30 minutes, and then the solvent was distilled continuously under reduced pressure. A saturated aqueous solution of sodium acid carbonate was added to the resulting residue, and the precipitated crystals were collected by filtration. The resulting crystals were washed successively with water and ethanol to give the title compound 25 (517 mg, 89%) as a yellow solid. XH-RM (DMSO-d6, d ppm): 2.18 (s, 3H), 6.59 (dd, J = 1.8, 3.3 Hz, 1H), 6.71 (dd, J = 0.7, 3.3 Hz, 1H), 7.44 (dd) , J = 1.5, 4.6 Hz, 2H), 7.66 (dd, J = 0.7, 1.8 Hz, 1H), 8.22 (dd, J = 1.5, 4.6 Hz, 2H), 12.5 (br s, 1H). ESIMS m / z: [M + H] + 302.

[Example 26] N- [4- (2-Furyl) -5-methylthiazol-2-yl] acetamide (Compound 26) In a manner similar to that in Example 2, the title compound 26 (206-mg, 80 %) is obtained from compound f (207 mg, 1.15 mmol) obtained in Reference Example 6 in place of compound a. X H NMR (DMSO-d 6, d ppm): 2.03 (s, 3 H), 2.55 (s, 3 H), 6.46 (d, J = 1.8, 3.3 Hz, 1 H), 6.56 (d, J = 3.3 Hz, 1 H) , 7.45 (d, J = 1.8 Hz, 1H). APCIMS m / z: [M + H] + 223.

[Example 27] N- [4- (2-Furyl) -5-phenylthiazol-2-yl] acetamide (Compound 27) In a manner similar to that in example 2, the title compound 27 (277 mg, 78% ) is obtained from compound c (300 mg, 1.24 mmol) obtained in reference example 3 in place of compound a. X H NMR (DMS0-d 6, d ppm): 2.17 (s, 3 H), 6.47-6.57 (m, 2 H), 7.35-7.49 (m, 5 H), 7.57 (d, J = 1.8 Hz, 1 H), 12.37 ( br s, 1 HOUR) . APCIMS m / z: [M + H] + 285.

[Example 28] N- [4- (2-Furyl) -5-phenylthiazol-2-yl] cyclohexanecarboxamide (Compound 28) In a manner similar to that in example 4, the title compound 28 (332 mg, 76% ) is obtained from compound c (300 mg, 1.24 mmol) obtained in reference example 3 in place of compound a. x NMR (DMSO-d6, d ppm): 1.24-1.86 (m, 10H), 2.50-2.56 (m, 1H), 6.51 (s, 2H), 7.42 (br s, 5H), 7.57 (s, 1H) , 12.30 (s, 1H). APCIMS m / z: [M + H] + 353.

[Example 29] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] pyridine-4-carboxamide (Compound 29) Step 1: Compound g (250 mg, 1.02 mmol) obtained in the example of Reference 7 was dissolved in DMF (4 mL), and morpholine (0.440 mL, 5.10 mmol) was added thereto, followed by stirring at 100 ° C for 6 hours. The reaction mixture was allowed to cool, and water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give 2-amino-4- (2-furyl) -5-morpholinothiazole (135 mg, 52%). . 2 H NMR (CDC13, d ppm): 2.86-2.89 (m, 4 H), 3.84-3.87 (m, 4 H), 4.94 (br s, 2 H), 6.47 (dd, J = 1.8, 3.3 Hz, 1 H), 6.85 (dd, J = 0.8, 3.3 Hz, 1H), 7.42 (dd, J = 0.8, 1.8 Hz, 1H).

Step 2: In a manner similar to that in Example 1, the title compound 29 (175 mg, 60%) is obtained from 2-amino-4- (2-furyl) -5-morpholinothiazole (206 mg, 0.82 mmol) obtained in step 1 in place of compound a. 1 H NMR (CDC13, d ppm): 3.02-3.05 (m, 4H), 3.89-3.92 (m, 4H), 6.43 (dd, J = 1.8, 3.3 Hz, 1H), 6.82 (dd, J = 0.8, 3.3 Hz, 1H), 7.31 (dd, J = 0.8, 1.8 Hz, 1H), 7.68 (dd, J = 1.5, 4.5 Hz, 2H), 8.76 (dd, J = 1.5, 4.5 Hz, 2H), 10.56 (br s, 1H). ESIMS m / z: [M-H] "355.

[Example 30] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] acetamide (Compound ) In a manner similar to that in Example 2, the title compound 30 (136 mg, 92%) is obtained from 2-amino-4- (2-furyl) -5-morpholinothiazole (127 mg, 0.51 mmol) obtained in step 1 of example 29 in place of the compound a obtained in reference example 1. α NMR (CDCl 3, d ppm): 2.17 (s, 3H), 2.98-3.01 (m, 4H), 3.86 (m, 4H), 6.50 (dd, J = 1.7, 3.3 Hz, 1H), 6.85 (d, J = 3.3 Hz, 1H), 7.44 (d, J = 1.7Hz, 1H), 9.25 (brs, 1H). ESIMS m / z: [M + H] + 294.

[Example 31] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] pyridine-3-carboxamide (Compound 31) In a manner similar to that in Example 1, by using nicotinoyl chloride hydrochloride (356 mg, 2.00 mmol) in place of isonicotinoyl chloride hydrochloride and using 2-amino-4- (2-furyl) -5-morpholinothiazole (251 mg, 1.00 mmol) obtained in step 1 of example 29 instead of compound obtained in reference example 1, the title compound 31 (216 mg, 61%) is obtained. 2 H NMR (CDC13, d ppm): 3.04 (t, J = 4.6 Hz, 4H), 3.90 (t, J = 4.6 Hz, 4H), 6.33 (dd, J = 1.9, 3.5 Hz, 1H), 6.85 (d , J = 3.5 Hz, 1H), 7.39 (d, J = 1.9 Hz, 1H), 7.45 (dd, J = 4.9, 7.8 Hz, 1H), 8.21 (ddd, J = 1.9, 2.2, 7.8 Hz, 1H) , 8.81 (dd, J = 1.9, 4.9 Hz, 1H), 9.14 (d, J = 2.2 Hz, 1H). APCIMS m / z: [M + H] + 357.

[Example 32] 2-Chloro-N- [4- (2-furyl) -5-morpholinothiazol-2-yl] pyridine-5-carboxamide (Compound 32) 2-Amino-4- (2-furyl) -5 -morpholinothiazole (2.15 g, 8.57 mmol) obtained in step 1 of example 29 was dissolved in pyridine (25 mL), and 6-chloronicotinoyl chloride (1.81 g, 10.3 mmol) and N, N-dimethylaminopyridine (105 mg, 0.86 g). mmol) were added to this. The mixture was stirred at room temperature for 10 hours, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1 to 1: 2) to give the title compound 32 (1.96 g, 59%). XH NMR (CDC13, d ppm): 3.04 (t, J = 4.3 Hz, 4H), 3.90 (t, J = 4.3 Hz, 4H), 6.41 (dd, J = 1.6, 3.5 Hz, 1H), 6.79 (d , J = 3.5 Hz, 1H), 7.23 (d, J = 1.6 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 8.11 (dd, J = 2.2, 8.4 Hz, 1H), 8.84 (d , J = 2.2 Hz, 1H).

[Example 33] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -2- [(2-hydroxyethyl) amino] pyridine-5-carboxamide (Compound 33) Compound 32 (391 mg, 1.00 mmol) was dissolved in 1,4-dioxane (4 mL), and ethanolamine (0.300 mL, 5.00 mmol) was added thereto, followed by stirring overnight under heating and reflux. The reaction mixture was concentrated under reduced pressure, and a saturated aqueous solution of sodium chloride and chloroform were added to the resulting residue, and the precipitated solid was collected by filtration to provide the title compound 33 (244 mg, 59%). X H NMR (DMSO-d 6, d ppm): 2.91 (t, J = 4.4 Hz, 4 H), 3.30-3.43 (m, 2 H), 3.51-3.54 (m, 2 H), 3.78 (t, J = 4.4 Hz, 4H), 4.74 (m, 1H), 6.55 (d, J = 8.9 Hz, 1H), 6.60 (dd, J = 1.9, 3.2 Hz, 1H), 6.81 (dd, J = 0.8, 3.2 Hz, 1H), 7.36 (t, J = 8.1 Hz, 1H), 7.68 (dd, J = 0.8, 1.9 Hz, 1H), 8.00 (dd, J = 2.2, 8.9 Hz, 1H), 8.75 (d, J = 2.2 Hz, 1H). APCIMS m / z: [M + H] + 416.

[Example 34] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -2-morpholinopyridine-5-carboxamide (Compound 34) Compound 32 (391 mg, 1.00 mmol) was dissolved in 1, 4- dioxane (10 mL) and morpholine (0.44 mL, 5.00 mmol) was added to this, followed by stirring under heating and reflux for 10 hours. The reaction mixture was concentrated under reduced pressure, and a saturated aqueous solution of sodium chloride was added to the resulting residue, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 19: 1) to give the title compound 34 (372 mg, 84%). a H NMR (CDC13, d ppm): 3.02 (t, J = 4.6Hz, 4H), 3.68 (t, J = 4.7 Hz, 4H), 3.82 (t, J = 4.7 Hz, 4H), 3.89 (t, J = 4.6 Hz, 4H), 6.51 (dd, J = 1.9, 3.5 Hz, 1H), 6.66 (d, J = 9.2 Hz, 1H), 6.88 (d, J = 3.5 Hz, 1H), 7.45 (d, J = 1.9 Rz, 1H), 7.98 (dd, J = 2.4, 9.2 Hz, 1H), 8.72 (d, J = 2.4 Hz, 1H). APCIMS m / z: [M + H] + 442.

[Example 35] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -2- (4-methylpiperazin-1-yl) pyridine-5-carboxamide (Compound 35) Compound 32 (391 mg , 1.00 mmol) was dissolved in 1,4-dioxane (10 mL), and 1-methylpiperazine (0.56 mL, 5.00 mmol) was added thereto, followed by stirring under heating and reflux for 10 hours. The reaction mixture was concentrated under reduced pressure, a saturated aqueous solution of sodium chloride was added to the resulting residue, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol: 28% aqueous ammonia = 10: 1: 1) to provide the title compound 35 (454 mg, 100%).

X H NMR (CDC1 d ppm): 2.36 (s, 3 H), 2.52 (t, J = 4.9 Hz, 4 H), 3. 02 (t, J = 4.6 Hz, 4H), 3.74 (t, J = 4.9 Hz, 4H), 3.89 (t, J = 4.6 Hz, 4H), 6.51 (dd, J = 1.9, 3.2 Hz, 1H), 6.66 (d, J = 9.4 Hz, 1H), 6.87 (d, J = 3.2 Hz, 1H), 7.45 (d, J = 1.9 Hz, 1H), 7.95 (dd, J = 2.4, 9.4 Hz, 1H), 8.70 (d, J = 2.4 Hz, 1H). APCIMS m / z: [M + H] + 455.

[Example 36] 2-Chloromethyl-N- [4- (2-furyl) -5-morpholinothiazol-2-yl] pyridine-5-carboxamide (Compound 36) Step 1: Methyl 6-chloromethyl-nicotinate (1.30 g, 7.00 mmol ) obtained according to the method described in W002 / 92455 was added to 2 mol / L hydrochloric acid, followed by stirring under heating and reflux for 5 hours. The reaction mixture was allowed to cool to room temperature, and the precipitated solid was collected by filtration to provide 6- (chloromethyl) nicotinic acid (539 mg, 45%). X H NMR (DMSO-d 6, d ppm): 4.87 (s, 2 H), 7.70 (d, J = 8.1 Hz, 1 H), 8.32 (dd, J = 2.2, 8.1 Hz 1 H), 9.04 (d, J = 2.2 Hz, 1H).

Step 2: 6- (Chloromethyl) nicotinic acid (172 mg, 1.00 mmol) obtained in step 1, 2-amino-4- (2-furyl) -5-morpholinothiazole (251 mg, 1.00 mmol) obtained in step 1 of Example 29 and PyBOP (572 mg, 1.10 mmol) were dissolved in DMF (4 mL), and triethylamine (0.307 mL, 2.20 mmol) was added thereto, followed by stirring at room temperature for 2 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 2: 1 to 1: 3) to provide the title compound 36 (194 mg, 48%). aH NMR (CDC13, d ppm): 3.04 (t, J = 4.6Hz, 4H), 3.85 (t, J = 4.6 Hz, 4H), 4.64 (s, 2H), 6.28 (dd, J = 2.2, 3.5 Hz , 1H), 6.69 (dd, J = 0.8, 3.5 Hz, 1H), 7.05 (dd, J = 0.8, 2.2 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 8.12 (dd, J = 2.4, 8.4 Hz, 1H), 8.98 (d, J = 2.4 Hz, 1H), 12.26 (br s, 1H).

[Example 37] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -2- (imidazol-1-ylmethyl) pyridine-5-carboxamide (Compound 37) Compound 36 (97.1 mg, 0.240 mmol) was dissolved in DMF (2.5 mL), imidazole (49.0 mg, 0.721 mmol) was added thereto, followed by stirring at 95 ° C for 2 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 17: 3) to give the title compound 37 (58.0 mg, 55%). 2 H NMR (CDCl 3, d ppm): 3.02 (t, J - 4.6 Hz, 4 H), 3.90 (t, J = 4.6 Hz, 4 H), 5.31 (s, 2 H), 6.42 (dd, J = 1.9, 3.2 Hz , 1H), 6.80 (d, J = 3.2 Hz, 1H), 6.97 (d, J = 8.1 Hz, 1H), 6.96-6.70 (m, 1H), 7.15-7.19 (m, 1H), 7.28 (d, J - 1.9 Hz, 1H), 7.62- 7.66 (m, 1H), 8.15 (dd, J = 2.2, 8.1 Hz, 1H), 9.09 (d, J = 2.2 Hz, 1H). APCIMS m / z: [M + H] + 437.

[Example 38] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -2- (4-hydroxypiperidinomethyl) pyridine-5-carboxamide (Compound 38) In a manner similar to that in Example 37, when using 4-hydroxypiperidine and 1,4-dioxane instead of imidazole and DMF, respectively, the title compound 38 (66.2 mg, 59%) is obtained from compound 36 (96.8 mg, 0. 239 mmol). aH NMR (CDCl 3, d ppm): 1.59-1.72 (m, 4H), 1.92-2.00 (m, 2H), 2.15-2.30 (m, 1H), 2.75-2.80 (m, 2H), 3.03 (t, J = 4.6 Hz, 4H), 3.73 (s, 2H), 3.96 (t, J = 4.6 Hz, 4H ), 6.47 (dd, J = 1.9, 3.5 Hz, 1H), 6.85 (dd, J = 0.8, 3.5 Hz, 1H), 7.38 (dd, J = 0.8, 1.9 Hz, 1H), 7.60 (d, J = 7.7 Hz, 1H), 8.18 (dd, J = 2.2, 7.7 Hz, 1H), 9.06 (d, J = 2.2 Hz, 1 HOUR) . APCIMS m / z: [M + H] + 470.

[Example 39] 2-Chloro-N- [4- (2-furyl) -5-morpholinothiazol-2-yl] pyridine-4-carboxamide (Compound 39) 2-Chloroisonicotinic acid (5.00 g, 31.7 mmol) was added to thionyl chloride (40 mL), followed by stirring under heating and reflux for 2 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in dichloromethane (1 mL). The resulting solution was added to a pyridine (16 mL) solution of 2-amino-4- (2-furyl) -5-morpholinothiazole (880 mg, 5.00 mmol) obtained in step 1 of Example 29, and then N / N Dimethylaminopyridine (48.8 mg, 0.400 mmol) was added thereto, followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 3 to ethyl acetate) to provide the title compound 39 (1.05 g, 66%) at H NMR (CDC13, d ppm): 3.03 (t, J = 4.6 Hz, 4H), 3.60 (t, J = 4.6 Hz, 4H), 6.52 (dd, J = 1.6, 3.5 Hz, 1H), 6.88 (dd, J = 0.8, 3.5 Hz, 1H), 6.95 (dd, J = 1.4, 5.1 Hz , 1H), 7.10-7.12 (m, 1H), 7.46 (dd, J = 0.8, 1.6 Hz, 1H), 8.35 (dd, J = 0.8, 5.1 Hz, 1H), 9.33 (br s, 1H).

[Example 40] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -2-morpholinopyridine-4-carboxamide (Compound 40) Compound 39 (391 mg, 1.00 mmol) was dissolved in NMP ( 10 mL), morpholine (1.05 mL, 12.0 mmol) was added thereto, followed by stirring at 150 ° C for 8 hours. The reaction mixture was purified through silica gel column chromatography (hexane: ethyl acetate = 2: 1 to 1: 3) to give the title compound 40 (118 mg, 27%). X H NMR (CDC13, d ppm): 3.03 (t, J = 4.6 Hz, 4H), 3.58 (t, J = 4.9 Hz, 4H), 3.84 (t, J = 4.9 Hz, 4H), 3.88 (t, J = 4.6 Hz, 4H), 6.50 (dd, J = 1.9, 3.5 Hz, 1H), 6.86 (d, J = 3.5 Hz, 1H), 6.94 (dd, J = 1.6, 5.1 Hz, 1H), 7.09 (d , J = 1.6 Hz, 1H), 7.42 (d, J = 1.9 Hz, 1H), 8.33 (d, J = 5.1 Hz, 1H). APCIMS m / z; [M + H] + 442.

[Example 41] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -2- (4-methylpiperazin-1-yl) pyridine-4-carboxamide (Compound 41) Compound 39 (391 mg , 1.00 mmol) was dissolved in NMP (10 mL), and 1-methylpiperazine (1.11 mL, 10.0 mmol) was added thereto, followed by stirring overnight at 150 ° C. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: ethanol = 19: 1) to give the title compound 41 (22.2 mg, 5%). XH NMR (CDC1, d Ppm): 2.37 (s, 3H), 2.55 (t, J = 4.9 Hz, 4H), 3.03 (t, J = 4.6 Hz, 4H), 3.66 (t, J = 4.9 Hz, 4H ), 3.90 (t, J = 4.6 Hz, 4H), 6.51 (dd, J = 1.9, 3.2 Hz, 1H), 6.87 (dd, J = 0.8, 3.2 Hz, 1H), 6.90 (dd, J = 1.3, 5.1 Hz, 1H), 7.11 (d, J = 1.3 Hz, 1H), 7.44 (dd, J = 0.8, 1.9 Hz, 1H), 8.32 (d, J = 5.1 Hz, 1H), 9.50 (brs, 1H) ). APCIMS m / z: [M + H] + 455.

[Example 42] 1- (tert-Butoxycarbonyl) -N- [4- (2-furyl) -5-morpholinothiazol-2-yl] piperidine-4-carboxamide (Compound 42) 2-Amino-4- (2- furil) -5-morpholinothiazole (3.58 q, 14.3 mmol) obtained in step 1 of example 29, 1- (tert-butoxycarbonyl) -4-piperidinecarboxylic acid (3.27 g, 14.3 mmol) and PyBOP (8.16 g, 15.7 mmol) were dissolved in DMF (30 L), and triethylamine (4.37 mL, 31.4 mmol) was added thereto, followed by stirring overnight at room temperature. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed successively with 1 mol / L hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give the title compound 42 (4.52 g, 68%). XH NMR (CDC13, d ppm): 1.45 (s, 9H), 1.60-1.80 (m, 4H), 2.20-2.28 (m, 1H), 2.49-2.58 (m, 2H), 3.00 (t, J = 4.6 Hz, 4H), 3.88 (t, J = 4.6 Hz, 4H), 3.95-4.15 (m, 2H), 6.52 (dd, J = 1.9, 3.5 Hz, 1H), 6.90 (d, J = 3.5 Hz, 1H ), 7.43 (d, J = 1.9 Hz, 1H), 10.28 (br s, 1H). APCIMS m / z: [M + H] + 463.

[Example 43] 1- (Benzyloxycarbonyl) -N- [4- (2-furyl) -5-morpholinothiazol-2-yl] piperidine-4-carboxamide (Compound 43) l-Benzyloxycarbonylpiperidine-4-carboxylic acid (5.00 g, 19.0 mmol) was dissolved in dichloromethane (80 mL), and thionyl chloride (6.93 mL, 95.0 mmol) and DMF mL, 1.90 mmol) were added thereto, followed by stirring under heating and reflux for 3 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in dichloromethane (2 mL). The resulting solution was added to a solution of 2-amino-4- (2-furyl) -5-morpholinothiazole (2.01 g, 8.00 mmol) in pyridine (32 mL) obtained in step 1 of the Example 29, and then N, N-dimethylaminopyridine (97.6 mg, 0.800 mmol) was added thereto, followed by stirring at room temperature for 1 hour. The solvent was distilled continuously under reduced pressure, and the resulting residue was purified through silica gel column chromatography (hexane-ethyl acetate = 1: 1 to 1: 3) to provide the title compound 43 (4.96 g, 100%). 2 H NMR (CDC13, 5 ppm): 1.61-1.78 (m, 4H), 2.30-2.38 (m, 1H), 2.70-2.78 (m, 2H), 2.98 (t, J = 4.6 Hz, 4H), 3.88 ( t, J = 4.6 Hz, 4H), 4.13-4.23 (m, 2H), 5.12 (s, 2H), 6.51 (dd, J = 1.6, 3.2 Hz, 1H), 6.87 (d, J = 3.2 Hz, 1H ), 7.29-7.36 (m, 5H), 7.44 (d, J = 1.6 Hz, 1H), 9.71 (br s, 1H). APCIMS m / z: [M + H] + 497.

[Example 44] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] piperidine-4-carboxamide (Compound 44) Compound 43 (4.71 g, 9.50 mmol) was dissolved in dichloromethane (100 L) , and dimethyl sulfide (29.4 mL, 400 mmol) and boron trifluoride diethyl ether complex (24.6 mL, 200 mmol) were added thereto, followed by stirring overnight at room temperature. The reaction mixture was poured into 28% aqueous ammonium, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled under reduced pressure to provide the title compound 44 (1.36 g, 38%). X H NMR (DMSO-de, 5 ppm): 1.43-1.57 (m, 2H), 1.67-1.71 (m, 2H), 2. 40-2.60 (m, 3H), 2.88 (t, J = 4.6 Hz, 4H), 2.95-3.00 (m, 2H), 3.77 (t, J = 4.6 Hz, 4H), 6.59 (dd, J = 1.9, 3.2 Hz, 1H), 6.77 (dd, J = 0.8, 3.2 Hz, 1H), 7.67 (dd, J = 0.8, 1.9 Hz, 1H). APCIMS m / z: [M + H] + 363.

[Example 45] 1- (5-Cyano-pyridin-2-yl) -N- [4- (2-furyl) -5-morpholinothiazol-2-yl] piperidine-4-carboxamide (Compound 45) Compound 44 (181 mg , 0.50 mmol), 2-chloro-5-cyanopyridine (104 mg, 0.75 mmol) and potassium carbonate (207 mg, 1.50 mmol) were suspended in 1,4-dioxane (4 mL), followed by stirring overnight under heating and reflux. The insoluble was removed through filtration, the filtrate was distilled off under reduced pressure, and the resulting residue was purified through silica gel column chromatography (chloroform-methanol = 20: 1) to give the title compound. (158 mg, 68%). XH NMR (CDC13, d ppm): 1.70-1.95 (m, 4H), 2.40-2.55 (m, 1H), 2.85-2.95 (m, 2H), 2.99 (t, J = 4.6 Hz, 4H), 3.88 (t, J = 4.6 Hz, 4H), 4.35-4.45 (m, 2H), 6.52 (dd, J = • 1.9, 3.5 Hz, 1H), 6.60 (d, J = 9.4 Hz, 1H), 6.87 (dd, J = 0. 8, 3.5 Hz, 1H), 7.45 (dd, J = 0.8, 1.9 Hz, 1H), 7.61 (dd, J = 2.2, 9.4 Hz, 1H), 8.40 (d, J = 2.2Hz, 1H.), 9.76 (brs, 1H). APCIMS m / z: [M + H] + 465.

[Example 46] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -1- [5- (methanesulfonyl) pyridin-2-yl] piperidine-4-carboxamide (Compound 46) In a manner similar to that in Example 45, when using 2-chloro-S- (methanesulfonyl) pyridine (144 mg, 0.75 mmol) obtained according to the method described in W002 / 51836 in place of 2-chloro-5-cyanopyridine, the Compound of title 46 (83.3 mg, 32%) is obtained from compound 44 (181 mg, 0.50 mmol). XH NMR (CDC13, d ppm): 1.70-1.90 (m, 2H), 1.90-2.00 (m, 2H), 2.45-2.55 (m, 1H), 2.99 (t, J = 4.7 Hz, 4H), 3.04 ( s, 3H), 3.05-3.10 (m, 2H), 3.88 (t, J = 4.7 Hz, 4H), 4.41-4.51 (m, 2H), 6.52 (dd, J = 1.9, 3.2 Hz, 1H), 6 , 63 (d, J = 9.2 Hz, 1H), 6.87 (d, J = 3.2 Hz, 1H), 7.45 (d, J = 1.9 Hz, 1H), 7.87 (dd, J = 2.4, 9.2 Hz, 1H) , 8.63 (d, J = 2.4 Hz, 1H), 9.51 (br s, 1H). APCIMS m / z: [M + H] + 518.

[Example 47] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -1- (5-nitropyridin-2-yl) piperidine-4-carboxamide (Compound 47). In a manner similar to that in example 45, when using 2-chloro-5-nitropyridine (238 mg, 1.50 mmol) in place of 2-chloro-5-cyanopyridine, the title compound 47 (78.5 mg, 41%) it is obtained from compound 44 (145 mg, 0.400 mmol). aH NMR (CDC13, d ppm): 1.75-1.95 (m, 4H), 2.40-2.55 (m, 1H), 2.90-3.00 (m, 2H), 3.00 (t, J = 4.6Hz, 4H), 3.80- 3.90 (m, 2H), 3.89 (t, J = 4.6 Hz, 4H), 6.52 (dd, J = 1.9, 3.5 Hz, 1H), 6.76 (dd, J = 4.6, 8.1 Hz, 1H), 6.88 (dd) , J = 0.8, 3.5 Hz, 1H), 7.45 (dd, J = 0.8, 1.9 Hz, 1H), 8.13 (dd, J = 1.8, 8.1 Hz, 1H), 8.32 (dd, J = 1.8, 4.6 Hz, 1H), 9.70 (br s, 1H) APCIMS m / z: [M + H] + 485.

[Example 48] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -1- (3-nitropyridin-2-yl) piperidine-4-carboxamide (Compound 48) In a manner similar to that in Example 45, using 2-chloro-3-nitropyridine (238 mg, 1.50 mmol) in place of 2-chloro-5-cyanopyridine, the title compound 48 (76.0 mg, 39%) is obtained from compound 44 ( 145 mg, 0.400 mmol). X H NMR (CDCl 3, d ppm): 2.37 (m, 1 H), 2.54 (t, J = 4.9 Hz, 4 H), 3.03 (t, J = 4.6 Hz, 4 H), 3.66 (t, J = 4.9 Hz, 4 H ), 3.89 (t, J = 4.6 Hz, 4H), 6.50 (dd, J = 1.6, 3.2 Hz, 1H), 6.86 (dd, J = 0.8, 1.6 Hz, 1H), 6.89 (dd, J = 1.6, 5.1 Hz, 1H), 7.10 (d, J = 1.6 Hz, 1H), 7.43 (dd, J = 0.8, 1.6 Hz, 1H), 8.31 (d, J = 5.1 Hz, 1H), 9.50 (br, s, 1H). APCIMS m / z: [M + H] + 485.

[Example 49] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -1- (2-pyrimidinyl) piperidine-4-carboxamide (Compound 49) In a manner similar to that in the example 45, using 2-chloropyrimidine (172 mg, 1.50 mmol) in place of 2-chloro-5-cyanopyridine, the title compound 49 (87.5 mg, 50%) is obtained from compound 44 (145 mg, 0.40 mmol). 2 H NMR (CDC13, d ppm): 1.72-1.78 (m, 2H), 1.85-1.95 (m, 2H), 2.40-2.50 (m, 1H), 2.83-2.89 (, 2H), 2.99 (t, J = 4.6 Hz, 4H), 3.88 (t, J = 4.6 Hz, 4H), 4.72-4.80 (m, 2H), 6.49 (t, J = 4.9 Hz, 2H), 6.51 (dd, J = 1.6, 3.5 Hz, 1H), 6.87 (dd, J = 0.8, 3.5 Hz, 1H), 7.45 (dd, J = 0.8, 1.6 Hz, 1H), 8.30 (d, J = 4.9 Hz, 1H), 9.54 (br s, 1H) . APCIMS m / z: [M + H] + 441.

[Example 50] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -1- (2-pyrazinyl) piperidine-4-carboxamide (Compound 50) In a manner similar to that in Example 45 , when using 2-chloropyrazine (0.69 L, 0.75 mmol) instead of 2- chloro-5-cyanopyridine, the title compound 50 (37.5 mg, 17%) is obtained from compound 44 (181 mg, 0.5 mmol). X H NMR (DMSO-d 6, d ppm): 2.91 (t, J = 4.6 Hz, 4H), 3.30-3.40 (m, 4H), 3.45-3.50 (m, 2H), 3.55-3.65 (m, 2H), 3.78 (t, J = 4.6 Hz, 4H), 4.72-4.76 (m, 1H), 6.55 (d, J = 9.2 Hz, 1H), 6.60 (dd, J = 1.9, 3.2 Hz, 1H), 6.82 (dd) , J = 0.8, 3.2 Hz, 1H), 7.68 (dd, J = 0.8, 1.9 Hz, 1H), 8.01 (dd, J = 2.4, 9.2 Hz, 1H), 8.75 (d, J = 2.4 Hz, 1H) , 12.26 (br s, 1H). APCIMS m / z: [M + H] + 441.

[Example 51] 1- (6-Chloropyrimidin-4-yl) -N- [4- (2-furyl) -5-morpholinothiazol-2-yl] piperidine-4-carboxamide (Compound 51) In a manner similar to that in Example 45, using 4,6-dichloropyrimidine (298 mg, 2.00 mmol) in place of 2-chloro-5-cyanopyridine, the title compound 51 (356 mg, 75%) is obtained from compound 44 (361 mg 1.00 mmol). X H NMR (CDC13, d ppm): 1.70-1.90 (m, 4H), 2.40-2.55 (m, 1H), 2.84-2.93 (m, 2H), 2.99 (t, J = 4.6 Hz, 4H), 3.88 (t, J = 4.6 Hz, 4H), 4.28-4.38 (, 2H), 6.50 (s, 1H), 6. 53 (dd, J = 1.9, 3.5 Hz, 1H), 6.88 (d, J = 3.5 Hz, 1H), 7.45 (d, J = 1.9 Hz, 1H), 8.37 (s, 1H), 10.24 (br s, 1H). APCIMS m / z: [31C1M + H] + 475, [37C1M + H] + 477.

[Example 52] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -1- (4-pyrimidinyl) piperidine -carboxamide (Compound 52) Compound 51 (300 mg, 0.63 mmol) was dissolved in ethanol (10 mL) and 10% carbon in palladium (500 mg) was added thereto, followed by stirring in a hydrogen atmosphere at room temperature for 4 hours. The reaction mixture was filtered through Celite, and the filtrate was distilled under reduced pressure to provide the title compound 52 (213 mg, 77%). X H NMR (CDC13, d ppm): 1.70-1.90 (, 2H), 1.90-2.05 (m, 2H), 2.45-2.55 (m, 1H), 2.99 (t, J = 4.6 Hz, 4H), 3.00-3.05 (m, 2H), 3.88 (t, J = 4.6 Hz, 4H), 4.37-4.47 (m, 2H), 6.50-6.54 (m, 2H), 6.86 (d, J = 3.2 Hz, 1H), 7.45 ( d, J = 1.6 Hz, 1H), 8.21 (d, J = 6.2 Hz, 1H), 8.60 (s, 1H), 9.20 (br s, 1H). APCIMS m / z: [M + H] + 441.

[Example 53] 1- (6-Chloropyridazin-3-yl) -N- [4- (2-furyl) -5-morpholinothiazol-2-yl] piperidine-4-carboxamide (Compound 53) In a manner similar to that in Example 45, using 3,6-dichloropyridazine (298 mg, 2.00 mmol) in place of 2-chloro-5-cyanopyridine, the title compound 53 (299 mg, 63%) is obtained from compound 44 (361 mg 1.00 mmol).

X H NMR (CDCl 3, d ppm): 1.70-2.00 (m, 4H), 2.45-2.55 (m, 1H), 2.90-3.05 (m, 2H), 2.99 (t, J = 4.6 Hz, 4H), 3.88 ( t, J = 4.6 Hz, 4H), 4.29-4.39 (m, 2H, 2H), 6.52 (dd, J = 1.6, 3.5 Hz, 1H), 6.87 (dd, J = 3.5 Hz, 1H), 6.91 (d , J = 9.4 Hz, 1H), 7.21 (d, J = 9.4 Hz, 1H), 7..45 (d, J = 1.6 Hz, 1H), 9.56 (br s, 1H). APCIMS m / z: [35CIM + H] + 475, [37CIM + H] + 477.

[Example 54] 1-Acetyl-N- [4- (2-furyl) -5-morpholinothiazol-2-yl] piperidine-4-carboxamide (Compound 54) Compound 44 (145 mg, 0.400 mmol) was dissolved in pyridine (5 mL), acetic anhydride (0.19 mL, 2.00 mmol) was added thereto, followed by stirring at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (ethyl acetate: methanol = 9: 1) to give the title compound 54 (40.0 mg, 25% ). E NMR (CDCl 3, d ppm): 1.60-1.95 (m, 4H), 2.11 (s, 3H), 2.40-2.55 (, 1H), 2.60-2.80 (m, 1H), 2.98 (t, J = 4.6 Hz , 4H), 3.00-3.15 (m, 1H), 3.88 (t, J = 4.6 Hz, 4H), 3.88-3.95 (m, 1H), 4.57 (d, J = 13.5 Hz, 1H), 6.51 (dd, J = 1.9, 3.5 Hz, 1H), 6.86 (dd, J = 0.8, 3.5 Hz, 1H), 7.45 (dd, J = 0.8, 1.9 Hz, 1H), 9.18 (br s, 1H). APCIMS m / z: [M + H] + 405.

[Example 55] 1- (N ', N-Dimethylcarbamoyl) -N- [4- (2-furyl) -5-morpholinothiazol-2-yl] piperidine-4-carboxamide (Compound 55) Step 1: A mixture of isonipecotinate of ethyl (1.54 mL, 10.0 mmol), triethylamine (4.18 mL, 30.0 mmol) and N, N-dimethylcarbamoyl chloride (2.20 mL, 24.0 mmol) was stirred overnight at room temperature. 28% aqueous ammonium was added to the reaction mixture, followed by stirring at room temperature for 10 minutes, and then extracted with chloroform. The organic layer was washed successively with 1 mol / L hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: ethyl acetate = 1: 1) to provide ethyl 1- (N, N-dimethylcarbamoyl) piperidine-4-carboxylate (2.28 g, 100% ). x NMR (CDC13, d ppm): 1.26 (t, J = 6.9 Hz, 3H), 1.65-1.76 (m, 2H), 1.85-1.94 (, 2H), 2.41-2.85 (m, 1H), 2.77-2.85 (m, 2H), 2.83 (s, 6H), 3.59-3.65 (m, 2H), 4.14 (q, J = 6.9 Hz, 2H).

Step 2: The ethyl 1- (N, N-dimethylcarbamoyl) piperidine-4-carboxylate (2.28 g, 10.0 mmol) obtained in step 1 was dissolved in a mixed solvent of methanol (30 mL) and water (10 mL), lithium hydroxide monohydrate (2.10 g, 50.0 mmol) was added thereto, followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and 6 mol / L hydrochloric acid was added to the resulting residue to adjust the pH to 1, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was continuously distilled under reduced pressure to provide 1- (N, N-dimethylcarbamoyl) piperidine-4-carboxylic acid (830 mg, 42%) -aH NMR (CDC13 , d ppm): 1.68-1.79 (m, 2H), 1.91-1.97 (m, 2H), 2.46-2.54 (m, 1H), 2.80-2.85 (m, 2H), 2.82 (s, 6H), 3.58- 3.66 (m, 2H).

Step 3: The 1- (N, N-dimethylcarbamoyl) piperidine-4-carboxylic acid (300 mg, 1.50 mmol) obtained in step 2 was dissolved in dichloromethane (15 mL), and thionyl chloride (0.547 mL, 7.50 mmol) was added thereto, followed by stirring under heating and reflux for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue The resulting solution was dissolved in chloroform (5 mL). The resulting solution was added to a pyridine (10 mL) solution of 2-amino-4- (2-furyl) -5-morpholinothiazole (126 mg, 0.50 mmol) obtained in step 1 of Example 29, followed by stirring at room temperature. environment for 1 hour. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (ethyl acetate: methanol = 9: 1) to give the title compound 55 (171 mg, 81% ). XH NMR (CDC13, d ppm): 1.60-1.95 (m, 4H), 2.35-2.50 (m, 1H), 2. 70-2.80 (m, 2H), 2.83 (s, 6H), 3.00. (t, J = 4.3 Hz, 4H), 3. 68 (d, J = 13.5 Hz, 2H), 3.88 (t, J = 4.3 Hz, 4H), 6.51 (dd, J = 1.6, 3.2 Hz, 1H), 6.86 (dd, J = 0.5, 3.2 Hz, 1H), 7.44 (dd, J = 0.5, 1.6 Hz, 1H), 9.54 (br s, 1H). APCIMS m / z: [M + H] + 434.

[Example 56] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -1- (morpholinocarbonyl) piperidine-4-carboxamide (Compound 56) In a manner similar to that in Example 55, using morpholinecarbonyl chloride in place of N, N-dimethylcarbamoyl chloride, the title compound 56 (167 mg, 72%) is obtained from 2-amino-4 ~ (2-furyl) -5- orfolinothiazole (126 mg , 0.50 mmol) obtained in step 1 of example 29.

X H NMR (CDCl 3, d ppm): 1.60-1.90 (m, 4H), 2.30-2.50 (m, 1H), 2.65-2.85 (m, 2H), 2.99 (t, J = 4.3 Hz, 4H), 3.26 ( t, J = 4.3 Hz, 4H), 3.68 (t, J = 4.3 Hz, 4H), 3.66-3.76 (m, 2H), 3.88 (t, J = 4.3 Hz, 4H), 6.51 (dd, J = 1.9 , 3.5 Hz, 1H), 6.87 (d, J = 3.5 Hz, 1H), 7.44 (d, J = 1.9 Hz, 1H), 9.73 (br s, 1H). APCIMS m / z: [M + H] + 476. [Example 57] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -1-methanesulfonylpiperidine-4-carboxamide (Compound 57) In a Similar to that in example 55, when using methanesulfonyl chloride instead of N, N-dimethylcarbamoyl chloride, the title compound 57 (123 mg, 56%) is obtained from 2-amino-4- (2 -furyl) -5-morpholinothiazole (126 mg, 0.50 mmol) obtained in step 1 of example 29. X H NMR (CDCl 3, d ppm): 1.80-2.00 (m, 4 H), 2.35-2.50 (m, 1 H), 2.70-2.85 (m, 2H), 2.80 (s, 3H), 2.99 (t, J = 4.3 Hz, 4H), 3.76 (ddd, J = 3.8, 3.8, 14.6 Hz, 2H), 3.88 (t, J = 4.3 Hz, 4H), 6.52 (dd, J = 1.9, 3.5 Hz, 1H), 6.87 (d, J = 3.5 Hz, 1H), 7.45 (d, J = 1.9 Hz, 1H), 9.67 (br s, 1H ). APCIMS m / z: [M + H] + 441. [Example 58] 1- (N, N-Dimethylsulfamoyl) -N- [4- (2-furyl) -5-morpholinothiazol-2-yl] piperidine-4- carboxamide (Compound 58) In a manner similar to that in Example 55, by using N, N-dimethylsulphamoyl chloride instead of chloroform.

N, N-dimethylcarbamoyl, the title compound 58 (103 mg, 44%) is obtained from 2-amino-4- (2-furyl) -5-morpholinothiazole (126 mg, 0.50 mmol) obtained in step 1 from Example 29. 2H NMR (CDC13, d ppm): 1.70-1.95 (m, 4H), 2.25-2.45 (m, 1H), 2.70-2.85 (m, 2H), 2.83 (s, 6H), 2.99 (t , J = 4.6 Hz, 4H), 3.78 (ddd, J = 3.8, 3.8, 14.8 Hz, 2H), 3.89 (t, J = 4.6 Hz, 4H), 6.52 (dd, J = 1.9, 3.2 Hz, 1H) , 6.87 (d, J = 3.2 Hz, 1H), 7.44 (d, J = 1.9 Hz, 1H), 9.75 (brs, 1H). APCIMS m / z: [M + H] + 470.

[Example 59] 4- (Bromomethyl) -N- [4- (2-furyl) -5-morpholinothiazol-2-yl] benzamide (Compound 59) 4- (Bromomethyl) benzoic acid (2.24 g, 10.4 mmol) was dissolved in toluene (80 mL) and thionyl chloride (7.59 mL, 104 mmol) was added thereto, followed by stirring under heating and refluxing for 6 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in THF (50 mL) and 2-amino-4- (2-furyl) -5-morpholinothiazole (2.00 g, 7.97 mmol) obtained in step 1 of Example 29, triethylamine (1.67 mL, 12.0 mmol ) and N, N-dimethylaminopyridine (97.6 mg, 0.800 mmol) were added thereto, followed by stirring under heating and reflux for 1 hour. The reaction mixture was allowed to cool to Room temperature, and then a 10% aqueous solution of sodium carbonate was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: ethyl acetate = 9: 1) to give the title compound 59 (3.29 g, 92%). x NMR (CDC13, d ppm): 3.03 (t, J = 4.6Hz, 4H), 3.89 (t, J = 4.6 Hz, 4H), 4.59 (s, 2H), 6.40 (dd, J = 1.6, 3.2 Hz , 1H), 6.79 (d, J = 3.2 Hz, 1H), 7.25 (d, J = 1.6 Hz, 1H), 7.43 (dd, J = 2.2, 8.6 Hz, 2H), 7.83 (dd, J = 2.2, 8.6 Hz, 2H), 10.56 (br s, 1H).

[Example 60] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -4- (imidazol-1-ylmethyl) benzamide (Compound 60) Compound 59 (448 mg, 1.00 mmol) was dissolved in DMF (4 L), imidazole (204 mg, 3.00 mmol) was added thereto, followed by stirring at 65 ° C for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 20: 1) to give the title compound 60 (348 mg, 80%). aH NMR (CDC13, d ppm): 3.03 (t, J = 4.6 Hz, 4H), 3.90 (t, J = 4.6 Hz, 4H), 5.23 (s, 2H), 6.52 (dd, J = 1.9, 3.2 Hz , 1H), 6.88 (d, J = 3.2 Hz, 1H), 6.93 (s, 1H), 7.15 (s, 1H), 7.28 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 1.9 Hz , 1H), 7.61 (s, 1H), 7.90 (d, J = 8.4 Hz, 2H), 9.45 (br s, 1H). APCIMS m / z: [M + H] + 436.

[Example 61] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -4- [4- (hydroxypiperidino) methyl] benzamide (Compound 61) In a manner similar to that in Example 60 , using 4-hydroxypiperidine and 1,4-dioxane instead of imidazole and DMF, respectively, the title compound 61 (351 mg, 75%) is obtained from compound 59 (448 mg, 1.00 mmol). X H NMR (CDCl 3, d ppm): 1.50-1.70 (m, 3 H), 1.88-1.93 (m, 2 H), 2.14-2.22 (m, 2 H), 2.72-2.76 (m, 2 H), 3.03 (t, J = 4.5 Hz, 4H), 3.55 (s, 2H), 3.70-3.75 (m, 1H), 3.90 (t, J = 4.5 Hz, 4H), 6.49 (dd, J = 1.9, 3.2 Hz, 1H), 6.86 (d, J = 3.2 Hz, 1H), 7.41 (d, J = 1.9 Hz, 1H), 7.46 (d, J = 8.1 Hz, 2H), 7.86 (d, J = 8.1 Hz, 2H), 9.70 (br s, 1H).

APCIMS m / z: [M + H] + 469.

[Example 62] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -4- (morpholinomethyl) benzamide (Compound 62) In a manner similar to that in Example 60, by using morpholine and , 4-dioxane instead of imidazole and DMF, respectively, the title compound 62 (36.5 mg, 8%) is obtained from compound 59 (448 mg, 1.00 mmol). 2 H NMR (CDC13, d ppm): 2.46 (t, J = 4.6Hz, 4H), 3.03 (t, J = 4.6 Hz, 4H), 3.57 (s, 2H), 3.73 (t, J = 4.6 Hz, 4H ), 3.90 (t, J = 4.6 Hz, 4H), 6.50 (dd, J = 1.6, 3.5 Hz, 1H), 6.87 (dd, J = 0.8, 3.5 Hz, 1H), 7.44 (dd, J = 0.8, 1.6 Hz, 1H), 7.49 (d, J = 8.1 Hz, 2H), 7.86 (d, J = 8.1 Hz, 2H), 9.51 (br s, 1H). APCIMS m / z: [M + HJ + 455.

[Example 63] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -4-. { [N- (2-methoxyethyl) -N-methylamino] methyl} Benzamide (Compound 63) In a manner similar to that in Example 60, when using N- (2-methoxyethyl) -N-methylamine and 1,4-dioxane instead of imidazole and DMF, respectively, the title compound 63 (173 mg, 38%) is obtained from compound 59 (448 mg, 1.00 mmol).

X H NMR (DMSO-d 6, d ppm): 2.74 (s, 3 H), 2.94 (t, J = 4.6 Hz, 4 H), 3.16-3.30 (m, 2 H), 3.31 (s, 3 H), 3.70-3.73 ( m, 2H), 3.79 (t, J = 4.6 Hz, 4H), 4.36 (d, J = 13.5 Hz, 1H), 4.48 (d, J = 13.5 Hz, 1H), 6.62 (dd, J = 1.6, 3.2 Hz, 1H), 6.84 (d, J = 3.2 Hz, 1H), 7.70 (d, J = 3.2 Hz, 1H), 7.73 (d, J = 8.1 Hz, 2H), 8.18 (d, J = 8.1 Hz, 2H). APCIMS m / z: [M + H] + 457.

[Example 64] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -4- [2- (oxopiperidino) methyl] benzamide (Compound 64) Step 1: 60% sodium hydride (600 mg, 15.0 mmol) was suspended in DMF (30 mL), 2-piperidone (1.49 g, 15.0 mmol) was added thereto, followed by stirring at room temperature for 30 minutes. A solution of methyl 4-bromomethylbenzoate (2.29 g, 10.0 mmol) in DMF (10 mL) was added to the reaction mixture, followed by stirring at room temperature for 3 hours. The reaction mixture was poured into a saturated aqueous solution of sodium chloride, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate: methanol = 9: 1) to give methyl 4- ((2-oxopiperidino) methyl] benzoate (2.47 g 100%). a H NMR (CDCl 3, d ppm): 1.74-1.85 (m, 4H), 2.46-2.51 (m, 2H), 3.20-3.22 (m, 2H), 3.91 (s, 3H), 4.64 (s, 2H), 7.31 (d, J = 8.0 Hz, 2H), 8.00 (d, J = 8.0 Hz, 2H).

Step 2: Methyl 4- [(2-oxopiperidino) methyl] benzoate (2.47 g, 10.0 mmol) obtained in step 1 was dissolved in a mixed solvent of methanol (30 mL) and water (10 mL), and monohydrate of lithium hydroxide (2.10 g, 50.0 mmol) was added thereto, followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and 6 mol / L hydrochloric acid was added to the resulting residue to adjust the pH to 1, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was continuously distilled under reduced pressure to provide 4 - [(2-oxopiperidino) methyl] benzoic acid (629 mg, 27%). JH NMR (DMSO-de, d ppm): 1.69-1.75 (m, 4H), 2.27-2.34 (, 2H), 3.14-3.22 (m, 2H), 4.56 (s, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 8.4 Hz, 2H).

Step 3: The 4 ~ [(2-oxopiperidino) methyl] benzoic acid (233 mg, 1.00 mmol) obtained in step 2 was dissolved in dichloromethane (10 mL) and thionyl chloride (5 mL) was added thereto, followed by stirring under heating and reflux for 1 hour. The The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in chloroform (5 mL). The resulting solution was added to a solution of 2-amino-4- (2-furyl) -5-morpholinothiazole (126 mg, 0.50 mmol) in pyridine (10 mL) obtained in step 1 of Example 29, followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (chloroform: methanol = 20: 1) to give the title compound 64 (68.3 mg, 29%). XH NMR (CDC13, d ppm): 1.81-1.84 (m, 4H), 2.48-2.51 (m, 2H), 3.03 (t, J = 4.6 Hz, 4H), 3.22-3.26 (m, 2H), 3.90 ( t, J = 4.6 Hz, 4H), 4.66 (s, 2H), 6.51 (dd, J = 1.9, 3.5 Hz, 1H), 6.88 (dd, J = 0.5, 3.5 Hz, 1H), 7.45 (dd, J = 0.5, 1.9 Hz, 1H), 7.67 (d, J = 13.5 Hz, 2H), 7.87 (d, J = 13.5 Hz, 2H), 9.45 (br s, 1H). APCIMS m / z: [M + H] + 467.

[Example 65] N- [4- (2-Furyl) -5-morpholinothiazol-2-yl] -4- [(2-oxo-l, 2-dihydropyridin-1-yl) methyl] benzamide (Compound 65) In a similar manner to that in Example 64, when using 2-hydroxypyridine instead of 2-piperidone, the compound of title 65 (66.2 mg, 29%) is obtained from 2-amino-4- (2-furyl) -5-morpholinothiazole (126 mg, 0.50 mmol) obtained in step 1 of example 29. XH NMR (CDC13 , d ppm): 3.02 (t, J = 4.6 Hz, 4H), 3.89 (t, J = 4.6 Hz, 4H), 5.21 (s, 2H), 6.20 (ddd, J = 1.4, 6.5, 6.5 Hz, 1H ), 6.51 (dd, J = 1.9, 3.5 Hz, 1H), 6.65 (dd, J = 1.4, 8.6 Hz, 1H), 6.87 (dd, J = 0.8, 3.5 Hz, 1H), 7.28 (dd, J = 2.2, 6.5 Hz, 1H), 7.36 (ddd, J = 2.2, 6.5, 8.6 Hz, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.45 (dd, J = 0.8, 1.9 Hz, 1H), 7.88 (d, J = 8.4 Hz, 2H) / 9.44 (br s, 1H). APCIMS m / z: [M + H] + 463.

[Example 66] N- [4- (2-Furyl) -5- (4-methylpiperazin-1-yl) thiazol-2-yl] pyridine-4-carboxamide (Compound 66) In a manner similar to that in the example 29, using 1-methylpiperazine (0.51 L, 4.56 mmol) in place of morpholine, the title compound 66 (108 mg, 32%) is obtained from compound g (224 mg, 0.91 mmol) obtained in reference example 7 2 H NMR (CDCl 3, d ppm): 2.47 (s, 3 H), 2.70-2.81 (m, 4 H), 3.10-3.19 (m, 4 H), 6.40 (dd, J = 1.8, 3.3 Hz, 1 H), 6.76. (d, J = 3.3 Hz, 1H), 7.28 (d, J = 1.8 Hz, 1H), 7.66 (d, J = 6.1 Hz, 2H), 8.74 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M + H] + 370.

[Example 67] N- [5- (4-Ethylpiperazin-1-yl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 67) In a manner similar to that in the example 29, using 1-ethylpiperazine (1.18 mL, 8.50 mmol) in place of morpholine, the title compound 67 (319 mg, 49%) is obtained from compound g (417 mg, 1.70 mmol) obtained in reference example 7 H NMR (CDC13, d ppm): 1.14 (t, J = 7.2 Hz, 3H), 2.52 (dd, J = 7.2, 14.5 Hz, 2H), 2.64-2.68 (m,, 4H), 3.07-3.10 ( m, 4H), 6. 42 (dd, J = 1.8, 3.3 Hz / 1H), 6.80 (dd, J = 0.6, 3.3 Hz, 1H), 7.29 (dd, J = 0.6, 1.8 Hz, 1H), 7.67 (dd, J = 1.7, 4.4 Hz, 2H), 8.76 (dd, J = .1.7, 4.4 Hz, 2H). APCIMS m / z: [M + H] + 384.

[Example 68] N- [5- (4-Benzylpiperazin-1-yl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 68) Step 1: In a manner similar to that in step 1 of Example 29, using 1-benzylpiperazine (3.46 mL, 19.9 mmol) in place of morpholine, 2-amino-5- (4-benzylpiperazin-1-yl) -4- (2-furyl) thiazole ( 1.09 g, 78%) is obtained from compound g (1.00 g, 4.08 mmol) obtained in reference example 7. a H NMR (CDCl 3, d ppm): 2.60-2.63 (m, 4H), 2.88-2.91 (m, 4H), 3.57 (s, 2H), 4.91 (br s, 2H), 6.46 (dd, J = 1.8, 3.5 Hz, 1H), 6.85 (dd, J = 0.9, 3.5 Hz, 1H), 7.26-7.34 (m, 5H), 7.40 (dd, J = 0.9, 1.8 Hz, 1H).

Step 2: In a manner similar to that in Example 1, the title compound 68 (359 mg, 55%) is obtained from 2-amino-5- (4-benzylpiperazin-1-yl) -4- ( 2-furyl) thiazole (500 mg, 1.46 mmol) obtained in step 1, instead of compound a. X H NMR (CDCl 3, d ppm): 2.70-2.88 (m, 4 H), 3.09-3.23 (m, 4 H), 3.74 (s, 2 H), 6.41 (dd, J = 1.8, 3.3 Hz, 1 H), 6.75 ( d, J = 3.3 Hz, 1H), 7.30-7.43 (m, 6H), 7.67 (d, J = 6.2 Hz, 2H), 8.75 (d, J = 6.2 Hz, 2H). ESIMS m / z: [M + H] + 446.

[Example 69] N- [4- (2-Furyl) -5-thiomorpholinothiazol-2-yl] pyridine-4-carboxamide (Compound 69) In a manner similar to that in Example 29, when using thiomorpholine (1.03 mL, 10.2 mmol) in place of morpholine, the title compound 69 (593 mg, 78%) is obtained from compound g (500 mg, 2.04 mmol) obtained in reference example 7.

X H NMR (CDCl 3, d ppm): 2.84-2.87 (m, 4 H), 3.25-3.28 (m, 4 H), 6.45 (d, J = 1.8, 3.5 Hz, 1 H), 6.81 (d, J = 3.5 Hz, 1H), 7.34 (d, J = 1.8 Hz, 1H), 7.69 (dd, J = 1.7, 4.6 Hz, 2H), 8.78 (dd, J = 1.7, 4.6 Hz, 2H), 10.2 (br s, 1H) . APCIMS m / z: [M + H] + 373.

[Example 70] N- [4- (2-Furyl) -5- (1-oxot iomorpholino) thiazol-2-yl] pyridine-4-carboxamide (Compound 70) Step 1: The 2-Amino-4- (2 -furyl) -5-t iomorpholinothiazole (972 mg, 3.64 mmol) obtained as the intermediate in Example 69 was dissolved in dichloromethane (18 mL), m-chloroperbenzoic acid (1.32 g, 7.63 mmol) was added thereto, followed by stirring at room temperature for 1 hour. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform-methanol = 50: 1) to give 2-amino-4- (2-furyl) -5- (1-oxothiomorpholino) thiazole (724 mg, 70%).

Step 2: In a manner similar to that in Example 1, the title compound 70 (752 mg, 76%) is obtained from 2-amino-4- (2-furyl) -5- (1-oxothiomorpholino) thiazole (724 mg, 2.55 mmol) obtained in step 1, instead of compound a. XH NMR (DMS0-d6, d ppm): 2.93-3.33 (m, 8H), 6.61 (dd, J = 1.8, 3.3 Hz, 1H), 6.88 (d, J = 3.3 Hz, 1H), 7.70 (d, J = 1.8 Hz, 1H), 7.97 (d, J = 6.2 Hz, 2H), 8.79 (d, J = 6.2 Hz, 2H). APCIMS m / z: [M + H] + 389.

[Example 71] N- [5- (1,1-Dioxothiomorpholino) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 71) In a manner similar to that in step 1 of Example 70, the title compound 71 (365 mg, 48%) is obtained from compound 69 in place of 2-amino-4- (2-furyl) -5-thiomorpholinothiazole. XH NMR (CDC13, d ppm): 3.21-3.24 (m, 4H), 3.52-3.56 (m, 4H), 6. 47 (dd, J = 1.8, 3.3 Hz, 1H), 6.74 (d, J = 3.3 Hz, 1H), 7. 42 (d, J = 1.8 Hz, 1H), 7.76 (d, J = 6.1 Hz, 2H), 8.80 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M + H] + 405.

[Example 72] N- [4- (2-Furyl) -5-piperidinothiazol-2-yl] pyridine-4-carboxamide (Compound 72) In a manner similar to that in Example 29, when using piperidine (0.740 mL, 7.44 mmol) in place of morpholine, the title compound 72 (354 mg, 67%) is obtained from compound g (365 mg, 1.49 mmol) obtained in reference example 7. aH NMR (CDC13, d ppm): 1.59 -1.62 (m, 2H), 1.72-1.79 (m, 4H), 2.92-2.96 (m, 4H), 6.34 (dd, J = 1.8, 3.3 Hz, 1H), 6.72 (d, J = 3.3 Hz, 1H ), 7.14 (d, J = 1.8 Hz, 1H), 7.65 (d, J = 6.1 Hz, 2H), 8.67 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M-H] ~ 353.

[Example 73] N- [4- (2-Furyl) -5- (2-methylpiperidino) thiazol-2-yl] pyridine-4-carboxamide (Compound 73) In a manner similar to that in example 29, using 2-methylpiperidine (0.750 L, 6.35 mmol) in place of morpholine, the title compound 73 (155 mg, 33%) is obtained from compound g (312 mg, 1.27 mmol) obtained in reference example 7. XH NMR ( CDCl 3, d ppm): 1.00-1.02 (m, 3H), 1.40-1.51 (m, 2H), 1. 66-1.83 (, 4H), 2.65-2.80 (, 2H), 3.07-3.11 (m, 1H), 6.29 (d, J = 1.8, 3.3 Hz, 1H), 6.94 (d, J = 3.3 Hz, 1H) , 7.08 (d, J = 1.8 Hz, 1H), 7.65 (d, J = 6.1 Hz, 2H), 8.63 (d, J = 6.1 Hz, 2H). APCIMS m / z: [MH] ~ 367. [Example 74] N- [4- (2-Furyl) -5- (4-oxopiperidino) thiazol-2-yl] pyridine-4-carboxy ida (Compound 74) Step 1: In a manner similar to that in step 1 of example 29, using 1,4-dioxa-S-azaspiro [4.5] decane (3.82 mL, 29.8 mmol) in place of morpholine, 2-amino-5- ( 1,4-dioxa-S-azaspiro [4.5] decan-8-yl) -4- (2-furyl) thiazole (1.54 g, 84%) is obtained from compound g (1.46 g, 5.96 mmol) obtained in the example of reference 7.

Step 2: 2-Amino-5- (1,4-dioxa-8-azaspiro [4.5] decan-8-yl) -4- (2-furyl) thiazole (1.00 g, 3.25 mmol) obtained in step 1 dissolved in THF (10 mL), 2 mol / L hydrochloric acid (5 mL) was added thereto, followed by stirring under heating and refluxing for 4 hours. The reaction mixture was neutralized with a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through chromatography of silica gel column (hexane: ethyl acetate = 1: 1) to give 2-amino-4- (2-furyl) -5- (4-oxopiperidino) thiazole (151 mg, 18%). Step 3: In a manner similar to that in Example 1, the title compound 74 (151 mg, 72%) is obtained from 2-amino-4- (2-furyl) -5- (4-oxopiperidino) thiazole (151 mg, 0.54 mmol) obtained in step 2, instead of compound a. aH NMR (CDC13, d ppm): 2.62-2.71 (m, 4H), 3.36-3.40 (m, 4H), 6.44 (d, J = 1.8, 3.3 Hz, 1H), 6.83 (d, J = 3.3 Hz, 1H), 7.29 (d, J = 1.8 Hz, 1H), 7.70 (d, J = 6.2 Hz, 2H), 8.76 (d, J = 6.2 Hz, 2H), 10.81 (br s, 1H). APCIMS m / z: [M-H] "367.

[Example 75] N- [4- (2-Furyl) -5- (1,2,3,4-tetrahydroisoquinolin-2-yl) thiazol-2-yl] pyridine-4-carboxamide (Compound 75) Step 1: In a manner similar to that in step 1 of example 29, using 1, 2, 3, 4-tetrahydroisoquinoline (1.28 mL, . 2 mmol) in place of morpholine, 2-amino-4- (2-furyl) -5- (1, 2, 3, 4-tetrahydroisoquinoli-n-2-yl) thiazole (524 mg, 86%) is obtained from compound g (500 mg, 2.04 mmol) obtained in reference example 7. X H NMR (CDCl 3, d ppm): 3.04-3.08 (m, 2 H), 3.17-3.21 (m, 2 H), 4. 08 (s, 2H), 4.86 (br s, 2H), 6.40 (dd, J = 1.8, 3.3 Hz, 1H), 6.80 (dd, J = 0.7, 3.3 Hz, 1H), 7.05-7.20 (m, 4H ), 7.40 (dd, J = 0.7, 1.8 Hz, 1H). Step 2: In a manner similar to that in Example 1, the title compound 75 (133 mg, 39%) is obtained from 2-amino-4- (2-furyl) -5- (1,2, 3,4-tetrahydroisoquinolin-2-yl) thiazole (250 mg, 0.84 mmol) obtained in step 1, instead of compound a. 1 H NMR (CDC13, d ppm): 3.09-3.03 (m, 2H), 3.33-3.37 (m, 2H), 4.24 (s, 2H), 6.41 (dd, J = 1.8, 3.3 Hz, 1H), 6.79 ( d, J = 3.3 Hz, 1H), 7.09-7.26 (ra, 4H), 7.34 (d, J = 1.8 Hz, 1H), 7.73 (d, J = 6.1 Hz, 2H), 8.80 (d, J = 6.1 Hz, 2H). ESIMS m / z: [M-H] "401.

[Example 76] N- [5-Dimethylamino-4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 76) In a manner similar to that in example 29, by using a methanol solution (1.53 mL, 3.06 mmol) of 2 mol / L dimethylamine in place of morpholine, the title compound 76 (79.2 mg, 41%) is obtained from the compound g (150 mg, 0.61 mmol) obtained in the reference example 7. X H NMR (CDCl 3, d ppm): 2.80 (s, 6 H), 6.41 (dd, J = 1.8, 3.3 Hz, 1H), 6.74 (d, J = 3.3 Hz, 1H), 7.31 (d, J = 1.8 Hz, 1H), 7. 71 (d, J = 6.2 Hz, 2H), 8.75 (d, J = 6.2 Hz, 2H). APCIMS m / z: [M + H] + 315. [Example 77] N-. { 4- (2-Furyl) -5- [N- (2-methoxyethyl) -N-methylamino] thiazol-2-yl} pyridine-4-carboxamide (Compound 77) Step 1: In a manner similar to that in step 1 of the example 29, when using N- (2-methoxyethyl) -N-methylamine (909 mg, 10.2 mmol) in place of morpholine, 2-amino-4- (2-furyl) -5- [N- (2-methoxyethyl) - N-methylamino] thiazole (363 mg, 70%) is obtained from compound g (500 mg, 2.04 mmol) obtained in reference example 7. aH NMR (CDC13, d ppm): 2.90 (s, 3H), 3.22- 3.25 (m, 2H), 3.31 (s, 3H), 3.51-3.54 (m, 2H), 6.40 (dd, J = 1.8, 3.3 Hz, 1H), 6.80 (dd, J = 0.7, 3.3 Hz, 1H), 7.05 (br s, 2H) 7.40 (dd, J = 0.7, 1.8 Hz, 1H).

Step 2: In a manner similar to that in Example 1, the title compound 77 (195 mg, 88%) is obtained from 2-amino-4- (2-furyl) -5- [N- (2 -methoxyethyl) -N-methylamino] thiazole (150 mg, 0.62 mmol) obtained in step 1, instead of compound a. XH NMR (CDC13, d ppm): 2.90 (s, 3H), 3.22-3.25 (m, 2H), 3.31 (s, 3H), 3.51-3.54 (m, 2H), 6.49 (dd, J = 1.8, 3.3 Hz, 1H), 6. 93 (d, J = 3.3 Hz, 1H), 7.46 (d, J = 1.8 Hz, 1H), 8.02 (d, J = 6.2 Hz, 2H), 8.84 (d, J = 6.2 Hz, 2H). APCIMS m / z: [M + H] + 359. [Example 78] N-. { 4- (2-Furil) -5-. { N-methyl-N- [2- (2-pyridyl) ethyl] amino} thiazol-2-il} pyridine-4-carboxamide (Compound 78) Step 1: In a manner similar to that in step 1 of example 29, by using N-methyl-N- [2- (2-pyridyl) ethyl] amine (1.41 mL, 10.2 mmol) in place of morpholine, 2-amino-4- (2-furyl) -5-. { N-methyl-N- [2- (2-pyridyl) ethyl] amino} thiazole (349 mg, 57%) is obtained from compound g (500 mg, 2.04 mmol) obtained in reference example 7. XH NMR (CDC13, d ppm): 2.70 (s, 3H), 2.95-3.00 (m, 2H), 3.20-3.25 (m, 2H), 5.03 (br s, 2H), 6.36 (dd, J = 1.8, 3.3 Hz, 1H), 6.57 (dd, J = 0.7, 3.3 Hz, 1H), 7.00-7.10 (m, 2H), 7.37 (dd, J = 0.7, 1.8 Hz, 1H), 7.45-7.51 (m, 1H), 8.50-8.52 (m, 1 HOUR) .

Step 2: In a manner similar to that in Example 1, the title compound 78 (143 mg, 53%) is obtained from 2-amino-4- (2-furyl) -5-. { N-methyl-N- [2- (2-pyridyl) ethyl] amino} thiazole (200 mg, 0.67 mmol) obtained in step 1, instead of compound a.

X H NMR (CDCl 3, d ppm): 2.83 (s, 3 H), 3.01-3.07 (m, 2 H), 3.41-3.46 (m, 2 H), 6.38 (dd, J = 1.8, 3.5 Hz, 1 H), 6.58 ( d, J = 3.5 Hz, 1H), 7.03-7.12 (m, 2H), 7.35 (d, J = 1.8 Hz, 1H), 7.49-7.55 (m, 1H), 7.72 (d, J = 6.1 Hz, 2H ), 8.51-8.53 (m, 1H), 8.82 (d, J = 6.1 Hz, 2H). ESIMS m / z: [M + H] + '406.

[Example 79] N- [5- (4-Benzylpiperazin-1-yl) -4- (2-furyl) thiazol-2-yl] acetamide (Compound 79) In a manner similar to that in Example 2, the compound of title 79 (550 mg, 77%) is obtained from 2-amino-5- (4-benzylpiperazin-1-yl) -4- (2-furyl) thiazole (458 mg, 1.87 mmol) obtained in step 1 of Example 68, in place of compound a. 2 H NMR (DMSO-d 6, d ppm): 1.99 (s, 3 H), 2.63-2.66 (m, 4 H), 3.01-3.04 (m, 4 H), 3.59 (s, 2 H), 6.49 (dd, J = 1.8 , 3.3 Hz, 1H), 6.85 (d, J = 3.3 Hz, 1H), 7.23-7.40 (m, 6H), 10.9 (br s, 1H). ESIMS m / z: [M + H] + 383.

[Example 80] N- [4- (2-Furyl) -5- (piperazin-1-yl) thiazol-2-yl] acetamide fumarate (Compound 80) Compound 79 (274 mg, 0.72 mmol) was dissolved in methanol (7 mL), and 10% palladium carbon (274 mg) was added thereto, followed by stirring in a hydrogen atmosphere at 50 ° C for 24 hours. The reaction mixture was filtered through Celite, and the resulting filtrate was concentrated to provide a free form of the title compound. The resulting free form was dissolved in ethanol (5 mL), fumaric acid (83.0 mg, 0.51 mmol) was added thereto, and the precipitated solid was collected by filtration to provide the title compound 80 (40.1 mg, 14%). 1 H NMR (CDC13, d ppm): 2.10 (s, 3H), 2.97-3.06 (m, 4H), 3.14-3.21 (m, 4H), 6.58 (dd, J = 1.8, 3.3 Hz, 1H), 6.54 ( s, 2H), 6.79 (d, J = 3.3 Hz, 1H), 7.67 (d, J = 1.8 Hz, 1H). APCIMS m / z: [M + H] + 293.

[Example 81] N- [4- (2-Furyl) -5- (1,2,3,4-tetrahydroisoquinolin-2-yl) thiazol-2-yl] acetamide (Compound 81) In a manner similar to that in Example 2, the title compound 81 (225 mg, 74%) is obtained from 2-amino-4- (2-furyl) -5- (1,2,3,4-tetrahydroisoquinolin-2-yl) thiazole (267 mg, 0.89 mmol) obtained in step 1 of example 75, instead of compound a. 2 H NMR (DMSO-d 6, d ppm): 2.11 (s, 3 H), 2.98-3.02 (m, 2 H), 3.21-3.25 (m, 2 H), 4.13 (s, 2 H), 6.55 (dd, J = 1.8 , 3.3 Hz, 1H), 6.67 (dd, J = 0.8, 3.3 Hz, 1H), 7.10-7.19 (m, 4H), 7.67 (dd, J = 0.8, 1.8 Hz, 1H), 12.08 (br s, 1H). ESIMS m / z: [M + H] + 340. [Example 82] N- [5- (1, 4-Dioxa-8-azaspiro [4.5] decan-8-ü) -4- (2-furyl) thiazole -2-yl] acetamide (Compound 82) In a manner similar to that in Example 2, the title compound 82 (488 mg, 84%) is obtained from 2-amino-5- (1,4-dioxa) -8-azaspiro [4.5] decan-8-yl) -4- (2-furyl) thiazole (510 mg, 1.66 mmol) obtained in step 1 of example 74, instead of compound a. 2 H NMR (CDC13, d ppm): 1.87-1.91 (m, 4H), 2.14 (s, 3H), 3.05- 3.09 (m, 4H), 3.98 (s, 4H), 6.47 (dd, J = 1.8, 3.3 Hz, 1H), 6. 80 (dd, J = 0.7, 3.3 Hz, 1H), 7.39 (dd, J = 0.7, 1.8 Hz, 1H), 10.61 (br s, 1H). APCIMS m / z: [M + H] + 350.

[Example 83] 0.5 Fumarate of N-. { - (2-Furyl) -5- [N- (2-methoxyethyl) -N-methylamino] thiazol-2-yl} acetamide (Compound 83) In a manner similar to that in Example 2, a free form of the title compound is obtained from 2-amino-4- (2-furyl) -5- [N- (2-methoxyethyl)) -N-methylamino] thiazole (160 mg, 0.63 mmol) obtained in step 1 of example 77, instead of compound a. The The resulting free form was dissolved in ethanol (5 mL), and fumaric acid (146 mg, 1.26 mmol) was added thereto, and the precipitated solid was collected by filtration to provide the title compound 83 (39.8 mg, 18%). . X H NMR (DMS0-d 6, d ppm): 2.09 (s, 3H), 2.72 (s, 3H), 3.03-3.07 (m, 2H), 3.19 (s, 3H), 3.41-3.45 (m, 2H), 6.56 (dd, J = 1.8, 3.3 Hz, 1H), 6.60 (s, 1H), 6.77 (dd, J = 0.7, 3.3 Hz, 1H), 7.64 (dd, J = 0.7, 1.8 Hz, 1H), 12.08 (br s, 1H). APCIMS m / z: [M + H] + 296.

[Example 84] N- fumarate. { 4- (2-Furil) -5-. { N-methyl-N- [2- (2-pyridyl) ethyl] amino} thiazol-2-il} acetamide (Compound 84) In a manner similar to that in Example 2, a free form of the title compound is obtained from 2-amino-4- (2-furyl) -5-. { N-methyl-N- [2- (2-pyridyl) ethyl] amino} thiazole (108 mg, 0.36 mmol) obtained in step 1 of example 78, in place of compound a. In a manner similar to that in Example 83, the title compound 84 (20.2 mg, 12%) is obtained from the free form thereof. X H NMR (DMS0-d 6, d ppm): 2.11 (s, 3 H), 2.76 (s, 3 H), 2.92 (t, J = 7.1 Hz, 2H), 3.27 (t, J = 7.1 Hz, 2H), 6.28-6.29 (m, 2H), 7.16-7.23 (m, 2H), 7.61-7.67 (m, 2H), 8.43-8.56 (m, 1H). ESIMS m / z: [M + H] + 343. [Example 85] N- [5-Formyl-4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 85) Compound i ( 684 mg, 3.52 mmol) obtained in Reference Example 9 was dissolved in DMF (17 mL), and isonicotinic acid (867 mg, 7.04 mmol), EDC Hydrochloride (1.35 g, 7.04 mmol) and 1-hydroxybenzotriazole monohydrate ( 1.08 g, 7.04 mmol) were added thereto, followed by stirring at 50 ° C for 3 hours. Water was added to the reaction mixture, and the precipitated crystals were collected by filtration to provide the title compound 85 (546 mg, 52%). 1 H NMR (DMSO-de, d ppm): 6.77 (dd, J = 1.7, 3.5 Hz, 1H), 7.18 (dd, J = 0.7, 3.5 Hz, 1H), 8.00-8.03 (m, 3H), 8.84 ( dd, J = 1.7, 4.6 Hz, 2H), 10.46 (s, 1H), 13.60 (br s, 1H).

[Example 86] N- [4- (2-Furyl) -5- (morpholinomethyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 86) Compound 85 (250 mg, 0.836 mmol) was dissolved in 1, 2-Dichloroethane (4 mL), and morpholine (0.15 mL, 1.67 mmol) and sodium triacetoxyborohydride (531 mg, 2.51 mmol) were added thereto, followed by stirring overnight room temperature. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 30: 1) to give the title compound 86 (302 mg, 98%). X H NMR (DMSO-d 6, d ppm): 3.31-3.34 (m, 4 H), 3.59-3.62 (m, 4 H), 3.95 (s, 2 H), 6.62 (dd, J = 1.8, 3.3 Hz, 1 H), 6.75 (dd, J = 0.9, 3.3 Hz, 1H), 7.79 (dd, J = 0.9, 1.8 Hz, 1H), 7.99 (dd, J = 1.7, 4.4 Hz, 2H), 8.81 (dd, J = 1.7, 4.4 Hz, 2H), 13.02 (br s, 1H). ESIMS m / z: [M-H] + 371.

[Example 87] N- [4- (2-Furyl) -5- (thiomorpholinomethyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 87) In a manner similar to that in Example 86, when using thiomorpholine ( 0.170 mL, 1.67 mmol) in place of morpholine, the title compound 87 (272 mg, 84%) is obtained from compound 85 (250 mg, 0.836 mmol). XH NMR (CDC13, d ppm): 2.71-2.74 (m, 4H), 2.86-2.89 (m, 4H), 3. 94 (s, 2H), 6.40 (dd, J = 1.8, 3.3 Hz, 1H), 6.56 (dd, J = 0.7, 3.3 Hz, 1H), 7.38 (dd, J = 0.7, 1.8 Hz, 1H), 7.71 (dd, J = 1.8, 4.4 Hz, 2H), 8.77 (dd, J = 1.8, 4.4 Hz, 2H), 10.61 (br s, 1H). APCIMS m / z: [M + H] + 387. [Example 88] N- [4- (2-Furyl) -5- (pyrrolidin-1-ylmethyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 88) In a manner similar to that in Example 86, when using pyrrolidine (0.141 mL, 1.67 mmol) in place of morpholine, the title compound 88 (249 mg, 84%) is obtained from compound 85 (250 mg, 0.836 mmol). X H NMR (CDC13, d ppm): 1.80-1.84 (m, 4H), 2.65-2.72 (m, 4H), 4. 05 (s, 2H), 6.42 (dd, J = 1.8, 3.3 Hz, 1H), 6.59 (d, J = 3. 3 Hz, 1H), 7.40 (d, J = 1.8 Hz, 1H), 7.70 (d, J = 6.1 Hz, 2H), 8.76 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M + H] + 355.

[Example 89] N- [4- (2-Furyl) -5- (4-methylpiperazin-1-ylmethyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 89) In a manner similar to that in the example 86, using 1-methylpiperazine (0.152 mL, 1.34 mmol) in place of morpholine, the title compound 89 (142 mg, 55%) is obtained from compound 85 (200 mg, 0.669 mmol). a H NMR (CD3OD, d ppm): 2.98 (s, 3 H), 3.37-3.72 (m, 8 H), 4.77 (s, 2 H), 6.61 (dd, J = 1.8, 3.3 Hz, 1 H), 6.96 (d. J = 3.3 Hz, 1H), 7.74 (d, J = 1.8 Hz, 1H), 8.58 (d, J = 6.1 Hz, 2H), 9.09 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M + H] + 384. [Example 90] N- [4- (2-Furyl) -5- (octahydropyrazino [2, 1-c] [1,4] oxazin-8-ylmethyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 90) In a manner similar to that in Example 86, when using octahydropyrazino [2, 1-c] [1,4] oxazine (300 mg, 2.11 mmol)) obtained in accordance with the method described in EP 472826, instead of morpholine, the title compound 90 (212 mg, 47%) is obtained from the compound 85 (316 mg, 1.05 mmol). ^ NMR (CDC13, d ppm): 1.91-1.98 (m, 1H), 2.37-2.50 (m, 4H), 2.64-2.78 (m, 3H), 2.96-2.99 (m, 1H), 3.20-3.27 (m , 1H), 3.63-3.69 (m, 2H), 3.82-3.84 (m, 1H), 3.92 (s, 2H), 6.41 (dd, J = 1.8, 3.3 Hz, 1H), 6.59 (d, J = 3.3 Hz, 1H), 7.39 (d, J = 1.8 Hz, 1H), 7.70 (d, J = 6.1 Hz, 2H), 8.78 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M + H] +426.

[Example 91] N- Dichlorohydrate. { 4- (2-Furyl) -5- [(2-morpholinethylamino) methyl] thiazol-2-yl} pyridine-4-carboxamide (Compound 91) In a manner similar to that in Example 86, by using N- (2-aminoethyl) morpholine (0.180 mL, 1.34 mmol) in place of morpholine, a free form of the title compound was obtain compound 85 (200 mg, 0.669 mmol). The resulting free form was dissolved in ethanol (4 L), and ethyl acetate solution (0.30 mL) of 4 mol / L hydrogen chloride was added to this, and the precipitated solid was collected by filtration to provide the title compound. titer 91 (40.3 mg, 12%). 1 H NMR (CD3OD, d ppm): 3.10-3.39 (m, 6H), 3.56-3.65 (m, 2H) 3.87-3.94 (m, 4H), 4.80 (s, 2H) ), 6.63 (dd, J = 1.8, 3.3 Hz, 1H), 6.98 (d, J = -3.3 Hz, 1H), 7.76 (d, J = 1.8 Hz, 1H), 8.10 (d, J = 6.1 Hz, 2H), 8.86 (d, J = 6.1 Hz, 2H) APCIMS m / z: [M + H] + 414.

[Example 92] 2- (tert-Butoxycarbonylamino) -5-formyl-4- (2-furyl) thiazole (Compound 92) Compound h (3.10 g, 8.98 mmol) obtained in reference example 8 was dissolved in THF ( 45 L), and a 1.58 mol / L solution of n-butylithium in n-hexane (14.2 mL, 22.5 mmol) was added thereto in a stream of argon at -78 ° C. The mixture was stirred at -78 ° C for 10 minutes, and then DMF (14.2 mL, 183 mmol) was added dropwise thereto, followed by stirring at room temperature for 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of Sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 4: 1) to give the title compound 92 (1.50 g, 57%). aH NMR (CDC13, d ppm): 1.50 (s, 9H), 6.57 (dd, J = 1.8, 3.4 Hz, 1H), 6.99 (dd, J = 0.8, 3.4 Hz, 1H), 7.60 (dd, J = 0.8, 1.8 Hz, 1H), 8.95 (br s, 1H), 10.52 (s, 1H).

[Example 93] 2- (tert-Butoxycarbonylamino) -4- (2-furyl) -5-morpholinomethylthiazole (Compound 93) Compound 92 (1.58 g, 5.37 mmol) and morpholine (0.64 mL, 10.7 mmol) were dissolved in 1 ml. , 2-dichloroethane (26 mL) and sodium triacetoxyborohydride (3.41 g, 16.1 mmol) was added thereto, followed by stirring overnight at room temperature. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform-methanol = 30: 1) to provide the compound of title 93 (1.15 g, 57%). aH NMR (CDC13, d ppm): 1.50 (s, 9H), 2.56-2.60 (m, 4H), 3.70-3.74 (m, 4H), 3.90 (s, 2H), 6.47 (dd, J = 1.8, 3.3 Hz, 1H), 6.63 (dd, J = 0.7, 3.3 Hz, 1H), 7.46 (dd, J = 0.7, 1.8 Hz, 1H).

[Example 94] N- [4- (2-Furyl) -5- (morpholinomethyl) thiazol-2-yl] -pyridine-3-carboxamide (Compound 94) Step 1: Compound 93 (1.15 g, 0.32 mmol) was dissolved in trifluoroacetic acid (12 mL), followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and 1 mol / L aqueous sodium hydroxide solution and a mixed solvent (4: 1) of chloroform and 2-propanol were added to the resulting residue, and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was continuously distilled under reduced pressure to provide 2-amino-4- (2-furyl) -5- (morpholinomethyl) thiazole (835 mg, 100%). XH NMR (CD3OD, d ppm): 2.50-2.53 (m, 4H), 3.65-3.68 (m, 4H), 3.83 (s, 2H), 6.47 (dd, J = 1.8, 3.3 Hz, 1H), 6.61 ( dd, J = 0.7, 3.3 Hz, 1H), 7.52 (dd, J = 0.7, 1.8 Hz, 1H).

Step 2: The 2-amino-4- (2-furyl) -5- (morpholinomethyl) thiazole (225 mg, 0.85 mmol) obtained in step 1 was dissolved in DMF (4 mL), and nicotinoyl chloride hydrochloride ( 302 mg, 1.70 mmol) and triethylamine (0.24 mL, 1.70 mmol) were added thereto, followed by stirring at room temperature for 4 hours. A saturated aqueous solution of sodium acid carbonate was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give the title compound 94 (73.0 mg, 23%). 1 H NMR (CDC13, d ppm): 2.60-2.63 (m, 4H), 3.74-3.77 (m, 4H), 3.94 (s, 2H), 6.42 (dd, J = 1.8, 3.3 Hz, 1H), 6.61 ( d, J = 3.3 Hz, 1H), 7.41 (d, J = 1.8 Hz, 1H), 7.42-7.44 (m, 1H), 8.24-8.28 (m, 1H), 8.78-8.83 (m, 1H), 9.18 -9.19 (m, 1H). APCIMS m / z: [M-H] "369.

[Example 95] N- [S-Carboxy-4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 95) Compound 24 (840 mg, 2.45 mmol) was dissolved in THF (5 mL ) and methanol (5 mL), and a sodium hydroxide solution aqueous 4 mol / L (3 mL) was added thereto, followed by stirring at 60 ° C for 2 hours. The reaction mixture was allowed to cool, and neutralized with 2 mol / L hydrochloric acid was added thereto. The precipitated solid was collected by filtration to provide the title compound 95 (411 mg, 53%). aH NMR (DMSO-d6, d ppm): 6.68 (dd, J = 1.8, 3.5 Hz, 1H), 7.61 (dd, J = 1.0, 3.5 Hz, 1H), 7.86 (dd, J = 1.0, 1.8 Hz, 1H), 8.20 (dd, J = 1.7, 4.8 Hz, 2H), 8.94 (dd, J = 1.7, 4.8 Hz, 2H).

[Example 96] N- [4- (2-Furyl) -5-morpholinocarbonylthiazol-2-yl] pyridine-4-carboxamide (Compound 96) Compound 95 (410 mg, 1.30 mmol), morpholine (0.141 mL, 1.60 mmol ), EDC hydrochloride (500 mg, 2.60 mmol), 1-hydroxybenzotriazole monohydrate (400 mg, 2.60 mmol) and triethylamine (0.36 mL, 2.60 mmol) were dissolved in DMF (5 mL), followed by stirring at room temperature for 3 hours . Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was recrystallized from ethanol to give the title compound 96 (159 mg, 34%) as colorless crystals. X H NMR (DMSO-d 6, d ppm): 3.59-3.68 (, 8H), 6.39 (dd, J = 1.8, 3.3 Hz, 1H), 6.67 (dd, J = 0.7, 3.3 Hz, 1H), 7.27 (dd) , J = 0.7, 1.8 Hz, 1H), 7.78 (dd, J = 1.6, 4.5 Hz, 2H), 8.81 (dd, J = 1.6, 4.5 Hz, 2H), 10.82 (br s, 1H). ESIMS m / z: [M-H] "383.

[Example 97] N- [5- (N, N-Dimethylcarbamoyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 97) In a manner similar to that in example 96, when using a 2 mol / L solution of dimethylamine (0.420 mL, 0.850 mmol) in methanol in place of morpholine, the title compound 97 (85.1 mg, 31%) is obtained from compound 95 (250 mg, 0.794 mmol). a H NMR (DMSO-d 6, d ppm): 2.81 (s, 3 H), 3.01 (s, 3 H), 6.62 (dd, J = 1.8, 3.3 Hz, 1 H), 6.74 (dd, J = 0.7, 3.3 Hz, 1H), 7.77 (dd, J = 0.7, 1.8 Hz, 1H), 7.94 (d, J = 6.1 Hz, 2H), 8.81 (d, J = 6.1 Hz, 2H). ESIMS m / z: [M-H] + 343.

[Example 98] N- [4- (2-Furyl) -5- (N-methoxy-N-methylcarbamoyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 98) In a manner similar to that in the example 96, al using N, O-dimethylhydroxyamine hydrochloride (810 mg, 8.30 mmol) in place of morpholine, the title compound 98 (1.20 g, 81%) is obtained from compound 95 (1.31 g, 4.15 mmol). X H NMR (CDC13, d ppm): 3.38 (s, 3 H), 3.70 (s, 3 H), 6.40 (dd, J = 1.8, 3.5 Hz, 1 H), 7.03 (dd, J = 0.7, 3.5 Hz, 1 H) , 7.37 (dd, J = 0.7, 1.8.Hz, 1H), 7.75 (dd, J = 1.7, 4.6 Hz, 2H), 8.82 (dd, J = 1.7, 4.6 Hz, 2H).

[Example 99] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 99) Compound 98 (354 mg, 0.989 mmol) was dissolved in THF (5 mL ), and a 3 mol / L diethyl ether solution of phenylmagnesium bromide (1.32 mL, 3.96 mmol) was added thereto under ice-cooling, followed by stirring at ambient temperature for 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue is reblended with ethanol to give the title compound 99 (220 mg, 59%) as pale yellow crystals. 2 H NMR (CDCl 3, d ppm): 6.52 (dd, J = 1.8, 3.5 Hz, 1H), 6.96 (dd, J = 0.7, 3.5 Hz 1H), 7.44-7.49 (m, 2H), 7.50 (dd, J = 0.7, 1.8 Hz, 1H), 7.58-7.63 (m, 1H), 7.72-7.75 (m, 2H), 8.03 (dd, J = 1.7, 4.4 Hz, 2H) / 8.84 (dd, J = 1.7, 4.4 Hz, 2H). ESIMS m / z: [M + H] + 376.

[Example 100] N- [4- (5-Broniofuran-2-yl) -5-morpholinothiazol-2-yl] pyridine-4-carboxamide (Compound 100) In a manner similar to that in Example 29, the compound of titre 100 (156 mg, 31%) is obtained from compound j (379 mg, 1.17 mmol) obtained in reference example 10, instead of Compound g obtained in reference example 7. a H NMR (CDCl 3, d ppm) : 3.01-3.05 (m, 4H), 3.88-3.91 (m, 4H), 6.36 (d, J = 3.3 Hz, 1H), 6.77 (d, J = 3.3 Hz, 1H), 7.72 (dd, J = 1.5 , 4.4 Hz, 2H), 8.80 (dd, J = 1.5, 4.4 Hz, 2H), 10.31 (br s, 1H). APCIMS m / z: [79BrM + H] + 435, [81BrM + H] + 437.

[Example 101] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] benzamide (Compound 101) In a manner similar to that in Example 2, Use benzoyl chloride (0.160 mL, 1.39 mmol) in place of acetyl chloride, the title compound 101 (183 mg, 64%) is obtained as a pale yellow solid of compound a (200 mg, 0.820 mmol) obtained in the reference example 1. XH NMR (DMSO-d6, d ppm): 6.60 (dd, J = 1.6, 3.2 Hz, 1H), 6.74 (d, J = 3.2 Hz, 1H), 7.45 (d, J = 6.2 Hz , 2H), 7.51-7.61 (m, 2H), 7.61-7.70 (m, 2H), 8.09-8.18 (m, 2H), 8.62 (d, J = 6.2 Hz, 2H), 13.01 (br s, 1H) . APCIMS m / z: [M + H] +248. p.f .: 270-300 ° C (decomposition).

[Example 102] 4-Fluoro-N- [4- (2-furyl) -5- (4-pyridyl) thiazol-2-yl] benzamide (Compound 102) In a manner similar to that in Example 2, using 4-Fluorobenzoyl chloride (0.170 mL, 1.39 mmol) in place of acetyl chloride, the title compound 102 (94.1 mg, 31%) is obtained as a pale yellow solid of compound a (200 mg, 0.820 mmol) obtained in reference example 1. 1R NMR (DMSO-d6, d ppm): 6.60 (dd, J = 1.6, 3.2 Hz, 1H), 6. 73 (d, J = 3.2 Hz, 1H), 7.40 (dd, J = 8.9, 8.9 Hz, 2H), 7. 45 (d, J = 6.2 Hz, 2H), 7.67 (d, J = 1.6 Hz, 1H), 8.22 (d, J = 5.4, 8.9 Hz, 2H), 8.62 (d, J = 6.2 Hz, 2H), 13.07 (br s, 1H). APCIMS m / z: [M + H] + 366. mp .: 270-300 ° C (dec.). [Example 103] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -4-methoxybenzamide (Compound 103) In a manner similar to that in example 2, when using chloride of 4-methoxybenzoyl (0.150 mL, 1.39 mmol) in place of acetyl chloride, the title compound 103 (133 mg, 43%) is obtained as a pale yellow solid of compound a (200 mg, 0.820 mmol) obtained in the reference example 1. XH NMR (DMSO-d5, d ppm): 3.86 (s, 3H), 6.61 (dd, J = 1.9, 3.2 Hz, 1H), 6.73 (dd, J = 0.8, 3.2 Hz, 1H) , 7.09 (d, J = 8.9 Hz, 2H), 7.44 (d, J = 6.2 Hz, 2H), 7.67 (dd, J = 0.8, 1.9 Hz, 1H), 8.15 (d, J = 8.9 Hz, 2H) , 8.62 (d, J = 6.2 Hz, 2H), 12.86 (br s, 1H). APCIMS m / z: [M + H] + 378. p.f .: 235-245 ° C.

[Example 104] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -2,2-dimethylpropanamide (Compound 104) In a manner similar to that in Example 2, use pivaloyl chloride (0.170 mL, 1.39 mmol) instead of acetyl chloride, the title compound 104 (107 mg, 40 %) is obtained as a white solid of compound a (200 mg, 0. 820 mmol) obtained in reference example 1. X H NMR (DMSO-d 6, d ppm): 1.27 (s, 9 H), 6.58 (dd, J = 1.6, 3.2 Hz, 1H), 6.70 (d, J = 3.2 Hz, 1H), 7.40 (d, J = 5.9 Hz, 2H), 7. 64 (d, J = 1.6 Hz, 1H), 8.60 (d, J = 5.9 Hz, 2H), 12.19 (br s, 1H). APCIMS m / z: [M + H] + 328. p. f. : 240-241 ° C.

[Example 105] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -2-methoxypyridine-4-carboxamide (Compound 105) In a manner similar to that in example 42 , using compound k obtained in reference example 11 instead of 1- (tert-butoxycarbonyl) piperidine-4-carboxylic acid, the title compound 105 (1.93 g, 85%) is obtained from compound a (1.46 g) , 6.00 mmol) obtained in reference example 1, instead of 2-amino-4- (2-furyl) -5-morpholinothiazole. ? E NMR (DMSO-d6, d ppm): 3.94 (s, 3H), 6.56 (dd, J = 1.9, 3.5 Hz, 1H), 6.69 (dd, J = 0.8, 3.5 Hz, 1H), 7.43 (dd) , J = 1.6, 4.6 Hz, 2H), 7.46 (dd, J = 0.5, 1.3 Hz, 1H), 7.57 (dd, J = 1.3, 5.4 Hz, 1H), 8.36 (dd, J = 0.5, 5.4 Hz, 1H), 8.61 (dd, J = 1.6, 4.6 Hz, 2H), 12.96 (br s, 1H). APCIMS m / z: [M + H] + 379. p.f .: 285-288 ° C. [Example 106] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -2- (4-methoxybenzyloxy) pyridine-4-carboxamide (Compound 106) In a manner similar to that in Example 42, by using compound 1 obtained in reference example 12 instead of 1- (tert-butoxycarbonyl) piperidine-4-carboxylic acid, the title compound 106 (2.41 g, 83%) is obtained from compound a (1.46 g, 6.00 mmol) obtained in reference example 1, instead of 2-amino-4- (2-furyl) -5-morpholinothiazole. X H NMR (DMSO-d 6, d ppm): 3.76 (s, 3 H), 5.35 (s, 2 H), 6.60 (d, J = 1.6, 3.2 Hz, 1 H), 6.74 (d, J = 3.2 Hz, 1 H) , 6.95 (d, J = 8.7 Hz, 2H), 7.42 (d, J = 8.7 Hz, 2H), 7.47 (dd, J = 1.6, 4.6 Hz, 2H), 7.48-7.50 (m, 1H), 7.59 ( dd, J = 1.1, 5.1 Hz, 1H), 7.67-7.68 (m, 1H), 8.40 (d, J = 5.1 Hz, 1H), 8.63 (dd, J = 1.6, 4.6 Hz, 2H), 13.29 (br s, 1H). APCIMS m / z: [M + H] + 485.

[Example 107] 2- (Chloromethyl) -N- [4- (2-furyl) -5- (4-pyridyl) thiazol-2-yl] iridine-4-carboxamide (Compound 107) In a manner similar to that in Example 3, when using 2- (Chloromethyl) isonicotinic acid (2.12 g, 12.3 mmol) obtained according to the method described in W003 / 043636 in place of methoxyacetic acid, the title compound 107 (1.75 g, 71%) is obtained from compound a (1.50 g, 6.17 mmol) obtained in reference example 1. X H NMR (DMSO-d 6, d ppm): 4.90 (s, 2 H), 6.61 - (dd, J = 1.8, 3.5 Hz, 1 H), 6.75 (d, J = 3.5 Hz, 1H), 7.47 (d, J = 6.1 Hz, 2H), 7.68 (d, J = 1.8 Hz, 1H), 8.01 (d, J = 5.1 Hz, 1H), 8.18 (s, 1H) , 8.63 (d, J = 6.1 Hz, 2H), 8.81 (d, J = 5.1 Hz, 1H).

[Example 108] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -2- (imidazol-1-ylmethyl) pyridine-4-carboxamide (Compound 108) Compound 107 (150 mg, 0.387 mmol) was dissolved in DMF (2 ml), and imidazole (129 mg, 1.89 mmol) was added thereto, followed by stirring at 90 ° C for 3 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform-methanol = 30: 1) to give the title compound 108 (120 mg, 74%).

E NMR (DMSO-d6, d ppm): 5.43 (s, 2H), 6.61 (dd, J = 1.8, 3.3 Hz, 1H), 6.75 (d, J = 3.3 Hz, 1H), 6.98 (s, 1H) , 7.23 (s, 1H), 7.46 (d, J = 6.2 Hz, 2H), 7.68 (d, J = 1.8 Hz, 1H), 7.81 (s, 1H), 7.85 (s, 1H), 7.97 (d, J = 5.1 Hz, 1H), 8.63 (d, J = 6.2 Hz, 2H), 8.79 (d, J = 5.1 Hz, 1H). APCIMS m / z: [M + H] + 429. p.f .: 239-250 ° C.

[Example 109] 2-. { N- [2- (Dimethylamino) ethyl] -N-methylaminomethyl} -N- [4- (2-furyl) -5- (4-pyridyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 109) Compound 107 (150 mg, 0.387 mmol) was dissolved in N, N , N'-trimethylethylenediamine (1 mL), followed by stirring at 60 ° C for 4 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform-methanol = 20: 1) and then crystallized from diisopropyl ether to give the title compound 109 (70 mg, 40%) as a solid. White. 2 H NMR (CDC13, d ppm): 2.30 (s, 6 H), 2.35 (s, 3 H), 2.50-2.54. (m, 2H), 3.81 (s, 2H), 6.46 (dd, J = 1.7, 3.2 Hz, 1H), 6.65 (d, J = 3.2 Hz, 1H), 7.38 (d, J = 1.7 Hz, 1H), 7.42 (d, J = 6.2 Hz, 2H), 7.81 (d, J = 5.1 Hz, 1H), 8.37 (s) , 1H), 8.64 (d, J = 6.2 Hz, 2H), 8.75 (d, J = 5.1 Hz, 1H). APCIMS m / z: [M + H] + 463. p.f .: 203-205 ° C. [Example 110] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -2- [N- (2-methoxyethyl) -N-methylaminomethyl] pyridine-4-carboxamide ( Compound 110) In a manner similar to that in Example 109, using N- (2-methoxyethyl) -N-methylamine (1 mL) in place of N, N, N'-trimethylethylenediamine, the title compound 110 (137 mg, 81%) is obtained from compound 107 (150 mg, 0.387 mmol). 2 H NMR (CDC13, d ppm): 2.42 (s, 3 H), 2.69 (t, J = 5.1 Hz, 2 H), 3. 51 (s, 3H), 3.59 (t, J = 5.1 Hz, 2H), 3.85 (s, 2H), 6.43 (dd, J = 1.8, 3.3 Hz, 1H), 6.61 (d, J = 3.3 Hz, 1H), 7.35 (d, J = 1.8 Hz, 1H), 7.43 (d, J = 6.1 Hz, 2H), 7.76 (d, J = 5.1 Hz, 1H), 8.20 (s, 2H), 8.65 (d, J = 6.1 Hz, 2H) , 8.75 (d, J = . 1 Hz, 1H). APCIMS m / z: [M + H] + 450. p. f. : 195-197 ° C.

[Example 111] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -2- (4-hydroxypiperidinomethyl) pyridine-4-carboxamide (Compound 111) In a manner similar to that in Example 108, using 4-hydroxypiperidine in place of imidazole, the title compound 111 (92.0 mg, 53%) is obtained from compound 107 (150 mg, 0.387 mmol). X H NMR (DMSO-de, d ppm): 0.84-0.89 (m, 4H), 1.24-1.37 (m, 4H), 1.60-1.68 (m, 1H), 4.14 (s, 2H), 6.60 (dd, J = 1.8, 3.3 Hz, 1H), 6.75 (d, J = -3.3 Hz, 1H), 7.47 (d, J = 1.8 Hz, 1H), 7.69 (d, J = 6.1 Hz, 2H), 7.91 (d, J = 5.1 Hz, 1H), 8.05 (s, 1H), 8.62 (s, J = 6.1 Hz, 2H), 8.73 (d, J = 5.1 Hz, 1H). APCIMS m / z: [M + H] + 462. p.f .: 203-208 ° C.

[Example 112] N- [4- (2-Furyl) -5- (4-pyridyl) thiazol-2-yl] -2-oxo-l, 2-dihydropyridine-4-carboxamide (Compound 112) Compound 106 ( 2.10 g, 4.33 mmol) and anisole (4.72 mL, 43.4 mmol) were suspended in trifluoroacetic acid (7 mL), followed by stirring at 65 ° C for 30 minutes. A saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture until the pH was adjusted to 8, and the precipitated solid was collected by filtration. The resulting solid was purified through silica gel column chromatography (chloroform: methanol = 4: 1) to give the title compound 112 (1.07 g, 68%). X H NMR (DMSO-d 6, d ppm): 6.66 (dd, J = 1.6, 3.2 Hz, 1H), 6.73 (d, J = 3.2 Hz, 1H), 7.00-7.05 (m, 2H), 7.45 (dd, J = 1.6, 4.0 Hz, 2H), 7.54 (d, J = 7.0 Hz, 1H), 7.67 (d, J = 1.6 Hz, 1H), 8.62 (dd, J = 1.6, 4.0 Hz, 2H), 11.98 ( br s, 1H), 13.17 (br s, 1H). APCIMS m / z: [M + H] + 365. p.f. 277-281 ° C. [Example 113] 1-Benzyl-N- [4- (2-furyl) -5- (4-pyridyl) thiazol-2-yl] -2-oxo-l, 2-dihydropyridine-4-carboxamide (Compound 113) Compound 112 (146 mg, 0.400 mmol) was dissolved in DMF (2 mL), 60% sodium hydride (35.2 mg, 0.880 mmol) was added thereto, followed by stirring at room temperature for 30 minutes. The benzyl bromide (0.0523 mL, 0.440 mmol) was added dropwise to the reaction mixture, followed by stirring overnight at room temperature. The reaction mixture was poured into water, and 1 mol / L hydrochloric acid was added thereto to adjust the pH to 7, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue is. purified by silica gel column chromatography (chloroform: methanol = 99: 1) to give the title compound 113 (25.0 mg, 14%). aH NMR (DMSO-d6, d ppm): 5.15 (s, 2H), 6.60 (dd, J = 1.6, 3.2 Hz, 1H), 6.73 (d, J = 3.2 Hz, 1H), 6.76 (dd, J = 1.9, 7.0 Hz, 1H), 7.16 (d, J = 1.9 Hz, 1H), 7.17-7.39 (m, 5H), 7.45 (dd, J = 1.6, 4.3 Hz, 2H), 7.67 (d, J = 1.6 Hz, 1H), 7.99 (d, J = 7.0 Hz, 1H), 8.62 (dd, J = 1.6, 4.3 Hz, 2H), 13.22 (br s, 1H). APCIMS m / z: [M + H] + 455. p.f .: 244-248 ° C. [Example 114] N- [4- (2-Furyl) -5- (3-methylpyridin-4-yl) thiazol-2-yl] pyridine-4-carboxamide (Compound 114) In a manner similar to that in the example 3, when using isonicotinic acid instead of methoxyacetic acid, the title compound 114 (502 mg, 73%) is obtained from compound m (514 mg, 2.00 mmol) obtained in reference example 13, instead of compound a. 1 H NMR (DMSO-d 6, d ppm): 2.08 (s, 3H), 6.49 (dd, J = 0.5, 3.2 Hz, 1H), 6.53 (dd, J = 1.9, 3.2 Hz, 1H), 7.38 (d, J = 4.9 Hz, 1H), 7.59 (dd, J = 0.5, 1.9 Hz, 1H), 8.03 (dd, J = 1.6, 6.2 Hz, 2H), 8.49 (d, J = 4.9 Hz, 1H), 8.58 (s, 1H), 8.83 (dd, J = 1.6, 6.2 Hz, 2H), 13.37 (br s, 1H). APCIMS m / z: [M + H] + 363.

[Example 115] N- [4,5-Di (2-furyl) thiazol-2-yl] benzamide (Compound 115) Compound n (300 mg, 0.760 mmol) obtained in reference example 14, tributyl (2- furil) (0.720 mL, 2.28 mmol), silver oxide (0.180 g, 0.760 mmol) and tetrakis (triphenylphosphine) palladium (0.130 g, 0.114 mmol) were suspended in DMF (7.6 mL), followed by stirring at 60 ° C. for 2 hours and at 100 ° C for 15 minutes. The reaction mixture was cooled with ice, ethyl acetate was added thereto, and the precipitated silver oxide was collected by filtration. The filtrate was concentrated under reduced pressure. A 10% aqueous solution (35 mL) of potassium fluoride was added to the resulting residue, followed by stirring at room temperature for 10 minutes, and then extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 10: 1 to 5: 1) to give the title compound 115 (20.6 mg, 8%). XH NMR (CDC13, d ppm): 6.48 (dd, J = 1.9, 3.5 Hz, 1H), 6.52 (dd, J = 1.9, 3.5 Hz, 1H), 6.77 (dd, J = 0.8, 3.5 Hz, 1H) , 6.80 (dd, J = 0.8, 3.5 Hz, 1H), 7.47-7.66 (m, 3H), 7.49 (dd, J = 0.8, 1.9 Hz, 1H), 7.51 (dd, J = 0.8, 1.9 Hz, 1H ), 7.90-7.97 (, 2H), 9.59 (br s, 1H). p.f .: 156-157 ° C.

[Example 116] N- [4- (2-Furyl) -5- (2-thienyl) thiazol-2-yl] benzamide (Compound 116) In a manner similar to that in example 115, when using tributyl (2- thienyl) stannane (0.240 mL, 0.750 mmol) in Place of tributyl (2-furyl) stannane, the title compound 116 (98.9 mg, 100%) is obtained from compound n (100 mg, 0.250 mmol) obtained in reference example 14. XH NMR (CDC13, d ppm) : 6.33 (dd, J = 1.8, 3.3 Hz, 1H), 6.46 (dd, J = 3.3 Hz, 1H), 7.11 (dd, J = 3.7, 5.1 Hz, 1H), 7.27 (dd, J = 1.5, 3.7 Hz, 1H), 7.34 (d, J = 1.8 Hz, 1H), 7.41 (dd, J = 1.5, 5.1 Hz, 1H), 7.43-7.53 (m, 2H), 7.54-7.62 (m, 1H), 7.86 -7.94 (m, 2H), 9.59 (br s, 1H). APCIMS m / z: [M + H] + 353.

[Example 117] N- [4- (2-Furyl) -5- (l-methylindol-2-yl) thiazol-2-yl] benzamide (Compound 117) In a manner similar to that in example 115, when using tributyl (l-methylindol-2-yl) stannane (1.37 mL, 3.78 mmol) in place of tributyl (2-furyl) stannane, the title compound 117 (395 mg, 78%) is obtained as a pale yellow solid of the compound n (500 mg, 1.26 mmol) obtained in Reference Example 14. 2 H NMR (CDCl 3, d ppm): 3.55 (s, 3 H), 6.05 (d, J = 3.5 Hz, 1 H), 6.29 (dd, J = 1.6, 3.5 Hz, 1H), 6.73 (s, 1H), 7.14-7.22 (m, 1H), 7.24-7.41 (, 2H), 7.35 (d, J = 1.6Hz, 1H), 7.50-7.71 (m, 4H), 7.91-7.97 (m, 2H), 9.76 (br s, 1H). p.f .: 195-196 ° C.

[Example 118] N- [4- (2-Furyl) -5- (2-methylphenyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 118) In a manner similar to that in Example 3, using isonicotinic acid instead of methoxyacetic acid, the title compound 118 (482 mg, 67%) is obtained from the compound o (512 mg, 2.00 mmol) obtained in reference example 15, instead of compound a. XR NMR (DMSO-d6, d ppm): 2.09 (s, 3H), 6.18 (d, J = 3.2 Hz, 1H), 6.46 (dd, J = 1.9, 3.2 Hz, 1H), 7.28-7.40 (m, 4H), 7.57 (d, J = 1.9 Hz, 1H), 8.01 (dd, J = 1.4, 5.9 Hz, 2H), 8.82 (dd, J = 1.4, 5.9 Hz, 2H), 12.27 (br s, 1H) . APCIMS m / z: [M + H] + 362.

[Example 119] N- [4- (2-Furyl) -5- (4-methoxyphenyl) thiazol-2-yl] benzamide (Compound 119) In a manner similar to that in example 115, when using tributyl (4-) oxyphenyl) stannane (1.15 mL, 3.78 mmol) in place of tributyl (2-furyl) stannane, the title compound 119 (137 mg, 29%) is obtained as a pale yellow solid. of compound n (500 mg, 1.26 mmol) obtained in Reference Example 14. X H NMR (CDC 13, d ppm): 3.87 (s, 3 H), 6.32 (dd, J = 0.8, 3.5 Hz, 1 H), 6.34 ( dd, J = 1.9, 3.5 Hz, 1H), 6.96 (d, J = 8.9, Hz, 2H), 7.37 (d, J = 0.-8, 1.9 Hz, 1H), 7.43 (d, J = 8.9 Hz , 2H), 7.48-7.57 (m, 2H), 7.58-7.66 (m, 1H), 7.90-7.97 (m, 2H), 9.61 (br s, 1H). APCIMS m / z: [M + H] + 377. m.p .: 90-98 ° C.

[Example 120] N- [4- (2-Furyl) -5- (3-methoxyphenyl) thiazol-2-yl] benzamide (Compound 120) In a manner similar to that in example 115, when using tributyl (3- methoxyphenyl) stannane (1.40 mL, 3.78 mmol) in place of tributyl (2-furyl) stannane, the title compound 120 (245 mg, 52%) is obtained as a pale yellow solid of compound n (500 mg, 1.26 mmol) obtained in reference example 14. a H NMR (CDCl 3, d ppm): 3.82 (s, 3 H), 6.31 (d, J = 1.6, 3.3 Hz, 1 H), 6.36 (d, J = 3.3 Hz, 1 H), 6.95 (dd, J = 2.5, 8.2 Hz, 1H), 7.05 (dd, J = 2.5, 2.5 Hz, 1H), 7.10 (dd, J = 2.5, 7.5 Hz, 1H), 7.32 (d, J = 1.6 Hz , 1H), 7.34 (dd, J = 7.5, 8.2 Hz, 1H), 7.45-7.54 (m, 2H), 7.56-7.63 (m, 1H), 7.89-7.95 (m, 2H), 8.74 (br s, 1 HOUR) .

APCIMS m / z: [M + H] + 377.

[Example 121] N- [4- (2-Furyl) -5- (2-methoxyphenyl) thiazol-2-yl] benzamide (Compound 121) In a manner similar to that in example 115, when using tributyl (2- methoxyphenyl) stannane (1.49 mL, 4.53 mmol) in place of tributyl (2-furyl) stannane, the title compound 121 (181 mg, 33%) is obtained from compound n (600 mg, 1.51 mmol) obtained in reference example 14.? E NMR (CDC13, d ppm): 3.77 (s, 3H), 6.08 (d, J = 3.3 Hz, 1H), 6.17 (dd, J = 1.8, 3.3 Hz, 1H), 6.96-7.06 (m, 2H), 7.15 (d, J = 1.8 Hz, 1H), 7.34-7.55 (m, 5H) , 7.86-7.92 (m, 2H), 10.91 (br s, 1H). APCIMS m / z: [M + H] + 377.

[Example 122] N- [4- (2-Furyl) -5- (2-trifluoromethylphenyl) thiazol-2-yl] benzamide (Compound 122) In a manner similar to that in Example 115, using tributyl (2-trifluoromethylphenyl) stannane (1.41 mL, 3.78 mmol) in place of tributyl (2-furyl) stannane, the title compound 122 (313 mg , 60%) is obtained as a pale yellow solid of compound n (500 mg, 1.26 mmol) obtained in reference example 14.

X H NMR (CDCl 3, d ppm): 5.88 (dd, J = 0.8, 3.2 Hz, 1H), 6.25 (dd, J = 1.9, 3.2 Hz, 1H), 7.26 (dd, J = 0.8, 1.9 Hz, 1H) , 7.46-7.67 (m, 6H), 7.81-7.87 (m, 1H), 7.91-7.97 (m, 2H), 9.72 (br s, 1H). p.f .: 205-206 ° C.

[Example 123] N- [4- (2-Furyl) -5- (l-methyl-2-oxo-l, 2-dihydropyridin-4-yl) thiazol-2-yl] pyridine-4-carboxamide (Compound 123 Step 1: Compound p (259 mg, 1.00 mmol) obtained in Reference Example 16 was suspended in methanol (4 mL), a 28% solution, of sodium methoxide (385 mg, 2.00 mmol) in methanol was added to this, followed by agitation for 30 minutes. In addition, methyl iodide (0.185 mL, 3.00 mmol) was added to the reaction mixture, followed by stirring overnight, and the reaction mixture was concentrated under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 9: 1) to give 2-amino-4- (2-furyl) -5- (1-methyl-2-oxo-1) , 2-dihydropyridin-4-yl) thiazole (222 mg, 81%) as a yellow solid. 1 H NMR (DMSO-d 5, d ppm): 3.39 (s, 3 H), 6.02 (dd, J = 2.1, 7.1 Hz, 1 H), 6.24 (d, J = 2.1 Hz, 1 H), 6.56 (dd, J = 1.7, 3.3 Hz), 6.63 (dd, J = 0.8, 3.3 Hz, 1H), 7.42 (brs, 2H), 7.59 (d, J = 7.1 Hz, 1H), 7.65 (dd, J = 0.8, 1.7 Hz, 1H). APCIMS m / z: [M + H] + 274.

Step 2: 2-Amino-4- (2-furyl) -5- (1-methyl-2-oxo-l, 2-dihydropyridin-4-yl) thiazole (222 mg, 0.812 mmol) obtained in step 1 was dissolved in DMF (4 mL), and isonicotinic acid (199 mg, 1.62 mmol), PyBOP (926 mg, 1.78 mmol) and triethylamine (0.497 mL, 3.56 mmol) were added thereto, followed by stirring at 80 ° C. 1 hour. The reaction mixture was poured into water, and the precipitated solid was collected by filtration. The resulting solid was purified through silica gel column chromatography (chloroform-methanol = 17: 3), followed by thickening with methanol to give the title compound 123 (158 mg, 52%) as a yellow solid. pale. 2 H NMR (DMSO-d 6, d ppm): 3.46 (s, 3 H), 6.21 (dd, J = 1.6, 7.0 Hz, 1 H), 6.46 (d, J = 1.6 Hz, 1 H), 6.62 (dd, J = 1.9, 3.5 Hz, 1H), 6.77 (dd, J = 0.8, 3.5 Hz, 1H), 7.74 (d, J = 7.0 Hz, 1H), 7.74 (dd, J = 0.8, 1.9 Hz, 1H), 8.01 (dd, J = 1.6, 4.6 Hz, 2H), 8.82 (dd, J = 1.6, 4.6 Hz, 2H), 13.35 (br s, 1H). APCIMS m / z: [M + H] + 379. p.f. : 280-282 ° C.

[Example 124] N- [5- (1-Ethyl-2-oxo-l, 2-dihydropyridin-4-yl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 124 Stage 1: In a manner similar to that in stage 1 of Example 123, when using ethyl iodide in place of methyl iodide, 2-amino-5- (l-ethyl-2-oxo-l, 2-dihydropyridine) -4-yl) -4- (2-furyl) thiazole (0.167 mg, 58%) is obtained from compound p (259 mg, 1.00 mmol) obtained in reference example 16. XH NMR (DMS0-d6, d ppm ) 1.21 (t, J = 7.1 Hz, 3H), 3.67 (q, J = 7.1 Hz, 2H), 6..04 (dd, J = 2.0, 7.1 Hz, 1H), 6.24 (d, J = 2.0 Hz, 1H), 6.56 (dd, J = 1.8, 3.4 Hz, 1H), 6.63 (dd, J = 0.9, 3.4 Hz, 1H), 7.43 (br s, 2H), 7.60 (d, J = 7.1 Hz, 1H), 7.66 (dd, J = 0.9, 1.8 Hz, 1H). APCIMS m / z [M + H] + 288.

Step 2: 2-Amino-5- (l-ethyl-2-oxo-l, 2-dihydropyridin-4-yl) -4- (2-furyl) thiazole (167 mg, 0.582 mmol) obtained in step 1 Dissolve in DMF (8 mL), and isonicotinic acid (143 mg, 1.16 mmol), PyBOP (664 mg, 1.28 mmol) and triethylamine (0.356 mL, 2.55 mmol) were added thereto, followed by stirring at 80 ° C for 1 h. hour. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer it was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate., and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform-methanol = 17 * 1), followed by making a thick mixture with a mixed solvent of methanol and diethyl ether to give the title compound 124 (83.5 mg, 37%) as a pale brown solid. NMR (DMSO-d6, d ppm): 1.25 (t, J = 7.0 Hz, 3H), 3.93 (g, J = 7.0 Hz, 2H), 6.23 (dd, J = 1.9, 7.0 Hz, 1H), 6.44 (d, J = 1.9 Hz, 1H), 6.62 (dd, J = 1.9, 3.2 Hz, 1H), 6.76 (dd, J = 0.8, 3.2 Hz, 1H), 7.74 (d, J = 7.0 Hz, 1H) , 7.74 (dd, J = 0.8, 1.9 Hz, 1H), 8.01 (dd, J = 1.6, 4.3 Hz, 2H), 8.82 (dd, J = .1.6, 4.3 Hz, 2H), 13.36 (br s, 1H ). APCIMS m / z: [M + H] + 393. p.f .: 245-248 ° C.

[Example 125] N- [5- (l-Benzyl-2-oxo-l, 2-dihydropyridin-4-yl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 125 ) Step 1: In a manner similar to that in step 1 of Example 123, when using benzyl bromide in place of methyl iodide, 2-amino-5- (1-benzyl-2-oxo-1, 2-dihydropyridin- 4-yl) -4- (2-furyl) thiazole (289 mg, 83%) is obtained from the compound p (259 mg, 1.00 mmol) obtained in reference example 16. X H NMR (DMSO-d 6, d ppm): 5.02 (s, 2 H), 6.07 (dd, J = 2.1, 7.2 Hz, 1 H), 6.28 (d , J = 2.1 Hz, 1H), 6.56 (dd, J = 1.8, 3.3 Hz, 1H), 6.64 (d, J = 3.3 Hz, 1H), 7.25-7.39 (m, 5H), 7.46 (br s, 2H ), 7.66 (d, J = 1.8 Hz, 1H), 7.69 (d, J = 7.2 Hz, 1H). APCIMS m / z: [M + H] + 350. Step 2: In a manner similar to that in step 2 of example 124, the title compound 125 (42.6 mg, 11%) is obtained as a pale brown 2-amino-5- (1-benzyl-2-oxo-l, 2-dihydropyridin-4-yl) -4- (2-furyl) thiazole (289 mg, 0.827 mmol) obtained in step 1, instead of 2-amino-5- (1-ethyl-2-oxo-l, 2-dihydropyridin-4-yl) -4- (2-furyl) thiazole. E NMR (DMSO-d6, d ppm): 5.13 (s, 2H), 6.26 (dd, J = 1.9, 7.0 Hz, 1H), 6.50 (d, J = 1.9 Hz, 1H), 6.62 (dd, J = 1.9, 3.2 Hz, 1H), 6.77 (dd, J = 0.5, 3.2 Hz, 1H), 7.25-7.45 (m, 5H), 7.74 (dd, J = 0.5, 1.9 Hz, 1H), 7.83 (d , J = 7.0 Hz, 1H), 8.01 (dd, J = 1.6, 5.9 Hz, 2H), 8.81 (dd, J = 1.6, 5.9 Hz, 2H), 13.36 (br s, 1H). APCIMS m / z: [M + H] + 455. m.p .: 137-140 ° C. [Example 126] N- [4- (2-Furyl) -5- (l-methyl-2-oxo-l, 2-dihydropyridin-5-yl) thiazol-2-yl] pyridine-4-carboxamide (Compound 126 Stage 1: The compound q (259 mg, 1.00 mmol) obtained in the Reference example 17 and sodium methoxide (119 mg, 2.20 mmol) were suspended in methanol (6 mL), followed by stirring at room temperature for 40 minutes. In addition, methyl iodide (0.218 mL, 3.50 mmol) was added to the reaction mixture, followed by stirring overnight, and the reaction mixture was concentrated under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 4: 1) to give 2-amino-4- (2-furyl) -5- (1-methyl-2-oxo-1) , 2-dihydro-iridin-5-yl) thiazole (203 mg, 74%) as a pale brown solid. XR NMR (DMSO-d6, d ppm): 3.44 (s, 3H), 6.38 (d, J = 9.2 Hz, 1H), 6.48 (m, 2H), 7.15 (br s, 2H), 7.34 (dd, J = 2.6, 9.2 Hz, 1H), 7.53-7.57 (m, 1H), 7.92 (d, J = 2.6Hz, 1H). APCIMS m / z: [M + H] + 274.

Step 2: 2-Amino-4- (2-furyl) -5- (1-methyl-2-oxo-l, 2-dihydropyridin-5-yl) thiazole (200 mg, 0.732 mmol) obtained in step 1 was dissolved in DMF (4 mL), and isonicotinic acid (180 mg, 1.46 mmol), PyBOP (838 mg, 1.61 mmol) and triethylamine (0.449 mL, 3.21 mmol) were added thereto, followed by stirring at 80 ° C for 1 hour. The reaction mixture was poured into water, and the precipitated solid was collected by filtration. The resulting solid was purified through silica gel column chromatography (chloroform: methanol = 17: 1), followed by thickening with methanol to give the title compound 126 (155 mg, 56%) as a pale yellow solid. X H NMR (DMSO-d 6, d ppm): 3.49 (s, 3 H), 6.46 (d, J = 9.4"Hz, 1 H), 6.57 (dd, J = 1.9, 3.5 Hz, 1 H), 6.66 (dd, J = 0.8, 3.5 Hz, 1H), 7.44 (dd, J = 2.7, 9.4 Hz, 1H), 7.67 (dd, J = 0.8, 1.9 Hz, 1H), 8.00 (d, J = 2.7 Hz, 1H), 8.01 (dd, J = 1.6, 4.3 Hz, 2H), 8.20 (dd, J = 1.6, 4.3 Hz, 2H), 13.22 (br s, 1H) APCIMS m / z: [M + H] + 379. pf : .294-295 ° C.

[Example 127] N- [5- (1-Ethyl-2-oxo-l, 2-dihydropyridin-5-yl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 127 Stage 1: In a manner similar to that in step 1 of example 126, when using ethyl iodide in place of methyl iodide, 2-amino-5- (l-ethyl-2-oxo-l, 2-dihydropyridine) -5-yl) -4- (2-furyl) thiazole (287 mg, 100%) is obtained from compound q (259 mg, 1.00 mmol) obtained in reference example 17. H NMR (DMSO-d6, d ppm ): 1.22 (t, J = 7.1 Hz, 3H), 3.92 (q, J = 7.1 Hz, 2H), 6.38 (d, J = 9.4 Hz, 1H), 6.45-6.50 (m, 2H), 7.16 (br s, 2H), 7.34 (dd, J = 2.6, 9.4 Hz, 1H) 7.53-7.57 (m, 1H), 7.82 (d, J = 2.6 Hz, 1H).

APCIMS m / z: [M + H] + 288. Stage 2: 2-Amino-5- (l-ethyl-2-oxo-l, 2-dihydropyridin-5-yl) -4- (2-furyl) thiazole (287 mg, 1.00 mmol) obtained in step 1 was dissolved in DMF (4 mL), and isonicotinic acid (246 mg, 2.00 mmol), PyBOP (1.14 g, 2.20 mmol) and triethylamine (0.613 mL, 4.40 mmol) were added to this, followed by stirring at 80 ° C for 1 hour. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: ethanol = 17: 1), followed by making a thick mixture with a mixed solvent of methanol and diethyl ether to give the title compound 127 (99.0 mg, 25%) as a pale brown solid. XR NMR (DMS0-d6, d ppm): 1.26 (t, J = 7.0 Hz, 3H), 3.97 (q, J = 7.0 Hz, 2H), 6.45 (d, J = 9.2 Hz, 1H), 6.58 (dd) , J = 1.6, 3.2 Hz, 1H), 6.66 (d, J = 3.2 Hz, 1H), 7.45 (d, J = 2.7, 9.2 Hz, 1H), 7.68 (d, J = 1.6 Hz, 1H) , 8.00 (d, J = 2.7 Hz, 1H), 8.04 (dd, J = 1.6, 4.3 Hz, 2H), 8.84 (dd, J = 1.6, 4.3 Hz, 2H), 13.24 (br s, 1H). APCIMS m / z: [M + H] + 393. p.f .: 285-289 ° C. [Example 128] N- [5- (l-Benzyl-2-oxo-l, 2-dihydropyridin-5-yl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 128 Stage 1: In a manner similar to that in step 1 of Example 126, when using benzyl bromide in place of methyl iodide, 2-amino-5- (l-benzyl-2-oxo-l, 2-dihydropyridine) -5-yl) -4- (2-furyl) thiazole (349 mg, 100%) is obtained from compound q (259 mg, 1.00 mmol) obtained in reference example 17.

Step 2: 2-Amino-5- (l-benzyl-2-oxo-l, 2-dihydropyridin-5-yl) -4- (2-furyl) thiazole (349 mg, 1.00 mmol) obtained in step 1 was dissolved in DMF (4 mL), and isonicotinic acid (246 mg, 2.00 mmol), PyBOP (1.14 g, 2.20 mmol) and triethylamine (0.613 mL, 4.40 mmol) were added thereto, followed by stirring at 80 ° C for 1 hour. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform-methanol = 17.1), followed by) Thicken mixture with a mixed solvent of methanol and diethyl ether to give the title compound 128 (128 mg, 28%) as a pale brown solid. ? E NMR (DMSO-d6, d ppm): 5.16 (s, 2H), 6.51 (d, J = 9.2 Hz, 1H), 6.54 (dd, J = 1.6, 3.5 Hz, 1H), '6.63 (dd, J = 0.8, 3.5 Hz, 1H), 7.26-7.44 (m, 5H), 7.49 (dd, J = 2.4, 9.2 Hz, 1H), 7.51 (dd, J = 0.8, 1.9 Hz, 1H), 8.00 (dd) , J = 1.6, 4. 6 Hz, 2H), 8.11 (d, J = 2.4 Hz, 1H), 8.81 (dd, J = 1.6, 4.6 Hz, 2H), 13.25 (br s, 1H). APCIMS m / z: [M + H] + 455. p.f .: 215-218 ° C.

[Example 129] N- [5- (1-Ethyl-6-oxo-l, 6-dihydropyridin-2-yl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 129 The compound r (660 mg, 2.30 mmol) obtained in Reference Example 18 was dissolved in DMF (8 mL), and isonicotinic acid (1.70 g, 13.8 mmol), EDC Hydrochloride (2.64 g, 13.8 mmol) and monohydrate of 1-hydroxybenzotriazole (2.11 g, 6.66 mmol) were added thereto, followed by stirring at 80 ° C for 3 hours. The reaction mixture was poured into water, and the precipitated solid was collected by filtration. The resulting solid was purified through silica gel column chromatography (chloroform-methanol = 19: 1), followed by thickening with a mixed solvent of methanol and diethyl ether to provide the title compound 129 (442 mg, 49%) as a pale brown solid. XH NMR (CDC13, d ppm): 1.16 (t, J = 6.5 Hz, 3H), 3.22 (q, J = 6.5 Hz, 2H), 6.32 (dd, J = 1.4, 6.8 Hz, 1H), 6.38-6.42 (m, 2H), 6.75 (dd, J = 1.4, 9.2 Hz, 1H), 7.33-7.40 (, 2H), 7.81 (dd, J = 1.6, 4.6 Hz, 2H), 8.88 (dd, J = 1.6, 4. 6 Hz, 2H) APCIMS m / z: [M + H] + 393. pf : > 300 ° C.

[Example 130] N- [5- (1-Ethyl-6-oxo-l, 6-dihydropyridazin-3-yl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 130 ) In a manner similar to that in Example 3, when using isonicotinic acid in place of methoxyacetic acid, the title compound 130 (200 mg, 87 %) is obtained from compound s (186 mg, 0.588 mmol) obtained in reference example 19, instead of compound a. X H NMR (CDCl 3, d ppm): 1.43 (t, J = 7.1 Hz, 3 H), 4.27 (q, J = 7.1 Hz, 2 H), 6.40 (dd, J = 1.8, 3.3 Hz, 1 H), 6.63 (d , J = 3.3 Hz, 1H), 6.91 (d, J = 9.6 Hz, 1H), 7.34 (d, J = 9.6 Hz, 1H), 7. 35 (d, J = 1.8 Hz, 1H), 7.77 (d, J = 6.1 Hz, 2H), 8.80 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M + H] + 394. p.f .: 235-239 ° C.

[Example 131] N- [4- (2-Furyl) -5- (l-isopropyl-6-oxo-l, 6-dihydropyridazin-3-yl) thiazol-2-yl] pyridine-4-carboxamide (Compound 131 ) In a manner similar to that in Example 3, when using isonicotinic acid in place of methoxyacetic acid, the title compound 131 (157 mg, 72%) is obtained from compound t (162 mg, 0.539 mmol) obtained in the example of reference 20, instead of compound a. X H NMR (DMS0-d 6, d ppm): 1.32-1.34 (m, 6H), 5.17-5.22 (m, 1H), 6.66 (dd, J = 1.8, 3.3 Hz, 1H), 6.85 (d, J = 3.3 Hz, 1H), 6. 96 (d, J = 9.7 Hz, 1H), 7.45 (d, J - 9.7 Hz, 1H), 7.78 (d, J = 1.8 Hz, 1H), 8.03 (d, J = 4.5 Hz, 2H), 8.85 (d, J = 4.5 Hz, 2H), 13.3 (s, 1H). APCIMS m / z: [M + H] + 408. p.f .: 190-194 ° C.

[Example 132] Ethyl 2- (tert-butoxycarbonylamino) -4- (2-furyl) thiazole-5-carboxylate (Compound 132) In a manner similar to that in reference example 8, the title compound 132 (5.12 g, 74%) is obtained from compound e (4.89 g, 20.5 mmol) obtained in reference example 5, instead of Compound g obtained in reference example 7.

X H NMR (CDCl 3, d ppm): 1.37 (t, J = 7.0 Hz, 3 H), 1.46 (s, 9 H), 4.35 (q, J = 7.0 Hz, 2 H), 6.55 (dd, J = 1.6, 3.5 Hz , 1H), 7.52 (dd, J = 0.3, 1.6 Hz, 1H), 7.79 (dd, J = 0.3, 3.5 Hz, 1H), 9.43 (br s, 1H). ESIMS m / z: [M + H] + 339.

[Example 133] 2- (tert-Butoxycarbonylamino) -4- (2-furyl) thiazole-5-carboxylic acid (Compound 133) In a manner similar to that in Example 95, the title compound 133 (4.65 g, 99 %) is obtained from compound 132 (5.12 g, 15.1 mmol), instead of Compound 24. H NMR (DMSO-d6, d ppm): 1.50 (s, 9H), 6.61 (dd, J = 1.9, 3.2 Hz, 1H), 7.55 (dd, J = 0.8, 3.2 Hz, 1H), 7.76 (dd, J = 0.8, 1.9 Hz, 1H), 12.00 (br s, 1H). APCIMS m / z: [M + H] + 311.

[Example 134] 2- (tert-Butoxycarbonylamino) -4- (2-furyl) -N-methoxy-N-methylthiazole-5-carboxamide (Compound 134) In a manner similar to that in example 96, by using chlorohydrate of N, O-dimethylhydroxylamine in place of morpholine, the title compound 134 (2.59 g, 49%) is obtained from compound 133 (4.65 g, 15.0 mmol), instead of Compound 95.

X H NMR (CDCl 3, 'd ppm): 1.46 (s, 9 H), 3.34 (s, 3 H), 3.67 (s, 3 H), 6.47 (dd, J = 1.6, 3.5 Hz, 1 H), 7.04 (dd, J = 0.8, 3.5 Hz, 1H), 7.47 (dd, J = 0.8, 1.6 Hz, 1H), 9.23 (br s, 1H).

[Example 135] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] tert-Butyl carbamate (Compound 135) Compound 134 (10.7 g, 30.3 mmol) was dissolved in THF (240 ml ), and a THF solution of 2.0 mol / L phenylmagnesium chloride (60.6 mL, 121 mmol) was added thereto at 0 ° C under an argon atmosphere, followed by stirring at room temperature for 2 hours. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 3: 1) to give the title compound 135 (6.18 g, 55%).

%) - XH NMR (CDC13, 6 ppm): 1.49 (s, 9H), 6.38 (dd, J = 1.8, 3.5 Hz, 1H), 7.10 (d, J = 3.5 Hz, 1H), 7.27 (d, J = 1.8 Hz, 1H), 7.36-7.53 (m, 3H), 7.76-7.78 (m, 2H).

[Example 136] 2-Amino-4- (2-furyl) thiazol-5-ylphenyl ketone (Compound 136) Compound 135 (6.18 g, 16.7 mmol) was dissolved in trifluoroacetic acid (17 mL), followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, ethyl acetate and a saturated aqueous solution of sodium acid carbonate were added to the residue, and the organic layer was separated. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 4) to give the title compound 136 (4.39 g, 97%). X H NMR (DMSO-d 6, d ppm): 6.40 (dd, J = 1.8, 3.5 Hz, 1H), 6.80 (dd, J = 0.7, 3.5 Hz, 1H), 7.30 (dd, J = 0.7, 1.8 Hz, 1H), 7.31-7.37 (m, 2H), 7.44-7.55 (m, 3H), 8.00 (s, 2H).

[Example 137] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -2-hydroxy-2-methylpropanamide (Compound 137) Compound 136 (150 mg, 0.555 mmol) was dissolved in DMF (2.5 mL), and 2-hydroxy-2-methylpropanoic acid (116 mg, 1.11 mmol), EDC hydrochloride (313 mg, 1.11 mmol) and 1-hydroxybenzotriazole monohydrate (170 mg, 1.11 mmol) were added to this, followed by stirring at 50 ° C for 3 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give the title compound 137 (158 mg, 80%). XH NMR (CDC13, d ppm): 1.63 (s, 6H), 6.44 (dd, J = 1.8, 3.5 Hz, 1H), 7.21 (dd, J = 0.7, 3.5 Hz, 1H), 7.38 (dd, J = 0.7, 1.8 Hz, 1H), 7.39-7.53 (m, 3H), 7.78-7.82 (m, 2H), 10.6 (s, 1H). APCIMS m / z: [M + H] + 357. m.p .: 153-154 ° C.

[Example 138] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -1-hydroxycyclopropanecarboxamide (Compound 138) In a manner similar to that in example 137, by using 1-hydroxycyclopropanecarboxylic acid in Place of 2-hydroxy-2-methylpropanoic acid, the title compound 138 (151 mg, 77%) is obtained from compound 136 (150 mg, 0.555 mmol). 1 H NMR (CDCl 3, d ppm): 1.26-1.32 (m, 2H), 1.51-1.56 (m, 2H), 6.41 (dd, J = 1.8, 3.5 Hz, 1H), 7.13 (dd, J = 0.7, 3. 5 Hz, 1H), 7.34 (dd, J = 0.7, 1.8 Hz, 1H), 7.37-7.42 (m, 2H), 7.49-7.52 (m, 1H), 7.77-7.80 (m, 2H), 10.31 (s) , 1 HOUR) . APCIMS m / z: [M + H] + 355. p.f .: 202-205 ° C.

[Example 139] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -3- (N, N-dimethylcarbamoyl) benzamide (Compound 139) Step 1: Methyl isophthalate (2.00 g, 11.1 mmol) was dissolved in THF (60 mL), and a 2.0 mol / L solution of dimethylamine (11.1 mL, 22.2 mmol) in methanol, EDC hydrochloride (4.27 g, 22.2 mmol) and 1-hydroxybenzotriazole monohydrate (3.40 g) were added. , 22.2 mmol) were added thereto, followed by stirring at room temperature for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 3) to provide methyl 3- (N, N-dimethylcarbamoyl) benzoate (2.30 g, 100%).

Step 2: The methyl 3- (N, N-dimethylcarbamoyl) benzoate (2.30 g, 11.1 mmol) obtained in step 1 was dissolved in a mixed solvent (1: 1) (50 mL) of methanol and water, and monohydrate of lithium hydroxide (932 mg, 22.2 mmol) was added thereto, followed by stirring at room temperature for 1 hour. The 3 mol / L hydrochloric acid was added to the reaction mixture until the pH was adjusted to 3, and the precipitated solid was collected by filtration to provide 3- (N, N-dimethylcarbamoyl) benzoic acid (2.12 g, 99%). XR NMR (DMSO-de, dppm): 2.89 (s, 3H), 2.97 (s, 3H), 7.36-7.37 (m, 2H), 7.89-7.95 (m, 2H).

Step 3: In a manner similar to that in Example 137, by using 3- (N, N-dimethylcarbamoyl) benzoic acid obtained in step 2 in place of 2-hydroxy-2-methylpropanoic acid, the title compound 139 ( 138 mg, 46%) is obtained from compound 136 (184 mg, 0.680 mmol). X H NMR (DMSO-d 6, d ppm): 2.94 (s, 3 H), 3.02 (s, 3 H), 6.50 (dd, J = 1.8, 3.5 Hz, 1 H), 6.94 (dd, J = 0.8, 3.5 Hz, 1H), 7.45-7.49 (m, 3H), 7.56-7.73 (m, 5H), 8.16-8.20 (m, 2H). APCIMS m / z: [M + H] + 386. p.f .: 222-224 ° C.

[Example 140] 2- (Chloromethyl) -N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 140) In a manner similar to that in Example 137, when using 2- (chloromethyl) isonicotinic acid obtained according to the method described in W003 / 043636 in place of 2-hydroxy-2-methylpropanoic acid, the title compound 140 (712 mg, 91%) is obtained from compound 136 ( 500 mg, 1.85 mmol). XH NMR (CDC13, d ppm): 4.69 (s, 2H), 6.22 (dd, J = 1.7, 3.3 Hz, 1H), 6.97 (d, J = 3.3 Hz, 1H), 7.12 (d, J = 1.7 Hz , 1H), 7.39-7.64 (m, 4H), 7.81-7.85 (m, 3H), 8.66-8.68 (m, 1H).

[Example 141] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -2- (dimethylaminomethyl) pyridine-4-carboxamide (Compound 141) Compound 140 (100 mg, 0.236 mmol) was dissolved in a methanol solution (2 mL) of 2.0 mol / L dimethylamine, followed by stirring overnight. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to give the title compound 141 (42.0 mg, 41%).

X H NMR (CDCl 3, d ppm): 2.30 (s, 6H), 3.65 (s, 2H), 6.30 (dd, J = 1.8, 3.3 Hz, 1H), 7.06 (d, J = 3.3 Hz, 1H), 7.21 (d, J = 1.8 Hz, 1H), 7.39-7.44 (m, 2H), 7.52-7.57 (m, 1H), 7.65 (dd, J = 1.5, 5.0 Hz, 1H), 7.80 (d, J = 1.5 Hz, 1H), 7.81-7.87 (m, 2H), 8.72 (d, J = 5.0 Hz, 1H). APCIMS m / z: [M + H] + 433. mp: 205-209 ° C.

[Example 142] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -2- [N- (2-dimethylaminoethyl) -N-methylaminomethyl] pyridine-4-carboxamide (Compound 142) In a similar manner to that in Example 141, using N, N, N'-trimethylethylenediamine instead of the 2.0 mol / L solution of dimethylamine in methanol, the title compound 142 (90.7 mg, 46%) is obtained from compound 140 (170 mg, 0.401 mmol). X H NMR (DMSO-de, d ppm): 2.31 (s, 3 H), 2.48 (s, 3 H), 2.49 (s, 3 H), 2.70 (t, J = 6.2 Hz, 2 H), 2.84 (t, J = 6.2 Hz, 2H), 3.78 (s, 2H), 6.42 (dd, J = 1.9, 3.2 Hz, 1H), 6.88 (dd, J = 0.8, 3.2 Hz, 1H), 7.35-7.44 (m, 3H), 7.47-7.55 (m, 1H), 7.64-7.69 (m, 2H), 7.88 (dd, J = 1.9, 5.1 Hz, 1H), 8.06 (m, 1H), 8.62 (dd, J = 0.8, 5.1 Hz, 1 HOUR) . APCIMS m / z: [M + H] + 490.

[Example 143] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -2- [N- (2-methoxyethyl) -N-methylaminomethyl] pyridine-4-carboxamide dichlorohydrate (Compound 143) In a manner similar to that in Example 141, by using N- (2-methoxyethyl) -N-methylethylenediamine in place of the 2.0 mol / L solution of dimethylamine in methanol, a free form of the title compound is obtained from the compound 140 (170 mg, 0.401 mmol). The resulting free form was treated with 4 mol / L hydrogen chloride in ethyl acetate to provide the title compound 143- (182 mg, 83 o). X H NMR (DMSO-d 6, d ppm): 2.87 (s, 3 H), 3.31 (s, 3 H), 3.41 (t, J = 5.4 Hz, 2 H), 3.77 (t, J = 5.4 Hz, 2 H), 4.59 (s, 2H), 6.48 (dd, J = 1.6, 3.2 Hz, 1H), 6.89 (dd, J = 0.8, 3.2 Hz 1H), 7.41-7.49 (m, 3H), 7.55-7.61 (m, 1H) , 7.70-7.76 (m, 2H), 8.11 (dd, J = 1.6, 5.1 Hz, 1H), 8.21 (d, J = 1.6 Hz, 1H), 8.90 (d, J = 5.1 Hz, 1H). APCIMS m / z: [M + H] + 477.

[Example 144] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -2- (morpholinomethyl) pyridine-4-carboxamide (Compound 144) In a manner similar to that in example 141, when using morpholine instead of the 2.0 mol / L solution dimethylamine in methanol, the title compound 144 (52.0 mg, 49%) is obtained from compound 140 (100 mg, 0.236 mmol). XH NMR (CDC13, d ppm): 2.52-2.53 (m, 4H), 3.71 (s, 2H), 3.72-3.75 (m, 4H), 6.29 (dd, J = 1.8, 3.5 Hz, 1H), 7.04, (d, J = 3.5 Hz, 1H), 7.21 (d, J = 1.8 Hz, 1H), 7.39-7.45 (m, 2H), 7.53-7.58 (m, 1H), 7.62 (dd, J = 1.8, 5.1 Hz, 1H), 7.80 (d, J = 1.8 Hz, 1H), 7.83-7.87 (m, 2H), 8.72 (d, J = 5.1 Hz, 1H). APCIMS m / z: [M + H] + 475. p.f .: 212-213 ° C.

[Example 145] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -2- [N- (2-methoxyethyl) -N-methylamino] pyridine-4-carboxamide (Compound 145) In a manner similar to that in Example 137, by using 2- [N- (2-methoxyethyl) -N-methylamino] pyridine-4-carboxylic acid in place of 2-hydroxy-2-methylpropanoic acid, the title compound 145 (40.0 mg, 23%) is obtained from compound 136 (100 mg, 0.370 mmol). XR NMR (DMSO-d6, d ppm): 3.13 (s, 3H), 3.35 (s, 3H), 3.59 (t, J = 5.5 Hz, 2H), 3.79 (t, J = 5.5 Hz, 2H), 6.35 (dd, J = 1.8, 3.5 Hz, 1H), 6.89 (dd, J = 1.3, 5.1 Hz, 1H), 7.01 (d, J = 1.8 Hz, 1H), 7.07 (d, J = 3.5 Hz, 1H) , 7.38-7.43 (m, 2H), 7.51-7.56 (, 1H), 7.79-7.82 (, 2H), 8.06 (d, J = 1.3 Hz, 1H), 8.26 (d, J = 5.1 Hz, 1H), 10.70 (br s, 1H).

APCIMS m / z: [M + H] + 463. mp .: 145-147 ° C.

[Example 146] N- [5-Benzoyl-4- (2-furyl) fchiazol-2-yl] -2-piperidinopyridine-4-carboxamide (Compound 146) In a manner similar to that in example 137, by using acid 2-piperidinoisonicotinic acid instead of 2-hydroxy-2-methylpropanoic acid, the title compound 146 (89.0 mg, 52%) is obtained from compound 136 (100 mg, 0.370 mmol). X H NMR (DMSO-de, d ppm): 1.55-1.64 (m, 6H), 3.61-3.65 (m, 4H), 6.51 (dd, J = 1.8, 3.5 Hz, 1H), 6.96 (d, J = 3.5 Hz, 1H), 7.12 (d, J = 5.0 Hz, 1H), 7.43-7.51 (m, 4H), 7.58-7.63 (m, 1H), 7.72-7.74 (m, 2H), 8.27 (d, J = 5.0 Hz, 1H), 13.38 (br s, 1H). APCIMS m / z: [M + H] + 459. p.f .: 195-198 ° C.

[Example 147] 2-Chloro-N- [5-benzoyl-4- (2-furyl) thiazol-2-yl] pyridine-5-carboxamide (Compound 147) In a manner similar to that in example 137, when using 6-chloronicotinic acid in place of 2-hydroxy-2-methylpropanoic acid, the title compound 147 (583 mg, 77%) is obtained from compound 136 (500 mg, 1.85 mmol).

X H NMR (CDCl 3, d ppm): 6.31 (dd, J = 1.8, 3.3 Hz, 1H), 7.02 (d, J = 3.3 Hz, 1H), 7.21 (d, J = 1.8 Hz, 1H), 7.39-7.46 (m, 3H), 7.52-7.57 (m, 1H), 7.79-7.82 (m, 2H), 8.16 (dd, J = 2.6, 8.1 Hz, 1H), 8.93 (d, J = 2.6 Hz, 1H).

[Example 148] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -2-morpholino-5-pyridinecarboxamide (Compound 148) Compound 147 (100 mg, 0.244 mmol) was dissolved in morpholine (1 mL), followed by stirring at 80 ° C for 1 hour. Water was added to the reaction system, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give the title compound 148 (81.0 mg, 72%). X H NMR (CDCl 3, d ppm): 3.67-3.70 (m, 4 H), 3.80-3.83 (m, 4 H), 6.37 (d, J = 1.8, 3.7 Hz, 1 H), 6.62 (d, J = 9.2 Hz, 1H), 7.14 (d, J = 3.7 Hz, 1H), 7.30 (d, J = 1.8 Hz, 1H), 7.38-7.43 (m, 2H), 7.51-7.56 (m, 1H), 7.80-7.83 (m , 2H), 7.97 (dd, J = 2.6, 9.2 Hz, 1H), 8.73 (d, J = 2.6 Hz, 1H), 10.02 (br s, 1H). APCIMS m / z: [M + H] + 461.

[Example 149] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -2-oxo-l, 2-dihydropyridine-5-carboxamide (Compound 149) In a manner similar to that in Example 137, using 6-hydroxynicotinic acid instead of 2-hydroxy-2-methylpropanoic acid, the title compound 149 (180 mg, 25%) is obtained from compound 136 (500 mg, 1.85 mmol). XH NMR (DMSO-d6, d ppm): 6.41 (d, J = 9.7 Hz, 1H), 6.48 (dd, J = 1.8, 3.5 Hz, 1H), 6.93 (d, J = 3.5 Hz, 1H), 7.41 -7.46 (m, 3H), 7.55-7.60 (m, 1H), 7.68-7.70 (m, 2H), 8.02 (dd, J = 2.8, 9.7 Hz, 1H), 8.44 (d, J = 2.8 Hz, 1H ). APCIMS m / z: [M + H] + 392. p.f .: > 300 ° C.

[Example 150] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -l-methyl-2-oxo-l, 2-dihydropyridine-5-carboxamide (Compound 150) Compound 149 ( 100 mg, 0.255 mmol) was dissolved in DMF (1.2 mL), and 55% sodium hydride (22.0 mg, 0.511 mmol) and methyl iodide (0.0159 mL, 0.255 mmol) were added thereto, followed by stirring at room temperature. environment for 3 hours. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue is redissolved in a thixide with diisopropyl ether to give the title compound 150 (71.0 mg, 68%). X H NMR (DMSO-d 6, d ppm): 3.99 (s, 3 H), 6.45 (dd, J = 1.8, 3.5 Hz, 1 H), 6.91 (d, J = 3.5 Hz, 1 H), 7.38-7.43 (m, 3H), 7.51-7.57 (m, 1H), 7.65-7.67 (m, 2H), 7.94 (d, J = 5.0 Hz, 1H), 8.09 (s, 1H), 8.71 (d, J = 5.0 Hz, 1H) ). APCIMS m / z: [M + H] + 406. p.f .: 220-225 ° C.

[Example 151] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -l-ethyl-2-oxo-l, 2-dihydropyridine-5-carboxamide (Compound 151) In a similar manner to that in Example 137, when using Compound or obtained in reference example 21 instead of 2-hydroxy-2-methylpropanoic acid, the title compound 151 (70.0 mg, 45%) is obtained from compound 136 (100 mg 0.370 mmol). X H NMR (DMSO-de, d ppm): 1.36 (t, J = 7.1 Hz, 3 H), 4.00 (q, J = 7.1 Hz, 2 H), 6.27 (dd, J = 1.8, 3.3 Hz, 1 H), 6.50 (d, J = 9.5 Hz, 1H), 6.95 (d, J = 3.3 Hz, 1H), 7.17 (d, J = 1.8 Hz, 1H), 7.37-7.42 (m, 2H), 7.50-7.56 (, 1H) ), 7.69 (dd, J = 2.6, 9.5 Hz, 1H), 7.78-7.82 (m, 2H), 8.23 (d, J = 2.6 Hz, 1H), 11.28 (br s, 1H). APCIMS m / z: [M + H] + 420. p.f. : 109-114 ° C.

[Example 152] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] -2-oxo-l- (pyridin-4-ylmethyl) -1,2-dihydropyridine-5-carboxamide (Compound 152) In a manner similar to that in example 137, when using Compound v obtained in reference example 22 instead of 2-hydroxy-2-methylpropanoic acid, the title compound 152 (75.0 mg, 42%) is obtained of compound 136 (100 mg, 0.370 mmol). X H NMR (DMSO-de, d ppm): 5.22 (s, 2H), 6.49 (dd, J = 1.8, 3.5 Hz, 1H), 6.55 (d, J = 9.6 Hz, 1H), 6.92 (d, J = 3.5 Hz, 1H), 7.28 (d, J = 5.9 Hz, 2H), 7.41-7.47 (m, 3H), 7.56-7.61 (m, 1H), 7.68-7.72 (m, 2H), 8.10 (dd, J = 2.5, 9.6 Hz, 1H), 8.54 (d, J = 5.9 Hz, 2H), 8.91 (d, J = 2.5 Hz, 1H), 13.01 (br s, 1H). APCIMS m / z: [M + H] + 483. mp .: 270-275 ° C.

[Example 153] N- [5-Benzoyl-4- (2-furyl) thiazol-2-yl] pyridazine-4-carboxamide (Compound 153) In a manner similar to that in example 137, by using pyridazine-4 acid -carboxylic acid instead of 2-hydroxy-2-methylpropanoic acid, the title compound 153 (154 mg, 74%) is obtained from compound 136 (150 mg, 0.555 mmol).

X H NMR (DMSO-de, d ppm): 6.49 (dd, J = 1.8, 3.5 Hz, 1H), 6.94 (d, J = 3.5 Hz, 1H), 7.41-7.47 (, 3H), 7.56-7.59 (m , 1H), 7.69-7.72 (m, 2H), 8.22-8.25 (m, 1H), 9.51-9.53 (m, 1H), 9.71-9.73 (, 1H). APCIMS m / z: [M + H] + 377. p.f .: 225-248 ° C.

[Example 154] N- [4- (2-furyl) -5- (2-methylbenzoyl) thiazol-2-yl] tert-Butyl carbamate (Compound 154) Step 1: The phenol (2.00 g, 12.3 mmol) was Dissolved in THF (40 mL), 55% sodium hydride (1.02 g, 23.4 mmol) was added thereto at 0 ° C, followed by stirring at 0 ° C for 30 minutes. A solution (10 mL) of 2-methylbenzoyl chloride (4.16 mL) in THF was added dropwise to the reaction mixture, followed by stirring overnight at room temperature. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 9: 1) to give phenyl 2-methylbenzoate (2.88 g, 64%).

X H NMR (CDCl 3, d ppm): 2.68 (s, 3 H), 7.15-7.35 (m, 5 H), 7.37- 7.51 (m, 3 H), 8.16 (dd, J = 1.9, 5.1 Hz, 1 H). APCIMS m / z: [M + H] + 213.

Step 2: Compound h (520 mg, 1.51 mmol) obtained in Reference Example 8 was dissolved in THF (4 mL), and a 1.58 mol / L solution of n-butylithium in n-hexane (2.10 mL, 3.32 mmol ) was added to it in an argon stream at -78 ° C, followed by stirring at -78 ° C for 10 minutes. A solution (4 mL) of phenyl 2-methylbenzoate (960 mg, 4.52 mmol) in THF obtained in step 1 was added dropwise to the reaction mixture, followed by stirring at room temperature for 1 hour. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 3: 2) to give the title compound 154 (250 mg, 43%). H NMR (CDCl 3, d ppm): 1.48 (s, 9H), 2.42 (s, 3H), 6.45 (dd, J = 1.6, 3.5 Hz, 1H), 7.13-7.40 (, 5H), 7.50-7.55 (m , 1H), 8.86 (br s, 1H). APCIMS m / z: [M + H] + 385.

[Example 155] 2-Amino-4- (2-furyl) thiazol-5-yl 2-methylphenyl ketone (Compound 155) In a manner similar to that in Example 136, the title compound 155 (132 mg, 30%) is obtained from compound 154 (250 mg, 0.650 mmol) in place of Compound 135.

X H NMR (DMSO-d 6, d ppm): 2.37 (s, 3 H), 6.40 (dd, J = 1.6, 3.2 Hz, 1H), 7.05-7.30 (m, 4H), 7.39 (dd, J = 0.5, 1.6 Hz, 1H), 8. 05 (br s, 2H). APCIMS m / z: [M + H] + 285.

[Example 156] N- [4- (2-Furyl) -5- (2-methylbenzoyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 156) In a manner similar to that in Example 3, using isonicotinic acid in place of methoxyacetic acid, followed by thickening with ethanol, the title compound 156 (120 mg, 55%) is obtained as a pale brown solid of compound 155 (160 mg, 0.561 mmol) in place of the compound a . X H NMR (DMSO-d 6, d ppm): 2.31 (s, 3 H), 6.52 (dd, J = 1.9, 3.5 Hz, 1 H), 6.95 (d, J = 3.5 Hz, 1 H), 7.30-7.45 (m, 2H), 7.51 (d, J = 1.9 Hz, 1H), 7.52-7.55 (m, 2H), 8.02 (dd, J = 1.6, 4. 6 Hz, 2H), 8.83 (dd, J = 1.6, 4.6 Hz, 2H), 13.58 (br s, 1H). APCIMS m / z: [M + H] + 390.

[Example 157] N- [4- (2-furyl) -5- (3-methylbenzoyl) thiazol-2-yl] tert-Butyl carbamate (Compound 157) In a manner similar to that in Example 154, using 3-methylbenzoyl chloride in place of 2-methylbenzoyl chloride, the title compound 157 (180 mg, 31%) is obtained from compound h (520 mg, 1.51 mmol) obtained in reference example 8. XH NMR (CDC13 , d ppm): 1.52 (s, 9H), 2.35 (s, 3H), 6.39 (dd, J = 1.9, 3.5 Hz, 1H), 7.09 (d, J = 3.5 Hz, 1H), 7.26-7.33 (m , 3H), 7.53-7.59 (m, 2H), 8.55 (br s, 1H). APCIMS m / z: [M + H] + 385.

[Example 158] 2-Amino-4- (2-furyl) thiazol-5-yl 3-methylphenyl ketone (Compound 158) In a manner similar to that in example 136, the title compound 158 (133 mg, 100% ) is obtained from compound 157 (180 mg, 0.468 mmol) instead of Compound 135. XH NMR (DMSO-ds, d ppm): 2.25 (s, 3H), 6.41 (dd, J = 1.6, 3.2 Hz, 1H) , 6.80 (d, J = 3.2 Hz, 1H), 7.18-7.36 (, 6H), 7.98 (br s, 2H). APCIMS m / z: [M + H] + 285.

[Example 159] N- [4- (2-Furyl) -5- (3-methylbenzoyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 159) In a manner similar to that in Example 3, using isonicotinic acid instead of methoxyacetic acid, followed by thickening with ethanol, the title compound 159 (97.0 mg, 51%) is obtained as a pale yellow solid of compound 158 (133 mg, 0.468 mmol) in place of the compound a . X H NMR (DMSO-d 6, d ppm): 2.35 (s, 3 H), 6.54 (dd, J = 1.6, 3.5 Hz, 1 H), 7.17-7.21 (m, 1 H), 7.23 (dd, J = 0.8, 3.5 Hz, 1H), 7.30-7.43 (m, 3H), 7.62 (dd, J = 0.8, 1.6 Hz, 1H), 8.00 (dd, J = 1.6, 4.6 Hz, 2H), 8.83 (dd, J = 1.6, 4.6 Hz, 2H), 13.61 (br s, 1H). APCIMS m / z: [M + H] + 390.

[Example 160] N- [4- (2-Furyl) -5- (4-methylbenzoyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 160) In a manner similar to that in example 99, when using a 1.0 mol / L solution of p-tolylmagnesium bromide in THF in place of phenylmagnesium bromide, followed by making a thick mixture with a mixed solvent of methanol and diethyl ether, the title compound 160 (113 mg, 52%) is obtained as a pale yellow solid of compound 98 (200 mg, 0.558 mmol).

H NMR (DMSO-d6, d ppm): 2.37 (s, 3H), 6.53 (dd, J = 1.8, 3.3 Hz, 1H), 6.95 (d, J = 3.3 Hz, 1H), 7.28 (d, J = 8.1 Hz, 2H), 7.54 (d, J = 1.8 Hz, 1H), 7.66 (d, J = 8.1 Hz, 2H), 8.03 (dd, J = 1.5, 4.5 Hz, 2H), 8.84 (dd, J = 1.5, 4.5 Hz, 2H), 13.58 (br s, 1H). APCIMS m / z: [M + H] + 390.

[Example 161] N- [4- (2-furyl) -5- (2-methoxybenzoyl) thiazol-2-yl] tert-Butyl carbamate (Compound 161) In a manner similar to that in Example 154, using 2-methoxybenzoyl chloride in place of 2-methylbenzoyl chloride, the title compound 161 (360 mg, 67%) is obtained from the compound h (520 mg, 1.51 mmol) obtained in Reference Example 8. XH NMR (CDC13, d ppm): 1.48 (s, 9H), 3.74 (s, 3H), 6.45 (dd, J = 1.9, 3.5 Hz, 1H ), 6.83-6.92 (, 1H), 6.97 (ddd, J = 0.8, 7. 3, 7.3 Hz, 1H), 7.35-7.37 (m, 1H), 7.39-7.43 (m, 2H), 7.54-7.57 (m, 1H), 8.78 (br s, 1H). APCIMS m / z: [M + H] + 401.

[Example 162] 2-Amino-4- (2-furyl) thiazol-5-yl-2-methoxyphenyl ketone (Compound 162) In a manner similar to that in Example 136, the title compound 162 (223 mg, 73%) was obtained from compound 161 (360 mg, 1.01 mmol) instead of Compound 135.

X H NMR (DMSO-d 6, d ppm): 3.64 (s, 3 H), .6.42 (dd, J = 1.6, 3.2 Hz, 1H), 6.88-7.04 (m, 3H), 7.19-7.23 (m, 1H), 7.30-7.40 (m, 1H), 7.41-7.43 (m, 1H), 7.97 (br s, 2H). APCIMS m / z: [M + H] + 301.

[Example 163] N- [4- (2-Furyl) -5- (2-methoxybenzoyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 163) In a manner similar to that in Example 3, using isonicotinic acid instead of methoxyacetic acid, followed by thickening with ethanol, the title compound 163 (220 mg, 73%) is obtained as a pale yellow solid of the compound 162 (223 mg, 0.741 mmol) in place of compound a. X H NMR (DMSO-d 6, d ppm): 3.67 (s, 3 H), 6.56 (dd, J = 1.6, 3.2 Hz, 1 H), 7.03 (dd, J = 7.5, 7.5 Hz, 1 H), 7.09 (d, J = 8.6 Hz 1H), 7.28 (dd, J = 0. 5, 3.2 Hz, 1H), 7.40 (dd, J = 1.6, 7.5 Hz, 1H), 7.50 (ddd, J = 1.6, 7. 5, 8.6 Hz, 1H), 7.53 (dd, J = 0.5, 1.6 Hz, 1H), 8.00 (dd, J = 1.6, 4. 3 Hz, 2H), 8.82 (dd, J = 1.6, 4.3 Hz, 2H), 13.55 (brs, 1H).

APCIMS m / z: [M + H] + 406.

[Example 164] N- [4- (2-Furyl) -5- (3-methoxybenzoyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 164) In a manner similar to that in example 99, when using a 1.0 mol / L solution of m-methoxybromide phenylmagnesium in THF in place of phenylmagnesium bromide, followed by thickening with a mixed solvent of ethanol and diethyl ether, the title compound 164 (165 mg, 72%) is obtained as a pale brown solid of compound 98 (200 mg 0.558 mmol). X H NMR (DMSO-d 6, d ppm): 3.75 (s, 3 H), 6.53 (dd, J = 1.6, 3.5 Hz, 1 H), 6.97 (dd, J = 0.5, 3.5 Hz, 1 H), 7.17 (ddd, J = 1.1, 2.7, 7.5 Hz, 1H), 7.22-7.32 (, 2H), 7.30-7.40 (m, 1H), 7.52 (dd, J = 0.5, 1.6 Hz, 1H), 8.03 (dd, J = 1.6 , 4.6 Hz, 2H), 8.84 (dd, J = 1.6, 4.6 Hz, 2H), 13.59 (br s, 1H). APCIMS m / z: [M + H] + 406.

[Example 165] N- [4- (2-Furyl) -5- (4-methoxybenzoyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 165) In a manner similar to that in example 99, when using a 0.5 mol / L solution of p-methoxyphenylmagnesium bromide in THF in place of phenylmagnesium bromide, followed by thick mixing with a mixed solvent of ethanol and diethyl ether, the title compound 165 (121 mg, 53%) is obtained as a pale brown solid of compound 98 (200 mg, 0.558 mmol). X H NMR (DMSO-de, d ppm): 3.09 (s, 3H), 6.53 (dd, J = 1.6, 3.5 Hz, 1H), 6.89 (dd, J = 0.8, 3.5 Hz, 1H), 7.00 (dd, J = 2.2, 8. 9 Hz, 2H), 7.55 (dd, J = 0.8, 1.6 Hz, 1H), 7.76 (dd, J = 2. 2, 8.9 Hz, 2H), 8.03 (dd, J = 1.6, 4.6 Hz, 2H), 8.84 (dd, J = 1.6, 4.6 Hz, 2H), 13.54 (br s, 1H). APCIMS m / z: [M + H] + 406.

[Example 166] N- [5- (2-fluorobenzoyl) -4- (2-furyl) thiazol-2-yl] tert-Butyl carbamate (Compound 166) In a manner similar to that in Example 154, using 2-Fluorobenzoyl chloride in place of 2-methylbenzoyl chloride, the title compound 166 (360 mg, 62%) is obtained from compound h (520 mg, 1.51 mmol) obtained in reference example 8. H NMR (CDC13 , d ppm): 1.51 (s, 9H), 6.43 (dd, J = 1.6, 3.5 Hz, 1H), 7.06 (ddd, J = 1.1, 8.7, 9.5 Hz, 1H), 7.18 (ddd, J = 1. 1, 7.6, 7.6 Hz, 1H), 7.35 (d, J = 3.5 Hz, 1H), 7.39-7.48 (m, 2H), 7.53 (ddd, J = 1.6, 7.6, 7.6 Hz, 1H), 8.56 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 389.

[Example 167] 2-Amino-4- (2-furyl) thiazol-5-yl 2-fluorophenyl ketone (Compound 167) In a manner similar to that in example 136, the title compound 167 (190 mg, 92%) is obtained from compound 166 (280 mg, 0.722 mmol) in place of Compound 135.

X H NMR (DMS0-d 6, d ppm): 6.40 (dd, J = 1.9, 3.5 Hz, 1H), 6.88 (dd, J = 0.8, 3.5 Hz, 1H), 7.14 (d, .J = 8.1 Hz, 1H), 7.18 (dd, J = 3.0, 3.8 Hz, 1H), 7.34 (dd, J = 0.8, 1.9 Hz, 1H), 7.36-7.49 (m, 2H), 8.17 (br s, 2H). APCIMS m / z: [M + H] + 289.

[Example 168] N- [5- (2-Fluorobenzoyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 168) In a manner similar to that in Example 3, using isonicotinic acid instead of methoxyacetic acid, followed by re-mixing in a thickened form with diethyl ether, the title compound 168 (207 mg, 80%) is obtained as a pale brown solid of compound 167 (190 mg, 0.659 mmol) in place of compound a.

X H NMR (DMS0-d 6, d ppm): 6.46 (dd, J = 1.9, 3.2 Hz, 1H), 7.15- 7.25 (m, 3H), 7.36-7.46 (, 2H), 7.49 (dd, J = 0.8, 1.9 Hz, 1H), 7.96 (d, J = 5.4 Hz, 2H), 8.63 (d, J = 5.4 Hz, 2H). APCIMS m / z: [M + H] + 394 [Example 169] N- [5- (3-Fluorobenzoyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 169) In a manner similar to that in example 99, when using a 0.5 mol / L solution of m-fluorobromide phenylmagnesium in THF in place of phenylmagnesium bromide, followed by thickening with diethyl ether, the title compound 169 (7.0.0 mg, 32%) is obtained as a pale yellow solid of compound 98 (200 mg, 0.558 mmol) . X H NMR (DMSO-d 6, d ppm): 6.53 (dd, J = 1.8, 3.6 Hz, 1H), 6.97 (d, J = 3.6 Hz, 1H), 7.40-7.55 (m, 5H), 8.03 (dd, J = 1.5, 4.2 Hz, 2H), 8.84 (dd, J = 1.5, 4.2 Hz, 2H), 13.64 (br s, 1H). ESIMS m / z: [M + H] + 394.

[Example 170] N- [5- (4-Fluorobenzoyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 170) In a manner similar to that in example 99, when using a 1.0 mol / L solution of p-fluorofenilmagnesium bromide in THF in place of phenylmagnesium bromide, followed by thickening with a mixed solvent of ethanol and diethyl ether, the title compound 170 (132 mg, 60%) obtained as a yellow solid of compound 98 (200 mg, 0.558 mmol). X H NMR (DMSO-d 6, d ppm): 6.53 (dd, J = 1.6, 3.5 Hz, 1H), 6.92 (dd, J = 0.8, 3.5 Hz, 1H), 7.28 (ddd, J = 1.9, 8.9, 8.9 Hz, 2H), 7.51 (dd, J = 0.8, 1.6 Hz, 1H), 7.81 (ddd, J = 1.9, 5.4, 8.9 Hz, 2H), 8.03 (dd, J = 1.9, 4.6 Hz, 2H), 8.84 (dd, J = 1.9, 4.6 Hz, 2H), 13.60 (br s, 1H). ESIMS m / z: [M + H] + 394.

[Example 171] N- [5- (2-chlorobenzoyl) -4- (2-furyl) thiazol-2-yl] tert-Butyl carbamate (Compound 171) In a manner similar to that in Example 154, using 2-Chlorobenzoyl chloride in place of 2-methylbenzoyl chloride, the title compound 171 (290 mg, 48%) is obtained from compound h (520 mg, 1.51 mmol) obtained in reference example 8. XH NMR (CDC13 , d ppm): 1.48 (s, 9H), 6.48 (dd, J = 1.6, 3.2 Hz, 1H), 7.20-7.42 (m, 6H), 7.68 (d, J =, 1.6 Hz, 1H), 8.87 (br s, 1H). APCIMS m / z: [35CIM + H] + 405, [37CIM + H] + 407. [Example 172] 2-Amino-4- (2-furyl) thiazol-5-yl 2-chlorophenyl ketone (Compound 172) In similar to that in Example 136, the title compound 172 (161 mg, 73%) is obtained from compound 171 (290 mg, 0.716 mmol) instead of Compound 135.

X H NMR (DMSO-de, d ppm): 6.42 (dd, J = 1.6, 3.2 Hz, 1H), 7.03 (d, J = 3.2 Hz, 1H), 7.26-7.47 (m, 5H), 8.19 (br s, 2H). APCIMS m / z: [35CIM + H] + 305, [37CIM + H] + 307. [Example 173] N- [5- (2-Chlorobenzoyl) -4- (2-furyl) thiazol-2-yl] pyridine -4-carboxamide (Compound 173) In a manner similar to that in Example 3, when using isonicotinic acid instead of methoxyacetic acid, followed by thickening with a mixed solvent of ethanol and diethyl ether, the title compound 173 (110 mg, 50%) is obtained as a pale brown solid of compound 172 (161 mg, 0.529 mmol) in place of compound a. XH NMR (DMS0-d6, d ppm): 6.58 (dd, J = 1.6, 3.5 Hz, 1H), 7.36 (dd, J = 0.8, 3.5 Hz, 1H), 7.42 (ddd, J = 3.2, 6.5, 7.8 Hz, 1H), 7.51-7.59 (m, 3H), 7.65 (dd, J = 0.8, 1.6 Hz, 1H), 8.00 (dd, J = 1.6, 4.6 Hz, 2H), 8.83 (dd, J = 1.6, 4.6 Hz, 2H), 13.69 (br s, 1H). APCIMS m / z: [35C1M + H] + 410, [37CIM + H] + 412. [Example 174] N- [5- (3-Chlorobenzoyl) -4- (2-furyl) thiazol-2-yl] pyridine -4-carboxamide (Compound 174) In a manner similar to that in example 99, when using a 0.5 mol / L solution of m-chlorophenylmagnesium bromide in THF in place of phenylmagnesium bromide, followed by thick mixing with a solvent After mixing ethanol and diethyl ether, the title compound 174 (124 mg, 54%) is obtained as a yellow solid of compound 98 (200 mg, 0.558 mmol). X H NMR (DMSO-d 6, d ppm): 6.53 (dd, J = 1.6, 3.5 Hz, 1H), 6.98 (d, J = 3.5 Hz 1H), 7.44-7.51 (m, 2H), 7.63 (d, J = 1.6 Hz, 1H), 7.65-7.69 (m, 2H), 8.03 (dd, J = 1.6, 4.6 Hz, 2H), 8.84 (dd, J = 1.6, 4.6 Hz, 2H), 13.63 (br s, 1 HOUR) . ESIMS m / z: [35CIM + H] + 410, [37CIM + H] + 412.

[Example 175] N- [5- (4-Chlorobenzoyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 175) In a manner similar to that in example 99, when using a 1.0 mol / L solution of p-chlorophenylmagnesium bromide in THF in place of phenylmagnesium bromide, followed by making a thick mixture with a mixed solvent of ethanol and diethyl ether, the title compound 175 (141 mg, 61%) is obtained as a yellow solid of compound 98 (200 mg, 0.558 mmol). X H NMR (DMSO-d 6, d ppm): 6.54 (dd, J = 1.8, 3.6 Hz, 1H), 6.95 (d, J = 3.6 Hz, 1H), 7.52 (d, J = 1.8 Hz, 1H), 7.52. (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 8.03 (d, J = 6.0 Hz, 2H), 8.84 (d, J = 6.0 Hz, 2H), 13.63 (br s, 1 HOUR) . ESIMS m / z: [35CIM-H] "408, [37CIM-H]" 410. [Example 176] N- [5- (2-Cyanobenzoyl) -4- (2-furyl) thiazol-2-yl] tert-Butyl carbamate (Compound 176) Step 1: 2-Cyanobenzoic acid (1.00 g, 6.80 mmol), phenol (576 mg, 6.12 mmol) and PyBOP (3.90 g, 7.48 mmol) were dissolved in DMF (12 mL), and triethylamine (2.10 mL, 15.0 mmol) was added thereto, followed by stirring at room temperature for 4 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed successively with a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was continuously distilled under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 3: 2) to give phenyl 2-cyanobenzoate (1.24 g, 82%). X H NMR (DMSO-d 6, d ppm): 7.31-7.39 (m, 3H), 7.41-7.55 (m, 2H), 7.90-7.97 (m, 2H), 8.08-8.14 (m, 1H), 8.33-8.38 (m, 1H). ESIMS m / z: [M + H] + 224.

Step 2: Compound h (520 mg, 1.51 mmol) obtained in Reference Example 8 was dissolved in THF (4 mL), a 1.58 mol / L solution of n-butyllithium in n-hexane (2.10 mL, 3.32 mmol) it was added to it in an argon stream at -78 ° C, followed by stirring at -78 ° C for 10 minutes. A solution (4 ml) of phenyl 2-cyanobenzoate (1.00 g, 4.52 mmol) in THF obtained in step 1 was added dropwise to the reaction mixture, followed by stirring at room temperature for 1 hour. The reaction mixture was emptied in a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 3: 2) to give the title compound 176 (355 mg, 60%). XH NMR (CDC13, d ppm): 1.52 (s, 9H), 6.39 (dd, J = 1.9, 3.5 Hz, 1H), 7.19-7.22 (m, 1H), 7.26-7.28 (m, 1H), 7.50- 7.65 (m, 3H), 7.67-7.75 (, 1H), 8.54 (br s, 1H). APCIMS m / z: [M + H] + 396.

[Example 177] 2-Amino-4- (2-furyl) thiazol-5-yl 2-cyanophenyl ketone (Compound 177) In a manner similar to that in example 136, the title compound 177 (157 mg, 59% ) is obtained from compound 176 (355 mg, 0.900 mmol) instead of Compound 135. XH NMR (DMSO-d6, d ppm): 6.38 (dd, J = 1.9, 3.5 Hz, 1H), 6.80 (dd, J = 0.8, 3.5 Hz, 1H), 7.22 (dd, J = 0.8, 1.9 Hz, 1H), 7.47-7.52 (m, 1H), 7.55-7.60 (m, 2H), 7.83-7.88 (m, 1H), 8.29 (br s, 2H). APCIMS m / z: [M + H] + 296.

[Example 178] N- [5- (2-Cyanobenzoyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 178) In a manner similar to that in Example 3, using isonicotinic acid instead of methoxyacetic acid, followed by thickening with methanol, the title compound 178 (90.6 mg, 43%) is obtained as a yellow solid of compound 177 (157 mg, 0.532 mmol) in place of compound a. X H NMR (DMSO-d 6, d ppm): 6.50 (dd, J = 1.6, 3.5 Hz, 1H), 7.04 (dd, J = 0.8, 3.5 Hz, 1H), 7.45 (dd, J = 0.8, 1.6 Hz, 1H), 7.67-7.73 (m, 3H), 7.95-8.00 (m, 1H), 8.03 (dd, J = 1.6, 4.3 Hz, 2H), 8.84 (dd, J = 1.6, 4.3 Hz, 2H), 13.70 (br s, 1H). APCIMS m / z: [M + H] + 401.

[Example 179] N- [5- (3-cyanobenzoyl) -4- (2-furyl) thiazol-2-yl] tert-Butyl carbamate (Compound 179) In a manner similar to that in Example 176, when using 3-cyanobenzoic acid in place of 2-cyanobenzoic acid, the title compound 179 (290 mg, 48%) is obtained from compound h (520 mg, 1.51 mmol) obtained in reference example 8. XH NMR (CDC13, d ppm): 1.54 (s, 9H), 6.40 (dd, J = 1.9, 3.5 Hz, 1H), 7.05 (d, J = 3.5 Hz, 1H), 7.18 (d, J = 1.9 Hz, 1H), 7.50 (dd, J = 7.8, 7.8 Hz, 1H), 7.75 (ddd, J = 1.3 , 1.3, 7.8 Hz, 1H), 7.94 (ddd, J = 1.3, 1.3, 7.8 Hz, 1H), 7.95-7.99 (m, 1H), 8.51 (br s, 1H). APCIMS m / z: [M + H] + 396.

[Example 180] 2-Amino-4- (2-furyl) thiazol-5-yl 3-cyanophenyl ketone (Compound 180) In a manner similar to that in example 136, the title compound 180 (155 mg, 72% ) is obtained from compound 179 (290 mg, 0.733 mmol) instead of Compound 135. XH NMR (DMSO-d6, d ppm): 6.41 (dd, J = 1.9, 3.5 Hz, 1H), 6.78 (dd, J = 0.8, 3.5 Hz, 1H), 7.27 (dd, J = 0.8, 1.9 Hz, 1H), 7.54 (dd, J = 7.8, 7.8 Hz, 1H), 7.79 (ddd, J = 1.3, 1.3, 7.8 Hz, 1H ), 7.85 (dd, J = 1.3, 1.3 Hz, 1H), 7.89 (ddd, J = 1.3, 1.3, 7.8 Hz, 1H), 8.17 (brs, 2H). APCIMS m / z: [M + H] + 296.

[Example 181] N- [5- (3-Cyanobenzoyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 181) In a manner similar to that in Example 3, using isonicotinic acid instead of methoxyacetic acid, followed by thickening with a mixed solvent of ethanol and diethyl ether, the title compound 181 (110 mg, 50%) is obtained as a pale brown solid of compound 180 (161 mg, 0.529). mmol) instead of compound a.

X H NMR (DMSO-d 6, d ppm): 6.51 (dd, J = 1.9, 3.5 Hz, 1H), 6.96 (d, J = 3.5 Hz, 1H), 7.46 (d, J = 1.9 Hz, 1H), 7.65 (dd, J = 7.8, 7.8 Hz, 1H), 7.96-8.08 (m, 5H), 8.84 (d, J = 5.9 Hz, 2H), 13.66 (br s, 1H). APCIMS m / z: [M + H] + 401.

[Example 182] N- [5- (4-cyanobenzoyl) -4- (2-furyl) thiazol-2-yl] tert-Butyl carbamate (Compound 182) In a manner similar to that in Example 176, when using 4-cyanobenzoic acid in place of 2-cyanobenzoic acid, the title compound 182 (321 mg, 54%) is obtained from compound h (520 mg, 1.51 mmol) obtained in reference example 8. XH NMR (CDC13, d ppm): 1.51 (s, 9H), 6.39 (dd, J = 1.9, 3.5 Hz, 1H), 7.07 (d, J = 3.5, Hz, 1H), 7.17 (d, J = 1.9 Hz, 1H), 7. 65 (dd, J = 1.9, 8.6 Hz, 2H), 7.79 (dd, J = 1.9, 8.6 Hz, 2H), 8.79 (br s, 1H). APCIMS m / z: [M + H] + 396. [Example 183] 2-Amino-4- (2-furyl) thiazol-5-yl 4-cyanophenyl ketone (Compound 183) In a manner similar to that in Example 136, the title compound 183 (161 mg, 73%) is obtained from compound 182 (290 mg, 0.716 mmol) instead of Compound 135. X H NMR (DMSO-d 6, d ppm): 6.41 (dd, J = 1.6, 3.2 Hz, 1H), 6.90 (dd, J = 0.5, 3.2 Hz, 1H), 7.27 (dd, J = 0.5, 1.6 Hz, 1H), 7.62 (dd, J = 1.9, 8.1 Hz, 2H), 7.78 (dd, J = 1.9, 8.1 Hz, 2H), 8.18 (br s, 2H). APCIMS m / z: [M + H] + 296.

[Example 184] N- [5- (4-Cyanobenzoyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 184) In a manner similar to that in Example 3, using isonicotinic acid instead of methoxyacetic acid, followed by thickening with a mixed solvent of ethanol and diethyl ether, the title compound 184 (130 mg, 77%) is obtained from compound 183 (129 mg, 0.438 mmol) instead of the compound a. X H NMR (DMSO-de, d ppm): 6.52 (dd, J = 1.9, 3.5 Hz, 1H), 6.98 (dd, J = 0.8, 3.5 Hz, 1H), 7.46 (dd, J = 0.8, 1.9 Hz, 1H), 7.82 (dd, J = 2.2, 8.6 Hz, 2H), 7.91 (dd, J = 2.2, 8.6 Hz, 2H), 8.03 (dd, J = 1.9, 4.6 Hz, 2H), 8.84 (dd, J = 1.9, 4.6 Hz, 2H), 13.67 (br s, 1H). ESIMS m / z: [M + H] + 401.

[Example 185] N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] tert-Butyl carbamate (Compound 185) Step 1: Picolinic acid (1.00 g, 8.12 mmol) was dissolved in DMF (40 mL), and N, O-dimethylhydroxylamine hydrochloride (1.58 g, 16.2 mmol), EDC hydrochloride (3.12 g, 16.2 mmol), 1-hydroxybenzotriazole monohydrate (2.48 g, 16.2 mmol) and triethylamine (2.25 ml, 16.2 mmol) were added thereto, followed by stirring at 50 ° C for 3 hours. A saturated aqueous solution of sodium acid carbonate was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 4) to give N-methoxy-N-methylpyridine-2-carboxamide (988 mg, 73%). X H NMR (CDC13, d ppm): 3.39 (s, 3 H), 3.73 (s, 3 H), 7.32-7.37 (m, 1 H), 7.60-7.68 (m, 1 H), 7.73-7.80 (m, 1 H), 8.59-8.61 (m, 1H). Step 2: Compound h (500 mg, 1.45 mmol) obtained in reference example 8 was dissolved in THF (7.5 mL) and a 1.58 mol / L solution of n-butyllithium in n-hexane (2.02 mL, 3.19 mmol) was added thereto in a stream of argon at -78 ° C, and the reaction mixture was stirred at -78 ° C for 15 minutes. The N-methoxy-N-methyl-2-pyridinecarboxamide (723 mg, 4.35 mmol) obtained in step 1 was added to the reaction mixture, followed by stirring at room temperature for 1.5 hours. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give the title compound 185 (286 mg, 53%). X H NMR (CDC13, d ppm): 1.46 (s, 9H), 6.53 (dd, J = 1.8, 3.7 Hz, 1H), 7.43-7.47 (m, 1H), 7.48 (d, J = 1.8 Hz, 1H) , 7.84 (d, J = 3.7 Hz, 1H), 7.84-7.89 (m, 1H), 8.14-8.17 (m, 1H), 8.70-8.71 (m, 1H).

[Example 186] 2-Amino-4- (2-furyl) thiazol-5-yl 2-pyridyl ketone (Compound 186): Compound 185 (286 mg, 0.770 mmol) was dissolved in trifluoroacetic acid (2 mL ), followed by agitation to room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and ethyl acetate and a saturated aqueous solution of sodium acid carbonate were added to the resulting residue, and the organic layer was separated. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 4) to give the title compound 186 (208 mg, 99%). X H NMR (CDC13, d ppm): 6.03 (br s, 2 H), 6.53 (dd, J = 1.8, 3.5 Hz, 1 H), 7.43-7.46 (m, 1 H), 7.51 (d, J = 1.8 Hz, 1 H ), 7.86-7.89 (m, 1H), 7.95 (d, J = 3.5 Hz, 1H), 8.14-8.17 (m, 1H), 8.60-8.61 (m, 1H).

[Example 187] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 187) Compound 186 (209 mg, 0.770 mmol) was dissolved in DMF (4 mL), and isonicotinic acid (190 mg, 1.54 mmol), EDC hydrochloride (296 mg, 1.54 mmol) and 1-hydroxybenzotriazole monohydrate (236 mg, 1.54 mmol) were added thereto, followed by stirring at 50 ° C for 3 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, followed by thickening with ethanol to give the title compound 187 (211 mg, 72%) as a yellow solid. X H NMR (DMS0-d 6, d ppm): 6.65 (dd, J = 1.7, 3.5 Hz, 1H), 7.47. (d, J = 3.5 Hz, 1H), 7.67-7.71 (m, 1H), 7.73 (d, J = 1.7 Hz, 1H), 8.05 (d, J = 6.1 Hz, 2H), 8.09-8.11 (m, 2H), 8.71-8.74 (m, 1H), 8.84 (d, J = 6.1 Hz, 2H), 13.5 (br s, 1H). APCIMS m / z: [M + H] + 377. p.f. : 218-227 ° C.

[Example 188] H- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] acetamide (Compound 188) Compound 186 (300 mg, 1.11 mmol) was dissolved in pyridine ( 3.7 mL) and acetyl chloride (0.130 mL, 1.89 mmol) and N, N-dimethylaminopyridine (6.75 mg, 0.0553 mmol) were added thereto, followed by stirring at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give the title compound 188 (233 mg, 67% ) as a pale yellow solid. XH NMR (CDC13, d ppm): 2.20 (s, 3H), 6.57 (dd, J = 1.8, 3.6 Hz, 1H), 7.49 (dd, J = 7.2, 11.3 Hz, 1H), 7.54 (d, J = 1.8 Hz, 1H), 7.85 (d, J = 3.6 Hz, 1H), 7.90 (dd, J = 11.3, 11.5 Hz, 1H), 8.19 (d, J = 11.5 Hz, 1H), 8.74 (d, J = 7.2 Hz, 1H), 9.72 (br s, 1H). APCIMS m / z: [M + H] + 314. mp .: 216-217 ° C.

[Example 189] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] butanamide (Compound 189) In a manner similar to that in Example 188, when using butyryl chloride (0.200 mL, 1.89 mmol) in place of acetyl chloride, the title compound 189 (297 mg, 78 i) is obtained from the compound 186 (288 mg, 1.11 mmol) as a pale yellow solid. X H NMR (CDC13, d ppm): 0.98 (t, J = 7.3 Hz, 3H), 1.68-1.84 (m, 2H), 2.37 (t, J = 7.3 Hz, 2H), 6.57 (dd, J = 1.9, 3.5 Hz, 1H), 7. 49 (dd, J = 4.9, 7.6 Hz, 1H), 7.53 (d, J = 1.9 Hz, 1H), 7.86 (d, J = 3.5 Hz, 1H), 7.89 (dd, J = 7.6, 7.8 Hz, 1H ), 8.19 (d, J) = 7.8 Hz, 1H), 8.73 (d, J = 4.9 Hz, 1H), 9.60 (br s, 1H). APCIMS m / z: [M + H] + 342. p.f. : 148-149 ° C. [Example 190] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2,2-dimethylpropanamide (Compound 190) In a manner similar to that in Example 188 , to Using pivaloyl chloride (0.230 mL, 1.89 mmol) in place of acetyl chloride, the title compound 190 (380 mg, 96%) is obtained from compound 186 (300 mg, 1.11 mmol) as a pale yellow solid. XH NMR (CDC13, d ppm): 1.36 (s, 9H), 6.58 (dd, J = 1.6, 3.2 Hz, 1H), 7.48 (dd, J = 4.9, 7.6 Hz, 1H), 7.57 (d, J = 1.6 Hz, 1H), 7.89 (dd, J = 7.6, 8.1 Hz, 1H), 7.92 (d, J = 3.2 Hz, 1H), 8.19 (d, J = 8.1 Hz, 1H), 8.74 (d, J = 4.9 Hz, 1H), 9.10 (br s, 1H). APCIMS m / z: [M + H] + 356. p.f .: 186-187 ° C.

[Example 191] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] cyclopropanecarboxamide (Compound 191) In a manner similar to that in example 188, by using cyclopropancarbonyl (0.170 mL, 1.89 mmol) in place of acetyl chloride, the title compound 191 (405 mg, 100%) is obtained from compound 186 (300 mg, 1.11 mmol) as a pale yellow solid. X H NMR (CDCl 3, d ppm): 0.82-0.92 (m, 2H), 1.12-1.21 (m, 2H), 1.37-1.48 (m, 1H), 6.55 (dd, J = 1.6, 3.5 Hz, 1H), 7.46 (dd, J = 4.9, 7.6 Hz, 1H), 7.53 (dd, J = 0.8, 1.6 Hz, 1H), 7.88 (dd, J = 7.6, 7.8 Hz, 1H), 7.89 (dd, J = 0.8, 1.6 Hz, 1H), 8. 17 (d, J = 7.8 Hz, 1H), 8.7 (d, J = 4.9 Hz, 1H), 10.91 (br s, 1H). APCIMS m / z: [M + H] + 340. p.f .: 191-192 ° C.

[Example 192] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -1-methylcyclopropanecarboxamide (Compound 192) In a manner similar to that in Example 187, use 1-methylcyclopropanecarboxylic acid (221 mg, 2. 22 mmol) in place of isonicotinic acid, the title compound 192 (305 mg, 78%) is obtained from compound 186 (300 mg, 1.11 mmol) as a pale yellow solid. X H NMR (DMSO-ds, d ppm): 0.77-0.84 (m, 2H), 1.25-1.31 (m, 2H), 1. 44 (s, 3H), 6.61 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (dd, J = 0. 5, 3.5 Hz, 1H), 7.60-7.69 (m, 1H), 7.68 (dd, J = 0.5, 1.9 Hz, 1H), 8.01-8.10 (m, 2H), 8.64-8.69 (, 1H), 12.14 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 354. p. f. : 195-196 ° C. [Example 193] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] cyclobutanecarboxamide (Compound 193) In a manner similar to that in Example 188, Using cyclobutanecarbonyl chloride (0.210 mL, 1.89 mmol) in place of acetyl chloride, the title compound 193 (348 mg, 89%) is obtained from compound 186 (300 mg, 1.11 mmol) as a pale yellow solid. XH NMR (CDC13, d ppm): 1.77-2.38 (m, 6H), 3.33-3.48 (m, 1H), 6.61 (d, J = 1.6, 3.2 Hz, 1H), 7.40 (d, J = 3.2 Hz, 1H), 7.61-7.71 (m, 1H), 7.67 (d, J = 1.6 Hz, 1H), 8.01-8.10 (m, 2H), 8.68 (d, J = 4.6 Hz, 1H), 12.56 (brs, 1H) ). APCIMS m / z: [M + H] + 354. p.f .: 165-170 ° C.

[Example 194] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] tetrahydropyran-4-carboxamide (Compound 194) In a manner similar to that in example 187, using 4-tetrahydropyrancarboxylic acid (288 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 194 (169 mg, 39%) is obtained from compound 186 (300 mg, 1.11 mmol) as a pale yellow solid. X H NMR (CDCl 3, d ppm); 1.62-1.98 (m, 4H), 2.44-2.64 (m, 1H), 3.33-3.46 (m, 2H), 3.95-4.07 (m, 2H), 6.57 (dd, J = 1.9, 3.8 Hz, 1H), 7.48 (ddd, J = 1.1, 4.9, 7.6 Hz, 1H), 7.54 (dd, J = 1.6, 1.9 Hz, 1H), 7.88 (ddd, J - = 1.6, 7.6, 7.8 Hz, 1H), 7.88 (dd) , J = 1.6, 3.8 Hz, 1H), 8.19 (ddd, J. = 0.8, 1.1, 7.8 Hz, 1H), 8.72 (ddd, J = 0.8, 1.6, 4.9 Hz, 1H), 9.67 (br s, 1H). APCIMS m / z: [M + H] + 384. mp .: 234-235 ° C.

[Example 195] 1- (tert-Butoxycarbonyl) -N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] piperidine-4-carboxamide (Compound 195) In a manner similar to that in example 187, when using 1- (tert-butoxycarbonyl) piperidine-4-carboxylic acid (5.07 g, 22.2 mmol) in place of isonicotinic acid, the title compound 195 (5.58 g, 100%) is obtained from compound 186 (3.00 g, 11.1 mmol) as a pale yellow oily substance. X H NMR (DMSO-de, d ppm): 1.30-1.59 (m, 2H), 1.41 (s, 9H), 1.81-1.93 (m, 2H), 2.67-2.89 (m, 3H), 3.92-4.11 (m, 2H), 6.62 (dd, J = 1.6, 3.2 Hz, 1H), 7.42 (dd, J = 0. 5, 3.2 Hz, 1H), 7.62-7.71 (m, 1H), 7.68 (d, J = 1.6 Hz, 1H), 8.02-8.10 (m, 2H), 8.66-8.70 (m, 1H), 12.76 (br s, 1H).

[Example 196] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] piperidine-4-carboxamide (Compound 196) In a manner similar to that in example 15, he compound of title 196 (4.25 g, 100%) is obtained as a reddish-brown solid of compound 195 (5.82 g, 11.1 mmol) in place of Compound 14. X H NMR (DMSO-d 6, d ppm): 1.74-1.92 (, 2H), 1.98-2.12 (m, 2H), 2.79-3.02 (m, 3H), 3.29-3.40 (m, 2H), 6.62 (dd, J = 1.6, 3.5 Hz, 1H), 7.42 (d, J = 3.5 Hz, 1H), 7.63-7.70 (, 1H), 7.68 (d, J = 1.6 Hz, 1H), 8.02-8.11 (m, 2H), 8.66-) 8.70 (m, 1H).

[Example 197] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -1- (pyridin-3-ylmethyl) piperidine-4-carboxamide (Compound 197) In a similar manner to that in Example 86, using 3-pyridinecarbaldehyde (0.370 mL, 3.90 mmol) in place of Compound 85, the title compound 197 (89.9 mg, 24%) is obtained as a pale yellow solid of compound 196 (300 mg, 0.780 mmol) in place of morpholine. X H NMR (DMSO-de, d ppm): 1.57-1.75 (, 2H), 1.77-1.89 (m, 2H), 1.94-2.07 (m, 2H), 2.38-2.68 (m, 1H), 2.79-2.91 ( m, 2H), 3.52 (s, 2H), 6.61 (dd, J = 1.6, 3.2 Hz, 1H), 7.36 (dd, J = 4.9, 7.8 Hz, 1H), 7.41 (d, J = 3.2 Hz, 1H ), 7.64 (dd, J = 4.6, 4.6 Hz, 1H), 7.67 (d, J = 1.6 Hz, 1H), 7.72 (d, J = 7.8 Hz, 1H), 8.03-8.09 (m, 2H), 8.47 (d, J = 4.9 Hz, 1H), 8.50 (s, 1H), 8.67 (d, J = 4.6 Hz, 1H), 12.67 (br s, 1H). APCIMS m / z: [M + H] + 474. p.f. : 208-209 ° C.

[Example 198] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -1- (pyridin-4-ylmethyl) piperidine-4-carboxamide (Compound 198) In a similar manner to that in Example 86, when using 4-pyridinecarbaldehyde (0.37 mL, 3.90 mmol) instead of Compound 85, the title compound 198 (114 mg, 31%) is obtained as a pale yellow solid of compound 196 (300 mg, 0.785 mmol) in place of morpholine. X H NMR (DMSO-de, d ppm): 1.61-1.79 (m, 2H), 1.89-1.92 (m, 2H), 1.96-2.08 (m, 2H), 2.41-2.63 (m, 1H), 2.79-2.88 (m, 2H), 3.52 (s, 2H), 6.61 (dd, J = 1.8, 3.3 Hz, 1H), 7.33 (d, J = 5.7 Hz, 2H), 7.42 (d, J = 3.3 Hz, 1H) , 7.66 (dd, J = 3.9, 4.8 Hz, 1H), 7.68 (d, J = 1.8 Hz, 1H), 8.05-8.10 (, 2H), 8.51 (d, J = 5.7 Hz, 2H), 8.69 (d , J = 4.8 Hz, 1H), 5 12.71 (br s, 1H). APCIMS m / z: [M + H] + 474. p.f .: 240-241 ° C.

[Example 199] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] benzamide (Compound 199) In a manner similar to that in Example 188, when using Chloride of benzoyl (0.210 mL, 1.89 mmol) in place of acetyl chloride, the title compound 199 (388 mg, 93%) is obtained as a pale yellow solid of compound 186 (288 mg, 1.11 mmol).

X H NMR (CDCl 3, d ppm): 6.58 (dd, J = 1.9, 3.8 Hz, 1H), 7.48-7.59 (, 4H), 7.60-7.69 (m, 1H), 7.87-8.00 (m, 4H), 8.22. (d, J = 7.6 Hz, 1H), 8.78 (d, J = 4.9 Hz, 1H), 9.79 (br s, 1H). APCIMS m / z: [M + H] + 376. m.p .: 165-171 ° C.

[Example 200] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2-methoxybenzamide (Compound 200) In a manner similar to that in Example 188, use 2-methoxybenzoyl chloride (0.0930 mL, 0.629 mmol) in place of acetyl chloride, the title compound 200 (183 mg, 100%) is obtained as a pale yellow solid of compound 186 (100 mg, 0.370 mmol) . X H NMR (CDCl 3, d ppm): 4.13 (s, 3 H), 6.57 (dd, J = 1.6, 3.5 Hz, 1 H), 7.08 (d, J = 8.4 Hz, 1 H), 7.16 (dd, J = 6.8, 7.8 Hz, 1H), 7.48 (ddd, J = 1.4, 4.9, 7.6 Hz, 1H), 7.56 (d, J = 1.6 Hz, 1H), 7.58 (ddd, J = 1.9, 6.8, 7.8 Hz, 1H), 7.81 (d, J = 3.5 Hz, 1H), 7.89 (ddd, J = 1.6, 7.6, 7.8 Hz, 1H), 8.17 (ddd, J = 0.8, 1.4, 7.8 Hz, 1H), 8.31 (dd, J = 1.9, 7.8 Hz, 1H), 8.75 (ddd, J = 0.8, 1.6, 4.9 Hz, 1H), 11.44 (br s, 1H). APCIMS m / z: [M + H] + 406. p. f. : 205-208 ° C.

[Example 201] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -3-methoxybenzamide (Compound 201) In a manner similar to that in Example 188, Using 3-methoxybenzoyl chloride (0.260 mL, 1.89 mmol) in place of acetyl chloride, the title compound 201 (311 mg, 69%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). XH NMR (CDC13, d ppm): 3.88 (s, 3H), 6.56 (dd, J = 1.9, 3.8 Hz, 1H), 7.16 (ddd, J = 1.4, 2.4, 5.6 Hz, 1H), 7.43 (dd, J = 5.6, 5.6 Hz, 1H), 7.46-7.57 (m, 3H), 7.54 (dd, J = 0.8, 1.9 Hz, 1H), 7.87-7.95 (m, 1H), 7.91 (dd, J = 0.8, 3.8 Hz, 1H), 8.22 (d, J = 7.8 Hz, 1H), 8.77 (d, J = 4.9 Hz, 1H), 9.85 (br s, 1H). APCIMS m / z: [M + H] + 406. m.p .: 165-166 ° C.

[Example 202] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -4-methoxybenzamide (Compound 202) In a manner similar to that in Example 188, using 3-methoxybenzoyl chloride (320 mg, 1.89 mmol) in place of acetyl chloride, the title compound 202 (254 mg, 56%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol) .

X H NMR (CDCl 3, d ppm): 3.90 (s, 3 H), 6.57 (dd, J = 1.9, 3.8 5 Hz, 1 H), 7.02 (d, J = 8.6 Hz, 2 H), 7.50 (dd, J = 4.9 , 7.8 Hz, 1H), 7.54 (d, J = 1.9 Hz, 1H), 7.86-7.97 (m, 2H), 7.93 (d, J = 8.6 Hz, 2H), 8.21 (d, J = 7.8 Hz, 1H ), 8.77 (d, J = 4.9 Hz, 1H), 9.75 (br s, 1H). APCIMS m / z: [M + H] + 406. p.f .: 187-188 ° C.

[Example 203] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -3,4-dimethoxybenzamide (Compound 203) In a manner similar to that in Example 187 , by using 3, 4-dimethoxybenzoic acid (368 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 203 (181 mg, 37%) is obtained as a pale yellow solid of the compound 186 (300 mg, 1.11 mmol). X H NMR (DMS0-d 6, d ppm): 3.86 (s, 3 H), 3.88 (s, 3 H), 6.63 (dd, J = 1.9, 3.5 Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H), 7.44 (d, J = 3.5 Hz, 1H), 7.64-7.72 (m, 1H), 7.70 (d, J = 1.9 Hz, 1H), 7.82 (d, J = 2.2 Hz, 1H), 7.85 (dd, J = 2.2, 8.4 Hz, 1H), 8.06-8.11 (m, 2H), 8.68-8.73 (, 1H), 13.04 (br s, 1H). APCIMS m / z: [M + H] + 436. p.f .: 169-170 ° C.

[Example 204] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -3,4,5-trimethoxybenzamide (Compound 204) In a manner similar to that in example 188, when using 3, 4, 5-benzoyl chloride (434 mg, 1.89 mmol) in place of acetyl chloride, the title compound 204 (526 mg, 100%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 3.77 (s, 3 H), 3.90 (s, 6 H), 6.64 (d, J = 1.6, 3.2 Hz, 1 H), 7.47 (d, J = 3.2 Hz, 1 H) 7.58 (s, 2H), 7. 65-7.73 (, 1H), 7.72 (d, J = 1.6 Hz, 1H), 8.04-8.12 (m, 2H), 8.69-8.74 (m, 1H), 13.16 (brs, 1H) -. APCIMS m / z: [M + H] + 466. m.p .: 172-180 ° C (dec.). [Example 205] 3-Cyano-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] benzamide (Compound 205) In a manner similar to that in Example 188, when using 3-cyanobenzoyl chloride (364 mg, 2.21 mmol) instead of acetyl chloride, the title compound 205 (241 mg, 46%) is obtained as a pale yellow solid of the compound 186 (350 mg, 1.30 mmol). XH NMR (CDC13, d ppm): 6.50 (dd, J = 1.6, 3.2 Hz, 1H), 7.46 I (d, J = 1.6 Hz, 1H), 7.52 (ddd, J = 1.1, 4.9, 7.6 Hz, 1H), 7.62 (d, J = 8.0, 8.1 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1 HOUR) , 7. 88 (d, J = 3.2 Hz, 1H), 7.92 (ddd, J = 1.6, 7.6, 7.8 Hz, 1H), 8.13 (d, J = 8.1 Hz, 1H), 8.22 (ddd, J = 0.8, 1.1, 7.8 Hz, 1H), 8.26 (s, 1H), 8.78 (ddd, J = 0.8, 1.6, 4.9 Hz, 1H).

APCIMS m / z: [M + H] + 401. p.f. : 234-237 ° C. [Example 206] 4-Cyano-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] benzamide (Compound 206) In a manner similar to that in Example 188, when using 4-cyanobenzoyl chloride (311 mg, 1.89 mmol) in place of acetyl chloride, the title compound 206 (231 mg, 52%) is obtained as a pale yellow solid of the compound 186 (300 mg, 1.11 mmol). XH NMR (CDC13, d ppm): 6.51 (dd, J = 1.6, 3.5 Hz, 1H), 7.45 (d, J = 1.6 Hz, 1H), 7.53 (dd, J = 4.6, 7.6 Hz, 1H), 7.79 (d, J = 8.1 Hz, 2H), 7.85 (d, J = 3.5 Hz, 1H), 7.93 (dd, J = 7.6, 8. 1 Hz, 1H), 8.03 (d, J = 8.1 Hz, 2H), 8.24 (d, J = 8.1 Hz, 1H), 8.78 (d, J = 4.6 Hz, 1H), 10.50 (br s, 1H). APCIMS m / z: [M + H] + 401. p.f .: 232-235 ° C. [Example 207] 3-Acetyl-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] benzamide (Compound 207) In a manner similar to that in example 187, when using 3-acetylbenzoic acid (363 mg, 2.22 mmol) instead of isonicotinic acid, the title compound 207 (479 mg, 100%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-de, d ppm): 2.70 (s, 3 H), 6.64 (dd, J = 1.3, 3.5 Hz, 1 H), 7.46 (d, J = 3.5 Hz, 1 H), 7.63-7.78 (m, 3H), 8.03-8.13 (m, 2H), 8.20 (d, J = 7.0 Hz, 1H), 8.37 (d, J = 6.8 Hz, 1H), 8.68-8.74 (m, 1H), 8.77 (s, 1H) ), 13.43 (br s, 1H). APCIMS m / z: [M + H] + 418. p.f .: 168-169 ° C.

[Example 208] 4-Acetyl-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] benzamide (Compound 208) In a manner similar to that in example 187 , using 4-acetylbenzoic acid (182 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 208 (422 mg, 91%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-dβ, d ppm): 2.66 (s, 3 H), 6.64 (dd, J = 1.6, 3.2 Hz, 1 H), 7.46 (d, J = 3.2 Hz, 1 H), 7.65-7.75 (m, 1H), 7.72 (d, J = 1.6 Hz, 1H), 8.04-8.14 (, 2H), 8.11 (d, J = 8.4 Hz, 2H), 8.28 (d, J = 8.4 Hz, 2H), 8.69-8.75 (m, 1H), 13.40 (br s, 1H). APCIMS m / z: [M + H] + 418. p.f .: 204-206 ° C.

[Example 209] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -3, 4-methylenedioxybenzamide (Compound 209) In a manner similar to that in Example 187, when using 3,4-methylenedioxybenzoic acid (367 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 209 (369 mg, 79 %) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). H NMR (DMSO-d6, d ppm): 6.17 (s, 2H), 6.63 (dd, J = 1.6, 3.5 Hz, 1H), 7.09 (d, J = 8.4 Hz, 1H), 7.44 (dd, J = 0.8, 3.5 Hz, 1H), 7.64-7.72 (m, 1H), 7.70 (dd, J = 0.8, 1.6 Hz, 1H), 7.73 (d, J = 1.9 Hz, 1H), 7.82 (dd, J = 1.9 , 8.4 Hz, lH), 8.05-8.11 (, 2H), 8.68-8.73 (m, 1H), 12.99 (br s, 1H). APCIMS m / z: [M + H] + 420. p.f .: 235-236 ° C. [Example 210] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -1,4-benzodioxane-6-carboxamide (Compound 210) In a manner similar to that in Example 187, using 1,4-benzodioxane-6-carboxylic acid (398 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 210 (412 mg, 86%) is obtained as a pale yellow compound 186 (300 mg, 1.11 mmol).

X H NMR (DMSO-d 6, d ppm): 4.28-4.38 (m, 4H), 6.63 (dd, J = 1.9, 3.5 Hz, 1H), 7.02 (d, J = 8.6 Hz, 1H), 7.44 (dd, J = 0.5, 3.5 Hz, 1H), 7.63-7.73 (, 1H), 7.71 (dd, J = 0.5, 1.9 Hz, 1H), 7.74 (dd, J = 2.2, 8.6 Hz, 1H), 7.77 (d, J = 5. "2.2 Hz, 1H), 8.03-8.11 (m, 2H), 8.68-8.73 (m, 1H), 13.00 (br s, 1H) APCIMS m / z: [M + H] + 434. mp: 189-191 ° C. 0 [Example 211] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -1,4-benzodioxane-2-carboxamide (Compound 211) In a manner similar to that in example 187, when using 1,4-benzodioxane-2-carboxylic acid (398 mg, 2.22 mmol) instead of. isonicotinic acid, the title compound 211 (394 mg, 82%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 4.44 (dd, J = 3.0, 12.2 Hz, 1H), 4.53 (dd, J = 3.8, 12.2 Hz, 1H), 5.24 (dd, J = 3.0, 3.8 Hz, 1H), 6.63 (dd, J = 1.9, 3.5 Hz, 1H), 6.84-6.95 (m, 3H), 6.99-7.05 (m, 1H), 7.46 (dd, J = 0.8, 3.5 Hz, 1H), 7.62-7.69 (m, 1H), 7. 71 (dd, J = 0.8, 1.9 Hz, 1H), 8.02-8.11 (, 2H), 8.66-8.70. (m, 1H), 13. 10 (br s, 1H). APCIMS m / z: [M + H] + 434. p. f. : 103-104 ° C.

[Example 212] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2-methylpyridine-4-carboxamide (Compound 212) In a manner similar to that in Example 187, using 2-methylisonicotinic acid (384 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 212 (186 mg, 43%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol ). X H NMR (DMSO-d 6, d ppm): 2.59 (s, 3 H), 6.65 (dd, J = 1.9, 3.5 Hz, 1 H), 7.46 (dd, J = 0.8, 3.5 Hz, 1 H), 7.66-7.75 ( m, 1H), 7.73 (dd, J = 0.8, 1.9 Hz, 1H), 7.85 (dd, J = 1.1, 5.1 Hz, 1H), 7.94 (d, J = 1.1 Hz, 1H), 8.05-8.14 (m , 2H), 8.69 (d, J = 5.1 Hz, 1H), 8.69-8.74 (m, 1H), 13.43 (br s, 1H). APCIMS m / z: [M + H] + 391. p.f. : 187-188 ° C. [Example 213] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (4-methoxybenzyl) pyridine-4-carboxamide (Compound 213) The compound 186 (600 mg, 2.22 mmol) was dissolved in DMF (11 mL), and Compound 1 (1.43 g, 5.53 mmol) obtained in Reference Example 12, N, N-diisopropylethylamine (2.34 mL, 13.3 mmol) and PyBOP (4.03 g, 7.74 mmol) were added to this-, "followed by stirring at 50 ° C for 10 hours.Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was continuously distilled under reduced pressure. The resulting residue was purified through silica gel column chromatography to provide the title compound 213 (912 mg, 81%) as a pale yellow oily substance. X H NMR (DMSO-de, d ppm): 3.78 (s, 3H), 5.31 (s, 2H), 6.42 (dd, J = 1.8, .3.6 Hz, 1H), 6.86 (d, J = 8.9 Hz, 2H ), 7.21 (dd, J = 1.0, 1.6 Hz, 1H), 7.31 (dd, J = 1.6, 5.4 Hz, 1H), 7.35 (d, J = 8.9 Hz, 2H), 7.36 (dd, J = 0.7, 1.8 Hz, 1H), 7.51 (ddd, J = 1.2, 4.8, 7.6 Hz, 1H), 7.70 (dd, J = 0.7, 3.6 Hz, 1H), 7.91 (ddd, J = 1.8, 7.6, 7.9 Hz, 1H ), 8.04 (brs, 1H), 8.19 (ddd, J = 1.0, 1.2, 7.9 Hz, 1H), 8.27 (dd, J = 1.0, 5.4 Hz, 1H), 8.77 (ddd, J = 1.0, 1.8, 4.8 Hz, 1H). [Example 214] 2-Chloro-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 214) In a manner similar to that in Example 187, by using 2-chloroisonicotinic acid (348 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 214 (270 mg, 59%) is obtained as a pale yellow solid of the compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 6.65 (dd, J = 1.6, 3.2 Hz, 1H), 7.47. (d, J = 3.2 Hz, 1H), 7.66-7.73 (m, 1H), 7.74 (d, J = 1.6 Hz, 1H), 8.04 (dd, J = 1.6, 5.4 Hz, 1H), 8.08-8.14 ( m, 2H), 8.20 (d, J = 1.6 Hz, 1H), 8.68 (d, J = 5.4 Hz, 1H), 8.70-8.75 (m, 1H), 13.57 (br s, 1H). APCIMS m / z: [35CIM + H] + 411, [37CIM + H] + 413. p. f. : 219-225 ° C.

[Example 215] 3-Chloro-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 215) In a manner similar to that in Example 187, when using 3-chloroisonicotinic acid (348 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 215 (452 mg, 99%) is obtained as a pale yellow solid of the compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-de, d ppm): 6.64 (dd, J = 1.6, 3.5 Hz, 1H), 7.46 (d, J = 3.5 Hz, 1H), 7.65-7.74 (m, 1H), 7.73 (d, J = 1.6 Hz, 1H), 7.78 (d, J = 4.9 Hz, 1H), 8.06-8.17 (m, 2H), 8.72 (d, J = 4. 9 Hz, 1H), 8.72-8.76 (m, 1H), 8.84 (s, 1H), 13.57 (br s, 1H).

APCIMS m / z: [35CIM + H] + 411, [37CIM + H] + 413. p.f. : • 206-207 ° C.

[Example 216] 2,6-Dichloro-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 216) In a manner similar to that in Example 187, by using 2,6-dichloroisonicotinic acid (424 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 216 (402 mg, 81%) is obtained as a pale yellow solid of compound 186 ( 300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 6.65 (dd, J = 1.6, 3.5 Hz, 1H), 7.48 (d, J = 0.5 Hz, 1H), 7.66-7.72 (m, 1H), 7.74 (d, J = 0.5 Hz, 1H), 8.05-8.15 (m, 2H), 8.19 (s, 2H), 8.69-8.75 (m, 1H), 13. 59 (br s, 1H). APCIMS m / z: [35C135C1 M + H] + 445, [35C1 37C1M + H] + 447. p. f. : 254 -258 ° C.

[Example 217] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- [N- (2-methoxyethyl) -N-methylamino] pyridine-4- carboxamide (Compound 217) In a manner similar to that in Example 187, by using 2- [N- (2-methoxyethyl) -N-methylamino] pyridine-4-carboxylic acid (465 mg, 2.22 mmol) instead of acid isonicotinic, the title compound 217 (273 mg, 59%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (CDC13, d ppm): 3.17 (s, 3 H), 3.34 (s, 3 H), 3.61 (t, J = 5.4 Hz, 2H), 3.82 (t, J = 5.4 Hz, 2H), 6.56 (dd, J = 1.9, 3.8 Hz, 1H), 6.91 (d, J = 5.1 Hz, 1H), 7.04-7- 08 (m, 1H), 7.50 (ddd, J = 1.6, 4.9, 7.3 Hz, 1H), 7.54 (d, J = 1.9 Hz, 1H), 7.90 (ddd, J = 1.6, 7.3, 7.8 Hz, 1H), 7.91 (d, J = 3.8 Hz, 1H), 8.21 (d, J = 7.8 Hz, 1H), 8.29 (d, J = 5.1 Hz, 1H), 8.75 (dd, J = 1.6, 4.9 Hz, 1H). APCIMS m / z: [M + H] + 464. p.f. : 114-117 ° C.

[Example 218] N- [4- (2-Furyl) -5- (pyridin-2-yl carboni 1) thiazol-2-yl] -2-piperidinopyridine-4-carboxamide (Compound 218) In a manner similar to that in Example 187, when using 2-piperidinopyridine-4-carboxylic acid (456 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 218 (300 mg, 59%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). XH NMR (CDC13, d ppm): 1.50-1.82 (m, 6H), 3.53-3.80 (m, 4H), 6.55 (d, J = 1.9, 3.8 Hz, 1H), 6.88 (d, J = 5.1 Hz, 1H), 7.14 (s, 1H), 7.50 (ddd, J = 1.4, 4.9, 7.8 Hz, 1H), 7.52) (dd, J = 0.5, 1.9 Hz, 1H), 7.90 (ddd, J = 1.9, 7.8) , 7.8 Hz, 1H), 7.90 (dd, J = 0.5, 3.8 Hz, 1H), 8.21 (ddd, J = 0.8, 1.4, 7.8 Hz, 1H), 8. 29 (d, J = 5.1 Hz, 1H), 8.75 (ddd, J = 0.8, 1.9, 4. 9 Hz, 1H), 9.97 (br s, 1H). APCIMS m / z: [M + H] + 460. mp .: 136-141 ° C.

[Example 219] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2-morpholinopyridine-4-carboxamide (Compound 219) In a manner similar to that in Example 187, using 2-morpholinopyridine-4-carboxylic acid (461 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 219 (233 mg, 45%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). XH NMR (CDC13, d ppm): 3.59-3.67 (m, 4H), 3.79-3.87 (, 4H), 3 6.57 (dd, J = 1.6, 3.5 Hz, 1H), 7.04 (d, J = 4.6 Hz, 1 HOUR) , 7. 21 (s, 1H), 7.52 (dd, J = 4.9, 7.6 Hz, 1H), 7.56 (d, J = 1. 6 Hz, 1H), 7.92 (ddd, J = 1.9, 7.6, 7.8 Hz, 1H), 7.95 (d, J = 3.5 Hz, 1H), 8.22 (d, J = 7.8 Hz, 1H), 8.35 (d, J = 4.6 Hz, 1H), 8.76 (dd, J = 1.9, 4.9 Hz, 1H). APCIMS m / z: [M + H] + 462. p.f .: 216-217 ° C. [Example 220] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-3-carboxamide (Compound 220) In a manner similar to that in example 188, when using nicotinoyl chloride hydrochloride (394 mg, 2.22 mmol) in place of acetyl chloride, the title compound 220 (252 mg, 60%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol) . X H NMR (DMSO-d 6, d ppm): 6.65 (dd, J = 1.9, 3.5 Hz, 1H), 7.48 (d, J = 3.5 Hz, 1H), 7.62 (dd, J = 5.1, 8.1 Hz, 1H) , 7.66-7.73 (, 1H), 7.73 (d, J = 1.9 Hz, 1H), 8.05-8.14 (m, 2H), 8.50 (ddd, J = 1.4, 2.2, 8.1 Hz, 1H), 8.71-8.75 ( m, 1H), 8.83 (dd, J = 1.4, 5.1 Hz, 1H), 9.28 (d, J = 2.2 Hz, 1H), 13.43 (br s, 1H). APCIMS m / z: [M + H] + 377.

[Example 221] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2-methylpyridine-3-carboxamide (Compound 221) In a manner similar to that in Example 187, using 2-methylnicotinic acid (303 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 221 (316 mg, 73%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol ). X H NMR (DMSO-d 6, d ppm): 2.63 (s, 3 H), 6.63 (dd, J = 1.9, 3.5 Hz, 1 H), 7.38 (dd, J = 4.9, 7.8 Hz, 1 H), 7.44 (dd, J = 0.8, 3.5 Hz, 1H), 7.65-7.73 (m 1H), 7.71 (dd, J = 0.8, 1.9 Hz, 1H), 8.04-8.14 (m, 2H), 8.05 (dd, J = 1.6, 7.8 Hz, 1H), 8.61 (dd, J = 1.6, 4.9 Hz, 1H), 8.71-8.75 (m 1H), 12.67 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 391. mp .: 186-187 ° C. [Example 222] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2-methylpyridine-5-carboxamide (Compound 222) In a manner similar to that in Example 187, when using 6-methylnicotinic acid (303 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 222 (326 mg, 75 %) is obtained as a pale yellow solid of the compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 2.58 (s, 3 H), 6.64 (dd, J = 1.6 3. 5 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.46 (dd, J = 0.8 3.5 Hz, 1H), 7.65-7.74 (, 1H), 7.72 (dd, J = 0.8, 1.6 Hz 1H), 8.04-8.13 (m, 2H), 8.38 (dd, J = 2.4, 7.8 Hz, 1H) 8. 69-8.74 (m, 1H), 9.17 (d, J = 2.4 Hz, 1H), 13.31 (br s 1 HOUR) . APCIMS m / z: [M + H] + 391. mp .: 210-215 ° C. [Example 223] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -5-methylpyridine-3-carboxamide (Compound 223) In a manner similar to that in example 187, when using 5-methyl nicotinic acid (303 mg, 2.22 mmol) instead of isonicotinic acid, the title compound 223 (391 mg, 90%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). H NMR (DMSO-d6, d ppm): 2.41 (s, 3H), 6.64 (dd, J = 1.9, 3.5 Hz, 1H), 7.46 (dd, J = 0.8, 3.5 Hz, 1H), 7.65-7.75 ( m, 1H), 7.73 (dd, J = 0.8, 1.9 Hz, 1H), 8.05-8.14 (m, 2H), 8.33 (dd, J = 1.4, 1.9 Hz, 1H), 8.67 (d, J = 1.4 Hz , 1H), 8.70-8.73 (m, 1H), 9.08 (d, J = 1.9 Hz, 1H), 13.35 (br s, 1H). APCIMS m / z: [M + H] + 391. p.f .: 245-248 ° C.

[Example 224] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2,6-dimethoxypyridine-3-carboxamide (Compound 224) In a manner similar to that in Example 187, when using 2,6-dimethoxynicotinic acid (405 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 224 (484 mg, 100%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMS0-d 6, d ppm): 3.97 (s, 3 H), 4.09 (s, 3 H), 6.58 (d, J = 8.6 Hz, 1 H), 6.63 (dd, J = 1.9, 3.2 Hz 1 H), 7.45 (d, J = 3.2 Hz, 1H), 7.64-7.71 (m, 1H), 7.71 (d, J = 1.9 Hz, 1H), 8.03-8.12 (m, 2H), 8.18 (d, J = 8.6 Hz , 1H), 8.69-8.73 (m, 1H), 11.97 (br s, 1H).

APCIMS m / z: [M + H] + 437. p.f .: 201-202 ° C.

[Example 225] 2-Chloro-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-5-carboxamide (Compound 225) In a manner similar to that in Example 187, using 6-chloronicotinic acid (348 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 225 (298 mg, 65%) is obtained as a pale yellow solid of the compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 6.64 (dd, J = 1.6, 3.2 Hz, 1H), 7.47 (d, J = 3.2 Hz, 1H), 7.65-7.74 (m, 1H), 7.72 (d, J = 1.6 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H), 8.04-8.14 (m, 2H), 8.52 (dd, J = 2.4, 8.4 Hz, 1H), 8.70-8.74 (m, 1H) ), 9.12 (d, J = 2.4 Hz, 1H), 13.47 (br s, 1H). p.f .: 136-138 ° C.

[Example 226] 5-Bromo-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-3-carboxamide (Compound 226) In a manner similar to that in Example 187, using 5-bromonicotinic acid (446 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 226 (303 mg, 60%) is obtained as a pale yellow solid of the compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 6.65 (dd, J = 1.9, 3.8 Hz, 1H), 7.48 (dd, J = 0.8, 3.8 Hz, 1H), 7.65-7.72 (m, 1H), 7.73 ( dd, J = 0.8, 1.9 Hz, 1H), 8.06-8.15 (m, 2H), 8.71-8.77 (m, 1H), 8.75 (dd, J = 1.9, 2.2 Hz, 1H), 8.97 (d, J = 2.2 Hz, 1H), 9.22 (d, J = 1.9 Hz, 1H), 13.46 (br s, 1H). APCIMS m / z: [79BrM + H] + 455, [81BrM + H] + 457. p.f .: 259-262 ° C.

[Example 227] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyridazine-4-carboxamide (Compound 227) In a manner similar to that in example 187, when using pyridazine-4-carboxylic acid (274 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 227 (275 mg, 90%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 6.66 (dd, J = 1.9, 3.5 Hz, 1H), 7. 51 (d, J = 3.5 Hz, 1H), 7.66-7.73 (m, 1H), 7.75 (d, J = 1.9 Hz, 1H), 8.05-8.16 (m, 2H), 8.30 (dd, J = 2.4, . 4 Hz, 1H), 8.71-8.77 (m, 1H), 9.56 (dd, J = 1.1, 5.4 Hz, 1H), 9.78 (dd, J = 1.1, 2.4 Hz, 1H), 13.73 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 378. p. f. : 270-274 ° C.

[Example 228] N- [4- (2-Furyl) -5-pyridin-2-ylcarbonyl) thiazol-2-yl] -2-methylpyrimidine-5-carboxamide (Compound 228) Compound 186 (50.0 mg, 0.18 mmol ) was dissolved in DMF (0.9 mL), and diisopropylethylamine (0.0500 L, 0.270 mmol) and a 0.5 mol / L solution of triethylamine salt of 2-methylpyrimidine-5-carboxylic acid (0.560 mL, 0.280 mmol) in DMF obtained from according to the method described in Synthesis, p. 720, 2002, and PyBOP (144 mg, 0.280 mmol) were added thereto under ice cooling, followed by stirring at 50 ° C for 2 hours. To the reaction mixture, diisopropylethylamine, triethylamine of 2-methylpyrimidine-5-carboxylic acid and PyBOP respectively the same amount previously added, were added to the reaction mixture, followed by stirring at 70 ° C for 1.5 hours. Again, the same amount of diisopropylethylamine, triethylamine salt of 2-methylpyrimidine-5-carboxylic acid and PyBOP as previously added, were added thereto, followed by stirring at 80 ° C for 1.5 hours. The reaction mixture was allowed to cool, water was added to it, and the precipitated solid was collected by. filtration. The resulting solid was purified through silica gel column chromatography (chloroform: methanol = 30: 1) to give the title compound 228 (66.9 mg, 95%) as pale yellow crystals. Then, the same procedure as above is repeated to provide the compound 228. The obtained compound 228 (14.3 g) was dissolved in a mixed solvent (4: 1, 1.80 L) of ethanol and water under heating and reflux. The resulting solution was allowed to cool to room temperature, and the precipitated crystals were collected by filtration to provide the title compound 228 (11.3 g,) re-crystallization affording 79%). X H NMR (DMSO-d 6, d ppm): 2.73 (s, 3 H), 6.65 (dd, J = 1.6, 3.5 Hz, 1 H), 7.50 (dd, J = 0.8, 3.5 Hz, 1 H), 7.66-7.73 ( m, 1H), 7.74 (dd, J = 0.8, 1.6 Hz, 1H), 8.05-8.15 (, 2H), 8.70-8.75 (m, 1H), 9.32 (s, 2H), 13.51 (br s, 1H) . APCIMS m / z: [M + H] + 392. p.f .: 255-265 ° C (decomposition).

[Example 229] 2-Cyclopropyl-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyrimidine-5-carboxamide (Compound 229) In a manner similar to that in Example 228, when using a 0.5 mol / L solution of the triethylamine salt of 2-cyclopropylpyrimidine-5-carboxylic acid (4.86 mL, 2.43 mmbl) in DMF obtained according to the method described in Synthesis, p. 720, 2002, in place of the triethylamine salt of 2-methylpyrimidine-5-carboxylic acid, the title compound 229 (217 mg, 96%) is obtained as a pale yellow solid of compound 186 (200 mg, 0.57 mmol) . X H NMR (DMS0-d 6, d ppm): 1.09-1.24 (m, 4H), 2.27-2.39 (m, 1H), 6. 64 (dd, J = 1.6, 3.5 Hz, 1H), 7.49 (d, J = 3.5 Hz, 1H), 7.65-7.73 (m, 1H), 7.73 (d, J = 1.6 Hz, 1H), 8.04-8.15 (m, 2H), 8.70-8.75 (m, 1H), 9.26 (s, 2H). APCIMS m / z: [M + H] + 418. p.f .: 150-154 ° C.

[Example 230] N- [4- (2-Furyl) -5- (pyridine-2-ylcarbonyl) thiazol-2-yl] -5-methylpyrazine-2-carboxamide (Compound 230) In a manner similar to that in Example 187, when using 5-methylpyrazine-2-carboxylic acid (186 mg, 1.34 mmol) in place of isonicotinic acid, the title compound 230 (284 mg, 100%) is obtained as a pale yellow solid of compound 186 (250 mg, 0.67 mmol). X H NMR (DMSO-d 6, d ppm): 2.65 (s, 3 H), 6.63 (dd, J = 1.6, 3.2 Hz, 1H), 7.41 (d, J = 3.2 Hz, 1H), 7.66-7: 74 (m, 1H), 7.71 (d, J = 1.6 Hz, 1H), 8.07-8.14 (m, 2H), 8.69-8.74 (m, 1H), 8. 75 (s, 1H), 9.22 (s, 1H), 12.94 (br s, 1H). APCIMS m / z: [M + H] + 392. p.f .: 208-209 ° C. [Example 231] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2-oxo-1,2-dihydropyridine-4-carboxamide (Compound 231) The compound 213 (912 mg, 1.78 mmol) was dissolved in trifluoroacetic acid (3.6 mL), followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the resulting residue was redissolved in ethyl acetate to give the title compound 231 (469 mg, 67%) as a pale yellow solid. X H NMR (DMSO-d 6, d ppm): 6.64 (dd, J = 1.9, 3.5 Hz, 1H), 6.69 (dd, J = 1.9, 6.8 Hz, 1H), 7.09 (d, J = 1.9 Hz, 1H) , 7.46 (d, J = 3.5 Hz, 1H), 7.56 (d, J = 6.8 Hz, 1H), 7.65-7.75 (m, 1H), 7.73 (d, J = 1.9 Hz, 1H), 8.04- 8.15 (m, 2H), 8.68-8.77 (m, 1H), 13.27 (br s, 1H). APCIMS m / z: [M + H] + 393. mp .: 170-180 ° C (decomposition) [Example 232] 1-Benzyl-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2-oxo-l, 2-dihydropyridine-4-carboxamide (Compound 232) In a manner similar to that in Example 187, when using Compound w (341 mg, 1.48 mmol) obtained in Reference Example 23 instead of isonicotinic acid, the title compound 232 (269 mg, 75%) obtained as a pale yellow solid of compound 186 (202 mg, 0.740 mmol). XH NMR (DMS0-d6, d ppm): 5.12 (s, 2H), 6.64 (dd, J = 1.9, 3.5 Hz, 1H), 6.78 (dd, J = 1.6, 7.3 Hz, 1H), 7.20 (d, J = 1.6 Hz, 1H), 7.28-7.41 (m, 5H), 7.45 (dd, J = 0.5, 3.5 Hz, 1H), 7.65-7.74 (m, 1H), 7.72 (dd, J = 0.5, 1.9 Hz, 1H), 8.00 (d, J = 7.3 Hz, 1H), 8.04-8.13 (m, 2H), 8.69-8.74 (m, 1H), 13.35 (br s, 1H). APCIMS m / z: [M + H] + 483. p.f. : 269-270 ° C.

[Example 233] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -1-methyl-2-oxo-l, 2-dihydropyridine-4-carboxamide (Compound 233) In a manner similar to that in Example 187, when using Compound x (190 mg, 1.24 mmol) obtained in Reference Example 24 in place of isonicotinic acid, the title compound 233 (233 mg, 92%) was obtained as a pale yellow solid of compound 186 (168 mg, 0.620 mmol). X H NMR (DMS0-d 6, d ppm): 3.54 (s, 3 H), 6.64 (dd, J = 1.9, 3. 5 Hz, 1H), 6.74 (dd, J = 2.2, 7.0 Hz, 1H), 7.15 (d, J = 2.2 Hz, 1H), 7.46 (dd, J = 0.8, 3.5 Hz, 1H), 7.65-7.72 ( m, 1H), 7.73 (dd, J = 0.8, 1.9 Hz, 1H), 7.88 (d, J = 7.0 Hz, 1H), 8.04-8.14 (m, 2H), 8.70-8.74 (m, 1H), 13.36 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 407. m.p .: 280-285 ° C.

[Example 234] N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] furan-2-carboxamide (compound 234) In a manner similar to that in example 188, using 2-furoyl chloride (0.190 ml, 1.89 mmol) in place of acetyl chloride, the title compound 234 (196 mg, 48%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). XH NMR (CDC13, d ppm): 6.57 (dd, J = 1.9, 3.8 Hz, 1H), 6.62 (dd, J = 1.9, 3.8 Hz, 1H), 7.41 (dd, J = 0.8, 3.8 Hz, 1H), 7.49 (ddd, J = 1.4, 4.9, 7.6 Hz, 1H), 7.56 (dd, J = 0.8, 1.9 Hz, 1H), 7.59 (dd, J = 0.8, 1.9 Hz, 1H), 7.89 (ddd, J = 1.9, 7.6, 8.1 Hz, 1H), 7.92 (dd, J = 0.8, 3.8 Hz, 1H), 8.19 (ddd, J = 0.8, 1.4, 8.1 Hz, 1H), 8.74 (ddd, J = 0.8, 1.9, 4.9 Hz, 1H), 10.11 (br s, 1H). APCIMS m / z: [M + H] + 366. mp .: 184-185 ° C.

[Example 235] 5-Bromo-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] furan-2-carboxamide (compound 235) In a manner similar to that in Example 187, when using 5-bromofuran-2-carboxylic acid (422 mg, 2.22 mmol) in isonicotinic acid, the title compound 235 (366 mg, 75 %) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 6.63 (dd, J = 1.9, 3.5 Hz, 1H), 6.92 (d, J = 3.5 Hz, 1H), 7.45 (dd, J = 0.5, 3.5 Hz, 1H) , 7.64-7.73 (m, 1H), 7.70 (dd, J = 0.5, 1.9 Hz, 1H), 7.81 (d, J = 3.5 Hz, 1H), 8.03-8.13 (m, 2H), 8.67-8.72 (m , 1H), 13.23 (br s, 1H). APCIMS m / z: [79BrM + H] + 444, [81BrM + H] + 446. p.f .: 211-212 ° C.

[Example 236] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -5-nitrofuran-2-carboxamide (Compound 236) In a manner similar to that in Example 187, when using 5-nitrofuran-2-carboxylic acid (347 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 236 (334 mg, 73%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 6.65 (dd, J = 1.6, 3.5 Hz, 1H), 7.48. (dd, J = 0.5, 1.6 Hz, 1H), 7.66-7.74 (m, 1H), 7.73 (dd, J = 0.5, 1.6 Hz, 1H), 7.85 (d, J = 4.1 Hz, 1H), 7.98 ( d, J = 4.1 Hz, 1H), 8.05-8.14 (m, 2H), 8.69-8.73 (m, 1H), 13.72 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 411. p. f. : 278-283 ° C (decomposition) [Example 237] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -3-methyl-furan-2-carboxamide (Compound 237) In a manner similar to that in Example 187, when using 3-methyl-furan-2-carboxylic acid (279 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 237 (377 mg, 90%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMS0-d 6, d ppm): 2.40 (s, 3 H), 6.62 (dd, J = 1.9, 3.5 Hz, 1 H), 6.67 (d, J = 1.6 Hz, 1 H), 7.40 (dd, J = 0.5, 3.5 Hz, 1H), 7.62-7.72 (m, 1H), 7.70 (dd, J = 0.5, 1.9 Hz, 1H), 7.88 (d, J = 1.6 Hz, 1H), 8.03-8.11 (m, 2H), 8.69-8.73 (m, 1H), 12. 87 (br s, 1H). APCIMS m / z: [M + H] + 380. m.p .: 174-176 ° C.

[Example 238] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] furan-3-carboxamide (Compound 238) In a manner similar to that in Example 188, when using 3-furoyl chloride (248 mg, 1.89 mmol) in place of acetyl chloride, the title compound 238 (241 mg, 59%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol) . X H NMR (DMSO-d 6, d ppm): 6.63 (dd, J = 1.6, 3.2 Hz, 1H), 7. 14 (d, J = 1.9 Hz, 1H), 7.44 (d, J = 3.2 Hz, 1H), 7.67 (ddd, J = 2.3, 4.6, 4.9 Hz, 1H), 7.69 (d, J = 1.6 Hz, 1H ), 7.87 (dd, J = 1.9, 1.9 Hz, 1H), 8.03-8.11 (m, 2H), 8.64-8.68 (m, 1H), 8.69 (d, J = 4.6 Hz, 1H), 13.00 (br s) , 1 HOUR) . APCIMS m / z: [M + H] + 366. p.f .: 187-189 ° C.

[Example 239] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2-methyl-furan-3-carboxamide (Compound 239) In a manner similar to that in Example 187, using 2-methyl-furan-3-carboxylic acid (279 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 239 (329 mg, 78%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 2.63 (s, 3 H), 6.63 (dd, J = 1.6, 3.5 Hz, 1H), 7.37 (d, J = 2.2 Hz, 1H), 7.44 (dd, J = 1.0, 3.5 Hz, 1H), 7.64-7.75 (m, 1H), 7.65 (d, J = 2.2 Hz, 1H), 7.70 (dd, J = 1.0, 1.6 Hz, 1H), 8.03-8.11 (m, 2H), 8.69-8.74 (m, 1H), 12. 74 (br s, 1H). APCIMS m / z: [M + H] + 380. p. f. : 183-186 ° C.

[Example 240] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2,5- dimethyl-furan-3-carboxamide (Compound 240) In a manner similar to that in Example 187, using 2,5-dimethylfuran-3-carboxylic acid (310 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 240 (290 mg, 66%) is obtained as a pale yellow compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 2.27 (s, 3 H), 2.58 (s, 3 H), 6.62 (dd, J = 1.9, 3.5 Hz, 1 H), 6.96 (s, 1 H), 7.44 (dd, J = 0.5, 3.5 Hz, 1H), 7.62-7.72 (m, 1H), 7.70 (dd, J = 0.5, 1.9 Hz, 1H), 8. 03-8.11 (m, 2H), 8.69-8.73 (m, 1H), 12.65 (br s, 1H). APCIMS m / z: [M + H] + 394. p.f .: 195-198 ° C.

[Example 241] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] thiophene-2-carboxamide (Compound 241) In a manner similar to that in Example 188, when using 2-thiophenecarbonyl chloride (0.200 mL, 1.89 mmol) in place of acetyl chloride, the title compound 241 (357 mg, 84%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol) . XH NMR (CDC13, d ppm): 6.55 (dd, J = 1.9, 3.5 Hz, 1H), 7.16 (dd, J = 4.1, 5.1 Hz, 1H), 7.49 (ddd, J = 1.1, 4.9, 7.6 Hz, 1H), 7.53 (dd, J = 1.1, 1.9 Hz, 1H), 7.66 (d, J = 5.1 Hz, 1H), 7.74 (dd, J = 1.1, 3.5 Hz, 1H), 7.89 (ddd, J = 1.6 , 7.6, 7.6 Hz, 1H), 7.92 (d, J = 4.1 Hz, 1H), 8.19 (ddd, J = 0.8, 1.1, 7.6 Hz, 1H), 8.75 (ddd, J = 0.8, 1.6, 4.9 Hz, 1 HOUR) . APCIMS m / z: [M + H] + 382. p.f .: 197-199 ° C.

[Example 242] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] isoxazole-5-carboxamide (Compound 242) In a manner similar to that in Example 188, when using 5-isoxazolecarbonyl chloride (240 mg, 1.89 mmol) in place of acetyl chloride, the title compound 242 (333 mg, 82%) is obtained as a brown solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 6.64 (dd, J = 1.9, 3.5 Hz, 1H), 7.46 (d, J = 3.5 Hz, 1H), 7.61 (d, -J = 1.9 Hz, 1H), 7.69 (ddd, J = 2.4, 4.9, 6.5 Hz, 1H), 7.72 (d, J = 1.9 Hz, 1H), 8.05-8.15 (m, 2H), 8.72 (d, J = 4.9 Hz, 1H), 8.88 (d, J = 1.9 Hz, 1H). APCIMS m / z: [M + H] + 367. p.f .: 223-230 ° C. [Example 243] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -5-methyl isoxazole-3-carboxamide (Compound 243) In a manner similar to that in example 187, when using 5-methylisoxazole-3-carboxylic acid (281 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 243 (277 mg, 66%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 2.53 (s, 3 H), 6.63 (dd, J = 1.6, 3.5 Hz, 1 H), 6.90 (s, 1 H), 7.42 (dd, J = 0.5, 3.5 Hz, 1H), 7.65-7.74 (m, 1H), '7.72 (dd, J = 0.5, 1.6 Hz, 1H), 8.04-8.13 (m, 2H), 8.68-8.74 (m, 1H), 13.47 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 381. p.f .: 209-213 ° C.

[Example 244] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -1,2,3-benzothiadiazole-5-carboxamide (Compound 244) In a similar manner to that in example 187, when using 1,2,3-benzothiadiazole-5-carboxylic acid (399 mg, 2.22 mmol) in place of isonicotinic acid, the title compound 244 (400 mg, 83%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-de, d ppm): 6.65 (dd, J = 1.6, 3.2 Hz, 1H), 7.48 (dd, J = 0.5, 3.2 Hz, 1H), 7.66-7.73 (m, 1H), 7.74 ( dd, J = 0. 5, 1.6 Hz, 1H), 8.05-8.15 (m, 2H), 8.47 (dd, J = 1.6, 8.6 Hz, 1H), 8.60 (dd, J = 0.8, 8.6 Hz, 1H), 8.72-8.77 (m, 1H), 9. 56 (dd, J = 0.8, 1.6 Hz, 1H), 13.58 (br s, 1H). APCIMS m / z: [M + H] + 434. p. f. : 213-218 ° C.

[Example 245] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -1-methyl-lH-benzotriazole-6-carboxamide (Compound 245) In a similar manner to that in example 187, when using l-methyl-lH-benzotriazole-6-carboxylic acid (392 mg, 2. 22 mmol) in place of isonicotinic acid, the title compound 245 (574 mg, 100%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol). X H NMR (DMSO-d 6, d ppm): 4.37 (s, 3 H), 6.64 (dd, J = 1.6, 3.5 Hz, 1 H), 7.46 (d, J = 3.5 Hz, 1 H), 7.65-7.74 (m, 1H), 7.72 (d, J = 1.6 Hz, 1H), 8.03 (d, J = 8.6 Hz, 1H), 8.07-8.13 (, 2H), 8.29 (dd, J = 1.4, 8.6 Hz, 1H), 8.70 -8.75 (m, 1H), 8.97 (d, J = 1.4 Hz, 1H), 13.38 (br s, 1H). APCIMS m / z: [M + H] + 431. mp .: 230-231 ° C.

[Example 246] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (1-hydroxyethyl) -1-benzofuran-5-carboxamide (Compound 246) In a manner similar to that in Example 187, by using 2- (1-hydroxyethyl) -l-benzofuran-5-carboxylic acid (304 mg, 1.48 mmol) obtained in accordance with the method described in Tetrahedron Letters, Vol. 38 , p. 2311, 1997, instead of isonicotinic acid, the title compound 246 (303 mg, 89%) is obtained as a pale yellow solid of the compound 186 (200 mg, 0.740 mmol). X H NMR (DMSO-d 6, d ppm): 1.50 (d, J = 6.6 Hz, 3 H), 4.89 (dq, J = 5.3, 6.6 Hz, 1 H), 5.63 (d, J = 5.3 Hz, 1 H), 6.64 (dd, J = 1.6, 3.2 Hz, 1H), 6.88 (s, 1H), 7.45 (d, J = 3.2 Hz, 1H), 7.65-7.75 (m, 1H), 7.72 (d, J = 7.8 Hz, 1H), 7.72 (d, J = 1.6 Hz, 1H), 8.07-8.14 (m, 2H), 8.11 (dd, J = 1.6, 7.8 Hz, 1H), 8.49 (d, J = 1.6 Hz, 1H), 8.70-8.75 (m, 1H), 13.19 (br s, 1H). APCIMS m / z: [M + H] + 460. p.f .: 246-249 ° C.

[Example 247] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (1-hydroxy-1-methylethyl) -l-benzofuran-5-carboxamide (Compound 247) In a manner similar to that in Example 187, when using 2- (1-hydroxy-1-methylethyl) -l-benzofuran-5-carboxylic acid (260 mg, 1.16 mmol) obtained in accordance with the method described in Tetrahedron-Letters, Vol. 38, p. 2311, 1997, in place of isonicotinic acid, the title compound 247 (274 mg, 100%) is obtained as a pale yellow solid of compound 186 (157 mg, 0.580 mmol). X H NMR (DMSO-d 6, d ppm): 1.55 (s, 6H), 5.52 (br s, 1H), 6.64 (dd, J = 1.6, .3.2 Hz, 1H), 6.84 (s, 1H), 7.45 ( d, J = 3.2 Hz, 1H), 7.65-7.75 (m, 1H), 7.71 (d, J = 8.9 Hz, 1H), 7.72 (d, J = 1.6 Hz, 1H), 8.04-8.12 (m, 2H ), 8.09 (dd, J = 1.4, 8.9 Hz, 1H), 8. 48 (d, J = 1.4 Hz, 1H), 8.69-8.74 (m, 1H), 13.19 (br s, 1H). APCIMS m / z: [M + H] + 474. p.f .: 230-231 ° C.

[Example 248] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] furo [2,3-b] pyridine-5-carboxamide (Compound 248) In one way similar to that in the example 187, by using furo [2, 3-b] pyridine-5-carboxylic acid (178 mg, 1.08 mmol) obtained according to the method described in Tetrahedron Letters, Vol. 35, p. 9355, 1994, instead of isonicotinic acid, the title compound 248 (209 mg, 93%) is obtained as a pale yellow solid of compound 186 (200 mg, 0.540 mmol). X H NMR (DMSO-d 6, d ppm): 6.65 (dd, J = 1.9, 3.5 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 7.47 (d, J = 3.5 Hz, 1H), 7.65 -7.75 (m, 1H), 7.73 (d, J = 1.9 Hz, 1H), 8.05-8.14 (m, 2H), 8.28 (d, J = 2.4 Hz ,. 1H), 8.70-8.76 (m, 1H) , 8.89 (d, J = 1.9 Hz, 1H), 9.07 (d, J = 1.9 Hz, 1H). APCIMS m / z: [M + H] + 417. p. f. : 234 -235 ° C.

[Example 249] Methyl N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] carbamate (Compound 249) In a manner similar to that in Example 188, using Methyl chloroformate (0.450 mL, 5.67 mmol) in place of acetyl chloride, the title compound 249 (157 mg, 43%) is obtained as a pale yellow solid of the compound 186 (300 mg, 1.11 mmol). X H NMR (CDC13, d ppm): 3.85 (s, 3 H), 6.56 (dd, J = 1.6, 3.2 Hz, 1 H), 7.44-7.53 (m, 2 H), 7.82-7.93 (, 2 H), 8.19 (d , J = 7.8 Hz, 1H), 8.71 (d, J = 4.5 Hz, 1H), 8.98 (br s, 1H). APCIMS m / z: [M + H] + 330.

[Example 250] N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] ethyl carbamate (Compound 250) In a manner similar to that in Example 188, using ethyl chloroformate (0.360 L, 3.78 mmol) in place of acetyl chloride, the title compound 250 (248 mg, 65 %) is obtained as a pale yellow solid of the compound 186 (300 mg, 1.11 mmol). X H NMR (CDCl 3, d ppm): 1.30 (t, J = 7.0 Hz, 3 H), 4.28 (q, J = 7. 0 Hz, 2H), 6.55 (dd, J = 1.9, 3.5 Hz, 1H), 7.48 (ddd, J = 0.8, 4.6, 7.6 Hz, 1H), 7.51 (dd, J = 0.8, 1.9 Hz, 1H), 7.85 (dd, J = 0.8, 3.5 Hz, 1H), 7.89 (ddd, J = 1.9, 7.6, 7.8 Hz, 1H), 8.19 (ddd, J = 0.8, 0.8, 7.8 Hz, 1H), 8.71 (ddd) , J = 0.8, 1.9, 4.6 Hz, 1H), 9.24 (br s, 1H). APCIMS m / z: [M + H] + 344. mp .: 158-159 ° C.

[Example 251] Cyclobutyl N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] carbamate (Compound 251) The compound y (249 mg, 0.839 mmol) obtained in the Reference example 25 was suspended in THF (4 mL), and cyclobutanol (0.328 mL, 4.20 mmol) was added thereto, followed by stirring for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give the title compound 251 (137 mg, 44% ) as a pale yellow solid. XH NMR (CDC13, d ppm): 1.54-1.90 (m, 2H), 2.04-2.22 (m, 2H), 2.32-2.46 (m, 2H), 5.01-5.15 (m, 1H), 6.57 (dd, J = 1.8, 3.5 Hz, 1H), 7.49 (ddd, J = 1.0, 4.8, 7.6 Hz, 1H), 7.54 (d, J = 1. 8 Hz, 1H), 7.90 (ddd, J = 1.6, 7.6, 7.9 Hz, 1H), 7.91 (d, J = 3.5 Hz, 1H), 8.19 (ddd, J = 0.9, 1.0, 7.9 Hz, 1H), 8.72 (ddd, J = 0.9, 1.6, 4.8 Hz, 1H). APCIMS m / z: [M + H] + 370. p.f .: 152-153 ° C.

[Example 252] Cyclopentyl N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] carbamate (Compound 252) In a manner similar to that in Example 251, using cyclopentanol (0.305 mL, 3.37 mmol) in place of cyclobutanol, the title compound 252 (87.3 mg, 23%) is obtained as a pale yellow solid of compound y (200 g, 0.670 mmol) obtained in reference example 25. XH NMR (CDC13, d ppm): 1.55-2.01 (m, 8H), 5.25-5.35 (m, 1H), 6.57 (dd, J = 1.6, 3.5 Hz, 1H), 7.49 (ddd, J = 1.2, 4.6 , 7.4 Hz, 1H), 7.54 (dd, J = 0.7, 1.6 Hz, 1H), 7.90 (ddd, J = 1.7, 7.4, 7.9 Hz, 1H), 7.90 (dd, J = 0.7, 3.5 Hz, 1H) , 8.19 (ddd, J = 1.0, 1.2, 7.9 Hz, 1H), 8.72 (ddd, J = 1.0, 1.7, 4.6 Hz, 1H). APCIMS m / z: [M + H] + 384. mp .: 162-163 ° C.

[Example 253] N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -carbamic acid 4-tetrahydropyranyl ester (Compound 253) In a manner similar to that in Example 251, when using tetrahydropyran-4-ol (0.321 mL, 3.37 mmol) in place of cyclobutanol, the title compound 253 (52.0 mg, 19%) was obtained as a pale yellow solid of compound y (200 mg, 0.670 mmol) obtained in Reference Example 25. XH NMR (CDC13, d ppm): 1.71-1.86 (m, 2H), 1.97-2.09 (, 2H), 3.51-3.62 (m 2H), 3.89-4.00 (m, 2H), 5.01-5.12 (m, 1H), 6.58 (dd, J = 1.8, 3.5 Hz, 1H), 7.50 (ddd, J = 1.3, 4.8, 7.6 Hz, 1H), 7.56 (dd, J = 0.7, 1.8 Hz, 1H), 7.91 (d, J = 0.7, 3.5 Hz, 1H), 7.92 (ddd, J = 1.7, 7.6, 7.9 Hz, 1H), 8.21 (ddd, J = 0.8, 1.3, 7.9 Hz, 1H), 8.72 (ddd, J = 0.8, 1.7, 4.8 Hz, 1H). APCIMS m / z: [M + H] + 400. p.f .: 144-145 ° C.

[Example 254] N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] carbamate of l-Methylpiperidin-4-yl (Compound 254) In a manner similar to that in Example 251, using l-methylpiperidin-4-ol (581 mg, 5.05 mmol) in place of cyclobutanol, the title compound 254 (167 mg, 40%) is obtained as a pale yellow solid of compound y (300 mg , 1.01 mmol) obtained in Reference Example 25. X H NMR (DMSO-d 6, d ppm): 1.59-1.74 (m, 2H), 1.87-1.99 (m, 2H), 2. 11-2.25 (m, 2H), 2.19 (s, 3H), 2.59-2.70 (m, 2H), 4.70-4.81 (, 1H), 6.61 (dd, J = 1.6, 3.2 Hz, 1H), 7.41 (dd, J = 0.5, 3. 2 Hz, 1H), 7.60-7.70 (m, 1H), 7.68 (dd, J = 0.5, 1.6 Hz, 1H), 8.03-8.08 (m, 2H), 8.64-8.69 (m, 1H). APCIMS m / z: [M + H] + 413. p.f .: 222-225 ° C.

[Example 255] N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] carbamic acid 2-Fluoro-l- (fluoromethyl) ethyl ester (Compound 255) In a similar manner to that in Example 251, using 1, 3-difluoropropan-2-ol (0.322 mL, 4.21 mmol) in place of cyclobutanol, the title compound 255 (93.2 mg, 28%) is obtained as a pale yellow compound y (250 mg, 0.841 mmol) obtained in Reference Example 25. XH NMR (CDC13, d ppm): 4.56-4.61 (m, 2H), 4.73-4.79 (m, 2H), 5.21-5.43 (m, 1H), 6.58 (dd, J = 1.8, 3.6 Hz, 1H), 7.51 (ddd, J = 1.3, 4.8, 7.6 Hz, 1H), 7.56 (dd, J = 0.7, 1.8 Hz, 1H), 7.90 (ddd) , J = 1.5, 7.6, 8.1 Hz, 1H), 7.90 (dd, J = 0.7, 3.6 Hz, 1H), 8.22 (ddd, J = 0.8, 1.3, 8.1 Hz, 1H), 8.73 (ddd, J = 0.8 , 1.5, 4.8 Hz, 1H). APCIMS m / z: [M + H] + 394. p.f .: 158-159 ° C.

[Example 256] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] morpholine-4-carboxamide (Compound 256) Compound 186 (100 mg, 0.369 mmol) was suspended in dichloromethane (3.7 mL), and carbonyldiimidazole (89.7 mg, 0.554 mmol) was added thereto at room temperature, followed by stirring for 12 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in THF (3.7 mL). The morpholine (0.0484 mL, 0.554 mmol) was added to the resulting solution, followed by stirring for 2 hours at room temperature. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 20: 1) to provide the title compound 256 (93.9 mg, 66%) as a pale yellow solid. XH NMR (CDC13, d ppm): 3.51-3.59 (m, 4H), 3.68-3.75 (m, 4H), 6.58 (dd, J = 1.8, 3.6 Hz, 1H), 7.48 (ddd, J = 1.2, 4.8 , 7.6 Hz, 1H), 7.55 (d, J = 1.8 Hz, 1H), 7.89 (ddd, J = 1.7, 7.6, 7.9 Hz, 1H), 7.96 (d, J = 3.6 Hz, 1H), 8.18 (ddd , J = 0.8, 1.2, 7.9 Hz, 1H), 8.74 (ddd, J = 0.8, 1.7, 4.8 Hz, 1H). APCIMS m / z: [M + H] + 385. p.f. : 144-145 ° C.

[Example 257] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] piperidine-1-carboxamide (Compound 257) The compound y (130 mg, 0.437 mmol) obtained in Reference Example 25 was suspended in THF (4.4 mL), and piperidine (64.9 μL, 0.656 mmol) was added thereto, followed by stirring at room temperature for 20 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled continuously under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give the title compound 257 (66.5 mg, 40%) as a pale yellow solid. XH NMR (CDC13, d ppm): 1.57-1.71 (m, 6H), 3.48-3.56 (m, 4H), 6.57 (dd, J = 1.7, 3.5 Hz, 1H), 7.46 (ddd, J = 1.0, 4.6 , 7.6 Hz, 1H), 7.55 (d, J = 1.7 Hz, 1H), 7.88 (ddd, J = 1.7, 7.6, 7.9 Hz, 1H), 7.94 (d, J = 3.5 Hz, 1H), 8.17 (ddd , J = 1.0, 1.1, 7.9 Hz, 1H), 8.73 (ddd, J = 1.1, 1.7, 4.6 Hz, 1H). APCIMS m / z: [M + H] + 383. p.f. : 182-185 ° C.

[Example 258] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -N'-isopropylurea (Compound 258) In a manner similar to that in Example 257, when using isopropylamine (0.0900 mL, 1.01 mmol) in place of piperidine, the title compound 258 (134 mg, 56%) is obtained as a pale yellow solid of compound y (200 mg, 0.670 mmol) obtained in the reference example 25. X H NMR (DMSO-d 6, d ppm): 1.51 (d, J = 6.5 Hz, 3 H), 3.30 (d, J = 6.5 Hz, 3 H), 3.75-3.87 (m, 1 H), 6.50 (br d , J = 7.3 Hz, 1H), 6.58 (dd, J = 1.9, 3.5 Hz, 1H), 7.37 (dd, J = 0.8, 3.5 Hz, 1H), 7.59-7.66 (m, 1H), 7.63 (dd, J = 0.8, 1.9 Hz, 1H), 7.99-8.08 (m, 2H), 8.62-8.66 (m, 1H), 10.90 (br s, 1H). APCIMS m / z: [M + H] + 357. m.p .: 182-186 ° C.

[Example 259] N-tert-Butyl-N '- [4- (2-furyl) -5-pyridin-2-ylcarbonyl) thiazol-2-yl] urea (Compound 259) In a manner similar to that in the example 257, using tert-butylamine (0.130 mL, 1.26 mmol) in place of piperidine, the title compound 259 (187 mg, 46%) is obtained as a pale yellow solid of compound y (250 mg, 0.840 mmol) obtained in the reference example 25.

X H NMR (DMSO-d 6, d ppm): 1.33 (s, 9 H), 6.49 (br s, 1 H), 6.59 (dd, J = 1.9, 3.5 Hz, 1 H), 7.40 (dd, J = 0.8, 3.5 Hz , 1H), 7.59-7.62 (, 1H), 7.65 (dd, J = 0.8, 1.9 Hz, 1H), 8.00-8.09 (m, 2H), 8.65-8.69 (m, 1H), 10.71 (br s, 1H ). . - APCIMS m / z: [M + H] + 371. m.p .: 123-124 ° C.

[Example 260] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -N '- (2-methoxyethyl) urea (Compound 260) In a manner similar to that in Example 257, using 2-methoxyethylamine (0.0790 mL, 1.01 mmol) in place of piperidine, the title compound 260 (142 mg, 57%) is obtained as a pale yellow solid of compound y (200 mg, 0.670 mmol ) obtained in reference example 25. XH NMR. (DMSO-de, d ppm): 3.27-3.38 (m, 2H), 3.29 (s, 3H), 3.42 (t, J = 4.9 Hz, 2H), 6.59 (dd, J = 1.9, 3.5 Hz, 1H) , 6.74 (t, J = 5.4 Hz, 1H), 7.38 (dd, J = 0.5, 3.5 Hz, 1H), 7.59-7.66 (m, 1H), 7.63 (dd, J = 0.5, 1.9 Hz, 1H), 8.00-8.09 (m, 2H), 8.01-8.07 (m, 1H), 11.09 (br s, 1H). APCIMS m / z: [M + H] + 373. mp .: 150-151 ° C.

[Example 261] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -N '- (3-methoxypropyl) urea (Compound 261) In a manner similar to that in Example 257, when using 3-methoxypropylamine (0.102 mL, 1.01 mmol) in place of piperidine, the title compound 261 (145 mg, 56%) is obtained as a pale yellow solid of compound y (200 mg, 0.670 mmol) obtained in reference example 25. XH NMR (DMS0 -d6, d ppm): 1.65-1.76 (m, 2H), 3.17-3.26 (m, 2H), 3.25 (s, 3H), 3.37 (t, J = 6.2 Hz, 2H), 6.58 (dd, J = 1.6, 3.2 Hz, 1H), 6.67 (t, J = 6.3 Hz, 1H), 7.38 (dd, J = 0.8, 3.2 Hz, 1H), 7.59-7.66 (m, 1H), 7.63 (dd, J = 0.8 , 1.6 Hz, 1H), 7.99-8.08 (m 2H), 8.62-8.66 (m, 1H), 11.18 (br s, 1H). APCIMS m / z: [M + H] + 387. p.f .: 169-170 ° C.

[Example 262] 2-Chloro-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] acetamide (Compound 262) Compound 186 (0.900 g, 2.42 mmol) was dissolved in THF (10 mL), and N, N-dimethylaminopyridine (29.6 mg, 0.242 nmol), triethylamine (0.740 mL, 5.32 mmol) and chloroacetyl chloride (0.390 mL, 4.84 mmol) were added thereto under ice cooling, followed by stirring at room temperature for 2 hours. In addition, triethylamine (0.740 mL, 5.32 mmol) and Chloroacetyl chloride (0.390 mL, 4.84 mmol) were added to the reaction mixture under cooling on ice, followed by stirring 1 hour at room temperature. Water and a saturated aqueous solution of sodium hydrogen carbonate were added to the reaction mixture, and the precipitated solid was collected by filtration. The resulting solid was purified through silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give the title compound 262 (0.810 g, 96%) as pale yellow crystals. XH NMR (CDC13, d ppm): 4.30 (s, 2H), 6.57 (dd, J = 1.6, 3.5 Hz, 1H), 7.49 (ddd, J = 1.1, 4.6, 7.6 Hz, 1H), 7.55 (dd, J = 0.8, 1.6 Hz, 1H), 7.85 (dd, J = 0.8, 3.5 Hz, 1H), 7.89 (ddd, J = 1.9, 7.6, 8.1 Hz, 1H), 8.19 (ddd, J = 1.0, 1.1, 8.1 Hz, 1H), 8.72 (ddd, J = 1.0, 1.9, 4.6 Hz, 1H), 10.10 (br s, 1H). APCIMS m / z: [35CIM + H] + 348, [37CIM + H] + 350. p.f .: 184-185 ° C.

[Example 263] 2-Bromo-N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl-acetamide (Compound 263) In a manner similar to that in Example 262, using Bromoacetyl bromide in place of chloroacetyl chloride, the title compound 263 (230 mg, 72%) is obtained as a pale yellow solid of compound 186 (300 mg, 1.11 mmol).

X H NMR (CDCl 3, d ppm): 4.05 (s, 2H), 6.56 (dd, J = 1.6, 3.5 Hz, 1H), 7.46 (ddd, J = 1.4, 4.6, 7.6 Hz, 1H), 7.52 (dd, J = 0.8, 1.6 Hz, 1H), 7.78 (dd, J = 0.8, 3.5 Hz, 1H), 7.89 (ddd, J = 1.9, 7.6, 7.8 Hz, 1H), 8.17 (ddd, J = 0.8, 1.4, 7.8 Hz, 1H), 8.71 (ddd, J = 0.8, 1.6, 4.6 Hz, 1H).

[Example 264] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] morpholinoacetamide (Compound 264) Compound 263 (196 mg, 0.49 mmol) was dissolved in THF (3.3 mL), morpholine (0.128 mL, 1.47 mmol) was added thereto, followed by stirring at room temperature for 1 hour.

The reaction mixture was concentrated under reduced pressure, and the resulting residue was recrystallized from a mixed solvent (5: 1) of hexane and acetone to give the title compound 264 (139 mg, 71%) as a pale yellow solid. . H NMR (DMSO-de, d ppm): 2.48-2.62 (m, 4H), 3.36 (s, 2H), 3.58-3.64 (m, 4H), 6.62 (dd, J = 1.9, 3.5 Hz, 1H), 7. 41 (dd, J = 0.8, 3.5 Hz, 1H), 7.63-7.70 (m, 1H), 7.68 (dd, J = 0.8, 1.9 Hz, 1H), 8.05-8.10 (m, 2H), 8.66-8.70 (m, 1H). APCIMS m / z: [M + H] + 399. p.f .: 170-171 ° C.

[Example 265] 2- (cis-2, 6-Dimethylmorpholino) -N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] acetamide (Compound 265) In one way similar to that in Example 264, using cis-2,6-dimethylmorpholine in place of morpholine, the title compound 265 (361 mg, 98%) is obtained as pale yellow crystals of compound 262 (300 mg, 0.860 mmol) instead of compound 263. X H NMR (DMS0-d 6, d ppm): 1.05 (d, J = 6.3 Hz, 6H), 1.84-1.97 (m, 2H), 2.74-2.82 (m, 2H), 3.34 (s) , 2H), 3.55-3.68 (m, 2H), 6. 61 (dd, J = 1.6, 3.5 Hz, 1H), 7.40 (d, J = 3.5 Hz, 1H), 7. 71-7.79 (m, 2H), 8.03-8.08 (m, 2H), 8.64-8.70 (m, 1H). APCIMS m / z: [M + H] + 427. p. f. : 188 -191 ° C.

[Example 266] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (4-methylpiperidino) acetamide (Compound 266) In a manner similar to that in Example 264, using 4-methylpiperidine in place of morpholine, the title compound 266 (297 mg, 84%) is obtained as pale yellow crystals of compound 262 (300 mg, 0.860 mmol) in place of Compound 263. XH NMR (DMSO-d6, d ppm): 0.90 (d, J = 6.1 Hz, 3H), 1.10-1.41 (, 3H), 1.52-1.63 (m, 2H), 2.13-2.24 (, 2H), 2.80-2.90 (m, 2H), 3.33 (s, 2H), 6.62 (dd, J = 1.6, 3.5 Hz, 1H), 7.41 (d, J = 3.5 Hz, 1H), 7.63-7.71 (m, 2H), 8.02-8.11 (, 2H), 8.66-8.70 (m, 1H). APCIMS m / z: [M + H] + 411. p.f .: 104-106 ° C.

[Example 267] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (4-methoxypiperidino) acetamide hydrochloride (Compound 267) In a manner similar to that in Example 264, using 4-methoxypiperidine (0.280 mL, 2.28 mmol) in place of morpholine, a free form of the title compound (299 mg, 92%) is obtained as pale yellow crystals of compound 263 (300 mg, 0.760 mmol). The resulting free form (227 mg, 0.531 mmol) was dissolved in ethanol (2.3 mL), a 4 mol / L solution of hydrogen chloride (0.15 mL, 0.584 mmol) in ethyl acetate was added thereto, followed by stirring at room temperature for 30 minutes. The precipitated solid was collected by filtration to provide the title compound 267 (187 mg, 76%) as pale yellow crystals. X H NMR (DMSO-d 6, d ppm): 1.62-2.24 (m, 4H), 3.13-3.68 (m, 8H), 4.33 (s, 2H), 6.65 (dd, J = 1.6, 3.5 Hz, 1H), 7.47 (d, J = 3. 5 Hz, 1H), 7.66-7.74 (m, 1H), 7.73 (d, J = 1.6 Hz, 1H), 8.05-8.15 (m, 2H), 8.68-8.73 (m, 1H). APCIMS m / z: [M + H] + 427. p.f .: 220-232 ° C (decomposition) [Example 268] 2- [3- (N, N-Diethylcarbamoyl) piperidino] -N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] acetamide hydrochloride (Compound 268) In a manner similar to that in Example 264, when using 3- (N, N-diethylcarbamoyl) piperidine in place of morpholine, a free form of the title compound (426 mg, 100%) is obtained as pale yellow crystals. of compound 262 (300 mg, 0.860 mmol) in place of Compound 263. The resulting free form (341 mg, 0.688 mmol) was dissolved in ethanol (3.4 mL), a 4 mol / L solution of hydrogen chloride (0.19 mL, 0.757 mmol) in ethyl acetate was added thereto, followed by stirring at room temperature for 12 hours. The precipitated solid was collected by filtration to give the title compound 268 (267 mg, 73%) as pale yellow crystals. X H NMR (DMS0-d 6, d ppm): 1.06 (t, J = 7.0 Hz, 3 H), 1.17 (t, J = 6.8 Hz, 3 H), 1.43-2.15 (m, 4 H), 3.08- 3. 83 (m, 9H), 4.36 (s, 2H), 6.65 (dd, J = 1.9, 3.5 Hz, 1H), 7.48 (d, J = 3.5 Hz, 1H), 7.66-7.77 (m, 2H), 8.05 -8.15 (m, 2H), 8.70-8.76 (m, 1H). APCIMS m / z: [M + H] + 496. p.f. : 180-185 ° C.

[Example 269] 2- (1, 4-Dioxa-8-azaspiro [4.5] of can-8 -i 1) -N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazole- 2-yl] acetamide (Compound 269) In a manner similar to that in Example 264, using 1,4-dioxa-8-azaspiro [4.5] decane in place of morpholine, the title compound 269 (284 mg, 73 %) is obtained as pale yellow crystals of compound 262 (300 mg, 0.860 mmol) in place of Compound 263. X H NMR (DMSO-d 6, d ppm): 1.62-1.70 (m, 4 H), 2.58-2.66 (m, 4H), 3.39 (s, 2H), 3.86 (s, 4H), 6.62 (dd, J = 1.6, 3.0 Hz, 1H), 7.42 (d, J = 3.0 Hz, 1H), 7.64-7.71 (m, 2H) ), 8.03-8.10 (m, 2H), 8.67-8.71 (m, 1H). APCIMS m / z: [M + H] + 455. p.f. : 188-204 ° C.

[Example 270] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (4-piperidinopiperidino) acetamide (Compound 270) In a manner similar to that in Example 264, using 4-piperidinespiperidine (0.390 mL, 2.28 mmol) in place of morpholine, the title compound 270 (362 mg, 99%) is obtained as pale yellow crystals of compound 263 (300 mg, 0.760 mmol). X H NMR (DMSO-d 6, d ppm): 1.22-2.01 (m, 14H), 2.16-2.42 (m, 2H), 2.91-3.12 (m, 3H), 3.39 (s, 2H), 6.62 (dd, J = 1.9, 3.5 Hz, 1H), 7.41 (d, J = 3.5 Hz, 1H), 7.63-7.71 (m, 2H), 8.05-8.12 (m, 2H), 8.65-8.70 (m, 1H). APCIMS m / z: [M + H] + 480. p.f. : 214-220 ° C (decomposition).

[Example 271] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (4-morpholinopiperidino) acetamide (Compound 271) In a manner similar to that in Example 264, by using 4-morph olinopiperidine (391 mg, 2.28 mmol) in place of morpholine, the title compound 271 (349 mg, 95%) is obtained as pale yellow crystals of compound 263 (300 mg, 0.760 mmol). X H NMR (DMSO-de, d ppm): 1.35-1.63 (m, 2H), 1.63-1.90 (m, 2H), 2.06-2.35 (m, 3H), 2.35-2.67 (m, 1H), 2.79- 3.02 (m, 2H), 3.22-3.49 (m, 5H), 3.49-3.73 (m, 4H) , 6.62 (dd, J = 1.6, 3.5 Hz, 1H), 7.42 (d, J = 3.5 Hz, 1H), 7.63-7.70 (m, 2H), 8.03-8.11 (m, 2H), 8.66-8.70 (m , 1 HOUR) . APCIMS m / z: [M + H] + 482. p.f .: 149-150 ° C.

[Example 272] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (4-methylpiperazin-1-yl) acetamide (Compound 272) In a manner similar to that in Example 264, using 1-methylpiperazine (0.0960 mg, 0.870 mmol) in place of morpholine, the title compound 272 (128 mg, 100%) is obtained as pale yellow crystals of compound 262 (100 mg, 0.290 mmol) instead of Compound 263. X H NMR (DMSO-d 6, d ppm): 2.68 (s, 3 H), 2.61-3.24 (m, 8H), 3.49 (s, 2H), 6.60-6.64 (m, 1H), 7.40-7.44 (m, 1H), 7.63-7.71 (m, 2H), 8.03-8.12 (m, 2H), 8.65-8.71 ( , 1 HOUR) . APCIMS m / z: [M + H] + 412. p.f .: 136-145 ° C.

[Example 273] 2- (4-Ethylpiperazin-1-yl) -N- [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -tatamide (Compound 273) In one way similar to that in example 264, when using 1-ethylpiperazine (0.330 mg, 2. "58 mmol) in place of morpholine, the title compound 273 (360 mg, 98%) is obtained as pale yellow crystals of the compound. 262 (300 mg, 0.860 mmol) instead of Compound 263. XH NMR (DMSO-d6, d ppm): 0.99 (t, J = 7.0 Hz, 3H), 2.32 (q, J = 7.0 Hz, 2H), 2.49 -2.60 (m, 4H), 3.21-3.44 (m, 4H), 3.34 (s, 2H), 6.61 (dd, J = 1.9, 4.1 Hz, 1H), 7.41 (d, J = 4.1 Hz, 1H), 7.62-7.70 (m, 1H), 7.68 (d, J = 1.9 Hz, 1H), 8.04-8.10 (m, 2H), 8.66-8.70 (m, 1H) APCIMS m / z: [M + H] + 426. mp: 142-144 ° C.

[Example 274] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (4-isopropylpiperazin-1-yl) acetamide (Compound 274) In one way similar to that in Example 264, when using 1-isopropylpiperazine (332 mg, 2.58 mmol) in place of morpholine, the title compound 274 (316 mg, 84%) is obtained as pale yellow crystals of the Compound 262 (300 mg, 0.860 mmol) in place of Compound 263. X H NMR (DMSO-d 6, d ppm): 0.97 (d, J = 6.5 Hz, 6 H), 2.43-2.68 (m, 5 H), 3.25-3.36 (m, 4H), 3.33 (s, 2H), 6.61 (dd, J = 1.9, 3.5 Hz, 1H), 7.41 (d, J = 3.5 Hz, 1H), 7.63-7.71 (m, 2H), 8.04- 8.09 (m, 2H), 8.66-8.70 (m, 1H). APCIMS m / z: [M + H] + 440. p.f .: 154-155 ° C.

[Example 275] 2- (4-Acetylpiperazin-1-yl) -N ~ [4- (2-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] acetamide (Compound 275) In one way similar to that in Example 264, using 1-acetylpiperazine (332 mg, 2.58 mmol) in place of morpholine, the title compound 275 (335 mg, 89%) is obtained as pale yellow crystals of compound 262 (300 mg, 0.860 mmol) instead of Compound 263. X H NMR (DMSO-d 6, d ppm): 1.99 (s, 3 H), 2.53-2.61 (m, 2 H), 3.27-3.35 (m, 2 H), 3.40-3.51 (m, 4 H), 3.42 (s, 2 H) ), 6.62 (dd, J = 1.9, 3.5 Hz, 1H), 7.43 (d, J = 3.5 Hz, 1H), 7.62-7.71 (m, 1H), 7.69 (d, J = 1.9 Hz, 1H), 8.05-8.11 (m, 2H), 8.67-8.71 (m, 1H). APCIMS m / z: [M + H] + 440. p.f .: 170-171 ° C.

[Example 276] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (4-phenylpiperazin-1-yl) acetamide (Compound 276) In one way similar to that in Example 264, using 1-phenylpiperazine (0.40 mL, 2.58 mmol) in place of morpholine, the title compound 276 (320 mg, 79%) is obtained as pale yellow crystals of compound 262 (300 mg, 0.860 mmol) in place of Compound 263. H NMR (DMS0-d6, d ppm): 2.66-2.74 (m, 4H), 3.13-3.21 (m, 4H), 3.43 (s, 2H), 6.61 (dd, J = 1.9, 3.2 Hz, 1H), 6.78 (t, J = 7. 6 Hz, 1H), 6.94 (d, J = 8.9 Hz, 2H), 7.21 (dd, J = 7.6, 8.9 Hz, 2H), 7.40 (d, J = 3.2 Hz, 1H), 7.62-7.69 (m, 2H), 8.05- 8.09 (m, 2H), 8.66-8.70 (m, 1H). APCIMS m / z: [M + H] + 474. p.f .: 203-204 ° C.

[Example 277] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- [4- (2-pyridyl) piperazin-1-yl] acetamide (Compound 277) In a manner similar to that in Example 264, using 1- (2-pyridyl) piperazine in place of morpholine, the title compound 277 (346 mg, 85%) is obtained as pale yellow crystals of compound 262 ( 300 mg, 0.860 mmol) instead of Compound 263. XH NMR (DMSO-d6, d ppm): 2.61-2.69 (m, 4H), 3.43 (s, 2H), 3.49-3.57 (m, 4H), 6.60-6.70 (m, 2H), 6.82 (d, J = 8.9 Hz, 1H), 7.42 (d, J = 3.5 Hz, 1H), 7.48-7.57 (m , 1H), 7.63-7.71 (m, 2H), 8.05-8.13 (m, 3H), 8.67-8.72 (m, 1H). APCIMS m / z: [M + H] + 475. p.f .: 215-218 ° C.

[Example 278] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- [4- (2-pyrimidinyl) piperazin-1-yl] acetamide (Compound 278) Compound 262 (300 mg, 0.860 mmol) was dissolved in THF (5.0 mL) and 1- (2-pyrimidinyl) piperazine (0.370 mL, 2.58 mmol) was added thereto, followed by stirring at room temperature for 16 hours. . In addition, 1- (2-pyrimidinyl) piperazine (0.370 mL, 2.58 mmol) was added to the reaction mixture, followed by stirring at room temperature for 2 hours. Water and saturated aqueous sodium bicarbonate solution were added to the reaction mixture, and the precipitated solid was collected by filtration. The resulting solid was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 2) to give the title compound 278 (345 mg, 84%) as pale yellow crystals.

X H NMR (DMSO-dg, d ppm): 2.55-2.65 (m, 4H), 3.43 (s, 2H), 3.73-3.82 (m, 4H), 6.62 (t, J = 4.9 Hz, 1H), 6.62 ( dd, J = 1.9, 3.5 Hz, 1H), 7.42 (d, J = 3.5 Hz, 1H), 7.63-7.70 (m, 1H), 7.68 (d, J = 1.9 Hz, 1H), 8.05-8.10 (m , 2H), 8.36 (d, J = 4.9 Hz, 2H), 8.67-8.71 (m, 1H), 12.60 (br s, 1H). APCIMS m / z: [M + H] + 476. p.f .: 199-200 ° C.

[Example 279] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- [4- (tetrahydropyran-4-yl) piperazin-1-yl] acetamide (Compound 279) In a manner similar to that in Example 264, when using tetrahydropyran-4-ylpiperazine (391 mg, 2.28 mmol) in place of morpholine, the title Compound 279 (267 mg, 73%) was obtained as yellow crystals. pale from Compound 263 (300 mg, 0.760 mmol). X H NMR (DMSO-de, d ppm): 1.28-1.47 (m, 2H), 1.64-1.76 (m, 2H), 2. 22-2.66 (m, 7H), 3.14-3.42 (m, 6H), 3.82-3.92 (m, 2H), 6.62 (dd, J = 1.6, 3.2 Hz, 1H), 7.42 (d, J = 3.2 Hz, 1H), 7.63-7.71 (m, 2H), 8.02-8.11 (m, 2H), 8.66-8.70 (m, 1H). APCIMS m / z: [M + H] + 482. p. f. : 172-188 ° C.

[Example 280] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (l-methyl-2-oxopiperazin-4-yl) acetamide hydrochloride ( Compound 280) In a manner similar to that in Example 264, by using 1-met il-2-oxopiperazine in place of morpholine, a free form of the title compound (307 mg, 95%) was obtained as pale yellow crystals. from Compound 263 (300 mg, 0.760 mmol). The resulting free form (250 mg, 0.588 mmol) was dissolved in ethanol (2.5 mL), a 4 mol / L solution of hydrogen chloride (0.16 mL, 0.647 mmol) in ethyl acetate was added thereto, followed by stirring at room temperature for 30 minutes. The precipitated solid was collected by filtration to provide the title compound 280 (177 mg, 65%) as pale yellow crystals. X H NMR (DMS0-d 6, d ppm): 2.89 (s, 3 H), 3.38-3.69 (m, 4 H), 3.84-3.90 (m, 2 H), 4.22-4.32 (m, 2 H), 6.64 (dd, J = 1.9, 3.5 Hz, 1H), 7.48 (d, J = 3.5 Hz, 1H), 7.65-7.75 (m, 2H), 8.05-8.15 (m, 2H), 8.68-8.73 (m, 1H). APCIMS m / z: [M + H] + 426. p.f .: 170-188 ° C.

[Example 281] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2- (1,3-thiazolidin-3-yl) acetamide (Compound 281) In a similar manner to that in Example 264, using 1,3-thiazolidine in place of morpholine, the title Compound 281 (288 mg, 83%) was obtained, as pale yellow crystals from Compound 262 (300 mg , 0.860 mmol) in place of Compound 263. XH NMR (DMSO-d6, d ppm): 2.82-2.90 (m, 2H), 3.07-3.15 (m, 2H), 3.36-3.48 (m, 2H), 4.11 ( s, 2H), 6.62 (dd, J = 1.9, 3.5 Hz, 1H), 7.42 (d, J = 3.5 Hz, 1H), 7.62-7.72 (m, 2H), 8.05-8.12 (m, 2H), 8.67 -8.71 (m, 1H). APCIMS m / z: [M + H] + 401. p.f .: 153-155 ° C.

[Example 282] N- [4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] -2-thiomorpholinoacetamide (Compound 282) In a manner similar to that in Example 264, using thiomorpholine (0.240 mL, 2.58 mmol) in place of morpholine, Title Compound 282 (326 mg, 92%) was obtained as pale yellow crystals from Compound 262 (300 mg, 0.860 mmol) in place of Compound 263 H NMR (DMSO-de, d ppm): 2.60-2.69 (m, 4H), 2.78-2.86 (, 4H), 3. 41 (s, 2H), 6.62 (dd, J = 1.9, 3.5 Hz, 1H), 7.42 (d, J = 3.5 Hz, 1H), 7.62-7.72 (m, 2H), 8.02-8.10 (m, 2H) , 8.66-8.71 (m, 1H). APCIMS m / z: [M + H] + 415. p.f .: 148-149 ° C.

[Example 283] N- [4- (2-Furyl) -5- (6-methoxypyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 283) The 2-bromo-6-methoxypyridine ( 0.274 mL, 2.23 mmol) was dissolved in THF (1 mL), and a 1.58 mol / L solution of n-butyllithium in n-hexane (1.42 L, 2.23 mmol) was added thereto in an argon stream at -78. ° C, followed by stirring for 15 minutes at -78 ° C. A solution of Compound 98 (200 mg, 0.558 mmol) in THF (2 mL) was added dropwise to the reaction mixture, followed by stirring at room temperature for 1.5 hours. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 9) to provide the title Compound 283 (77.0 mg, 34%).

H NMR (DMSO-d6, d ppm): 4.02 (s, 3H), 6.66 (dd, J = 1.7, 3.5 Hz, 1H), 7.15 (d, J = 8.3 Hz, 1H), 7.51 (d, J = 3.5 Hz, 1H), 7.74-7.77 (m, 2H), 7.98 (dd, J = 8.3, 8.3 Hz, 1H), 8.03 (d, J = 6.1 Hz, 2H), 8.83 (d, J = 6.1 Hz, 2H), 13.49 (br s, 1H). APCIMS m / z: [M + H] + 407. p.f .: 247-250 ° C. [Example 284] N- [4- (2-Furyl) -5- (6-methylpyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 284) In a manner similar to that in Example 283, using 2-bromo-6-methylpyridine in place of 2-bromo-6-methoxypyridine, the title Compound 284 (70.0 mg, 32%) was obtained from Compound 98 (200 mg, 0.558 mmol). X H NMR (DMSO-d 6, d ppm): 2.56 (s, 3 H), 6.64 (dd, J = 1.7, 3.6 Hz, 1 H), 7.44 (d, J = 3.6 Hz, 1 H), 7.52-7.55 (m, 1H), 7.71 (d, J = 1.7 Hz, 1H), 7.89-7.99 (m, 2H), 8.05 (d, J = 5.9 Hz, 2H), 8.84 (d, J = 5.9 Hz, 2H), 13.49 ( br s, 1H). APCIMS m / z: [M + H] + 391. mp .: 238-241 ° C.

[Example 285] N- [4- (2-Furyl) -5- (6-methylpyridin-2-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 285) In a manner similar to that in Example 283, when using 2-bromo-6-methylpyridine instead of 2-bromo-6- methoxypyridine, Compound of title 285 (765 mg, 99%) was obtained from Compound 134 (707 mg, 2.00 mmol) in place of Compound 98. XH NMR (CDC13, d ppm): 1.48 (s, 9H), 2.68 (s, 3H), 6.54 (dd, J = 1.7, 3.3 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 1.7 Hz, 1H), 7.75 (t, J) = 7.6 Hz, 1H), 7.82 (d, J = 3.3 Hz, 1H), 7.95 (d, J = 7.6Hz, 1H), 9.33 (brs, 1H).

[Example 286] 2-Amino-4- (2-furyl) thiazol-5-yl-6-methylpyridin-2-yl ketone (Compound 286) In a manner similar to that in Example 186, using Compound 285 (765 mg, 1.98 mmol) in place of Compound 185, Compound of title 286 (553 mg, 98%) was obtained. 1 H NMR (DMSO-d 6, 5 Ppm): 2.45 (s, 3 H), 6.53 (dd, J = 1.8, 3.3 Hz, 1 H), 7.36 (d, J = 3.3 Hz, 1 H), 7.39-7.42 (m, 1H) / 7.54 (d, J = 1.8 Hz, 1H), 7.73-7.89 (m, 2H), 8.00 (br s, 2H).

[Example 287] N- [4- (2-Furyl) -5- (6-methylpyridin-2-ylcarbonyl) thiazol-2-yl] -2-morpholinoacetamide (Compound 287) Compound 286 (150 mg, 0.526 mmol) and triethylamine (0.367 mL, 2.63 mmol) were dissolved in THF (4 mL), and bromoacetyl bromide (0.206 mL, 2.37 mmol) was added thereto at 0 ° C, followed by stirring for 1 hour at room temperature. ambient. In addition, a solution (2 mL) of morpholine (0.689 mL, 7.89 mmol) and triethylamine (1.10 mL, 7.89 mmol) in THF was added thereto at 0 ° C, followed by stirring for 1 hour at room temperature. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography to provide the title Compound 287 (150 mg, 69%). X H NMR (DMSO-d 6, d ppm): 2.51 (s, 3 H), 2.54 (t, J = 4.6 Hz, 4 H), 3.36 (s, 2 H), 3.62 (t, J = 4.6 Hz, 4 H), 6.61 (dd, J = 1.7, 3.5 Hz, 1H), 7.38 (d, J = 3.5 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.66 (d, J = 1.7 Hz, 1H), 7.85 -7.97 (m, 2H), 12.5 (br s, 1H). APCIMS m / z; [M + H] + 413.

[Example 288] N- [4- (2-Furyl) -5- (6-methylpyridin-2-ylcarbonyl) thiazol-2-yl] -2- (4-hydroxypiperidino) acetamide (Compound 288) In a manner similar to that in Example 287, by using 4-hydroxypiperidine in place of morpholine, the title Compound 288 (143 mg, 64%) was obtained from Compound 286 (150 mg, 0.526 mmol). X H NMR (CDC13, d ppm): 1.65-1.78 (m, 2H), 1.95-2.05 (m, 2H), 2. 41-2.50 (m, 2H), 2.69 (s, 3H), 2.80-2.88 (m, 2H), 3.29 (s, 2H), 3.79-3.85 (, 1H), 6.58 (dd, J = 1.7, 3.5 Hz , 1H), 7.33 (d, J = 7.9 Hz, 1H), 7.56 (dd, J = 0.7, 1.7 Hz, 1H), 7.77 (dd, J = 7.9, 7.9 Hz, 1H), 7.85 (dd, J = 0.7, 3.5 Hz, 1H), 7.98 (d, J = 7.9 Hz, 1H). APCIMS m / z: [M + H] + 427. [Example 289] N- [4- (2-Furyl) -5- (6-methylpyridin-2-ylcarbonyl) thiazol-2-yl] -2- dichlorohydrate (4-methylpiperazin-1-yl) acetamide (Compound 289) In a manner similar to that in Example 287, by using 1-methylpiperazine in place of morpholine, a free form of the title Compound 289 was obtained from Compound 286 (150 mg, 0.526 mmol). The resulting free form was dissolved in acetone (3 mL), and a solution of ethyl acetate of 4 mol / L hydrogen chloride (0.394 mL, 1.58 mmol) was added thereto. The precipitated solid was collected by filtration to provide the title Compound 289 (163 mg, 62%). X H NMR (DMSO-dg, d ppm): 2.52 (s, 3H), 2.77 (s, 2H), 2.79 (s, 3H), 2.93-3.89 (m, 8H), 6.62 (dd, J = 1.7, 3.3 Hz, 1H), 7.41 (d, J = 3.3 Hz, 1H), 7.51-7.54 (m, 1H), 7.68 (d, J = 1.7 Hz, 1H), 7.87-7.98 (m, 2H). APCIMS m / z: [M + H] + 426.

[Example 290] 2- (4-Ethylpiperazin-1-yl) -N- [4- (2-furyl) -5- (6-methylpyridin-2-ylcarbonyl) thiazol-2-yl] acetamide dichlorohydrate (Compound 290) In a manner similar to that in Example 287, by using 1-ethylpiperazine in place of morpholine, a free form of the title Compound 290 was obtained from the Compound 286 (100 mg, 0.350 mmol). The resulting free form was dissolved in acetone (3 mL), and a 4 mol / L solution of hydrogen chloride (0.263 mL, 1.05 mmol) in ethyl acetate was added thereto. The precipitated solid was collected by filtration to provide the title Compound 290 (89.0 mg, 49%). X H NMR (DMSO-d 6, d ppm): 1.23-1.28 (m, 3H), 2.52 (s, 3H), 3.05-3.81 (m, 12H), 6.63 (dd, J = 1.8, 3.3 Hz, 1H), 7.41 (d, J = 3.3 Hz, 1H), 7.52-7.54 (m, 1H), 7.68 (d, J = 1.8 Hz, 1H), 7. 87-7.98 (m, 2H). APCIMS m / z: [M + H] + 440.

[Example 291] 2- (4-Acetylpiperazin-1-yl) -N- [4- (2-furyl) -5- (6-methylpyridin-2-ylcarbonyl) thiazol-2-yl] acetamide (Compound 291) In a manner similar to that in Example 287, when using 1-acetylpiperazine in place of morpholine, the title Compound 291 (136 mg, 86%) was obtained as color crystals. pale yellow from Compound 286 (100 mg, 0.350 mmol). X H NMR (CDC13, d ppm): 2.12 (s, 3 H), 2.70 (s, 3 H), 2.59-2.64 (m, 4 H), 3.33 (s, 2 H), 3.56-3.74 (m, 4 H), 6.58 ( dd, J = 1.7, 3.5 Hz, 1H), 7.34 (d, J = 7.7 Hz, 1H), 7.57 (d, J = 1.7 Hz, 1H), 7.78 (dd, J = 7.7, 7.7 Hz, 1H), 7.88 (d, J = 3.5 Hz, 1H), 7.99 (d, J = 7.7 Hz, 1H), 10.39 (br s, 1H). APCIMS m / z: [M + H] + 454.

[Example 292] N- [4- (2-Furyl) -5- (6-methylpyridin-2-ylcarbonyl) thiazol-2-yl] -2- [4- (2-pyridyl) piperazin-1-yl] acetamide (Compound 292) In a manner similar to that in Example 287, by using 1- (2-pyridyl) piperazine in place of morpholine, the title Compound 292 (104 mg, 61%) was obtained as pale yellow crystals a from Compound 286 (100 mg, 0.350 mmol). X H NMR (DMSO-d 6, d ppm): 2.70 (s, 3 H), 2.74 (t, J = 5.1 Hz,) 4H), 3.36 (s, 2H), 3.66 (t, J = 5.1 Hz, 4H), 6.57 (dd, J = 1.7, 3.5 Hz, 1H), 6.65-6.68 (m, 2H), 7.34 (d, J = 7.8 Hz, 1H), 7.48-7.54 (m, 1H), 7.55 (d, J = 1.7 Hz, 1H), 7.77 (t, J = 7. 8 Hz, 1H), 7.85 (d, J = 3.5 Hz, 1H), 7.99 (d, J = 7.8 Hz, 1H), 8.20-8.22 (m, 1H), 10.45 (br s, 1H). APCIMS m / z: [M + H] + 489.

[Example 293] N- [4- (2-Furyl) -5- (6-methylpyridin-2-ylcarbonyl) thiazol-2-yl] -2- (4-morpholinopiperidino) acetamide (Compound 293) In a manner similar to that in Example 287, when using 4-morpholinopiperidine instead of morpholine, the Title 293 compound (157 mg, 90%) was obtained as pale yellow crystals from Compound 286 (100 mg, 0.350 mmol). XH NMR (CDC13, d ppm): 1.58-1.87 (m, 5H), 2.28-2.36 (m, 2H), 2.57 (t, J = 4.5 Hz, 4H), 2.69 (s, 3H), 2.94-2.98 ( m, 2H), 3. 27 (s, 2H), 3.74 (t, J = 4.5 Hz, 4H), 6.57 (dd, J = 1.7, 3. 5 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.56 (d, J = 1.7 Hz, 1H), 7.77 (dd, J = 7.8, 7.8 Hz, 1H), 7.84 (d, J = 3.5 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H). APCIMS m / z: [M + H] + 496.

[Example 294] N- [4- (2-Furyl) -5- (5-methylpyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 294) In a manner similar to that in Example 283, using 2-bromo-5-methylpyridine in place of 2-bromo-6-methoxypyridine, the title Compound 294 (128 mg, 59%) was obtained from Compound 98 (200 mg, 0.558 mmol). X H NMR (DMSO-d 6, d ppm): 2.43 (s, 3 H), 6.66 (dd, J = 1.7, 3.5 Hz, 1 H), 7.49 (dd, J = 0.7, 3.5.Hz, 1 H), 7.76 (dd) , J = 0.7, 1. 7 Hz, 1H), 7.88-7.92 (, 1H), 8.03-8.06 (, 3H), 8.59-8.60 (m, 1H), 8.84 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M + H] + 391. p.f .: 255-257 ° C.

[Example 295] N- [4- (2-Furyl) -5- (4-methylpyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 295) In a manner similar to that in Example 283, using 2-bromo-4-methylpyridine in place of 2-bromo-6-methoxypyridine, Title Compound 295 (50.0 mg, 23%) was obtained from Compound 98 (200 mg, 0.558 mmol). X H NMR (DMSO-d 6, d ppm): 2.46 (s, 3 H), 6.65 (dd, J = 1.7, 3.5 Hz, 1 H), 7.48 (dd, J = 0.7, 3.5 Hz, 1 H), 7.52 (d, J = 4.8 Hz, 1H), 7.75 (dd, J = 0.7, 1.7 Hz, 1H), 7.96 (s, 1H), 8.05 (d, J = 6.1 Hz, 2H), 8.59 (d, J = 4.8 Hz, 1H), 8.84 (d, J = 6.1 Hz, 2H), 13.49 (br s, 1H). APCIMS m / z: [M + H] + 391. p.f .: 240-245 ° C.

[Example 296] N-. { 4- (2-furyl) -5- [1-hydroxy-1- (5-methoxypyridin-2-yl) methyl] thiazol-2-yl} tert-butyl carbamate (Compound 296) In a manner similar to that in Example 92, at using Compound z (1.11 g, 8.00 mmol) obtained in Reference Example 26 instead of DMF, Compound of title 296 (697 mg, 43%) was obtained from. Compound h (1.38 g, 4.00 mmol). XH NMR (CDC13, d ppm): 1.42 (s, 9H), 3.86 (s, 3H), 5.29 (d, J = 4.3 Hz, 1H), 6.48 (dd, J = 1.9, 3.5 Hz, 1H), 6.59 (d, J = 4.3 Hz, 1H), 6.77 (dd, J = 0.8, 3.5 Hz, 1H), 7.15 (dd, J = 2.7, 8.7 Hz, 1H), 7.21 (d, J = 8.7 Hz, 1H) , 7.47 (dd, J = 0.8, 1.9 Hz, 1H), 8.28 (d, J = 2.7 Hz, 1H), 9.24 (br s, 1H).

[Example 297] N- [4- (2-Furyl) -5- (5-methoxypyridin-2-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 297) Compound 296 (697 mg, 1.73 mmol ) was dissolved in dichloromethane (10 mL), and DMP (848 mg, 2.00 mmol) was added thereto, followed by stirring at room temperature for 1 hour. The methanol (10 mL) was added to the reaction mixture, followed by stirring for 10 minutes, and the solvent was distilled under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to provide the title Compound 297 (632 mg, 91%). X H NMR (CDCl 3, d ppm): 1.57 (s, 9 H), 3.95 (s, 3 H), 6.54 (dd, J = 1.6, 3.4 Hz, 1 H), 7.32 (dd, J = 3.0, 8.8 Hz, 1 H) , 7.51 (dd, J = 0.8, 1.6 Hz, 1H), 7.70 (dd, J = 0.8, 3.4 Hz, 1H), 8.18 (dd, J = 0.7, 8.8 Hz, 1H), 8.39 (dd, J = 0.7, 3.0 Hz, 1H).

[Example 298] 2-Amino-4- (2-furyl) thiazol-5-yl-5-methoxypyridin-2-yl ketone (Compound 298) In a manner similar to that in Example 186, the title Compound 298 (269) mg, 51%) was obtained from Compound 2.97 (697 mg, 1.74 mmol) in place of Compound 185. XH NMR (DMSO-d6, d ppm): 3.91 (s, 3H), 6.56 (dd, J = 1.7, 3.5 Hz, 1H), 7.44 (dd, J = 0.7, 3.5 Hz, 1H), 7.56 (dd, J = 3.0, 8.7 Hz, 1H), 7.63 (dd, J = 0.7, 1.7 Hz, 1H) , 7.92 (br s, 2H), 8.02 (d, J = 9.2 Hz, 1H), 8.26 (d, J = 3.0 Hz, 1H).

[Example 299] [4- (2-Furyl) -5- (5-methoxypyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 299) In a manner similar to that in Example 187, a Crude Compound 299 was obtained from Compound 298 (250 mg, 0.831 mmol) in place of Compound 186. The resulting crude Compound 299 was recrystallized from ethanol to provide the title Compound 299 (133 mg, 40%). X H NMR (DMSO-d 6, d ppm): 3.97 (s, 3 H), 6.64 (dd, J = 1. 8, 3.5 Hz, 1H), 7.43 (d, J = 3.5 Hz, 1H), 7.64 (dd, J = 3.0, 8.8 Hz, 1H), 7.75 (d, J = 1.8 Hz, 1H), 8.05 (dd, J = 1.7, 4.5 Hz, 2H), 8.15 (d, J = 8.8 Hz, 1H), 8.43 (d, J = 3.0 Hz, 1H), 8.84 (dd, J = 1.7, 4.5 Hz, 2H), 13.46 ( br s, 1H).

[Example 300] N- [5- (6-Bromopyridin-2-yl carbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 300) A THF solution (10 L) of 2,6-dibromopyridine (4.97) g, 21.0 mmol) 2.0 mol / L of isopropylmagnesium chloride in THF (9.56 mL, 19.1 mmol) was added at 0 ° C, followed by stirring for 3 hours at room temperature. A THF solution (5 mL) of Compound 98 (1.37 g, 3.82 mmol) was added dropwise to the reaction mixture, followed by stirring for 3 hours at room temperature. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 9: 1) to provide the Compound of title 300 (520 mg, 31%). [Example 301] N- [4- (2-Furyl) -5- (6-morpholinopyridin-2-ylcarbonyl) thiazol-2-yl] pyridin-4-ylcarboxamide (Compound 301) Compound 300 (133 mg, 0.300 mmol ) was suspended in 1,4-dioxane (2 mL), and morpholine (0.525 mL, 6.00 mmol) was added thereto, followed by stirring under heating and reflux for 5 hours. The reaction mixture was purified through silica gel column chromatography (chloroform-methanol = 9: 1) to give the title Compound 301 (31.0 mg, 23%) as a brown solid. X H NMR (DMSO-dg, d ppm): 3.60-3.64 (m, 4H), 3.75-3.79 (m, 4H), 6. 66 (dd, J = 1.6, 3.5 Hz, 1H), 7.15 (d, J = 8.6 Hz, 1H), 7. 43 (d, J = 7.3 Hz 1H), 7.55 (d, J = 3.5 Hz, 1H), 7.78 (d, J = 1.6 Hz, 1H), 7.81 (dd, J = 7.3, 8.6 Hz, 1H), 8.04 (dd, J = 0. 8, 5.4 Hz, 2H), 8.83 (dd, J = 0.8, 5.4 Hz, 2H), 13.47 (br s, 1H). APCIMS m / z: [M + H:] + 450. p. f. : 258-262 ° C. [Example 302] N- [4- (2-Furyl) -5- (pyridin-3-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 302) In a manner similar to that in Example 185 , when using nicotinic acid in place of picolinic acid, the title Compound 302 (102 mg, 19%) was obtained from the Compound h (500 mg, 1.45 mmol) obtained in Reference Example 8. XH NMR (CDC13, d ppm): 1.51 (s, 9H), 6.25 (dd, J = 1.9, 3.4 Hz, 1H), 6.68 (d , J = 3.4 Hz, 1H), 7.03 (d, J = 1.9 Hz, 1H), 7.37 (dd, J = 4.9, 7.9 Hz, 1H), 8.12 (dd, J = 1.9, 7.9 Hz, 1H), 8. 65 (dd, J = 1.9, 4.9 Hz, 1H), 9.10 (s, 1H), 10.32 (br s, 1H).

[Example 303] 2-Amino-4- (2-furyl) thiazol-5-yl 3-pyridyl ketone (Compound 303) In a manner similar to that in Example 186, the Compound 303 title (75.0 mg, 100%) was obtained from Compound 302 (102 mg, 0.275 mmol) instead of Compound 185. X H NMR (CDCl 3, d ppm): 6.32 (dd, J = 1.8, 3.3 Hz, 1H), 6.91 (d, J = 3.3 Hz, 1H), 7.10 (d, J = 1.8 Hz, 1H), 7.27-7.31 (m, 1H), 7.93-7.96 (m, 1H), 8.62-8.64 (m, 1H), 8.83-8.84 (m, 1H).

[Example 304] N- [4- (2-Furyl) -5- (pyridin-3-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 304) In a manner similar to that in Example 187, the Compound of title 304 (69.0 mg, 57%) was obtained from of Compound 303 (75.0 mg, 0.276 mmol) instead of Compound 186. XH NMR (DMS0-d6, d ppm): 6.50 (dd, J = 1.8, 3.5 Hz, 1H), 6.97 (d, J = 3.5 Hz, 1H), 7.46 (d, J = 1.8 Hz, 1H), 7.44-7.48 (m, 1H), 8.01-8.06 (m, 1H), 8.02 (d, J = 6.2.Hz) , 2H), 8.04-8.07 (m, 1H), 8.70-8.72 (m, 1H), 8.80-8.81 (m, 1H), 8.83 (d, J = 6. 2 Hz, 2H). APCIMS m / z: [M + H] + 377. p.f .: 245-248 ° C. [Example 305] N- [4- (2 ~ Furyl) -5- (pyridin-3-ylcarbonyl) thiazol-2-yl] cyclopropanecarboxamide (Compound 305) In a manner similar to that in Example 188, by using cyclopropanecarbonyl (109 mg, 1.04 mmol) in place of acetyl chloride, the title Compound 305 (33.2 mg, 20%) was obtained from Compound 303 (131 mg, 0. 482 mmol) in place of Compound 186. XH NMR (CDC13, d ppm): 0.92-0.98 (m, 2H), 1.15-1.19 (m, 2H), 1. 50-1.59 (m, 1H), 6.30-6.31 (m, 1H), 6.80 (s, 1H), 7.12 (s, 1H), 7.41 (dd, J = 4.8, 8.0 Hz, 1H), 8.17 (dd, J = 1.5, 8.0 Hz, 1H), 8.70 (dd, J = 1.5, 4.8 Hz, 1H), 9.14 (s, 1H). ESIMS m / z: [M + H] + 340. p. f. : 231-233 ° C.

[Example 306] 4-Cyano-N- [4- (2-furyl) -5- (pyridin-3-ylcarbonyl) thiazol-2-yl] benzamide (Compound 306) In a manner similar to that in Example 187, when using 4-cyanobenzoic acid (344 mg, 2.34 mmol) in place of isonicotinic acid, the title compound 306 (33.8 mg, 22%) was obtained from Compound 303 (106 mg, 0.390 mmol) in place of Compound 186. XH NMR (DMSO-de, d ppm): 6.51 (dd, J = 1.7, 3.2 Hz, 1H), 6.98 ( d, J = 3.2 Hz, 1H), 7.45-7.49 (m, 2H), 8.04-8.05 (m, 1H), 8. 06 (d, J = 8.1 Hz, 2H), 8.28 (d, J = 8.1 Hz, 2H), 8.71 (d, J = 4.8 Hz, 1H), 8.80-8.81 (m, 1H). ESIMS m / z: [M + H] + 401. p. f. : 288-290 ° C.

[Example 307] N- [4- (2-Furyl) -5- (pyridin-3-ylcarbonyl) thiazol-2-yl] furan-2-carboxamide (Compound 307) In a manner similar to that in Example 188, when using 2-furoyl chloride (75.5 μL, 0.766 mmol) in place of acetyl chloride, the title Compound 307 (20.7 mg, 13%) was obtained from Compound 303 (116 mg, 0.428 mmol) instead of the Compound 186. XH NMR (DMSO-de, d ppm): 6.50 (dd, J = 2.0, 3.3 Hz, 1H), 6.78 (dd, J = 1.6, 3.5 Hz, 1H), 6.96 (d, J = 3.5 Hz , 1H), 7.43- 7. 48 (m, 2H), 7.79 (s, 1H), 8.03 (d, J = 7.9 Hz, 1H), 8.07 (s, 1H), 8.70 (dd, J = 1.6, 4.9 Hz, 1H), 8.80 (d , J = 2.2 Hz, 1H), 13.34 (br s, 1H). ESIMS m / z: [M + H] + 366. p.f .: 234-236 ° C.

[Example 308] N- [4- (2-Furyl) -5- (2-methylpyridin-3-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 308) Compound h (500 mg / 1.45 mmol ) obtained in Reference Example 8 was dissolved in THF (7.5 mL), and a 1.58 mol / L solution of n-butyllithium in n-hexane (2.02 mL, 3.19 mmol) was added thereto in a stream of argon to -78 ° C, followed by stirring at -78 ° C for 15 minutes. The ethyl 2-methylnicotinate (723 mg, 4.35 mmol) was added dropwise to the reaction mixture, followed by stirring at room temperature for 1.5 hours. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to provide the title Compound 308 (83.0 mg, 15%).

X H NMR (CDCl 3, d ppm): 1.43 (s, 9H), 2.61 (s, 3H), 6.41 (dd, J = 1.8, 3.5 Hz, 1H), 7.05-7.10 (m, 1H), 7.24 (d, J = 1.8 Hz, 1H), 7.40 (d, J = 3.5 Hz, 1H), 7.57-7.60 (m, 1H), 8.52-8.54 (m, 1H).

[Example 309] 2-Amino-4- (2-furyl) thiazol-5-yl 2-methylpyridin-3-yl ketone (Compound 309) Compound 308 (83.0 mg, 0.215 mmol) was dissolved in trifluoroacetic acid (1 mL), followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and ethyl acetate and a saturated aqueous solution of sodium acid carbonate were added to the resulting residue, and the organic layer was separated. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 4) to provide the title Compound 309 (60.0 mg, 99%). X H NMR (CDC13, d ppm): 2.53 (s, 3 H), 6.12-6.14 (m, 1 H), 6.93-7.05 (m, 2 H), 7.44-7.47 (, 1 H), 8.19-8.21 (m, 1 H) , 8.51-8.54 (m, 1H).

[Example 310] N- [4- (2-Furyl) -5- (2-methylpyridin-3-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 310) In a manner similar to that in Example 187, the title compound 310 (42.0 mg, 50%) was obtained from Compound 309 (60.0 mg, 0.215 mmol) instead of the Compound 186. XH NMR (DMSO-de, d ppm): 2.53 (s, 3H), 6.53 (dd, J = 1.7, 3.5 Hz, 1H), 7.15 (dd, J = 0.7, 3.5 Hz, 1H), 7.21 (dd, J = 4.8, 7.7 Hz, 1H), 7.55 (dd, J = 0.7, 1.7 Hz, 1H), 7.75 (dd , J = 1. 8, 7.7 Hz, 1H), 8.01 (d, J = 6.1 Hz, 2H), 8.53 (dd, J = 1. 8, 4.8 Hz, 1H), 8.84 (d, J = 6.1 Hz, 2H), 13.7 (br s, 1H).

APCIMS m / z: [M + H] + 391. p. f. : 230-234 ° C.

[Example 311] N- [4- (2-Furyl) -5- (2-methylpyridin-5-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 311) In a manner similar to that in Example 185, when using 6-methylnicotinic acid instead of picolinic acid, the Compound of title 311 (1.44 g, 73%) was obtained from Compound h (1.77 g, 5.13 mmol) obtained in the Example of Reference 8. XH NMR (CDC13, d ppm): 1.49 (s, 9H), 3.31 (s, 3H), 6.48 (dd, J = 1.7, 3.3 Hz, 1H), 6.91 (d, J = 3.3 Hz, 1H ), 7.29 (d, J = 8. 3 Hz, 1H), 7.46 (d, J = 1.7 Hz, 1H), 7.89 (dd, J = 2.3, 8.3 Hz, 1H), 8.65 (d, J = 2.3 Hz, 1H), 12.2 (brs, 1H) .

[Example 312] 2-Amino-4- (2-furyl) thiazol-5-yl 2-methylpyridin-5-yl ketone (Compound 312) In a manner similar to that in Example 186, the title Compound 312 (1.04) g, 100%) was obtained from Compound 311 (1.41 g, 3.66 mmol) instead of Compound 185. XH NMR (DMS0-d6, d ppm): 2.45 (s, 3H), 6.41 (dd, J = 1.7 , 3.3 Hz, 1H), 6.79 (d, J = 3.3 Hz, 1H), 7.20 '(d, J = 7.9 Hz, 1H), 7.32 (d, J = 1.7 Hz, 1H), 7.75 (dd, J = 2.3, 7.9 Hz, 1H), 8.51 (d, J = 2.3 Hz, 1H).

[Example 313] N- [4- (2-Furyl) -5- (2-methylpyridin-5-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 313) Compound 312 (200 mg, 0.701 mmol ) was dissolved in DMF (3.5 L), and isonicotinic acid (259 mg, 2.10 mmol), EDC hydrochloride (403 mg, 2.10 mmol) and 1-hydroxybenzotriazole monohydrate (322 mg, 2.10 mmol) were added thereto, followed by stirring at 60 ° C for 3 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with an aqueous solution saturated sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from 2-propanol to provide the title Compound 313 (170 mg, 62%). X H NMR (DMSO-de, d ppm): 2.51 (s, 3 H), 6.52 (dd, J = 1.8, 3.5 Hz, 1 H), 6.97 (dd, J = 0.7, 3.5 Hz, 1 H), 7.32 (d, J = 8.1 Hz, 1H), 7.50 (dd, J = 0.7, 1.8 Hz, 1H), 7.95 (dd, J = 2.3, 8.1 Hz, 1H), 8.02 (d, J = 6.1 Hz, 2H), 8.70 ( d, J = 2.3 Hz, 1H), 8.83 (d, J = .6.1 Hz, 2H), 13.6 (s, 1H). APCIMS m / z: [M + H] + 391. p.f .: 230-232 ° C (decomposition) [Example 314] 4-Cyano-N- [4- (2-furyl) -5- (2-methylpyridin-5-ylcarbonyl) thiazol-2-yl] benzamide (Compound 314) In a manner similar to that in Example 313, when using 4-cyanobenzoic acid in place of isonicotinic acid, the title Compound 314 (253 mg, 72%) was obtained from Compound 312 (242 mg, 0.848 mmol). X H NMR (DMSO-d 6, d ppm): 2.51 (s, 3 H), 6.52 (dd, J = 1.7, 3.5 Hz, 1 H), 6.97 (dd, J = 0.8, 3.5 Hz, 1 H), 7.32 (d, J = 8.1 Hz, 1H), 7.51 (dd, J = 0.8, 1.7 Hz, 1H), 7.95 (dd, J = 2.3, 8.1 Hz, 1H), 8.06 (d, J = 8.4 Hz, 2H), 8.26 ( d, J = 8.4 Hz, 2H), 8.70 (d, J = 2.3 Hz, 1H), 13.6 (br s, 1H).

APCIMS m / z: [M + H] + 415. p.f .: 261-265 ° C.

[Example 315] N- [4- (2-Furyl) -5- (2-methylpyridin-5-ylcarbonyl) thiazol-2-yl] furan-2-carboxamide (Compound 315) In a manner similar to that in Example 313, when using 2-furancarboxylic acid in place of isonicotinic acid, Title Compound 315 (155 mg, 52%) was obtained from Compound 312 (200 mg, 0.701 mmol). X H NMR (DMSO-de, d ppm): 2.51 (s, 3H), 6.50 (dd, J = 1.8, 3.3 Hz, 1H), 6.76 (dd, J = 1.8, 3.5 Hz, 1H), 6.94 (d, J = 3.3 Hz, 1H), 7.30 (d, J = 8.1 Hz, 1H), 7.48 (d, J = 1.8 Hz, 1H), 7.77 (d, J = 3.5 Hz, 1H), 7.92 (dd, J = 2.1, 8.1 Hz, 1H), 8.05 (d, J = 1.8 Hz, 1H), 8.68 (d, J = 2.1 Hz, 1H), 13.3 (br s, 1H). APCIMS m / z: [M + H] + 380. p.f .: 197-209 ° C.

[Example 316] N- [4- (2-Furyl) -5- (2-methylpyridin-5-ylcarbonyl) thiazol-2-yl] furan-3-carboxamide (Compound 316) In a manner similar to that in Example 313, when using 3-furancarboxylic acid in place of isonicotinic acid, the title Compound 316 (102 mg, 27%) was obtained from Compound 312 (200 mg, 0.701 mmol).

X H NMR (DMSO-d 6, d ppm): 2.47 (s, 3 H), 6.50 (dd, J = 1.8, 3.5 Hz, 1 H), 6.94 (d, J = 3.5 Hz, 1 H), 7.11-7.12 (m, 1H), 7.30 (d, J = 8.1 Hz, 1H), 7.47 (d, J = 1.8 Hz, 1H), 7.84-7.86 (m, 1H), 7.92 (dd, J = 2.3, 8.1 Hz, 1H), 8.63-8.64 (m, 1H), 8.67 (d, J = 2.3 Hz, 1H). APCIMS m / z: [M + H] + 380. m.p .: 229-231 ° C. [Example 317] N- [4- (2-furyl) -5- (2-methoxypyridin-5-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 317) In a manner similar to that in Example 283, using 5-bromo-2-methoxypyridine in place of 2-bromo-6-methoxypyridine, the title compound 317 (2.09 g, 83%) was obtained from Compound 134 (2.49 g, 7.05 mmol) instead of Compound 98. XH NMR (CDC13, d ppm); 1.47 (s, 9H), 3.99 (s, 3H), 6.39 (dd, J = 1.8, 3.3 Hz, 1H), 6.74 (dd, J = 0.9, 8.4 Hz, 1H), 6.98 (d, J = 0.6, 3.3 Hz, 1H), 7.23 (dd, J = 0.9, 2.4 Hz, 1H), 8.02 (dd, J = 2.4, 8.4 Hz, 1H), 8.66 (dd, J = 0.6, 1.8 Hz, 1H), 9.48 (br s, 1H). APCIMS m / z: [M + H] + 402. [Example 318] 2-Amino-4- (2-furyl) thiazol-5-yl-2-methoxypyridin-5-yl ketone (Compound 318) In a manner similar to that in Example 186, the Compound of title 318 (1.51 g, 86%) was obtained as a pale yellow solid from Compound 317 (2.09 g, 5.85 mmol) in place of Compound 185. XH NMR (DMSO-de, d ppm): 3.85 (s) , 3H), 6.43 (dd, J = 1.6, 3.2 Hz, 1H), 6.74 (d, J = 8.7 Hz, 1H), 6.77 (d, J = _ 3.2 Hz, 1H), 7.37 (d, J = 1.6 Hz, 1H), 7.81 (dd, J = 2.4, 8.7 Hz, 1H), 8.03 (br s, 2H), 8.32 (d, J = 2.4 Hz, 1H). APCIMS m / z: [M + H] + 302.

[Example 319] N- [4- (2-Furyl) -5- (2-methoxypyridin-5-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 319) In a manner similar to that in Example 283, when using 5-bromo-2-methoxypyridine in place of 2-bromo-6-methoxypyridine, followed by re-mixing in methanol, the title Compound 319 (44.5 mg, 20%) was obtained as a solid coffee from Compound 98 (200 mg, 0. 558 mmol). X H NMR (DMSO-de, d ppm): 3.91 (s, 3H), 6.54 (dd, J = 1.9, 3.5 Hz, 1H), 6.87 (dd, J = 0.8, 8.4 Hz, 1H), 6.95 (dd, J = 0.8, 3. 5 Hz, 1H), 7.54 (dd, J = 0.8, 1.9 Hz, 1H), 8.01 (dd, J = 2. 7, 8.4 Hz, 1H), 8.03 (dd, J = 1.3, 5.4 Hz, 2H), 8.52 (dd, J = 0.8, 2.7 Hz, 1H), 8.81 (dd, J = 1.3, 5.4 Hz, 2H), 3.60 (br s, 1H). APCIMS m / z: [M + H] + 407. p.f .: 246-257 ° C (decomposition) [Example 320] N- [5- (2-chloropyridin-5-ylcarbonyl) -4- (2-furyl) thiazol-2-yl] tert-butyl carbamate (Compound 320) In a manner similar to that in Example 176, using 6-chloronicotinic acid instead of 2-cyanobenzoic acid, title Compound 320 (1.65 g, 41%) was obtained from Compound h (3.45 g, 10.0 mmol) obtained in Reference Example 8. XH NMR (CDC13, d ppm): 1.53 (s, 9H), 6.41 (dd, J = 1.9, 3.5 Hz, 1H), 7.02 (dd, J = 0.5, 3.5 Hz, 1H), 7.21 (dd, J = 0.5, 1.9 Hz, 1H), 7.34 (dd, 0.5, 8.1 Hz, 1H), 7.98 (dd, J = 2.4, 8.1 Hz, 1H), 8.59 (br s, 1H), 8.71 (dd, J = 0.5, 2.4 Hz, 1H).

[Example 321] 2-Amino-4- (2-furyl) thiazol-5-yl 2-chloropyridin-5-yl ketone (Compound 321) In a manner similar to that in Example 186, Compound of title 321 (752 mg, 100%) was obtained from Compound 320 (1.00 g, 2.46 mmol) in place of Compound 185. XH NMR ( DMSO-de, d ppm): 6.45 (dd, J = 1.6, 3.2 Hz, 1H), 6.79 (d, J = 3.2 Hz, 1H), 7.35 (d, J = 1.6, Hz, 1H), 7.47 (d, J = 8.1 Hz, 1H), 7.90 (dd, J = 2.2, 8.1 Hz, 1H), 8.22 (br s, 2H), 8. 45 (d, J = 2.2 Hz, 1H). APCIMS m / z: [M + H] + 306.

[Example 322] N- [5- (2-chloropyridin-5-ylcarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 322) In a manner similar to that in Example 187, Compound of title 322 (920 mg, 91%) was obtained as a yellow solid from Compound 321 (750 mg, 2.46 mmol) in place of Compound 186. XH NMR (DMSO-d6, d ppm): 6.54 (dd, J = 1.6, 3.2 Hz, 1H), 6.93 (d, J = 1.6 Hz, 1H), 7.50-7.56 (m, 2H), 7.67-7.69 (m, 1H), 8.02 (d, J = 6.0 Hz, 2H), 8.33-8.35 (m, 1H), 8.83 (d, J = 6.0 Hz, 2H), 13.65 (br s, 1H). APCIMS m / z: [35C1M-H] "409, [37C1M-H]" 411.

[Example 323] N-. { 5- [2- (Dimethylaminopyri5-ylcarbonyl] -4- (2-furyl) thiazol-2-yl) pyri-4-carboxamide (Compound 323) Compound 322 (200 mg, 0.486 mmol) was suspended in 1, 4-dioxane (1 mL), and a 2 mol / L solution of dimethylamine in THF (2.43 mL, 4.86 mmol) was added thereto, followed by stirring under heating and refluxing for 4 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was made as a thick mixture with ethanol to provide the title Compound 323 (111 mg, 54%) as a brown solid. X H NMR (DMSO-de, d ppm): 3.12 (s, 6H), 6.55 (dd, J = 1.6, 3.2 Hz, 1H), 6.67 (d, J = 8.6 Hz, 1H), 6.88 (d, J = 3.2 Hz, 1H), 7.61 (d, J = 1.6 Hz, 1H), 7.86 (dd, J = 2.4, 8.6 Hz, 1H), 8.03 (dd, J = 1.6, 4.6 Hz, 2H) 8.47 (d, J = 2.4 Hz, 1H), 8.84 (dd, J = 1.6, 4.6 Hz, 2H), 13.51 (brs, 1H). APCIMS m / z: [M + H] + 420. p.f .: 260-265 ° C (decomposition) [Example 324] N- [4- (2-Furyl) -5- (2-morpholinopyri5-ylcarbonyl) thiazol-2-yl] pyri-4-carboxamide (Compound 324) In a manner similar to that in Example 323, by using morpholine in place of dimethylamine, the title Compound 324 (46.4 mg, 21%) was obtained as a pale yellow solid from Compound 322 (200 mg, 0.486 mmol). X H NMR (DMSO-de, d ppm): 3.25-3.35 (m, 4H), 3.60-3.70 (m, 4H), 6. 55 (dd, J = 1.9, 3.2 Hz, 1H), 6.86 (d, J = 9.2 Hz, 1H), 6. 90 (dd, J = 0.8, 3.2 Hz, 1H), 7.61 (dd, J = 0.8, 1.9 Hz, 1H), 7.88 (dd, J = 2.4, 9.2 Hz, 1H), 8.03 (dd, J = 1.6, 6.2 Hz, 2H), 8.48 (d, J = 2.4 Hz, 1H), 8.84 (dd, J = 1.6, 6.2 Hz, 2H), 13.52 (br s, 1H). APCIMS m / z: [M + H] + 462. p.f .: 195-205 ° C.

[Example 325] N-. { 4- (2-Furyl) -5- [2- (4-methyl-piperazin-1-yl) -pyri5-ylcarbonyl] -thiazol-2-yl} pyri-4-carboxamide (Compound 325) In a manner similar to that in Example 323, by using 1-methylpiperazine in place of dimethylamine, Title 325 Compound (110 mg, 47%) was obtained from Compound 322 (200 mg, 0.486 mmol). X H NMR (DMSO-de, d ppm): 2.28 (s, 3 H), 2.47-2.50 (m, 4 H), 3.65-3.75 (m, 4 H), 6.55 (dd, J = 1.6, 3.2 Hz, 1 H), 6.87 (d, J = 9.2 Hz, 1H), 6.90 (d, J = 3.2 Hz, 1H), 7.60 (d, J = 1.6 Hz, 1H), 7.86 (dd, J = 2.4, 9.2 Hz, 1H), 8.02 (dd, J = 1.4, 4.5 Hz, 2H), 8.47 (d, J = 2.4 Hz, 1H), 8.81 (dd, J = 1.4, 4.5 Hz, 2H). APCIMS m / z: [M + H] + 475. p.f. : 195-205 ° C.

[Example 326] N-. { 4- (2-Furyl) -5- [2- (4-hydroxypiperi) pyri5-ylcarbonyl] thiazol-2-yl} pyri-4-carboxamide (Compound 326) In a manner similar to that in Example 323, al Using 4-hydroxypiperi in place of dimethylamine, the title Compound 326 (95.0 mg, 41%) was obtained as a brown solid from Compound 322 (200 mg, 0.486 mmol). X H NMR (DMSO-de, d ppm): 1.28-1.41 (m, 2H), 1.75-1.80 (m, 2H), 3.16-3.17 (m, 2H), 3.72-3.78 (m, 1H), 4.06-4.12 (m, 2H), 4.76 (d, J = 4.0 Hz, 1H), 6.55 (dd, J = 1.6, 3.5 Hz, 1H), 6.86 (d, J = 9.2 Hz, 1H), 6.88 (dd, J = 0.8, 3.5 Hz, 1H), 7.60 (dd, J = 0.8, 1.6 Hz, 1H), 7.83 (dd, J = 2.4, 9.2 Hz, 1H), 8.03 (dd, J = 1.6, 4.6 Hz, 2H), 8.45 (d, J = 2.4 Hz, 1H), 8.84 (dd, J = 1.6, 4.6 Hz, 2H), 13.51 (br s, 1H). APCIMS m / z: [M + H] + 476. p.f. : 264-268 ° C.

[Example 327] N- [4- (2-Furyl) -5- (pyri4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 327) In a manner similar to that in Example 185, when using isonicotinic acid in place of picolinic acid, Title Compound 327 (125 mg, 23%) was obtained from Compound h (500 mg, 1.45 mmol) obtained in Reference Example 8. XH NMR (CDC13, d ppm): 1.51 (s, 9H), 6.40 (dd, J = 1.7, 3.3 Hz, 1H), 7.14 (d, J = 3.3 Hz, 1H), 7.16 (d, J = 1.7 Hz, 1H), 7.55 ( d, J = 6.1 Hz, 2H), 8.67 (d, J = 6.1 Hz, 2H).

[Example 328] 2-Amino-4- (2-furyl) thiazol-5-yl 4-pyridyl ketone (Compound 328) In a manner similar to that in Example 186, the title compound 328 (91.0 mg, 100%) was obtained from Compound 327 (125 mg, 0.337 mmol) in place of Compound 185. XH NMR (CDC13, d ppm): 5.68 (br s, 2H), 6.35 (dd, J = 1.8, 3.3 Hz, 1H), 6.98 (d, J = 3.3 Hz, '1H), 7.04 (d, J = 1.8 Hz, 1H) , 7.51 (d, J = 6.1 Hz, 2H), 8.62 (d, J = 6.1 Hz, 2H).

[Example 329] N- [4- (2-Furyl) -5- (pyridin-4-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 329) In a manner similar to that in Example 187, he Compound of title 329 (72.0 mg, 57%) was obtained from Compound 328 (91.0 mg, 0.335 mmol) instead of Compound 186. XH NMR (DMSO-de, d ppm): 6.53 (dd, J = 1.8, 3.5 Hz, 1H), 7.05 (dd, J = 0.7, 3.5 Hz, 1H), 7.47 (dd, J = 0.7, 1.8 Hz, 1H), 7. 55 (d, J = 5.8 Hz, 2H), 8.03 (d, J = 6.1 Hz, 2H), 8.65 (d, J = 5.8 Hz, 2H), 8.84 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M + H] + 377. p. f. : 276-285 ° C.

[Example 330] N- [4- (2-Furyl) -5- (2-methylpyridin-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 330) In a manner similar to that in Example 185, using 2-methylisonicotinic acid in place of picolinic acid, Title Compound 330 (1.26 g, 61%) was obtained from Compound h (1.84 g, 5.33 mmol) obtained in the Example of Reference 8. H NMR (CDC1, d ppm): 1.53 (s, 9H), 2.57 (s, 3H), 6.42 (dd, J = 1.1, 3.5 Hz, 1H), 7.20 (d, J = 3.5 Hz, 1H ), 7.24 (d, J = 1.7 Hz, 1H), 7.30 (d, J = 5.1 Hz, 1H), 7.35 (s, 1H), 8.56 (d, J = 5.1 Hz, 1H).

[Example 331] 2-Amino-4- (2-furyl) thiazol-5-yl 2-methylpyridin-4-yl ketone (Compound 331) In a manner similar to that in Example 186, the Compound of title 331 (872 mg, 93%) was obtained from Compound 330 (1.26 g, 3.27 mmol) in place of Compound 185. X H NMR (CDCl 3, d ppm): 2.53 (s, 3 H), 5.67 (br s, 2 H), 6.36 (dd, J = 1.8, 3.5 Hz, 1H), 7.03 (d, J = 3.5 Hz, 1H), 7.14 (d, J = 1.8 Hz, 1H), 7.24 (d, J = 5.1 Hz, 1H), 7.28 (s, 1H), 8.50 (d, J = 5.1 Hz, 1H).

[Example 332] N- [4- (2-Furyl) -5- (2-methylpyridin-4-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 332) Compound 331 (150 mg, 0.526 mmol ) was dissolved in DMF (2 mL), and isonicotinic acid (259 mg, 2.10 mmol), EDC hydrochloride (403 mg, 2.10 mmol) and 1-hydroxybenzotriazole monohydrate (322 mg, 2.10 mmol) were added thereto, followed by stirring at 60 ° C for 3 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from 2-propanol to provide the title Compound 332 (78.0 mg, 38%). XH NMR (CDC13, 6 ppm): 2.59 (s, 3H), 6.38 (dd, J = 1.7, 3.5 Hz, 1H), 7.17 (d, J = 3.5 Hz, 1H), 7.22 (d, J = 1.7 Hz , 1H), 7.35 (d, J = 5.1 Hz, 1H), 7.40 (s, 1H), 7.76 (d, J = 6.1 Hz, 2H), 8.59 (d, J = 5.1 Hz, 1H), 8.85 (d , J = 6.1 Hz, 2H). APCIMS m / z: [M + H] + 391. p.f .: 223-225 ° C. [Example 333] N- [4- (2-Furyl) -5- (2-methylpyridin-4-ylcarbonyl) thiazol-2-yl] -2-methylpyridine-4-carboxamide (Compound 333) In a manner similar to that in Example 332, at using 2-methylisonicotinic acid in place of isonicotinic acid, Compound of title 333 (59.0 mg, 28%) was obtained from Compound 331 (150 mg, 0.526 mmol). X H NMR (DMSO-de, d ppm): 2.47 (s, 3 H), 2.59 (s, 3 H), 6.54 (d, J = 1.8, 3.3 Hz, 1 H), 7.05 (d, J = 3.3 Hz, 1 H) , 7.35 (d, J = 5.1 Hz, 1H), 7.40 (s, 1H), 7.48 (d, J = 1.8 Hz, 1H), 7.83 (d, J = 5.0 Hz, 1H), 7.92 (s, 1H) , 8.54 (d, J = 5.0 Hz, 1H), 8.69 (d, J = 5.1 Hz, 1H), 13.6 (br s, 1H). APCIMS m / z: [M + H] + 405. p.f .: 205-229 ° C.

[Example 334] N- [4- (2-Furyl) -5- (2-methoxypyridin-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 334) In a manner similar to that in Example 176, using Compound k obtained in Reference Example 11 instead of 2-cyanobenzoic acid, Compound of title 334 (2.34 g, 47%) was obtained from Compound h (4.45 g, 12.9 mmol) obtained in Reference Example 8. XH NMR (CDC13, d ppm): 1.47 (s, 9H), 3.94 (s, 3H), 6.44 dd, J = 1.9, 3.5 Hz, 1H), 6.96 (dd, J = 0.8, 1.4 Hz, 1H), 7.09 (dd, J = 1.4, 5.1 Hz, 1H), 7.28-7.34 (m, 2H), 8.21 (dd, J = 0.8, 5.1 Hz, 1H), 9.26 (br s, 1H). APCIMS m / z: [M + H] + 402. 108 [Example 335] 2-Amino-4- (2-furyl) thiazol-5-yl 2-methoxypyridin-4-yl ketone (Compound 335) In a manner similar to that in Example 186, the Compound of title 335 (1.49 g, 76%) was obtained from Compound 334 (2.34 g, 6.55 mmol) in place of Compound 185. XH NMR ( DMSO-de, d ppm): 3.82 (s, 3H), 6.45 (dd, J = 1.6, 3.2 Hz, 1H), 6.75 (dd, J = 0.8, 1.4 Hz, 1H), 6.92 (dd, J = 0.5 , 3.2 Hz, 1H), 6.96 (dd, J = 1.4, 5.1 Hz, 1H), 7.35 (dd, J = 0.5, 1.6 Hz, 1H), 8.13 (dd, J = 0.8, 5.1 Hz, 1H), 8.22 (br s, 2H). APCIMS m / z: [M + H] + 302.

[Example 336] N- [4- (2-Furyl) -5- (2-methoxypyridin-4-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 336) In a manner similar to that in Example 187, a Crude compound 336 was obtained from Compound 335 (100 mg, 0.332 mmol) in place of Compound 186. Crude Compound 336 was made thick in mixture with ethanol to provide Title Compound 336 (101 mg, 77%) as a yellow solid. X H NMR (DMSO-de, d ppm): 3.87 (s, 3 H), 6.54-6.58 (m, 1 H), 6.96. (s, 1H), 7.12 (d, J = 3.2 Hz, 1H), 7.16 (d, J = 5.1 Hz, 1H), 7.55 (s, 1H), 8.03 (d, J = 4.9 Hz, 2H), 8.26 (d, J = 5.1 Hz, 1H), 8.84 (d, J = 4.9 Hz, 2H), 13.69 (br s, 1H) APCIMS m / z: [M + H] + 407. p.f .: 237-239 ° C.

[Example 337] N- [4- (2-furyl) -5- (2-morpholinopyridin-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 337) In a manner similar to that in Example 176, by using 2-morpholinonicotinic acid in place of 2-cyanobenzoic acid, the title Compound 337 (672 mg, 43%) was obtained from Compound h (1.31 g, 3.80 mmol) obtained in Reference Example 8. XH NMR (CDC13, d ppm): 1.49 (s, 9H), 3.49 (t, J = 4.8 Hz, 4H), 3.80 (t, J = 4.8 Hz, 4H), 6.44 (dd, J = 1.8, 3.6 Hz , 1 HOUR) , 6. 82-6.84 (m, 1H), 6.86 (dd, J = 1.8, 4.8 Hz, 1H), 7.24-7.27 (m, 1H), 7.30-7.32 (m, 1H), 8.23 (dd, J = 0.6, 4.8 Hz, 1H), 9. 11 (br s, 1H). APCIMS m / z: [M + H] + 457.

[Example 338] 2-Amino-4- (2-furyl) thiazol-5-yl 2-morpholinopyridin-4-yl ketone (Compound 338) In a manner similar to that in Example 186, the Compound of title 338 (484 mg, 83%) was obtained from Compound 337 (672 mg, 1.63 mmol) in place of Compound 185.

XH NMR (DMSO-de, d ppm) 3.33 (t, J = 5.1 Hz, 4H), 3.64 (t, J = 5.1 Hz, 4H), 6.46 (dd, J = 1.6, 3.5 Hz, 1H), 6.70 (dd, J = 0.8, 3.5 Hz, 1H), 6.71-6.72 (m, 1H), 6.92 ( d, J = 3.5 Hz, 1H), 7.36-7.38 (m, 1H), 8.12 (d, J = 5.1 Hz, 1H), 8.16 (br s, 2H). APCIMS m / z: [M + H] + 357.

[Example 339] N- [4- (2-Furyl) -5- (2-morpholinopyridin-4-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 339) In a manner similar to that in Example 187, a crude Compound 339 was obtained from the Compound 338 (485 mg, 1.36 mmol) in place of Compound 186. Crude Compound 339 was re-made in a thick mixture with ethanol to give Compound 339 (447 mg, 71%). XH NMR (DMS0-d6, d ppm) 3.40 (dd, J = 4.1, 5.1 Hz, 4H), 3.66 (dd, J = 4.1, 5.1 Hz, 4H), 6.57 (dd, J = 1.6, 3.2 Hz, 1H), 6.86 (d, J = 4.9 Hz, 1H), 6.93 (s, 1H), 7.10 (d, J = 3.2 Hz, 1H), 7.56 (d, J = 1.6 Hz, 1H), 8.03 (dd, J = 1.6, 4.4 Hz, 2H), 8.22 (d, J = 4.9 Hz, 1H), 8.84 (dd, J = 1.6, 4.4 Hz, 2H), 13.67 (br s, 1H). APCIMS m / z: [M + H] + 462. p. f. : 270-273 ° C.

[Example 340] N- [4- (2-furyl) -5- (furan-2-ylcarbonyl) thiazol-2-yl] carbamate (Compound 340) In a manner similar to that in Example 185, using acid 2 -furancarboxyl instead of picolinic acid, Compound of title 340 (187 mg, 36%) was obtained from Compound h (500 mg, 1.45 mmol) obtained in Example Reference 8. XH NMR (CDC13, d ppm): 1.51 (s, 9H), 6.47 (dd, J = 1.8, 3.3 Hz, 1H), 6.53 (dd, J = 1.7, 3.5 Hz, 1H), 7.28 (d , J = 3.3 Hz, 1H), 7.45-7.46 (m, 2H), 7.60 (d, J = 1.7 Hz, 1H). [Example 341] 2-Amino-4- (2-furyl) thiazol-5-yl furan-2-yl ketone (Compound 341) In a manner similar to that in Example 186, the Compound of title 341 (115 mg, 85%) was obtained from Compound 340 (187 mg, 0.519 mmol) in place of the Compound 185. X H NMR (CDC13, d ppm): 6.45-6.46 (m, 1H), 6.49-6.51 (m, 1H), 7.17-7.18 (, 1H), 7.40-7.44 (m, 2H), 7.51-7.52 (m, 1 HOUR) .

[Example 342] N- [4- (2-furyl) -5- (furan-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 342) In a manner similar to that in Example 187, he Compound of title 342 (112 mg, 70%) was obtained from Compound 341 (115 mg, 0.442 mmol) in place of Compound 186. XH NMR (DMSO-de, d ppm): 6.60 (dd, J = 1.8, 3.7 Hz, 1H), 6.73 (dd, J = 1.5, 3.7 Hz, 1H), 7.09 (d, J = 3.7 Hz, 1H), 7.32 (d, J = 3.7? Z, 1H), 7.68 (d, J = 1.8 Hz, 1H), 8.00 (d, J = 1.5 Hz, 1H), 8.01 (d, J = 5.5 Hz, 2H), 8.82 (d, J = 5.5 Hz, 2H). APCIMS m / z: [M + H] + 366. p.f.-. 245-248 ° C.

[Example 343] N- [4- (2-Furyl) -5- (5-methyl-furan-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 343) In a manner similar to that in Example 283, using 2-methylfuran in place of 2-bromo-6-methoxypyridine, the title Compound 343 (195 mg, 61%) was obtained from Compound 98 (300 mg, 0.837 mmol). X H NMR (DMSO-de, d ppm): 2.41 (s, 3 H), 6.21 (d, J = 3.5 Hz, 1 H), 6.44 (dd, J = 1.8, 3.5 Hz, 1 H), 7.26 (d, J = 3.5 Hz, 1H), 7.32 (dd, J = 0.7, 3.5 Hz, 1H), 7.41 (dd, J = 0.7, 1.8 Hz, 1H), 7.75 (d, J = 6.1 Hz, 2H), 8.85 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M + H] + 380. m.p .: 185-189 ° C.

[Example 344] N- [4- (2-furyl) -5- (furan-3-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 344) In a manner similar to that in Example 185, when using 3-furancarboxylic acid in place of picolinic acid, the title Compound 344 (79.0 mg, 15%) was obtained from Compound h (500 mg, 1.45 mmol) obtained in the Example of Reference 8. XH NMR (CDC13, d ppm): 1.50 (s, 9H), 6.44-6.48 (m, 1H), 6.82-6.83 (m, 1H), 7.31-7.45 (m, 3H), 7.94-7.96 ( m, 1H), 8.67 (br s, 1H).

[Example 345] 2-Amino-4- (2-furyl) thiazol-5-yl 3-furyl ketone (Compound 345) In a manner similar to that in Example 186, the Compound of title 345 (40.0 mg, 70%) was obtained from Compound 344 (79.0 mg, 0.219 mmol) instead of Compound 185. XH NMR (CDCl 3, d ppm): 6.39 (dd, J = 1.8, 3.7 Hz, 1H), 6.67. (dd, J = 0.7, 1.8 Hz, 1H), 7.21 (dd, J = 0.7, 3.7 Hz, 1H), 7. 32-7.33 (m, 1H), 7.34-7.35 (m, 1H), 7.78-7.79 (m, 1H).

[Example 346] N- [4- (2-furyl) -5- (furan-3-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 346) In a manner similar to that in Example 187, Compound of title 346 (34.0 mg, 61%) was obtained from Compound 345 (40.0 mg, 0.154 mmol) in place of Compound 186. XH NMR (DMSO-de, d ppm): 6.61 (dd, J = 1.8 , 3.5 Hz, 1H), 6.83-6.84 (m, 1H), 7.09 (dd, J = 0.8, 3.5 Hz, 1H), 7.71 (dd, J = 0.8, 1.8 Hz, 1H), 7.83-7.84 (m, 1H), 8.03 (d, J = 5.9 Hz, 2H), 8.31-8.32 (m, 1H), 8.84 (d, J = 5.9 Hz, 2H). APCIMS m / z; [M + H] + 366. p.f .: 217-231 ° C.

[Example 347] N- [4- (2-Furyl) -5- (thiophen-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 347.) In a manner similar to that in Example 283 , when using thiophene in place of 2-bromo-6-methoxypyridine, the title Compound 347 (80.0 mg, 75%) was obtained from Compound 98 (100 mg, 0.279 mmol). X H NMR (DMSO-de, d ppm): 6.59 (dd, J = 1.8, 3.5 Hz, 1H), 7.02 (d, J = 3.5 Hz, 1H), 7.20 (dd, J = 3.9, 5.2 Hz, 1H), 7.67 (d, J = 1.8 Hz, 1H), 7.68 (dd, J = 1.1, 3.9 Hz, 1H), 8.03 (d, J = 6.1 Hz, 2H), 8.09 (dd, J- = 1.1, 5.2 Hz, 1H), 8.84 (d, J = 6.1 Hz, 2H), 13.6 (br s, 1H). APCIMS m / z: [M + H] + 382. p.f .: 208-210 ° C.

[Example 348] N- [4- (2-Furyl) -5- (thiazol-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 348) In a manner similar to that in Example 283, when using thiazole in place of 2-bromo-6-methoxypyridine, the title Compound 348 (19.0 mg, 18%) was obtained from Compound 98 (100 mg, 0.279 mmol). X H NMR (DMSO-de, d ppm): 6.72 (dd, J = 1.7, 3.5 Hz, 1H), 7.73. (d, J = 3.5 Hz, 1H), 7.89 (d, J = 1.7 Hz, 1H), 8.06 (d, J = 6. 1 Hz, 2H), 8.26 (d, J = 3.1 Hz, 1H), 8.30 (d, J = 3.1 Hz, 1H), 8.85 (d, J = 6.1 Hz, 2H), 13.7 (br s, 1H). APCIMS m / z: [M + H] + 383. p.f .: 228-240 ° C.

[Example 349] N- [4- (2-Furyl) -5- (5-methylthiazol-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 349) In a manner similar to that in Example 283, using 5-methylthiazole in place of 2-bromo-6-methoxypyridine, the title Compound 349 (150 mg, 68%) was obtained from Compound 98 (200 mg, 0.558 mmol).

X H NMR (DMSO-d 6, d ppm): 2.59 (s, 3 H), 6.71 (dd, J = 1.8, 3.5 Hz, 1 H), 7.71 (d, J = 3.5 Hz, 1 H), 7.88 (d, J = 1.8 Hz, 1H), 7.96 (s, 1H), 8.05 (d, J = 6.1 Hz, 2H), 8.85 (d, J = 6.1 Hz, 2H), 13.6 (br s, 1H). APCIMS m / z: [M + H] + 397. mp: 275-277 ° C (dec.) [Example 350] N- [4- (2-Furyl) -5- (4-methylthiazol-2-ylcarbonyl) thiazole -2-yl] pyridine-4-carboxamide (Compound 350) In a manner similar to that in Example 283, when using 4-methylthiazole in place of 2-bromo-6-methoxypyridine, the title Compound 350 (175 mg, 79%) was obtained from Compound 98 (200 mg, 0.558 mmol). X H NMR (DMSO-de, d ppm): 2.50 (s, 3H), 6.69 (dd, J = 1.8, 3.5 Hz, 1H), 7.64 (d, J = 3.5 Hz, 1H), 7.83-7.85 (m, 2H), 8.04 (d, J = 6.1 Hz, 2H), 8.83 (d, J = 6.1 Hz, 2H), 13.6 (br s, 1 HOUR) . - APCIMS m / z: [M + H] + 397. p. f. : 250-255 ° C.

[Example 351] N- [5- (4,5-Dimethylthiazol-2-ylcarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 351) In a manner similar to that in Example 283, using 4,5-dimethylthiazole instead of 2-bromo-6-methoxypyridine, Compound of title 351 (131 mg, 57%) was obtained from Compound 98 (200 mg, 0.558 mmol). X H NMR (DMSO-de, d ppm): 2.41 (s, 3 H), 2.48 (s, 3 H), 6.69 (dd, J = 1.8, 3.5 Hz, 1 H), 7.64 (dd, J = 0.7, 3.5 Hz, 1H), 7.86 (dd, J = 0.7, 1.8 Hz, 1H), 8.05 (d, J = 6.1 Hz, 2H), 8.84 (d.J = 6.1 Hz, 2H), 13.6 (br s, 1H). APCIMS m / z: [M + H] + 411. p.f .: 270-272 ° C (decomposition) [Example 352] N-. { 4- (2-Furyl) -5- [1- (triisopropylsilyl) pyrrol-3-ylcarbonyl] thiazol-2-yl} pyridine-4-carboxamide (Compound 352) In a manner similar to that in Example 283, when using 3-bromo-l- (triisopropylsilyl) pyrrole in place of 2-bromo-6-methoxypyridine, the title Compound 352 (156 mg, 60%) was obtained from of Compound 98 (179 mg, 0.500 mmol). X H NMR (DMSO-d 6, d ppm): 0.96-1.03 (m, 18H), 1.41-1.49 (m, 3H), 6.52 (dd, J = 1.8, 3.5 Hz, 1H), 6.64-6.65 (m, 1H ), 6.91-6.92 (m, 2H), 7.31-7.32 (m, 1H), 7.80 (dd, J = 0.7, 1.8 Hz, 1H), 8.00 (d, J = 6.1 Hz, 2H), 8.80 (d, J = 6.1 Hz, 2H).

[Example 353] N- [4- (2-Furyl) -5- (pyrrol-3-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxy ida (Compound 353) Compound 352 (155 mg, 0.298 mmol) and acid hydrochloric 0.1 mol / L (2.5 mL) were dissolved in ethanol (2.5 mL), followed by stirring at 90 ° C for 2 hours. The reaction mixture was neutralized with a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 4) to provide the title Compound 353 (89.0 mg, 82%). X H NMR (DMSO-de, d ppm): 6.51-6.54 (m, 1H), 6.57 (dd, J = 1.8, 3.3 Hz, 1H), 6.89-6.90 (, 1H), 6.97 (d, J = 3.3 Hz , 1H), 7.41-7.42 (m, 1H), 7.68 (d, J = 1.8 Hz, 1H), 8.03 (d, J = 6.1 Hz, 2H), 8.83 (d, J = 6.1 Hz, 2H), 11.6 (br s, 1H), 13.5 (br s, 1H). p.f .: 259-260 ° C.

[Example 354] N- [4- (2-Furyl) -5- (l-methylpyrrol-3-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 354) Compound 353 (105 mg, 0.288 mmol ) was dissolved in DMF (1.4 mL), and 55% sodium hydride (25.3 mg, 0.576 mmol) and methyl iodide (0.0179 mL, 0.288 mmol) were added thereto, followed by stirring at room temperature for 2 hours.

The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give the title Compound 354 (97.0 mg, 89%). X H NMR (DMSO-dg, d ppm): 3.69 (s, 3 H), 6.36 (dd, J = 1.8, 3.5 Hz, 1 H), 6.61-6.62 (m, 1 H), 6.71-6.72 (m, 1 H), 7.16 (d, J = 3.5 Hz, 1H), 7.29 (d, J = 1.8 Hz, 1H), 7.33-7.34 (m, 1H), 7.74 (d, J = 6.1 Hz, 2H), 8.82 (d, J = 6.1 Hz, 2H), 10.7 (br s, 1H). APCIMS m / z: [M + H] + 379. p.f .: 209-211 ° C.

[Example 355] N- [5- (l-Ethylpyrrol-3-ylcarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 355) In a manner similar to that in Example 354, when using ethyl iodide instead of methyl iodide, the Compound title 355 (99.0 mg, 88%) was obtained from Compound 353 (105 mg, 0.288 mmol). X H NMR (DMSO-de, d ppm): 1.44 (t, J = 7.3 Hz, 3 H), 3.94 (q, J = 7.3 Hz, 2 H), 6.34 (dd, J = 1.7, 3.3 Hz, 1 H), 6.66 -6.72 (m, 2H), 7.11 (d, J = 3.3 Hz, 1H), 7.31 (d, J = 1.7 Hz, 1H), 7.33-7.34 (, 1H), 7.73 (d, J = 6.1 Hz, 2H), 8.80 (d , J = 6.1 Hz, 2H), 10.9 (br s, 1H). APCIMS m / z: [M + H] + 393. mp .: 127-134 ° C.

[Example 356] N- [5- (l-Benzylpyrrol-3-ylcarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 356) In a manner similar to that in Example 354, when using benzyl chloride in place of methyl iodide, the title Compound 356 (106 mg, 85%) was obtained from Compound 353 (100 mg, 0.274 mmol). X H NMR (DMSO-de, d ppm): 5.06 (s, 2H), 6.35 (dd, J = 1.8, 3.5 Hz, 1H), 6.65-6.75 (m, 2H), 7.11-7.14 (m, 3H), 7.31-7.37 (m, 5H), 7.73 (d, J = 6.1 Hz, 2H), 8.81 (d, J = 6.1 Hz, 2H), 10.6 (br s, 1H). APCIMS m / z: [M + H] + 455. p. f. : 175-178 ° C.

[Example 357] N- [5- (5-tert-Butyl-1,3,4-oxadiazol-2-ylcarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 357 ) 2-tert-Butyl-l, 3,4-oxadiazole (116 mg, 0.919 mmol) obtained according to the method described in WO 01/57004 was dissolved in THF (4 mL), and a 2.00 mol / L solution of lithium diisopropylamide (0.420 mL, 0.840 mmol) in THF was added thereto in a stream of argon at -78 ° C, followed by stirring for 15 hours. minutes at -78 ° C. A solution of Compound 98 (100 mg, 0.279 mmol) in THF (2 mL) was added dropwise to the reaction mixture, followed by stirring at room temperature for 1.5 hours. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was made as a thick mixture with ethanol to provide the title Compound 357 (80.7 mg, 68%). X H NMR (DMSO-de, d ppm): 1.40 (s, 9H), 6.71 (dd, J = 1.9, 3.5 Hz, 1H), 7.59 (d, J = 3.5 Hz, 1H), 7.84 (d, J = 1.9 Hz, 1H), 8.05 (dd, J = 1.6, 6.2 Hz, 2H), 8.85 (dd, J = 1.6, 6.2 Hz, 2H), 13.77 (br s, 1H). ESIMS m / z: [M + H] + 424. p.f .: 190-255 ° C (decomposition).

[Example 358] 2-Amino-4- (2-furyl) thiazol-5-yl 2-oxo-l, 2-dihydropyridin-5-yl ketone (Compound 358) Compound 318 (1.36 g, 4.51 mmol) was dissolved in acetic acid (4 mL), and 48% hydrobromic acid (4 mL) was added thereto, followed by stirring at 100 ° C for 1 hour. The reaction mixture was poured into an aqueous saturated sodium carbonate solution, and the precipitated solid was collected by filtration to provide the title Compound 358 (1.20 g, 93%). X H NMR (DMSO-de, d ppm): 6.18 (d, J = 9.5 Hz, 1H), 6.50 (dd, J = 1.6, 3.2 Hz, 1H), 6.73 (d, J = 3.2 Hz, 1H), 7.54 (d, J = 1. 6 Hz, 1H), 7.60 (dd, J = 2.4, 9.5 Hz, 1H), 7.74 (d, J = 2.4 Hz, 1H), 7.83 (br s, 2H).

[Example 359] 2-Amino-4- (2-furyl) thiazol-5-yl-l-methyl-2-oxo-l, 2-dihydropyridin-5-yl ketone (Compound 359) In a manner similar to that in Example 126, the Compound of 359 title (160 mg, 53%) was obtained as a yellow solid from Compound 358 (287 mg, 1.00 mmol) in place of Compound q. X H NMR (DMSO-de, d ppm): 3.30 (s, 3H), 6.30 (d, J = 9.7 Hz, 1H), 6.51 (dd, J = 1.6, 3.2 Hz, 1H), 6.74 (dd, J = 0.5, 3.2 Hz, 1H), 7.51 (dd, J = 0.5, 1.6 Hz, 1H), 7.60 (dd, J = 2.7, 9. 7 Hz, 1H), 7.94 (br s, 2H), 8.11 (d, J = 2.7 Hz, 1H). ESIMS m / z: [M + H] + 302.

[Example 360] N- [4- (2-Furyl) -5- (l-methyl-2-oxo-l, 2-dihydropyridin-5-ylcarbonyl) thiazol-2-yl] - iridin-4-carboxamide (Compound 360) In a manner similar to that in Example 187, a Crude Compound 360 was obtained from Compound 359 (160 mg, 0.530 mmol) in place of Compound 186. The resulting crude Compound 360 was made back into a thickened mixture with methanol to provide the title compound 360 (134 mg, 64%) as a yellow solid. X H NMR (DMSO-de, d ppm): 3.33 (s, 3 H), 6.41 (d, J = 9.7 Hz, 1 H), 6.59 (d, J = 2.2, 3.2 Hz, 1 H), 6.88 (d, J = 3.2 Hz, 1H), 7.65 (d, J = 2.2 Hz, 1H), 7.77 (dd, J = 2.4, 9.7 Hz 1H), 8.03 (dd, J = 1.6, 4.6 Hz, 2H), 8.37 (d, J = 2.4 Hz, 1H), 8.84 (dd, J = 1.6, 4.6 Hz, 2H), 13.58 (brs, 1H). APCIMS m / z: [M + H] + 407. p.f .: 294-295 ° C.

[Example 361] 2-Amino-4- (2-furyl) thiazol-5-yl-l-ethyl-2-oxo-l, 2-dihydropyridin-5-yl ketone (Compound 361) In a manner similar to that in Example 126, when using ethyl iodide in place of methyl iodide, the title Compound 361 (160 mg, 51%) was obtained as a yellow solid from Compound 358 (287 mg, 1.00 mmol) instead of Compound q .

X H NMR (DMSO-d 6, d ppm): 1.01 (t, J = 6.5 Hz, 3 H), 3.79 (q, J = 6.5 Hz, 2 H), 6.34 (d, J = 9.5 Hz, 1 H), 6.50 (dd) , J = 1.6, 3.2 Hz, 1H), 6.74 (d, J = 3.2 Hz, 1H), 7.51 (d, J = 1.6 Hz, 1H), 7.64 (dd, J = 2.4, 9.5 Hz, 1H), 7.93 (br s, 2H), 8.11 (d, J = 2.4 Hz, 1H). APCIMS m / z: [M + H] + 316.

[Example 362] N- [5- (1-Ethyl-2-oxo-l, 2-dihydropyridin-5-ylcarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 362 ) In a manner similar to that in Example 187, a Crude compound 362 was obtained from Compound 361 (160 mg, 0.510 mmol) in place of Compound 186. The resulting crude Compound 362 was made as a thickened mixture with methanol to provide the title Compound 362 (80.7 mg, 38%) as a yellow solid. X H NMR (DMSO-de, d ppm): 1.04 (t, J = 7.3 Hz, 3H), 3.85 (q, J = 7.3 Hz, 2H), 6.43 (d, J = 9.7 Hz, 1H), 6.58 (dd, J = 1.6, 3. 2 Hz, 1H), 6.88 (d, J = 3.2 Hz, 1H), 7.64 (d, J = 1.6 Hz, 1H), 7.98 (dd, J = 2.7, 9.7 Hz, 1H), 8.04 (dd, J = 1.6, 4.4 Hz, 2H), 8.32 (d, J = 2.7 Hz, 1H), 8.85 (dd, J = 1.6, 4.4 Hz 2H), 13.59 (br s, 1H). APCIMS m / z: [M + H] + 421. p. f. : 295-296 ° C.

[Example 363] 2-Amino-4- (2-furyl) thiazol-5-yl-l-benzyl-2-oxo-l, 2-dihydropyridin-5-yl ketone (Compound 363) In a manner similar to that in Example 126, when using benzyl bromide in place of methyl iodide, the Compound of title 363 (130 mg, 34%) was obtained from Compound 362 (287 mg, 1.00 mmol) instead of Compound q. X H NMR (DMSO-d 6, d ppm): 5.02 (s, 2 H), 6.36 (d, J = 9.7 Hz, 1 H), 6.45 (dd, J = 1.6, 3.2 Hz, 1 H), 6.70 (dd, J = 0.5, 3.2 Hz, 1H), 7.10 (dd, J = l. ~ 6, 7.5 Hz, 2H), 7.20-7.30 (m, 3H), 7.43 (dd, J = 0.5, 1.6 Hz, 1H), 7.64 ( dd, J = 2.7, 9.7 Hz, 1H), 7.90 (br s, 2H), 8.29 (d, J = 2.7 Hz, 1H). APCIMS m / z: [M + H] + 378.

[Example 364] N- [5- (l-Benzyl-2-oxo-l, 2-dihydropyridin-5-ylcarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 364 ) In a manner similar to that in Example 187, a Crude Compound 364 was obtained from Compound 363 (130 mg, 0.340 mmol) in place of Compound 186. The resulting crude Compound 364 was made back into a thickened mixture with methanol for give the title compound 364 (98.1 mg, 60%) as a yellow solid. X H NMR (DMSO-de, d ppm): 5.05 (s, 2H), 6.45 (d, J = 9.5 Hz, 1H), 6.54 (dd, J = 1.9, 3.2 Hz, 1H), 6.83 (d, J = 3.2 Hz, 1H), 7.04-7.12 (m, 2H), 7.24-7.30 (m, 3H), 7.58 (d, J = 1.9 Hz, 1H), 7.82 (dd, J = 2.7, 9.5 Hz, 1H), 8.02 (dd, J = 1.6, 4. 6 Hz, 2H), 8.51 (d, J = 2.7 Hz, 1H), 8.83 (dd, J = 1.6, 4.6 Hz, 2H), 13.57 (br s, 1H). APCIMS m / z: [M + H] + 483. mp: 265-282 ° C (dec.) [Example 365] 2-Amino-4- (2-furyl) thiazol-5-yl 2-oxo-l, 2 dihydropyridin-4-yl ketone (Compound 365) In a manner similar to that in Example 358, the Compound of title 365 (444 mg, 41%) was obtained from Compound 335 (1.14 g, 3.78 mmol) in place of Compound 318.

X H NMR (DMSO-de, d ppm): 6.15 (dd, J = 1.6, 6.2 Hz, 1H), 6.22 (d, J = 1.6 Hz, 1H), 6.51 (dd, J = 1.9, 3.5 Hz, 1H) , 6.98 (d, J = 3.5 Hz, 1H), 7.33 (d, J = 6.2 Hz, 1H), 7.52 (d, J = 1.9 Hz, 1H), 11.65 (br s, 1H). APCIMS m / z: [M + H] + 288.

[Example 366] 2-Amino-4- (2-furyl) thiazol-5-yl-l-methyl-2-oxo-l, 2-dihydropyridin-4-yl ketone (Compound 366) In a manner similar to that in Example 126, the Compound of title 366 (114 mg, 77%) was obtained as a yellow solid from Compound 365 (140 mg, 0.487 mmol) instead of Compound q. X H NMR (DMSO-de, d ppm): 3.39 (s, 3 H), 6.19 (dd, J = 1.9, 7.0 Hz, 1 H), 6.30 (d, J = 1.9 Hz, 1 H), 6.51 (dd, J = 1.9, 3.5 Hz, 1H), 7.00 (dd J = 0.8, 3.5 Hz, 1H), 7.51 (dd, J = .0.8, 1.9 Hz, - 1H), 7.66 (d, J = 7.0 Hz, 1H), 8.20 (br s, 2H). APCIMS m / z: [M + H] + 302.

[Example 367] N- [4- (2-Furyl) -5- (l-methyl-2-oxo-l, 2-dihydropyridin-4-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 367 ) In a manner similar to that in Example 187, a Crude compound 367 was obtained from Compound 366 (114 mg, 0.378 mmol) in place of Compound 186. The resulting crude Compound 367 was made to make a thickened mixture with methanol to provide the title Compound 367 (35.2 mg, 23%) as a yellow solid. X H NMR (DMSO-de, d ppm): 3.44 (s, 3 H), 6.38 (dd, J = 1.9, 7.0 Hz, 1 H), 6.53 (d, J = 1.9 Hz, 1 H), 6.62 (dd, J = 1.6, 3.5 Hz, 1H), 7.19 (dd, J = 0.5, 3.5 Hz, 1H), 7.70-7.77 (m, 2H), 8.03 (dd, J = 1.6, 4.6 Hz, 2H), 8.84 (dd, J = 1.6, 4.6 Hz, 2H), 13.69 (br s, 1H). APCIMS m / z: [M + H] + 407. p.f .: 243-255 ° C (decomposition) [Example 368] 2-Amino-4- (2-furyl) thiazol-5-yl-l-ethyl-2-oxo-l, 2-dihydropyridin-4-yl ketone (Compound 368) In a manner similar to that in Example 126, when using ethyl iodide in place of methyl iodide, the Compound of title 368 (91.0 mg, 59%) was obtained as a yellow solid from Compound 365 (140 mg, 0.487 mmol) in place of Compound q. X H NMR (DMSO-de, d ppm): 1.18 (t, J = 7.3 Hz, 3 H), 3.86 (q, J = 7.3 Hz, 2 H), 6.20 (dd, J = 1.6, 4.9 Hz, 1 H), 6.26 (d, J = 1.6 Hz, 1H), 6.49 (dd, J = 1.6, 3.2 Hz, 1H), 6.95 (dd, J = 0.5, 3. 2 Hz, 1H), 7.48 (dd, J = 0.5, 1.6 Hz, 1H), 7.66 (d, J = 4.9 Hz, 1H), 8.21 (br s, 2H) APCIMS m / z: [M + H] + 316.

[Example 369] N- [5- (l-Ethyl-2-oxo-l, 2-dihydropyridin-4-ylcarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 369 ) In a manner similar to that in Example 187, a Crude Compound 369 was obtained from Compound 368 (81.5 mg, 0.258 mmol) instead of Compound 186. The Resulting crude compound 369 was made back into a thick mixture with methanol to provide the title Compound 369 (31.4 mg, 29%) as a yellow solid. X H NMR (DMSO-de, d ppm): 1.21 (t, J = 7.0 Hz, 3H), 3.91 (q, J = 7.0 Hz, 2H), 6.38 (dd, J = 1.9, 7.3 Hz, 1H), 6.50 (d, J = 1.9 Hz, 1H), 6.60 (dd, J = 1.9, 3.2 Hz, 1H), 7.15 (dd) , J = 0.8, 3.2 Hz, 1H), 7.65 (dd, J = 0.8, 1.9 Hz, 1H), 7.78 (d, J = 7.3 Hz, 1H), 8.02 (dd, J = 1.6, 4.4 Hz, 2H) , 8.84 (dd, J = 1.6, 4.4 Hz, 2H), 13.69 (br s, 1H). APCIMS m / z: [M + H] + 421. mp .: 277-281 ° C.

[Example 370] 2-Amino-4- (2-furyl) thiazol-5-yl-l-benzyl-2-oxo-l, 2-dihydropyridin-4-yl ketone (Compound 370) In a manner similar to that in Example 126, when using benzyl bromide in place of methyl iodide, theCompound 370 title (142 mg, 77%) was obtained from Compound 365 (140 mg, 0.487 mmol) in place of Compound q.

X H NMR (DMSO-de, d ppm): 5.07 (s, 2H), 6.23 (dd, J = 2.2, 7.0 Hz, 1H), 6.32 (d, J = 2.2 Hz, 1H), 6.42 (dd, J = 1.9, 3.5 Hz, 1H), 6.91 (dd, J = 0.8, 3.5 Hz, 1H), 7.20-7.24 (m, 2H), 7.29-7.41 (m, 4H), 7.74 (d, J = 7.0 Hz, 1H ), 8.22 (br s, 2H) APCIMS m / z: [M + H] + 378.

[Example 371] N- [5- (l-Benzyl-2-oxo-l, 2-dihydropyridin-4-ylcarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 371 ) In a manner similar to that in Example 187, a Crude compound 371 was obtained from Compound 370 (121 mg, 0.319 mmol) in place of Compound 186. The resulting crude Compound 371 was made to make a thickened mixture with methanol to provide the title Compound 371 (25.1 mg, 16%) as a yellow solid. X H NMR (DMSO-de, d ppm): 5.11 (s, 2 H), 6.41 (dd, J = 1.9, 6.7 Hz, 1 H), 6.54 (d, J = 1.9 Hz, 1 H), 6.55 (dd, J = 1.9, 3.5 Hz, 1H), 7.09 (dd, J = 0.8, 3.5 Hz, 1H), 7.20-7.41 (m, 5H), 7.55 (dd, J = 0.8, 1.9 Hz, 1H), 7.85 (d, J = 6.7 Hz, 1H), 8.02 (dd, J = 1.6, 4.3 Hz, 2H), 8.83 (dd, J = 1.6, 4.3 Hz, 2H), 13.68 (br s, 1H). APCIMS m / z: [M + H] + 483. p.f .: 288-291 ° C.

[Example 372] N- [4- (2-Furyl) -5- (pyrazin-2-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 372) In a manner similar to that in Example 185, when using 2-pyrazinecarboxylic acid in place of picolinic acid, the title Compound 372 (60.0 mg, 11%) was obtained from Compound h (500 mg, 1.45 mmol) obtained in the Example of Reference 8. XH NMR (CDC13, d ppm): 1.53 (s, 9H), 6.54 (dd, J = 1.8, 3.7 Hz, 1H), 7.47 (d, J = 1.8 Hz, 1H), 7.82 (d, J = 3.7 Hz, 1H), 8.63-8.64 (m, 1H), 8.72-8.73 (m, 1H), 9.34-9.35 (, 1H).

[Example 373] 2-Amino-4- (2-furyl) thiazol-5-yl pyrazin-2-yl ketone (Compound 373) In a manner similar to that in Example 186, the title compound 373 (44.0 mg, 100%) was obtained from Compound 372 (60.0 mg, 0.161 mmol) in place of Compound 185. XH NMR (CDC13, d ppm): 6.48 (dd, J = 1.8, 3.5 Hz, 1H), 7.42 (d, J = 1.8 Hz, 1H), 7.84 (d, J = 3.5 Hz, 1H), 8.49 (dd, J = 1.5, 2.5 Hz, 1H), 8.66 (d, J = 2.5 Hz, 1H), 9.29 (d, J = 1.5 Hz, 1H).

[Example 374] N- [4- (2-Furyl) -5- (pyrazin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 374) In a manner similar to that in Example 187, Compound of title 374 (50.0 mg, 82%) was obtained from Compound 373 (44.0 mg, 0.161 mmol) in place of Compound 186. XH NMR (DMSO-de, d ppm): 6.63 (dd, J = 1.8 , 3.5 Hz, 1H), 7.40 (d, J = 3.5 Hz, 1H), 7.66 (d, J = 1.8 Hz, 1H), 8.05 (d, J = 5.9 Hz, 2H), 8.74 (dd, J = 1.3 , 2.5 Hz, 1H), 8.85 (d, J = 5.9 Hz, 2H), 8.89 (d, J = 2.5 Hz, 1H), 9.23 (d, J = 1.3 Hz, 1H). APCIMS m / z; [M + H] + 378. p.f .: > 300 ° C.

[Example 375] N- [4- (2-Furyl) -5- (pyrimidin-4-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 375) The 2, 2, 6, 6-tetramethylpiperidine ( 0.233 L, 1.38 mmol) was dissolved in THF (6 mL), and a 1.58 mol / L solution of n-butyllithium in n-hexane (0.880 mL, 1.38 mmol) was added thereto under a stream of argon at -78. ° C, followed by stirring at room temperature for 30 minutes. At -78 ° C, a solution of Compound 98 (150 mg, 0.419 mmol) and pyrimidine (0.0990 mL, 1.26 mmol) in THF (2 mL) was added to the reaction mixture, followed by stirring at room temperature for 2 hours. hours. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to provide the title Compound 375 (11.0 mg, 7%). H NMR (DMSO-de, ppm): 6.64 (dd, J = 1.8, 3.5 Hz, 1H), 7.42. (dd, J = 0.7, 3.5 Hz, 1H), 7.66 (dd, J = 0.7, 1.8 Hz, 1H), 8. 02-8.03 (m, 1H), 8.05 (d, J = 6.1 Hz, 2H), 8.85 (d, J = 6.1 Hz, 2H), 9.12-9.14 (m, 1H), 9.33-9.34 (, 1H), 13.6 (br s, 1H).

APCIMS m / z: [M + H] + 378. p.f .: > 300 ° C.

[Example 376] N- [4- (2-Furyl) -5- (pyridazin-3-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 376) In a manner similar to that in Example 375, when using pyridazine in place of pyrimidine, the title Compound 376 (117 mg, 75%) was obtained from Compound 98 (150 mg, 0.419 mmol). X H NMR (DMSO-de, d ppm): 6.36 (d, J = 9.6 Hz, 1H), 6.46 (dd, J = 1.8, 3.3 Hz, 1H), 6.94 (dd, J = 0.7, 3.3 Hz, 1H) , 7.38-7.53 (m, 4H), 7.65 (d, J = 6.1 Hz, 2H), 8.05 (dd, J = 2.5, 9.6 Hz, 1H). APCIMS m / z: [M + H] + 378. m.p .: 280-281 ° C.

[Example 377] N- [5-Acetyl-4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 377) Compound 98 (1.01 g, 2.82 mmol) was suspended in THF (20 mL), and a 0.93 mol / L solution of methylmagnesium bromide (12.0 mL, 11.2 mmol) in THF was added thereto under cooling on ice, followed by stirring at room temperature for 2.5 hours. An aqueous solution Saturated ammonium chloride was added to the reaction mixture, and the precipitated solid was collected by filtration to provide the title Compound 377 (609 mg, 69%) as a pale yellow solid. X H NMR (DMSO, d ppm): 3.33 (s, 3 H), 6.71 (dd, J = 1.8, 3.5 Hz, 1 H), 7.43 (dd, J = 0.7, 3.5 Hz, 1 H), 7.91 (dd, J = 0.7, 1.8 Hz, 1H), 8.02 (d, J = 4.4 Hz, 2H), 8.83 (d, J = 4.4 Hz, 2H), 13.55 (br s, 1H). ESIMS m / z: [M + H] + 314. mp .: 252-259 ° C (decomposition).

[Example 378] N- [4- (2-Furyl) -5- (trifluoroacetyl) thiazol-2-yl] tert-butyl carbamate (Compound 378) In a manner similar to that in Step 2 of Example 176, when using phenyl trifluoroacetate instead of Phenyl 2-cyanobenzoate, Compound of title 378 (366 mg, 67%) was obtained from Compound h (520 mg, 1.51 mmol) obtained in Reference Example 8. XH NMR (CDC13, d ppm): 1.53 (s, 9H), 6.61 (dd, J = 1.6, 3.5 Hz, 1H), 7.61 (dd, J = 0.8, 1.6 Hz, 1H), 8.06 (dd, J = 0.8, 3. 5 Hz, 1H), 8.90 (br s, 1H) ESIMS m / z: [M-H] "361.

[Example 379] 2-Amino-4- (2-furyl) thiazol-5-yl trifluoromethyl ketone (Compound 379) In a manner similar to that in Example 186, Compound of title 379 (172 mg, 65%) was obtained from Compound 378 (366 mg, 1.01 mmol) in place of Compound 185. XH NMR ( DMSO-de, d ppm): 6.71 (dd, J = 1.6, 3.5 Hz, 1H), 7.83 (d, J = 3.5 Hz, 1H), 7.92 (d, J = 1.6 Hz, 1H), 8.75 (br , 2H) APCIMS m / z: [M + H] + 263.

[Example 380] N- [4- (2-Furyl) -5- (trifluoroacetyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 380) In a manner similar to that in Example 187, the title Compound 380 (52.3 mg, 22%) was obtained from Compound 379 (172 mg, 0.656 mmol) in place of Compound 186. XH NMR (DMSO-de, d ppm): 6.79 (dd, J = 1.6, 3.5 Hz, 1H), 7.81 (dd, J = 0.8, 3.5 Hz, 1H), 8.01 (dd, J = 0.8, 1.6 Hz, 1H), 8. 05 (dd, J = 1.6, 4.3 Hz, 2H), 8.86 (dd, J = 1.6, 4.3 Hz, 2H). APCIMS m / z: [M-H] ~ 366. p. f. : 268-270 ° C.

[Example 381] N- [4- (2-Furyl) -5-propionylthiazol-2-yl] pyridine-4-carboxamide (Compound 381) Compound 98 (200 mg, 0.559 mmol) was suspended in THF (2 mL) , and a 0.89 mol / L solution of ethylmagnesium bromide (2.00 mL, 1.78 mmol) in THF was added thereto under cooling on ice, followed by stirring overnight at room temperature. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with a mixed solvent (4: 1) of chloroform and 2-propanol. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 200: 1) to provide the title Compound 381 (27.2 mg, 15%) as a pale yellow solid. X H NMR (DMSO, d ppm): 1.08 (t, J = 7.2 Hz, 3 H), 2.88 (q, J = 7.2 Hz, 2 H), 6.70 (dd, J = 1.8, 3.7 Hz, 1 H), 7.46 (dd, J = 0.7, 3.7 Hz, 1H), 7.89 (dd, J = 0.7, 1.8 Hz, 1H), 8.02 (d, J = 4.4 Hz, 2H), 8.83 (d, J = 4.4 Hz, 2H) , 13.52 (br s, 1H). ESIMS m / z: [M + H] + 328. p.f .: 225-240 ° C (decomposition).

[Example 382] N- [5-Butyryl-4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 382) Compound 98 (200 mg, 0.559 mmol) was suspended in THF (5 mL ), and a 1.01 mol / L solution of propylmagnesium bromide (2.00 mL, 2.02 mmol) in THF was added thereto under cooling on ice, followed by stirring for 1 hour at room temperature. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by -extraction with. ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 4) to provide the title Compound 382 (76.3 mg, 40%) as a yellowish-green solid. X H NMR (DMSO, d ppm): 0.90 (t, J = 7.3 Hz, 3H), 1.60-1.66 (m, 2H), 2.82 (t, J = 7.3 Hz, 2H), 6.70 (dd, J = 1.8, 3.5 Hz, 1H), 7.46 (dd, J = 0.8, 3.5 Hz, 1H), 7.90 (dd, J = 0.8, 1.8 Hz, 1H), 8.02 (d, J = 4.5 Hz, 2H), 8.83 (d, J = 4.5 Hz, 2H), 13.55 (br s, 1H). ESIMS m / z: [M-H] "340. p.f .: 191-194 ° C.

[Example 383] N- [5-Butyryl-4- (2-furyl) thiazol-2-yl] tert-butyl carbamate (Compound 383) In a manner similar to that in Example 185, using butyric acid instead of picolinic acid, Title 383 compound (733 mg, 48%) was obtained from Compound h (1.57 g, 4.55 mmol) obtained in the Example of Reference 8. XH NMR (CDC13, d ppm): 0.86 (t, J = 7.3 Hz, 3H), 1.15-1.60 (m, 2H), 1.50 (s, 9H), 1.70-2.05 (m, 2H), 6.48 (dd, J = 1.8 Hz, 3.3 Hz, 1H), 6.99 (dd, J = 0.8, 1.8 Hz, 1H), 7.47 (dd, J = 0.8, 3.3 Hz, 1H), 8.20 (br s, 1H). ESIMS m / z: [M + H] + 337.

[Example 384] 2-Amino-4- (2-furyl) thiazol-5-yl-propyl ketone (Compound 384) In a manner similar to that in Example 186, the title compound 384 (159 mg, 15%) was obtained from Compound 383 (618 mg, 1.84 mmol) in place of Compound 185. H NMR (CDCl 3, d ppm ): 0.86 (t, J = 7.3 Hz, 3H), 1.15-2.05 (m, 4H), 5.46 (br s, 2H), 6.53 (dd, J = 1.8 Hz, 3.6 Hz, 1H), 7.54 (dd, J = 0.7, 1.8 Hz, 1H), 7.66 (dd, J = 0.7 Hz, 3.6 Hz, 1H). ESIMS m / z: [M + H] + 237.

- [Example 385] N- [5-Butyryl-4- (2-furyl) thiazol-2-yl] cyclopropancarboxamide (Compound 385) Compound 384 (79.8 mg, 0.338 mmol) and N, N-dimethylaminopyridine (2.10 mg, 0.0172 mmol) were dissolved in pyridine (1.5 mL), and cyclopropancarbonyl chloride (0.0521 mL, 0.570 mmol) was added thereto under cooling on ice, followed by stirring at room temperature for 5.5 hours. Aqueous saturated sodium acid carbonate solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from ethanol to provide Title Compound 385 (57.1 mg, 55%) as a white solid. XH NMR (CDC13, d ppm): 0.92-1.02 (m, 2H), 0.95 (t, J = 7.3 Hz, 3H), 1.16-1.25 (m, 2H), 1.42-1.53 (m, 1H), 1.73- 1.79 (m, 2H), 2.81 (t, J = 7.3 Hz, 2H), 6.56 (dd, J = 1.8, 3.7 Hz, 1H), 7.56 (dd, J = 0.7, 1.8 Hz, 1H), 7.84 (dd) , J = 0.7, 3.7 Hz, 1H), 9.95 (br s, 1H). ESIMS m / z: [M + H] + 305. p.f. : 170-172 ° C.

[Example 386] N- [5-Butyryl-4- (2- (furyl) thiazol-2-yl] furan-2-carboxamide (Compound 386) In a manner similar to that in Example 385, by using -furoyl (57.1 mL, 0.582 mmol) in place of cyclopropanecarbonyl chloride, the title compound 386 (28.9 mg, 76%) was obtained as a white solid from Compound 384 (80.0 mg, 0.339 mmol). XH NMR (CDC13, d ppm): 1.00 (t, J = 7.3 Hz, 3H), 1.76-1.82 (m, 2H), 2.85 (t, J = 7.3 Hz, 1H), 6.57 (dd, J = 1.7 Hz , 3.3 Hz, 1H), 6.65 (dd, J = 1.8, 3.7 Hz, 1H), 7.41 (dd, J = 0.7, 3.7 Hz, 1H), 7.59 (dd, J = 0.7, 1.8 Hz, 1H), 7.60 (dd, J = 0.7, 1.8 Hz, 1H), 7.82 (dd, J = 0.7 Hz, 3.3 Hz, 1H), 9.80 (br s, 1H). ESIMS m / z: [M + H] + 331. p.f.-. 172-176 ° C.

[Example 387] N- [5-Butyryl-4- (2-furyl) thiazol-2-yl] -2- (chloromethyl) pyridine-4-carboxamide (Compound 387) In a manner similar to that in Example 187, when using 2- (chloromethyl) isonicotinic acid obtained in accordance with the method described in WO 03/043636 in place of isonicotinic acid, Title Compound 387 (151 mg, 92%) was obtained from Compound 384 (100 mg, 0.423 mmol) instead of Compound 186. H NMR (CDCl 3, d ppm): 1.02 (t, J = 7.4 Hz, 3H), 1.78-1.84 (m, 2H), 2.87 (t, J = 7.4 Hz, 2H), 4.71 (s, 2H), 6.44 (dd, J = 1.8, 3.6 Hz, 1H), 7.38 (dd, J = 0.7, 1.8 Hz, 1H), 7.61-7.71 (m, 1H), 7.74 (dd, J = 0.7, 3.6 Hz, 1H), 7.88 (s, 1H), 8.73- (d, J = 5.1 Hz, 1H).

[Example 388] N- [5-Butyryl-4- (2-furyl) thiazol-2-yl] -2- (methoxymethyl) pyridine-4-carboxamide (Compound 388) Compound 387 (262 mg, 0.671 mmol) was dissolved in methanol (5 mL), and 55% sodium hydride (34.0 mg, 0.775 mmol) was added thereto, followed by stirring under heating and reflux for 4 hours. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 99: 1) to provide the title Compound 388 (142 mg, 55%). X H NMR (CDCl 3, d ppm): 1.01 (t, J = 7.3 Hz, 3 H), 1.77-1.83 (m, 2 H), 2.87 (t, J = 7.3 Hz, 2 H), 4.60 (s, 2 H), 6.43. (d, J = 1.8, 3.5 Hz, 1H), 7.39 (d, J = 1.8 Hz, 1H), 7.61-7.71 (m, 1H), 7.73 (d, J = 3.5 Hz, 1H), 7.79 (s, 1H), 8.71 (d, J = 5.0 Hz, 1H).

APCIMS m / z: [M + H] + 386.

[Example 389] N- [5-Butyryl-4- (2-furyl) thiazol-2-yl] -2- [2- (dimethylamino) ethoxymethyl] pyridine-4-carboxamide hydrochloride (Compound 389) Compound 387 ( 247 mg, 0.635 mmol) was dissolved in 2- (dimethylamino) ethanol (3 L), and 55% sodium hydride (55.0 mg, 1.27 mmol) was added thereto, followed by stirring at room temperature for 2 hours. The precipitated solid was collected by filtration to provide a free form of the title compound. A solution of ethyl acetate of 4 mol / L hydrogen chloride was added to the resulting free form, and the precipitated solid was collected by filtration to provide the title Compound 389 (248 mg, 82%).

X H NMR (DMSO-d 6, d ppm): 0.88 (t, J = 7.4 Hz, 3 H), 1.57-1.63 (m, 2 H), 2.64 (t, J = 7.4 Hz, 2 H), 3.16 (s, 6 H) , 3.53 (t, J = 5.0 Hz, 2H), 3.95 (t, J = 5.0 Hz, 2H), 4.76 (s, 2H), 6.60 (dd, J = 1.8, 3.3 Hz, 1H), 7.34 (dd, J = 0.8, 3.3 Hz, 1H), 7.77 (dd, J = 0.8, 1.8 Hz, 1H), 8.05-8.15 (m, 1H), 8.35 (s, 1H), 8.77 (d, J = 5.0 Hz, 1H ). APCIMS m / z: [M + H] + 443.

[Example 390] N- [5-Butyryl-4- (2-furyl) thiazol-2-yl] -2-morpholineacetamide (Compound 390) In a manner similar to that in Example 287, the title Compound 390 (150 mg, 69%) was obtained from Compound 384 (150 mg, 0.526 mmol) in place of Compound 286. XH NMR (CDC13, d ppm): 0.987 (t, J = 7.4 Hz, 3H), 1.74-1.80 ( m, 2H), 2.67 (t, J = 4.6 Hz, 4H), 2.82 (t, J = 7.4 Hz, 2H), 3.79 (t, J = 4.6 Hz, 4H), 6.57 (dd, J = 1.7, 3.5 Hz, 1H), 7.59 (dd, J = 0.7, 1.7 Hz, 1H), 7.80 (dd, J = 0.7, 3.5 Hz, 1H). APCIMS m / z: [M + H] + 364.

[Example 391] N- [4- (2-furyl) -5-isobutyrylthiazol-2-yl] tert-butyl carbamate (Compound 391) In a manner similar to that in Example 176, by using isobutyric acid instead of 2-Cyanobenzoic acid, Compound of title 391 (618 mg, 55%) was obtained from Compound h (1.16 g, 3.36 mmol) obtained in Reference Example 8. X H NMR (CDCl 3, d ppm): 1.22 ( d, J = 7.0 Hz, 6H), 1.54 (s, 9H), 3.16 (septet, J = 7.0 Hz, 1H), 6.54 (dd, J = 1.8, 3.7 Hz, 1H), 7.55 (dd, J = 0.7 , 1.8 Hz, 1H), 7.79 (dd, J = 0.7, 3.7 Hz, 1H), 8.52 (br s, 1H).

ESIMS m / z: [M + H] + 337.

[Example 392] 2-Amino-4- (2-furyl) thiazol-5-yl isopropyl ketone (Compound 392) In a manner similar to that in Example 186, the title compound 392 (217 mg, 27%) was obtained as a pale yellow solid from Compound 391 (618 mg, 1.80 mmol) in place of Compound 185. XH NMR (CDC13, d ppm): 1.18 (d, J = 6.8 Hz, 6H), 3.00 (septet, J = 6.8 Hz, 2H), 5.46 (br s, 2H), 6.53 (dd, J = 1.8, 3.6 Hz, 1H), 7.54 (dd, J = 0.7, 1.8 Hz, 1H), 7.66 (dd, J = 0.7 , 3.6 Hz, 1H). ESIMS m / z: [M + H] + 237. p.f .: 195-199 ° C.

[Example 393] N- [4- (2-Furyl) -5-isobutyrylthiazol-2-yl] pyridine-4-carboxamide (Compound 393) Compound 392 (100 mg, 0.424 mmol) was dissolved in DMF (5 mL) , and isonicotinic acid (205 mg, 1.68 mmol), EDC hydrochloride (324 mg, 1.69 mmol) and 1-hydroxybenzotriazole monohydrate (259 mg, 1.69 mmol) were added thereto, followed by stirring at 60 ° C for 3 hours. . The reaction mixture was concentrated under reduced pressure, and a solution Aqueous saturated carbonate of sodium acid was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from ethanol to provide the title Compound 393 (103 mg, 71%) as a pale green solid. XH NMR (CDC13, d ppm): 1.27 (d, J = 6.6 Hz, 6H), 3.26 (septet, J = 6.6 Hz, 1H), 6.53 (dd, J = 1.8, 3.7 Hz, 1H), 7.52 (dd) , J = 0.8, 1.8 Hz, 1H), 7.74 (d, J = 4.4 Hz, 2H), 7.82 (dd, J = 0.8, 3.7 Hz, 1H), 8.87 (d, J = 4.4 Hz, 2H), 10.17 (br s, 1H). ESIMS m / z: [M + H] + 342. p.f .: 179-182 ° C.

[Example 394] N- [4- (2-Furyl) -5-isobutyrylthiazol-2-yl] cyclopropane carboxamide (Compound 394) In a manner similar to that in Example 385, the Compound of title 394 (95.3 mg, 73%) was obtained as a pink solid from Compound 392 (100 mg, 0.424 mmol) in place of Compound 384. X H NMR (CDCl 3, d ppm): 0.93-1.03 (m , 2H), 1.15-1.25 (m, 2H), 1.23 (d, J = 7.0 Hz, 6H), 1.43-1.53 (m, 1H), 3.16 (septet, J = 7.0 Hz, 1H), 6.55 (dd, J = 1.8, 3.7 Hz, 1H), 7.56 (dd, J = 0.7, 1.8 Hz, 1H), 7.85 (dd, J = 0.7, 3.7 Hz, 1H), 10.07 (br s, 1H). ESIMS m / z: [M + H] + 305. p.f .: 178-182 ° C.

[Example 395] N- [4- (2-Furyl) -5- (1-hydroxypentyl) thiazole-2-ylcarbamate tert-butyl compound (Compound 395) Compound 92 (298 mg, 1.01 mmol) was dissolved in THF (10 mL), and a 1.59 mol / L solution of n-butyllithium in n-hexane (5.70 L, 9.06 mmol) was added thereto in a stream of argon at -78 ° C, followed by stirring at room temperature during 2 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 3: 1) to give the title compound 395 (224 mg, 63%). XH NMR (CDC1, d ppm): 0.90 (t, J = 7.0 Hz, 3H), 1.34-1.45 (, 13H), 1.79-1.97 (m, 2H), 5.43-5.49 (m, 1H), 5.46 (t , J = 6.7 Hz, 1H), 6.47 (dd, J = 1.8, 3.4 Hz, 1H), 6.68 (dd, J = 0.8, 3.4 Hz, 1H), 7.46 (dd, J = 0.8, 1.8 Hz, 1H) .

[Example 396] N- [4- (2-Furyl) -5-valerylthiazol-2-yl] tert-butyl carbamate (Compound 396) In a manner similar to that in Example 297, the "" Compound of title 396 (134 mg, 60%) was obtained as a pink solid from Compound 395 (224 mg, 0.635 mmol) in place of Compound 296. XH NMR (CDC13, d ppm): 0.93 (t, J = 7.3 Hz, 3H), 1.31-1.42 (m, 2H), 1.53 (s, 9H), 1.62-1.77 (m, 2H), 2.82 (t, J = 7.3 Hz, 2H), 6.55 (dd, J = 1.8, 3.4 Hz , 1H), 7.55 (dd, J = 0.8, 1.8 Hz, 1H), 7.78 (d, J = 0.8, 3.4 Hz, 1H), 8.62 (br s, 1H).

[Example 397] 2-Amino-4- (2-furyl) thiazol-5-yl butyl ketone (Compound 397) In a manner similar to that in Example 186, the Compound of title 397 (71.7 mg, 75%) was obtained from Compound 396 (134 mg, 0.384 mmol) instead of Compound 185. X H NMR (CDCl 3, d ppm): 0.91 (t, J = 7.3 Hz, 3 H), 1.29-1.41 (m, 2 H), 1.61-1.72 (m, 2 H), 2.69 (t, J = 7.3 Hz, 2 H) , 5.99 (br s, 2H), 6.55 (dd, J = 1.8, 3.5 Hz, 1H), 7.56 (dd, J = 1.0, 1.8 Hz, 1H), 7.62 (dd, J = 1.0, 3.5 Hz, 1H).

[Example 398] N- [4- (2-Furyl) -5-pivaloylthiazol-2-yl] tert-butyl carbamate (Compound 398) In a manner similar to that in Example 176, when using pivalic acid instead of 2-cyanobenzoic acid, Compound of title 398 (286 mg, 12%) was obtained from Compound h (2.26 g, 6.55 mmol) obtained in the Example of Reference 8. H NMR (CDC13, d ppm): 1.33 (s, 9H), 1.51 (s, 9H), 6.47 (dd, J = 1.8 Hz, 3.5 Hz, 1H), 7.10 (d, J = 3.5 Hz, 1H), 7.46 (d, J = 1.8 Hz, 1H), 8.63 (br s, 1H). ESIMS m / z: [M + H] + 351. [Example 399] 2-Amino-4- (2-furyl) thiazol-5-yl tert-butyl ketone (Compound 399) In a manner similar to that in Example 186, using Compound 398 (286 mg, 0.817 mmol) in place of Compound 185, the title compound 399 (205 mg, 100%) was obtained. X H NMR (CDCl 3, d ppm): 1.30 (s, 9 H), 5.26 (br s, 2 H), 6.47 (dd, J = 1.8 Hz, 3.5 Hz, 1 H), 7.30 (d, J = 3.5 Hz, 1 H) , 7.47 (d, J = 1.8 Hz, 1H). ESIMS m / z: [M + H] + 251.

[Example 400] N- [4- (2-Furyl) -5-pivaloylthiazol-2-yl] pyridine-4-carboxamide (Compound 400) Compound 399 (102 mg, 0.408 mmol) was dissolved in DMF (5 mL) , and isonicotinic acid (199 mg, 1.63 mmol), EDC hydrochloride (309 mg, 1.61 mmol) and 1-hydroxybenzotriazole monohydrate (245 mg, 1.60 mmol) were added thereto, followed by stirring at 60 ° C for 1.5 hours. . The reaction mixture was concentrated under reduced pressure, and a saturated aqueous solution of sodium acid carbonate was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from ethanol to provide the title Compound 400 (115 mg, 79%) as a pale yellowish green solid. XH NMR (CDC13, d ppm): 1.36 (s, 9H), 6.45 (dd, J = 1.8 Hz, 3.5 Hz, 1H), 7.09 (dd, J = 0.5, 3.5 Hz, 1H), 7.44 (dd, J = 0.5 Hz, 1.8 Hz, 1H), 7.75 (d, J = 4.5 Hz, 2H), 8.86 (d, J = 4.5 Hz, 2H), 10.05 (br s, 1H). ESIMS m / z: [M + H] + 356. p.f. : 240-245 ° C.

[Example 401] N- [4- (2-Furyl) -5-pivaloylthiazol-2-yl] cyclopropanecarboxamide (Compound 401) In a manner similar to that in Example 400, when using cyclopropanecarboxylic acid (0.130 mL, 1.61 mmol) instead of isonicotinic acid, the title compound 401 (94.8 mg, 76%) was obtained as a white solid from Compound 399 (98.2 mg, 0.393 mmol). XH NMR (CDC13, d ppm): 0.88-0.98 (, 2H), 1.13-1.20 (m, 2H), 1.32 (s, 9H), 1.40-1.50 (m, 1H), 6.48 (dd, J = 1.8, 3.7 Hz, 1H), 7.16 (dd, J = 0.7, 3.7 Hz, 1H), 7.48 (dd, J = 0.7, 1.8 Hz, 1H), 10.15 (br s, 1H). ESIMS m / z: [M + H] + 319. p.f .: 133-134 ° C. [Example 402] N- [4- (2-Furyl) -5- (methoxyacetyl) thiazol-2-yl] tert-butyl carbamate (Compound 402) In a manner similar to that in Example 185, by using methoxyacetic acid instead of picolinic acid, the title compound 402 (1.12 g, 42%) was obtained from the Compound h (2.69 g, 7.79 mmol) obtained in the Example of Reference 8. X H NMR (CDCl 3, d ppm): 1.46 (s, 9 H), 3.47 (s, 3 H), 4.41 (s, 2 H), 6.54 (dd, J = 1.7, 3.5 Hz, 1 H), 7.53 (d , J = 1.7 Hz, 1H), 7.80 (d, J = 3.5 Hz, 1H).

[Example 403] 2-Amino-4- (2-furyl) thiazol-5-yl methoxymethyl ketone (Compound 403) In a manner similar to that in Example 186, the title compound 403 (296 mg, 98%) was obtained from Compound 402 (428 mg, 1.26 mmol) in place of Compound 185.

X H NMR (CDC13, d ppm): 3.43 (s, 3 H), 4.29 (s, 2 H), 6.54 (d, J = 1.8, 3.5 Hz, 1 H), 7.55 (d, J = 1.8 Hz, 1 H), 7.69 (d, J = 3.5 Hz, 1H).

[Example 404] 2-Chloro-N- [4- (2-furyl) -5- (methoxyacetyl) thiazol-2-ylpyridine-5-carboxamide (Compound 404) In a manner similar to that in Example 187, when using 6-chloronicotinic acid in place of isonicotinic acid, Compound of titer 404 (129 mg, 81%) was obtained from Compound 403 (100 mg, 0.420 mmol) instead of Compound 186. X H NMR (CDCl 3, d ppm): 3.51 (s, 3 H), 4.44 (s, 2 H), 6.48 (dd, J = 1.8, 3.7 Hz, 1 H), 7.44-7.46 (m, 2 H), 7.77 (d, J = 3.7 Hz, 1H), 8.18 (dd, J = 2.2, 8.4 Hz, 1H), 8.92 (d, J = 2.2 Hz, 1 HOUR) . APCIMS m / z: [M + H] + 378. p. f. : 174-183 ° C.

[Example 405] 4-Fluoro-N- [4- (2-furyl) -5- (methoxyacetyl) thiazol-2-yl-benzamide (Compound 405) In a manner similar to that in Example 187, when using 4-fluorobenzoic acid in place of isonicotinic acid, Title Compound 405 (138 mg, 91%) was obtained from Compound 403 (100 mg, 0.420 mmol) instead of Compound 186. XH NMR (CDC13, d ppm): 3.50 (s, 3H), 4.45 (s, 2H), 6.51 (dd, J = 1.8, 3.3 Hz, 1H), 7.15-7.21 ( m, 2H), 7.50 (d, J = 1.8 Hz, 1H), 7.82 (d, J = 3.3 Hz, 1H), 7.93-7.97 (m, 2H). APCIMS m / z: [M + H] + 361. mp .: 166-167 ° C. [Example 406] N- [5- (ethoxyacetyl) -4- (2-furyl) thiazol-2-yl] tert-butyl carbamate (Compound 406) In a manner similar to that in Example 185, when using ethoxyacetic acid in place of picolinic acid, Compound of title 406 (450 mg, 28%) was obtained from Compound h (1.59 g, 4.60 mmol) obtained in Reference Example 8. H NMR (CDCl 3, d ppm): 1.27 (t, J = 6.9 Hz, 3H), 1.51 (s, 9H), 3.61 (q, J = 6.9 Hz, 2H), 4.44 (s, 2H), 6.54 (dd, J = 1.8, 3.5 Hz, 1H) , 7.55 (d, J = 1.8 Hz, 1H), 7.81 (d, J = 3.5 Hz, 1H).

[Example 407] 2-Amino-4- (2-furyl) thiazol-5-yl-ethoxymethyl ketone (Compound 407) In a manner similar to that in Example 186, the title compound 407 (247 mg, 77%) was obtained from Compound 406 (450 mg, 1.28 mmol) in place of Compound 185. XH NMR (CDC13, d ppm): 1.24 (t, J = 7.1 Hz, 3H), 3.57 (q, J = 7.1 Hz, 2H), 4.31 (s, 2H), 6.54 (dd, J = 1.8, 3.5 Hz, 1H), 7.56 (d, J = 1.8 Hz, 1H), 7.75 (d, J = 3.5 Hz, 1H).

[Example 408] N- [5-Acryloyl-4- (2-furyl) thiazol-2-yl] tert-butyl carbamate (Compound 408) Compound 98 (1.00 g, 2.83 mmol) was dissolved in THF (6 mL ), and a 1.0 mol / L solution of vinylmagnesium bromide in THF (8.49 mL, 8.49 mmol) was added thereto in an argon atmosphere at 0 ° C, followed by stirring at room temperature for 2 hours. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 3: 1) to provide the Compound title 408 (697 mg, 74%). - XH NMR (CDC13, d ppm): 1.45 (s, 9H), 5.76 (dd, J = 1.7, 10.2 Hz, 1H), 6.42. (dd, J = 1.7, 16.8 Hz, 1H), 6.53 (dd, J = 1.8, 3.5 Hz, 1H), 6.83 (dd, J = 10.2, 16.8 Hz, 1H), 7.53 (d, J = 1.8 Hz, 1H), 7.56 (d, J = 3.5 Hz, 1H).

[Example 409] N- [4- (2-Furyl) -5- (2-methoxyethylcarbonyl) -thiazol-2-yl] tert-butyl carbamate (Compound 409) Compound 408 (110 mg, 0.343 mmol) was dissolved in methanol (10 mL), and potassium hydroxide (20.0 mg, 0.356 mmol) was added thereto, followed by stirring under heating and refluxing for 2.5 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to provide the title Compound 409 (124 mg, 0.343 mmol). X H NMR (CDCl 3, d ppm): 1.47 (s, 9 H), 3.07 (t, J = 6.1 Hz, 2 H), 3.33 (s, 3 H), 3.76 (t, J = 6.1 Hz, 2 H), 6.52 (dd) , J = 1.8, 3.5 Hz, 1H), 7.53 (d, J = 1.8 Hz, 1H), 7.72 (d, J = 3.5 Hz, 1H).

[Example 410] 2-Amino-4- (2-furyl) thiazol-5-yl 2-methoxyethyl ketone (Compound 410) Compound 409 (124 mg, 0.343 mmol) was dissolved in trifluoroacetic acid (3 mL), followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and a saturated aqueous solution of sodium acid carbonate was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate., and then the solvent was distilled under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to provide the title Compound 410 (79.0 mg, 87%). XH NMR (CDC13, d ppm): 2.96 (t, J = 6.2 Hz, 2H), 3.33 (s, 3H), 3.72 (t, J = 6.2 Hz, 2H), 5.61 (br s, 2H), 6.52 ( dd, J = 1.8, 3.5 Hz, 1H), 7.53-7.54 (m, 2H).

[Example 411] N- [5- (2-Ethoxyethylcarbonyl) -4- (2-furyl) -thiazol-2-yl] tert-butyl carbamate (Compound 411) In a manner similar to that in Example 409, using ethanol in place of methanol, the title Compound 411 (126 mg, 100%) was obtained from Compound 408 (110 mg, 0.343 mmol). X H NMR (CDCl 3, d ppm): 1.16 (t, J = 6.9 Hz, 3 H), 3.08 (t, J = 6.4 Hz, 2 H), 3.49 (q, J = 6.9 Hz, 2 H), 3.80 (t, J = 6.4 Hz, 2H), 6.52 (dd, J = 1.8, 3.6 Hz, 1H), 7.53 (d, J = 1.8 Hz, 1H), 7.70 (d, J = 3.6 Hz, 1H).

[Example 412] 2-Amino-4- (2-furyl) thiazol-5-yl 2-ethoxyethyl ketone (Compound 412) In a manner similar to that in Example 410, the Compound of title 412 (79.0 mg, 87%) was obtained from Compound 411 (126 mg, 0.343 mmol) in place of Compound 409.

X H NMR (CDCl 3, d ppm): 1.16 (t, J = 7.0 Hz, 3 H), 2.97 (t, J = 6. 6 Hz, 2H), 3.48 (q, J = 7.0 Hz, 2H), 3.76 (t, J = 6.6 Hz, 2H), 5.70 (br s, 2H), 6.51 (dd, J = 1.8, 3.5 Hz, 1H ), 7.53 (dd, J = 0.7, 1.8 Hz, 1H), 7.56 (dd, J = 0.7, 3.5 Hz, 1H).

[Example 413] N- [4- (2-Furyl) -5- (3-methoxypropa-1-ynylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 413) In a manner similar to that in Example 283, when using methyl propargyl ether (65.5 mg, 0.935 mmol) instead of 2-bromo-6-methoxypyridine, Compound of title 413 (86.3 mg, 80%) was obtained from Compound 98 (105 mg, 0.292 mmol).

X H NMR (DMSO-d 6, d ppm): 3.37 (s, 3 H), 4.45 (s, 2 H), 6.74 (dd, J = 1.7, 3.5 Hz, 1 H), 7.76 (dd, J = 0.8, 3.5 Hz, 1H), 7.95 (dd, J = 0.8, 1.7 Hz, 1H), 8.04 (dd, J = 1.6, 4.5 Hz, 2H), 8.84 (dd, J = 1.6, 4.5 Hz, 2H), 13.80 (br s, 1 HOUR) . ESIMS m / z: [M + H] + 368. p.f. : 198-200 ° C.

[Example 414] N- [4- (2-Furyl) -5- (3-methoxypropa-1-ynylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 414) In a manner similar to that in Example 283, when using methyl propargyl ether (380 mg, 5.42 mmol) in place of 2-bromo-6-methoxypyridine, the title Compound 414 (479 mg, 78%) was obtained from Compound 134 (602 mg, 1.70 mmol ) in place of Compound 98. XH NMR (CDC13, d ppm): 1.55 (s, 9H), 3.47 (s, 3H), 4.34 (s, 2H), 6.58 (dd, J = 1.8, 3.0 Hz, 1H) , 7.59 (dd, J = 1.2, 1.8 Hz, 1H), 8.02 (dd, J = 1.2, 3.0 Hz, 1H), 8.67 (br s, 1H).

[Example 415] N- [4- (2-furyl) -5- (3-methoxypropylcarbonyl) -thiazol-2-yl] tert-butyl carbamate (Compound 415) Compound 414 (92.3 mg, 0.255 mmol) was dissolved in ethanol (5 mL), and 10% palladium carbon (15.8 mg) was added thereto, followed by stirring under a hydrogen atmosphere room temperature for 1.5 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to provide Title Compound 415 (93.3 mg, 100%). XH NMR (CDC13, d ppm): 1.48 (s, 9H), 1.98-2.03 (, - 2H), 2.93 (t, J = 7.0 Hz, 2H), 3.32 (s, 3H), 3.43 (t, J = 7.0 Hz, 2H), 6. 55 (dd, J = 1.0, 3.3 Hz, 1H), 7.54 (d, J = 1.0 Hz, 1H), 7.79 (d, J = 3.3 Hz, 1H), 9.28 (br s, 1H).

[Example 416] 2-Amino-4- (2-furyl) thiazol-5-yl-3-methoxypropyl ketone (Compound 416) In a manner similar to that in Example 186, the Compound of title 416 (67.4 mg, 99%) was obtained from Compound 415 (93.3 mg, 0.263 mmol) in place of Compound 185. X H NMR (CDCl 3, d ppm): 1.96 (t, J = 7.0 Hz, 2 H ), 2.76-2.81 (m, 2H), 3.31 (s, 3H), 3.42 (t, J = 7.0 Hz, 2H), 6.00 (br s, 2H), 6. 54 (dd, J = 1.8, 3.3 Hz, 1H), 7.55 (d, J = 1.8 Hz, 1H), 7. 63 (d, J = 3.3 Hz, 1H).

[Example 417] N- [5- (Cyclopropylcarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 417) Compound 98 (127 mg, 0.355 mmol) was suspended in THF ( 2.5 mL), and a 0.5 mol / L solution of bromide Cyclopropylmagnesium in THF (4.00 mL, 2.00 mmol) was added thereto under cooling on ice, followed by stirring at room temperature for 2.5 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with a mixed solvent (4: 1) of chloroform and 2-propanol. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate., and then the solvent was distilled under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to provide the title Compound 417 (94.1 mg, 78%) as a pale yellow solid. X H NMR (CDC13, d ppm): 1.03-1.10 (m, 2H), 1.29-1.34 (m, 2H), 2.35-2.43 (m, 1H), 6.50 (dd, J = 1.7, 3.5 Hz, 1H), 7.50 (dd, J = 0.7 Hz, 3.5 Hz, 1H), 7.61 (dd, J = 0.7 Hz, 1.7 Hz, 1H), 7.76 (d, J = 4.4 Hz, 2H), 8.85 (d, J = 4.4 Hz , 2H), 10.34 (br s, 1H). ESIMS m / z: [M + H] + 340. p.f .: 225-230 ° C (decomposition).

[Example 418] N- [5- (Cyclopropylcarbonyl) -4- (2-furyl) thiazol-2-yl] tert-butyl carbamate (Compound 418) In a manner similar to that in Example 176, when using cyclopropanecarboxylic acid instead of acid 2- cyanobenzoic, Compound of title 418 (884 mg, 67%) was obtained from Compound h (1.36 g, 3.94 mmol) obtained in Reference Example 8. XH NMR (CDC13, d ppm): 0.90-1.03 (m , 2H), 1.16-1.36 (m, 2H), 1.52 (s, 9H), 1.78-1.99 (, 1H), 6.53 (dd, J = 1.7 Hz, 3.3 Hz, 1H), 6.74 (d, J = 3.3 Hz, 1H), 7.55 (d, J = 1.7 Hz, 1H), 8.30 (br s, 1H). ESIMS m / z: [M + H] + 335. [Example 419] 2-Amino-4- (2-furyl) thiazol-5-yl-cyclopropyl ketone (Compound 419) In a manner similar to that in Example 186, Compound of title 419 (352 mg, 57%) was obtained from Compound 418 (884 mg, 2.65 mmol) in place of Compound 185. XH NMR (CDCl 3, d ppm): 1.03-1.10 (m, 2H), 1.28-1.35 (m, 2H), 2. 35-2.45 (m, 1H), 5.46 (br s, 2H), 6.53 (dd, J = 1.8, 3.6 Hz, 1H), 7.54 (dd, J = 0.7, 1.8 Hz, 1H), 7.66 (dd, J = 0.7, 3.6 Hz, 1H). ESIMS m / z: [M + H] + 235.

[Example 420] N- [5- (Cyclopropylcarbonyl) -4- (2-furyl) thiazol-2-yl] -2-methoxybenzamide (Compound 420) In a manner similar to that in Example 187, by using acid 2-methoxybenzoic acid (208 mg, 1.37 mmol) in Place of isonicotinic acid, Compound of title 420 (73.3 mg, 58%) was obtained as a pink colored solid from Compound 419 (79.1 mg, 0.338 mmol) in place of Compound 186. XH NMR (CDC13, d ppm) : 0.80-1.07 (m, 2H), 1.24-1.32 (m, 2H), 2.37-2.42 (m, 1H), 4.12 (s, 3H), 6.55 (dd, J = 1.8, 3.5 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 7.18 (ddd, J = 1.0 Hz, 7.4 Hz, 7.8 Hz, 1H), 7.55-7.65 (, 3H), 8.32 (dd, J = 1.8 Hz, 7.8 Hz, 1H ), 11.23 (br s, 1H). ESIMS m / z: [M + H] + 369. p.f .: 150-154 ° C.

[Example 421] N- [5- (Cyclopropylcarbonyl) -4- (2-furyl) thiazol-2-yl] -2-morpholinoacetamide (Compound 421) Compound 419 (192 mg, 0.824 mmol) and triethylamine (0.379 mL, 2.72 mmol) were dissolved in THF (4 mL), and bromoacetyl bromide (0.215 mL, 2.47 mmol) was added thereto at 0 ° C, followed by stirring at room temperature for 1 hour. At 0 ° C, a solution (2 mL) of morpholine (1.08 mL, 12.4 mmol) in THF and triethylamine (1.73 mL, 12.4 mmol) was added to the reaction mixture, followed by stirring at room temperature for 1 hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer is washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography to provide the title Compound 421 (229 mg, 77%). H NMR (CDC13, d ppm): 1.00-1.03 (, 2H), 1.22-1.18 (m, 2H), 2.30-2.38 (m, 1H), 2.61 (t, J = 4.6 Hz, 4H), 3.77 (t , J = 4.6 Hz, 4H), 6.53 (dd, J = 1.8, 3.5 Hz, 1H), 7.56 (dd, J = 0.7, 1.8 Hz, 1H), 7.60 (J = 0.7, 3.5 Hz, 1H). APCIMS m / z: [M + H] + 362.

[Example 422] N- [5- (cyclobutylcarbonyl) -4- (2-furyl) thiazol-2-yl] tert-butyl carbamate (Compound 422) In a manner similar to that in Example 176, using cyclobutanecarboxylic acid instead of acid 2-Cyanobenzoic, Compound of title 422 (628 mg, 44%) was obtained from Compound h (1.41 g, 4.09 mmol) obtained in Reference Example 8. X H NMR (CDCl 3, d ppm): 1.48 (s) , 9H), 1.80-2.10 (m, 2H), 2. 15-2.33 (m, '2H), 2.35-2.48 (m, 2H), 3.70-3.77 (m, 1H), 6.55 (dd, J = 1.8, 3.5 Hz, 1H), 7.55 (dd, J = 0.7 Hz, 1.8 Hz, 1H), 7.87 (dd, J = 0.7, 3.5 Hz, 1H), 9.28 (brs, 1H).

[Example 423] 2-Amino-4- (2-tfuryl) thiazol-5-yl-cyclobutyl ketone (Compound 423) In a manner similar to that in Example 186, the title Compound 423 (448 mg, 100%) was obtained at Compound 422 (628 mg, 1.81 mmol) in place of Compound 185. XH NMR (CDC13, d ppm): 1.80-2.05 (m, 2H), 2.10-2.22 (, 2H), 2.30-2.45 (m, 2H) ), 3.55-3.61 (m, 1H), 5.56 (br s, 2H), 6.55 (dd, J = 1.8, 3.5 Hz, 1H), 7.55 (dd, J = 0.8, 1.8 Hz, 1H), 7.70 (dd) , J = 0.8, 3.5 Hz, 1H). ESIMS m / z: [M + H] + 249. p.f .: 125-160 ° C (decomposition) [Example 424] N- [5- (Cyclobutylcarbonyl) -4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 424) In a manner similar to that in Example 187, the title Compound 424 (106 mg, 72%) was obtained as a pale brown solid from Compound 423 (103 mg, 0. 415 mmol) in place of Compound 186. XH NMR (CDCl 3, ppm): 1.85-2.18 (m, 2H), 2.25-2.40 (m, 2H), 2.40-2.55 (, 2H), 3.76-3.82 (m, 1H ), 6.53 (dd, J = 1. 8, 3.5 Hz, 1H), 7.50 (dd, J = 0.8, 1.8 Hz, 1H), 7.73 (d, J = 4.5 Hz, 2H), 7.85 (dd, J = 0.8, 3.5 Hz, 1H), 8.84 ' (d, J = 4.5 Hz, 1H), 8.85 (d, J = 4.5 Hz, 1H), 10.27 (br s, 1H). ESIMS m / z: [M + H] + 354. p.f .: 227-235 ° C (decomposition) [Example 425] N- [5- (Cyclobutylcarbonyl) -4- (2-furyl) thiazol-2-yl] furan-2-carboxamide (Compound 425) In a manner similar to that in Example 385, by using 2-furoyl (0.0702 mL, 0.721 mmol) in place of cyclopropanecarbonyl chloride, Compound of title 425 (106 mg, 76%) was obtained from Compound 423 (100 mg, 0.403 mmol) in place of the Compound 384. X H NMR (CDC13, d ppm): 1.93-2.13 (m, 2H), 2.23-2.50 (m, 4H), 3.74-3.80 (m, 1H), 6.58 (dd, J = 1.8, 3.7 Hz, 1H), 6.64 (dd, J = 1.8, 3.7 Hz, 1H), 7.39-7.41 (m, 3H), 7.90 (dd, J = 0.7, 3.7 Hz, 1H), 9.81 (br s, 1H). ESIMS m / z: [M + H] + 343. p.f. : 188-192 ° C.

[Example 426] 4-Cyano-N- [5- (cyclobutylcarbonyl) -4,4- (2-furyl) thiazol-2-yl] benzamide (Compound 426) In a similar manner to that in Example 385, Using 4-cyanobenzoyl chloride (127 mg, 0.767 mmol) in place of cyclopropanecarbonyl chloride, Compound of title 426 (122 mg, 75%) was obtained from Compound 423 (106 mg, 0.427 mmol) instead of Compound 384. H NMR (CDC13, d ppm): 1.85-2.14 (m, 2H), 2.24-2.50 (, 4H), 3.76-3.82 (m, 1H), 6.51 (dd, J = 1.8, 3.7 Hz, 1H) , 7.47 (dd, J = 0.7, 1.8 Hz, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.85 (dd, J = 0.7, 3.7 Hz, 1H), 8.01 (d, J = 8.8 Hz, 2H), 10.41 (br s, 1H). ESIMS m / z: [M-H] "376. p.f .: 220-225 ° C.

[Example 427] N- [5- (Cyclobutylcarbonyl) -4- (2-furyl) thiazol-2-yl] cyclopropanecarboxamide (Compound 427) In a manner similar to that in Example 385, the title Compound 427 (109 mg , 84%) was obtained from Compound 423 (102 mg, 0.411 mmol) in place of Compound 384. X H NMR (CDCl 3, d ppm): 0.91-0.99 (m, 2 H), 1.15-1.25 (m, 2 H) , 1.80-2.10 (m, 2H), 2.20-2.49 (m, 5H), 3.69-3.75 (m, 1H), 6.56 (dd, J = 1.7, 3.5 Hz, 1H), 7.56 (dd, J = 0.7, 1.7 Hz, 1H), 7.91 (dd, J = 0.7, 3.5 Hz, .1H), 10.09 (br s, 1H). ESIMS m / z: [M + H] + 317. p.f .: 200-205 ° C.

[Example 428] N-. { - (2-furyl) -5- [1-hydroxy-1- (3-methyloxetan-3-yl) ethyl] thiazol-2-yl} tert-butyl carbamate (Compound 428) Step 1: The (3-methyloxetan-3-yl) methanol (1.00 g, 9.79 mmol) and a 2.0 mol / L solution (5.4 mL) of oxalyl chloride in dichloromethane were dissolved in dichloromethane (200 mL), followed by stirring at -60 ° C for 10 minutes. DMSO (1.67 mL, 23.5 mmol) was added to the reaction mixture, followed by stirring for 15 minutes. Triethylamine (6.82 mL, 49.0 mmol) was added thereto, and followed by stirring addition at room temperature for 30 minutes. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled under reduced pressure to provide 3-methyloxetan-3-carbaldehyde (340 mg, 35%). X H NMR (CDC13, d ppm): 1.45 (s, 3 H), 4.47 (d, J = 6.3 Hz, 2 H), 4.84 (d, J = 6.3 Hz, 2 H), 9.92 (s, 1 H).

Step 2: Compound h (500 mg, 1.45 mmol) obtained in the Reference Example 8 was dissolved in THF (14 mL), and a 1.58 mol / L solution of n-butyllithium in n-hexane (2.03 mL, 3.21 mmol) was added thereto in an argon stream at -78 ° C. , followed by stirring at -78 ° C for 15 minutes. The 3-methyloxetan-3-carbaldehyde (436 mg, 4.35 mmol) obtained in the »Step 1 was added dropwise to the reaction mixture, followed by stirring at room temperature for 1.5 hour. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to provide the title Compound 428 (141 mg, 27%). XH NMR (CDC13, d Ppm): 1.27-1.35 (m, 3H), 1.50 (s, 9H), 4.27-4.38 (m, 2H), 4.84-4.98 (m, 2H), 5.67 (m, 1H), 6.47 (dd, J = 1. 8, 3.5 Hz, 1H), 6.73 (d, J = 3.5 Hz, 1H), 7.45 (d, J = 1.8 Hz, 1H).

[Example 429] N- [4- (2-furyl) -5- (3-methyloxetan-3-ylcarbonyl) -thiazol-2-yl] tert-butyl carbamate (Compound 429) In a manner similar to that in Example 297, Compound of title 429 (85.0 mg, 61%) was obtained from Compound 428 (140 mg, 0.382 mmol) in place of Compound 296. H NMR (CDC13, d ppm): 1.38 (s, 9H) , 1.77 (s, 3H), 4.44 (d, J = 6.1 Hz, 2H), 5.05 (d, J = 6.1 Hz, 2H), 6.50 (dd, J = 1.8, 3.6 Hz, 1H), 7.48 (dd, J = 0.8, 1.8 Hz, 1H), 7.84 (dd) , J = 0. 8, 3.6 Hz, 1H). [Example 430] 2-Amino ~ 4- (2-furyl) thiazol-5-yl 3-methyloxetan-3-yl ketone (Compound 430) In a manner similar to that in Example 186, the Compound of title 430 (62.0 mg, 100%) was obtained from Compound 429 (85.0 mg, 0.233 mmol) instead of Compound 185. X H NMR (CDCl 3, d ppm): 1.75 (s, 3 H), 4.37 (d, J = 6.1 Hz, 2 H), 5.02 (d, J = 6.1 Hz, 2 H), 6.56 (dd, J = 1.8 , 3.6 Hz, 1H), 7. 57 (d, J = 1.8 Hz, 1H), 7.88 (d, J = 3.6 Hz, 1H). [Example 431] N- [5- (cyclopentylcarbonyl) -4- (2-furyl) thiazol-2-yl] -pyridine-4-carboxy ida (Compound 431) Compound 98 (74.0 mg, 0.207 mmol) was dissolved in THF (1.5 mL), and a 2 mol / L solution of cyclopentylmagnesium bromide in diethyl ether (0.500 mL, 1.00 mmol) was added thereto under cooling with ice, followed by stirring at room temperature for 1.5 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane ethyl acetate = 1-1) to give the title Compound 431 (5.60 mg, 1%) as a pale brown solid. XH NMR (CDC13, d ppm) 1.62-1.84 (, 4H), 1.90-2.03 (m, 4H), 3.42-3.48 (, 1H), 6.53 (dd, J = 1.8, 3.5 Hz, 1H), 7.52 ( dd, J = 0.7, 3.5 Hz, 1H), 7.74 (d, J = 4.4 Hz, 2H), 7.85 (dd, J = 0. 7, 1.8 Hz, 1H), 8.86 (d, J = 4.4 Hz, 1H), 8.88 (d, J = 4.4 Hz, 1H), 10.16 (br s, 1H). ESIMS m / z¡ [M + H] + 368. p.f .: 168-181 ° C.

[Example 432] N- [5- (cyclopentylcarbonyl) -4- (2-furyl) thiazol-2-yl] tert-butyl carbamate (Compound 432) In a manner similar to that in Example 176, Using cyclopentanecarboxylic acid in place of 2-cyanobenzoic acid, Compound of title 432 (251 mg, 17%) was obtained from Compound h (1.44 g, 4.17 mmol) obtained in Reference Example 8. XH NMR (CDC13, d ppm): 1.20-2.10 (m, 8H), 1.51 (s, 9H), 2.96- 3.02 (m, 1H), 6.45 (dd, J = 1.8 Hz, 3.3 Hz, 1H), 6.65 (d, J = 3. 3 Hz, -1H), 7.41 (d, J = 1.8 Hz, 1H), 8.45 (br s, 1H). ESIMS m / z: [M + H] + 363. [Example 433] 2-Amino-4- (2-furyl) thiazol-5-yl cyclopentyl ketone (Compound 433) In a manner similar to that in Example 186, Compound of title 433 (246 mg, 79%) was obtained from Compound 432 (433 mg, 1.20 mmol) in place of Compound 185. XH NMR (CDCl 3, d ppm): 1.20-2.10 (m, 8H), 2.96-3.02 (m, 1H), 5.46 (br s, 2H), 6.53 (dd, J = 1.8, 3.6 Hz, 1H), 7.54 (dd, J = 0.7, 1.8 Hz, 1H), 7.66 (dd, J = 0.7, 3.6 Hz, 1H). ESIMS m / z: [M + H] + 263.

[Example 434] N- [5- (Cyclopentylcarbonyl) -4- (2-furyl) thiazol-2-yl] cyclopropanecarboxamide (Compound 434) In a manner similar to that in Example 385, the Compound of title 434 (28.2 mg, 44%) was obtained as a white solid from Compound 433 (49.6 mg, 0.189 mmol) instead of Compound 384. XH NMR (CDCl 3, d ppm): 0.94-1.04 (m, 2H), 1.16-1.25 (m, 2H), 1.46-1.82 (m, 6H), 1.86-1.99 (m, 3H), 3.32-3.41 (m, 1H), 6.55 (dd, J = 1.8, 3.5 Hz, 1H), 7.56 (dd, J = 0.7, 1.8 Hz, 1H), 7.87 (dd, J = 0.7, 3.5 Hz , 1H), 9.83. (brs, 1H). ESIMS m / z: [M + H] + 331. mp .: 182-187 ° C.

[Example 435] N- [5- (Cyclopentylcarbonyl) -4- (2-furyl) thiazol-2-yl] -morpholine-4-carboxamide (Compound 435) Compound 432 (251 mg, 0.693 mmol) was dissolved in 1 , 4-dioxane (5 mL), and morpholine (6.19 mL, 70.9 mmol) were added thereto, followed by stirring overnight under heating and reflux. The reaction mixture was concentrated under reduced pressure, and water was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 3: 1) to give the title Compound 435 (168 mg, 64%) as a pale brown solid. X H NMR (CDCl 3, d ppm): 1.55-1.80 (m, 4H), 1.85-2.00 (, 4H), 3. 35-3.41 (m, 1H), 3.45-3.53 (m, 4H), 3.65-3.73 (m, 4H), 6.56 (dd, J = 1.8, 3.5 Hz, 1H), 7.52 (dd, J = 0.7, 1.8 Hz, 1H), 7.93 (dd, J = 0.7, 3.5 Hz, 1H), 9.23 (br s, 1H). ESIMS m / z: [M + H] + 376. m.p .: 108-110 ° C.

[Example 436] N- [5- (1-cyclohexyl-l-hydroxymethyl) -4- (2-furyl) thiazol-2-yl] tert-butyl carbamate (Compound 436) In a manner similar to that in Example 92, using cyclohexanecarbaldehyde in place of DMF, Compound of title 436 (173 mg, 46%) was obtained from Compound h (3.45 g, 1.00 mmol) obtained in Reference Example 8. XH NMR (CDC13, d ppm): 0.86-1.40 (m, 6H), 1.45 (s, 9H), 1.50-1.80 (m, 4H), 2.05-2.15 (m, 1H), 5.21 (d, J = 8.1 Hz, 1H), 6.46 (dd, J = 1.9, 3.5 Hz, 1H), 6.65 (dd, J = 0.8, 3.5 Hz, 1H), 7.45 (dd, J = 0.8, 1.9 Hz, 1H), 8.55 (br s, 1H).

[Example 437] N- [5- (cyclohexylcarbonyl) -4- (2-furyl) thiazol-2-yl] tert-butyl carbamate (Compound 437) In a manner similar to that in Example 297, the Compound of title 437 (109 mg, 63%) was obtained from Compound 436 (173 mg, 0.458 mmol) in place of Compound 296.

X H NMR (CDCl 3, d ppm): 1.15-1.35 (m, 4H), 1.56 (s, 9H), 1.65-1.95 (m, 6H), 2.85 (tt, J = 3.4, 11.0 Hz, 1H), 6.53 ( dd, J = 0.9, 1.8 Hz, 1H), 7.54 (dd, J = 0.9, 3.3 Hz, 1H), 7.75 (dd, J = 1.7, 3.3 Hz, "1H). [Example 438] 2-Amino-4 - (2-furyl) thiazol-5-yl cyclohexyl ketone (Compound 438) In a manner similar to that in Example 186, the Compound of title 438 (55.8 mg, 70%) was obtained from Compound 437 (109 mg , 0.290 mmol) in place of Compound 185. XH NMR (DMSO-de, d ppm): 1.10-1.45 (m, 4H), 1.50-1.80 (m, 6H), 2.80-2.95 (m, 1H), 6.64 ( dd, J = 1.8-, 3.5 Hz, 1H), 7.21 (d, J = 3.5 Hz, 1H), 7.82 (d, J = 1.8 Hz, 1H), 7.87 (br s, 1H).

[Example 439] N- [5- (Cyclohexylcarbonyl) -4- (2-furyl) thiazol-2-yl] -pyridine-4-carboxamide (Compound 439) In a manner similar to that in Example 187, a crude Compound 439 was obtained from Compound 438 in place of Compound 186. Crude Compound 439 was re-mixed in a mixed solvent of ethanol and diethyl ether to provide Compound of title 439 (41.6 mg, 55%) as a w solid. X H NMR (DMSO-de, d ppm): 1.05-1.45 (m, 4H), 1.55-1.90 (m, 6H), 2. 86-2.94 (m, 1H), 6.70 (dd, J = 1.6, 3.2 Hz, 1H), 7.40 (d, J = 3.2 Hz, 1H), 7.89 (d, J = 1.6 Hz 1H), 8.02 (dd, J = 1.9, 4.3 Hz, 2H), 8.83 (dd, J = 1.9, 4.3 Hz, 2H) ~, 13.54 (br s, 1H). p.f .: 197-199 ° C.

[Example 440] N- [4- (2-furyl) -5- (4-methoxycyclohexyl-carbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 440) In a manner similar to that in Example 185, when using 4-methoxycyclohexanecarboxylic acid in place of picolinic acid, Title Compound 440 (149 'mg, 18%) was obtained from Compound h (500 mg, 2.04 mmol) obtained in Reference Example 8. XH NMR ( CDC13, d ppm): 1.23-2.17 (, 19H), 3.30-3.36 (m, 4H), 6. 53 (dd, J = 1.7, 3.5 Hz, 1H), 7.54 (d, J = 1.7, Hz, 1H), 7. 76 (d, J = 3.5 Hz, 1H).

[Example 441] 2-Amino-4- (2-furyl) thiazol-5-yl 4-methoxycyclohexyl ketone (Compound 441) In a manner similar to that in Example 186, the Compound of title 441 (90.0 mg, 80%) was obtained from Compound 440 (149 mg, 0.367 mmol) in place of Compound 185.

X H NMR (CDCl 3, d ppm) -: 1.26-2.02 (m, 8H), 2.70-2.78 (m, 1H), 3.29-3.36 (m, 3H), 5.57-5.60 (m, 2H), 6.52-6.55 ( m, 1H), 7.53-7.54 (m, 1H), 7.59-7.60 (m, 1H).

[Example 442] N- [4- (2-Furyl) -5- (4-methoxycyclohexylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 442) Compound 441 (579 mg, 1.89 mmol) was dissolved in THF (9.0 mL), and isonicotinic acid (931 mg, 7.57 mmol), EDC hydrochloride (1.45 g, 7.57 mmol) and 1-hydroxybenzotriazole monohydrate (1.16 g, 7.57 mmol) were added thereto, followed by stirring at 60 ° C for 3 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from 2-propanol to provide the title Compound 442 (664 mg, 85%). X H NMR (DMSO-de, d ppm): 1.08-2.08 (m, 8H), 2.84-3.01 (m, 1H), 3.20-3.23 (m, 3H), 6.68-6.71 (m, 1H), 7.39-7.42 (m, 1H), 7.89-7.90 (, 1H), 8.02 (d, J = 5.9 Hz, 2H), 8.82 (d, J = 5.9 Hz, 2H), 13.6 (br s, 1H). APCIMS m / z: [M + H] + 412. p.f .: 180-187 ° C.

[Example 443] 4-Cyano-N- [4- (2-furyl) -5- (4-methoxycyclohexylcarbonyl) -thiazol-2-yl] benzamide (Compound 443) In a manner similar to that in Example 442, using 4-cyanobenzoic acid in place of isonicotinic acid, Compound of title 443 (199 mg, 62%) was obtained from Compound 441 (226 mg, 0.738 mmol). X H NMR (DMSO-de, d ppm): 1.10-2.17 (m, 9H), 2.88-2.97 (m, 1H), 3.20-3.23 (m, 3H), 6.69-6.71 (m, 1H), 7.40-7.43 (m, 1H), 7.88-7.91 (, 1H), 8.06 (d, J = 8.3 Hz, 2H), 8.26 (d, J = 8.3 Hz, 2H), 13.5 (br s, 1H). APCIMS m / z: [M + H] + 436. p.f .: 105-109 ° C.

[Example 444] 2-Amino-4- (2-furyl) thiazol-5-yl 4-hydroxycyclohexyl ketone (Compound 444) Step 1: The ethyl 4-hydroxycyclohexanecarboxylate (3.44 g, 20.0 mmol) was dissolved in DMF (7%). L), and imidazole (3.40 g, 50.0 mmol) and tert-butyldimethylsilyl chloride (3.62 g, 24 mmol) were added thereto, followed by stirring overnight at room temperature. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 10: 1) to provide ethyl 4- (tert-butyldimethylsilyloxy) cyclohexanecarboxylate (5.73 g, 100%). XH NMR (CDC13, d ppm): 0.00-0.03 (m, 6H), 0.85-0.86 (m, 9H), 1.19-1.25 (m, 3H), 1.42-2.26 (m, 10H), 4.05-4.13 (, 2H).

Step 2: The ethyl 4- (tert-butyldimethylsilyloxy) cyclohexane-carboxylate (5.73 g, 20.0 mmol) obtained in Step 1 and N, O-dimethylhydroxylamine hydrochloride (2.93 g, 30.0 mmol) were suspended in THF (40 mL ), and a 2.0 mol / L solution of isopropylmagnesium chloride in THF (30.0 mL, 60.0 mmol) was added dropwise thereto under an argon atmosphere at -20 ° C, followed by stirring at 0 ° C for 1 hour. . A saturated aqueous solution of ammonium chloride and ethyl acetate were added to the reaction mixture by extraction. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 4) to give 4- (tert-butyldimethylsilyloxy) -N-methoxy-N- methylcyclohexanecarboxamide (6.03 g, 100%). XH NMR (CDC13, d ppm): 0.00-0.03 (m, 6H), 0.85-0.86 (m, 9H), 1.45-1.97 (m, 10H), 3.14-3.15 (m, 3H), 3.66-3.67 (m , 3H). Step 3: Compound h (690 mg, 2.00 mmol) obtained in the Reference Example 8 was dissolved in THF (20 mL), and a 1.57 mol / L solution of n-butyllithium in n-hexane (2.80 mL, 4.40 mmol) was added thereto in an argon stream at -78 ° C. , followed by stirring at -78 ° C for 15 minutes. 4- (tert-Butyldimethylsilyloxy) -N-methoxy-N-methylcyclohexane-carboxamide (1.21 g, 4.00 mmol) obtained in Step 2 was added dropwise to the reaction mixture, followed by stirring overnight at room temperature. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue is dissolved in trifluoroacetic acid (2 L), followed by stirring for 1 hour. The reaction mixture was concentrated under reduced pressure, and a saturated aqueous solution of sodium acid carbonate was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. He The resulting residue was purified through silica gel column chromatography (ethyl acetate) to provide the title Compound 444 (76.0 mg, 13%). X H NMR (CDC13, d ppm): 1.55-2.15 (m, 10H), 5.82-5.92 (m, 2H), 6.52-6.54 (m, 1H), 7.54-7.59 (m, 2H). [Example 445] N- [5- (1,4-dioxaespiro [4, 5] undecan-8-ylcarbonyl) -4- (2-furyl) thiazol-2-yl] tert-butyl carbamate (Compound 445) Step 1: The ethyl 4-oxocyclohexanecarboxylate (5.00 g, 29.4 mmol) was dissolved in toluene (200 mL), and ethylene glycol (15 mL) and oxalic acid (500 mg) were added thereto, followed by stirring under heating and reflux for 5 hours. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 8: 2) to give 1,4-dioxaespiro [4, 5] decan-8-carboxylic acid ethyl ester (6.28 g, 99%). Stage 2: The 1,4-dioxaespiro [4,5] decan-8-carboxylic acid ethyl ester (6.28 g, 29.3 mmol) obtained in Step 1 was dissolved in THF, and N, O-dimethylhydroxylamine hydrochloride (4.30 g, 44.1 mmol) it was added to it, followed by agitation. In an argon atmosphere at -30 ° C, a 2.0 mol / L solution of isopropylmagnesium chloride in THF (44.1 mL, 88.2 mmol) was added dropwise to the reaction mixture, followed by stirring at -5 ° C for 1 hour. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to give N-methoxy-N-methyl-1,4-dioxaespiro [4,5] decan-8-carboxamide (6.61 g, 99%). X H NMR (CDC13, d ppm): 1.51-1.62 (m, 2H), 1.76-1.90 (m, 6H), 2.68-2.71 (m, 1H), 3.18 (s, 3H), 3.71 (s, 3H), 3.95 (s, 4H).

Step 3: Compound h (1.50 g, 4.34 mmol) obtained in Reference Example 8 was dissolved in THF (30 mL), and a 1.58 mol / L solution of n-butyllithium in n-hexane (8.58 mL, 13.5 mmol ) was added thereto in an argon stream at -78 ° C, followed by stirring at -78 ° C for 15 minutes. The N- methoxy-N-methyl-1,4-dioxa-spiro [4, 5] decan-8-carboxamide (2.80 g, 12.2 mmol) obtained in Step 2 was added dropwise to the reaction mixture, followed by stirring at room temperature for 1.5 hours. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 1) to provide the title Compound 445 (1.79 g, 95%). X H NMR (CDC13, d ppm): 1.52 (s, 9H), 1.57-1.64 (m, 2H), 1.82-1.95 (m, 6H), 2.85-3.00 (m, 1H), 3.95 (s, 4H), 6.54 (dd, J = 1.8, 3.3 Hz, 1H), 7.53 (d, J = 1.8 Hz, 1H), 7.73 (d, J = 3.3 Hz, 1H).

[Example 446] 2-Amino-4- (2-furyl) thiazol-5-yl 1,4-dioxaespiro [4, 5] decan-8-yl ketone (Compound 446) Compound 445 (500 mg, 1.15 mmol) it was dissolved in diphenyl ether (5 mL), followed by stirring at 170 ° C for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was added. distilled under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 1: 3) to provide the title Compound 446 (223 mg, 58%). X H NMR (DMSO-de, d ppm) ,: 1.35-1.73 (m. 8H), 2.67-2.74 (m, 1H), 3.84 (s, 3H), 6.65 (dd, J = 1.8, 3.5 Hz, 1H) , 7.22 (dd, J = 0.7, 3.5 Hz, 1H), 7.84 (dd, J = 0.7, 1.8 Hz, 1H), 7.97 (brs, 2H).

[Example 447] 2-Amino-4- (2-furyl) thiazol-5-yl-4-oxocyclohexyl ketone (Compound 447) Compound 445 (1.00 g, 2.30 mmol) was dissolved in THF (14 L), and 2 mol / L of hydrochloric acid (7 mL) was added thereto, followed by stirring under heating and reflux for 8 hours. The reaction mixture was neutralized with a saturated aqueous solution of sodium acid carbonate added thereto, followed by extraction with ethyl acetate. the organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was crystallized from diethyl ether to provide the title Compound 447 (399 mg, 60%). H NMR (DMSO-d6, d ppm): 1.70-1.79 (m, 2H), 2.01-2.08 (m, 2H), 2. 20-2.36 (, 4H), 3.18-3.26 (m, 1H), 6.64 (dd, J = 1.8, 3.5 Hz, 1H), 7.28 (dd, J = 0.8, 3.5 Hz, 1H), 7.85 (dd, J = 0.8, 1.8 Hz, 1H), 8.01 (br s, 2H).

[Example 448] N- [4- (2-Furyl) -5- (4-oxocyclohexylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 448) Compound 447 (150 mg, 0.517 mmol) was dissolved in DMF (2.5 mL), and isonicotinic acid (191 mg, 1.55 mmol), EDC hydrochloride (298 mg, 1.55 mmol) and 1-hydroxybenzotriazole monohydrate (237 mg, 1.55 mmol) were added thereto, followed by stirring at 60 ° C for 3 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from 2-propanol to provide the title Compound 448 (115 mg, 66%). X H NMR (DMSO-de, d ppm): 2.07-2.60 (m, 8H), 3.36-3.23 (m, 1H), 6.56 (dd, J = 1.8, 3.5 Hz, 1H), 7.54 (dd, J = 0.7 , 1.8 Hz, 1H), 7.75 (dd, J = 0.7, 3.5 Hz, 1H), 7.80 (d, J = 6.1 Hz, 2H), 8.88 (d, J = 6.1 Hz, 2H). APCIMS m / z: [M + H] + 396. p.f .: 206-212 ° C. [Example 449] N- [4- (2-Furyl) -5- (4-oxocyclohexylcarbonyl) thiazol-2-yl] -2-methylpyridine-4-carboxamide (Compound 449) In a manner similar to that in Example 448, by using acid 2-methylisonicotinic acid in place of isonicotinic acid, Compound of title 449 (.73.0 mg, 43%) was obtained from Compound 447 (120 mg, 0.413 mmol). XH NMR (CDC13, d ppm): 2.04-2.60 (m, 8H), 2.66 (s, 3H), 3.35-3.43 (m, 1H), 6.54 (dd, J = 1.8, 3.6 Hz, 1H), 7.52 ( dd, J = 0.7, 1.8 Hz, 1H), 7.57 (d, J = 5.1 Hz, 1H), 7.62 (s, 1H), 7.75 (dd, J = 0.7, 3.6 Hz, 1H), 8.72 (d, J = 5.1 Hz, 1H). APCIMS m / z: [M + H] + 410. p.f .: 108-115 ° C.

[Example 450] N- [4- (2-Furyl) -5- (4-oxocyclohexylcarbonyl) thiazol-2-yl] furan-2-carboxamide (Compound 450) In a manner similar to that in Example 448, when using furan-2-carboxylic acid in place of isonicotinic acid, Compound of title 450 (124 mg, 62%) was obtained from Compound 447 (150 mg, 0.517 mmol). H NMR (CDCl 3, d ppm): 2.03-2.57 (m, 8H), 3.30-3.39 (, 1H), 6.57 (dd, J = 1.8, 3.5 Hz, 1H), 6.64 (dd, J = 1.7, 3.6 Hz , 1H), 7.42 (d, J = 3.6 Hz, 1H), 7.59-7.60 (, 2H), 7.79 (d, J = 3.5 Hz, 1H). APCIMS m / z: [M + H] + 385. p.f .: 232-235 ° C.

[Example 451] N- [4- (2-Furyl) -5- (4-oxocyclohexylcarbonyl) thiazol-2-yl] -3-methoxybenzamide (Compound 451) In a manner similar to that in Example 448, by using acid 3-methoxybenzoic instead of isonicotinic acid, Compound of title 451 (72.0 mg, 33%) was obtained from Compound 447 (150 mg, 0.517 mmol). H NMR (CDC13, d ppm): 2.06-2.58 (m, 8H), 3.33-3.41 (m, 1H), 3.88 (s, 3H), 6.56 (dd, J = 1.7, 3.6 Hz, 1H), 7.16- 7.20 (m, 1H), 7.41-7.51 (m, 3H), 7.58 (d, J = 1.7 Hz, 1H), 7.82 (d, J = 3.6 Hz, 1H). APCIMS m / z: [M + H] + 425. m.p .: 176-183 ° C.

[Example 452] 4-Cyano-N- [4- (2-furyl) -5- (4-oxocyclohexylcarbonyl) thiazol-2-yl] benzamide (Compound 452) In a manner similar to that in Example 448, when using 4-Cyanobenzoic acid in place of isonicotinic acid, Title Compound 452 (164 mg, 76%) was obtained from Compound 447 (150 mg, 0.517 mmol). X H NMR (CDCl 3, d ppm): 2.06-2.58 (m, 8H), 3.32-3.40 (m, 1H), 6.51 (dd, J = 1.8, 3.5 Hz, 1H), 7.48 (dd, J = 0.7, 1.8 Hz, 1H), 7.74 (dd, J = 0.7, 3.5 Hz, 1H), 7.81 (d, J = 8.6 Hz, 2H), 8.06 (d, J = 8.6 Hz, 2H). APCIMS m / z: [M-H] "418. p.f .: 211-212 ° C.

[Example 453] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 453) In a manner similar to that in Example 176, when using tetrahydropyran-4-carboxylic acid instead of 2-cyanobenzoic acid, the title Compound 453 (350 mg, 35%) was obtained from Compound h (1.04 g, 3.00 mmol) obtained in Reference Example 8. X H NMR (CDC13, d ppm): 1.53 (s, 9H), 1.76-1.94 (m, 4H), 3.06-3.18 (m, 1H), 3.46 (ddd, J = 2.7, 11.6, 11.6 Hz, 2H), 4.03 (ddd, J = 2.7, 4.0, 11.6 Hz, 2H), 6.55 (dd, J = 1.9, 3.5 Hz, 1H), 7.55 (dd, J = 0.8, 1.9 Hz, 1H), 7.76 (dd, J = 0.8, 3.5 Hz, 1H), 8.68 (br s, 1H). APCIMS m / z: [M + H] + 379.

[Example 454] 2-Araino-4- (2-furyl) thiazol-5-yl tetrahydropyran-4-yl ketone (Compound 454) In a manner similar to that in Example 186, the Title 454 compound (212 mg, 72%) was obtained from Compound 453 (350 mg, 1.05 mmol) in place of Compound 185. XH NMR (DMSO-de, d ppm): 1.52-1.64 (m, 4H) , 2.89-3.03 (m, 1H), 3.24 (ddd, J = 3.8, 11.3, 11.3 Hz, 2H), 3.85 (ddd, J = 2.7, 3.8, 11.3 Hz, 2H), 6.65 (dd, J = 1.9, 3.5 Hz, 1H), 7.24 (d, J = 3.5 Hz, 1H), 7.84 (d, J = 1.9 Hz, 1H), 7.96 (br s, 2H). APCIMS m / z: [M + H] + 279.

[Example 455] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 455) Compound 454 (6.95 g, 25.0 mmol) was dissolved in DMF (100 L), and isonicotinic acid (36.9 g, 300 mmol), EDC hydrochloride (57.6 g, 300 mmol) and 1-hydroxybenzotriazole monohydrate (45.9 g, 300 mmol) were added thereto, followed by stirring at 80 ° C for 6 hours. The reaction mixture was poured into a mixture of a saturated aqueous sodium hydrogen carbonate solution (600 mL) and water (200 mL), and the precipitated solid was collected by filtration. The resulting solid was recrystallized from ethanol to provide the title Compound 455 (4.41 g, 48%) as a gray white solid. X H NMR (DMSO-d 6, d ppm): 1.50-1.90 (m, 4H), 3.15-3.25 (m, 1H), 3.35 (ddd, J = 2.7, 11.6, 11.6 Hz, 2H), 3.89 (ddd, J = 2.7, 4.0, 11.6 Hz, 2H), 6.71 (dd, J = 1.9, 3.5 Hz, 1H), 7.43 (dd, J = 0.8, 3.5 Hz, 1H), 7.91 (dd, J = 0.8, 1.9 Hz, 1H), 8.02 (dd, J = 1.6, 4.6 Hz, 2H), 8.84 (dd, J = 1.6, 4.6 Hz, 2H ) -, 13.56 (br s, 1H). APCIMS m / z: [M + H] + 384. mp: 202-209 ° C.

[Example 456] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] cyclopropancarboxamide (Compound 456) Compound 454 (1.67 g, 6.00 mmol) and DMAP (36.7 mg) , 0.300 mmol) were suspended in pyridine (24 mL), and cyclopropanecarbonyl chloride (1.09 mL, 12.0 mmol) was added thereto, followed by stirring at 60 ° C for 90 minutes. The reaction mixture was poured into water, and the precipitated solid was collected by filtration. The resulting solid was purified through silica gel column chromatography (chloroform: methanol = 99: 1), followed by recrystallization from ethanol to provide the title Compound 456 (1.35 g, 65%) as a white solid. X H NMR (DMSO-d 6, 5 ppm): 0.90-1.04 (m, 4H), 1.50-1.76 (m, 4H), 1.92-2.03 (m, 1H), 3.07-3.21 (m, 1H), 3.25-3.40 (m, 2H), 3.83-3.91 (m, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.41 (d, J = 3.5 Hz, 1H), 7.88 (d, J = 1.9 Hz, 1H), 13.04 (br s, 1H). APCIMS m / z: [M + H] + 347. p.f .: 182-183 ° C.

[Example 457] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 457) In a manner similar to that in Example 456, by using benzoyl in place of cyclopropanecarbonyl chloride, the title Compound 457 (151 mg, 88 %) was obtained as a white solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.13-3.26 (m, 1H), 3.36 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.84-3.93 (m , 2H), 6. 70 (dd, J = 1.6, 3.5 Hz, 1H), 7.44 (d, J = 3.5 Hz, 1H), 7. 53-7.61 (m, 2H), 7.64-7.72 (m, 1H), 7.91 (d, J = 1.6 Hz, 1H), 8.11-8.18 (, 2H), 13.27 (br s, 1H). APCIMS m / z: [M + H] + 383. p.f .: 221-222 ° C.

[Example 458] N- [4- (2-Furyl) -5- (tetrahydro-drahipin-4-ylcarbonyl) thiazol-2-yl] -2-methylbenzamide (Compound 458) In a manner similar to that in Example 456, Using 2-methylbenzoyl chloride in place of cyclopropanecarbonyl chloride, title Compound 458 (159 mg, 88%) was obtained as a gray white solid from Compound 454 (125 mg, 0.450 mmol). H NMR (DMSO-de, d ppm): 1.55-1.85 (m, 4H), 2.44 (s, 3H), 3. 14-3.26 (m, 1H), 3.36 (ddd, J = 2.2, 11.9, 11.9 Hz, 2H), 3.84-3.92 (m, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.27- 7.51 (m, 4H), 7.60-7.66 (m, 1H), 7.89 (d, J = 1.9 Hz, 1H), 13.14 (br s, 1H). APCIMS m / z: [M + H] + 397. p.f .: 204-206 ° C. [Example 459] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -3-methylbenzamide (Compound 459) In a manner similar to that in Example 456, Using 3-methylbenzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 459 (151 mg, 89%) was obtained as a white solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.52-1.74 (m, 4H), 2.38 (s, 3H), 3.03-3.16 (m, 1H), 3.34 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H ), 3.84-3.94 (m, 2H), 6.62 (dd, J = 1.9, 3.5 Hz, 1H), 7.20-7.37 (m, 2H), 7.40 (dd, J = 0.5, 3.5 Hz, 1H), 7.80 ( dd, J = 0.5, 1.9 Hz, 1H), 7.90-7.95 (m, 1H), 7.97-8.01 (m, 1H), 13.17 (br s, 1H). APCIMS m / z: [M + H] + 397. p. f. : 197 -201 ° C.

[Example 460] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -4-methylbenzamide (Compound 460) In a manner similar to that in Example 456, use 4-methylbenzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 460 (128 mg, 72%) was obtained as a white grayish solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.54-1.76 (m, 4H), 2.40 (s, 3H), 3.13-3.26 (m, 1H), 3.36 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H ), 3. 84-3.94 (m, 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 3.5 Hz, 1H), 7.91 (d, J = 1.9 Hz, 1H), 8.06 (d, J = 8.4Hz, 2H), 13.18 (brs, 1H). APCIMS m / z: [M + H] + 397. p. f. : 190-192 ° C.

[Example 461] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-methoxybenzamide (Compound 461) In a manner similar to that in Example 456, when using 2-methoxybenzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 461 (152 mg, 82%) was obtained as a gray white solid from Compound 454 (125 mg, 0.450 mmol). H NMR (DMSO-de, d ppm): 1.55-1.80 (m, 4H), 3.15-3.25 (; 1H), 3. 35 (ddd, J = 2.2, 11.6, 11.6 Hz, 2H), 3.80-3.95 (m, 2H), 3.92 (s, 3H), 6.69 (dd, J = 1.6, 3.2 Hz, 1H), 7.05-7.15 ( m, 1H), 7.16-7.24 (m, 1H), 7.41 (d, J = 3.2 Hz, 1H), 7.55-7.63 (m, 1H), 7.70 (dd, J = 1.3, 8.6 Hz, 1H), 7.90 (d, J = 1.6 Hz, 1H), 12.47 (br s, 1H). APCIMS m / z: [M + H] + 413. p.f .: 181-184 ° C.

[Example 462] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -3-methoxybenzamide (Compound 462) In a manner similar to that in Example 456, Using 3-methoxybenzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 462 (1.91 g, 77%) was obtained as a gray white solid from Compound 454 (1.67 g, 6.00 mmol). X H NMR (DMSO-de, d ppm): 1.55-1.80 (m, 4H), 3.14-3.24 (m, 1H), 3. 36 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.86 (s, 3H), 3.87-3.92 (m, 2H), 6.70 (dd, J = 1.6, 3.5 Hz, 1H), 7.20-7.26 ( m, 1H), 7.45 (dd, J = 0.8, 3.5 Hz, 1H), 7.43-7.53 (m, 1H), 7.69-7.77 (m, 2H), 7.91 (dd, J = 0.8, 1.6 Hz, 1H) , 13.27 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 413. p. f. : 198-200 ° C.

[Example 463] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -4-methoxybenzamide (Compound 463) In a manner similar to that in Example 456, use 4-methoxybenzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 463 (152 mg, 82%) was obtained as a white grayish solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-d 6, d ppm): 1.54-1.76 (m, 4H), 3.13-3.24 (, 1H), 3.36 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.86 (s, 3H) , 3.89- 3.91 (m, 2H), 6.70 (dd, J = 1.6, 3.2 Hz, 1H), 7.10 (dd, J = 1. 9, 8.9 Hz, 2H), 7.45 (dd, J = 0.5, 3.2 Hz, 1H), 7.90 (dd, J = 0.5, 1.6 Hz, 1H), 8.15 (dd, J = 1.9, 8.9 Hz), 13.10 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 413. p.f .: 184-188 ° C.

[Example 464] 3- (Dimethylamino) -N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 464) Compound 454 (125 mg, 0.450 mmol) was dissolved in DMF (2 mL), and 3- (dimethylamino) benzoic acid (296 mg, 1.80 mmol), EDC hydrochloride (344 mg, 1.80 mmol) and 1-hydroxybenzotriazole monohydrate (276 mg, 1.80 mmol) were added to this, followed by stirring at 80 ° C for 2 hours. The mixture of The reaction was poured into water (200 mL), followed by extraction with chloroform. The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 19: 1), followed by re-mixing in methanol to provide the title Compound 464 (78.5 mg, 41%) as a pale yellow solid. X H NMR (DMSO-de, d ppm): 1.55-1.75 (m, 4H), 2.99 (s, 6H), 3.13-3.23 (m, 1H), 3.35 (ddd, J = 2.2, 11.6, 11.6 Hz, 2H ), 3.89 (ddd, J = 2.2, 3.8, 11.6 Hz, 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 6.99 (ddd, J = 1.4, 2.7, 8.1 Hz, 1H), 7.31- 7.48 (m, 4H), 7.90 (dd, J = 0.8, 1.9 Hz, 1H), 13.19 (br s, 1H). APCIMS m / z: [M + H] + 426. p.f .: 239-243 ° C.

[Example 465] 4- (Dimethylamino) -N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 465) Compound 454 (125 mg, 0.450 mmol ) was dissolved in DMF (2 mL), and 4- (dimethylamino) benzoic acid (296 mg, 1.80 mmol), EDC hydrochloride (344 mg, 1.80 mmol) and 1-hydroxybenzotriazole monohydrate (276 mg, 1.80 mmol) were added thereto, followed by stirring at 80 ° C for 2 hours. The water (200 mL) was added to the reaction mixture, and the precipitated solid was collected by filtration. The resulting solid was purified through silica gel column chromatography (chloroform: methanol = 9: 1), followed by re-mixing in a thick mixture with ethanol to provide the title Compound 465 (5.30 mg, 3%) as a pale brown solid. X H NMR (DMSO-de, d ppm): 1.55-1.80 (, 4H), 3.03 (s, 6H), 3.11-3.22 (m, 1H), 3.35 (ddd, J = 2.2, 11.6, 11.6 Hz, 2H) , 3.85-3.93 (m, 2H), 6.69 (dd, J = 1.6, 3.5 Hz, 1H), 6.77 (d, J = 9.2 Hz, 2H), 7.45 (dd, J = 0.8, 3.5 Hz, 1H), 7.89 (dd, J = 0.8, 1.6 Hz, 1H), 8.05 (d, J = 9.2 Hz, 2H), 12.81 (br s, 1H). APCIMS m / z: [M + H] + 426. p.f .: 238-240 ° C.

[Example 466] 2-Fluoro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 466) In a manner similar to that in Example 456, when using 2-fluorobenzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 466 (155 mg, 86%) was obtained as a pale brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.54-1.76, (m, 4H), 3.15-3.25 (m, 1H), 3.36 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.84-3.93 (m, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.35-7.50 (m, 3H) 7.61- 7. 71 (m, 1H), 7.75-7.83 (m, 1H), 7.89 (d, J = 1.9 Hz, 1H), 13. 23 (br s, 1H). APCIMS m / z: [M + H] + 401. p.f .: 172-176 ° C.

[Example 467] 3-Fluoro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 467) In a manner similar to that in Example 456 , by using 3-fluorobenzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 467 (160 mg, 89%) was obtained as a gray white solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (, 1H), 3.36 (ddd, J = 2.2, 11.6, 11.6 Hz, 2H), 3.89 (ddd, J = 2.2, 4. 0, 11.6 Hz, 2H), 6.70 (dd, J = 1.6, 3.2 Hz, 1H), 7.44 (d, J = 3.2 Hz, 1H), 7.49-7.68 (m, 2H), 7.90 (dd, J = 0.8, 1.6 Hz, 1H), 7.94-8.02 (m, 2H), 13.34 (br s, 1H). APCIMS m / z: [M + H] + 401. p.f .: 229-231 ° C.

[Example 468] 4-Fluoro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 468) Compound 454 (834 mg, 3.00 mmol) was dissolved in DMF (12 mL), and 4-fluorobenzoic acid (3.36 g, 24.0 mmol), EDC hydrochloride (4.12 g, 24.0 mmol.) And 1-hydroxybenzotriazole monohydrate (3.68 g, 24.0 mmol) were added thereto, followed by stirring at 80 ° C for 2 hours The reaction mixture was poured into a mixture of a saturated aqueous solution of sodium hydrogen carbonate (30 mL) and water (30 mL), and the precipitated solid was collected by filtration. The resulting product was purified through silica gel column chromatography (chloroform: methanol = 19: 1), followed by recrystallization from ethanol to provide the title Compound 468 (270 mg, 23%) as a white solid. NMR (DMSO-de, d ppm): 1.58-1.78 (m, 4H), 3.15-3.25 (m, 1H), 3.35-3.55 (m, 2H), 3.88 (ddd, J = 1.9, 3.8, 11.3 Hz, 2H), 6.70 (dd, J = 1.6, 3.2 Hz, 1H), 7.37-7.46 (m, 3H), 7.90 (dd, J = 0.8, 1.6 Hz, 1H), 8.20-8.26 (m, 2H), 13.27 (br s, 1H) APCIMS m / z: [M + H] + 401. mp: 131-132 ° C.

[Example 469] 2-Chloro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 469) In a manner similar to that in Example 456, when using 2-chlorobenzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 469 (140 mg, 75%) was obtained as a white solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.55-1.85 (m, 4H), 3.15-3.25 (m, 1H), 336 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.88 (ddd, J = 2.4, 3.8, 11.3 Hz, 2H), 6.69 (dd, J = 1.6, 3.5 Hz, 1H), 7.39 (d, J = 3.5 Hz, 1H), 7.45-7.70 (m, 5H), 7.89 (dd, J = 0.8, 1.6 Hz, 1H), 13.34 (br s, 1H). APCIMS m / z: [35C1M + H] + 417, [37C1M + H] + 419. p.f .: 160-162 ° C.

[Example 470] 3-Chloro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 470) In a manner similar to that in Example 456, when using 3-chlorobenzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 470 (131 mg, 70%) was obtained from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-d 6, d ppm): 1.55-1.80 (m, 4H), 3.12-3.25 (m, 1H), 3. 36 (ddd, J = 2.2, 12.1, 12.1 Hz, 2H), 3.86-3.92 (m, 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 7.43 (d, J = 3.5 Hz, 1H) , 7. 60 (dd, J = 7.8, 7.8 Hz, 1H), 7.72-7.76 (m, 1H), 7.90 (d, J = 1.9 Hz, 1H), 8.09 (dd, J = 1.1, 7.8 Hz, 1H), 8.19-8.20 (m, 1H), 13.36 (br s, 1H). APCIMS m / z: [35C1M + H] + 417, [37C1M + H] + 419. p.f .: 210-212 ° C.

[Example 471] 4-Chloro-N- [4- (2-furyl) -5- (tetrahydro-drahipin-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 471) In a manner similar to that in Example 456, when using 4-chlorobenzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 471 (129 mg, 69%.) Was obtained as a white solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.55-1.85 (m, 4H), 3.15-3.25 (m, 1H), 3.34-3.42 (m, 2H), 3.84-3.93 (m, 2H), 6.70 (dd) , J = 1.9, 3.5 Hz, 1H), 7.44 (dd, J = 0.8, 3.5 Hz, 1H), 7.65 (dd, J = 1.6, 8.4 Hz, 2H), 7.90 (dd, J = 0.8, 1.9 Hz, 1H), 8.15 (dd, J = 1.6, 8.4 Hz, 2H), 13.35 (br s, 1H). APCIMS m / z: [35C1M + H] + 417, [37C1M + H] + 419. p.f .: 204-206 ° C.

[Example 472] 2-Cyano-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 472) In a manner similar to that in Example 465, when using 2-cyanobenzoic acid in place of 3- (dimethylamino) benzoic acid, the title Compound 472 (35.3 mg, 19%) was obtained as a yellow solid from Compound 454 (125 mg, 0.450 mmol).

X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.12-3.22 (m, 1H), 3.28-3.38 (m, 2H), 3.88 (ddd, J = 2.2, 11.3, 11.3 Hz , 2H), 6.73 (dd, J = 1.9, 3.5 Hz, 1H), 7.50 (d, J = 3.5 Hz, 1H), 7.80-8.20 (m, 5H), 11.27 (brs, 1H). APCIMS m / z: [M + H] + 408. p.f. : 221-224 ° C.

[Example 473] 3-Cyano-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 473) In a manner similar to that in Example 465, when using 3-cyanobenzoic acid in place of 3- (dimethylamino) benzoic acid, the title Compound 473 (166 mg, 90%) was obtained as a pink solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.55-1.76 (m, 4H), 3.15-3.25 (m, 1H), 3.37 (ddd, J = 1.6, 11.6, 11.6 Hz, 2H), 3.80-3.91 (m , 2H), 6.71 (dd, J = 1.6, 3.2 Hz, 1H), 7.45 (d, J = 3.2 Hz, 1H), 7.79 (dd, J = 7.8, 7.8 Hz, 1H), 7.92 (d, J = 1.6 Hz, 1H), 8.14 (d, J = 7.8 Hz, 1H), 8.40 (d, J = 7.8 Hz, 1H), 8.58 (s, 1H), 13.47 (br s, 1H). APCIMS m / z: [M + H] + 408. p.f. : 257-260 ° C.

[Example 474] 4-Cyano-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 474) In a manner similar to that in Example 465, when using 4-cyanobenzoic acid in place of 3- (dimethylamino) benzoic acid, the title Compound 474 (35.3 mg, 19%) was obtained from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-d 6, d ppm): 1.50-1.80 (m, 4H), 3.10-3.30 (m, 1H), 3.35-3.50 (m, 2H), 3.84-3.93 (m, 2H), 6.70 (dd) , J = 1.9, 3.5 Hz, 1H), 7.44 (d, J = 3.5 Hz, 1H), 7.90 (d, J = 1.9 Hz, 1H), 8.05 (d, J = 8.4 Hz, 2H), 8.26 (d , J = 8.4 Hz, 2H), 13.53 (br s, 1H). APCIMS m / z: [M-H] "406. p.f .: 231-234 ° C.

[Example 475] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) aiazol-2-yl] -2- (trifluoromethoxy) benzamide (Compound 475) Compound 454 (125 mg, 0.450 mmol ) and DMAP (2.69 mg, 0.022 mmol) were suspended in pyridine (2 mL), and 2- (trifluoromethoxy) benzoyl chloride (202 mg, 0.900 mmol) was added thereto, followed by stirring at 80 ° C for 6 hours. hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a solution aqueous solution saturated with sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from ethanol to provide Title Compound 475 (111 mg, 53%) as a pale yellow solid. X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.10-3.22 (m, 1H), 3.36 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.85-3.92 (m , 2H), 6.70 (dd, J = 1.6, 3.5 Hz, 1H), 7.41 (d, J = 3.5 Hz, 1H), 7.52-7.60 (m, 2H), 7.73 (ddd, J = 1.6, 7.6, 7.6 Hz 1H), 7.83 (dd, J = 1.6, 7.6 Hz, 1H), 7.89 (d, J = 1.6 Hz, 1H), 13.41 (br; s, 1H). APCIMS m / z: [M + H] + 467. m.p .: 131-134 ° C.

[Example 476] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -3- (trifluoromethoxy) benzamide (Compound 476) In a manner similar to that in Example 456, when using 3- (trifluoromethoxy) benzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 476 (170 mg, 81%) was obtained as a brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-d 6, d ppm): 1.50-1.80 (m, 4H), 3.10-3.25 (m, 1H), 3. 36 (ddd, J = 2.2, 11.6, 11.6 Hz, 2H), 3.85-3.93 (m, 2H), 6.71 (dd, J = 1.6, 3.2 Hz, 1H), 7.45 (d, J = 3.2 Hz, 1H) , 7. 68-7.75 (m, 2H), 7.90 (d, J = 1.6 Hz, 1H), 8.12-8.21 (m, 2H), 13.49 (br s, 1H). APCIMS m / z: [M + H] + 467. p.f. : 197-198 ° C.

[Example 477] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -4- (trifluoromethoxy) benzamide (Compound 477) In a manner similar to that in Example 456, when using 4- (trifluoromethoxy) benzoyl chloride in place of cyclopropanecarbonyl chloride, the title Compound 477 (156 mg, 74%) was obtained as a pale brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3.36 (ddd, J = 2.2, 11.6, 11.6 Hz, 2H), 3.85-3.94 (m , 2H), 6. 70 (dd, J = 1.6, 3.2 Hz, 1H), 7.44 (d, J = 3.2 Hz, 1H), 7.57 (d, J = 8.1 Hz, 2H), 7.90 (d, J = 1.6 Hz, 1H), 8.27 (d, J = 8. 1 Hz, 2H), 13.39 (br s, 1H). APCIMS m / z: [M + H] + 467. p.f .: 177-180 ° C.

[Example 478] 4- (Chloromethyl) -N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 478) 4- (Chloromethyl) benzoyl chloride (942 mg, 4.99 mmol) was dissolved in THF (16 mL), and Compound 454 (1.11 g, 3.99 mmol), triethylamine (0.840 mL, 5.98 mmol) and DMAP (50.0 mg, 0.400 mmol) were added thereto, followed by stirring under heating and reflux for 2 hours. The reaction mixture was concentrated under reduced pressure, and water was added to the resulting residue, followed by chloroform extraction. The organic layer was washed successively with a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 99: 1), followed by re-mixing in methanol to provide the title Compound 478 (1.42 g, 83%) as an ocher solid. X H NMR (DMSO-de, d ppm): 1.55-1.78 (m, 4H), 3.13-3.27 (m, 1H), 3.36 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.89 (ddd, J = 2.4, 3.8, 11.3 Hz, 2H), 4.86 (s, 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 7.44 (dd, J = 0.5, 3.5 Hz, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.90 (dd, J = 0.5, 1.9 Hz, 1H), 8.14 (d, J = 8.4 Hz, 2H), 13.30 (br s, 1H). APCIMS m / z: [35C1M + H] + 431, [37C1M + H] + 433.

[Example 479] 4- (Dimethylaminomethyl) -N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 479) Compound 478 (340 mg, 0.789 mmol ) 2 mol / L of dimethylamine in THF (20 mL, 39.5 mmol) was added to a solution, followed by stirring overnight at 60 ° C. The solvent was distilled under reduced pressure, and the resulting residue was purified through silica gel column chromatography (chloroform-methanol = 19: 1), followed by re-mixing in a mixed mixture of ethanol and ether. of diethyl to provide the title Compound 479 (153 mg, 44%) as a yellow solid. X H NMR (DMSO-de, d ppm): 1.55-1.80 (m, 4H), 2.20 (s, 6H), 3.10-3.20 (m, 1H), 3.36 (ddd, J = 2.4, 11.6, 11.6 Hz, 2H ), 3.52 (s, 2H), 3.85-3.93 (m, 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 7.44 (d, J = 3.5 Hz, 1H), 7.48 (d, J = 8.1 Hz, 2H), 7..90 (d, J = 1.9 Hz, 1H), 8.12 (d, J = 8.1 Hz, 2H), 13.06 (br s, 1H). APCIMS m / z: [M + H] + 440. p.f .: 109-112 ° C.

[Example 480] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -4- (piperidinomethyl) benzamide (Compound 480) Compound 478 (340 mg, 0.789 mmol ) was suspended in THF (3 mL), and piperidine (0.390 mL, 3.95 mmol) were added thereto, followed by stirring under heating and refluxing for 1.5 hours. The solvent was distilled under reduced pressure, and the resulting residue was purified through silica gel column chromatography (chloroform-methanol = 4: 1), followed by re-mixing in a thick mixture with diethyl ether to give the title Compound 480 (262 mg, 69%) as a white solid. X H NMR (DMSO-de, d ppm): 1.20-1.50 (m, 6H), 1.50-1.80 (m, 6H), 2.30-2.45 (m, 2H), 3.10-3.25 (m, 1H), 3.30-3.45 (m, 2H), 3.55 (s, 2H), 3.85-3.93 (m, 2H), 6.69 (dd, J = 1.6, 3.2 Hz, 1H), 7.44 (d, J = 3.2 Hz, 1H), 7.48 ( d, J = 8.1 Hz, 2H), 7.90 (d, J = 1.6 Hz, 1H), 8.11 (d, J = 8.1 Hz, 2H), 13.07 (br s, 1H). APCIMS m / z :. [M + H] + 480. p.f .: 160-162 ° C.

[Example 481] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -4- (4-hydroxypiperidinmethyl) benzamide (Compound 481) In a manner similar to that in Example 480, using 4-hydroxypiperidine in place of piperidine, the title Compound 481 (380 mg, 97%) was obtained as a pale yellow solid from Compound 478 (340 mg, 0.789 mmol). X H NMR (DMSO-de, d ppm): 1.40-1.50 (m, 2H), 1.65-1.85 (m, 4H), 2. 00-2.10 (m, 2H), 2.85-2.90 (m, 2H), 2.84 (ddd, J = 3.5, 9.4, 11.3 Hz, 2H), 3.05-3.20 (m, 1H), 3.20-3.40 (m, 3H) ), 3.45 (s, 2H), 3.70-3.80 (m, 1H), 3.85-3.95 (m, 2H), 4.45-4.50 (m, 1H), 6.63 (dd, J = 1.6, 3.5 Hz, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 3.5 Hz, 1H), 7.80 (d, J = 1.6 Hz, 1H), 8.09 (d, J = 8.4 Hz, 2H). APCIMS m / z: [M + H] + 496. p.f .: 194-195 ° C.

[Example 482] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -4- (morpholinomethyl) benzamide (Compound 482) In a manner similar to that in Example 480, using morpholine in place of piperidine, the title Compound 482 (322 mg, 85%) was obtained as a pale yellow solid from Compound 478 (340 mg, 0.789 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 2.38 (t, J = 4.3) Hz, 4H), 3.10-3.25 (m, 1H), 3.36 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.56 (s, 2H), 3.59 (t, J = 4.3 Hz, 4H), 3.85-3.93 (m, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.44 (dd , J = 0.8, 3. 5 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.89 (dd, J = 0.8, 1.9 Hz, 1H), 8.12 (d, J = 8.4 Hz, 2H), 12.67 (br s, 1H). APCIMS m / z: [M + H] + 482. p.f .: 92-96 ° C.

[Example 483] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2,3-dimethoxybenzamide (Compound 483) In a manner similar to that in Example 465 , when using 2,3-dimethoxybenzoic acid in place of 4- (dimethylamino) benzoic acid, the title Compound 483 (158 mg, 79%) was obtained as a pale yellow solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.75 (m, 4H), 3.15-3.25 (m, 1H), 3.36 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.83 (s, 3H) ), 3.84- 3.94 (m, 2H), 3.87 (s, 3H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7. 17-7.21 (m, 2H), 7.23-7.30 (m, 1H), 7.41 (dd, J = 0.5, 3.5 Hz, 1H), 7.89 (dd, J = 0.5, 1.9 Hz, 1H), 12.80 (br s, 1H).

APCIMS m / z: [M + H] + 443. p.f. : 198-200 ° C.

[Example 484] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2,4-dimethoxybenzamide (Compound 484) In a manner similar to that in Example 456 , by using 2,4-dimethoxybenzoyl chloride in place of cyclopropanecarbonyl chloride, followed by re-making in a thickened mixture with methanol, the title Compound 484 (156 mg, 78%) was obtained as a brown solid from Compound 454 (125 mg, 0.150 mmol).

X H NMR (DMSO-de, d ppm): 1.54-1.75 (m, 4H), 3.12-3.22 (m, 1H), 3.34 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.89 (s, 3H ), 3.90- 3.95 (m, 2H), 3.97 (s, 3H), 6.69 (dd, J = 1.9, 3.2 Hz, 1H), 6.72-6.77 (m, 2H), 7.41 (d, J = 3.2 Hz, 1H), 7.80 (dd, J = 3.0, 8.4 Hz, 1H), 7.89 (d, J = 1.9 Hz, 1H) / 11.94 (br s, 1H). APCIMS m / z: [M + H] + 443. mp .: 219-222 ° C.

[Example 485] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2,5-dimethoxybenzamide (Compound 485) In a manner similar to that in Example 465 , using 2, 5-dimethoxybenzoic acid in place of 4- (dimethylamino) benzoic acid, followed by re-mixing in a thick mixture with ethanol, the title Compound 485 (172 mg, 86%) was obtained as a pale yellow solid. from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.10-3.25 (m, 1H), 3. 35 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.77 (s, 3H), 3.80-3.92 (, 2H), 3.88 (s, 3H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H ), 7.15- 7.24 (m, 2H), 7.25-7.31 (m, 1H), 7.41 (d, J = 3.5 Hz, 1H), 7. 90 (d, J = 1.9 Hz, 1H) / 12.44 (br s, 1H). APCIMS m / z: [M + H] + 443. p. f. : 107-110 ° C.

[Example 486] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2, 6-dimethoxybenzamide (Compound 486) In a manner similar to that in Example 456, by using 2,6-dimethoxybenzoyl chloride in place of cyclopropanecarbonyl chloride, followed by recrystallization from a mixed solvent of ethanol, diethyl ether and ethyl acetate, the title Compound 486 (91.1 mg, 46%) was obtained as a pink solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.54-1.76 (m, 4H), 3.12-3.24 (m, 1H), 3.32-3.42 (m, 2H), 3.76 (s, 6H), 3.84-3.92 (m , 2H), 6.68 (dd, J = 1.6, 3.0 Hz, 1H), 6.75 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 3.0 Hz, 1H), 7.42 (t, J = 8.4 Hz , 1H), 7.88 (d, J = 1.6 Hz, 1H), 12.93 (br s, 1H). APCIMS m / z: [M + H] + 443. mp .: 152-156 ° C.

[Example 487] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -3,4-dimethoxybenzamide (Compound 487) In a manner similar to that in Example 456 , by using 3,4-dimethoxybenzoyl chloride in place of cyclopropanecarbonyl chloride, followed by re-mixing in a thick mixture with ethanol, the title Compound 487 (150 mg, 75%) it was obtained as a brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-d 6, d ppm): 1.55-1.80 (m, 4H), 3.10-3.25 (m, 1H), 3.35 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.86 (s, 3H ), 3.87 (s, 3H), 3.88-3.92 (m, 2H), 6.70 (dd, J = 1.6, 3.2 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 3.2 Hz, 1H), 7.78-7.82 (m, 2H), 7.84 (d, J = 1.6 Hz, 1H), 13.11 (br s, 1H). APCIMS m / z: [M + H] + 443. p.f .: 289-292 ° C.

[Example 488] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -3,5-dimethoxybenzamide (Compound 488) In a manner similar to that in Example 456 , by using 3, 5-dimethoxybenzoyl chloride in place of cyclopropanecarbonyl chloride, followed by re-making in a thickened mixture with methanol, the title Compound 488 (179 mg, 93%) was obtained as a pale brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.10-3.25 (m, 1H), 3.36 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.84 (s, 6H) ), 3.80-3.92 (m, 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 6.78 (t, J = 2.7 Hz, 1H), 7.35 (d, J = 2.7 Hz, 2H), 7.45 (dd, J = 0.8, 3.5 Hz, 1H), 7.91 (dd, J = 0.8, 1.9 Hz, 1H), 13.25 (br s, 1H). APCIMS m / z: [M + H] + 443. 'p.f .: 278-280' ° C.

[Example 489] 2, 3-Difluoro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyi) thiazol-2-yl-benzamide (Compound 489) In a manner similar to that in Example 456, when using 2,3-difluorobenzoyl chloride in place of cyclopropanecarbonyl chloride, followed by recrystallization from a mixed solvent of ethanol and diethyl ether, the title Compound 489 (116 mg, 62%) was obtained as a brown solid. from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3.36 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.84-3.93 (m , 2H), 6.70 (dd, J = 1.6, 3.5 Hz, 1H), 7.34-7.41 (m, 1H), 7.42 (dd, J = 0.8, 3.5 Hz, 1H), 7.57-7.77 (m, 2H), 7.90 (dd, J = 0.8, 1.6 Hz, 1H), 13.42 (brs, 1H). APCIMS m / z: [M + H] + 419. p.f .: 154-160 ° C.

[Example 490] 2,4-Difluoro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 490) In a manner similar to that in Example 456, when using 2,4-difluorobenzoyl chloride in place of cyclopropanecarbonyl chloride, followed by re-mixing in a thickened mixture with ethanol, the title Compound 490 (170 mg, 90%) it was obtained as a brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3.36 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.84-3.93 (m , 2H), 6.70 (dd, J = 1.6, 3.5 Hz, 1H), 7.22-7.32 (m, 1H), 7.42 (dd, J = 0.8, 3.5 Hz, 1H), 7.44-7.52 (, 1H), 7.85 -7.92 (m, 2H), 13.28 (br s, 1H). APCIMS m / z: [M + H] + 419. p.f .: 213-215 ° C.

[Example 491] 2, 5-Difluoro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 491) In a manner similar to that in Example 456, by using 2,5-difluorobenzoyl chloride in place of cyclopropanecarbonyl chloride, followed by re-mixing in a thickened mixture with diethyl ether, the title Compound 491 (164 mg, 87%) was obtained as a brown solid. from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3.36 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.88 (ddd, J = 2.2, 4. 3, 11.3 Hz, 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 7.41 (dd, J = 0.8, 3.5 Hz, 1H), 7.43-7.58 (m, 2H), 7.68 (ddd, J = 3.0, . 4, 8.4 Hz, 1H), 7.90 (dd, J = 0.8, 1.9 Hz, 1H), 13.37 (br s, 1H).

APCIMS m / z: [M + H] + 419. p.f .: 172-174 ° C.

[Example 492] 2,6-Difluoro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 492) In a manner similar to that in Example 456, by using 2,6-difluorobenzoyl chloride in place of cyclopropanecarbonyl chloride, followed by re-mixing in a thickened mixture with a mixed solvent of ethanol and diethyl ether, the title Compound 492 (120 mg, 69%) was obtained as a brown solid from Compound 454 (125 mg, 0.450 mmol).

X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3. 36 (ddd, J = 2.4, 11.6, 11.6 Hz, 2H), 3.83-3.92 (m, 2H), 6.70 (dd, J = 1.6, 3.5 Hz, 1H), 7.29 (t, J = 8.1 Hz, 1H) , 7. 40 (d, J = 3.5 Hz, 1H), 7.60-7.73 (m, 2H), 7.90 (d, J = 1.9 Hz, 1H), 13.60 (br s, 1H). APCIMS m / z: [M + H] + 419. p. f. : 168-170 ° C.

[Example 493] 3,4-Difluoro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 493) In a manner similar to that in Example 456, when using 3,4-difluorobenzoyl chloride in place of Cyclopropancarbonyl, followed by re-mixing in a thick mixture with diethyl ether, Compound of title 493 (145 mg, 77%) was obtained as a brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3.36 (ddd, J = 2.4, 11.6, 11.6 Hz, 2H), 3.83-3.92 (m , 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 7.45 (d, J = 3.5 Hz, 1H), 7.63-7.73 (m, 1H), 7.90 (d, J = 1.9 Hz, 1H) , 8.02-8.08 (m, 1H), 8.24 (ddd, J = 2.2, 7.5, 11.3 Hz, 1H), 13.37 (br s, 1H). APCIMS m / z: [M + H] + 419. p.f .: 208-210 ° C.

[Example 494] 3, 5-Difluoro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 494) In a manner similar to that in Example 456, by using 3, 5-difluorobenzoyl chloride in place of cyclopropanecarbonyl chloride, followed by re-mixing in a mixed mixture of ethanol and diethyl ether, the title Compound 494 (165 mg, 88%) obtained as a brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-d 6, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3.36 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.83-3.93 (m , 2H), 6.71 (dd, J = 1.9, 3.5 Hz, 1H), 7.44 (dd, J = 0.8, 3.5 Hz, 1H), 7.58-7.67 (m, 1H), 7.84-7.90 (m, 2H), 7.91 (dd, J = 0.8, 1. 9 Hz, 1H), 13.43 (br s, 1H). APCIMS m / z: [M + H] + 419. p.f .: 259-265 ° C.

[Example 495] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -1,4-benzodioxane-5-carboxamide (Compound 495) In a manner similar to that in Example 455, by using 1,4-benzodioxane-5-carboxylic acid in place of isonicotinic acid, Title Compound 495 (145 mg, 73%) was obtained as a brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.10-3.22 (m, 1H), 3.35 (ddd, J = 2.4, 11.6, 11.6 Hz, 2H), 3.83-3.93 (, 2H), 4.29-4.34 (m, 2H), 4.39-4.43 (m, 2H), 6.69 (dd, J = 1.6, 3.2 Hz, 1H), 6.96 (dd, J = 7.8, 7.8 Hz, 1H), 7.09 (dd, J = 1.6, 7.8 Hz, 1H), 7.23 (dd, J = 1.6, 7.8 Hz, 1H), 7.42 (d, J = 3.2 Hz, 1H), 7.89 (d, J = 1.6 Hz, 1H) , 12.52 (br s, 1H). APCIMS m / z: [M + H] + 441. p.f .: 188-190 ° C.

[Example 496] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -1,3-benzodioxol-5-carboxamide (Compound 496) In a manner similar to that in Example 456, at use 1,3-benzodioxole-5-carbonyl chloride in place of cyclopropanecarbonyl chloride, followed by reagent. to be made in a thick mixture with ethanol, the title compound 496 (143 mg, 75%) was obtained as a brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3.36 (ddd, J = 2.4, 11.6, 11.6 Hz, 2H), 3.83-3.93 (m , 2H), 6.16 (s, 2H), 6.70 (dd, J = 1.6, 3.2 Hz, 1H), 7.09 (d, J = 8.1 Hz, 1H), 7.45 (d, J = 3.2 Hz, 1H), 7.70 (d, J = 1.9 Hz, 1H), 7.79 (dd, J = 1.9, 8.1 Hz, 1H), 7.90 (d, J = 1.6 Hz, 1H), 13.07 (br s, 1H). APCIMS m / z: [M + H] + 427. p.f .: 194-196 ° C.

[Example 497] 2, 2-Difluoro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -1,3-benzodioxol-4-carboxaraide (Compound 497) In a manner similar to that in Example 456 ,. when using 2, 2-difluoro-1,3-benzodioxol-4-carbonyl chloride in place of cyclopropanecarbonyl chloride, followed by re-mixing in a thick mixture with ethanol, the title Compound 497 (161 mg, 77%) was obtained as a brown solid from Compound 454 (125 mg, 0.450 mmol). 1 H NMR (DMSO-d 6, d ppm): 1.50-1.80 (m, 4H), 3.10-3.30 (m, 1H), 3.36 (ddd, J = 2.2, 11.6, 11.6 Hz, 2H), 3.85-3.92 (m , 2H), 6.70 (dd, J = 1.6, 3.2 Hz, 1H), 7.37 (dd, J = 8.1, 8.1 Hz, 1H), 7.45 (d, J = 3.2 Hz, 1H), 7.69 (dd, J = 0.8, 8.1 Hz, 1H), 7.82 (dd, J = 0.8, 8.1 Hz, 1H), 7.90 (d, J = 1.6 Hz, 1H), 13.43 (br s, 1H). APCIMS m / z: [M + H] + 463. mp .: 206-207 ° C.

[Example 498] 2, 2-Difluoro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -1,3-benzodioxol-5-carboxamide (Compound 498) In a manner similar to that in Example 456, by using 2, 2-difluoro-1,3-benzodioxole-5-carbonyl chloride in place of cyclopropanecarbonyl chloride, followed by re-mixing in a thick mre with ethanol, the Compound of title 498 (98.5 mg, 47%) was obtained from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3.36 (ddd, J = 2.4, 11.6, 11.6 Hz, 2H), 3.85-3.92 (m , 2H), 6.70 (dd, J = 1.6, 3.5 Hz, 1H), 7.45 (d, J = 3.5 Hz, 1H), 7.63 (d, J = 8.6 Hz, 1H), 7.90 (d, J = 1.6 Hz , 1H), 8.08 (dd, J = 1.6, 8.6 Hz, 1H), 8.18 (d, J = 1.6 Hz, 1H), 13.33 (br s, 1H). APCIMS m / z: [M + H] + 463. p. f. : 124-129 ° C.

[Example 499] 2-Chloro-N- (4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 499) Step 1: The 2-chloroisonicotinic acid (707 mg, 4.49 mmol) was suspended in thionyl chloride (10 mL), followed by stirring under heating and refluxing for 7 hours. The reaction mre was concentrated under reduced pressure to provide the 2-chloroisonicotinoyl chloride.

Step 2: In a manner similar to that in Example 456, by using 2-chloroisonicotinoyl chloride obtained in Step 1, instead of cyclopropanecarbonyl chloride, and crystallizing the product from ethanol, the title Compound 499 (90.3 mg, 48%) was obtained from Compound 454 (125 mg, 0. 450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3. 36 (ddd, J = 2.7, 11.3, 11.3 Hz, 2H), 3.85-3.92 (m, 2H), 6.71 (dd, J = 1.6, 3.5 Hz, 1H), 7.44 (dd, J = 0.8, 3.5 Hz, 1H), 7.92 (dd, J = 0.8, 1.6 Hz, 1H), 8.01 (dd, J = 1.4, 5.1 Hz, 1H), 8.17 (dd, J = 0.8, 1.4 Hz, 1H), 8.67 (dd, J = 0.8, 5.1 Hz, 1H), 13.64 (br s, 1H). APCIMS m / z: [35C1M + H] + 418, [3C1M + H] + 420. p.f .: 185-186 ° C.

[Example 500] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-methylpyridine-4-carboxamide (Compound 500) In a manner similar to that in Example 465, by using 2-methylisonicotinic acid in place of 3- (dimethylamino) benzoic acid, followed by re-mixing in a thickened form with diethyl ether, the title Compound 500 (22.0 mg, 12%) was obtained from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 2.58 (s, 3H), 3.15-3.25 (, 1H), 3.35-3.38 (m, 2H), 3.83-3.93 (m, 2H), 6.71 (dd, J = 1.9, 3.5 Hz, 1H), 7.43 (dd, J = 0.8, 3.5 Hz, 1H), 7.81 (dd, J = 1.1, 5.1 Hz, 1H), 7.89-7.92 (m , 2H), 8.68 (d, J = 5.1 Hz, 1H), 13.48 (br s, 1H). APCIMS m / z: [M + H] + 398. p.f .: 169-173 ° C.

[Example 501] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] pyridine-3-carboxamide (Compound 501) In a manner similar to that in Example 464, when using nicotinic acid in place of 3- (dimethylamino) benzoic acid, followed by recrystallization from ethanol, Title Compound 501 (1.72 g, 75%) was obtained as a pale yellow solid from Compound 454 (1.67 g, 6.00 mmol). X H NMR (DMSO-de, d ppm): 1.54-1.76 (m, 4H), 3.15-3.25 (m, 1H), 3.36 (ddd, J == 2.2, 11.3, 11.3 Hz, 2H), 3.84-3.93 ( m, 2H), 6.71 (dd, J = 1.9, 3.5 Hz, 1H), 7.45 (d, J = 3.5 Hz, 1H), 7.61 (dd, J = 4.9, 8.4 Hz, 1H), 7.90 (d, J = 1.9 Hz, 1H), 8.46 (ddd, J = 2.2, 2.2, 8.4 Hz, 1H), 8.80 (dd, J = 2.2, 4.9 Hz, 1H), 9.25 (d, J = 2.2 Hz, 1H), 13.50 (br s, 1H). APCIMS m / z: [M + H] + 384. p.f .: 209-212 ° C.

[Example 502] 2-Chloro-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] pyridine-5-carboxamide (Compound 502) Compound 454 (125 mg, 0.450 mmol) and DMAP (3.0 mg, 0.022 mmol) were suspended in pyridine (2 mL), and 6-chloronicotinoyl chloride (158 mg, 0.897 mmol) was added thereto, followed by stirring at 80 ° C for 1 hour. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was redissolved in ethanol to provide the title Compound 502 (138 mg, 73%) as a pale brown solid. X H NMR (DMSO-d 6, d ppm): 1.50-1.80 (m, 4H), 3.15-3.27 (m, 1H), 3.36 (ddd, J = 2.2, 11. 6, 11.6 Hz, 2H), 3.89 (ddd, J = 2.2, 4.0, 11.6 Hz, 2H), 6.71 (dd, J = 1.9, 3.5 Hz, 1H), 7.44 (dd, J = 0.5, 3.5 Hz, 1H ), 7.76 (dd, J = 0.5, 8.6 Hz, 1H), 7.91 (dd, J = 0.5, 1.9 Hz, 1H), 8.49 (dd, J = 2.7, 8.6 Hz, 1H), 9.90 (dd, J = 0.5, 2.7 Hz, 1H), 13.55 (br s, 1H). APCIMS m / z: [35 ClM + H] + 416, [37C1M + H] + 418. p.f .: 233-235 ° C.

[Example 503] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-morpholinopyridine-5-carboxamide (Compound 503) Compound 502 (100 mg, 0.239 mmol) was suspended in 1,4-dioxane (1 mL), and morpholine (0.063 mL, 0.72 mmol) was added thereto, followed by stirring overnight at 100 ° C. The reaction mixture was concentrated under reduced pressure, and the resulting residue was redissolved in ethanol to provide the title Compound 503 (109 mg, 97 mmol) as a pale brown solid. X H NMR (DMSO-de, d ppm): 1.50-1.75 (m, 4H), 3.12-3.23 (m, 1H), 3.35 (ddd, J = 2.4, 11.6, 11.6 Hz, 2H), 3.60-3.70 (m , 8H), 3.83-3.93 (m, 2H), 6.69 (dd, J = 1.6, 3.2 Hz, 1H), 6.94 (d, J = 9.4 Hz, 1H), 7.45 (d, J = 3.2 Hz, 1H) , 7.89 (d, J = 1.6, Hz, 1H), 8.24 (dd, J = 2.4, 9.4 Hz, 1H), 8.90 (d, J = 2.4 Hz, 1H), 12.98 (br s, 1H). APCIMS m / z: [M + H] + 469. p.f .: 166-170 ° C.

[Example 504] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-methylpyridine-5-carboxamide (Compound 504) In a manner similar to that in Example 455, when using 6-methylnicotinic acid (247 mg, 1.80 mmol) in place of isonicotinic acid, followed by recrystallization from ethanol, the title Compound 504 (97.5 mg, 55%) was obtained as a pale brown solid. from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMS0-d 6, d ppm): 1.54-1.78 (m, 4H), 2.57 (s, 3H), 3.16-3.25 (m, 1H), 3.32-3.48 (m, 2H), 3.84-3.93 (m , 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 7.43-7.49 (m, 2H), 7.91 (d, J = 1.9 Hz, 1H), 8.35 (dd, J = 2.4, 8.1 Hz, 1H), 9.14 (d, J = 2.4 Hz, 1H), 13.40 (br s, 1H). APCIMS m / z: [M + H] + 398. p.f .: 209-211 ° C.

[Example 505] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (trifluoromethyl) pyridine-5-carboxamide (Compound 505) In a manner similar to that in Example 464, by using 6- (trifluoromethyl) nicotinic acid in place of 3- (dimethylamino) benzoic acid, the title Compound 505 (168 mg, 82%) was obtained from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3.37 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.89 (ddd, J = 2.4, 4.3, 11.3 Hz, 2H), 6.72 (dd, J = 1.9, 3.5 Hz, 1H), 7.45 (dd, J = 0.8, 3.5 Hz, 1H), 7.92 (dd, J = 0.8, 1.9 Hz, 1H), 8.15 (dd, J = 0.8, 8.1 Hz, 1H), 8.72 (dd, J = 1.6, 8.1 Hz, 1H), 9.39 (dd, J = 0.8, 1.6 Hz, 1H), 13.71 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 452. p.f .: 217-222 ° C.

[Example 506] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -5-methylpyridine-3-carboxamide (Compound 506) In a manner similar to that in Example 464, when using 5-methylnicotinic acid in place of 3- (dimethylamino) benzoic acid, followed by re-mixing in a thick mixture with ethanol, the title Compound 506 (147 mg, 82%) was obtained as a pale brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm) 1.50-1.80 (m, 4H), 2.40 (s, 3H), 3.15-3.25 (m, 1H), 3.36 (ddd, J = 2.4, 11.6, 11.6 Hz, 2H ), 3.89 (ddd, J = 2.2, 4.4, 11.6 Hz, 2H), 6.71 (dd, J = 1.9, 3.2 Hz, 1H), 7.43 (dd, J = 0.8, 3.2 Hz, 1H), 7.91 (dd, J = 0.8, 1.9 Hz, 1H), 8.28-8.31 (m, 1H), 8.67 (d, J = 1.6 Hz, 1H), 9.05 (d, J = 1.6 Hz, 1H), 13.42 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 398. p.f. : 239-243 ° C.

[Example 507] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] pyridine-2-carboxamide (Compound 507) In a manner similar to that in Example 464, when using picolinic acid in place of 3- (dimethylamino) benzoic acid, followed by re-mixing in a thick mixture with ethanol, the title Compound 507 (105 mg, 61%) was obtained as a pale brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.53-1.78 (m, 4H), 3.15-3.27 (m, 1H), 3. 35 (ddd, J = 2.4, 11.6, 11.6 Hz, 2H), 3.88 (ddd, J = 2.4, 4. 3, 11.6 Hz, 2H), 6.71 (dd, J = 1.6, 3.2 Hz, 1H), 7.37 (dd, J = 0.8, 3.2 Hz, 1H), 7.74 (ddd, J = 1.3, 4.9, 7.5 Hz, 1H), 7. 92 (dd, J = 0.8, 1.6 Hz, 1H), 8.11 (ddd, J = 1.6, 7.5, 7.5 Hz, 1H), 8.20 (ddd, J = 1.3, 1.3, 7.5 Hz, 1H), 8.78 (ddd, J = 1. 3, 1.6, 4.9 Hz, 1H), 12.62 (br s, 1H). APCIMS m / z: [M + H] + 384. mp .: 185-186 ° C.

[Example 508] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-methylpyrimidine-5-carboxamide (Compound 508) In a manner similar to that in Example 228, a Crude Compound 508 was obtained from Compound 454 (200 mg, 0.719 mmol) in place of Compound 186. Crude Compound 508 was recrystallized from a mixed solvent of ethanol and water to provide the title Compound 508 (118 mg, 41%) as a pale brown solid. X H NMR (DMSO-de, d ppm): 1.55-1.76 (m, 4H), 2.73 (s, 3H), 3.16-3.30 (m, 1H), 3.30-3.50 (m, 2H), 3.80-3.93 (m , 2H), 6.71 (dd, J = 1.6, 3.2 Hz, 1H), 7.44 (d, J = 3.2 Hz, 1H), 7.92 (d, J = 1.6 Hz, 1H), 9.29 (s, - 2H), 13.58 (br s, 1H). APCIMS m / z: [M + H] + 399.

[Example 509] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] piperazine-2-carboxamide (Compound 509) In a manner similar to that in Example 455, when using piperazine-2-carboxylic acid in place of isonicotinic acid, followed by re-mixing in a thick mixture with ethanol, the title Compound 509 (111 mg, 64%) was obtained as a brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.10-3.30 (m, 1H), 3. 35 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.85-3.94 (m, 2H), 6.71 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (d, J = 3.5 Hz, 1H) , 7.92 (d, J = 1.9 Hz, 1H), 8.85 (dd, J = 1.3, 2.4 Hz, 1H), 8.96 (d, J = 2.4 Hz, 1H), 9.33 (d, J = 1.3 Hz, 1H) , 13.18 (br s, 1H). APCIMS m / z: [M + H] + 385. p.f .: 200-205 ° C.

[Example 510] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) aiazol-2-yl] -5-methyl-piperazine-2-carboxamide (Compound 510) In a manner similar to that in Example 455, when using 5-methylpiperazine-2-carboxylic acid in place of isonicotinic acid, followed by re-mixing in a thick mixture with ethanol, the title Compound 510 (118 mg, 66%) was obtained as a brown solid from of Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-d 6, d ppm): 1.50-1.80 (m, 4H), 2.65 (s, 3H), 3. 15-3.25 (m, 1H), 3.35 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.85-3.93 (m, 2H), 6.71 (dd, J = 1.9, 3.5 Hz, 1H), 7.38 ( dd, J = 0.5, 3.5 Hz, 1H), 7.92 (dd, J = 0.5, 1.9 Hz, 1H), 8.74 (d, J = 1.1 Hz, 1H), 9.20 (d, J = 1.1 Hz, 1H), 13.07 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 399. p.f .: 130-131 ° C.

[Example 511] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] furan-2-carboxamide (Compound 511) Compound 454 (556 mg, 2.00 mmol) and DMAP (24.4 mg, 0.200 mmol) was suspended in pyridine (8 mL), and 2-furoyl chloride (0.394 L, 4.00 mmol) was added thereto, followed by stirring at 50 ° C for 2 hours. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 19: 1), followed by recrystallization from ethanol to provide the title Compound 511 (491 mg, 66%) as a white solid. . X H NMR (DMSO-d 6, d ppm): 1.54-1.74 (m, 4H), 3.13-3.24 (m, 1H), 3.26-3.40 (m, 2H), 3.84-3.92 (m, 2H), 6.70 (dd) , J = 1.6, 3.5 Hz, 1H), 6.77 (dd, J = 1.6, 3.5 Hz, 1H), 7.42 (d, J = 3.5 Hz, 1H), 7.78 (d, J = 3.5 Hz, 1H), 7.90 (d, J = 1.6 Hz, 1H), 8.06 (d, J = 1.6 Hz, 1H), 13.22 (br s, 1H). APCIMS m / z: [M + H] + 373. p.f. : 196-198 ° C.

[Example 512] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -5-methyl-furan-2-carboxamide (Compound 512) Step 1: 2-Methylfuran ( 9.02 mL, 100 mmol) and N, N, N ', N'-tetramethylethylenediamine (12.1 mL, 80.0 mmol) were dissolved in THF (200 mL), and a 1.59 mol / L solution of n-butyllithium in n-hexane ( 50.3 mL, 80.0 mmol) was added thereto under a stream of argon at -78 ° C, followed by stirring at room temperature for 1 hour. At -78 ° C, the DMF (31.0 mL, 400 mmol) was added dropwise to the reaction mixture, followed by stirring at room temperature for 1.5 hour. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane-ethyl acetate = 7 ¡3) to give 5-methylfuran-2-carbaldehyde (7.46 g, 68%). XH NMR (CDC13, d ppm) 2.42 (s, 3H), 6.23 (d, J = 3.6 Hz, 1H), 7.22 (d, J = 3.6 Hz, 1H), 9.51 (s, 1H).

Step 2: The 5-methylfuran-2-carbaldehyde (2.20 g, 20.0 mmol) obtained in Step 1 was dissolved in a mixed solvent of 2-methyl-2-propanol (150 mL) and water (40 mL), and 2 -methyl-2-butene (10.6 mL, 100 mmol) and sodium diacid phosphate (2.40 g, 20.0 mmol) were added thereto, followed by stirring at room temperature for 15 minutes. The 79% sodium chlorite (8.01 g, 70.0 mmol) was added to the reaction mixture little by little, followed by stirring at room temperature for 1 hour. The 4 mol / L hydrochloric acid was added to the reaction mixture to adjust the pH to 3, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform-methanol = 17.3) to provide 5-methyl-furan-2-carboxylic acid (606 mg, 24%). XH NMR (CDC13, 6 ppm): 2.41 (s, 3H), 6.17 (d, J = 3.5 Hz, 1H), 7.26 (d, J = 3.5 Hz, 1H).

Step 3: In a manner similar to that in Example 455, by using 5-methyl-furan-2-carboxylic acid obtained in Step 2, instead of isonicotinic acid, followed by re-mixing in a thick mixture with ethanol, Compound title 512 (123 mg, 71%) was obtained as a brown solid from Compound 454 (125 mg, 0.450 mmol). aH NMR (DMSO-d6, d ppm): 1.50-1.80 (m, 4H), 2.40 (s, 3H), 3.13-3.24 (m, 1H), 3.34 (ddd, J = 2.4, 11.6, 11.6 Hz , 2H), 3.84-3.91 (m, 2H), 6.41 (d, J = 3.5 Hz, 1H), 6.70 (dd, J = 1.6, 3.5 Hz, 1H), 7.41 (dd, J = 0.8, 3.5 Hz, 1H), 7.70 (d, J = 3.5 Hz, 1H), 7.90 (dd, J = 0.8, 1.9 Hz, 1H), 13.08 (br s, 1H). APCIMS m / z: [M + H] + 387. p.f. 209-212 ° C.

[Example 513] 5-Formyl-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] furan-2-carboxamide (Compound 513) In a manner similar to that in Example 465, when using 5-formylfuran-2-carboxylic acid in place of 4- (dimethylamino) benzoic acid, followed by re-mixing in a thick mixture with ethanol, the title Compound 513 (2.43 g, 61%) was obtained as a yellow solid from Compound 454 (2.78 g, 10.0 mmol). H NMR (DMSO-de, d ppm) 1.50-1.80 (m, 4H), 3.10-3.22 (m, 1H), 3.35 (ddd, J = 2.2, 11.6, 11.6 Hz, 2H), 3.82-3.92 (m , 2H), 6.70 (dd, J = 1.6, 3.5 Hz, 1H), 7.41 (d, J = 3.5 Hz, 1H), 7.67 (d, J = 3.8 Hz 1H), 7.87 (d, J = 3.8 Hz, 1H), 7.90 (d, J = 1.6 Hz, 1H), 9.78 (s, 1H), 13.63 (br s, 1H).

APCIMS m / z: [M + H] + 401.

[Example 514] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -5- (hydroxyimino) furan-2-carboxamide (Compound 514) Compound 513 (2.40 g, 6.00 mmol) was suspended in ethanol (24 mL), and hydroxylamine hydrochloride (438 mg, 6.30 mmol) was added thereto, followed by stirring at 60 ° C for 1 hour. The precipitated solid was collected by filtration to provide Title Compound 514 (2.09 g, 84%) as a pale brown solid.

[Example 515] 5-Cyano-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] furan-2-carboxamide (Compound 515) Compound 514 (2.08 g, 5.00 mmol) and triethylamine (0.836 mL, 6.00 mmol) were suspended in dichloromethane (20 mL), and 2-chloro-l, 3-dimethylimidazolinium chloride (2.03 g, 12. 0 mmol) was added thereto at 0 ° C. This was stirred at 0 ° C for 30 minutes, and then triethylamine (0.836 mL, 6.00 mmol) was added thereto, followed by stirring at 0 ° C for 5 minutes. An aqueous saturated sodium acid carbonate solution was added to the reaction mixture, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 49: 1), followed by recrystallization from a mixed solvent (3: 1) of ethanol and water to provide the title Compound 515 (1.26 g, .63%) as a pale brown solid. X H NMR (DMSO-de, d ppm): 1.50-1.75 (m, 4H), 3.15-3.35 (m, 3H), 3.85-3.92 (m, 2H), 6.71 (dd, J = 1.6, 3.2 Hz, 1H ), 7.43 (d, J = 3.2 Hz, 1H), 7.82 (d, J = 4.1 Hz, 1H), 7.86 (d, J = 4.1 Hz, 1H), 7.91 (d, J = 1.6 Hz, 1H), 13.66 (br s, 1H). APCIMS m / z: [M + H] + 398. p.f .: 222-223 ° C.

[Example 516] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] furan-3-carboxamide (Compound 516) In a manner similar to that in Example 464, when furan-3-carboxylic acid was used in place of 3- (dimethylamino) benzoic acid, followed by re-mixing in a thick mixture with ethanol, the title Compound 516 (111 mg, 66%) was obtained as a pale pink solid at from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-d 6, d ppm): 1.53-1.73 (, 4H), 3.13-3.24 (m, 1H), 3. 40 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.88 (ddd, J = 2.4, 4.0, 11.3 Hz, 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 7.12-7.14 ( m, 1H), 7. 43 (dd, J = 0.8, 3.5 Hz, 1H), 7.85-7.89 (m, 1H), 7.90 (dd, J = 0.8, 1.9 Hz, 1H), 8.65-8.69 (m, 1H), 13.08 (br s , 1 HOUR) . APCIMS m / z: [M + H] + 373. mp .: 236-238 ° C.

[Example 517] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] thiophene-2-carboxamide (Compound 517) In a manner similar to that in Example 455, using thiophene-2-carboxylic acid in place of isonicotinic acid, followed by re-mixing in a thick mixture with ethanol, the title Compound 517 (158 mg, 90%) was obtained as a pale brown solid from Compound 454 ( 125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.53-1.77 (m, 4H), 3.12-3.24 (m, 1H), 3.35 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.89 (ddd, J = 2.4, 3.8, 11.3 Hz, 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 7.28 (dd, J = 1.4, 4.9 Hz, 1H), 7.45 (dd, J = 0.5, 3.5 Hz 1H ), 7.90 (dd, J = 0.5, 1.9 Hz, 1H), 8.04 (dd, J = 0.8, 4.9 Hz, 1H), 8.34 (dd, J = 0.8, 1.4 Hz, 1H), 13.35 (br s, 1H) ). APCIMS m / z: [M + H] + 389. p.f .: 231-232 ° C.

[Example 518] N- [-4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] thiophene-3-carboxamide (Compound 518) In a manner similar to that in Example 455 , using thiophene-3-carboxylic acid in place of isonicotinic acid, followed by re-mixing in a thick mixture with ethanol, the title Compound 518 (148 mg, 85%) was obtained as a pale brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-ds, d ppm): 1.54-1.76 (m, 4H), 3.13-3.25 (m, 1H), 3.35 (ddd, J = 2.2, 11.6, 11.6 Hz, 2H), 3.84-3.93 (m , 2H), 6.70 (dd, J = 1.6, 3.2 Hz, 1H), 7.44 (d, J = 3.2 Hz, 1H), 7.72 (dd, J = 2.7, 5.1"Hz, 1H), 7.78 (dd, J = 1.3, 2.7 Hz, 1H), 7.90 (d, J = 1.6 Hz, 1H), 8.70 (dd, J = 1.3, 2.7 Hz, 1H), 13.13 (br s, 1H) APCIMS m / z: [M + H] + 389. mp: 227-229 ° C.

[Example 519] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -l-methylpyrazole-4-carboxamide (Compound 519) In a manner similar to that in Example 499, when using l-methylpyrazole-4-carboxylic acid in place of 2-chloroisonicotinic acid, followed by re-mixing in a thickened mixture with ethanol, the title Compound 519 (67.2 mg, 39%) it was obtained as a pale yellow solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-d 6, d ppm): 1.50-1.75 (m, 4H), 3.10-3.20 (m, 1H), 3.35 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.88 (ddd, J = 2.2, 4.1, 11.3 Hz, 2H), 3.92 (s, 3H), 6.70 (dd, J = 1.6, 3.5 Hz, 1H), 7.44 (dd, J = 0.8, 1.6 Hz, 1H), 7.90 (dd, J = 0.8, 3.5 Hz, 1H), 8.22 (s, 1H), 8.53 (s, 1H), 12.94 (br s, 1H). APCIMS m / z: [M + H] + 387. p.f .: 243-247 ° C.

[Example 520] 1-Ethyl-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] pyrazole-4-carboxamide (Compound 520) In a manner similar to that in Example 499, by using l-ethylpyrazole-4-carboxylic acid in place of 2-chloroisonicotinic acid, followed by re-mixing in a thick mixture with diethyl ether, the title Compound 520 (74.9 mg, 42%) was obtained as a pale yellow solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.41 (t, J = 7.0 Hz, 3H), 1.50-1.80 (m, 4H), 3.10-3.25 (m, 1H), 3.30-3.45 (m, 2H), 3.83-3.92 (, 2H), 4.21 (q, J = 7.0 Hz, 2H), 6.70 (dd, J = 1.6, 3.5 Hz, 1H), 7.43 (d, J = 3.5 Hz, 1H), 7.90 ( d, J = 1.6 Hz, 1H), 8.23 (s, 1H), 8.58 (s, 1H), 12.93 (br s, 1H). APCIMS m / z: [M + H] + 401. p.f .: 170-174 ° C.

[Example 521] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -1-phenylpyrazole-4-carboxamide (Compound 521) In a manner similar to that in Example 499, when using 1-phenylpyrazole-4-carboxylic acid in place of 2-chloroisonicotinic acid, followed by re-mixing in a thick mixture with ethanol, the title Compound 521 (131 mg, 65%) was obtained as a yellow solid pale from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.20-3.30 (m, 1H), 3.30-3.45 (m, 2H), 3.82-3.92 (m, 2H), 6.71 (dd) , J = 1.6, 3.2 Hz, 1H), 7.38-7.44 (m, 2H), 7.43 (d, J = 3.2 Hz, 1H), 7.55-7.62 (m, 2H), 7.85-7.93 (m, 2H ), 8.50 (s, 1H), 9.30 (s, 1H), 13.08 (br s, 1H). APCIMS m / z: [M + H] + 449. p.f .: 217-220 ° C.

[Example 522] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] isoxazole-5-carboxamide (Compound 522) In a manner similar to that in Example 456, when using isoxazole-5-carbonyl chloride instead of cyclopropanecarbonyl chloride, followed by re-mixing thick with a mixed solvent of ethanol and diethyl ether, the title Compound 522 (118 mg, 70%) was obtained as a yellow solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.53-1.79 (m, 4H), 3.15-3.26 (m, 1H), 3.36 (ddd, J = 2.2, 11.6, 11.6 Hz, 2H), 3.83-3.92 (m , 2H), 6.71 (dd, J = 1.6, 3.5 Hz, 1H), 7.42 (d, J = 3.5 Hz, 1H), 7.59 (d, J = 1.9 Hz, 1H), 7.91 (d, J = 1.6 Hz , 1H) 8.87 (d, J = 1.9 Hz, 1H), 13.78 (br s, 1H). APCIMS m / z: [M + H] + 372.

[Example 523] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] tetrahydrofuran-2-carboxamide (Compound 523) In a manner similar to that in Example 465, when using tetrahydrofuran-2-carboxylic acid in place of 4- (dimethylamino) benzoic acid, followed by re-mixing in a thickened mixture with diethyl ether, the title Compound 523 (111 mg, 66%) was obtained from the Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.75 (m, 4H), 1.80-2.20 (m, 3H), 2.20-2.30 (m, 1H), 3.10-3.25 (m, 1H), 3.33 (ddd) , J = 2.2, 11.3, 11.3 Hz, 2H), 3.77-4.02 (m, 4H), 4.58 (dd, J = 5.4, 8.1 Hz, 1H), 6. 69 (dd, J = 1.9, 3.5 Hz, 1H ), 7.38 (dd, J = 0.8, 3.5 Hz, 1H), 7.89 (dd, J = 0.8, 1.9 Hz, 1H), 12.66 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 377. p. f. : 115-117 ° C.

[Example 524] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] tetrahydrofuran-3-carboxamide (Compound 524) Tetrahydrofuran-3-carboxylic acid (1.72 mL, 1.8 mmol), EDC hydrochloride (344 mg, 1.80 mmol) and 1-hydroxybenzotriazole monohydrate (276 mg, 1.80 mmol) were added to Compound 454 (125 mg, 0.450 mmol), followed by stirring at 60 ° C for 3.5 hours. . The reaction mixture was poured into a saturated aqueous solution of sodium hydrogen carbonate, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was redissolved in thickened with diethyl ether to provide the title Compound 524 (142 mg, 84%). XH NMR (DMSO-d6, d ppm) 1.50-1.80 (m, 4H), 2.05-2.15 (m, 2H), 3.10-3.25 (m, 1H), 3.30-3.45 (m, 3H), 3.70-4.00 (m, 6H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.40 (dd, J = 0.8, 3.5 Hz, 1H), 7.89 (dd, J = 0.8, 1.9 Hz, 1H), 12.90 ( br s, 1H). APCIMS m / z, [M + H] + 377. p.f .: 164-166 ° C.

[Example 525] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (tetrahydropyran-4-yl) acetamide (Compound 525) In a manner similar to that in Example 465, when using tetrahydropyran-4-ylacetic acid in place of 4- (dimethylamino) benzoic acid, followed by re-mixing in a thickened mixture with diethyl ether, the title Compound 525 (139 mg, 76%) - was obtained as a pale brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.20-1.40 (m, 2H), 1.50-1.75 (m, 8H), 1.95-2.10 (m, 1H), 2.43 (d, J = 7.0 Hz, 2H), 3.15-3.30 (m, 1H), 3.33 (ddd, J = 2.2, 11.6, 11.6 Hz, 2H), 3.80-3.90 (m, 4H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 ( dd, J = 0.8, 3.5 Hz, 1H), 7.88 (dd, J = 0.8, 1.9 Hz, 1H), 12.77 (br s, 1H). APCIMS m / z; [M + H] + 405. p.f .: 206-209 ° C [Example 526] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-phenylacetamide (Compound 526) In a manner similar to that in Example 511, using phenylacetyl chloride in place of 2-furoyl chloride, followed by re-mixing in a mixed solvent of ethanol and hexane, the title Compound 526 (81.4 mg, 46%) was obtained as an orange solid. from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.49-1.75 (m, 4H), 3.08-3.20 (m, 1H), 3.36-3.50 (m, 2H), 3.82 (s, 2H), 3.83-3.90 (m , 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.20-7.35 (m, 5H), 7.40 (d, J = 3.5 Hz, '5 1H), 7.89 (d, J = 1.9 Hz, 1H), 13.02 (br s, "1H) APCIMS m / z: [M + H] + 397. mp: 140-142 ° C.

[Example 527] 10 N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -3-phenylpropanamide (Compound .527) In a manner similar to that in Example 502 , by using 3-phenylpropionyl chloride in place of 6-chloronicotinoyl chloride, followed by re-mixing in a thick mixture with ethanol, the title Compound 527 (96.4 mg, 52%) was obtained as a pale brown solid from of Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.67 (m, 4H), 2.81 (t, J = 6.7 Hz, 2H), 2.94 (t, J = 6.7 Hz, 2H), 3.10-3.22 (m, 1H), 3.34 20 (ddd, J = 2.4, 10.8, 10.8 Hz, 2H), 3.83-3.93 (m, 2H ), 6.68 (dd, J = 1.9, 3.5 Hz, 1H), 7.15-7.29 (m, 5H), 7.38 (d, J = 3. 5 Hz, 1H), 7.88. (d, J = 1.9 Hz, 1H), 12.78 (br s, 1H). APCIMS m / z: [M + H] + 411. p.f .: 161-164 ° C. 25 [Example 528] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -3-phenylacrylamide (Compound 528) In a manner similar to that in Example 456, using cinnamoyl chloride in place of cyclopropanecarbonyl chloride, followed by re-mixing in a methanol-thick mixture, Title Compound 528 (146 mg, 79%) was obtained as a pale orange solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.75 (m, 4H), 3.10-3.30 (m, 1H), 3.35-3.45 (m, 2H), 3.83-3.93 (m, 2H), 6.70 (dd) , J = 1.6, 3.2 Hz, 1H), 6.92 (d, J = 15.6 Hz, 1H), 7.40 (d, J = 3.2 Hz, 1H), 7.45-7.51 (m, 3H), 7.63-7.69 (m, 2H), 7.80 (d, J = 15.6 Hz, 1H), 7.91 (d, J = 1.6 Hz, 1H), 13.04 (br s, 1H). APCIMS m / z: [M + H] + 409. p.f .; 253-256 ° C.

[Example 529] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-phenoxyacetamide (Compound 529) In a manner similar to that in Example 455, use phenoxyacetic acid instead of isonicotinic acid, followed by re-mixing in methanol, the Compound title 529 (140 mg, 75%) was obtained as a pale brown solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-d 6, d ppm): 1.50-1.78 (m, 4H), 3.11-3.23 (m, 1H), 3.32-3.38 (, 2H), 3.82-3.88 (m, 2H), 4.92 (s, 2H), 6.70 (dd, J = 1.9, 3.5 Hz, 1H), 6.95-7.02 (m, 3H), 7.31 (dd, J = 7.8, 7.8 Hz, 2H), 7.39 (d, J = 3.5 Hz, 1H ), 7.90 (d, J = 1.9 Hz, 1H), 13.05 (br s, 1H). APCIMS m / z: [M + H] + 413. p.f .: 148-150 ° C.

[Example 530] N- [4- (2-Furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-methoxyacetamide (Compound 530) In a manner similar to that in Example 456, using methoxyacetyl chloride in place of cyclopropanecarbonyl chloride, followed by re-mixing in a thick mixture with ethanol, Title Compound 530 (81.2 mg, 51%) was obtained as a purple reddish solid from Compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-d 6, d ppm): 1.50-1.80 (m, 4 H), 3.10-3.22 (m, 1 H), 3.34 (ddd, J = 2.2, 11.3, 11.3 Hz, 2 H), 3.36 (s 3 H) ), 3.87 (ddd, J = 2.2, 4.3, 11.3 Hz, 2H), 4.20 (s, 2H), 6.69 (dd, J = 1. 6, 3.2 Hz, 1H), 7.38 (dd, J = 0.8, 3.2 Hz, 1H), 7.89 (dd, J = 0.8, 1.6 Hz, 1H), 12.75 (br s, 1H). APCIMS m / z: [M + H] + 351. mp .: 148-149 ° C.

[Example 531] 2-Bromo-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] acetamide (Compound 531) Compound 454 (1.39 g, 5.00 mmol), triethylamine (3.06 mL, 22.0 mmol) and DMAP (61.0 mg, 0.500 mmol) were suspended in THF (30 mL), and bromoacetyl bromide (1.64 mL, 20.0 mmol) was added dropwise thereto at 0 ° C, followed by stirring at room temperature for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (chloroform: methanol = 99: 1), followed by re-mixing in a thick mixture with diethyl ether to give the title compound 531 (1.59 g, 80% ) as a pale brown solid. XH NMR (CDC13, d ppm): 1.65-2.00 (m, 4H), 3.15 (tt, J = 4.3, 10.7 Hz, 1H), 3.49 (ddd, J = 2.8, 11.4, 11.4 Hz, 2H), 4. -00-4.08 (m, 2H), 4.05 (s, 2H), 6.58 (dd, J = 1.8, 3.6 Hz, 1H), 7.58 (dd, J = 0.8, 1.8 Hz, 1H), 7.74 (dd, J = 0.8, 3.6 Hz, 1H).

[Example 532] 2-Ethoxy-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] acetamide (Compound 532) Sodium ethoxide (62.0 mg, 0.900 mmol) was dissolved in ethanol (2 mL), and compound 531 (120 mg, 0.300 mmol) was added thereto, followed by stirring at 60 ° C for 3 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel (chloroform: methanol = 99: 1) and crystallized from 2-propanol to give the title compound 532 ( 53.4 mg, 49%). X H NMR (DMSO-de, d ppm): 1.16 (t, J = 7.0 Hz, 3H), 1.50-1.75 (m, 4H), 3.10-3.25 (m, 1H), 3.34 (ddd, J = 2.7, 11.6, 11.6 Hz, 2H), 3.56 (q, J = 7.0 Hz, 2H), 3.87 (ddd, J = 2.7, 4.3, 11.6 Hz, 2H), 4.23 (s, 2H), 6.69 (dd, J = 1.9, 3.5 Hz , 1H), 7.38 (dd, J = 0.8, 3.5 Hz, 1H), 7.89 (dd, J = 0.8, 1.9 Hz, 1H), 12.70 (br s, 1H). APCIMS m / z: [M + H] + 365. m.p .: 121-126 ° C.

[Example 533] 2- (Dimethylamino) -N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] acetamide (Compound 533) Compound 531 (120 mg, 0.300 mmol ) was dissolved in THF (2 mL), and a 2 mol / L solution of dimethylamine in THF (0.90). mL, 1.80 mmol) was added thereto, followed by stirring at room temperature for 4.5 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel (chloroform), followed by re-mixing in a mixed solvent of 2-propanol and diethyl ether. to provide the title compound 533 (64.1 mg, 10%). X H NMR (DMSO-de, d ppm): 1.50-1.75 (m, 4H), 2.32 (s, 6H), 3.10-3.22 (m, 1H), 3.30 (s, 2H), 3.30-3.45 (, 2H) , 3.83-3.92 (m, 2H), 6.68 (dd, J = 1.6, 3.5 Hz, 1H), 7.38 (d, J = 3.5 Hz, 1H), 7.88 (d, J = 1.6 Hz, 1H). APCIMS m / z: [M + H] + 364. mp .: 129-130 ° C.

[Example 534] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [N- (2-methoxyethyl) -N-methylamino] acetamide (Compound 534 ) In a manner similar to that in Example 533, when using N- (2-methoxyethyl) -N-methylamine in place of the solution of dimethylamine in THF, the title compound 534 (78.1 mg, 64%) is obtained from the compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.75 (m, 4H), 2.37 (s, 3H), 2.69 (t, J = 5.4 Hz, 2H), 3.10-3.20 (m, 1H), 3.26 ( s, 3H), 3.34 (ddd, J = 2.4, 11.3, 11.3 Hz, 2H), 3.44 (s, 2H), 3.44 (q, J = . 4 Hz, 2H), 3.87 (ddd, J = 2.4, 3.8, 11.3 Hz, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.38 (d, J = 3.5 Hz, 1H), 7.89 ( d, J = 1.9 Hz, 1H). APCIMS m / z: [M + H] + 408. p.f. : 103-105 ° C.

[Example 535] 2- [N, N-Bis (2-methoxyethyl) amino] -N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] acetamide (Compound 535 ) In a manner similar to that in Example 533, using N, N-bis (2-methoxyethyl) amine in place of the solution of dimethylamine in THF, followed by recrystallization from 2-propanol, the title compound 535 (51.0 mg, 38%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (CDC13, d ppm): 1.70-2.00 (m, 4H), 2.88 (t, J = 5.1 Hz, 4H), 3.10-3.20 (m, 1H), 3.23 (s, 6H), 3.30-3.40 ( m, 2H), 3.49 (t, J = 5.1 Hz, 4H), 3.58 (s, 2H), 4.03 (ddd, J = 2.7, 3.8, 11.3 Hz, 2H), 6.55 (dd, J = 1.6, 3.5 Hz , 1H), 7.56 (dd, J = 0.8, 1.6 Hz, 1H), 7.64 (dd, J = 0.8, 3.5 Hz, 1H), 11.55 (br s, 1H). APCIMS m / z: [M + H] + 452.

[Example 536] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (1-pyrrolidinyl) acetamide (Compound 536) In a manner similar to that in Example 533, using pyrrolidine (0.076 mL, 0.90 mmol) in place of the solution of dimethylamine in THF, followed by re-mixing in a thick mixture with diethyl ether, the title compound 536 (66.1 mg, 57%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 6H), 2.63-2.71 (m, 4H), 3. 10-3.22 (m, 1H), 3.25-3.40 (m, 4H), 3.51 (s, 2H), 3.87 (ddd, J = 2.2, 4.0, 12.1 Hz, 2H), 6.68 (dd, J = 1.9, 3.5 Hz, 1H), 7.38 (dd, J = 0.8, 3.5 Hz, 1H), 7.87 (dd, J = 0.8, 1.9 Hz, 1H). APCIMS m / z: [M + H] + 390. p.f .: 115-117 ° C.

[Example 537] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [(2R) -2- (methoxymethyl) pyrrolidin-1-yl] acetamide (Compound 537) In a manner similar to that in Example 533, when using (R) -2-methoxymethylpyrrolidine (104 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by re-mixing in a thick mixture with a mixed solvent of 2-propanol and hexane, the title compound 537 (100 mg, 77%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 1.45-1.95 (m, 8H), 2.84-2.89 (m, 1H), 3.00-3.05 (m, 1H), 3.10-3.40 (m, 6H), 3.20 (s) , 3H), 3.48 (d, J = 16.7 Hz, 1H), 3.72 (d, J = 16.7 Hz, 1H), 3.87 (ddd, J = 2.4, 4.0, 11.6 Hz, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (dd, J = 0.8, 3.5 Hz, 1H), 7.89 (dd, J = 0.8, 1.9 Hz, 1H). APCIMS m / z: [M + H] + 434. p.f. : 103-104 ° C.

[Example 538] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [(2S) -2- (methoxymethyl) pyrrolidin-1-yl] acetamide (Compound 538) In a manner similar to that in Example 533, when using (S) -2-methoxymethylpyrrolidine (104 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by re-mixing in a thick mixture with a mixed solvent of 2-propanol and hexane, the title compound 538 (92.6 mg, 71%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). - XH NMR (DMSO-de, d ppm): 1.45-1.95 (m, 8H), 2.84-2.89 (m, 1H), 3.00-3.05 (m, 1H), 3.10-3.40 (m, 6H), 3.20 ( s, 3H), 3.48 (d, J = 16.7 Hz, 1H), 3.72 (d, J = 16.7 Hz, 1H), 3.87 (ddd, J = 2.4, 4.0, 11.6 Hz, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (dd, J = 0.8, 3.5 Hz, 1H), 7.89 (dd, J = 0.8, 1.9 Hz, 1H). APCIMS m / z: [M + H] + 434. mp .: 102-103 ° C.

[Example 539] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [3- (dimethylamino) pyrrolidin-1-yl] acetamide (Compound 539) In a manner similar to that in Example 533, using 3- (dimethylamino) pyrrolidine (103 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization from diethyl ether, the title compound 539 (73.9 mg, 57%) was obtained as a pale brown solid of compound 531 (120 mg, 0.300 mmol). X H NMR (CDC1, d ppm): 1.70-2.15 (m, 6H), 2.26 (m, 6H), 2.45-2.55 (m, 1H), 2.55-2.80 (m, 2H), 2.85-3.05 (m, 2H) ), 3.10-3.20 (m, 1H), 3.40-3.60 (m, 4H), 4.00-4.09 (m, 2H), 6.58 (dd, J = 1. 6, 3.2 Hz, 1H), 7.59 (d, J = 1.6 Hz, 1H), 7.78 (d, J = 3.2 Hz, 1H). APCIMS m / z: [M + H] + 433.

[Example 540] N- [4- (2 ~ furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (isoindolin-2-yl) acetamide (Compound 540) In a manner similar to that in Example 533, when using isoindoline (110 mg, 0.900 mmol) instead of the solution of dimethylamine in THF, followed by re-mixing in a mixed solvent of ethanol and diethyl ether, the title compound 540 (87.2 mg, 66%) was obtained as a brown solid of compound 531 (120 mg, 0.300 mmol). X H NMR (CDC13, d ppm): 1.70-2.00 (m, 4H), 3.10-3.20 (m, 1H), 3.49 (ddd, J = 2.7, 11.3, 11.3 Hz, 2H), 3.73 (s, 2H), 4.04 (ddd, J = 2.7, 3.5, 11.3 Hz, 2H), 4.16 (s, 4H), 6.55 (dd, J = 1.9, 3.8 Hz, 1H), 7.20-7.30 (m, 4H), 7.54 (dd, J = 0.8, 1.9 Hz, 1H), 7.77 (dd, J = 0.8, 3.8 Hz, 1H). APCIMS m / z: [M + H] + 438.

[Example 541] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (thiazolidin-3-yl) acetamide (Compound 541) In a manner similar to that in Example 533, when using thiazolidine (0.071 mL, 0.90 mmol) in place of the solution of dimethylamine in THF, followed by re-mixing in a thickened mixture with diethyl ether, the title compound 541 (70.7 mg, 58% ) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (CDCl 3, d ppm): 1.75-2.00 (m, 4H), 2.96-3.03 (m, 2H), 3.10-3.20 (m, 3H), 3.37 (s, 2H), 3.49 (ddd, J = 3.0 , 11.6, 11.6 Hz, 2H), 4.04 (ddd, J = 3.0, 4.0, 11.6 Hz, 2H), 4.04 (s, 2H), 6.58 (dd, J = 1.9, 3.5 Hz, 1H), 7.59 (dd, J = 0.8, 1.9 Hz, 1H), 7.82 (dd, J = 0.8, 3.5 Hz, 1H), 10.71 (br s, 1H).

APCIMS m / z: [M + H] + 408.

[Compound 542] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-piperidinoacetamide (Compound 542) In a manner similar to that in Example 533, - when using piperidine (0.09 mL, 0.9 mmol) in place of the solution of dimethylamine in THF, followed by re-mixing in a thick mixture with diethyl ether, the title compound 542 (78.5 mg, 65%) was obtained as a solid pale yellow of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 1.35-1.45 (m, 2H), 1.50-1.80 (m, 8H), 3.05-3.20 (m, 1H), 3.29 (s, 2H), 3.30-3.50 (m , 6H), 3.87 (ddd, J = 2.4, 3.8, 11.6 Hz, 2H), 6.68 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (dd, J = 0.5, 3.5 Hz, 1H), 7.88 ( dd, J = 0.5, 1.9 Hz, 1H). APCIMS m / z: [M + H] + 404. mp .: 146-147 ° C.

[Example 543] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (4-hydroxypiperidino) acetamide (Compound 543) In a manner similar to that in Example 533, when using 4-hydroxypiperidine (92 mg, 0.90 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization of diethyl ether, the title compound 543 (79.2 mg, 63%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 1.30-1.50 (m, 2H), 1.50-1.75 (m, 6H), 2.28 (ddd, J = 2.4, 9.7, 12.1 Hz, 2H), 2.80-2.90 (m , 2H), 3.10-3.22 (m, 1H), 3.30-3.50 (m, 4H), 3.33 (s, 2H), 3.83-3.92"(m, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (dd, J = 0.8, 3.5 Hz, 1H), 7.88 (dd, J = 0.8, 1.9 Hz, 1H) APCIMS m / z: [M + H] + 420. pf: 178-180 ° C.

[Example 544] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (3-hydroxypiperidino) acetamide (Compound 544) In a manner similar to that in Example 533, using 3-hydroxypiperidine in place of the solution of dimethylamine in THF, followed by recrystallization from diisopropyl ether, the title compound 544 (78.5 mg, 65%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (CDC13, d ppm): 1.75-2.00 (m, 8H), 2.45-2.60 (m, 2H), 2.55-2.70 (m, 1H), 2.82 (dd, J = 2.4, 8.1 Hz, 1H), 3.10-3.20 (m, 1H), 3.31 (s, 2H), 3.48 (ddd, J = 2.7, 11.3, 11.3 Hz, 2H), 3.80-3.95 (m, 1H), 4.03 (ddd, J = 2.4, 4.0 , 11.3 Hz, 2H), 6.57 (dd, J = 1.6, 3.2 Hz, 1H), 7.58 (d, J = 1.6 Hz, 1H), 7.74 (d, J = 3.2 Hz, 1H). APCIMS m / z: [M + H] + 420.

[Example 545] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (4-methoxypiperidino) acetamide (Compound 545) Compound 531 (120 mg, 0.300 mmol) and 4-methoxypiperidine hydrochloride (139 mg, 0.900 mmol) was suspended in THF (4 mL), and triethylamine (0.140 mL, 0.990 mmol) was added dropwise thereto, followed by stirring at room temperature for 1.5 hour. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by co chromatography on silica gel (chloroform: methanol = 49: 1), followed by re-mixing in a mixed solvent of ether of diisopropyl and diethyl ether to provide the title compound 545 (96.0 mg, 74%) as a white solid. X H NMR (DMSO-de, d ppm): 1.40-1.85 (m, 8H), 2.32 (ddd, J = 2.7, 9.2, 11.6 Hz, 2H), 2.70-2.80 (, 2H), 3.22 (s, 3H) , 3.30-3.80 (m, 4H), 3.34 (s, 2H), 3.87 (ddd, J = 2.2, 4.3, 11.3 Hz, 2H), 6.69 (dd, J = 1.6, 3.5 Hz, 1H), 7.39 (dd) , J = 0.8, 3.5 Hz, 1H), 7.88 (dd, J = 0.8, 1.6 Hz, 1H). APCIMS m / z: [M + H] + 434. mp .: 109-111 ° C.

[Example 546] N- [4- (2-furyl) -5- (tetrahydro-drahipham-4-ylcarbonyl) thiazol-2-yl] -2- (4-hydroxy-4-methylpiperidino) acetamide (Compound 546) In one way similar to that in Example 533, using 4-hydroxy-4-methylpiperidine in place of the solution of dimethylamine in THF, followed by re-mixing in a thickened mixture with diisopropyl ether, the title compound 546 (105 mg, %) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). XH NMR (CDC13, d ppm): 1.11 (s, 3H), 1.45-1.75 (m, 8H), 2.50-2.55 (m, 4H), 3.10-3.20 (m, 1H), 3.34 (ddd, J = 2.7 , 11.3, 11.3 Hz, 2H), 3.34 (s, 2H), 3.87 (ddd, J = 2.7, 4.3, 11.3 Hz, 2H), 6.68 (dd, J = 1.6, 3.5 Hz, 1H), 7.39 (dd, J = 0.5, 3.5 Hz, 1H), 7.88 (dd, J = 0.5, 1.6 Hz, 1H). APCIMS m / z: [M + H] + 434. mp .: 151-153 ° C.

[Example 547] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (3-hydroxymethylpiperidino) acetamide (Compound 547) In a manner similar to that in Example 533, using 3-hydroxymethylpiperidine (104 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization from diisopropyl ether, the title compound 547 (79.8 mg, 61%) was obtained as a solid coffee pale of compound 531 (120 mg, 0.300 mmol). X H NMR (CDC13, d ppm): 1.60-2.00 (m, 9H), 2.08-2.18 (m, 1H), 2.18-2.38 (m, 1H), 2.71-2.91 (m, 1H), 2.94 (dd, J = 1.6, 10.8 Hz, 1H), 3.10-3.20 (m, 1H), 3.28 (s, 2H), 3.48 (ddd, J = 3.0, 11.3, 11.3 Hz, 2H), 3.50-3.64 (m, 2H), 4.04 (ddd, J = 3.0, 4.0, 11.3 Hz, 2H), 6.57 (dd, J = 1.6, 3.5 Hz, 1H), 7.59 (dd, J = 0.8, 1.6 Hz, 1H), 7.76 (dd, J = 0.8, 3.5 Hz, 1H). APCIMS m / z: [M + H] + 434.

[Example 548] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (4-hydroxymethylpiperidino) acetamide (Compound 548) In a manner similar to that in Example 533, using 4-hydroxymethylpiperidine (104 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization from diethyl ether, the title compound 548 (104 mg, • 80%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (CDCl 3, d ppm): 1.30-1.60 (m, 3H), 1.70-2.00 (m, 8H), 2.31 (ddd, J = 2.4, 11.9, 11.9 Hz, 2H), 2.86-2.96 (m, 2H) ), 3.10-3.20 (m, 1H), 3.28 (s, 2H), 3.48 (ddd, J = 3.0, 11.6, 11. 6 Hz, 2H), 3.55 (d, J = 3.5 Hz, 2H), 4.04 (ddd, J = 3.0, 4. 0, 11.6 Hz, 2H), 6.58 (dd, J = 1.6, 3.5 Hz, 1H), 7.59 (dd, J = 0.8, 1.6 Hz, 1H), 7.77 (dd, J = 0.8, 3.5 Hz, 1H). APCIMS m / z: [M + H] + 434.

[Example 549] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [4- (2-hydroxypropan-2-yl) piperidino] acetamide (Compound 549) In a manner similar to that in Example 533, when using 4- (2-hydroxypropan-2-yl) piperidine (130 mg, 0.900 mmol) instead of the solution of dimethylamine in THF, followed by redoing thick mixture with a mixed solvent of ethanol and diethyl ether, the title compound 549 (121 mg, 87%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). XH NMR (CDC13, d ppm): 1.22 (s, 6H), 1.40-1.60 (m, 4H), 1.70-2.00 (m, 6H), 2.26 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 2.93-3.00 (m, 2H), 3.05-3.15 (m, 1H), 3.27 (s, 2H), 3.49 (ddd, J = 2.7, 11.3, 11.3 Hz, 2H), 4.03 (ddd, J = 2.7, 3.8 , 11.3 Hz, 2H), 6.57 (dd, J = 1.6, 3.5 Hz, 1H), 7.59 (dd, J = 0.8, 1.6 Hz, 1H), 7.79 (dd, J = 0.8, 3.5 Hz, 1H). APCIMS m / z: [M + H] + 462.

[Example 550] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [4- (2-hydroxy-2-methylpropyl) piperidino] acetamide (Compound 550) In a manner similar to that in Example 533, when using 4- (2-hydroxy-2-methylpropyl) piperidine (142 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization from diethyl ether, the title compound 550 (108 mg, 76%) was obtained as a grayish white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (CDC13, d ppm): 1.26 (s, 6H), 1.40-1.70 (m, 3H), 1.70-2.00 (, 8H), 2.27-2.34 (m, 2H), 2.80-2.90 (m, 2H) , 3.10-3.20 (m, 1H), 3.25 (s, 2H), 3.42-3.54 (m, 3H), 3.99-4.09 (m, 2H), 6.57 (dd, J = 1.6, 3.5 Hz, 1H), 7.59 (d, J = 1.6 Hz, 1H), 7.78 (d, J = 3.5 Hz, 1H). APCIMS m / z: [M + H] + 476.

[Example 551] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [4- (1-pyrrolidinyl) piperidino] acetamide (Compound 551) In a similarly to that in Example 533, using 4- (1-pyrrolidinyl) piperidine (140 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by re-mixing in a thick mixture with diethyl ether, Compound of title 551 (55.1 mg, 39%) was obtained as a pale orange solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 1.30-1.75 (m, 12H), 1.95-2.05 (m, 1H), 2.10-2.20 (m, 2H), 2.70-2.85 (m, 2H), 3.10-3.20 (m, 1H), 3.25-3.40 (, 8H), 3.83-3.93 (, 2H), 6.68 (dd, J = 1.6, 3.2 Hz, 1H), 7.39 (d, J = 3.2 Hz, 1H), 7.88 ( d, J = 1.6 Hz, 1H).

ESIMS m / z: [M + H] + 473. mp .: 183-184 ° C.

[Example 552] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (4-piperidinopiperidino) acetamide (Compound 552) In a manner similar to that in Example 533, using 4-piperidinopiperidine (152 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by re-mixing in a mixed solvent of ethanol and diethyl ether, the title compound 552 (82.7 mg, 57%) . was obtained as a pale brown solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 1.30-1.75 (m, 12H), 2.13-2.20 (m, 2H), 2.50-2.60 (m, 3H), 2.80-2.95 (m, 2H), 3.15-3.25 (m, 1H), 3. 25-3.40 (m, 6H), 3.33. (s, 2H), 3.83-3.93 (m, 2H), 6.69 (dd, J = 1.6, 3.5 Hz, 1H), 7.39 (dd, J = 0.8, 3.5 Hz, 1H), 7.88 (dd, J = 0.8, 1.6 Hz, 1H). APCIMS m / z: [M + H] + 487. p.f .: 177-179 ° C.

[Example 553] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (4-morpholinopiperidino) acetamide (Compound 553) In a manner similar to that in Example 533, at Use 4-morpholinopiperidine (153 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by re-mixing in a thick mixture with diethyl ether, the title compound 553 (109 mg, 75%) was obtained "" as a pale yellowish green solid of compound 531 (120 mg, 0.300 mmol).

X H NMR (DMSO-de, d ppm) 1.30-1.55 (m, 2H), 1.55-1.80 (m, 6H), 2.05-2.30 (m, 3H), 2.44 (t, J = 4.3 Hz, 4H), 2.90 (d, J = 11.6 Hz, 2H), 3.10-3.25 (m, 1H), 3.34 (ddd, J = 2.2, 11.3, 11.3 Hz, 2H), 3.34 (s, 2H), 3.56 (t, J = 4.3 Hz, 4H), 3.87 (ddd, J = 2.2, 3.8, 11.3 Hz, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (dd, J = 0.5, 3.5 Hz, 1H), 7.88 (dd, J = 0.5, 1.9 Hz, 1H). APCIMS m / z [M + H] + 489. p. f. : 193-195 ° C.

[Example 554] 2- (1, 4-Dioxa-8-azaspiro [4.5] decan-8-yl) -N- [4- (2-furyl) -5- "(tetrahydropyran-4-ylcarbonyl) thiazole-2 -yl] acetamide (Compound 554) In a manner similar to that in Example 533, when using 1,4-dioxa-8-azaspiro [4.5] decane (0.240 mL, 1.80 mmol) instead of the solution of dimethylamine in THF , followed by re-mixing in a thick mixture with diethyl ether, the title compound 554 (122 mg, 88%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol).

X H NMR (DMSO-de, d ppm) 1.52-1.75 (m, 8H), 2.55-2.70 (m, 4H), 3.15-3.25 (m, 1H), 3.25-3.35 (m, 2H), 3.37 (s) , 2H), 3.86 (s, 4H), 3.86-3.93 (m, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (d, J = 3.5 Hz, 1H), 7.89 (d, J = 1.9 Hz, 1H). APCIMS m / z: [M + H] + 462. p.f .: 186-187 ° C [Example 555] 2- (4-Cyanopiperidino) -N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] acetamide (Compound 555) In a manner similar to that in Example 533, when using 4-cyanopiperidine (99.0 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by re-mixing in a thickened mixture with diethyl ether, the title compound 555 (88.9 mg, 69% ) was obtained as a pale brown solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm); 1.50-1.80 (m, 6H), 2.65-2.75 (m, 2H), 2. 85-3.00 (m, 1H), 3.10-3.20 (m, 1H), 3.30-3.50 (m, 6H), 3.40 (s, 2H), 3.83-3.93 (m, 2H), 6.69 (dd, J = 1.9 , 3.5 Hz, 1H), 7. 40 (d, J = 3.5 Hz, 1H), 7.89 (d, J = 1.9 Hz, 1H), 12.59 (br s, 1H). APCIMS m / z: [M + H] + 429.

[Example 556] 2- (4,4-Difluoropiperidino) -N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] acetamide (Compound 556). • In a manner similar to that in Example 545, by using 4,4-difluoropiperidine hydrochloride (142 mg, 0.900 mmol) in place of 4-methoxypiperidine hydrochloride, followed by re-mixing in a thick mixture with diethyl ether, the title compound 556 (104 mg, 79%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (CDC13, d ppm): 1.70-2.00 (m, 4H), 2.00-2.20 (m, 4H), 2.70-2.80 (m, 4H), 3.05-3.20 (m, 1H), 3.37 (s, 2H) ), 3.47 (ddd, J = 2.7, 11.3, 11.3 Hz, 2H), 4.04 (ddd, J = 2.7, 4.0, 11.3 Hz, 2H), 6.58 (dd, J = 1.9, 3.8 Hz, 1H), 7.59 ( d, J = 1.9 Hz, 1H), 7.77 (d,, J = 3.8 Hz, 1H), 10.43 (br s, 1H). APCIMS m / z: [M + H] + 440.

[Example 557] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (1, 2, 3, 6-tetrahydropyridin-1-yl) acetamide ( Compound 557) In a manner similar to that in Example 533, using 1, 2, 3, 6-tetrahydropyridine (0.825 mL, 0.900 mmol) instead of the solution of dimethylamine in THF, followed by re-mixing in a thick mixture With a mixed solvent of ethanol and diethyl ether, the title compound 557 (63.0 mg, 52%) is obtained from compound 531 (120 mg, 0.300 mmol).

X H NMR (CDCl 3, d ppm) ~: 1.70-1.95 (m, 4H), 2.20-2.35 (m, 2H), 2. 73-2.77 (m, 1H), 3.05-3.20 (m, 3H), 3.37 (s, 2H), 3.49 (ddd, J = 2.7, 11.6, 11.6 Hz, 2H), 4.04 (ddd, J = 2.7, 4.0, 11. 6 Hz, 2H), 5.60-5.70 (m, 1H), 5.75-5.85 (m, 1H), 6.57 (dd, J = 1.9, 3.5 Hz, 1H), 7.59 (d, J = 1.9 Hz, 1H), 7.79 (d, J = 3.5 Hz, 1H). APCIMS m / z: [M + H] + 402.

[Example 558] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-morpholinoacetamide (Compound 558) Compound 454 (13.9 g, 50.0 mmol) and triethylamine (15.3 mL, 110 mmol) was suspended in THF (200 mL), and a solution (50 mL) of bro oacetyl bromide (8.80 mL, 100 mmol) in THF was added dropwise thereto at 0 ° C, followed by stirring at room temperature for 1 hour. At 0 ° C, a solution (100 L) of bromoacetyl bromide (17.6 mL, 200 mmol) in THF was added to the reaction mixture, followed by stirring at room temperature for 2 hours. At 0 ° C, a solution (100 mL) of morpholine (61.2 mL, 700 mmol) and triethylamine (97.6 mL, 700 mmol) in THF was added dropwise to the reaction mixture, followed by stirring at room temperature for 30 minutes. minutes The reaction mixture was poured into a mixture of water (500 mL) and ethyl acetate (500 mL), followed by filtration, and the resulting filtrate was subjected to liquid-liquid separation. The organic layer was washed successively with a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography on silica gel (chloroform: methanol = 97: 3), followed by recrystallization from ethanol to provide the title compound 558 (8.17 g, 40%) as a pale brown solid. X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 3.15-3.25 (m, 1H), 3.33-3.38 (m, 6H), 3.39 (s, 2H), 3.60 (t, J = 4.6Hz, 4H), 3.87 (ddd, J = 2.4, 4.0, 11.6 Hz, 2H), 6.71 (dd, J = 1.6, 3.5 Hz, 1H), 7.39 (dd, J = 0.8, 3.5 Hz, 1H) , 7.89 (dd, J = 0.8, 1.6 Hz, 1H), 12.63 (br s, 1H). APCIMS m / z: [M + H] + 406. p.f .: 110-104 ° C.

[Example 559] 2- (cis-2, 6-Dimethylmorpholino) -N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -ethamide (Compound 559) In one way similar to those in Example 533, when using cis-2, 6-dimethylmorpholine (0.110 mL, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization of a mixed solvent of ethanol and diethyl, the title compound 559 (76.7 mg, 59%) was obtained as a grayish white solid of compound 531 (120 mg, 0.300 mmol). XH NMR (CDC13, d ppm): 1.18 (d, J = 6.2 Hz, 6H), 1.70-2.00 (m, 4H), 2.00-2.10 (m, 2H), 2.65-2.80 (m, 4H), 3.05- 3.20 (m, 1H), 3. 28 (s, 2H), 3.49 (ddd, J = 3.0, 11.3, 11.3 Hz, 2H), 4.04 (ddd, J = 3.0, 4.0, 11.3 Hz, 2H), 6.58 (dd, J = 1.9, 3.8 Hz, 1H), 7.60 (dd, J = 0.8, 1.9 Hz, 1H), 7.78 (dd, J = 0.8, 3.8 Hz, 1H), 10.45 (br s, 1H). APCIMS m / z: [M + H] + 434.

[Example 560] 2- [4- (tert-Butoxycarbonyl) piperazin-1-yl] -N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] acetamide (Compound 560) In a manner similar to that in Example 533, using 1- (tert-butoxycarbonyl) piperazine (504 mg, 2.70 mmol) in place of the solution of dimethylamine in THF, the title compound 560 (428 mg, 94%). %) was obtained from compound 531 (360 mg, 504 mmol). X H NMR (CDCl 3, d ppm): 1.44 (s, 9 H), 1.70-2.00 (m, 4 H), 2.57 (t, J = 4.9 Hz, 4 H), 3.05-3.20 (m, 1 H), 3.32 (s, 2H), 3.49 (ddd, J = 2.7, 11.6, 11.6 Hz, 2H), 3.53 (t, J = 4.9 Hz, 4H), 4. 04 (ddd, J = 2.7, 4.0, 11.6 Hz, 2H), 6.58 (dd, J = 1.9, 3.8 Hz, 1H), 7.59 (dd, J = 0.8, 1.9 Hz, 1H), 7.78 (dd, J = 0.8, 3. 8 Hz, 1H), 10.46 (br s, 1H). APCIMS m / z: [M + H] + 505.

[Example 561] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (1-piperazinyl) acetamide (Compound 561) Compound 560 (428 mg, 0.849 mmol) was dissolved in dichloromethane (3 mL), and trifluoroacetic acid (3 mL) was added thereto at 0 ° C, followed by stirring at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and a saturated aqueous solution of sodium acid carbonate was added to the resulting residue, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was made to make the mixture thick with diethyl ether to give the title compound 561 (263 mg, 77%). XH NMR (CDC13, d ppm): 1.50-1.80 (m, 4H), 2.74-2.80 (m, 4H), 3.10-3.20 (m, 1H), 3.34 (s, 2H), 3.35-3.45 (m, 8H) ), 3.87 (ddd, J = 2.2, 4.3, 11.1 Hz, 2H), 6.67 (dd, J = 1.9, 3.5 Hz, 1H), 7.38 (dd, J = 0.5, 3.5 Hz, 1H), 7.87 (dd, J = 0.5, 1.9 Hz, 1H). APCIMS m / z: [M + H] + 405.

[Example 562] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (4-methylpiperazin-1-yl) acetamide (Compound 562) In one way similar to that in Example 533, using 1-methylpiperazine (0.100 mL, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization from diethyl ether, the title compound 562 (43.4 mg, 35%) it was obtained as a pale orange solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 1.40-1.75 (m, 4H), 2.30-2.45 (m, 4H), 3. 10-3.22 (, 1H), 3.33 (s, 3H), 3.34-3.50 (, 8H), 3.87 (ddd, J = 2.2, 12.1, 12.1 Hz, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (dd, J = 0.8, 3.5 Hz, 1H), 7.89 (dd, J = 0, 8, 1.9 Hz, 1H). APCIMS m / z: [M + H] + 419. p.f .: 106-112 ° C.

[Example 563] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (4-isopropylpiperazin-1-yl) acetamide (Compound 563) In one way similar to that in Example 533, when using 1-isopropylpiperazine (115 mg, 0.900 mmol) instead of the solution of dimethylamine in THF, followed by re-mixing in a mixed mixture of ethanol and diethyl ether, the composed of the title 563 (85.5 mg, 64%) was obtained as a gray solid of compound 531 (120 mg, 0.300 mmol). XH NMR (DMSO-de, d ppm): 1.08 (d, J = 6.5 Hz, 6H), 1.70-2.00 (m, 4H), 2.65-2.80 (m, 9H), 3.05-3.20 (m, 1H), 3.30 (s, 2H) , 3.49 (ddd, J = 2.7, 11.3, 11.3 Hz, 2H), 3.95-4.05 (m, 2H), 6.58 (dd, J = 1.6, 3.2 Hz, 1H), 7.59 (d, J = 1.6 Hz, 1H ), 7.79 (d, J = 3.2 Hz, 1H). APCIMS m / z: [M + H] + 447. [Example 564] 2- [4- (Ethoxycarbonyl) piperazin-1-yl] -N- [4- (2-furyl) -5- (tetrahydropyran-4-) ylcarbonyl) thiazol-2-yl] acetamide (Compound 564) In a manner similar to that in Example 533, using 1-ethoxycarbonylpiperazine (0.266 mL, 18.0 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization of Ethanol, the title compound 564 (58.7 mg, 41%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 1.28 (t, J = 7.0 Hz, 3H), 1.75-2.00 (m, 4H), 2.59 (dd, J = 7.5, 7.8 Hz, 4H), 3.05-3.20 ( , 1H), 3.33 (s, 2H), 3.48 (ddd, J = 3.0, 11.6, 11.6 Hz, 2H), 3.59 (dd, J = 7.5, 7.8 Hz, 4H), 4.04 (ddd, J = 3.0, 4.0 , 11.6 Hz, 2H), 4.16 (q, J = 7.0 Hz, 2H), 6.58 (dd, J = 1.9, 3.8 Hz, 1H), 7.59 (dd, J = 0.5, 1.9 Hz, 1H), 7.78 (dd) , J = 0.5, 3.8 Hz, 1H), 10.44 (br s, 1H).

APCIMS m / z: [M + H] + 477. [Example 565] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [4- ( 2-hydroxy-2-methylpropyl) piperazin-1-yl] acetamide (Compound 565) In a manner similar to that in Example 533, using 1- (2-hydroxy-2-methylpropyl) piperazine (143 mg, 9.00 mmol ) in place of the solution of dimethylamine in THF, followed by re-mixing in a thickened mixture with a mixed solvent of diisopropyl ether and hexane, the title compound 565 (112 mg, 78%) was obtained as a pale orange solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-d 6, d ppm): 1.07 (s, 6H), 1.50-1.80 (m, 4H), 2. 48-2.58 (, 4H), 3.10-3.40 (m, 10H), 3.38 (s, 2H), 3.83-3.92 (m, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (d , J = 3. 5 Hz, 1H), 7.88 (d, J = 1.9 Hz, 1H). APCIMS m / z: [M + H] + 477. p. f. : 106-108 ° C.

[Example 566] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [4- (2-methoxy-2-methylpropyl) piperazin-1-yl] ] acetamide (Compound 566) In a manner similar to that in Example 533, when using 1- (2-methoxy-2-methylpropyl) piperazine (155 mg, 9.00 mmol) in place of the solution of dimethylamine in THF, followed by re-mixing in a thick mixture with a mixed solvent of diisopropyl ether and hexane, the title compound 566 (66.5 mg, 45%) was obtained as a pale orange solid of the compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 1.08 (s, 6H), 1.50-1.80 (m, 4H), 2.51-2.53 (m, 4H), 3.07 (s, 3H), 3.10-3.22 (m, 3H) ), 3.30-3.45 (m, 6H), 3.32 (s, 2H), 3.83-3.92 (m, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (d, J = 3.5 Hz, 1H), 7.88 (d, J = 1.9 Hz, 1H). APCIMS m / z: [M + H] + 491. p.f .: 105-107 ° C [Example 567] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-. { 4- [(1-methoxycyclopropyl) methyl] piperazin-1-yl} acetamide (Compound 567) In a manner similar to that in Example 533, when using 1- [(1-methoxycyclopropyl) methyl] piperazine (154 mg, 9.00 mmol) in place of the solution of dimethylamine in THF, followed by return to thick mixture with a mixed solvent of ethanol and diethyl ether, the title compound 567 (56.0 mg, 38%) was obtained as a pale brown solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 0.40-0.44 (m, 2H), 0.65-0.69 (m, 2H), 1.50-1.80 (m, 4H), 2.46 (s, 2H), 2.49-2.55 (m, 4H), 3.10-3.20 (m, 1H), 3.20 (s, 3H), 3.30-3.80 (m, 6H), 3.33 (s, 2H), 3.83-3.92 (m, 2H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (d, J = 3.5 Hz, 1H), 7.88 (d, J = 1.9 Hz, 1H). APCIMS m / z: [M + H] + 489. p.f .: 155-157 ° C.

[Example 568] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [(7R, 8aS) -7-methoxyoctahydropyrrolo [1,2-a] pyrazin-2-yl] acetamide (Compound '568) in a manner similar to that in Example 533, when using (7R, 8aS) -7-methoxyoctahydropyrrolo [1,2-a] pyrazine (141 mg, 9.00 mmol) in Place the dimethylamine solution in THF, followed by recrystallization from diethyl ether, the title compound 568 (63.2 mg, 44%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMS0-d 5, d ppm): 1.40-1.80 (m, 7H), 1.95-2.05 (m, 2H), 2. 20-2.35 (m, 2H), 2.70-2.97 (m, 4H), 3.15-3.20 (m, 1H), 3.16 (s, 3H), 3.25-3.40 (m, 1H), 3.38 (s, 2H), 3.83-3.93 (m, 4H), 6. 69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (d, J = 3.5 Hz, 1H), 7. 88 (d, J = 1.9 Hz, 1H). APCIMS m / z: [M + H] + 475.

[Example 569] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [(73,8aS) -7-hydroxyoctahydropyrrolo [1, 2-a] pyrazin-2-yl] acetamide (Compound 569) Compound 531 (120 mg, 0.300 mmol) was dissolved in THF (2 mL), and (73, 8aS) -7- (tetrahydropyran-2-yl) ) oxoctahydropyrrolo [1,2-a] pyrazine (204 mg, 0.900 mmol) was added thereto, followed by stirring at room temperature for 2.5 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in ethanol (3 mL), and 2 mol / L hydrochloric acid (3 mL) was added thereto, followed by stirring overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and the resulting residue was poured into water. A 2 mol / L sodium hydroxide solution was added thereto to adjust the pH to 8, followed by extraction with chloroform. The organic layer was washed with a solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (chloroform: methanol = 23: 2), followed by recrystallization from a mixed solvent of ethanol and diethyl L ether to give the title compound 569 (46.5 mg, 3. 4 %) .

X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 6H), 1.90-2.00 (m, 2H), 2.10-2.20 (m, 3H), 2.35-2.45 (m, 2H), 2.45-2.50 (m, 1H), 3.10-3.20 (m, 1H), 3.30-3.50 (m, 3H), 3.34 (s, 2H), 3.83-3.92 (m, 2H), 4.14-4.20 (m, 1H), 6.69 (dd, J = 1.9, 3.5 Hz, 1H), 7.39 (d, J = 3.5 Hz, 1H), 7.89 (d, J = 1.9 Hz, 1H). APCIMS m / z: [M + H] + 461.

[Example 570] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [octahydropyrazino [2, 1-c] [1,4] thiazin-8 -yl] acetamide (Compound 570) in a manner similar to that in Example 533, when using octahydropyrazino [2, 1-c] [1,4] thiazine (143 mg, 9.00 mmol) instead of the dimethylamine solution in THF, followed by recrystallization from diethyl ether, the title compound 570 (113 mg, 79%) is obtained from compound 531 (120 mg, 0. 300 mmol). X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 1.95-2.00 (m, 1H), 2. 05-2.40 (m, 6H), 2.55-2.80 (m, 4H), 2.95-3.05 (m, 1H), 3.10-3.20 (m, 1H), 3.30-3.50 (m, 5H), 3.83-3.93 (m , 2H), 6.69 (dd, J = 1.6, 3.2 Hz, 1H), 7.39 (d, J = 3.2 Hz, 1H), 7.88 (d, J = 1.6 Hz, 1H), 12.60 (br s, 1H). APCIMS m / z: [M + H] + 477.

[Example 571] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- [4- (tetrahydropyran-4-yl) piperazin-1-yl] acetamide (Compound 571) In a manner similar to that in Example 533, when using 1- (tetrahydropyran-4-yl) piperazine (154 mg, 9.00 mmol) instead of the solution of dimethylamine in THF, followed by re-making in thick mixture with a mixed solvent of ethanol and diethyl ether, the title compound 571 (79.8 mg, 54%) is obtained from compound 531 (120 mg, 0.300 mmol). X H NMR (CDC13, d ppm): 1.75-2.00 (m, 6H), 2.75-2.85 (m, 45H), 3.05-3.20 (m, 1H), 3.31 (s, 2H), 3.36-3.54 (m, 6H) ), 4.00-4.10 (m, 8H), 6.58 (dd, J = 1.9, 3.5 Hz, 1H), 7.60 (dd, J = 0.8, 1.9 Hz, 1H), 7.79 (dd, J = 0.8, 3.5 Hz, 1 HOUR) . APCIMS m / z: [M + H] + 489.

[Example 572] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (4-oxooctahydropyrazino [2, 1-c] [1,4] oxazin -8-yl) acetamide (Compound 572) in a manner similar to those in Example 533, by using 4-oxooctahydropyrazino [2, 1-c] [1,4] oxazine (141 mg, 9.00 mmol) instead of the solution of dimethylamine in THF, followed by recrystallization from ethanol, the title compound 572 (127 mg, 89%) was obtained as a pale pink solid from the compound 531 (120 mg, 0.300 mmol). XH NMR (CDC13, d ppm): 1.75-2.00 (m, 4H), 2.29 (dd, J = 11.0, 11.0 Hz, 1H), 2.41 (ddd, J = 3.6, 11.0, 11.0 Hz, 1H), 2.75- 2.88 (m, 1H), 2.88-3.00 (m, 2H), 3.05-3.20 (, .1H), 3.37 (s, 2H), 3.49 (ddd, J = 2.7, 11. "0, 11.0 Hz, 2H) , 3.55 (dd, J = 7.0, 11.0 Hz, 1H), 3.65-3.80 (m, 1H), 3.96-4.08 (m, 3H), 4.18 (d, J = 7.0 Hz, 2H), 4.66 (dd, J = 2.7, 11.9 Hz, 1H), 6.59 (dd, J = 1.9, 3.8 Hz, 1H), 7.60 (d, J = 1.9 Hz, 1H), 7.78 (d, J = 3.8 Hz, 1H), 10.35 (br s, 1H) APCIMS m / z: [M + H] + 475.

[Example 573] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (octahydropyrazino [2, 1-c] [1,4] oxazin-8 -yl) acetamide (Compound 573) in a manner similar to that in Example 533, when using octahydropyrazino [2, 1-c] [1,4] oxazine (128 mg, 9.00, mmol) instead of the dimethylamine solution in THF, followed by recrystallization from ethanol, the title compound 573 (75.8 mg, 55%) is obtained from compound 531 (120 mg, 0.300 mmol). X H NMR (CDCl 3, d ppm): 1.70-2.00 (m, 4H), 2.11 (dd, J = 13.2, 13.2 Hz, 1H), 2.35-2.85 (m, 8H), 3.05-3.20 (m, 1H), 3.23 (dd, J = 13.2, 13.2 Hz, 1H), 3.30 (s, 2H), 3.48 (ddd, J = 2.7, 11.3, 11.3 Hz, 2H), 3.60-3.72 (m, 2H), 3.88 (dd, J = 3.5, 11.1 Hz, 1H), 4.04 (ddd, J = 2.7, 4.0, 11.3 Hz, 2H), 6.58 (dd, J = 1.6, 3.5 Hz, 1H), 7.60 (dd, J = 0.8, 1.6 Hz, 1H), .7.78 (dd, J = 0.8, 3.5 Hz., 1H), 10.46 (brs, 1H) . APCIMS m / z: [M + H] + 461.

[Example 574] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (l-methyl-2-oxopiperazin-4-yl) acetamide (Compound 574 ) In a manner similar to that in Example 533, when using l-methyl-2-oxopiperazine (103 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization from a mixed solvent of ethanol and diethyl ether, the title compound 574 (86.1 mg, 66%) was obtained as a brown solid of compound 531 (120 mg, 0.300 mmol). X H NMR (CDC13, d ppm): 1.75-2.00 (m, 4H), 2.92 (dd, J = 5.1, 5.6 Hz, 2H), 3.02 (s, 3H), 3.10-3.20 (m, 1H), 3.32 ( s, 2H), 3.41 (s, 2H), 3.45 (dd, J = 5.1, 5.6 Hz, 2H), 3.48 (ddd, J = 2.7, 11.3, 11.3 Hz, 2H), 4.04 (ddd, J = 2.7, 4.0, 11.3 Hz, 2H), 6.57 (dd, J = 1.9, 3.8 Hz, 1H), 7.59 (dd, J = 0.8, 1.9 Hz, 1H), 7.79 (dd, J = 0.8, 3.8 Hz, 1H), 10.40 (br s, 1H). APCIMS m / z: [M + H] + 433.

[Example 575] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (1,4-perhydroxazepin-4-yl) acetamide (Compound 575) In a similar manner to that in Example 545, by using 1,4-perhydroxazepine hydrochloride (125 mg, 0.900 mmol) instead of 4-methoxypiperidine hydrochloride, followed by re-mixing in a thick mixture with diethyl ether, the compound of title 575 (83.5 mg, 66%) was obtained as a white solid of compound 531 (120 mg, 0.300 mmol). X H NMR (CDC13, d ppm): 1.70-2.00 (m, 6H), 2.86-2.93 (m, 4H), 3.10-3.20 (m, 1H), 3.47 (s, 2H), 3.48 (ddd, J = 2.7 , 11.1, 11.1 Hz, 2H), 3.75-3.87 (m, 4H), 4.03 (ddd, J = 2.7, 3.7, 11.1 Hz, 2H), 6.57 (dd, J = 1.9, 3.5 Hz, 1H), 7.59 ( d, J = 1.9 Hz, 1H), 7.78 (d, J = 3.5 Hz, 1H). APCIMS m / z: [M + H] + 420.

[Example 576] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (4-methyl-1,4-diazepane-1-yl) acetamide ( Compound 576) In a manner similar to that in Example 533, by using 1-methyl-1,4-diazepam (143 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization from a mixed solvent of Ethanol and diethyl ether, the title compound 576 (50.3 mg, 39%) is obtained from compound 531 (120 mg, 0.300 mmol).

X H NMR (DMSO-de, d ppm): 1.50-1.80 (m, 4H), 1.85-2.00 (m, 2H), 2.78 (s, 3H), 2.80-2.90 (m, 2H), 2.95-3.05 (m , 2H), 3.10-3.20 (m, 1H), 3.30-3.45 (m, 6H), 3.62 (s, 2H), 3.83-3.93 (m, 2H), 6.69 (dd, J = 1.6, 3.5 Hz, 1H ), 7.40 (d, J = 3.5 Hz, 1H), 7.89 (d, J = 1.6 Hz, 1H). APCIMS m / z: [M + H] + 433. mp .: 94-96 ° C.

[Example 577] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (adamantan-1-ylamino) acetamide (Compound 577) In a manner similar to that in Example 533, when using 1-adamantylamine (136 mg, 0.900 mmol) instead of the solution of dimethylamine in THF, followed by re-mixing in a thick mixture with diethyl ether, the title compound 577 (92.6 mg, 66%) was obtained as a pale brown solid of compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-d 6, d ppm): 1.50-1.80 (m, 16H), 2.00--2.05 (m, 3H), 3.10-3.25 (m, 1H), 3.35-3.50 (m, 2H), 3.53 (s, 2H), 3.87 (ddd, J = 2.4, 4.0, 12.1 Hz, 2H), 6.66 (dd, J = 1.6, 3.2 Hz, 1H), 7.33 (dd, J = 0.8, 3.2 Hz, 1H), 7.84 (dd, J = 0.8, 1.6 Hz, 1H). APCIMS m / z: [M + H] + 470. p. f. : 168-170 ° C.

[Example 578] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (3-hydroxyamino-mantan-l-ylamino) acetamide (Compound 578) In one way similar to that in Example 533, when using l-amino-3-hydroxiadamantane (151 mg, 0.900 mmol) instead of the solution of dimethylamine in THF, followed by re-mixing in a thickened mixture with diethyl ether, the compound of title 578 (102 mg, 70%) is obtained from compound 531 (120 mg, 0.300 mmol). X H NMR (DMSO-de, d ppm): 1.25-1.75 (m, 16H), 2.10-2.15 (m, 2H), 3.05-3.20 (m, 1H), 3.30-3.40 (m, 2H), 3.51 (s) , 2H), 3.84-3.90 (m, 2H), 6.66 (dd, J = 1.9, 3.5 Hz, 1H), 7.34 (dd, J = 0.5, 3.5 Hz, 1H), 7.85 (dd, J = 0.5, 1.9 Hz, 1H). APCIMS m / z: [M + H] + 486. m.p .: 176-178 ° C.

[Example 579] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (1-imidazolyl) acetamide (Compound 579) In a manner similar to that in Example 533, using imidazole (62.0 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization from a mixed solvent of ethanol and diethyl ether, the title compound 579 (43.2 mg, 37%) . it is obtained from compound 531 (120 mg, 0.300 mmol).

X H NMR (CDCl 3, d ppm): 1.70-2.00 (m, 4H), 3.05-3.20 (m, 1H), 3.40-3.50 (m, 2H), 3.90-4.10 (m, 2H), 4.98 (s, 2H) ), 6.54 (dd, J = 1.6, 3.2 Hz, 1H), 7.07 (s, 1H), 7.18 (s, 1H), 7.53 (d, J = 1.6 Hz, 1H), 7.65 (d, J = 3. .2 Hz, 1H), 7.73 (s, 1H). APCIMS m / z: [M + H] + 387.

[Example 580] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (2-methylimi azol-1-yl) acetamide (Compound 580) In one similar to that in the Example 533, when using 2-methylimidazole (74.0 mg, 0.900 mmol) in place of the solution of dimethylamine in THF, followed by recrystallization from a mixed solvent of ethanol and diethyl ether, the title compound 580 (9.1 mg, 8%) is obtained from compound 531 (120 mg, 0. 300 mmol). X H NMR (DMSO-de, d ppm): 1.70-1.95 (m, 4H), 2.43 (s, 3H), 3.10-3.20 (m, 1H), 3.45 (ddd, J = 2.7, 11.3, 11.3 Hz, 2H ), 4.00-4.05 (m, 2H), 4.93 (s, 2H), 6.53 (dd, J = 1.6, 3.2 Hz, 1H), 6.96 (d, J = 0.5 Hz, 1H), 7.03 (d, J = 0.5 Hz, 1H), 7.43 (d, J = 1.6 Hz, 1H), 7.66 (d, J = 3.2 Hz, 1H). APCIMS m / z: [M + H] + 401.

[Example 581] N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] ethyl carbamate (Compound 581) In a manner similar to that in Example 456, using ethyl chloroformate in place of cyclopropanecarbonyl chloride, the title compound 581 (73.6 mg, 47%) is obtained from compound 454 (125 mg, 0.450 mmol). X H NMR (DMSO-de, d ppm): 1.27 (t, J = 7.0 Hz, 3H), 1.50-1.76 (, 4H), 3.05-3.18 (m, 1H), 3.22-3.40 (m, 2H), 3.82-3.92 (m, 2H), 4.25 (q, J = 7.0 Hz, 2H), 6.68 (dd, J = 1.6, 3.2 Hz, 1H), 7.36 (d, J = 3.2 Hz, 1H),. 7.88 (d, J = 1.6 Hz, 1H), 12. 39 (br s, 1H). APCIMS m / z: [M + H] + 351. p. f. : 152-153 ° C.

[Example 582] N- [4- (2-furyl) -5- (4-methyltetrahydropyran-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 582) Step 1: Methyl tetrahydropyran-4-carboxylate (2.88 g, 20.0 mmol) was dissolved in THF (100 mL), and a solution of lithium diisopropylamide 2.0 mol / L in THF (22.0 mL, 44.0 mmol) was added to this at 0 ° C, followed by stirring at room temperature for 30 minutes. Methyl iodide (4.98 ml, 40.0 mmol) was added dropwise to the reaction mixture, followed by stirring for 1 hour. The reaction mixture is poured into water, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the. The solvent was distilled off under reduced pressure, and the resulting residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 1: 1) to give methyl 4-methyltetrahydropyran-4-carboxylate (1.93 g, 61%). %). X H NMR (CDC13, d ppm): 1.20 (s, 3 H), 1.42-1.52 (m, 2 H), 2.01-2.08 (m, 2 H), 3.40-3.49 (m, 2 H), 3.9 (s, 3 H), 3.73-3.81 (m, 2H).

Step 2: In a manner similar to that in step 2 of Example 445, N-methoxy-4, N-dimethyltetrahydropyran-4-carboxamide (886 mg, 32%) was obtained from methyl 4-methyltetrahydropyran-4-carboxylate ( 2.32 g, 14.6 mmol) was obtained in step 1, instead of ethyl 1,4-dioxaespiro [4, 5] decane-8-carboxylate.

Step 3: Compound h (817 mg, 2.37 mmol) obtained in Reference Example 8 was dissolved in THF (17 mL), and a solution of n-butyllithium 1.57 mol / L in n-hexane (3.32 mL, . 21 mmol) was added thereto in an argon stream at -78 ° C, followed by stirring at -78 ° C for 15 minutes. N-methoxy-4, N-dimethyltetrahydropyran-4-carboxamide (886 mg, 4.73 mmol) was obtained in step 2 was added dropwise to the reaction mixture, followed by stirring overnight at room temperature. The reaction mixture is poured into an aqueous saturated ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 1: 1) to give the title compound 582 (449 mg, 48%). XH NMR (CDC13, d ppm): 1.40 (s, 3H), 1.52 (s, 9H), 1.60-1.68 (m, 2H), 3.55-3.71 (m, 4H), 6.46 (dd, J = 1.8, 3.5 Hz, 1H), 7.14 (d, J = 3.5 Hz, 1H), 7.46 (d, J = 1.8Hz, 1H).

[Example 583] 2-Amino-4- (2-furyl) thiazol-5-yl 4-methyltetrahydropyran-4-yl ketone (Compound 583) Compound 582 (210 mg, 0.535 mmol) was dissolved in trifluoroacetic acid (2 mL ), followed by stirring at room temperature for 1 hour. The solvent was distilled under reduced pressure, and a saturated aqueous solution ofTON Sodium carbonate acid was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (ethyl acetate) to give the title compound 583 (156 mg, 100%). XH NMR (CDC13, d ppm): 1.25 (s, 3H), 1.48-1.54 (m, 2H), 1.98-2.09 (m, 2H), 3.30-3.62 (m, 4H), 6.54 (dd, J = 1.8 , 3.5 Hz, 1H), 6.98 (dd, J = 0.8, 3.5 Hz, 1H), 7.68 (dd, J = 0.8, 1.8 Hz, 1H), 7.72 (br s, 2H).

[Example 584] N- [4- (2-furyl) -5- (4-methoxytetrahydropyran-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 584) In a manner similar to that in Example 185, when using 4-methoxytetrahydrofuran-4-carboxylic acid in place of picolinic acid, the title compound 584 (167 mg, 20%) is obtained from compound h (690 mg, 2.00 mmol) obtained in reference example 8. X H NMR (CDCl 3, d ppm): 1.52 (s, 9 H), 1.93-2.11 (m, 4 H), 3.23 (s, 3H), 3.76-3.79 (m, 4H), 6.53 (dd, J = 1.8, 3.3 Hz, 1H), 7.55 (d, J = 1.8 Hz, 1H), 7.80 (d, J = 3.3 Hz, 1 HOUR) .

[Example 585] 2-Amino-4- (2-furyl) thiazol-5-yl-4-methoxytetrahydropyran-4-yl ke (Compound 585) In a manner similar to that in Example 583, the title compound 585 (124 mg, 98%) is obtained from compound 584 (167 mg, 0.409 mmol) in place of compound 582. XH NMR (CDC13, d ppm): 1.85-2.09 (m, 4H), 3.22 (s, 3H), 3.73- 3.78 (m, 4H), 5.64 (br s, 2H), 6.52 (dd, J = 1.8, 3.6 Hz, 1H), 7.54 (dd, J = 0.8, 1.8 Hz, 1H), 7.91 (dd, J = 0.8 , 3.6 Hz, 1H).

[Example 586] N-. { 4- (2-furyl) -5- [1-hydroxy-1- (tetrahydrothiopyran-4-yl) methyl] thiazol-2-yl} tert-butyl carbamate (Compound 586) In a manner similar to that in Example 92, when using tetrahydrothiopyran-4-carbaldehyde in place of DMF, the title compound 586 (2.17 g, 65%) is obtained from compound h (2.92 g, 8.45 mmol) obtained in the reference example 8. X H NMR (CDCl 3, d ppm): 1.46 (s, 9 H), 1.66-1.86 (m, 4 H), 2.50-2.67 (m, 5 H), 5.26-5.29 (m, 1 H), 6.45 ( dd, J = 1.8, 3.3 Hz, 1H), 6.66 (dd, J = 0.8, 3.3 Hz, 1H), 7.43 (dd, J = 0.8, 1.8 Hz, 1H).

[Example 587] N- [4- (2-furyl) -5- (tetrahydrothiopyran-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 587) In a manner similar to that in Example 297, the title compound 587 (444 mg, 66%) is obtained from compound 586 (680 mg, 1.71 mmol) in place of compound 296. XH NMR (CDC13, d ppm): 1.42 (s, 9H), 1.95-2.26 ( m, 4H), 2.69-2.94 (m, 5H), 6.55 (dd, J = 1.8, 3.5 Hz, 1H), 7.52 (d, 1.8 Hz, 1H), 7.77 (d, J = 3.5 Hz, 1H).

[Example 588] 2-Amino-4- (2-furyl) thiazol-5-yl tetrahydrothiopyran-4-yl ke (Compound 588) In a manner similar to that in Example 583, the title compound 588 (241 mg, 62%) is obtained from compound 587 (497 mg, 1.26 mmol) in place of compound 582. XH NMR (CDC13, d ppm): 1.84-1.93 (m, 2H), 2.13-2.20 (m, 2H), 2.65-2.83 (m, 5H), 6.56 (dd, J = 1.7, 3.3 Hz, 1H), 7.52 (d, J = 3.3 Hz, 1H), 7.56 (d, J = 1.7 Hz, 1H).

[Example 589] N- [4- (2-furyl) -5- (tetrahydrothiopyran-4-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 589) Compound 588 (120 mg, 0.408 mmol) was dissolved in DMF (2 mL), and isonicotinic acid (150 mg, 1.22 mmol), EDC hydrochloride (234 mg, 1.22 mmol) and 1-hydroxybenzotriazole monohydrate (187 mg, 1.22 mmol) were added thereto, followed by stirring at 60 ° C for 3 hours. The reaction mixture is poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from 2-propanol to give the title compound 589 (106 mg, 65%). X H NMR (CDC13, d ppm): 1.88-2.05 (m, 2H), 2.22-2.29 (m, 2H), 2.68-2.84 (m, 4H), 2.94-3.03 (m, 1H), 6.51 (dd, J = 1.8, 3.6 Hz, 1H), 7.48 (dd, J = 0.7, 3.6 Hz, 1H), 7.71-7.48 (m, 3H), 8.85 (d, J = 6.3 Hz, 2H), 10.6 (br s, 1H ). APCIMS m / z: [M + H] + 398. p.f. : 203-210 ° C.

[Example 590] N- [4- (2-furyl) -5- (tetrahydrothiopyran-4-ylcarbonyl) thiazol-2-yl] -2-methylpyridine-5-carboxamide (Compound 590) In a manner similar to that in Example 228, the title compound 590 (40.0 mg, 28%) was obtain compound 588 (100 mg, 0.340 mmol) in place of compound 186. XH NMR (DMSO-de, d ppm): 1.65-1.69 (m, 2H), 2.13-2.17 (m, 2H), 2.65-2.73 ( m, 4H), 2.73 (s, 3H), 3.04-3.20 (m, 1H), 6.71 (dd, J = 1.7, 3.5 Hz, 1H), 7.43 (d, J = 3.5 Hz, 1H), 7.92 (d , J = 1.7 Hz, 1H), 9.29 (s, 2H). APCIMS m / z: [M + H] + 415. p.f. : 238-240 ° C.

[Example 591] N- [4- (2-furyl) -5- (l-oxotetrahydrothiopyran-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 591) Compound 587 (500 mg, 1.27 mmol ) was dissolved in chloroform (13 mL), and m-chloroperbenzoic acid (219 mg, 1.27 mmol) was added thereto, followed by stirring at room temperature for 3 hours. The reaction mixture is poured into water, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (ethyl acetate) to give the title compound 591 (359 mg, 69%).

%) • XH NMR (CDCl 3, d ppm): 1.51 (s, 9H), 1.93-2.09 (m, 2H), 2.41-2.76 (m, 4H), 3.08-3.30 (m, 3H), 6.56 (dd, J = 1.8, 3.3 Hz, 1H), 7.56 (d, J = 1.8 Hz, 1H), 7.60 (d, J = 3.3 Hz, 1H).

[Example 592] 2-Amino-4- (2-furyl) thiazol-5-yl-l-oxotetrahydrothiopyran-4-yl ketone (Compound 592) In a manner similar to that in Example 583, the title compound 592 (234) mg, 86%) is obtained from compound 591 (359 mg, 0.874 mmol) instead of the compound 582. X H NMR (DMSO-de, d ppm): 1.62-1.75 (m, 2H), 2.01-2.26 (m, 2H), 2.51-2.68 (m, 2H), 2.85-3.24 (m, 3H), 6.64-6.67 (m, 1H), 7. 26-7.32 (m, 1H), 7.84-7.89 (m, 1H), 8.02-8.04 (m, 2H).

[Example 593] N- [4- (2-furyl) -5- (1, l-dioxotetrahydrothiopyran-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 593) In a manner similar to that in Example 591, using m-chloroperbenzoic acid (870 mg, 5.04 mmol), the title compound 593 (242 mg, 22%) is obtained from compound 587 (995 mg, 2.52 mmol).

X H NMR (CDCl 3, d ppm): 1.51 (s, 9H), 2.29-2.48 (m, 4H), 2.96-3.01 (m, 2H), 3.15-3.28 (m, 3H), 6.5 (dd, J = 1.7 , 3.5 Hz, 1H), 7.55 (d, J = 1.7 Hz, 1H), 7.63 (d, J = 3.5 Hz, 1H).

[Example 594] 2-Amino-4- (2-furyl) thiazol-5-yl 1, l-dioxotetrahydrothiopyran-4-yl ketone (Compound 594) In a manner similar to that in Example 583, the title compound 594 (167 mg, 90%) is obtained from compound 593 (242 mg, 0.567 mmol) in place of compound 582. XH NMR (DMSO-d6, d ppm): 1.96-2.15 (m, 4H), 3.05-3.20 (m , 5H), 6.66 (dd, J = 1.8, 3.5 Hz, 1H), 7.33 (d, J = 3.5 Hz, 1H), 7.88 (d, J = 1.8 Hz, 1H).

[Example 595] N- [4- (2-furyl) -5- (l-hydroxy-2-phenylethyl) thiazol-2-yl] tert-butyl carbamate (Compound 595) In a manner similar to that in Example 99, when using a solution of benzylmagnesium chloride 1.03 mol / L in THF (2.60 mL, 2.68 mmol) in place of phenylmagnesium bromide, the title compound 595 (255 mg, 100%) is obtained from compound 92 (194 mg , 0.660 mmol) in place of compound 98. X H NMR (CDCl 3, d ppm): 1.47 (s, 9 H), 2.44-2.46 (m, 1 H), 2.92 (s, 1H), 6.46 (dd, J = 1.8, 3.3 Hz, .1H), 6.60 (d, J = 3.3 Hz, 1H), 7.01-7.40 (m, 7H), 8.95 (br s, 1H). ESIMS m / z: [M + H] + 387.

[Example 596] N- [4- (2-furyl) -5-phenylacetylthiazol-2-yl] tert-butyl carbamate (Compound 596) In a manner similar to that in Example 297, the title compound 596 (130 mg, 51%) is obtained from compound 595 (255 mg, 0.66 mmol) in place of compound 296. XH NMR (CDC13, d ppm): 1.54 (s, 9H), 4.13 (s, 2H), 6.53 ( dd, J = 1.8, 3.3 Hz, 1H), 7.20-7.40 (m, 5H), 7.56 (d, J = 1.8 Hz, 1H), '7.79 (d, J = 3.3 Hz, 1H), 8.60 (brs, 1 HOUR) . ESIMS m / z: [M + H] + 385.

[Example 597] 2-Amino-4- (2-furyl) thiazol-5-yl-benzyl ketone (Compound 597) In a manner similar to that in Example 583, the title compound 597 (91.2 mg, 97%) was obtain compound 596 (126 mg, 0.330 mmol) in place of compound 582. X H NMR (CDCl 3, d ppm): 4.01 (s, 2 H), 5.68 (br s, 2 H), 6.53 (dd, J = 1.7 Hz, 3.6 Hz, 1H), 7.18-7.35 (m, 5H), 7.55 (dd, J = 0.7, 1.8 Hz, 1H), 7.68 (dd, J = 0.7 Hz, 3.6 Hz, 1H). ESIMS m / z: [M + H] + 285.

[Example 598] N- [4- (2-furyl) -5- [l-hydroxy-2- (2-methoxyphenyl) ethyl] thiazol-2-yl] tert-butyl carbamate (Compound 598) In a similar manner to that in Example 99, when using a solution of (2-methoxy) benzylmagnesium chloride 0.25 mol / L in THF (25.0 mL, 6.25 mmol) in place of phenylmagnesium bromide, the title compound 598 (716 mg, 100 %) is obtained from compound 92 (506 mg, 1.72 mmol) in place of compound 98. XH NMR (CDC13, d ppm): 1.50 (s, 9H), 3.75 (s, 3H), 4. 69 (s, 2H), 5.65 (brs, 1H), 6.46 (dd, J = 1.8, 3.5 Hz, 1H), 6.70 (dd, J = 0.7 Hz, 1.8 Hz, 1H), 6.75-7.00 (m, 2H ), 7.10-7.35 (m, 2H), 7.46 (dd, J = 0.7 Hz, 3.5 Hz, 1H), 8.45 (br s, 1H). ESIMS m / z: [M + H] + 417.

[Example 599] N- [4- (2-furyl) -5- [2- (2-methoxyphenyl) acetyl] thiazol-2-yl] tert-butyl carbamate (Compound 599) In a manner similar to that in Example 297, the title compound 599 (218 mg, 31%) is obtained from compound 598 (716 mg, 1.72 mmol) in place of compound 296. H NMR (CDCl 3, d ppm): 1.54 (s, 9 H), 3.77 (s, 3H), 4.13 (s, 2H), 6.50 (dd, J = 1.8, 3.7 Hz, 1H), 6.88 (dd, J = 1.1 Hz, 8.4 Hz, 1H), 6.93 (ddd, J = 1.1 Hz , 7.3 Hz, 7.4 Hz, 1H), 7.15 (dd, J = 1.6 Hz, 7.3 Hz, 1H), 7.25 (ddd, J = 1.6 Hz, 7.4 Hz, 7. 5 Hz, 1H), 7.54 (dd, J = 0.7 Hz, 1.8 Hz, 1H), 7.79 (dd, J = 0.7 Hz, 3.7 Hz, 1H), 8.58 (brs, 1H). ESIMS m / z: [M + H] + 415.

[Example 600] 2-Amino-4- (2-furyl) thiazol-5-yl-2-methoxybenzyl ketone (Compound 600) In a manner similar to that in Example 583, the title compound 600 (162 mg, 98% ) is obtained from compound 599 (218 mg, 0.527 mmol) instead of compound 582. XH NMR (CDC13, d ppm): 3.77 (s, 3H), 4.01 (s, 2H), 5.51 (brs, 2H), 6.49 (dd, J = 1.8, 3.5 Hz, 1H), 6.82-6.95 (m, 2H), 7.10-7.29 (m, 2H), 7.59 (dd, J = 0.7, 1.8 Hz, 1H), 7.75 (dd, J = 0.7, 3.5 Hz, 1H). ESIMS m / z: [M + H] + 315.

[Example 601] N- [4- (5-Methylfuran-2-yl) -5- (4-pyridyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 601) In a manner similar to that in Example 1, when using Compound aa (46.1 mg, 0.179 mmol) obtained in reference example 27 instead of compound a, the title compound 601 (31.1 mg, 48%) was obtained. X H NMR (DMSO-de, d ppm): 2.23 (s, 3 H), 6.21 (s, 1 H), 6.58 (s, 1H), 7.51 (d, J = 6.0 Hz, 2H), 8.03 (d, J = 6.0 Hz, 2H), 8.64 (d, J = 6.0 Hz, 2H), 8.84 (d, J = 6.0 Hz, 2H) . ESIMS m / z: [M + H] + 363. mp .: 274-276 ° C.

[Example 602] N- [4- (3-Methylfuran-2-yl) -5- (4-pyridyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 602) In a manner similar to that in Example 1, when using Compound ab (106 mg, 0.413 mmol) obtained in Reference Example 28 instead of compound a, the title compound 602 (61.1 mg, 41%) was obtained. X H NMR (DMSO-d 3, d ppm): 1.99 (s, 3 H), 6.50 (s, 1 H), 7.27 (dd, J = 1.6, 6.1 Hz, 2 H), 7.63 (s, 1 H), 8.02 (dd, J = 1.6, 6.1 Hz, 2H), 8.57 (dd, J = 1.6, 6.1 Hz, 2H), 8.84 (dd, J = 1.6, 6.1 Hz, 2H). ESIMS m / z: [M + H] + 363. mp .: 254-257 ° C.

[Example 603] N- [4- (3-Phenylfuran-2-yl) -5- (4-pyridyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 603) In a manner similar to that in Example 1, when using Compound ac (22.5 mg, 0.070 mmol) obtained in reference example 29 instead of compound a, the compound of Title 603 (14.5 mg, 49%) was obtained. XH NMR (CD3OD, d ppm): 6.70 (d, J = 1.5 Hz, 1H), 7.07-7.14 (m, 5H), 7.29 (d, J = 5.8 Hz, 2H), 7.61 (d, J = 1.5 Hz , 1H), 7.89 (d, J = 5.8 Hz, 2H), 8.32-8.35 (m, 2H), 8.65-8.72 (m, 2H). ESIM3 m / z: [M + H] + 425. p.f .: 190-192 ° C.

[Example 604] N-. { 5- (4-Pyridyl) -4- [3- (4-pyridyl) furan-2-yl] thiazol-2-yl} pyridine-4-carboxamide (Compound 604) In a manner similar to that in Example 1, when using Compound ad (35.2 mg, 0.110 mmol) obtained in reference example 30 instead of compound a, title compound 604 (9.90 mg, 21%) was obtained. XH NMR (CD3OD, d ppm): 6.92 (d, J = 2.0 Hz, 1H), 7.17 (dd, J = 1. 3, 4.8 Hz, 2H), 7.33 (d, J = 4.8 Hz, 2H), 7.72 (d, J = 2.0 Hz, 1H), 7.98 (dd, J = 1.3, 4.8 Hz, 2H), 8.34-8.37 (m, 4H), 8. 78 (d, J = 4.8 Hz, 2H). ESIMS m / z: [M + H] + 426.

[Example 605] N- [4- (3-furyl) -5- (4-pyridyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 605) In a manner similar to that in Example 1, using Compound ae (109 mg, 0.450 mmol) obtained in the example of reference 31 instead of compound a, the title compound 605 (155 mg, 99%) was obtained. X H NMR (DMSO-de, d ppm): 6.43 (dd, J = 0.8, 2.0 Hz, 1H), 7.48 (dd, J = 1.6, 4.5 Hz, 2H), 7.72 (dd, J = 1.5, 2.0 Hz, 1H), 7.88 (dd, J = 0.8, 1.5 Hz, 1H), 8.02 (dd, J = 1.6, 4.4 Hz, 2H), 8.63 (dd, J = 1.6, 4.5 Hz, 2H), 8.83 (dd, J = 1.6, 4.4 Hz, 2H), 13.31 (br s, 1H). ESIMS m / z: [M + H] + 349. p.f .: 251-254 ° C.

[Example 606] N- [4- (3-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 606) In a manner similar to that in Example 185, when using Compound af (508 mg, 1.47 mmol) obtained in reference example 32 instead of compound h, the title compound 606 (310 mg, 57%) was obtained.

[Example 607] 2-Amino-4- (3-furyl) thiazol-5-yl 2-pyridyl ketone (Compound 607) In a manner similar to that in Example 186, when using Compound 606 (331 mg, 0.892 mmol) in place of compound 185, the title compound 607 (199 mg, 88%) was got. X H NMR (CDCl 3, d ppm): 5.66 (br s, 2 H), 7.07 (dd, J = 0.6, 1.8 Hz, 1 H), 7.44-7.46 (m, 1 H), 7.45-7.51 (m, 1 H), 7.85. -7.91 (m, 1H), 8.16-8.22 (m, 1H), 8.64-8.67 (m, 1H), 8.72-8.73 (m, 1H).

[Example 608] N- [4- (3-furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 608) In a manner similar to that in Example 1, when using Compound 607 (87.4 mg, 0.322 mmol) in place of compound a, the title compound 608 (96.8 mg, 80%) was obtained. X H NMR (DMSO-de, d ppm): 7.07-7.08 (m, 1H), 7.70-7.76 (m, 1H), 7.78-7.79 (m, 1H), 8.05 (d, J = 5.9 Hz, 2H), 8.07-8.17 (m, 2H), 8.66-8.70 (m, 1H), 8.82-8.86 (m, 3H), 13.4 (br s, 1H). ESIMS m / z: [M + H] + 377. p.f .: 264-266 ° C.

[Example 609] N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 609) In a manner similar to that in Example 185, when using tetrahydropyran-4-carboxylic acid instead of picolinic acid, the title compound 609 (2.66 g, 66%) is obtained from the compound af (3.68 g, 10.7 mmol) obtained in reference example 32 instead of compound h .

X H NMR (CDCl 3, d ppm): 1.49 (s, 9H), 1.76-1.97 (m, 4H), 3.09 --- (tt, J = 4.0, 11.0 Hz, 1H), 3.49 (ddd, J = 2.6, 11.4, 11.4 Hz, 2H), 4.06 (ddd, J = 2.6, 4.0, 11.4 Hz, 2H), 7.01 (dd, J = 0. 7, 1.8 Hz, 1H), 7.44 (dd, J = 1.5, 1.8 Hz, 1H), 8.69 (dd, J 5 = 0.7, 1.5 Hz, 1H), 9.24 (br s, 1H). APCIMS m / z: [M + H] + 379.

[Example 610] 2-Amino-4- (3-furyl) thiazol-5-yl tetrahydropyran-4-yl ketone 0 (Compound 610) In a manner similar to that in Example 186, using Compound 609 (1.92 g, 5.07 mmol) instead of the compound 185, the title compound 610 (1.41 g, 99%) was obtained.

X H NMR (CDCl 3, d ppm): 1.69-1.95 (m, 4H), -2.88 (tt, J = 3.9, 11.0 Hz, 1H), 3.41 (ddd, J = 2.4, 11.6, 11.6 Hz, 2H), 4.02 (ddd, J = 2.4, 4.2, 11.6 Hz, 2H), 5.34 (br s, 2H), 6.95 (dd, J = 0.7, 1.8 Hz, 1H), 7.45 (dd, J = 1.6, 1.8 Hz, 1H), 8.52 (dd, J = 0.7, 1.6 Hz, 1H). APCIMS m / z: [M + H] + 279.

[Example 611] N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] cyclopropanecarboxamide (Compound 611) In a manner similar to that in Example 187, by using acid cyclopropanecarboxylic acid instead isonicotinic, followed by recrystallization from a mixed solvent of ethanol and water, the title compound 611 (98.6 mg, 66%) was obtained as a white solid of compound 610 (150 mg, 0.435 mmol) in place of compound 186. XH NMR (CDC13, d ppm): 0.90-1.00 (m, 2H), 1.14-1.22 (m, 2H), 1.42-1.52 (m, 1H), 1.76-1.98 (m, 4H), 3.08 (tt, J = 4.4 , 10.6 Hz, 1H), 3.48 (ddd, J = 2.6, 11.4, 11.4 Hz, 2H), 4.04 (ddd, J = 2.6, 4.0, 11.4 Hz, 2H), 7.02 (dd, J = 0.7, 1.8 Hz, 1H), 7.47 (dd, J = 1.5, 1.8 Hz, 1H), 8.66 (dd, J = 0.7, 1.5 Hz, 1H), 10.11 (br s, 1H). APCIMS m / z: [M + H] + 347. p.f .: 231-232 ° C.

[Example 612] 2-Chloro-N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] pyridine-5-carboxamide (Compound 612) In a manner similar to that in Example 188, by using 6-chloronicotinoyl chloride in place of acetyl chloride, followed by re-mixing in a thick mixture with ethanol, the title compound 612 (110 mg, 73%) was obtained as a white solid of compound 610 (100 mg, 0.359 mmol) in place of compound 186. X H NMR (CDCl 3, d ppm): 1.74-2.00 (m, 4H), 3.13 (tt, J = 4.2, . 6 Hz, 1H), 3.50 (ddd, J = 2.8, 11.4, 11.4 Hz, 2H), 4.04 (ddd, J = 2.8, 4.3, 11.4 Hz, 2H), 6.97 (dd, J = 0.8, 1.8 Hz, 1H), 7.43 (dd, J = 1.6, 1.8 Hz, 1H), 7.51 (dd, J = 0.7, 8.4 Hz, 1H), 8.21 (dd, J = 2.5, 8.4 Hz, 1H), 8.57 (dd, J = 0.8, 1.6 Hz, 1H), 8.95 (dd, J = 0.7, 2.5 Hz, 1H). APCIMS m / z: [35C1M-H] "416, [37C1M-H]" 418. p.f .: 237-239 ° C.

[Example 613] N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -5-methylpyridine-3-carboxamide (Compound 613) In a manner similar to that in Example 187, using 5-methylnicotinic acid in place of isonicotinic acid, followed by recrystallization from a mixed solvent of ethanol and water, the title compound 613 (46.5 mg, 53%) was obtained as a white solid of compound 610 (59.8 mg, 0.215 mmol) in place of compound 186. XH NMR (CDC13, d ppm): 1.79-2.01 (m, 4H), 2.48 (s, 3H), 3.15 (tt, J = 4.0, 10.6 Hz, 1H), 3.52 (ddd, J = 2.7, 11.4, 11.4 Hz, 2H), 4.06 (ddd, J = 2.7, 4.0, 11.4 Hz, 2H), 7.01 (dd, J = 0. 7, 1.8 Hz, 1H), 7.46 (dd, J = 1.6, 1.8 Hz, 1H), 8.06-8.10 (m, 1H), 8.66 (dd, J = 0.7, 1.6 Hz, 1H), 8.71 (d, J = 2.2 Hz, 1H), 9.01 (d, J = 2.2 Hz, 1H). APCIMS m / z: [M + H] + 398. p.f. : 244-246 ° C.

[Example 614] N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-methylpyridine-5-carboxamide (Compound 614) In a manner similar to that in Example 187, when using 6-methylnicotinic acid (290 mg, 2.11 mmol) in place of isonicotinic acid, the title compound 614 (120 mg, 87 %) is obtained from compound 610 (96.0 mg, 0.345 mmol) in place of compound 186. XH NMR (DMSO-de, d ppm): 1.56-1.78 (m, 4H), 2.58 (s, 3H), 3.16-3.24 (m, 1H), 3.36-3.44 (m, 2H), 3.88-3.92 (m, 2H), 7.05 (dd, J = 0.8, 1.5 Hz, 1H), 7.47 (d, J = 8.3 Hz, 1H), 7.80 (dd, J = 1.0, 1.5 Hz, 1H), 8.35 (dd, J = 2.4, 8.3 Hz, 1H), 8.62 (dd, J = 0.8, 1.0 Hz, 1H), 9.14 (d, J = 2.4 Hz , 1H), 13.30 (br s, 1H). ESIMS m / z: [M + H] + 398. p.f .: 217-219 ° C.

[Example 615] N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-methylpyridine-4-carboxamide (Compound 615) Compound 610 (100 mg, 0.359 mmol) was dissolved in DMF (3 mL), and 2-methylisonicotinic acid hydrochloride (249 mg, 1.44 mmol), EDC hydrochloride (558 mg, 2.91 mmol), 1-hydroxybenzotriazole monohydrate (463 mg, 3.02 mmol) and triethylamine (0.400 mL, 2.87 mmol). mmol) were added to this, followed by stirring overnight at 80 ° C. The reaction mixture is poured into aqueous sodium hydrogen carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 3: 1), followed by recrystallization from a mixed solvent of ethanol and water to provide the title compound 615 (73.1 mg, 51%). %) as a white solid. X H NMR (CDC13, d ppm): 1.76-2.01 (m, 4H), 2.71 (s, 3H), 3.15 (tt, J = 4.0, 10.6 Hz, 1H), 3.52 (ddd, J = 2.8, 11.4, 11.4 Hz, 2H), 4.02-4.12 (m, 2H), 7.02 (dd, J = 0.7, 1.8 Hz, 1H), 7.48 (dd, J = 1.6, 1.8 Hz, 1H), 7.57-7.63 (m, Í_H) , 7.67 (m, 1H), 8.67, (dd, J = 0.7, 1.6 Hz, 1H), 8.78 (d, J = 5.1 Hz, 1H), 9.74 (br s, 1H). APCIMS m / z: [M-H] + 396. p.f. : 202-204 ° C.

[Example 616] 2-Chloro-N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 616) Compound 610 (100 mg, 0.359 mmol) was dissolved in pyridine (3 mL), and 6-chloroisonicotinoyl chloride (560 mg, 3. 18 mmol) and DMAP (4.40 mg, 0.0360 mmol) were added thereto, followed by stirring at 80 ° C for 3 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was poured into a saturated aqueous solution of sodium hydrogencarbonate, and the precipitated solid was collected by filtration. The resulting solid was purified through column chromatography on silica gel (hexane: ethyl acetate = 3: 1), followed by recrystallization from a mixed solvent of ethanol and water to provide the title compound 616 (54.5 mg, 36%). %) as a white solid. XH NMR (CDC13, d ppm): 1.79-2.01 (m, 4H), 3.14 (tt, J = 4.0, 10.8 Hz, 1H), 3.53 (ddd, J = 2.5, 11.6, 11.6 Hz, 2H), 4.07 ( ddd, J = 2.5, 4.0, 11.6 Hz, 2H), 6.99 (dd, J = 0.7, 1.8 Hz, 1H), 7.47 (dd, J = 1.6, 1.8 Hz, 1H), 7.70 (dd, J = 1.6, 5.1 Hz, 1H), 7.82 (dd, J = 0.7, 1.6 Hz, 1H), 8.65 (dd, J = 0.6, 1.6 Hz, 1H), 8.67 (dd, J = 0.6, 5.1 Hz, 1H), 9.73 ( br s, 1H). APCIMS m / z: [35C1M-H] "416, [37C1M-H]" 418. p.f .: 202-204 ° C.

[Example 617] N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-methylpyridine-5-carboxamide (Compound 617) In a manner similar to that in Example 228, the title compound 617 (42.6 mg, 29%) is obtained from compound 610 (104 mg, 0.372 mmol) in place of compound 186. H NMR (CDC13, d ppm): 1.80-2.00 (, 4H), 2.86 (s, 3H), 3.14 (tt, J = 4.4, 10.5 Hz, 1H), 3.52 (ddd, J = 2.8, 11.4, 11.4 Hz, 2H), 4.02-4.12 (m, 2H), 6.92 (dd, J = 0.7, 1.8 Hz, 1H), 7.41 (dd, J = 1.5, 1.8 Hz, 1H), 8.56 (dd, J = 0.7, 1.5 Hz, 1H), 9.15 (s, 2H), 10.39 (br s, 1H). ESIMS m / z: [M + H] + 399. p.f .: 225-227 ° C.

[Example 618] N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2- (3-pyridyl) acetamide (Compound 618) Compound 610 (102 mg, 0.366 mmol) was dissolved in DMF (3 mL), and 3-pyridylacetic acid hydrochloride (635 mg, 3.66 mmol), EDC hydrochloride (702 mg, 3.66 mmol), 1-hydroxybenzotriazole monohydrate (561 mg, 3.66 mmol) and triethylamine (0.510 mL, 3.66 mmol) were added thereto, followed by stirring at 80 ° C for 10 hours. The reaction mixture was poured into a saturated aqueous solution of sodium hydrogen carbonate, and the precipitated solid was collected by filtration. The resulting solid was purified through column chromatography on silica gel (hexane: ethyl acetate = 2: 1), followed by recrystallization from a mixed solvent of ethanol and water to give the title compound 618 (74.6 mg, 52 %) as a white solid.

H NMR (CDCl 3, d ppm): 1.75-1.94 (m, 4H), 3.08 (tt, J = 4. 4, 10.5 Hz, 1H), 3.48 (ddd, - J = 2.5, 11.4, 11.4 Hz, 2H) , 3.82 (s, 2H), 4.04 (ddd, J = 2.5, 4.1, 11.4 Hz, 2H), 6.92 (dd, J = 0.8, 1.8 Hz, 1H), 7.36 (ddd, J = 0.7, 4.8, 7.7 Hz , 1H), 7.47 (dd, J = 1.6, 1.8 Hz, 1H), 7.67-7.73 (m, 1H), 8.55-8.67 (m, 3H), 9.41 (br s, 1H). APCIMS m / z: [M + H] + 398. p.f .: 195-197 ° C.

[Example 619] N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -3-methoxybenzamide (Compound 619) In a manner similar to that in Example 188, Using 3-methoxybenzoyl chloride in place of acetyl chloride, followed by recrystallization from a mixed solvent of ethanol and water, the title compound 619 (90.0 mg, 61%) was obtained as a white solid of compound 610 (100 mg, 0. 359 mmol) in place of compound 186. XH NMR. { CDCI3, d ppm): 1.79-2.01 (m, 4H), 3.15 (tt, J = 4.6, 10.7 Hz, 1H), 3.52 (ddd, J = 2.6, 11.6, 11.6 Hz, 2H), 3.90 (s, 3H), 4.06 (ddd, J = 2.6, 3.9, 11.6 Hz, 2H), 7.04 (dd, J = 0. 7, 1.8 Hz, 1H), 7.20 (ddd, J = 2.6, 2.6, 6.6 Hz, 1H), 7.46- 7.54 (m, 4H), 8.68 (dd, J = 0.7, 1.5 Hz, 1H), 9.52 (br s, 1 HOUR) . APCIMS m / z: [M + H] + 413. p.f .: 194-196 ° C.

[Example 620] 4-Fluoro-N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] benzamide (Compound 620) In a manner similar to that in Example 188, when using 4-fluorobenzoyl chloride in place of acetyl chloride, followed by recrystallization from a mixed solvent of ethanol and water, the title compound 620 (68.3 mg, 47%) was obtained as a white solid of compound 610 (100 mg , 0.359 mmol) instead of the compound 186. XH NMR (CDC13, d ppm): 1.79-2.01 (m, 4H), 3.15 (tt, J = 4.4, . 6 Hz, 1H), 3.52 (ddd, J = 2.6, 11.4, 11.4 Hz, 2H), 4.06 (ddd, J = 2.6, 4.0, 11.4 Hz, 2H), 7.02 (dd, J = 0.7, 1.8 Hz, 1H), 7.20-7.30 (m, 2H), 7.46 (dd, J = 1.5, 1.8 Hz, 1H), 7.96- 8.04 (m, 2H), 8.67 (0.7, 1.5 Hz, 1H), 9.63 (brs, 1H) ). APCIMS m / z: [M + H] + 401. p. f. : 231-232 ° C.

[Example 621] N- [4- (3-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -2-morpholinoacetamide (Compound 621) In a manner similar to that in Example 287, Use Compound 610 (204 mg, 0.745 mmol) instead of compound 286, the title compound (68.4 mg, 23%) was obtained. XH NMR (CDC13, d ppm): 1.76-1.97 (m, 4H), 2.62-2.69 (m, 4H), 3.10 (t, J = 4.2, 10.8 Hz, 1H), 3.31 (s, 2H), 3.49 ( ddd, J = 2.8, 11.6, 11.6 Hz, 2H), 3.80-3.86 (m, 4H), 4.04 (ddd, J = 2.4, 4.4, 11.6 Hz, 2H), 7.04 (dd, J = 0.7, 1.8 Hz, 1H), 7.48 (dd, J = 1.5, 1.8 Hz, 1H), 8.64 (dd, J = 0.7, 1.5 Hz, 1H), 10.35 (br s, 1H).

[Example 622] N- [5- (Cyclopentylcarbonyl) -4- (2-furyl) thiazol-2-yl] dicyclopropanecarboxamide (Compound 622) Compound 452 (88.9 mg, 0.339 mmol) was dissolved in THF (5 mL), and cyclopropanecarbonyl chloride (0.188 mL, 1.98 mmol) and triethylamine (0.279 mL, 2.00 mmol) were added thereto, followed by stirring overnight at 50 ° C. The saturated aqueous sodium carbonate solution added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 3: 1) to give the title compound 622 (135 mg, 100%) as pale brown crystals.

X H NMR (CDCl 3, d ppm): 1.06-1.14 (m, 4H), 1.30-1.36 (m, 4H), 1.56-1.80 (m, 4H), 1.87-1.96 (m, 4H), 2.08-2.18 (m , 1H), 3.38-3.44 (m, 2H), 6.53 (dd, J = 1.7 Hz, 3.5 Hz, 1H), 7.50 (dd, J = 0.7 Hz, 3.5 Hz, 1H), 7.55 (dd, J = 0.7 Hz, 1.7 Hz, 1H). ESIMS m / z: [M + H] + 331. mp .: 87-88 ° C.

[Example 623] N- [5- (2-ethoxyacetyl) -4- (2-furyl) thiazol-2-yl] -N-methyl tert-butylcarbamate (Compound 623) Step 1: Compound h (2.00 g, 5.79 mmol) obtained in Reference Example 8 was dissolved in DMF (29 mL), and 55% sodium hydride (278 mg, 6.37 mmol) was added thereto, followed by stirring at room temperature for 30 minutes. The methyl iodide (0.793 mL, 12.7 mmol) was added dropwise to the reaction mixture, followed by stirring at room temperature for 1 hour. The reaction mixture is poured into water, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 1: 1) to provide N- [5-bromo-4- (2-furyl) thiazol-2-yl] -N-methyl tert-butylcarbamate (2.08 g, 100%). X H NMR (CDC13, d ppm): 1.57 (s, 9H), 3.54 (s, 3H), 6.48 (dd, J = 1.8, 3.5 Hz, 1H), 6.97 (dd, J = 0.7, 3.5 Hz, 1H) , 7.50 (dd, J = 0.7, 1.8 Hz, 1H) _.

Step 2: N- [5-bromo-4- (2-furyl) thiazol-2-yl] -N-methyl tert-butylcarbamate (1.41 g, 3.93 mmol) was obtained in stage 1 was dissolved in THF (19 mL), and a solution of n-butyllithium 1.57 mol / L in n-hexane (2.75 mL, 4.32 mmol) was added thereto in a Argon stream at -78 ° C, followed by stirring at -78 ° C for 15 minutes. The 2-ethoxy-N-methoxy-N-methylacetamide (1.74 g, 11.8 mmol) was added to the reaction mixture, followed by stirring at room temperature for 2 hours. The reaction mixture is poured into an aqueous saturated ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 1: 1) to give the title compound 623 (550 mg, 38%). X H NMR (CDCl 3, d ppm): 1.24 (t, J = 6.9 Hz, 3 H), 1.59 (s, 9 H), 3. 58 (q, J = 6.9 Hz, 2H), 3.61 (s, 3H), 4.46 (s, 2H), 6.52 (dd, J = 1.8, 3.5 Hz, 1H), 7.55 (d, J = 1.8 Hz, 1H ), 7.59 (d, J = 3.5 Hz, 1H).

[Example 624] Ethoxymethyl 4- (2-furyl) -2- (methylamino) thiazol-5-yl ketone (Compound 624) Compound 623 (550 mg, 1.50 mmol) was dissolved in trifluoroacetic acid (2 mL), followed by stirring for 1 hour. The reaction mixture was concentrated under reduced pressure, and saturated sodium acid carbonate was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (ethyl acetate) to give the title compound 624 (344 mg, 86%). XH NMR (CDC13, d ppm): 1.24 (t, J = 6.9 Hz, 3H), 3.00 (d, J = 4.3 Hz, 3H), 3.57 (q, J = 6.9 Hz, 2H), 4.45 (s, 2H) ), 6.53 (dd, J = 1.8, 3.5 Hz, 1H), 6.72-6.74 (m, 1H), 7.54 (d, J = 1.8 Hz, 1H), 7.69 (d, J = 3.5 Hz, 1H).

[Example 625] 2- (Benzylamino) -4- (2-furyl) thiazol-5-yl tetrahydropyran-4-yl ketone (Compound 625) In a manner similar to that in Example 623, by using benzyl bromide in place of methyl iodide and using N-methoxy-N-methyltetrahydropyran-4-carboxamide in place of 2-ethoxy-N-methoxy-N-methylacetamide, N-benzyl-N- [4- (2-furyl) -5- ( Tert-butyl tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] carbamate is obtained from compound h obtained in reference example 8. In a manner similar to that in Example 624, the title compound 625 was obtained from N -benzyl-N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate obtained herein in place of Compound 623. XH NMR (CDC13, d ppm): 1.65-1.90 (m, 4H), 2.98 (tt, J = 3.8, 10.9 Hz, 1H), 3.38 (ddd, J = 2.4, 10.9, 10.9 Hz, 2H), 4.00 (ddd, J = 2.4, 4.8, 10.9 Hz, 2H), 4.50 (d, J = 4.4 Hz, 2H), 6.53 (dd, J = 1.8, 3.5 Hz, 1H), 7.33-7.41 (m, 5H), 7.49 (dd, J = 0.8 , 1.8 Hz, 1H), 7.52 (d d, J = 0.8, 3.5 Hz, 1H).

[Example 626] 4- (2-Furyl) -2- (methylamino) thiazol-5-yl tetrahydropyran-4-yl ketone (Compound 626) In a manner similar to that in Example 623, when using N-methoxy-N -methyl tetrahydropyran-4-carboxamide instead of 2-ethoxy-N-methoxy-N-methylacetamide, N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -N-methylcarbamate tert-butyl is obtained from compound h obtained in reference example 8. In a manner similar to that in Example 624, the title compound 626 was obtained from N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazole -2-yl] -N-methyl tert-butylcarbamate obtained herein in place of compound 623. XH NMR (CDC13, d ppm): 1.65-1.90 (m, 4H), 2.95-3.10 (m, 1H), 3.11-3.20 (m, 3H), 3.38 (ddd, J = 2.4, 10.9, 10.9 Hz, 2H), 4.00 (ddd, J = 2.4, 4.8, 10.9 Hz, 2H), 4.50 (d, J = 4.4 Hz, 2H), 6.53 (dd, J = 1.8, 3.5 Hz, 1H), 7.49 (dd, J = 0.8, 1.8 Hz, 1H), 7.52 (dd, J = 0.8, 3.5 Hz, 1H).

[Example 627] 2- (tert-Butylamino) -4- (2-furyl) thiazol-5-yl tetrahydropyran-4-yl ketone (Compound 627) In a manner similar to that in Example 623, when using 2-iodine -2-methylpropane instead of methyl iodide and using N-methoxy-N-methyltetrahydropyran-4-carboxamide in place of 2-ethoxy-N-methoxy-N-methylacetamide, N- (tert-butyl) -N- [4 Tert-butyl (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] carbamate is obtained from compound h obtained in reference example 8. In a manner similar to that in Example 624 , the title compound 627 was obtained from N- (tert-butyl) -N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate obtained herein in place of compound 623. XH NMR (CDC13, d ppm): 1.49 (s, 9H), 1.72-1.96 (, 4H), 3.05 (tt, J = 3.8, 11.1 Hz, 1H), 3.41 (ddd, J = 2.3, 11.1, 11.1 Hz, 2H), 4.02 (ddd, J = 2.3, 4.0, 11.1 Hz, 2H), 5.84 (br s, 1H), 6.55 (dd, J = 1.8, 3.5 Hz, 1H), 7.48 (d, J = 3.5 Hz, 1H), 7.54 (d, J = 1.8 Hz, 1H).

[Example 628] 4- (2-furyl) -2- (2,2,4,4-tetramethylbutylamino) thiazol-5-yl tetrahydropyran-4-yl ketone (Compound 628) In a manner similar to that in Example 623 , when using 2-chloro-2,2,4,4-tetramethylbutane instead of methyl iodide and using N-methoxy-N-methyltetrahydropyran-4-carboxamide instead of 2-ethoxy-N-methoxy-N-methylacetamide, N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazol-2-yl] -N- (2,2,4,4-tetramethylbutylamino) tert-butyl carbamate is obtained from compound h obtained in reference example 8. In a manner similar to that in Example 624, the title compound 628 was obtained from N- [4- (2-furyl) -5- (tetrahydropyran-4-ylcarbonyl) thiazole-2 -yl] -N- (2,2,4,4-tetramethylbutylamino) tert-butyl carbamate obtained herein in place of compound 623. X H NMR (CDCl 3, d ppm): 1.03 (s, 9 H), 1.50 ( s, 6H), 1.71-1.80 (m, 4H), 1.80 (s, 2H), 3.05 (tt, J = 3.9, 11.2 Hz, 1H), 3.40 ddd, J = 1.6, 11.6, 11.6 Hz, 2H), 3.95-4.10 (m, 2H) , 5.87 (br s, 1H), 6.55 (dd, J = 1.8, 3.5 Hz, 1H), 7.45 (d, J = 3.5 Hz, 1H), 7.54 (d, J = 1.8 Hz, 1H).

[Example 629] N- [4- (2-furyl) -5- (4-hydroxy-l-methylpiperidin-4-yl) thiazol-2-yl] benzamide (Compound 629) In a manner similar to that in Example 92, when using l-methyl-4-piperidone (1.39 mL, 113 mmol) in place of DMF, the title compound 629 (48.5 mg, 4%) was obtained from N- [5-bromo-4- (2- furyl) thiazol-2-yl] benzamide (1.13 g, 3.23 mmol) was obtained in step 1 of Reference Example 14 in place of compound h. XH NMR (CDC13, d ppm): 2.03-2.39 (m, 4H), 2.37 (s, 3H), 2.59-2.67 (m, 2H), 2.70-2.83 (m, 2H), 6.44 (dd, J = 1.9 , 3.5 Hz, 1H), 6.75 (dd, J = 0.5, 3.5 Hz, 1H), 7.41-7.50 (m, 2H), 7.45 (dd, J = 0.5, 1.9 Hz, 1H), 7.52-7.60 (m, 1H), 7.84-7.91 (m, 2H).

[Example 630] 2-Amino-4- (2-pyridyl) thiazol-5-yl 2-pyridyl ketone (Compound 630) 1, 3-Di (2-pyridyl) propan-1,3-dione (1.17 g, 5.15 mmol) was dissolved in acetic acid (20 mL), and bromide (856 mg, 5.35 mmol) was added thereto, followed by stirring at 80 ° C for 1 hour. The reaction mixture was concentrated under reduced pressure, and the resulting residue was suspended in ethanol (30 mL), and triethylamine (0.750 mL, 5.38 mmol) and thiourea (416 mg, 5.47 mmol) were added thereto, followed by low stirring. heat and reflux for 30 minutes. The saturated aqueous sodium acid carbonate solution was added to the reaction mixture, followed by extraction with chloroform. The solvent was distilled off under reduced pressure, and the resulting residue was purified by column chromatography on silica gel (chloroform: methanol = 9: 1) to give the title compound 630 (739 mg, 51%). X H NMR (DMSO-de, d ppm): 7.09-7.27 (m, 2H), 7.32-7.37 (m, 1H), 7.58 (d, J = 0.9, 7.8 Hz, 1H), 7.70-7.75 (m, 2H) ), 7.80-7.88 (m, 1H), 8.01 (br s, 2H), 8.15 (d, J = 4.8 Hz, 1H).

[Example 631] N- [4- (2-Pyridyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 631) In a manner similar to that in Example 1 , using Compound 630 (739 mg, 2.62 mmol) in place of compound a, the title compound 631 (680 mg, 67%) was obtained. X H NMR (DMSO-de, d ppm): 7.19-7.24 (m, 1H), 7.45-7.50 (m, 1H), 7.82-7.85 (m, 2H), 7.96-7.98 (m, 2H), 8.05 (d , J = 6.0 Hz, 2H), 8.12 (d, J = 4.6 Hz, 1H), 8.32 (d, J = 4.6 Hz, 1H), 8.85 (d, J = 6.0 Hz, 2H), 13.5 (br s, 1H). ESIMS m / z: [M + H] + 388. p.f .: 232-234 ° C.

[Example 632] N- [4-phenyl-5- (pyridin-2-ylcarbonyl) thiazol-2-yl] tert-butyl carbamate (Compound 632) Step 1: In a manner similar to that in Reference Example 7, when using acetophenone (3.18 g, 26.5 mmol) in place of 2-acetylfuran, 2-amino-5-bromo-4-phenylthiazole (3.56 g, 53% ) it was obtained. X H NMR (CDC13, d ppm): 5.03 (br s, 2H), 7.31-7.44 (m, 3H), 7.84 (dd, J = 1.6, 8.4 Hz, 2H).

Stage 2: In a similar way to that in stage 1 of the Example 92, using 2-amino-5-bromo-4-phenylthiazole (691 mg, 2.71 mmol) was obtained in step 1 in place of compound g, N- [5-bromo-4-phenylthiazol-2-yl] tert-butyl carbamate (499 mg, 52%) was obtained. X H NMR (DMSO-de, d ppm): 1.50 (s, 9H), 7.37-7.50 (m, 3H), 7.83 (d, J = 6.7 Hz, 2H).

Step 3: In a manner similar to that in Example 185, using tert-butyl N- [5-bromo-4-phenylthiazol-2-yl] carbamate (499 mg, 1.41 mmol) was obtained in step 2 in Place of compound h, the title compound 632 (355 mg, 66%) was obtained. XH NMR (CDC13, d ppm): 1.55 (s, 9H), 7.35-7.46 (m, 4H), 7.55-7.59 (m, 2H), 7.76-7.86 (m, 1H), 8.00-8.06 (m, 1H ), 8.31 (br s, 1H), 8.63-8.67 (m, 1H).

[Example 633] 2-Amino-4-phenylthiazol-5-yl 2-pyridyl ketone (Compound 633) In a manner similar to that in Example 186, using Compound 632 (355 mg, 0.931 mmol) instead of compound 185 , the title compound 633 (256 mg, 98%) was obtained. X H NMR (DMSO-d 6, d ppm): 7.28-7.21 (m, 3H), 7.40 (d, J = 7.4 Hz, 2H), 7.47 (dd, J = 7.0, 7.7 Hz, 1H), 7.79 (d, J = 7.7 Hz, 1H), 7.89 (dd, J = 7.0, 7.7 Hz, 1H), 8.03 (br s, 2H), 8.45 (d, J = 7.0 Hz, 1H).

[Example 634] N- [4-Phenyl-5- (pyridin-2-ylcarbonyl) thiazol-2-yl] pyridine-4-carboxamide (Compound 634) In a manner similar to that in Example 187, Use Compound 633 (256 mg, 0.911 mmol) in place of compound 186, title compound 634 (247 mg, 70%) was obtained. X H NMR (DMSO-de, d ppm): 7.35-7.38 (m, 3H), 7.54-7.57 (m, 2H), 7.61-7.66 (m, 1H), 8.00-8.03 (m, 2H), 8.04 (dd) , J = 1.3, 4.6 Hz, 2H), 8.67 (d, J = 4.8 Hz, 1H), 8.84 (dd, J = 1.3, 4.6 Hz, 2H), 13.39 (br s, 1H). ESIMS m / z: [M + H] + 387. p.f .: 231-235 ° C.

[Reference Example 1] 2-Amino-4- (2-furyl) -5- (4-pyridyl) thiazole (Compound a) Step 1: 1- (2-furyl) -2- (4-pyridyl) ethane (4.15 g, 22.2 mmol) obtained according to the method described in WO 03/35639 was dissolved in acetic acid (22 mL), and bromide ( 3.54 g, 22.2 mmol) was added thereto, followed by stirring at 80 ° C for 1 hour. The reaction mixture was cooled with ice in water, and then ethyl acetate was added thereto. The precipitated crystals were collected by filtration to give 2-bromo-l- (2-furyl) -2- (4-pyridyl) ethanone bromohydrate (7.59 g, 99%). X H NMR (DMSO-de, d ppm): 6.58 (dd, J = 1.7, 3.7 Hz, 1H), 7.01 (1H, s), 7.91 (dd, J = 0.8, 3.7 Hz, 1H), 8.19 (dd, J = 0. 8, 1.7 Hz, 1H), 8.21 (d, J = 5.6 Hz, 2H), 8.97 (d, J = 5.6 Hz, 2H).

Step 2: 2-Bromo-l- (2-furyl) -2- (4-pyridyl) ethanone bromohydrate (7.59 g, 21.9 mmol) was suspended in ethanol (110 mL), and triethylamine (3.35 mL, 24.1 mmol) was added thereto, followed by stirring at room temperature for 30 minutes. Thiourea (1.83 g, 24.1 mmol) was added to the reaction mixture, followed by stirring under reflux and heat for 30 minutes. The reaction mixture was allowed to cool to room temperature, and then a saturated aqueous solution of sodium acid carbonate was added thereto, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (chloroform: methanol = 10: 1) to give the title compound a (5.10 g, 96%) as pale yellow crystals.

X H NMR (DMSO-de, d ppm): 6.55 (dd, J = 1.7, 3.3 Hz, 1H), 6.63 (dd, J = 0.7, 3.3 Hz, 1H), 7.34 (dd, J = 1.7, 6.3 Hz, 2H), 7.43 (br s, 2H), 7.60 (dd, J = 0.7, 1.7 Hz, 1H), 8.50 (dd, J = 1.7, 6.3 Hz, 2H).

[Reference Example 2] 2-Amino-4- (2-furyl) -5- (2-pyridyl) thiazole (Compound b) In a manner similar to that in Reference Example 1, the title compound b (155 mg, 13%, 2 steps) was obtained from 1- (2-furyl) -2- (2-pyridyl) ethanone (936 mg, 5.00 mmol) instead of 1- (2-furyl) -2- (4- pyridyl) ethanone. X H NMR (DMSO-de, d ppm): 6.56 (dd, J = 1.8, 3.3 Hz, 1H), 6.62 (dd, J = 0.7, 3.3 Hz, 1H), 7.26 (dd, J = 1.7, 4.4 Hz, 2H), 7.44 (br s, 2H), 7.60 (dd, J = 0.7, 1.8 Hz, 1H), 8.50 (dd, J = 1.7, 4.4 Hz, 2H).

[Reference Example 3] 2-Amino-4- (2-furyl) -5-phenylthiazole (Compound c) In a manner similar to that in Reference Example 1, the title compound c (1.47 g, 41%, 2 steps) was obtained from 1- (2-furyl) -2-phenylethanone (2.75 g, 14.8 mmol) in place of 1- (2-furyl) -2- (4-pyridyl) ethanone. X H NMR (DMSO-d 6, d ppm): 6.43-6.47 (m, 2H), 7.14 (br s, 2H), 7.28-7.35 (m, 5H), 7.49 (d, J = 1.7 Hz, 1H).

[Reference Example 4] 2-Amino-5-benzyl-4- (2-furyl) thiazole hydrobromide (Compound d) In a manner similar to that in step 1 of Reference Example 1, using 1- (2 -furyl) -3-phenylpropanone (1.19 g, 5.94 mmol) in place of 1- (2-furyl) -2- (4-pyridyl) ethanone, 2-bromo-l- (2-furyl) -3-phenylpropanone (1.66 g, 5.94 mmol) is got. The resulting compound was dissolved in acetonitrile (15 mL), thiourea (0.49 g, 6.44 mmol) was added thereto, followed by stirring under heat and reflux for 1 hour. The reaction mixture was allowed to cool to room temperature, and the precipitated solid was collected by filtration to provide the title compound of (1.21 g, 60%). X H NMR (DMSO-de, d ppm): 4.25 (s, 2H), 6.70 (dd, J = 1.7, 3.3 Hz, 1H), 6.91 (dd, J = 3.3 Hz, 1H), 7.27-7.35 (m, 5H), 7.90 (d, J = 1.7 Hz, 1H), 9.05 (br s, 2H).

[Reference Example 5] 2-Amino-5- (ethoxycarbonyl) -4- (2-furyl) thiazole Bromohydrate (Compound e) In a manner similar to that in Reference Example 4, the title compound e (2.91 g, 61%) was obtained from ethyl froilacetate (2.73 g, 15 mmol) in place of 1- (2-furyl) -2- (4-pyridyl) ethanone. X H NMR (DMSO-de, d ppm): 1.25 (t, J = 7.2 Hz, 3H), 4.19 (q, J = 7.2 Hz, 2H), 6.63 (dd, J = 1.7, 3.5 Hz, 1H), 7.50 (dd, J = 0.7, 3.5 Hz, 1H), 7.67 (br s, 2H), 7.79 (dd, J = 0.7, 1.7 Hz, 1H).

[Reference Example 6] 2-Amino-4- (2-furyl) -5-methylthiazole (Compound f) In a manner similar to that in Reference Example 1, the title compound f (245 mg, 34%) it was obtained from 1- (2-furyl) propane (500 mg, 4.03 mmol) in place of 1- (2-furyl) -2- (4-pyridyl) ethanone. X H NMR (CDC13, d ppm): 2.48 (s, 3 H), 4.82 (br s, 2 H), 6.45 (dd, J = 1.8, 3.3 Hz, 1 H), 6.53 (dd, J = 0.7, 3.3 Hz, 1 H ), 7.43 (dd, J = 0.7, 1.8 Hz, 1H) [Reference Example 7] 2-Amino-5-bromo-4- (2-furyl) thiazole (Compound g) Step 1: 2-Acetylfuran (5.1 g, 46.0 mmol) was dissolved in a mixed solvent of dichloromethane (50 mL) and methanol (50 mL) and tetra (n-butyl) ammonium bromide (22.3 g, 46.0 mmol) was added to this, followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, water was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was dissolved in acetonitrile (60 mL), thiourea (3.5 g, 46.0 mmol) was added thereto, followed by stirring under heating and reflux for 30 minutes. The precipitated solid was collected by filtration, and the resulting solid was dissolved in a mixed solvent of a saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate, and subjected to liquid-liquid separation. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 3: 1) to give 2-amino-4- (2-furyl) thiazole (1.53 g, 20%). X H NMR (CDCle, d ppm): 5.17 (br s, 2 H), 6.43 (dd, J = 2.0, 3.3, Hz, 1 H), 6.61 (d, J = 3.3 Hz, 1 H), 6.69 (s, 1 H) , 7.49 (d, J = 2.0 Hz, 1H).

Step 2: 2-Amino-4- (2-furyl) thiazole (330 mg, 1.99 mmol) was obtained in step 1 was suspended in chloroform (4 mL), and N-bromcinimide (360 mg, 2.02 mmol) was added to this, followed by stirring at room temperature for 1 hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was added.

Distilled under reduced pressure to provide the title compound g (438 mg, 90%). X H NMR (CDC13, d ppm): 5.08 (br s, 2 H), 6.48 (dd, J = 2.0, 3.3 Hz, 1 H), 6.96 (d, J = 3.3 Hz, 1 H), 7.48 (d, J = 2.0 Hz, 1H).

[Reference Example 8] N- [5-bromo-4- (2-furyl) thiazol-2-yl] tert-butyl carbamate (Compound h) The compound g (12.0 g, 49.0 mmol) obtained in the example of reference 7, di-tert-butyl bicarbonate (21.3 g, 97.9 mmol), triethylamine (17.1 mL, 122 mmol) and N, N-dimethylaminopyridine (0.60 g, 4.91 mmol) were dissolved in DMI (200 L), followed by stirring overnight at room temperature. The water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane: ethyl acetate = 5: 1) to give the title compound h (14.2 g, 84%). X H NMR (DMSO-de, d ppm): 1.49 (s, 9H), 6.64 (dd, J = 2.0, 3.3 Hz, 1H), 6.91 (dd, J = 0.7, 3.3 Hz, 1H), 7.80 (dd, J = 0.7, 2.0 Hz, 1H).

[Reference Example 9] 2-Amino-5-bromo-4- (5-bromo-2-furyl) thiazole (Compound i) Compound g (500 mg, 2.04 mmol) obtained in Reference Example 7 was dissolved in DMF (10 mL), and N-bromosuccinimide (363 mg, 2.04 mmol) was added thereto, followed by stirring at room temperature for 1 hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 4: 1) to give the title compound i (379 mg, 57%). H NMR (CDC13, d ppm): 5.16 (br s, 2H), 6.44 (d, J = 3.3 Hz, 1H), 6.91 (d, J = 3.3 Hz, 1H) [Reference Example 10] N- [5-Bromo-4- (2-furyl) thiazol-2-yl] pyridine-4-carboxamide (Compound j) In a manner similar to that in Example 1, by using Compound g (332 mg, 1.36 mmol) obtained in Reference Example 7 instead of compound a, the title compound j (382 mg, 81%) was obtained. X H NMR (DMS0-d 6, d ppm): 6.68 (dd, J = 1.8, 3.5 Hz, 1H), 7.01 (d, J = 3.5 Hz, 1H), 7.85 (d, J = 1.8 Hz, 1H), 8.01 (d, J = 4.8 Hz, 2H), 8.82 (d, J = 4.8 Hz, 2H), 13.48 (br s, 1H). ESIMS m / z: [79BrM-H] "348, [8XBrM-H]" 350.

[Reference Example 11] 2-methoxyisonicotinic acid (Compound k) The methyl 2-methoxyisonicotinate (6.35 g, 38.0 mmol) obtained according to the method described in US 6,509,361 was dissolved in a mixed solvent of methanol (39 mL) and water (13 mL), and lithium hydroxide monohydrate (7.97 g, 190 mmol) was added thereto, followed by stirring at room temperature for 2 hours. The methanol was distilled under reduced pressure, and 4 mol / L hydrochloric acid was added to the resulting aqueous solution to adjust the pH to 3. The precipitated solid was collected by filtration to provide the title compound k (4.72 g, 81%) as a white solid. X H NMR (DMSO-de, d ppm): 3.90 (s, 3H), 7.19 (d, J = 1.3 Hz, 1H), 7.39 (dd, J = 5.3, 1.9 Hz, 1H), 8. dd (d, J = 5.3 Hz, 1H). APCIMS m / z: [M + H] + 154.

[Reference Example 12] 2- (4-methoxybenzyloxy) isonicotinic acid (Compound 1) 55% sodium hydride (2.49 g, 57.0 mmol) was suspended in DMF (19 mL), and under ice-cooling, 4-methoxybenzyl alcohol (7.12 mL, 57.0 mmol) was added thereto, followed by stirring at room temperature for 1 hour. 2-Chloroisonicotinic acid (3.00 g, 19.0 mmol) was added to the reaction mixture, followed by stirring at 80 ° C for 2 hours. The reaction mixture is poured into a mixture of a saturated aqueous solution and sodium chloride (60 mL) and water (60 mL)., and 10% hydrochloric acid was added to the resulting solution to adjust the pH to 5, followed by stirring under ice cooling for 1 hour. The precipitated solid was collected by filtration to provide the title compound 1 (5.26 g, quantitative) as a white solid. X H NMR (DMSO-de, d ppm): 3.75 (s, 3 H), 5.31 (s, 2 H), 6.94 (d, J = 8.1 Hz, 2 H), 7.21 (s, 1 H), 7.39 (d, J = 5.4 Hz, 1H), 7.40 (d, J = 8.1 Hz, 2H), 8.34 (d, J = 5.4 Hz, 1H). APCIMS m / z: [M + H] + 260.

[Reference Example 13] 2-Ami'no-4- (2-furyl) -5- (2-methylpyridin-4-yl) thiazole (Compound m) Stage 1: 3, 4-dimethylpyridine (2.25 mL, 20.0 mmol) and ethyl furan-2-carboxylate (5.02 mL, 40.0 mmol) were dissolved in THF (20 mL), and at 0 ° C, a solution of hexamethyldisilazide of 1.0 mol / L lithium in THF (40.0 L, 40.0 mmol) was added dropwise thereto, followed by stirring at room temperature for 1.5 hour. The reaction mixture is poured into an aqueous saturated ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was washed successively with a saturated aqueous solution of ammonium chloride and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 1: 2) to give 1- (2-furyl) -2- (3-methylpyridin-4-yl) ethanone (3.34. g, 16.6 mmol). X H NMR (CDC13, d ppm): 2.32 (s, 3 H), 4.18 (s, 2 H), 6.58 (dd, J = 1.8, 3.6 Hz, 1 H), 7.11 (d, J = 5.0 Hz, 1 H), 7.26 (dd, J = 0.7, 3.6 Hz, 1H), 7.62 (dd, J = 0.7, 1.8 Hz, 1H), 8.38 (d, J = 5.0 Hz, 1H), 8.41 (s, 1H). APCIMS m / z: [M + H] + 260.

Stage 2: . In a manner similar to that in Reference Example 1, using 1- (2-furyl) -2- (3-methylpyridin-4-yl) ethanone (1.61 g, 8.00 mmol) was obtained in step 1 instead of 1- (2-furyl) -2- (4-pyridyl) ethanone, the title compound m (1.67 g, 81%) was obtained.

X H NMR (DMSO-de, d ppm): 2.05 (s, 3H), 6.39 (dd, J = 0.8, 3.5 Hz, 1H), 6.45 (dd, J = 1.7, 3.5 Hz, 1H), 7.25 (d, J = 5.0 Hz, 1H), 7.29 (br s, 2H), 7.46 (dd, J = 0.8, 1.7 Hz, 1H), 8.39 (d, J = 5.0 Hz, 1H), 8.48 (s, 1H).

[Reference Example 14] N- [4- (2-furyl) -5-yodothiazol-2-yl] benzamide (Compound n) Step 1: Compound g (10.0 g, 40.8 mmol) obtained in Reference Example 7 was dissolved in pyridine (136 mL), and under cooling with ice, 4-dimethylaminopyridine (250 mg, 2.04 mmol) and benzoyl chloride ( 8.05 mL, 69.4 mmol) were added thereto, followed by stirring at room temperature for 30 minutes. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 10: 1) to give N- [5-bromo-4- (2-furyl) thiazol-2-yl] benzamide ( 12.0 g, 84%) as a white solid. XH NMR (CDC13, d ppm): 6.67 (dd, J = 1.6, 3.5 Hz, 1H), 7.01 (d, J = 3.5 Hz, 1H), 7.46-7.71 (, 3H), 7.84 (d, J = 1.6 Hz, 1H), 8.09-8.17 (m, 2H).

Step 2: In a manner similar to that in Example 92, when using iodide (26.3 g, 104 mmol) in place of DMF and using N- [5-bromo-4- (2-furyl) thiazol-2-yl] Benzamide (10.3 g, 29.6 mmol) was obtained in step 1 instead of compound h, the title compound n (6.56 g, 56%) was obtained as a white solid. XH NMR (CDC13, d ppm): 6.48 (dd, J = 1.8, 3.3 Hz, 1H), 7.15 (d, J = 3.3 Hz, 1H), 7.42-7.65 (m, 3H), 7.45 (d, J = 1.8 Hz, 1H), 7.85-7.93 (m, 2H), 10.04 (br s, 1H).

[Reference Example 15] 2-Amino-4- (2-furyl) -5- (2-methylphenyl) thiazole (Compound O) Step 1: At 0 ° C, trimethylsilylcyanide (3.52 mL, 26.4 mmol) was added to a mixture of dry zinc iodide (100 mg) and furfural (1.99 mL, 24.0 mmol), followed by stirring at 0 ° C for 30 minutes . THF (20 mL) was added to the reaction mixture, and at -78 ° C, a solution of 1.0 mol / L lithium hexamethyldisilazide in THF (24.0 mL, 24.0 mmol) was added dropwise thereto, followed by stirring at the same temperature for 15 minutes. A solution (10 mL) of 2-methylbenzyl bromide (2.68 mL, 20.0 mmol) in THF was added to the reaction mixture, followed by stirring at room temperature for 1 hour. 1.0 mol / L of tetra (n-butyl) ammonium fluoride (26.4 mL, 26.4 mmol) was added to the mixture. reaction, followed by stirring at room temperature for 30 minutes. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed successively with a saturated aqueous solution of ammonium chloride and a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 4: 1) to provide 1- (2-furyl) -2- (2-methylphenyl) ethanone (3.33 g, 83% ). XH NMR (CDC13, d ppm): 2.31 (s, 3H), 4.16 (s, 2H), 6.53 (dd, J = 1.8, 3.6 Hz, 1H), 7.15-7.21 (m, 5H), 7.59 (dd, J = 0.8, 1.8 Hz, 1H).

Step 2: In a manner similar to that in Reference Example 1, using 1- (2-furyl) -2- (2-methylphenyl) ethanone (3.33 g, 16.6 mmol) was obtained in step 1 in place of l- (2-furyl) -2- (4-pyridyl) ethanone, the title compound or (1.62 g, 38%) was obtained.

[Reference Example 16] 2-Amino-4- (2-furyl) -5- (2-oxo-l, 2-dihydropyridin-4-yl) thiazole (Compound p) Step 1: In a manner similar to that in Reference Example 1, using 2- (2-fluoropyridin-4-yl) -1- (2-furyl) ethanone (6.16 g, 30.0 mmol) obtained according to the method described in WO 03/35639, in place of 1- (2-furyl) -2- (4-pyridyl) ethanone, 2-amino-5- (2-fluoropyridin-4-yl) -4- (2-furyl) Thiazole (4.86 g, 62%) was obtained. APCIMS m / z: [M + H] + 262.

Step 2: 2-Amino-5- (2-fluoropyridin-4-yl) -4- (2-furyl) thiazole (2.00 g, 7.65 mmol) was obtained in step 1 was suspended in 6 mol / L hydrochloric acid (20 L), followed by stirring under heat and reflux for 1 hour. The reaction mixture was neutralized with 10 mol / L aqueous sodium hydroxide solution was added thereto, and the precipitated solid was collected by filtration. The resulting solid was purified through column chromatography on silica gel (chloroform: methanol = 17: 3) to give the title compound p (1.01 g, 51%) as a yellow solid. X H NMR (DMSO-de, d ppm): 5.98 (dd, J = 1.8, 6.9 Hz, 1H), 6.18 (d, J = 1.8 Hz, 1H), 6.56 (dd, J = 1.7, 3.5 Hz, 1H), 6.62 (d, J = 3.5 Hz, 1H), 7.28 (d, J = 6.9 Hz, 1H), 7.42 (br s, 2H), 7.65 (d, J = 1.7 Hz, 1H), 11.44 (br s, 1H). APCIMS m / z: [M + H] + 260.

[Reference Example 17] 2-Amino-4- (2-furyl) -5- (2-oxo-l, 2-dihydropyridin-5-yl) thiazole (Compound q) Step 1: In a manner similar to that in Reference Example 1, using 2- (2-chloropyridin-5-yl) -1- (2-furyl) ethanone (13.8 g, 62.0 mmol) obtained according to the method described in WO 03/35639, instead of 1- (2-furyl) -2- (4-pyridyl) ethanone, 2-amino-5- (2-chloropyridin-5-yl) -4- (2-furyl) thiazole (11.6 g, 67%) is got. X H NMR (DMSO-de, d ppm): 6.52 (dd, J = 1.7, 3.5 Hz, 1H), 6.57 (d, J = 3.5 Hz, 1H), 7.36 (br s, 2H), 7.50-7.52 (m , 2H), 7.80 (dd, J = 2.6, 8.3 Hz, 1H), 8.37 (d, J = 2.6 Hz, 1H). APCIMS m / z: [35C1M + H] + 278, [37C1M + H] + 280.

Step 2: 2-Amino-5- (2-chloropyridin-5-yl) -4- (2-furyl) thiazole (2.22 g, 80.0 mmol) was obtained in step 1 and a methanol solution of 28% methoxide Sodium (4.63 g, 24.0 mmol) was suspended in 1,4-dioxane (8 mL), followed by stirring at 95 ° C for 2 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified through silica gel column chromatography. (chloroform methanol = 9: 1) to give 2-amino-4- (2-furyl) -5- (2-methoxypyridin-5-yl) thiazole (1.32 g, 60%). X H NMR (DMSO-d 6, d ppm): 3.88 (s, 3 H), 6.47-6.49 (m, 2 H), 6.84. (d, J = 8.4 Hz, 1H), 7.20 (br s, 2H), 7.51 (d, J = 1.2 Hz, 1H), 7.66 (dd, J = 2.5, 8.6 Hz, 1H), 8.16 (d, J) = 2.5 Hz, 1H). APCIMS m / z: [M + H] + 274.

Step 3: 2-Amino-4- (2-furyl) -5- (2-methoxypyridin-5-yl) thiazole (1.32 g, 4.83 mmol) was obtained in step 2 was suspended in a mixture of hydrobromic acid at 48 ° C. % (4 mL) and acetic acid (4 mL), followed by stirring at 100 ° C for 2 hours. The reaction mixture was neutralized with an aqueous solution of sodium hydroxide 10 mol / L was added thereto, and the precipitated solid was collected by filtration. The resulting solid was purified through column chromatography on silica gel (chloroform: methanol = 4: 1) to provide the title compound q (870 mg, 70%). X H NMR (DMSO-de, d ppm): 6.33 (d, J = 9.2 Hz, 1H), 6.47-6.49 (m, 2H), 7.14 (br s, 2H), 7.35-7.39 (m, 2H), 7.56 (dd, J = 0.8, 1.7 Hz, 1H), 11.78 (br s, 1H).

APCIMS m / z: [M + H] + 260.

[Reference Example 18] 2-Amino-5- (l-ethyl-6-oxo-l, 6-dihydropyridin-2-yl) -4- (2-furyl) thiazole (Compound r) Step 1: The ethyl 6-oxo-l, 6-dihydropyridine-2-carboxylate (16.7 g, 100 mmol) obtained according to the method described in Heterocycles, Vol. 24, p. 2169, 1986, was dissolved in DMF (200 mL), and potassium carbonate (20.7 g, 150 mmol) was added thereto, followed by stirring at room temperature for 1 hour. Ethyl iodide (16.0 mL, 200 mmol) was added to the reaction mixture, followed by stirring at 60 ° C for 3 hours. The reaction mixture is poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 1: 1) to give ethyl 1-ethyl-6-oxo-l, 6-dihydropyridine-2-carboxylate (3.17 g). , 16%).

Step 2: The ethyl l-ethyl-6-oxo-l, 6-dihydropyridine-2-carboxylate (2.25 g, 11.5 mmol) obtained in Step 1 was dissolved in ethanol (50 mL), and at 0 ° C, chloride Calcium (2.56 g, 23.1 mmol) and sodium borohydride (2.18 g, 57.6 mmol) were added thereto, followed by stirring at 0 ° C for 2 hours. The reaction mixture was concentrated under reduced pressure, and a saturated aqueous solution of ammonium chloride was added to the resulting residue, followed by stirring at room temperature for 30 minutes. The reaction mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography on silica gel (chloroform: methanol = 49: 1) to give l-ethyl-6- (hydroxymethyl) -2-oxo-1,2-dihydropyridine (1.51 g, %). X H NMR (CDC13, d ppm): 1.31 (t, J = 7.0 Hz, 3 H), 4.14 (q, J = 7.0 Hz, 2 H), 3.22 (t, J = 5.7 Hz, 1 H), 4.60 (d, J = 5.7 Hz, 1H), 6.27 (dd, J = 1.4, 7.0 Hz, 1H), 6.49 (dd, J = 1.4, 9.2 Hz, 1H), 7.27 (dd, J = 7.0, 9.2 Hz, 1H). APCIMS m / z: [M + H] + 154. Step 3: L-ethyl-6- (hydroxymethyl) -2-oxo-l, 2-dihydropyridine (1.51 g, 9.86 mmol) was obtained in step 2 and triethylamine (2.06 mL, 14.8 mmol) was dissolved in dichloromethane (40 mL), and at 0 ° C, methanesulfonyl chloride (0.920 mL, 11.8 mmol) was added dropwise thereto, followed by stirring at 0 ° C for 30 minutes. The water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled under reduced pressure to provide l-ethyl-6- (methanesulfonyloxymethyl) -2-oxo-l, 2-dihydropyridine (2.29 g, 100%). XH NMR (CDC13, d ppm): 1.36 (t, J = 7.5 Hz, 3H), 3.07 (s, 3H), 4.12 (q, J = 7.5 Hz, 2H), 5.13 (s, 2H), 6.32 (dd) , J = 1.5, 6.6 Hz, 1H), 6.65 (dd, J = 1.5, 9.3 Hz, 1H), 7.29 (dd, J = 6.6, 9.3 Hz, 1H). APCIMS m / z: - [M + H] + 232.

Step 4: In a manner similar to that in Reference Example 15, using l-ethyl-6- (methanesulfonyloxymethyl) -2-oxo-1,2-dihydropyridine (2.23 g, 9.86 mmol) was obtained in step 3 in place of 2-methylbenzyl bromide, the title compound r (913 mg, 32%) was obtained. X H NMR (DMSO-de, d ppm): 1.01 (t, J = 6.9 Hz, 3H), 3.30-3.50 (m, 2H), 6.29 (dd, J = 1.5, 6.9 Hz, 1H), 6.43-6.49 ( m, 3H), 7.39 (dd, J = 6.9, 9.0 Hz, 1H), 7.44-7.46 (br s, 2H), 7.54-7.56 (m, 1H).

APCIMS m / z: [M + H] + 288.

[Reference Example 19] 2-Amino-5- (l-ethyl-6-oxo-l, 6-dihydropyridazin-3-yl) -4- (2-furyl) thiazole (Compound s) Step 1: 2- Acetylfuran (3.30 g, 30.0 mmol) was dissolved in THF (30 mL), and cooled to -78 ° C. A 1.0 mol / L solution of lithium hexamethyldisilazide in THF (33.3 L, 33.0 mmol) was added thereto, and warmed to room temperature, and then stirred at room temperature for 15 minutes. The reaction mixture was cooled to -78 ° C, and a solution of l-ethyl-6-oxo-3- (trifluoromethanesulfonyloxy) -1,6-dihydropyridazine (4.08 g, 15.0 mmol) in THF (5 mL) obtained according to the method described in WO 03/039451 was added drop by drop to this, followed by stirring at room temperature for 1.5 hours. The reaction mixture is poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 1: 1) to give 2- (1-ethyl-6-oxo-l, 6-dihydro-pyridazin-3-yl). ) -1- (2-furyl) ethanone (1.01 g, 29%). X H NMR (CDC13, d ppm): 1.33 (t, J = 7.3 Hz, 3H), 4.13 (s, 2H), 4. 16 (q, J = 7.3 Hz, 2H), 6.57 (dd, J = 1.8, 3.6 Hz, 1H), 6.88 (d, J = 9.6 Hz, 1H), 7.21 (d, J = 9.6 Hz, 1H), 7.29 (d, J = 3.6 Hz, 1H), 7.62 (d, J = 1.8 Hz, 1H).

Step 2: In a manner similar to that in Reference Example 1, using 2- (1-ethyl-6-oxo-l, 6-dihydropyridazin-3-yl) -1- (2-furyl) ethanone (1.00 g, 4.31 mmol) was obtained in step 1, instead of 1- (2-furyl) -2- (4-pyridyl) ethanone, the title compound s (191 mg, 14%) was obtained. X H NMR (CDC13, d ppm): 1.38 (t, J = 7.0 Hz, 3 H), 4.20 (q, J = 7.0 Hz, 2 H), 5.41 (br s, 2 H), 6.47 (dd, J = 1.8, 3.3 Hz, 1H), 6.71 (d, J = 3.3 Hz, 1H), 6.81 (d, J = 9.9 Hz, 1H) 7.33 (d, J = 9.9 Hz, 1H), 7.41 (d, J = 1.8 Hz, 1H ).

[Reference Example 20] 2-Amino-5- (l-isopropyl-6-oxo-l, 6-dihydropyridazin-3-yl) -4- (2-furyl) thiazole (Compound t) Step 1: In a manner similar to that in step 1 of Reference Example 19, when using l-isopropyl-6-oxo-3- (trifluoromethanesulfonyloxy) -1,6-dihydropyridazine (2.86 g, 10.0 mmol) obtained according to the method described in WO 03 / 039451, in place of l-ethyl-6-oxo-3- (trifluoromethanesulfonyloxy) -1,6-dihydropyridazine, 1- (2-furyl) -2- (l-isopropyl-6-oxo-l, 6- dihydropyridazin-3-yl) ethanone (961 mg, 39%) was obtained. X H NMR (CDC13, d ppm): 1.28-1.30 (m, 6H), 4.14 (s, 2H), 5.20- 5.30 (m, 1H), 6.56 (dd, J = 1.8, 3.6 Hz, 1H), 6.85 ( d, J = 9.4 Hz, 1H), 7.17 (d, J = 9.4 Hz, 1H), 7.29 (d, J = 3.6 Hz, 1H), 7.61 (d, J = 1.8 Hz, 1H).

Stage 2: In a manner similar to that in the Example of Reference 1, when using 1- (2-furyl) -2- (l-isopropyl-6-oxo-l, 6-dihydropyridazin-3-yl) ethanone (960 mg, 3.90 mmol) was obtained in step 1, in Place of 1- (2-furyl) -2- (4-pyridyl) ethanone, the title compound t (331 mg, 28%) was obtained. X H NMR (CDCl 3, d ppm): 1.36-1.39 (m, 6H), 5.27-5.36 (m, 1H), 6. 49 (dd, J = 1.8, 3.3 Hz, 1H), 6.69 (dd, J = 0.8, 3.3 Hz, 1H), 6.82 (d, J = 9.7 Hz, 1H), 7.34 (d, J = 9.7 Hz, 1H ), 7.44 (dd, J = 0.8, 1.8 Hz, 1H).

[Reference Example 21] l-Ethyl-2-oxo-l, 2-dihydropyridine-5-carboxylic acid (Compound u) Step 1: The 4-methoxybenzyl alcohol (11.9 mL, 95.2 mmol) was dissolved in DMF (150 mL), and at 0 ° C, 55% sodium hydride (4.15 g, 95.2 mmol) was added thereto, followed by stirring at room temperature for 1 hour. A solution of DMF (10 mL) of 6-chloronicotinic acid (5.00 g, 31.7 mmol) was added to the reaction mixture, followed by stirring at 80 ° C for 2 hours. Water (200 mL) was added to the reaction mixture, and 4 mol / L hydrochloric acid (30 mL) was added dropwise thereto, and the precipitated solid was collected by filtration to provide 6- (4-methoxybenzyloxy) acid. ) nicotinic (8.15 g, 99%). X H NMR (DMSO-de, d ppm): 3.75 (s, 3 H), 5.35 (s, 2 H), 6.92 (d, J = 8.6 Hz, 1H), 6.94 (d, J = 8.6 Hz, 2H), 7.40 (d, J = 8.6 Hz, 2H), 8.15 (dd, J = 2.4, 8.6 Hz, 1H), 8.74 (d, J = 2.4 Hz, 1H).

Step 2: 6- (4-Methoxybenzyloxy) nicotinic acid (8.10 g, 31.2 mmol) was obtained in step 1 was dissolved in DMF (250 ml), and potassium carbonate (8.64 g, 62.5 mmol) and methyl iodide ( 3.89 mL, 62.5 mmol) were added thereto, followed by stirring at room temperature for 1 hour. The water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography on silica gel (ethyl acetate) to give methyl 6- (4-methoxybenzyloxy) nicotinate (3.78 g, 44%). XH NMR (CDC13, d ppm) 3.81 (s, 3H), 3.91 (s, 3H), 5.37 (s, 2H), 6.78 (dd, J = 0.7, 8.6 Hz, 1H), 6.91 (d, J = 8.8 Hz, 2H), 7.39 (d, J = 8.8 Hz, 2H), 8.15 (dd, J = 2.4, 8.6 Hz, 1H), 8.84 (dd, J = 0.7, 2.4 Hz, 1H).

Step 3 - Methyl 6- (4-methoxybenzyloxy) nicotinate (2.66 g, 9.73 mmol) was obtained in step 2 and anisole (10.6 mL) was dissolved in trifluoroacetic acid (15 mL), followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and saturated sodium acid carbonate was added to the resulting residue, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The precipitated solid was collected by filtration to provide methyl 2-oxo-l, 2-dihydropyridine-5-carboxylate (1.33 g, 89%). XH NMR (CDC13, d ppm) 3.87 (s, 3H), 6.58 (dd, J = 0.7, 9.5 Hz, 1H), 8.00 (dd, J = 2.6, 9.5 Hz, 1H), 8.20 (dd, J = 0.7, 2.6 Hz, 1H).

Step 4: Methyl 2-oxo-l, 2-dihydropyridine-5-carboxylate (400 mg, 2.61 mmol) was obtained in step 3 was dissolved in DMF (3 mL), and 55% sodium hydride (125 mg , 2.87 mmol) and ethyl iodide (0.230 mL, 2.87 mmol) were added to this, followed by stirring at room temperature for 2 hours. The water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (ethyl acetate) to provide methyl l-ethyl-2-oxo-1,2-dihydropyridine-5-carboxylate (375 mg, 79%). XH NMR (CDC13, d ppm) 1.39 (t, J = 7.2 Hz, 3H), 3.86 (s, 3H), 4.03 (q, J = 7.2 Hz, 2H), 6.53 (d, J = 9.5 Hz, 1H ), 7.83 (dd, J = 2.6, 9.5 Hz, 1H), 8.18 (d, J = 2.6 Hz, 1H).

Stage 5 l-ethyl-2-oxo-l, 2-dihydropyridine-5-carboxylic acid methyl (375 mg, 2.07 mmol) was obtained in step 4 was dissolved in a mixed solvent (1: 1) (20 mL) of water and methanol, and lithium hydroxide monohydrate (191 mg, 4.55 mmol) was added to this , followed by stirring at room temperature for 1 hour. The reaction mixture was neutralized with 3 mol / L hydrochloric acid was added thereto, and the precipitated solid was collected by filtration to provide the title compound u (224 mg, 65%). X H NMR (DMS0-d 6, d ppm): 1.21 (t, J = 7.1 Hz, 3 H), 3.97 (q, J = 7.1 Hz, 2 H), 6.39 (d, J = 9.4 Hz, 1 H), 7.76 (dd) , J = 2.5, 9. 4 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H).

[Reference Example 22] 2-Oxo-l- (4-pyridylmethyl) -1,2-dihydropyridine-5-carboxylic acid (Compound v) In a manner similar to that in steps 4 and 5 of Reference Example 21, when using 4-chloromethylpyridine hydrochloride in place of ethyl iodide, the title compound v (490 mg, 82%) was obtained from methyl 2-oxo-l, 2-dihydropyridine-5-carboxylate (400 mg, 2.61 mmol ) was obtained in step 3 of Reference Example 21. X H NMR (DMSO-d 6, d ppm): 5.16 (s, 2 H), 6.30 (d, J = 9.2 Hz, 1 H), 7.15 (d, J = 5.9 Hz, 2H), 7.89 (dd, J = 2.3, 9.2 Hz, 1H), 8.15 (d, J = 2.3 Hz, 1H), 8.50 (d, J = 5.9 Hz, 2H).

[Reference Example 23] l-Benzyl-2-oxo-l, 2-dihydropyridine-4-carboxylic acid (Compound w) Step 1; Compound 1 (20.4 g, 84.0 mmol) obtained in Reference Example 12 was dissolved in trifluoroacetic acid (168 mL), and anisole (91.1 mL, 0.840 mol) was added thereto, followed by stirring at room temperature for 3 hours. . The reaction mixture was concentrated under reduced pressure, and the resulting residue was made to make the Thicken mixture with ethyl acetate to provide 2-oxo-1,2-dihydropyridine-4-carboxylic acid (6.99 g, 60%) as a white solid. rH NMR (DMSO-de, d ppm): 6.51 (d, J = 6.8 Hz, 1H), 6.80 (d, 1H), 7.49 (d, J = 6.8 Hz, 1H).

Step 2: 2-Oxo-l, 2-dihydropyridine-4-carboxylic acid (2.00 g, 14.4 mmol) was obtained in step 1 was dissolved in DMF (29 mL), and potassium carbonate (7.95 g, 57.6 mmol ) and benzyl bromide (5.13 mL, 43.2 mmol) were added thereto, followed by stirring at 50 ° C for 2 hours. The water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 2.01) to give benzyl l-benzyl-2-oxo-1,2-dihydropyridine-4-carboxylate (1.58 g) , 34%) as a white solid. XH NMR (CDC13, d ppm) 5.14 (s, 2H), 5.31 (s, 2H), 7.23-7.41 (m, 13H).

Step 3: benzyl l-benzyl-2-oxo-l, 2-dihydropyridine-4-carboxylate (1.08 g, 3.38 mmol) was obtained in step 2 was dissolved in a mixed solvent of methanol (7 mL) and water ( 7 mL), and sodium hydroxide (0.680 g), 16.9 mmol) was added thereto, followed by stirring under heat and reflux for 30 minutes. The reaction mixture was poured into water (50 mL), and 10% hydrochloric acid was added thereto to adjust the pH to 4.5, followed by stirring at room temperature for 1 hour. The precipitated solid was collected by filtration to provide the title compound w (151 mg, 20%) as a white solid. X H NMR (DMSO-de, d ppm): 5.10 (s, 2H), 6.57 (dd, J = 1.9, 7.0 Hz, 1H), 6.78 (d, J = 1.9 Hz, 1H), 7.23-7.39 (m, 5H), 7.76 (d, J = 7.0 Hz, 1H).

[Reference Example 24] l-Methyl-2-oxo-l, 2-dihydropyridine-4-carboxylic acid (Compound x) In a manner similar to that in steps 2 and 3 of Reference Example 23, when using methyl iodide in place of benzyl bromide, the title compound x (1.20 g, 50%) was obtained as a colorless oily substance of 2-oxo-1,2-dihydropyridine-4-carboxylic acid (2.00 g, 14.4 mmol) was obtained in step 1 of Reference Example 23.

X H NMR (CDCl 3, d ppm): 3.55 (s, 3 H), 3.89 (s, 3 H), 6.64 (dd, J = 1.9 Hz, 1 H), 7.19 (d, J = 1.9 Hz, 1 H), 7.33 (d , J = 7.0 Hz, 1H).

[Reference Example 25] 4- (2-Furyl) -5- (pyridin-2-ylcarbonyl) thiazol-2-yl isocyanate (Compound y) Compound 186 (200 mg, 0.737 mmol) was suspended in dichloromethane (15%). mL), and carbonyldiimidazole (179 mg, 1.11 mmol) was added thereto at room temperature, followed by stirring at room temperature for 2 hours. Hexane (7.5 mL) was added to the reaction mixture, and the precipitated solid was collected by filtration to give the title compound y (133 mg, 61%) as a brown solid.

[Reference Example 26] 2-Formyl-5-methoxypyridine (Compound z) 2-Methoxy-5- (hydroxymethyl) pyridine (11.6 g, 83.5 mmol) obtained according to the method described in Tetrahedron Asymmetry, Vol. 12, p . 1047, 2001 was dissolved in chloroform (160 mL), and manganese dioxide (14.5 g, 167 mmol) was added thereto, followed by stirring under heat and reflux for 1 hour. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 3: 2) to provide the composed of the title z (4.32 g, 37%) as a white solid.

XH NMR (CDC13, d ppm): 3.96 (s, 3H), 7.31 (dd, J = 2.8, 8.7 Hz, 1H), 7.97 (d, J = 2.8 Hz, 1H), 8.44 (d, J = 8.7 Hz, 1H), 9. 99 (s, 1H).

[Reference Example 27] 2-Amino-4- (5-methyl-furan-2-yl) -5- (4-pyridyl) thiazole (Compound aa) In a manner similar to that in Example Reference 13, using 4-methylpyridine instead of 3,4-dimethylpyridine and using ethyl 5-methyl-furan-2-carboxylate (163 mg, 1.06 mmol) in place of ethyl furan-2-carboxylate, the title compound aa (80.0 mg, 30%) was obtained. X H NMR (CDCl 3, d ppm): 2.28 (s, 3 H), 5.28 (br s, 2 H), 6.04 (d, J = 3.2 Hz, 1H), 6.53 (d, J = 3.2 Hz, 1H), 7.43 (d, J = 6.5 Hz, 2H), 8.53 (d, J = 6.2 Hz, 2H).

[Reference Example 28] 2-Amino-4- (3-methyl-furan-2-yl) -5- (4-pyridyl) thiazole (Compound ab) In a manner similar to that in Reference Example 13, using 4 -methylpyridine in place of 3,4-dimethylpyridine and using ethyl 3-methylfuran-2-carboxylate (572 mg, 3.71 mmol) in place of ethyl furan-2-carboxylate, the title compound ab (536 mg, 71% ) it was obtained. X H NMR (CD 3 OD, d ppm): 1.81 (s, 3 H), 6.28 (d, J = 1.9 Hz, 1 H), 6. 99 (d, J = 6.3 Hz, 2H), 7.35 (d, J = 1.9 Hz, 1H), 8.26 (d, J = 6.3 Hz, 2H).

[Reference Example 29] 2-Amino-4- (3-phenylfuran-2-yl) -5- (4-pyridyl) thiazole (Compound ac) Step 1: 3-Bromofuran-2-carboxylic acid (1.86 g, 9.75 mmol), ethyl iodide (3.1 mL, 38.8 mol) and cesium carbonate (4.80 g, 14.7 mmol) was suspended in acetonitrile (50 L), followed by stirring at 80 ° C for 3 hours. The saturated aqueous sodium acid carbonate solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 9: 1) to give ethyl 3-bromofuran-2-carboxylate (1.16 g, 54%). X H NMR (CDC13, d ppm): 1.40 (t, J = 7.1 Hz, 3 H), 4.39 (q, J = 7.1 Hz, 2 H), 6.59 (d, J = 1.8 Hz, 1 H), 7.49 (d, J = 1.8 Hz, 1H).

Step 2: Ethyl 3-bromofuran-2-carboxylate (307 mg, 1.40 mmol) was obtained in step 1, phenylboronic acid (208 mg, 1.71 mmol), dichlorobis (tri-O-tolylphosphine) palladium (II) (60.3 mg, 0.008 mmol) and potassium carbonate (387 mg, 2.80 mmol) were dissolved in a mixed solvent of toluene (13 mL), ethanol (0.65 mL) ) and water (1.4 mL), followed by stirring at 90 ° C for 6 hours. The saturated sodium-saturated aqueous carbonate solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution and sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 6: 6) to provide ethyl 3-phenylfuran-2-carboxylate (290 mg, 96%). XH NMR (CDC13, d ppm): 1.30 (t, J = 7.3 Hz, 3H), 4.31 (q, J = 7.3 Hz, 2H), 6.61-6.62 (m, 1H), 7.35-7.44 (m, 3H) , 7.54-7.60 (m, 3H). Step 3: In a manner similar to that in Reference Example 13, using 4-methylpyridine in place of 3,4-dimethylpyridine and using ethyl 3-phenylfuran-2-carboxylate (277 mg, 1.28 mmol) was obtained in step 2 in place of ethyl furan-2-carboxylate, 2- (3-phenylfuran-2-yl) -1- (4-pyridyl) ethanone (230 mg, 75% ) it was obtained. X H NMR (CDCl 3, d ppm): 4.20 (s, 2 H), 6.71-6.72 (m, 1 H), 7.23 d, J = 6.0 Hz, 2 H), 7.37-7.44 (m, 3 H), 7.61-7.65 (m , 3H), 8. 54 (d, J = 6.0 Hz, 2H).

Step 4: In a manner similar to that in Reference Example 1, using 1- (2-furyl) -2- (3-phenylfuran-2-yl) ethanone (292 mg, 0.850 mmol) was obtained in the step 3 instead of 1- (2-furyl) -2- (4-pyridyl) ethanone, the title compound ac (22.5 mg, 8%) was obtained. X H NMR (CD3OD, d ppm): 5.47 (br s, 2 H), 6.64 (d, J = 1.9 Hz, 1 H), 6.84 (d, J = 6.2 Hz, 2 H), 7.11-7.22- (m, 5 H) , 7.51 (d, J = 1.9 Hz, 1H), 8.28 (d, J = 5.9 Hz, 2H).

[Reference Example 30] 2-amino-5- (4-pyridyl) -4- [3- (4-pyridyl) furan-2-yl] thiazole (Compound ad) Step 1: 3-bromofuran-2-carboxylate of ethyl (296 mg, 1.35 mmol) was obtained in step 1 of Reference Example 29, 4- (tri-n-butylstannyl) pyridine (550 mg, 1.51 mmol) and tetrakis (triphenylphosphine) palladium (0) (157 mg, 0.136 mmol) were dissolved in THF (10 mL), followed by stirring under heat and reflux for 4 hours. The aqueous ammonium fluoride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled under reduced pressure. The resulting residue was purified through column chromatography on silica gel (hexane: ethyl acetate = 2: 3) to give ethyl 3- (4-pyridyl) furan-2-carboxylate (133 mg, 45%). X H NMR (CDC13, d ppm): 1.33 (t, J = 7.2 Hz, 3 H), 4.34 (q, J 7.2 Hz, 2 H), 6.66 (d, J = 1.8 Hz, 1 H), 7.51 (d, J = 6.2 Hz, 2H), 7.63 (d, J = 1.8 Hz, 1H), 8.66 (d, J = 6.2 Hz, 2H).

Step 2: In a manner similar to that in Reference Example 13, using 4-methylpyridine in place of 3,4-dimethylpyridine and using ethyl 3- (4-pyridyl) furan-2-carboxylate (133 mg, 0.612 mmol) was obtained in step 1, instead of ethyl furan-2-carboxylate, the title compound ad (35.3 mg, 18%) was obtained. X H NMR (CDCl 3, d ppm): 5.21 (br s, 2 H), 6.69 (d, J = 1.9 Hz, 1 H), 6.87 (d, J = 6.1 Hz, 2 H), 7.18-7.21 (, 2 H), 7.55 (d, J = 1.9 Hz, 1H), 8.36 (d, J = 6.1 Hz, 2H), 8.43 (d, J = 6.1 Hz, 2H).

[Reference Example 31] 2-Amino-4- (3-furyl) -5- (4-pyridyl) thiazole (Compound ae) In a manner similar to that in Reference Example 13, using 4-methylpyridine instead of 3,4-dimethylpyridine, the title compound ae (216 mg, 25%) was obtained from ethyl furan-3-carboxylate (502 mg, 3.58 mmol).

XH NMR (CD3OD, d ppm): 6.38 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 6.3 Hz, 2H), 7.50 (dd, J = 2.3, 2.8 Hz, 1H), 7.67. (d, J = 2.3 Hz, 1H), 8.41 (d, J = 6.3 Hz, 2H).

[Reference Example 32] N- [5-bromo-4- (3-furyl) thiazol-2-yl] tert-butyl carbamate (Compound af) In a manner similar to that in Reference Example 7, when using 3-acetylfuran (1.00 g, 8.82 mmol) instead of 2-acetylfuran, 2-amino-5-bromo-4- (3-furyl) thiazole was obtained. In a manner similar to that in Reference Example 8, the title Compound af (845 mg, 28%) is obtained from 2-amino-5-bromo-4- (3-furyl) thiazole instead of 2 -amino-5-bromo-4- (2-furyl) thiazole. X H NMR (CDCl 3, d ppm): 1.54 (s, 9 H), 6.97 (dd, J = 0.9, 1.7 Hz, 1 H), 7.46 (dd, J = 1.7, 1.7 Hz, 1 H), 8.07 (0.9, 1.7 Hz) , 1 HOUR) . [Preparation Example 1] Tablets (Compound 1) In an ordinary method, tablets having the composition mentioned below were prepared. Compound 1 (40 g), lactose (286.8 g) and potato starch (60 g) were mixed, and 10% aqueous solution of hydroxypropyl cellulose (120 g) was added thereto. The mixture was kneaded into an ordinary form, granulated and dried, and arranged to give granules for tabletting. Magnesium stearate added (1.2 g) and mixed, and tablets were formed, by using a tablet-forming machine with a pestle having a diameter of 8 mm (Model RT-15 of Kikushi-sha), in tablets (containing 20 g. mg / tablet of active ingredient). Formulation Compound 1 20 mg Lactose 143.4 mg Potato starch 30 mg Hydroxypropyl cellulose 6 mg Magnesium stearate 0.6 mg 200 mg [Preparation Example 2] Tablets (Compound 86) In a manner similar to that in Preparation Example 1, by using Compound 86 (40 g), the title tablets were prepared (containing 20 mg / tablet of active ingredient ) Formulation Compound 86 20 mg Lactose 143.4 mg Potato starch 30 mg Hydroxypropyl cellulose 6 mg Magnesium stearate 0.6 mg 200 mg [Preparation Example 3] Preparation of Injection (Compound 99) In an ordinary method, an injection preparation having the composition below was prepared. Compound 99 (1 g) and D-mannitol (5 g) were added to the distilled water for injection, and hydrochloric acid and aqueous sodium hydroxide solution were added thereto to adjust the pH to 6. Then water was added thereto. distilled for injection to be 1000 mL in total. In a germ-free condition, the resulting mixture was filled into glass vials in an amount of 2 mL / vial to prepare injection vials (containing 2 mg / vial of the active ingredient). Formulation Compound 99 2 mg D-mannitol 10 mg Hydrochloric acid ad lib. Aqueous solution of sodium hydroxide ad lib. Distilled water for Injection ad lib. 2.00 mL Industrial Applicability The present invention provides A2 adenosine receptor antagonists comprising a thiazole derivative or a pharmaceutically acceptable salt thereof, such as the active ingredient, thiazole derivatives or pharmaceutically acceptable salts thereof which have an A2A adenosine receptor antagonism and are useful for agents for the prevention and / or treatment of diseases associated with the A2A adenosine receptor; and the similar ones. It is noted that with this date, the best method known to the applicant to carry out the practice of said invention, is that which is clear from the present description of the invention.

Claims

Claims: Having described the invention as above, the content of the following claims is claimed as property. An adenosine A2A receptor antagonist, characterized in that it comprises, as the active ingredient, a thiazole derivative represented by the general formula (I):

(OR . { where; n represents an integer from 0 to 3; Rx represents substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted aromatic heterocyclic group; R2 represents a halogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl, -NR5R6 (wherein R5 and R6 may be the same or different, and each one represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted lower alkanoyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted aralkyl or unsubstituted, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl, -OR7 (wherein R7 represents a hydrogen atom, rent the substituted or unsubstituted lower, substituted or unsubstituted lower alkanoyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, heterocyclic alkyl substituted or unsubstituted alicyclic, or substituted or unsubstituted aromatic heterocyclic alkyl), or -COR8 [wherein - R8 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted lower alkynyl or not substituted, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted aromatic heterocyclic alkyl or unsubstituted -NR9RX0 (wherein R9 and R10 may be the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, lower alkanoyl replaced or not replaced, a substituted or unsubstituted lower alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl substituted, substituted or unsubstituted aromatic heterocyclic alkyl), or -OR11 (wherein R11 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl , substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl)]; and R3 and R4 may be the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, lower-substituted or unsubstituted alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted aralkyl, heterocyclic alkyl substituted or unsubstituted alicyclic, substituted or unsubstituted aromatic heterocyclic alkyl, -COR 12 [wherein R 12 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted cycloalkyl or not replaced, aryl substituted or unsubstituted, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl, -NR13R14 (wherein R13 and R14 may be the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted lower alkanoyl, substituted lower alkoxy or unsubstituted, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic ilo), or -OR15 (wherein R15 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, aryl substituted or unsubstituted, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl)]; with the proviso that, when R x is substituted or unsubstituted phenyl and n is 0, then R 2 is not 6-oxo-l, 6-dihydropyridazin-3-yl} substituted or unsubstituted, or a pharmaceutically acceptable salt thereof.
2. The A2A adenosine receptor antagonist according to claim 1, characterized in that Rx is substituted or unsubstituted aryl, or a substituted or unsubstituted aromatic heterocyclic group.
3. The A2A adenosine receptor antagonist according to claim 1 or 2, characterized in that n is 0.
4. The A2A adenosine receptor antagonist according to claim 1 to 3, characterized in that R2 is substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, a heterocyclic group substituted or unsubstituted alicyclic, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl, or -COR8 (wherein R8 has the same meaning as defined above).
5. The A2A adenosine receptor antagonist according to any of claims 1 to 3, characterized in that R2 is substituted or unsubstituted aryl.
6. The A2A adenosine receptor antagonist according to any of claims 1 to 3, characterized in that R2 is a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted aromatic heterocyclic group.
7. The A2A adenosine receptor antagonist according to any one of claims 1 to 3, characterized in that R2 is -COR8 (wherein R8 has the same meaning as defined above).
8. The A2A adenosine receptor antagonist according to any one of claims 1 to 4 and 7, characterized in that R is a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl substituted, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl.
9. The A2A adenosine receptor antagonist according to any of claims 1 to 4 and 7, characterized in that R8 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, or an aromatic heterocyclic group replaced or not replaced.
10. The A2A adenosine receptor antagonist according to any of claims 1 to 4 and 7, characterized in that R8 is substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted aromatic heterocyclic group.
11. The antagonist of the Ane adenosine receptor according to any of claims 1 to 10, characterized in that R3 is a hydrogen atom.
12. The A2A adenosine receptor antagonist according to any of claims 1 to 10, characterized in that R3 is lower alkyl or aralkyl.
13. The A2A adenosine receptor antagonist according to claims 11 or 12, characterized in that R4 is -COR12 (wherein R12 has the same meaning as defined above).
14. The A2A adenosine receptor antagonist according to claim 11 or 12, characterized in that R4 is -CORX2a (wherein RX2a is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted cycloalkyl, substituted aryl or unsubstituted, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl).
15. The A2A adenosine receptor antagonist according to claim 1 or 10, characterized in that R3 and R4 can be the same or different, and each represents -COR12 (wherein R12 has the same meaning as defined above).
16. The A2A adenosine receptor antagonist according to claim 1, characterized in that n is 0; R x is a substituted or unsubstituted 5-membered aromatic heterocyclic group containing at least one oxygen atom; and R2 is -C0R8a (wherein R8a represents a substituted or unsubstituted alicyclic heterocyclic group).
17. The A2A adenosine receptor antagonist according to claim 16, characterized in that Rx is substituted or unsubstituted furyl.
18. The A2A adenosine receptor antagonist according to claim 16 or 17, characterized in that R8a is a substituted or unsubstituted alicyclic heterocyclic group containing at least one oxygen atom.
19. The A2A adenosine receptor antagonist according to any of claims 1 to 10 and 16 to 18, characterized in that R3 is a hydrogen atom; and R 4 is substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted aromatic heterocyclic alkyl.
20. The A2A adenosine receptor antagonist according to any of claims 1 to 10 and 16 to 18, characterized in that R3 is a hydrogen atom; and R 4 is lower alkyl, aralkyl, or aromatic heterocyclic alkyl.
21. The A2A adenosine receptor antagonist according to any of claims 1 to 10 and 16 to 18, characterized in that R3 and R4 can be the same or different, and each represents substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl or substituted or unsubstituted aromatic heterocyclic alkyl.
22. An agent for treating and / or preventing diseases associated with the A2A adenosine receptor, characterized in that it comprises, as the active ingredient, a thiazole derivative according to any of claims 1 to 21, or a pharmaceutically salt acceptable of them.
23. The agent for treating and / or preventing diseases according to claim 22, characterized in that the disease associated with the A2A adenosine receptor is Parkinson's disease.
24. A thiazole derivative represented by a formula (IA): (IA) [characterized in that Rxa represents a substituted or unsubstituted 5-membered aromatic heterocyclic group containing at least one oxygen atom (excluding a group selected from 5-phosphonofuran-2-yl and 5-nitrofuran-2-yl); R12 and n have the same meaning as defined above, respectively; R3A represents a hydrogen atom; substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, lower alkynyl substituted or unsubstituted, substituted or unsubstituted aralkyl, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl, or -CORX2A (wherein R12A has the same meaning as that of R12); and R2A represents substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group , a substituted or unsubstituted aromatic heterocyclic group (excluding 2-furyl), substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl, -NR5R6 (wherein R5 and R6 have the same meaning as defined above, respectively ), -OR7 (wherein R7 has the same meaning as defined above), or -COR8 (wherein R8 has the same meaning as defined above)], or a pharmaceutically acceptable salt thereof.
25. The thiazole derivative according to claim 24, characterized in that R1A is furyl substituted or unsubstituted, or a pharmaceutically acceptable salt thereof.
26. The thiazole derivative according to claim 24 or 25, characterized in that n is 0, or a pharmaceutically acceptable salt thereof.
27. The thiazole derivative according to any of claims 24 to 26, characterized in that R2A is substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl, or -COR8 (wherein R8 has the same meaning as defined above), or a pharmaceutically acceptable salt thereof.
28. The thiazole derivative according to any of claims 24 to 26, characterized in that R2A is substituted or unsubstituted aryl, or a pharmaceutically acceptable salt thereof.
29. The thiazole derivative according to any of claims 24 to 26, characterized in that R2 is a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof.
30. The thiazole derivative according to any of claims 24 to 26, characterized in that R2A is -COR8 (wherein R8 has the same meaning as defined above), or a pharmaceutically acceptable salt thereof.
31. The thiazole derivative according to claim 30, characterized in that R8 is a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted aryl or unsubstituted, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, substituted or unsubstituted aromatic heterocyclic alkyl, or a pharmaceutically acceptable salt of the same.
32. The thiazole derivative according to claim 30, characterized in that R8 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted aromatic heterocyclic group, or a salt pharmaceutically acceptable thereof.
33. The thiazole derivative according to claim 30, characterized in that R8 is a substituted or unsubstituted aryl, a substituted or unsubstituted alicyclic heterocyclic group, or a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof.
34. The thiazole derivative according to any of claims 24 to 33, characterized in that R3A is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
35. The thiazole derivative according to any of claims 24 to 33, characterized in that R3A is lower alkyl or aralkyl, or a pharmaceutically acceptable salt thereof.
36. The thiazole derivative according to any of claims 24 to 33, characterized in that R3A is -COR12A (wherein RX2A has the same meaning as defined above), or a pharmaceutically acceptable salt thereof.
37. The thiazole derivative according to claim 36, characterized in that RX2A is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a group substituted or unsubstituted alicyclic heterocyclic, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl, or a pharmaceutically acceptable salt thereof.
38. The thiazole derivative according to any of claims 24 to 37, characterized in that R12 is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl , a substituted or unsubstituted alicyclic heterocyclic group, a "substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl, or a pharmaceutically acceptable salt thereof.
39. A thiazole derivative represented by the formula (IB): (IB) (characterized in that n and R1A have the same meaning as defined above, respectively: R38 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl, R4B represents substituted or unsubstituted lower alkyl, substituted lower alkenyl or non-substituted substituted, substituted or unsubstituted lower alkynyl, substituted or unsubstituted aralkyl, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl; and R8B represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, a heterocyclic group substituted or unsubstituted alicyclic, a substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted alicyclic heterocyclic alkyl, or substituted or unsubstituted aromatic heterocyclic alkyl), or a pharmaceutically acceptable salt thereof.
40. The thiazole derivative according to claim 39, characterized in that RXA is substituted or unsubstituted furyl, or a pharmaceutically acceptable salt thereof.
41. The thiazole derivative according to claim 39 or 40, characterized in that n is 0, or a pharmaceutically acceptable salt thereof.
42. The thiazole derivative according to any of claims 39 to 41, characterized in that R8B is a substituted or unsubstituted alicyclic heterocyclic group containing at least one oxygen atom, or a pharmaceutically acceptable salt thereof.
43. The thiazole derivative according to any of claims 39 to 42, characterized in that R3B is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
44. The thiazole derivative according to claim 43, characterized in that R4B is aromatic heterocyclic lower alkyl, aralkyl or aralkyl, or a pharmaceutically acceptable salt thereof.
45. A pharmaceutical composition, characterized in that it comprises, as the active ingredient, a thiazole derivative according to any of claims 24 to 44, or a pharmaceutically acceptable salt thereof.
46. An A2A adenosine receptor antagonist, characterized in that it comprises, as the ingredient active, a thiazole derivative according to any of claims 24 to 44, or a pharmaceutically acceptable salt thereof.
47. An agent for treating and / or preventing diseases associated with A2A adenosine receptor, characterized in that it comprises, as the active ingredient, a thiazole derivative according to any of claims 24 to 44, or a pharmaceutically acceptable salt thereof.
48. An agent for treating and / or preventing diseases of the central nervous system, characterized in that it comprises, as the active ingredient, a thiazole derivative according to any of claims 24 to 44, or a pharmaceutically acceptable salt thereof.
49. An agent for treating and / or preventing Parkinson's disease characterized in that it comprises, as the active ingredient, a thiazole derivative according to any of claims 24 to 44, or a pharmaceutically acceptable salt thereof.
50. A method to treat and / or prevent diseases associated with the A2A adenosine receptor, characterized in that it comprises administering an effective amount of a thiazole derivative represented by a general formula (I): (I) (wherein n, R1, R2, R3 and R4 have the same meaning as defined above, respectively), or a pharmaceutically acceptable salt thereof.